Field Anaesthesia: A Report of Mercy Malaysia’s Mission 1 to Kashmir following the 2005 South Asia Earthquake

Full text

MALAYSIAN SOCIETY
OF ANAESTHESIOLOGISTS
Year Book 2006/2007
K
E
S
E
L
A
M
A
T
A
N
D
A
L
A
M
B
I
U
S

2
Foreword
As a fellow of the Australian and New Zealand College of Anaesthetists, I receive the year
book “Australasian Anaesthesia” from the College and I find this collection of lectures by
fellows at local scientific meetings extremely useful. At a time when clinicians are expected
to maintain professional competency, keeping abreast with current literature is one of many
learning activities expected of us. For most practitioners, it is a demanding task to try to keep
up with journal reading. A quick reference or a digest covering ‘hot topics’ or updates related
to clinical practice is always much appreciated. It is with this in mind that the idea of intro-
ducing a similar year book was mooted.
In the past, regional scientific meetings organised by the MSA and ‘evening talks’ by industry
sponsored foreign speakers provided most of our continuous professional development
activities. However, with dwindling industry sponsorship and increasing expectation from
our members, it becomes obvious that we must now aggressively pursue a CPD programme
which is locally driven. The highly successful annual scientific meetings held in conjunction
with the last two annual general meetings as well as the success of local intensive care confer-
ences of the last four years have proved our ability to sustain a local CPDprogramme. This
year book again proves our academic capability and reflects the MSA’s commitment to
promote continuous professional development.
In this year book, an update of thirteen clinical topics which have been peer reviewed is
provided. It is my hope that members will find this book essential reading and beneficial to
their daily practice.
This inaugural year book will not be possible without the hard work of its editors, Dr Rafidah
Atan and Dr Nor’azim Yunos, to whom I am deeply indebted. They have shown their com-
mitment and capability by successfully producing this book.
I am extremely grateful to my colleagues who have contributed to this publication. In spite of
their busy clinical work, they have managed to write their chapters. It is a huge sacrifice
spending hours researching and putting evidence together. The rest of us have benefited from
their work. On behalf of the MSA, I express my profound gratitude and appreciation.
Ng Siew Hian

3
Preface
To be given the task to edit the first ever issue of the MSA Yearbook is truly a big honour. Such
honour nevertheless carries with it the high expectation of all MSA members. It is therefore
our sincere hope that this humble effort matches that expectation.
Our idea of the Yearbook is one that updates the reader on various aspects of anaesthesia and
intensive care in a concise and ‘easy’ manner. This, however, by no means indicates a lesser
quality. A special thank you goes to all authors and reviewers who have worked very hard,
sacrificing their precious time in the process, in an attempt to produce a Yearbook that MSA
members can be proud of. Similarly, our heartfelt gratitude goes to the ‘silent contributors’;
family members of those involved and their significant others.
We have made a conscious effort to involve as many members as possible either as main
contributors, co-writers or peer reviewers, introducing some new talents in the process. We
envisage the Yearbook to be a regular avenue for ‘expert’ authors to revisit the joy of writing
scholarly articles and for ‘novices’ to discover their penchant for writing. We hope that
subsequent editors will take on this idea as well.
Happy reading!
Rafidah binti Atan
Nor’azim bin Mohd Yunos

We would like to acknowledge the following peer reviewers (in alphabetical order) for their contributions:
Dr Chiu Chiaw Ling
Subang Jaya Medical Centre, Selangor
Professor Felicia Lim
Faculty of Medicine, Universiti Kebangsaan Malaysia
Professor Lucy Chan
Faculty of Medicine, University of Malaya
Assoc. Prof Mohd Basri Mat Nor
Faculty of Medicine, International Islamic University
Dr Mohd Yani Bahari
Hospital Serdang, Selangor
Assoc Professor Norsidah Abd Manap
Faculty of Medicine, Universiti Kebangsaan Malaysia
Professor Ramani Vijayan
Faculty of Medicine, University of Malaya
Dr Sabariah Faizah Jamaluddin
Hospital Sungai Buloh, Selangor
Dr Suresh Anselm Rao
Gleneagles Intan Medical Centre, Kuala Lumpur.
Dr Tan Cheng Cheng
Hospital Sultanah Aminah, Johor Bahru
Dr Toh Khay Wee
Subang Jaya Medical Centre, Selangor
Dr Wahida Abdul Latiff
Hospital Sultanah Aminah, Johor Bahru
4
Acknowledgements

INTRODUCTION
Acute care is the provision of appropriate care to a
patient in life-threatening or impending
life-threatening situation with the aim of preventing
irreversible damage. To attain this goal, well trained
care-providers in adequate numbers must be
available, when necessary, to recognize, manage and
reverse these situations.
Current surveys suggest that our health care services
are inadequately equipped to cope with this need.
Many doctors neither have the skills nor the
knowledge necessary. Even in areas like intensive
care where the provision of acute care is supposedly
at its premium, care is often suboptimal out of hours.
SOURCE OF PROBLEMS AND INITIATIVES TO
IMPROVE SITUATION
The importance of acute care has been unrecognized
until recently and many medical schools have
allowed thousands of doctors to be produced
worldwide without adequate knowledge of handling
the acutely ill. Many schools had hitherto assumed
that if doctors are trained in the basics of medicine,
they will instinctively be able to handle the acutely ill
patient as well. They have failed to recognize that
managing the acutely ill patient requires knowledge
and skills that are unique to the discipline of acute
care.
There are initiatives now in place especially in the
United Kingdom, to catch up on these deficiencies in
training, both in the undergraduate as well as
postgraduate years. In the last few years, many
medical schools have modified their curriculum to
accommodate this need, and the United Kingdom
Acute Care Initiative is one such move. The Royal
College of Physicians in the United Kingdom has
5
Acute Care
also produced working reports calling for acute care
to be included in the specialty training curriculum at
postgraduate level. This might require a review of
the content of all postgraduate courses to
accommodate dual training, emphasising not only
general internal medicine but also acute care.
Recently, there is a parallel move worldwide to
streamline health care systems to focus on acutely ill
patients. The International Partnership on Acute
Care Safety (IPACS), which is in turn endorsed by the
WHO World Alliance for Patient Safety, has enlisted
many health care bodies to look at improving
systems in their respective countries to focus initially
on acutely ill patients. IPACS hopes to ultimately
benefit all patients using these systems
improvement.
SCOPE OF SUBJECT
It is essential during the training of young doctors to
emphasize on basic concepts in acute care. These
include the importance of ensuring the integrity of
all processes aiming for continued delivery of
oxygen to all organs, chief of which are the brain and
the heart. These processes involve ensuring airway
patency for the passage of oxygen to the lungs,
adequate breathing or ventilation to ensure that
oxygen is continuously brought to the lungs at a rate
commensurate with body requirements, and
adequate circulation to ensure that the oxygen is
subsequently delivered to the tissues by adequate
flow of blood. Continuous oxygen delivery to all
organs as a basis of life is poorly grasped by a
significant number of health care providers. Most
programs that teach care providers life-support fail
to emphasize physiological aspects and trainees are
left to rote-learn the program without understanding
much of the process of oxygen delivery to the tissues
to maintain life.
Chan Yoo Kuen, MBBS (Malaya), FFARCS (Ireland).
Department of Anaesthesiology and Intensive Care, Faculty of Medicine, University of Malaya.
Professor Chan Yoo Kuen is the Head of Department of Anaesthesiology and Intensive Care at University of Malaya. Her
main interests are Obstetric Analgesia & Anaesthesia and Acute Care. She has been actively promoting Acute Care aware-
ness in Malaysia and has co-edited two books on the subject: Practical Aspects of Acute Care and Management Aspects of
Acute Care.

YEAR BOOK 2006/2007
The knowledge base is extremely wide, so it appears
rational to emphasize on certain principles of
sustaining life.
A race against time
A lot has been said about the race against time for the
acutely ill patient. For the trauma patient, the concept
of the Golden Hour was first coined by Donald
Trunkey. Subsequently the concept of the platinum ten
minutes evolved – each an improvement in the
previously accepted norm of trying to limit time to
definitive care, in order to improve outcome.
Impressive though these time frames may sound,
minutes may be too long a delay in situations where
cardiac output is absent, since it is enough for a mere
10 seconds of anoxia to the brain to produce loss of
consciousness and four more minutes of
uninterrupted anoxia to cause brain death.
Many studies have shown that in many acutely ill
patients, premonitory signs and symptoms were
missed by care providers, which if detected would
have allowed more definitive management and
prevented deterioration. Many modern hospitals
currently have systems in place to rapidly alert
relevant care providers, before deterioration of
patients to the point of no return.
Airway, breathing and support of the
circulation
Integrity or achieving integrity of the airway,
breathing and circulation is essentially what acute
care is all about. These three basic tenets of care will
ensure adequate oxygen delivery to the tissues,
necessary for the survival of the patient.
Recognizing an unstable patient
This is represented by a patient whose airway,
breathing and circulation are not under good control
either by the patient or his care-provider. An
inadequate airway, a patient who is barely breathing
and one whose blood flow to the tissues is
suboptimal can deteriorate further and threaten the
patient’s survival. It is important to recognize these
patients, the earlier the better, and to train all
care-providers to be on the look out for them, and
equip them with the necessary skills to minimize
6
patient morbidity and mortality. If these three main
causes of instability in an acutely ill patient are
appropriately handled, further deterioration in most
patients can be prevented. It is within the ability of
all hospitals, in terms of personnel, equipment,
drugs and other resources, to do this but in order to
successfully manage life threatening situations with
good outcomes, concerted effort on the part of
administrators and medical staff will be required.
A threat to life as opposed to a threat to an organ
In acute care, a differentiation needs to be made
between reversing circumstances, which are a threat
to a patient’s life, as opposed to those which are
threatening an organ in the body. There is no doubt
that both may be interlinked. A threat to important
organs like the brain, the heart and the lungs may
threaten life itself but threat to lesser organs like the
eye may only mean loss of function to that particular
organ. Under such circumstances, more priority
must be given to managing that which threatens life
first, before focusing on threats to an organ.
Damage control – do not save the limb and
hazard the patient’s life
In the current climate where the medical field has
become super-specialized, there are fewer of us who
look at the patient as a whole. We tend to focus on a
disease condition or a problem in an organ or a
problem in a limb, rather than getting the best
outcome out of life threatening situations. Damage
control is the theme which should be stressed in
acute care. In an endeavour to salvage patients’ limbs
or other body parts, we may end up exposing
patients to continued instability that can ultimately
compromise the whole patient and result in a life
threatening situation. Prolonged procedures on
patients without due focus on optimal tissue oxygen
delivery and survival can either cause an immediate
life threat or cause subsequent damage. This occurs
through the introduction of hypothermia, excessive
blood loss and other physiological trespass from
which patients may find difficulty in recovering.
The wider knowledge
Of course, besides the very basic tenets of the patent

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
7
airway, the process of breathing and ensuring flow to
the tissues through an intact circulation, acute care
providers need to know a myriad of other principles
that can make a difference to outcome. This includes
oxygen therapy, fluid and blood therapy, monitoring,
eliciting signs of a rapidly deteriorating patient,
keeping patients warm, effective communication to
seek appropriate further support and even safe
transport of acutely ill patients to other areas for more
definitive care.
Parallel skills
Besides knowledge, there are skills that need to be
learnt in parallel. These include airway control skills,
skills to oxygenate and ventilate the patient with
appropriate equipment, and maintenance of blood
flow during cardiac arrest by way of closed cardiac
massage. These skills are very basic and form part of
basic life support skills. The ability to further enhance
life-support management with appropriate drugs,
defibrillation and other organ support form the basis
of advanced life support. All these can be learnt
separately as a module (eg module for airway
management, oxygen therapy etc) and all
care-providers can be tested for competency in each of
the modules.
TEACHING OPPORTUNITIES
Acute care is needed by up to 16% of the patients
admitted to the wards. Situations where teaching
opportunities arise should not be difficult to come by.
The recovery area in operating theatres is another
fertile ground where teaching of acute care can be
particularly rewarding. In these areas, there is a
constant supply of patients whose airway, breathing
and circulation may be compromised. The accident
and emergency area is of course another ideal place
for exposure of trainees to a variety of skills and
processes in the management of acute care patients.
Even the wards can be suitable if trainers take
advantage of acute care situations, as and when they
arise.
Teaching must be commensurate with the knowledge
base of the trainee. As these life-sustaining processes
are skills, teaching on the job involving small groups
is the best means of achieving the goal. Obviously this
is going to be labour intensive, as well as counting on
the presence of enthusiastic trainees and trainers
being at the correct place when a life threatening event
occurs.
Simulation of the acute care situation allows programs
to be arranged so that teaching and learning can occur
at suitable times for both trainees and trainers. This,
though realistic, may never approximate the real
event but offers a good substitute. Here again, the
throughput of the trainees may be limited because we
have to understand that in skills learning, supervision
of trainees is essential and thus, the numbers per
supervisor have to be kept low for effective learning.
Not all medical schools are equipped with this facility
as they come with a fairly high price tag, both for
purchase as well as maintenance.
THE TRAINEES
All care providers, whether in the capacity of a doctor,
nurse or paramedic, should be equipped with the skill
and know-how to do the job of sustaining life by
ensuring oxygen is properly delivered to the tissues.
Currently, medical students during their training are
taught respiratory, cardiovascular and tissue
physiology in great detail, but effort is often not made
to correlate knowledge with principles involved in
sustaining life in clinical practice. The skills involved
are obviously harder to come by and unfortunately,
physiological knowledge and clinical skills are often
learnt separately, without attempts to integrate them,
making it harder to understand and master the subject
of acute care. As a result many young doctors
graduate with few skills to provide acute care and
learn by trial and error, over many years at the job, to
acquire them. Most may not even bother, preferring to
leave the job to others.
Post-graduate doctors are also a target group. It is
only appropriate that whilst they may spend time
acquiring skills and knowledge in a sub-discipline of
medicine, they should also have the ability to save the
lives of acutely ill patients. General practitioners are
another set of care providers, identified for retraining
of such knowledge and skills. We may have to change
the mindset of all doctors not trained in acute care
medicine to recognize the importance of acquiring
such skills.

YEAR BOOK 2006/2007
8
Nurses who form the bulk of care-providers in the
ward should probably be the target of this initiative as
well, as provision of acute care are fairly simple
processes, requiring skills within the grasp of all care
providers. As nurses outnumber doctors in all
countries, this would be a good way of providing
some temporary solution to the problem. They should
also be provided with the basic knowledge to sustain
life whilst awaiting further help.
THE TRAINERS
There are a limited numbers of doctors or specialists
with the correct skills to teach acute care and they are
already stretched with provision of care, much less to
cope with training. The emergency room physician or
acute care physician are rare breeds. The fully trained
anaesthesiologists are physicians with much of the
knowledge and skills required in acute care and they
would be the most useful doctors in the medical
speciality to fill the void. Most disciplines have a
sub-field where management of the acutely ill patient
is emphasized and these should be merged into one
entity by all trainers under the umbrella of acute care.
Many colleges are recognizing the need as well as the
lack of trainers for this new field. We are at an early
stage of this recognition and are putting in much effort
to address the problem, not only of training, but of
provision as well. Currently in the United Kingdom,
acute care medicine comes under the realm of the
College of Physicians and has been set up as a
sub-speciality of this college.
SUMMARY
Acute care is a new sub-discipline of medicine that is
being recognized as being important in the provision
of complete care to all patients. Many initiatives, both
at the training as well as the provision level, are
attempting to address the current shortfall in terms of
human resources to cope with the acutely ill patient.
When all systems are in place, the acutely ill patient
will no longer become a formidable issue in the life of
a doctor.
FURTHER READING
Practical Aspects of Acute Care. Drs. Chan Yoo Kuen
& Ng Kwee Peng (eds) Publishers – University of
Malaya Press, Kuala Lumpur 2005
Bion JF, Heffner JE Challenges in the care of the
acutely ill. Lancet 2004; 363: 970-977
Smith GB, Poplett N. Knowledge of aspects of acute
care in trainee doctors. Postgraduate Medical Journal
2002; 78:335-338
Perkins GD, Barret H, Bullock I, Gabbott DA, Nolan
JP, et al. The Acute Care Undergraduate TEaching
(ACUTE) Initiative: consensus development of core
competencies in acute care for undergraduates in the
United Kingdom. Intensive Care Med 2005;31(12):
1627-1633

9
Updates On Ambulatory Surgery
Introduction
The first ether anesthetic was given for ambulatory
surgery. James M. Venable had a small cystic tumor
removed from the back of his neck by Dr Crawford W.
Long on the evening of March 30, 1842.1
For the past 20 years day care surgery has undergone
a rapid increase in volume. Currently an estimated
70% of surgical procedures in North America are
completed in ambulatory settings. In Europe these
figures vary widely but in England up to 65% of all
surgical procedures are performed on a day case
basis.2
The types of procedures which are considered suitable
to be performed on outpatients vary considerably
between different countries and even between differ-
ent regions within a country.
Patients benefit from ambulatory surgery because it
minimizes costs, decreases separation from home and
family environments, reduces surgery waiting times,
decreases likelihood of contracting hospital acquired
infections, and appears to reduce postoperative
complications.
Settings for outpatient surgery
The various designs of a prototypical ambulatory
surgical unit include hospital integrated, hospital
separated (but with access to a hospital), satellite
ambulatory unit which operates under the same
administration, totally independent free standing unit
and office based unit. The majority of outpatient
surgeries are still performed in hospital settings,
either in integrated or separated units.
The decision as to where to perform the surgery
depends upon the levels of ambulatory surgery. The
levels of ambulatory surgery are classified as follows:
a) Minor ambulatory surgery (under local
anesthesia)
b) Major ambulatory surgery (under G.A, central
neural blockade with or without I.V. sedation)
c) In-patient ambulatory surgery
Screening of patients
At the present time, there are several commonly used
approaches to screening patients for ambulatory
surgery. These include the following:
1. Facility visit prior to the day of surgery
2. Office visit prior to the day of surgery
3. Telephone interviews/no visit
4. Review of health survey /no visit
5. Preoperative screening and visit on the morning of
surgery
6. Computer – assisted information gathering
A visit by the anaesthetist on the day before surgery is
desirable because it minimizes cancellation due to
inadequate preoperative assessment and preparation,
as well as reduces the patient’s anxiety about anaes-
thesia and surgery. Unfortunately, this is not possible
in many busy outpatient centres.
Selection of patient
This is the key to successful day care surgery, patients
must be selected and prepared properly. Selection is
Asmarawati Mohd Yatim, MBBS (Malaya), M Anaes (Malaya)
Nordini Mohd Dani, MBBS (Mal), M Med(Anaes) USM
Department of Anaesthesiology and Intensive Care, Hospital Tengku Ampuan Afzan, Kuantan.
Dr Asmarawati Mohd Yatim’s main interest is in neuroanaesthesia and neurointensive care. She is currently the
Head of Department of Anaesthesiology and Intensive Care in Hospital Tengku Ampuan Afzan, which is one of
the first hospitals in Malaysia with a large designated day care centre
Dr Nordini Mohd Dani is a Specialist Anaesthesiologist at Hospital Tengku Ampuan Afzan. Her areas of interest
include neuroanaesthesia and trauma anaesthesia.

YEAR BOOK 2006/2007
10
not simply a matter of choosing patients with
conditions that may be treated on a day care basis, but
also involves excluding patients who are unsuitable
due to medical and social reasons. The complexity of
surgery and the patient’s medical condition must also
be considered. Common exclusion criteria for patient
selection are shown in Table 1.
Table 1: Exclusion criteria for outpatient surgery
1. Medical
a. Unfit ASA III & IV
b. Obese: Body mass index >35
c. Nature of pathology: large scrotal hernias, major intrathoracic, intrabdominal or intracranial surgery
d. Procedures requiring more than one hour
e. Surgery expected to have major fluid loss or blood loss
2. Patient
a. Concept of day care surgery unacceptable to the patient
b. Psychologically unstable patient
c. Patients who live far away from the hospital
d. Infants < 3months of age and preterm babies
3. Social: No competent relatives or friends to
a. Accompany or drive patient home after the operation
b. Attend to the patient at home for the next 24-48hours
Table 2: Controversial exclusion criteria
Controversial exclusion criteria
a. Extremes of age
b. Morbid obesity
c. COPD
d. Fragile diabetes
e. Patients prone to malignant hyperpyrexia
f. Monoamine Oxidase Inhibitor use
g. Acute substance abuse

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
11
The elderly and ASA physical status
Extremes of age are no longer a deterrent to outpatient
surgery. A prospective trial involving a cohort of
15,172 patients undergoing ambulatory surgery found
that age did not predict unanticipated admission.3
Conversely, another cohort of 4,786 outpatients
identified an association between age above 65 and an
increased risk of intraoperative adverse events.4
These events were mainly related to changes in
haemodynamic variables and were found to increase
in proportion with age.
A prospective study involving more than 13,000
patients by Natof at a freestanding ambulatory
surgical centre demonstrated that ASA 3 patients in
whom systemic diseases were well controlled
preoperatively, were at no higher risk for
postoperative complications than ASA 1 or 2
patients.5 Chung et al. have recently published data
examining predictors of adverse events in ambulatory
surgery in the elderly as well as factors contributing to
prolonged stay after ambulatory surgery in elderly
patients.6,7 These data demonstrated that outpatient
surgery is safe in this patient population, with elderly
patients sustaining more minor cardiovascular events
than their counterparts and less, pain, drowsiness and
postoperative nausea and vomiting.6,7
In summary, geriatric and higher-risk (physical status
3 and 4) patients may be considered for ambulatory
surgery if their systemic diseases are well controlled
and their medical conditions optimized before
surgery.
The ex-premature infant
Premature infants less than 60 weeks postconceptual
age should not be considered for ambulatory surgery.
The risk of postoperative apnea has been evaluated in
a number of retrospective and prospective studies.
Cote’ pooled individual patient data from 255
ex-premature infants in eight prospective studies8 and
calculated the probability of postoperative apnea
occurring using a logistic regression model.
Postoperative apnea occurred in approximately 25%
of these patients. The incidence is inversely related to
gestational age and post conceptual age (PCA), with
an incidence of less than 5% when the PCA is over 60
weeks. A haematocrit level of less than 30% also
correlated with the likelihood of apnea. A systematic
review has demonstrated that caffeine reduces the
rate of apnea9 and some randomized control trials
have demonstrated a reduced apnea rate with
regional rather than general anesthesia.10,11
Cardiac disease
The patients with the greatest risk of complications
from anaesthesia are those with cardiac disease,
mainly uncontrolled hypertension, congestive cardiac
failure (CHF) or angina. In a study of existing medical
conditions as predictors of perioperative adverse
events from ambulatory surgery, Chung et al found
that patients with CHF had a 12% longer
postoperative stay, which in some instances led to
hospital admissions.6 They also found a twofold
increase in intraoperative cardiovascular events in
patients with hypertension. However the study was of
insufficient size to demonstrate an association
between coronary artery disease (CAD) and
intraoperative events.
The guidelines by the American Heart Association
stratified risk according to the type of surgery, patient
functional capacity and clinical predictors.
Intermediate clinical predictors include mild
ischaemic heart disease, prior myocardial infarction
(over 1 month old), compensated heart failure,
diabetes mellitus and renal insufficiency. These
patients may undergo low-risk surgical procedures
without further cardiac investigations.
Pulmonary disease
Chronic obstructive pulmonary disease (COPD),
asthma and tobacco abuse often lead to pulmonary
complications. Arozullah et al found that patients
with COPD had twice the standard risk for
pulmonary complications from ambulatory surgery as
did patients without COPD.12 In a recent prospective
evaluation of preexisting medical conditions in
ambulatory surgery, patients with asthma and
smokers were identified as having an increased risk
for postoperative respiratory events.6 There was
however no significant association between
respiratory disease and length of stay in recovery after

YEAR BOOK 2006/2007
ambulatory surgery.7 This may be an indication that
the events were relatively minor. Asymptomatic
patients with asthma have very low complications,
approaching that of non–asthmatic population.13,14
However, those experiencing respiratory symptoms at
the time of surgery faced a 50% incidence of
postoperative respiratory complications compared
with less than 2% of those without symptoms.
A cohort study of 489 patients evaluated the influence
of smoking on the incidence of perioperative
complications following ambulatory surgery.14
Smokers experienced an increased risk of respiratory
and wound complications. Patients who stopped
smoking less than four weeks preoperatively suffered
adverse events at a rate similar to current smokers. On
the other hand, a randomized controlled trial of 120
patients undergoing joint arthroplasty demonstrated
that smoking cessation six to eight weeks
preoperatively yielded improvements in wound
related complications.15
Morbid Obesity
The morbidly obese frequently have comorbidities,
including CAD, CHF, hypertension, and obstructive
sleep apnea. A health survey found that the
prevalence of cardiovascular diseases was 37% in
adults with a BMI of >30kg.m-2, 21% in those with a
BMI 25-30kg.m-2, and only 10% in those with a BMI of
< 25kg.m-2.16 Approximately 5% of morbidly obese
patients have obstructive sleep apnea.17 The study by
Chung et al found a fourfold increase in adverse
pulmonary events in morbidly obese patients
compared with those of normal body weight.
Although morbidly obese patients without systemic
disease are acceptable candidates for ambulatory
surgery, most centres prefer overnight hospitalization
and postoperative observation for morbidly obese
patients with pre-existing cardiac, pulmonary, hepatic
or renal compromise or for patients with complex
sleep apnea.
Diabetes Mellitus
IDDM is not considered a contraindication for
ambulatory surgery. A study looking at preexisting
medical conditions as predictors of adverse events in
12
day case surgery did not find IDDM to be a significant
predictor of intra- or postoperative events in
ambulatory surgery.18 Comorbid conditions including
difficult airway, must be identified and managed
appropriately. Recommendations to withdraw
metformin >48hour preoperatively are not supported
by evidence. Tighter control of perioperative blood
glucose is encouraged.
Malignant Hyperthermia (MH)
MH is a rare condition and therefore has not been
studied in large prospective trials. Knowledge of this
condition and its management in the ambulatory
setting is largely derived from case reports and
retrospective reviews. Authorities support
ambulatory surgery in MH patients as long as a
minimum of four hours of temperature monitoring
can be provided postoperatively. The Malignant
Hyperthermia Association of the United States
(MHAUS) advises that the MH patients may be
discharged three to four hours following uneventful
anesthetics.19 The Malignant Hyperthermia
Association of Canada (MHA Canada) recommends a
four hour monitoring period.
Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors (MAOI) increase brain
monoamine and cytoplasmic concentration of
monoamine oxidase (MAO) substrates by inhibiting
metabolism of cytoplasmic neurotransmitters.20
Classic MAOI such as phenelzine and
tranylcypromine, irreversibly inhibit MAO for two to
three weeks until new enzyme is synthesized.20
Moclobemide, a reversible inhibitor of MAO–A
(RIMA) causes enzyme inhibition for less than 24hour.
Selegiline, an anti-Parkinsonian agent, is a short
acting, reversible MAO-B inhibitor at its usual dose.
Serotonergic reactions to pethidine have been
described for all MAOI, including moclobemide and
selegiline. Pethidine blocks neuronal serotonin
reuptake, resulting in serotonergic overactivity which
manifests as agitation, hyper/hypotension,
convulsions, hyperthermia, and coma.21 Case reports
of sporadic MAOI-related drug interactions led to
many advisories to discontinue classic MAOI two to
three weeks before surgery.20,22,23 There is no

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
13
literature specifically concerning MAOI and
ambulatory anesthesia. Although MAOI related drug
interactions are possible and have been reported,
patients continuing to take either classic or selective
MAOI remain suitable candidates for ambulatory
anesthesia if pethidine, cocaine and indirect acting
catecholamines are avoided.24
Premedication
Ambulatory surgery is known to elicit anxiety. The
use of premedication in outpatients has been a subject
of considerable interest and debate. Inpatients usually
receive premedication, but outpatients have not been
given sedative premedication because of the mistaken
belief that drugs could prolong recovery and delay
discharge. Interestingly, most prospective studies
have failed to demonstrate prolonged recovery times
following premedication in outpatients. Shorter
acting benzodiazepines can give reliable sedation,
amnesia and anxiolysis without delaying recovery
even after short procedures. A Cochrane Database
Systematic Review concluded that there is no
evidence of a difference in time to discharge from
hospital in patients who received anxiolytic
premedication.
Anaesthetic technique
The ideal anesthetic technique for ambulatory surgery
should result in a rapid and smooth onset of action,
intraoperative amnesia and analgesia, good surgical
conditions and a short recovery period without side
effects. Choice of anesthetic technique could either be
general anesthesia, regional anesthesia, local
anaesthesia or monitored anesthesia care. The choice
of anesthetic technique can affect postoperative
morbidity at home.25
General anesthesia
For many procedures, general anesthesia remains to
be the most popular technique. The introduction of
increasingly rapid and shorter acting volatile
anesthetics (e.g. desflurane and sevoflurane), opioid
analgesics (eg. remifentanil), and muscle relaxants has
allowed practitioners to more consistently achieve a
recovery profile that facilitates “fast tracking”
following general anesthesia.26,27 The use of
electroencephalographic bispectral index monitoring
can improve titration of maintenance anesthetic and
thereby facilitate the early recovery process.28,29
Intravenous (IV) agents are used for the induction of
anesthesia in both adults and older children. Propofol
is the IV induction agent of choice for outpatient
anesthesia. It gives rapid emergence and very low
incidence of postoperative side effects. Euphoria on
emergence is often seen after propofol and
postoperative nausea and vomiting (PONV) are rare,
in particular when combined with the ultra short
acting opioid remifentanil.27,30 However, remifentanil
has a limited role in ambulatory surgery because its
advantages of rapid postoperative recovery and lack
of residual respiratory depression are negated by the
requirement for a longer acting opioid or alternative
analgesic as soon as the infusion is stopped.31 In spite
of increasing interests in IV anesthetic techniques,
inhaled anaesthetics remain to be the most popular
agent for maintenance of general anesthesia. The
newer halogenated ether compounds, sevoflurane
and desflurane, have significantly lower blood:gas
solubility characteristics, resulting in more rapid
onset and recovery. In addition, these less-soluble
volatile agents give more intraoperative
hemodynamic stability because they are easily
adjustable. Desflurane has rapidly gained popularity
for maintenance of anesthesia during ambulatory
surgery. It has the lowest blood:gas solubility of all
volatile anaesthetics, and the most rapid awakening
after ambulatory surgery. Sevoflurane has slightly
faster awakening times and fewer postoperative side
effects than isoflurane. Because it is non-irritating to
the airway, sevoflurane can also be used for induction
of anesthesia as an alternative to propofol in both
adults and children. Maintenance with propofol
infusion can improve the quality of recovery from
general anaesthesia, but this does not result in earlier
recovery or discharge when compared to both
sevoflurane and desflurane. When these newer
anaesthetic agents are combined with low dose
remifentanil infusion, emergence from anesthesia is
extremely rapid, facilitating the fast tracking
process.27
Use of muscle relaxant in ambulatory surgery remains
an open-ended problem. To date the ideal drug with
rapid onset, minimal side effects and short duration of

YEAR BOOK 2006/2007
14
action is not yet available. Suxamethonium still has a
place for when muscle relaxation is needed only
during intubation. Atracurium and rocuronium are
non-depolarizing agents commonly used. Doses
selected should seek the best compromise between
ideal intubating conditions and duration of muscle
relaxation required. Neuromuscular monitoring
should be applied to minimize the risk of residual
recurarization and reversal agents should be
administered as needed.
Sugammadex may be the answer to the use of
neuromuscular blocking agent for ambulatory
surgery in the near future. It acts as a chelant by
removing rocuronium from acetylcholine receptors,
thus reversing neuromuscular blockade with no major
adverse effects.
Although the facemask and oropharyngeal airways
are often used for brief, superficial ambulatory
procedure, tracheal intubation remains popular as it
minimizes the risk of airway complications. However,
the laryngeal mask airway (LMA) and the cuffed
oropharyngeal airway (COPA) devices are now used
where in the past either a face mask or tracheal tube
would have been preferred.32 These airway devices
reduce requirement for anesthetic agents, cause less
postoperative sore throat and less acute
hemodynamic changes during induction and
emergence, as well as allow avoidance of both muscle
relaxants and reversal agents compared to the use of
endotracheal tubes.
Regional anaesthesia
Regional anaesthesia, whether by epidural, spinal,
peripheral nerve block or field block technique, offers
a number of advantages to outpatients undergoing
surgery. These techniques allow analgesia without
sedation and provide prolonged postoperative
analgesia. The decreased requirements for opioids
reduces the incidence of PONV. Spinal anesthesia is
the most common central neuraxial block in day
surgery setting. It has distinct advantages over
epidural anesthesia, with less time required to achieve
an adequate block, lower incidence of incomplete
sensory and motor block and pain during surgery.33 A
17- nation European survey of 105 hospitals showed
that almost 40% of all ambulatory surgery in the
participating hospitals was performed under regional
blocks. Spinal and epidural blocks were used in
20-30% of hospitals.
Lignocaine is most frequently used, though recent
studies have shown that transient neurological
symptoms (TNS) can occur in 16-40% of
outpatients.34,35,36 Alternative local anesthetic drugs
such as bupivacaine in small doses (5-10mg) and
ropivacaine are associated with very low incidence of
TNS but are not always appropriate for day case
surgery. Adjuvants such as fentanyl 10ug can improve
the success rate of low dose hyperbaric bupivacaine (eg
5mg) spinal anaesthesia without prolonging discharge
time.37 A postoperative follow up did not show TNS in
any of the 60 patients who received spinal mepivacaine
as part of combined spinal-epidural (CSE) block for
anterior cruciate ligament repair.37
A former barrier to outpatient spinal administration,
namely post-dural puncture headache, has been
largely eliminated with the introduction of
conical–tipped needles that result in less dural
trauma.38 Although recovery after neuroaxial
blockade is improved by decreasing the local
anaesthetic dosage and adding a potent opioid
analgesic (eg. fentanyl, sufentanil),39 discharge times
are still prolonged compared with general anesthesia
or local anesthesia with sedation.40,41 Increasingly,
practitioners are turning to monitored anesthesia care
(MAC) as an alternative to both general and regional
anesthesia.42
The availability of improved sedation and analgesia
techniques to complement local anaesthetic
infiltration and peripheral nerve blocks has increased
the popularity of performing surgery utilizing MAC.
Management of postoperative pain
Pain has been found to be a major factor complicating
recovery and delaying discharge after ambulatory
surgery.46 A multimodal approach to providing
postoperative analgesia is essential in the ambulatory
setting.42-45 The role of opioid in day case surgery is
controversial because of their well known side effects,
especially PONV. Although patients who receive
opioids are more likely to experience PONV, average
recovery times are not significantly prolonged by the

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
15
use of intraoperative opioid per se. Several studies
have demonstrated early ambulation and
discharge after fentanyl or alfentanil –based
anaesthetic techniques.47
As a result of concerns regarding opioid–related
side effects, there has been an increased interest in
the use of potent non steroidal analgesics after
ambulatory surgery, leading to an earlier
discharge home. Other less expensive oral
non-steroidal analgesics (e.g. ibuprofen,
naproxen) may be acceptable alternatives to
fentanyl and the parenteral non selective anti
–inflammatory drugs if administered in a
preemptive fashion.4 8 Recently premedication
with the COX-2 inhibitors has become more
popular because they are devoid of potential
adverse effects on platelet function.50
Acetaminophen is a very cost effective alternative
to the COX-2 inhibitors if it can be given in high
enough doses prior to the end of surgery.51,52 Pain
should be controllable with oral analgesics before
patients are discharged.
Use of local anaesthetic techniques for
intraoperative analgesia, as well as adjuncts to
general (and spinal) anesthesia, can provide
excellent analgesia during the early postoperative
recovery and postdischarge periods.53-55 Even
simple wound infiltration and instillation
techniques have been shown to improve
postoperative analgesia following a variety of
lower abdominal, peripheral extremity and even
laparoscopic procedures. More recently, use of
continuous local anesthetic delivery systems have
been found to improve pain control after major
ambulatory orthopaedic surgery by extending
peripheral nerve blocks.56-58 Patient-controlled
local anesthetic delivery has also been described
for improving pain relief after discharge home.57
Installation of 30 ml of bupivacaine 0.5% into the
joint space reduces postoperative opiate
requirements and permits earlier ambulation and
discharge after arthroscopic surgery.59 The
addition of morphine (1-2mg), ketorolac
(15-30mg), clonidine (0.1-0.2mg) and
triamcinolone (10-20mg) to the intraarticular local
anesthetic solution can further reduce pain after
arthroscopic surgery.59
Postoperative nausea and vomiting
Despite pharmacological and technological
advancements, nausea and vomiting still remain
common problems for post surgical outpatients,
seen in 20%-30% of patients after general
anesthesia,60 and reported by 35% of patients after
discharge home.61 Prophylactic measures are
advised for the highly vulnerable patients –
females, patients in the luteal and perimenstrual
phases of the menstrual cycle, history of PONV,
non smokers and those with motion sickness.62
Droperidol, metoclopramide, and prochloperazine
are effective against PONV in the ambulatory
setting; however, their effectiveness is often
negated by undesirable side effects such as
extrapyramidal reactions, marked sedation and
drowsiness. Anti-serotonin drugs (e.g.
ondansetron, dolasetron), in contrast, provide
effective PONV management without these
undesirable side effects, and work by blocking
central and peripheral receptors that modulate the
vomiting reflex. Side effects, although infrequent,
may include headache, dizziness, and transient
elevation of liver enzymes.
Antiemetic prophylaxis with droperidol 0.625mg
IV, droperidol 1.25mg IV, ondasetron 4mg IV or
dolasetron 12.5mg is similarly efficacious in adults
compared to metoclopramide 10mg IV.63
Ondansetron, however, is more effective than
droperidol in preventing vomiting in children.63
While the timing of prophylactic ondansetron does
not appear to affect the overall incidence of PONV,
the need for rescue antiemetics to treat
breakthrough PONV may be reduced when
ondansetron is administered at the end of surgery.64
In addition, dexamethasone prophylaxis
(150ug/kg,up to 8 mg) appears to
further decrease
the risk of PONV, and provide an extended
duration of action lasting up to 24-h
postoperatively. Watcha has provided an algorithm
ranging from routine multimodal antiemetic
prophylaxis for the high risk patients to none for
low risk patients (< 10% risk of PONV), and also
identified risk factors.70 Ultimately, a multimodal
approach to antiemetic therapy, particularly in high
risk patients, will provide the most effective
outcome.98,100 Recent studies have shown that
alleviating dehydration with adequate

YEAR BOOK 2006/2007
16
perioperative fluid therapy (20-mL/kg for 8-h NPO
) will reduce the incidence of postoperative adverse
outcomes, such as thirst, nausea and vomiting, in
the outpatient.72
Conclusion
Ambulatory surgery has expanded rapidly in recent
years. The number and complexities of surgery
performed in the outpatient setting will no doubt
continue to rise. Improvement of anaesthetic and
surgical techniques, resulting in extremely good
safety record, was a prerequisite for the radical
increase in the number of surgical procedures
performed in ambulatory surgical units. The correct
evaluation of patients for ambulatory surgery is of
critical importance. Careful patient selection can
minimize adverse perioperative events and
improve outcome measures.
The success of ambulatory surgery depends, to a
large extent, on both effective control of
postoperative pain and minimization of side effects
such as sedation, nausea and vomiting.
References
1. Packard FR: History of medicine in the United States, New
York, Paul B Hoeber, 1931.3
2. Jarrett PEM. Day care surgery. Eur J Anaesthesiol
2001;18:32-35.
3. Fortier J, Chung F, Su J. Unanticipated admission after
ambulatory surgery-a prospective study. Can J Anaesth.
1998;45:612-9.
4. Chung F, Mezei G, Tong D: Adverse events in ambulatory
surgery. A comparison between elderly and younger
patient. Can J Anaesth 1999;46:309-21.
5. Natof HE: Preexisting medical problems. Ambulatory
surgery. IMJ 111 Med J 1984; 166:101-4
6. Chung F, Mezei G, Tong D. Preexisting medical condition
as predictors of adverse events in day case surgery. Br J
Anaesth 1999;83:262-70
7. Chung F, Mezei G: Factors contributing to a prolonged
stay after ambulatory surgery. Anesth Analg
1999;89:1352-9
8. Cote CJ, Zaslavsky A, Downes JJ, et al. Postoperative
apnea in former infants after inguinal herniorapphy. A
combined analysis. Anesthesiology 1995;82:809-22.
9. Henderson –Smart DJ, Steer P. Prophylactic caffeine to
prevent postoperative apnea following general
anaesthesia in preterm infants .Cochrane Database Syst
Rev 2002;4:CD000048.
10. Williams JM, Stoddart PA ,Williams SA, et al
.Postoperative recovery after inguinal herniotomy in
ex-premature infants :comparison between sevoflurane
and spinal anesthesia. Br J Anesth 2001;86:366-371.
11. Somri M, Gaitini L, Vaida S, et al. Postoperative outcome
in high risk infants undergoing herniorapphy; a
comparison between spinal and general anesthesia.
Anesthesia 1998;53:762-766.
12. Arozullah AM, Khuri SF, Henderson WG, Daley
J;Participants in the National Veterens Affairs Surgical
Quality Improvement Program. Development and
validation of multifactorial risk index for predicting
postoperative pneumonia after major non cardiac surgery.
Ann Intern Med 2001;135:847-857.
13. Warner DO, Warner MA ,Barnes RD, et al. Perioperative
respiratory complications in patients with Asthma.
Anesthesiology 1996;85:460-7
14. Kumeta Y, Hattori A, Mimura M, Namiki A. A survey of
perioperative bronchospasm in105 patients with reactive
airway disease (Japanese). Masui 1995;44:396-401.
15. Moller AM, Villebro N, Pederson T, Tonnase H. Effects of
preoperayive smoking intervention on postoperative
complications; a randomized clinical trial .Lancet
2002;359:114-7.
16. Lean ME. Obesity and cardiovascular disease. The wasted
years. Br J Cardiology 1999;6:269-73.
17. Young T, Palta M, Dempsey J,Skatrud J,Weber S, Badrr S.
The occurrence of sleep disordered breathing among
middle aged adults. N Engl J Med 1993;328:1230-5.
18. FriedmanZ,Wong DT, Chung F. What are the ambulatory
surgical patient selection criteria in Canada? Can J
Anaesth 2003;50 (suppl) A16 Absract.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
17
19. Malignant Hyperthermia Association of the United States.
Medical FAQs.2003; URL;http//www.mhaus.org/
index.cfm/fuseaction/Content.Display/PagePK/
MedicalFAQs.cfm
20. Wells DG, Bjorksten AR. Monoamine oxidase inhibitors
revisited. Can J Anaesth 1989;36:64-74.
21. Martyr JW, Orlikowski CE. Epidural anaesthesia,
ephedrine and phenylephrine in a patient taking
moclobemidew, a new monoamine oxidase inhibitors.
Anaesthesia 1994;49:597-9.
22. Stack CG, RogersP, Linter SP, Monoamine oxidase
inhibitors and anaesthesia. A review. Br J Anaesth
1988;60:222-7.
23. El Ganzouri AR, Ivankovich AD, Braverman B, Mc Carthy
R. MAOI should they be discontinued preoperatively?
Anaesth Analg.1985;64:592-6.
24. Gregory L, Bryson, Frances Chung Patient selection in
Ambulatory Anaesthesia-An evidence based review Part
11
25. Kotiniemi LH, Ryhanen PT, Valanne J, Jokela R, Mustonen
A, Poukkula E. Postoperative symptoms at home
following day case surgery in children: a multicentre
survey of 551 children. Anaesthesia 1998;52:563-9.
26. Song D, Joshi GP, White PF. Fast track eligibility after
ambulatory anesthesia; a comparison of desflurane,
sevoflurane and propofol. Anaesth Analg 1998;86:267-73.
27. Song D, White PF. Remifentanil as an adjuvant during
desflurane anesthesia facilitates early recovery after
ambulatory surgery. J Clinical Anesth 1999;11:364-7.
28. Song D, Joshi GP, White PF. Titration of volatile
anaesthetic using bispectral index facilitates recovery after
ambulatory anaesthesia. Anesthesiology 1997;87:842-4.
29. Gan TJ, Glass PS, Windsor A, et al. Bispectral index
monitoring allows faster emergence and improved
recovery from propofol , alfentanil, and nitrous oxide
anesthesia :BIS utility study group. Anesthesiology
1997;87: 808-15.
30. Philip BK, Sanden PE, Chung F, et al. Remifentanil
compared with alfentanil for ambulatory surgery using
total intravenous anesthesia. Anaesth Analg
1997,84:515-20.
31. Van Vlymen JM, Fu W, White PF; Use of oropharyngeal
airway as an alternative to the LMA with positive pressure
ventilation. Anesthesiology 1999;90:1306-10.
32. Leach A. Old ideas ,new application Br J Anaesth
1998;81:113-14.
33. Rudkin GE. Local and regional anesthesia in the adult day
surgery patient. Practical Anesthesia and Analgesia for
Day Surgery Oxford: BIOS Scientific
Publishers,1997;207-10.
34. Hampl KF, Heinzmann-Wiedener S,Luginbuehl. Transient
neurologic symptoms after spinal anesthesia.
Anesthesiology 1998;88:629-33.
35. Ligouri GA, Zayes VM, Chisolm MI. Transient neurologic
symptoms after spinal anesthesia with mepivacaine and
lidocaine. Anesthesiology 1999;88:619-23.
36. Pollock JE, Liu SS, Neel JM. Dilution of spinal lidocaine
does not alter the incidence of TNS. Anesthesiology
1999;90:445-50.
37. Hodgson PS, Liu SS. Spinal anesthesia for day surgery.
Tech Reg Anesth.Pain Management 2000;4:3-9.
38. Pawloski J, Sukhari R,Pappas et al. The anesthetic and
recovery profile of two doses (60 and 80mg) of plain
mepivacaine for ambulatory spinal anesthesia. Anaesth
Analg 2000;91:580-4.
39. Vaghadia H, Mc LEOD DH, Mitchell GW et al. Small dose
hypobaric lidocaine –fentanyl spinal for short duration
outpatient laparoscopy. A.randomised comparison with a
conventional dose hyperbaric lidocaine. Anaesth Analg
1997;84:59-64.
40. Song D, Greileich, Tongier K et al. Recovery profiles of
outpatient undergoing unilateral inguinal herniorraphy. A
comparison of the costs and recovery profiles of three
anesthetic techniques. Anaesth Analg 1999;88:S30.
41. Li S, Coloma M, White PF, et al. A comparison of the costs
and recovery profile of three anaesthetic techniques for
ambulatory surgery. Anesthesiology . In press.
42. Sa’ R ego MM, Watcha MF, White PF. The changing role of
monitored anaesthesia care in the ambulatory setting.
Anaesth Analg 1997;85:1020-36.
43. Kehlet H, Postoperative pain relief-What is the issue?
[Editorial] Br J Anaesth 1994;72:387-40.
44. Erikson H, Tenhunen A, Kortilla K: Balanced analgesia
improves recovery and outcome after outpatient tubal
ligation. Acta Anaesth Scand 1996;40:151-5.
45. Michaloliakou C, Chung F, Sharma S. Preoperative
multimodal analgesia facilitates recovery after
ambulatory laparoscopic choleycstectomy. Anaesth Analg
1996;82:44-51.
46. Pavlin DJ, Chen C, Penaloza DA, et al. Pain as a factor
complicating recovery and discharge after ambulatory
surgery. Anaesth Analg 2002;95:627-34.

YEAR BOOK 2006/2007
18
47. Zuurmond WWA, Van Leeuween L. Alfentanil vs
isoflurane for outpatient arthroscopy. Acta Anaesthesiol
Scand 1986;30:329-31.
48. White PF. The role of non opioid analgesic technique in the
management of pain after ambulatory surgery. Anaesth
Analg 2002;94:577-85.
49. Rosenblum M, Weller RS, Conrad PL, et al. Ibuprofen
provides longer lasting analgesia than fentanyl after
laparoscopic surgery. Anaesth.Analg 1991;73:255-9.
50. Raeder JC, Steine S, Vatsgar TT. Oral ibuprofen versus
paracetamol plus codeine for analgesia after ambulatory
surgery. Anaesth Analg 2001;92:1470-2.
51. Rusy LM, Houck CS, Sullivan LJ, et al. A double blind
evaluation of ketorolac versus acetaminophen in
paediatric tonsillectomy: analgesia and bleeding. Anesth
Analg 1995;80:226-9.
52. Korpela R. Konvenoja P, Meretoja OA. Morphine sparing
effect of acetaminophen in paediatric day care surgery.
Anesthesiology 1999;91:442-7.
53. Tverskoy M, Cozacov C Ayache Met al. Postoperative
pain after inguinal herniorapphy with different types of
anaesthesia. Anaesth Analg 1990;70:29-35.
54. Harrison CA, Morris S, Harvey JS. Effect of Ilioinguinal
and Iliohypogastric nerve block and wound infiltration
with 0.5% bupivacaine on postoperative pain after hernia
repair.Br J Anaesth 1994;72:691-3.
55. Ding Y, White PF. Post herniorraphy pain in outpatients
after pre incision Ilioinguinal –hypogastric nerve block
during monitored anesthesia care. Can J Anaesth
1995;42:12-5.
56. Grant SA, Nielsen KC, Greengrass RA, et al. Continuous
peripheral nerve block for ambulatory surgery. Reg
Anesth Pain Med 2001;26:209-14.
57. Illfeld BM, Morey TE, Wang RD, Enneking FK.
Continuous popliteal sciatic nerve block for postoperative
pain control at home. Anesthesiology 2002;97:959-65.
58. White PF, Issoui T, Skrivanek GD, et al .Use of a
continuous popliteal sciatic nerve block for the
management of pain after major paediatric surgery: does
it improve quality of recovery? Anesth Analg
2003;97:1303-9.
59. Smith I, Shiverly RA, White PF. Effect of ketorolac and
bupivacaine on recovery after outpatient arthroscopy.
Anesth Analg 1992;75:208-12.
60. Watcha MF ( 2000 ) The cost effective management of
postoperative nausea and vomiting.
Anesthesiology;92:931-3.
61. Caroll NV, et al ( 1995 ) Postoperative nausea and
vomiting after discharge from outpatient surgery centers.
Anesth Analg;80:903-9.
62. Apfel CC, et al ( 1999 ) A simplified risk score for
predicting postoperative nausea and vomiting:
Conclusion from cross validations between two centers.
Anesthesiology;91:693-700.
63. Hill RP,et al ( 2000 ) Cost effectiveness of prophylactic
antiemetic therapy with ondasetron,droperidol or
placebo. Anesthesiology 92:958-67.
64. Frighetto L, et al, (1999) Cost effectiveness of prophylactic
dolasetron, or droperidol vs. rescue therapy in the
prevention of PONV in ambulatory gynaecologic surgery
.Can J Anaesth;46:536-43.
65. Fortney JT, et al (1998) A comparison of the efficacy, safety
and patient satisfaction of ondasetron versus droperidol
as antiemetic for elective outpatient surgical procedures.
Anesth Analg;86:731-8.
66. Domino KB, et al. (1999) Comparative efficacy and safety
of ondasetron, droperidol and metaclopramide for
preventing nausea and vomiting: a meta analysis. Anesth
Analg;88:1370-9.
67. Sun R et al (1997). The effect of timing ondasetron
administration in outpatients undergoing otolaryngologic
surgery. Anesth Analg;84: 331-6.
68. Henzi I et al ( 2000) Dexamethasone for the prevention of
postoperative nausea and vomiting : a quantitative
systemic review. Anesth Analg;90(1):186-94.
69. Scuderi PE, et al (1999) Antiemetic prophylaxis does not
improve outcomes after outpatient surgery when
compared to symptomatic treatment
.Anesthesiology;90:360-71.
70. Watcha MF, White PF (1999) Postoperative nausea and
vomiting: Prophylaxis vs. treatment. Anesth
Analg;89:1337-9.
71. Tramer MR, et al (1997) A quantitative systemic review of
ondasetron in the treatment of established postoperative
nausea and vomiting. BMJ;314:1088-92
72. Yogendran S et al (1995) A prospective randomized double
–blinded study of the effect of intravenous fluid therapy
on adverse outcomes on outpatient surgery. Anesth
Analg;80:682-6.

19
Field Anaesthesia: A Report of Mercy Malaysia’s Mission 1
to Kashmir following the 2005 South Asia Earthquake
On October 8, 2005 at approximately 8.50 a.m., a
massive earthquake with a magnitude of 7.6 on the
Richter scale struck south Asia, involving three
nations – Pakistan, India and Afghanistan, killing
73,000 people and completely destroying homes,
schools, hospitals and businesses. The epicenter was
located right in the middle of the disputed
mountainous regions along the Pakistani-Indian
border. Faced with the Himalayan terrain and the
coming harsh winter, this natural disaster was set to
become one of the worst humanitarian crises that the
region had ever faced in centuries.
Malaysian Medical Relief Society (MERCY Malaysia)
deployed its first mission to Pakistan within 48 hours of
the incident. It consisted of an orthopaedic surgeon, an
anaesthetist, a physician, a nurse, two logisticians and a
non-medical team leader. MERCY Malaysia Mission
One was part of a multi-organizational Malaysian
Team assembled by the Malaysian Prime Minister.
Other organizations involved included the Special
Malaysian Disaster Relief and Rescue Team (SMART),
Malaysian Red Crescent Society (MRCS) volunteers, as
well as doctors and medical assistants from the
Emergency Department, Hospital Kuala Lumpur.
We first arrived in Islamabad on October 11 after a
grueling 13-hour flight on board the Royal Malaysian
Air Force (RMAF) C-130 Hercules. After liaising with
Pakistani and United Nations (UN) officials,
Muzafarrabad was chosen as our destination. Located
some 20 to 30km from the epicenter, it is the capital of
the State of Azad Kashmir, the Pakistani-controlled
part of the former princely state of Kashmir.
Following the earthquake, the disputing parties in the
area declared a cease-fire to allow swift delivery of
humanitarian aid. We departed by bus from
Islamabad on October 12 and due to hazardous
landslides, were forced to stop overnight in a hill
station called Murree, therefore arriving in
Muzafarrabad only a day later.
In Muzaffarabad, we witnessed the devastation
caused by the earthquake (figure 1). Only then did
we realize the gravity of the disaster. We were
informed by UN officials that all search and rescue
(S&R) operations had been called off, as it was
already into Day 6 after the initial disaster. For our
SMART team, it was a case of ‘not too little, but too
late’.
A field had been converted into a large helipad with
numerous helicopters from the UN, Pakistani and
foreign military, transporting medical and
humanitarian aid together with casualties from
affected areas unaccessible by road. Patients were laid
on a ‘triage’ area near the helipad. The local field
hospital located next to the helipad, run by the
Shahridan Fathil, MBBS (Malaya), FRCA.
Emergency Department, Hospital Universiti Kebangsaan Malaysia (HUKM)
Shalimar Abdullah, BMedSci BM BS M.S.(Ortho)(UKM)
Department of Orthopaedics, Faculty of Medicine, Universiti Kebangsaan Malaysia.
Husyairi Harunarashid, MB BCh BAO (Ireland)
Emergency Department, Hospital Universiti Kebangsaan Malaysia (HUKM)
Dr Shahridan is an Anaesthetic Clinical Specialist at the Emergency Department, HUKM. His special interests include
regional anaesthesia and resuscitative medicine. He has been a volunteer on 3 MERCY missions to date, at Nias, Kashmir and
Jogjakarta.
Dr Shalimar Abdullah is a lecturer and hand/orthopaedic surgeon in HUKM. She is a MERCY exco, and has volunteered on
several missions including the one to Kashmir.
Dr Husyairi Harunarashid is a medical officer at Emergency Department, HUKM.

YEAR BOOK 2006/2007
20
Pakistani military was overwhelmed. Other
non-governmental organizations (NGOs) e.g
Medicins Sans Frontieres (MSF) transferred some of
these patients to their own field hospitals which were
set up elsewhere.
We made ourselves useful by treating patients at the
‘triage’ area whilst waiting for definitive
management. A large number of patients had
sustained spinal cord injury secondary to vertebral
fractures caused by falling debris of ceilings and as a
result, had distended bladders. Others had dirty open
wounds with limb fractures splinted by hastily made
cardboard splints. Treatment for these patients
included bladder cathetherisation, simple surgical
debridement, toilet and suturing, analgesia and
changing of splints.
On October 16, the Malaysian Team was selected to go
on a medical relief and evacuation mission. A
Luftwaffe (German Air Force) Sikorsky CH-53
helicopter transported us to a remote village
inaccessible by road. Within just 4 hours, the team had
treated a total of 60 patients. Approximately 25 of
these patients were treated for minor surgery such as
debridement, toilet and suturing; done mainly under
procedural sedation. More definitive treatment such
as limb amputations and skin grafts were required for
10 patients and we therefore evacuated them.
On October 17, MERCY Mission 1 parted company
with the rest of the Malaysian team, as we felt our
services were very much needed elsewhere. Up to this
point MERCY Mission 2 had been busy providing
surgical services in a field hospital set up by Pakistani
Islamic Medical Association (PIMA) in the
neighboring city of Bagh. Our journey from
Muzaffarabad to Bagh took the whole day, travelling
through treacherous mountain roads littered with
debris and rubble. The earthquake had marred the
breathtaking views of majestic mountain ranges,
beautiful conifer forests and idyllic picturesque
villages.
Bagh literally means garden in Farsi, but it was
certainly no garden when we arrived. It was heavily
damaged with 60% of its buildings collapsed. There
was no water and only intermittent electricity. Moving
masses of people, with belongings, lingered about
looking for safe shelters. The district hospital was
non-functional.
Mercy Malaysia and our local partner operated a total
of 5 tents. We had a field operation theatre (OT), a
clinic, a rudimentary pharmacy, a ward tent crammed
with 20 patients and a small tent containing a basic
sterilization area. Unlucky patients overflowed
outside, sleeping in the open air.
The OT that was set up in a tent is shown in Figure 2.
There were two operating tables but only one Boyle
anaesthesia machine equipped with halothane
vaporizer and very limited oxygen supply. Pulse
oximetry powered by battery was the only monitoring
device available. Over the next 2 days, we treated
approximately 35 patients. The majority of cases were
fractures (both open and closed) and infected wounds.
Mercy Mission 1 and Mission 2 finally left for
Islamabad after two weeks, on October 19.
Subsequent missions, up to Mercy Mission 27,
continued our effort. We had a two day break before
returning to Kuala Lumpur on October 21.
Technique of Anaesthesia and Perioperative
Care
Although we arrived in Bagh approximately 10 days
after the initial earthquake, throngs of patients were
still coming in. Those with major trauma would have
probably succumbed to injuries in the initial few days.
Some patients had to travel long distances, some
Figure 1: Muzaffarabad: Survivors covering their faces
from the stench of decomposing bodies underneath the
rubble

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
21
patients, considering the extent of their wounds. Their
injuries were the result of trauma from collapsed
buildings, as most were not built to withstand
earthquakes. Cases of infected wounds involving the
limbs, scalp and perineum required repeated
debridements (figure 3). Some gangrenous and
severely crushed injuries ended up with amputations.
A few cases of open fractures required external fixators.
Numerous closed fractures required traction or closed
manipulation and reduction(CMR) followed by full
length casting . Open reduction and internal fixation
were not practiced as OT sterility was questionable.
Each morning during the ward rounds, an OT list was
prepared, although this subsequently had continuous
additions of fresh arrivals. We were fortunate to work
with volunteers of Al-Khidmat Foundation who
functioned not only as our nurses and attendants, who
prepared and carried patients, but also as our
interpreters. Preoperative anaesthetic assessment was
limited, and if there was any, usually involved a quick
examination in the OT. No patient was turned away for
‘further optimization’. Consideration had to be given to
the long distance traveled by patients, limited ward
space, increasing number of patients turning up and
limited medical resources. Our aim was to treat each
patient as quickly as possible and allow home
rehabilitation. We were lucky to have radiographs
available. The field hospital had been set up next to a
small private hospital equipped with basic X-ray
facility, which was subsequently abandoned for fear of
aftershocks. This did not seem to deter the brave
radiographers from providing the much needed
investigations.
Blood investigations were unfortunately unavailable.
Fasting time was not an issue, as most patients had
not had a decent meal for the past few days. Despite
that, we were very likely to have anaesthetized a
number of unfasted patients as well.
Although we had a Boyle anaesthetic machine at our
disposal, general anaesthesia with Halothane was
scarcely used due to the very limited availability of
oxygen, volatile anaesthetic and power supply.
During our short stint in Bagh, Mission 1 used
Halothane anaesthesia for only one case, which was a
small toddler with scalp abscess in whom there was
difficulty establishing intravenous (i.v.) access.
Our technique of choice for most cases, was
spontaneous ventilation under iv ketamine
anaesthesia for both induction and maintenance. A
typical induction dose/regime would be iv
midazolam 3 to 5 mg followed by iv ketamine 1 to 1.5
mg/kg. In paediatric patients, ketamine would be the
sole iv anaesthetic used. We did not supplement
anaesthesia with iv atropine, as excessive salivation
was very rarely a problem. Surgical anaesthesia was
achieved within 30 seconds. Patients then breathed
spontaneously on room air. Maintenance was with
intermittent boluses of iv ketamine, usually one
quarter to half the induction dose every 5 to 10
minutes, administered when patients have increased
vocalization or purposeful movements in response to
surgical stimuli. Duration of all operations were less
than an hour.
Figure 3: A child undergoing Ketamine anaesthesia for
surgical debridement.
Figure 2: Field OT in Bagh.

YEAR BOOK 2006/2007
22
Patients tend to maintain their airway very well
under ketamine anaesthesia. Some required some
degree of chin-lift, but none needed oral airway or
intubation. There were no cases of aspiration.
Ketamine and its efficacy and safety in field and
military anaesthesia has been well documented by
Australian civilian and military surgical teams
serving in disaster- stricken areas of Papua New
Guinea, Dili and Banda Aceh.1,2,3
Pulse oximetry was only used during the one case of
Halothane general anaesthesia, because of limited
battery reserve. As there was no other form of
monitoring, we had to resort to intermittent manual
monitoring in the form of palpating the carotid pulse
for pulse rate and volume, and feeling for breath
during chin-lift maneuvers for airway patency and
determination of breath rate.
Intraoperatively, crystalloids in the form of normal
saline 0.9% or Hartmann’s solution were infused
routinely.
Although equipment and local anaesthetic (LA) for
spinal anaesthesia were available, it was not
performed, as we felt it to be too time consuming and
uneconomical considering the amount of time
available and the number of patients. However, we
did perform wrist and femoral blocks. One wrist block
was initially performed under ketamine anaesthesia.
Once the effects of ketamine wore off, the block was
then used for intraoperative anaesthesia. We found
that this technique avoided delays whilst waiting for
the regional block to set in. Femoral block using
perivascular technique was also used for intra and
postoperative analgesia.
All patients with infected wounds were given i.v.
antibiotics and tetanus prophylaxis. As the pharmacy
was well stocked with locally produced
cephalosporins, broad spectrum cephalosporins such
as cefuroxime or ceftriaxone were given.
Following the surgical procedure, patients were then
sent to the ward immediately for recovery. In the case
of the child who received Halothane anaesthesia, he
was monitored in OT until he showed signs of waking
up. There was neither space nor staff to run a recovery
area.
Postoperative requirements of opiates were minimal.
Undoubtedly, oligoanalgesia was rampant, although
none of the patients complained of pain.
Discussion
Based on our limited experience and other well
published experiences of Australian surgical teams,
ketamine appears to be the anaesthetic agent of choice
for disaster situations.1, 2, 3 Its positive points include
airway preservation,5,6 stimulation of the
cardiovascular system,6 minimal need for complex
equipment e.g. Boyle anaesthetic machine or oxygen
supply,4 minimal need for recovery ward5 and
reduced need for administration by trained
anaesthetists.5,10 The unpleasant psychogenic
side-effects were not seen in our patients even for
those undergoing repeated procedures. Pleasant
dreams have instead been described in patients from
the Banda Aceh experience.1
Ketamine appears ideal for superficial and deep
surgery e.g. wound debridement.1,3 but is not the
anaesthetic of choice for surgery involving body
cavities i.e. intraabdominal operations and burr-hole
procedures in the Papua New Guinea experience.3 It is
safe and effective for children undergoing painful or
disturbing procedures. For this group of patients, the
i.m. route is a valid alternative to the i.v. route. The
optimal i.m. dose of ketamine for procedural sedation
in children was determined to be 4 to 5 mg/kg.12
There is, however, yet to be a prospective randomised
control study to validate this premise.
The safety and efficacy of regional techniques in field
anaesthesia was demonstrated by the Regional
Anaesthesia Section at Walter Reed Army Medical
Center during a deployment in Burkina Faso.7 In their
series, 110 out of 118 surgical procedures were
conducted under regional anaesthesia. The
commonest technique was central neural blockade.
Other techniques used were LA infiltration, thoracic
paravetebral block, brachial plexus blocks, lumbar
and sacral plexus blocks. The authors emphasized on
the importance of intensive regional anaesthesia
training to ensure the success of regional blocks in
austere environments. Continuous lumbar plexus and
sciatic nerve blocks for anaesthesia and analgesia
have been successfully used in an American soldier

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
23
during the 2nd invasion of Iraq (the authors used the
name ‘Operation Iraqi Freedom’).8
The use of volatile agents is still applicable in field
anaesthesia, albeit only in body-cavity surgeries. We
were fortunate to have a Boyle anaesthetic machine on
loan by a private hospital. In reality, however, it is a
logistical nightmare to transport the machine to a
distant place. Other more portable and versatile
options have been described in the literature. The
ULCO Portable Field Anaesthesia Machine which
weighs only 32 kg when fully loaded,9 was used by
the Australian Defence Force (ADF).3 It can be used in
both drawover and plenum modes.9 The Triservice
Apparatus (TSA) which is essentially two Oxford
Miniature Vaporisers (OMV) connected in series13 can
only function as a drawover device but is favoured by
the British military.10 Drawover systems require much
less oxygen when compared to plenum systems.
Another example of a drawover system is Ohmeda
Universal PAC drawover apparatus,14 which has also
been used in combinations with other anaesthetic
circuits in the field.
Total intravenous anaesthesia using target-controlled
infusion of Propofol has also been used by the ADF in
Dili.11
Oxygen supply is a precious commodity in disaster
areas. Oxygen concentrators, producing 3-4 L/min of
90 – 95% oxygen were used by the ADF successfully.12
Monitoring of patients in the field should ideally
include all minimum monitoring standards i.e
electrocardiogram, pulse oxymetry, non-invasive
blood pressure and capnometer. New portable devices
that are available commercially include finger pulse
oxymeter, portable gas analyzer, hand-held
capnometer and compact combined pulse
oxymeter/capnometer robust enough for different
environments.12
Patients at risk for aspiration undergoing volatile
anaesthesia should undergo rapid sequence
intubation with cricoid pressure to minimize the risk
of aspiration. The Laryngeal Mask Airway (LMA) was
extensively used in wound debridement procedures
under general anaesthesia by the ADF in Papua New
Guinea.2
Conclusions
Volunteerism is clearly not for everyone. Unfavorable
living conditions, appalling toilets, psychological
trauma, concern for personal safety and unfamiliar
food affected everyone in our team, one way or the
other. Courage, compassion, humility, hardiness and
flexibility are among the traits that volunteers should
have. Different people volunteer for different reasons
but most enjoy the experience and keep on
volunteering.
MERCY Malaysia has always been dependent on local
partners in delivering emergency medical help to
disaster areas. The experience gained from this South
Asia earthquake medical relief work has exposed its
volunteers to field surgery and anaesthesia. During
the writing of this article, MERCY Malaysia is setting
up an Emergency Response Unit (ERU) capable of
being an independent surgical and medical unit.
The provision of field anaesthesia presents unique
challenges not often seen in hospital-based practice.
Poorly prepared patients may require life-saving
surgeries under austere conditions. From our limited
experience after the South Asia earthquake, we’ve
found that most surgery conducted under these
conditions was superficial in nature. Intravenous
ketamine was the anaesthetic agent of choice in most
instances.

YEAR BOOK 2006/2007
24
References
1. Paix BR, Capps R, Neumeister G, Semples. Anaesthesia in
a Disaster Zone: A Report on the Experience of an
Australian Medical Team in Banda Aceh Following the
‘Boxing Day Tsunami”. Anaesth Intensive Care
2005;33:629-634
2. Taylor RP, Emonson DI, Schlimmer JE. Operation
Shaddock—the Australian Defence Force response to the
tsunami disaster in Papua New Guinea. Med J Aust
1998;169:606-609
3. Bradley JP, Lee D. Asia Pacific Forum: Anaesthesia in the
United Nations Military Hospital, Dili, East Timor.
Anaesth Intesive Care 2001;29: 527-529
4. Dobson MB. Anaesthesia for difficult
locations-developing countries and military conflicts. In:
Prys-Roberts C, Brown Burnell R Jr, eds International
Practice of Anaesthesia Vol 2 pp1- 10
5. King M. Primary Anaesthesia. Oxford University Press,
1990; pp60.
6. Morgan GE, Mikhail MS. (eds) Nonvolatile Anaesthetic
Agents. In:Clinical Anesthesiology. Appleton and Lange,
1999, pp141
7. Buckenmaier CC, Lee EH, Shields CH, Sampson, Chiles
JH. Regional Anaesthesia in Austere Environments. Reg
Anesth Pain Med 2003:28, 321-327
8. Buckenmaier CC,.McKnight GM, Winkley JV, Bleckner,
Shannon C, Klein MK, Lyons RC, Chiles JH. Continous
Peripheral Nerve Block for Battlefield Anaesthesia and
Evacuation. Reg Anaest Pain Med 2005;30: 202-205
9. Perndt HKS. The ULCO Anaesthesia Suitcase. Anaest
Intensive Care 2002;30: 800-803
10. Mellor AJ. Anaesthesia in Austere Environtments. J R
Army Med Corps 2005;5: 272-276
11. Harding JN, Wilson M.Use of Target-Controlled Infusion
of Propofol for Military Field Anaesthesia. ADF Health
2003;4:23-26.
12. Tang KC, Chiu JW, Low E. Airway and Ventilatory
Equipment in Field Anaesthesia: What’s New? Military
Med 2004;169:342-349
13. Green SM et al. What is the optimal dose of intramuscular
ketamine for pediatric sedation? Acad Emerg Med
1999;6:21-26
14. Houghton IT. The Triservice anaesthetic apparatus.
Anaesthesia 1981; 36:1094-108
15. Lunn DV. The Ohmeda Universal PAC drawover
apparatus. A Technical and clinical evaluation.
Anaesthesia 1995;50(10): 870-874

25
Prevention and Management of Hypotension
during Regional Anaesthesia for Caesarean Section
Introduction
Audit studies on anaesthesia-related maternal
mortality worldwide have repeatedly emphasised
that the risk of mortality is higher with general
anaesthesia (GA) compared to regional anaesthesia
(RA).1,2 As such, it is strongly recommended that
caesarean section (CS) should be performed under
regional anaesthesia unless specifically
contraindicated. Regional anaesthetic techniques for
CS include single-shot spinal, combined
spinal-epidural (CSE) and epidural anaesthesia.
Single-shot spinal anaesthesia is often the RA
technique of choice because of its rapid, reliable and
profound sensory and motor blockade. However,
maternal hypotension is the most frequent
complication of this technique; the incidence of
spinal-induced hypotension is reported to be in the
range of 40-85%.3 Hypotension often results in
unpleasant maternal symptoms such as nausea,
vomiting and light-headedness. There is a distinct
association of intraoperative nausea and vomiting
with maternal hypotension, and strict control of blood
pressure can dramatically reduce emetic symptoms.4
When hypotension is severe and sustained (systolic
BP < 80 mmHg greater than 4 min duration),
uteroplacental perfusion may be jeopardized resulting
in fetal acidosis and neonatal depression. Several
strategies are currently used to prevent or minimize
hypotension but there is no established ideal
technique.
In a meta-analysis by Reynolds,5 it was noted that
there was a significant reduction in neonatal umbilical
cord blood pH following CS under spinal anaesthesia
than either epidural or general anaesthesia. This could
be secondary to hypotension associated with spinal
anaesthesia, or a side-effect of ephedrine used in its
treatment or prevention. They also noted that routine
co-administration of phenylephrine with ephedrine is
associated with higher umbilical arterial and venous
pHs, and with less fetal acidosis, than when
ephedrine is used alone. However, the authors
concluded that the differences observed, though
significant, were not large; and that in many instances
the advantages of spinal anaesthesia outweighed the
concerns regarding funic pH and base deficit.
Haemodynamic consequences of spinal anaesthesia
are manifold. Sympathetic blockade induces
reductions in systemic vascular resistance (SVR),
venous return, stroke volume, cardiac output and
blood pressure.6 Regional perfusion is altered by
shunting of blood into the mesenteric bed, which may
result in decreased uteroplacental blood flow. When
the block extends above T4, the cardiac sympathetic
nerves are affected, resulting in hypotension and
bradycardia.
Prevention of Spinal-induced Hypotension
Suggested prophylactic measures against
spinal-induced hypotension include recognition and
modification of factors affecting outcome of spinal
anaesthesia, measures to increase central blood
volume (positioning, leg compression, fluid preload),
and the use of vasopressors, either singly or in
combination. However, as stated in a recently
published Cochrane Collaboration Systematic
Review, no intervention reliably prevents hypotension
during spinal anaesthesia for caesarean section.7
Furthermore, prophylactic management has been
associated with side-effects – large volumes of
intravenous fluids increase the risk of iatrogenic
pulmonary oedema in high risk pregnant patients,
prophylactic vasopressors can cause hypertension
and prophylactic ephedrine has been associated with
fetal acidosis.8
Lee Choon Yee, MBBS (Malaya), MMed (Anaes) UKM, FANZCA, FAMM.
Department of Anaesthesiology & Intensive Care, Faculty of Medicine, Universiti Kebangsaan Malaysia.
Professor Lee Choon Yee is a Clinical Professor and Consultant Anaesthesiologist at Universiti Kebangsaan Malaysia. Well
known for her book Manual of Anaesthesia, she has special interests in Obstetric Anaesthesia & Analgesia and Airway Manage-
ment.

YEAR BOOK 2006/2007
26
a) Factors Affecting Outcome of Spinal
Anaesthesia
Many different factors may influence the
outcome of spinal anaesthesia in terms of
sensorimotor blockade and haemodynamic
consequences. Factors such as the amount of local
anaesthetic injected, baricity and temperature of
the local anaesthetic solution,9-12 positioning of the
patient during 13-14 and after 15-17 spinal injection,
and the speed of injection,18-19 are expected to be
of importance in the development of hypotension
following spinal blockade.
In an in vitro study on a spinal canal model, Lui
concluded that baricity was an important
determinant of local anaesthetic distribution in the
subarachnoid space.11 Hallworth investigated the
effect of posture and baricity on the spread of
intrathecal bupivacaine for elective CS and found
that hypotension incidence and ephedrine use
increased with decreasing baricity, with the
hypobaric sitting position having the most
frequent incidence of hypotension (76%) as well as
cervical blocks (24%).12
Inglis compared the right lateral with the sitting
position during induction of spinal anaesthesia,
and found that the incidence of hypotension was
higher in the lateral group.13 The Oxford position
(full lateral with shoulder elevation), first
described by Carrie,20 was shown to be associated
with a slower onset of the spinal block, more stable
blood pressure, less ephedrine use, a more
predictable final block height and later
requirement for postoperative analgesia compared
to the sitting position.21
The speed of intrathecal injection may be
important, as it was noted that slow injection (2
ml/min) significantly reduced incidence (68%
versus 92% control) and severity of hypotension.19
However, in a much earlier study, Bucx did not
find clinically relevant influence on the maximum
level of sensory blockade when 0.5% bupivacaine
at room temperature was injected with a ten-fold
difference in speed.18 The incidence of
hypotension was not investigated in Bucx’s study.
The addition of various doses of different
intrathecal opioids may allow reduction in the
b) Central blood volume expansion
Methods used to for central blood volume
expansion include patient positioning, leg
compression, and intravenous fluid
administration.
i)
local anaesthetic dose, with an equivalent success
rate and less severe side-effects such as
hypotension, nausea and vomiting, and
prolonged motor blockade.22 Ben-David reported
that bupivacaine 5 mg with fentanyl 25 µg
provided adequate surgical anaesthesia with less
hypotension, vasopressor requirements, and
nausea than bupivacaine 10 mg.23
In terms of central neuraxial block technique, Goy
reported that subarachnoid block induced by CSE
produced greater sensorimotor anaesthesia and
prolonged recovery compared with single shot
spinal technique, with a greater incidence of
hypotension and vasopressor use despite using
identical doses and baricity of local anaesthetic.24
The low dose sequential CSE technique, with a
small intrathecal dose topped up via the epidural
route if required, is another method to reduce the
likelihood of hypotension. This technique has
been successfully utilized in the anaesthetic
management of patients with significant cardiac
disease for CS.25
Positioning
One should be meticulous in making sure that
left uterine displacement is properly instituted
in order to avoid aortocaval compression. This
entails some degree of left pelvic tilt, in the form
of 15° left lateral tilt as advocated by
Crawford,26 or the supine wedged position
(wedge placed under the right hip), or mainte-
nance of full lateral position until the moment of
skin preparation. Rees studied the effects of
positioning following initiation of spinal anaes-
thesia for CS, and recommended the use of the
lateral position rather than tilt for elective cases
because aortic compression was more
pronounced in the tilt position.15 However,
block onset was found to be quicker when the
patient was turned directly to the tilt position
and hence would be advantageous in urgent
Caesarean delivery.16 In another study using
CSE for CS, Mendonca found that early

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
27
hypotension was less frequent and was easier to
treat when the patients were placed in the full
left lateral position compared with the tilted
supine position.17
It must be noted that the supine tilted position
may be less than Crawford’s recommendation
of 15°, due to unreliable estimation of the degree
of tilt.27 This is an important finding as lesser
degrees of tilt are associated with residual
inferior vena cava compression, and it could
make anaesthetists discount inadequate tilt as a
cause of hypotension or collapse in a pregnant
woman. Indeed Crawford’s recommendation
might seem rather empirical, as aortocaval
compression has even been demonstrated with
up to 34° of lateral tilt.28
Leg compression
Leg compression is a mechanical means of
central blood volume expansion. Various
methods have been described, such as leg
wrapping with Esmarch bandage,
anti-thromboembolic stockings, inflatable boots
or splints, and leg elevation while tilting the OT
table head down. Rout regarded the use of leg
compression immediately post-spinal as a
simple means of reducing the accompanying
hypotension and advocated its wider usage.29
In a systematic review on the effects of an
increase of central blood volume before spinal
anaesthesia for CS, Morgan noted that leg
wrapping and anti-thromboembolic stockings
decreased the incidence of hypotension
compared with leg elevation or control.30
Intravenous fluids
The use of intravenous fluid as volume preload
prior to subarachnoid block is an established
part of anaesthetic practice. Intravenous fluid
preloading is thought to minimize severity of
hypotension and reduce vasopressor
requirements by expanding the central blood
volume. In addition, it may result in reduction
of red blood cell loss by haemodilution.
However, there are wide variations in the type,
amount, speed, and timing of intravenous fluid
administration. Routine fluid preload consists
of 15-20 ml/kg Ringer’s lactate over 20 min
before the subarachnoid block. In a survey of
practice among the anaesthetists in the UK, the
fluid chosen by 83.3% of the preloaders was
Hartmann’s solution and the usual volume was
1000 ml.31 However, the incidence of
hypotension remains disappointingly at 40%
even with fluids.30
The use of colloids has also been advocated,
ranging from a combination of 6% hetastarch &
Ringer’s lactate, 10% hydroxyethyl starch, and
gelatin solution. Problems associated with
colloid solutions, namely cost, risks of fluid
overload, anaphylactoid reactions and
coagulopathy should be taken into
consideration. In the same systematic review,
Morgan found that crystalloid preload was
inconsistent in preventing hypotension,
whereas colloid appeared to be effective in all
but one study.30
The timing of fluid administration has also been
investigated, and rapid crystalloid loading
appears more effective when delayed until
intrathecal injection and then very quickly
infused – a “coload” rather than preload. Dyer
found that requirement for vasopressor therapy
was reduced in the coload group, and may be
advantageous in terms of managing maternal
blood pressure prior to delivery.32 It certainly
seems more logical to give a fluid load during
the onset of vasodilation rather than before.
There is a confusing array of choices and
preferences for vasopressors, such as the use of
ephedrine versus α-adrenergic agonists, single
versus combination therapy, and prophylactic
versus therapeutic use. Similarly, the route of
administration (intramuscular, intravenous bolus
or intravenous infusion) and the dose (bolus doses
or infusion) are many and varied. In the UK
survey conducted in 1999, ephedrine was the sole
vasopressor used by 95.2% of the respondents.31
This is likely to change with the increasing
popularity and widespread use of α-adrenergic
agonists, phenylephrine in particular.
Ayorinde evaluated pre-emptive intramuscular
ii)
iii)
c) Vasopressor Prophylaxis

YEAR BOOK 2006/2007
28
phenylephrine and ephedrine for reduction of
spinal anaesthesia-induced hypotension during
CS.33 He found that pre-emptive IM
phenylephrine 4 mg and ephedrine 45 mg
reduced the severity of hypotension and the total
dose of rescue IV ephedrine used. However, the
use of intramuscular injection for rescue therapy
is becoming less popular in view of its
unpredictable systemic absorption and peak
effect, and the possibility of rebound
hypertension.
Prophylactic administration of vasopressors has
been recommended as a proactive rather than
reactive step, as placental hypoperfusion may
occur before maternal hypotension is manifest.
Vasopressor prophylaxis aims to reduce the
incidence and severity of hypotension, as well as
the total dose of rescue vasopressor therapy.
However, it may result in problems of its own,
such as over-treatment with reactive
hypertension, tachyphylaxis to ephedrine, and
maternal bradycardia associated with
phenylephrine. In addition, the vast majority of
patients who develop hypotension respond to
therapy with bolus doses of vasopressor. The
safety and efficacy of vasopressor prophylaxis
should be established before it could be
embarked upon as a standard practice.
Choice of Vasopressors
Historically, ephedrine has been regarded as the
vasopressor of choice in obstetric anaesthesia.
Ralston34 showed that, in gravid ewes, ephedrine
was more effective for increasing arterial BP with
better preservation of uteroplacental blood flow
compared with other vasopressors. In contrast,
α-adrenergic agonists increased uterine vascular
resistance and thus reduced uteroplacental blood
flow – reduction by 45% in metaraminol and 62% in
methoxamine. This finding was reiterated by
McGrath, who experimented on ewes receiving
ritodrine infusion and found that ephedrine
increased uterine blood flow while phenylephrine
increased uterine vascular resistance.35 However, it
is doubtful whether such experiments conducted on
sheep could be extrapolated to humans because of
species difference. In addition, the sheep were not
under regional anaesthesia and were not placed in
supine position with left lateral tilt (as in Caesarean
delivery). Furthermore, the test drug was
administered to increase BP by 50% instead of being
used as treatment for hypotension.
Interest in phenylephrine in obstetric anaesthesia
was rekindled by Ramanathan, who compared
ephedrine with phenylephrine during epidural
anaesthesia for CS.36 He concluded that bolus doses
of phenylephrine 100 μg provided an adequate
perfusion pressure with similar maternal and fetal
outcomes to ephedrine group, and that an α-agent
such as phenylephrine did not cause fetal acidosis
when used for treating maternal hypotension.
Following this, there was an increasing use of
α-agonists and other vasopressors such as
phenylephrine, methoxamine, metaraminol,
adrenaline, dopamine, paredrine, mephentermine,
vasopressin and angiotensin II.
In the 1990s, the status of ephedrine as the
vasopressor of choice in obstetric anaesthesia has
been increasingly questioned. Being a combined α-
and β-adrenergic receptor agonist, ephedrine has less
effect on SVR and venous capacitance vessels
compared to a pure α-agonist, and the cardiovascular
system remains vasodilated and relatively
under-filled. Blood pressure is maintained by
β-mediated increases in myocardial contractility,
heart rate and cardiac output to offset decreases in
SVR, hence the development of unwanted maternal
tachycardia as a side-effect of ephedrine
administration.3 It is also difficult to titrate, has a
relatively slow onset and long duration of action,
and may demonstrate tachyphylaxis during which
large doses are frequently required. The incidence of
nausea and vomiting is significantly higher than
phenylephrine despite similar BP control.4
Ephedrine also readily crosses the placenta and may
increase fetal metabolic rate secondary to
ß-adrenergic stimulation; it may even result in fetal
acidosis from direct fetal effects.8
In contrast, phenylephrine, being a pure α-agonist,
increases preload by vasoconstriction. It
demonstrates a selective vasoconstrictive effect on
mesenteric bed than on uteroplacental vasculature
and may in fact improve uteroplacental perfusion
and fetal acid-base status.3 Reflex bradycardia occurs

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
29
in up to 20% of patients receiving phenylephrine. It
is aggravated by sympathetic denervation in high
block but is often well-tolerated, transient, and
responsive to treatment with atropine or
glycopyrrolate.
Lee et al 3 7 performed a systematic review of
randomized controlled trials on ephedrine versus
phenylephrine for the management of hypotension
during spinal anaesthesia for CS. They found no
difference in efficacy of management (prevention
and treatment) of maternal hypotension in both
groups. Phenylephrine was associated with a
higher incidence of maternal bradycardia and
higher umbilical arterial pH values. However, there
were no differences in the incidence of true fetal
acidosis (umbilical arterial pH < 7.2) or Apgar score
of < 7 at 1 and 5 min. They found no support for the
traditional idea of ephedrine as the vasopressor of
choice for the management of maternal
hypotension, thus its routine use could not be
recommended.
The use of prophylactic ephedrine for the
prevention of hypotension during spinal anesthesia
for elective CS was also reviewed by Lee et al.8 They
found that the efficacy of ephedrine for preventing
hypotension was small. The use of larger doses of
ephedrine (>14 mg) did not eliminate hypotension
but caused reactive hypertension and a minor
decrease in umbilical arterial pH. As in the
previous systematic review, they concluded that
prophylactic IV ephedrine could not be
recommended.
In the literature, various regimes of vasopressor
prophylaxis and rescue therapy have been studied
and advocated. Examples include prophylactic
phenylephrine infusion 100 µg/min and rescue IV
ephedrine bolus or phenylephrine infusion; and
prophylactic infusion of 2 mg/min ephedrine with
10 µg/min phenylephrine and rescue ephedrine
bolus of 6 mg.
In a study on phenylephrine prophylaxis, Ngan
Kee38 compared the use of phenylephrine infusion
at 100 µg/min for 3 min immediately after
intrathecal injection, then at 100 µg/min when
systolic BP was less than baseline. This was,
compared to controls of IV bolus 100 µg when
SBP was less than 80% baseline. He found that
phenylephrine prophylaxis resulted in significantly
lower incidence (23% versus 88%) and magnitude
of hypotension, higher total phenylephrine dose
and similar fetal outcome in terms of umbilical cord
blood gases and Apgar scores.
In another study by the same author 39 to compare
phenylephrine infusion regimens for maintaining
maternal blood pressure during spinal anaesthesia
for CS; phenylephrine infusion of 100 µg/min was
administered for 2 min immediately after
intrathecal injection, then at 100 µg/min to
maintain systolic BP at either 100%, 90% or 80% of
baseline. It was found that titration of
phenylephrine to maintain SBP at 100% of baseline
achieved the best outcome with the lowest episodes
of hypotension, the lowest incidence of nausea and
vomiting, and the highest umbilical artery pH.
Word of Caution
It has been demonstrated that extrapolation of
results from animal studies to humans can be
fraught with uncertainties, due to species
differences in α- and ß-adrenergic receptor, and
differences in vascular responses to vasopressors.
In addition, many of these randomized controlled
trials are conducted on healthy non-labouring
parturients with term, low risk fetuses for elective
CS. Question marks must be raised when dealing
with less than healthy mothers, labouring mothers,
fetuses at risk (intrauterine growth retardation,
preterm, fetal distress) and CS done under
emergency situations. Erkinaro demonstrated that
in a chronic sheep model of increased placental
vascular resistance, phenylephrine impaired
uterine and placental haemodynamics and
increased fetal lactate concentrations.40 Datta
compared healthy with diabetic parturients and
showed that while healthy mothers had a slight
decrease in umbilical arterial pH following
transient hypotension under spinal anaesthesia,
diabetic mothers had clinically significant
reductions in umbilical arterial pH following
similar degrees of hypotension.41

YEAR BOOK 2006/2007
30
Summary
There is a lack of efficacy of individual modalities in
preventing spinal anaesthesia-induced hypotension,
and a single perfect antidote for prevention and
treatment of maternal hypotension may never be
found. A multimodal approach, including fluid
preloading and prophylactic vasopressor use, may
represent the optimal approach. The position of
ephedrine as the vasopressor of choice in obstetric
anaesthesia has been challenged, and the use of pure
α-agonist such as phenylephrine may be more
advantageous. As long as hypotension is transient,
the choice of vasopressor should depend on the
clinical situation, considering not only the blood
pressure but the heart rate as well.42 As Riley
suggested in an editorial, “Spinal anaesthesia for
Caesarean delivery: keep the pressure up and don’t
spare the vasoconstrictors”.43
References
1. Why mothers die. Report on confidential enquiries into
maternal deaths in the United Kingdom 2000-2002.
London; 2004.
2. Hawkins JL, Koonin LM, Palmer SK, Gibbs CP.
Anesthesia-related deaths during obstetric delivery in the
United States, 1979-1990. Anesthesiology 1997;86:277.
3. McKinlay J, Lyons G. Obstetric neuraxial anaesthesia:
which pressor agents should we be using? Int J Obstet
Anesth 2002;11;117-21.
4. Balki M, Carvalho JCA. Intraoperative nausea and
vomiting during cesarean section under regional
anesthesia. Int J Obstet Anesth 2005;14:230-41.
5. Reynolds F, Seed PT. Anaesthesia for caesarean section
and neonatal acid-base status: a meta-analysis.
Anaesthesia 2005;60:636-53.
6. Mark JB, Steele SM. Cardiovascular effects of spinal
anesthesia. Intern Anesth Clin 1989;27:31-9.
7. Emmett RS, Cyna AM, Andrew M, Simmons SW.
Techniques for preventing hypotension during spinal
anaesthesia for caesarean section. Cochrane Pregnancy
and Childbirth Group Cochrane Database of Syst Rev
2006;3.
8. Lee A, Ngan Kee WD, Gin T. Prophylactic ephedrine
prevents hypotension during spinal anesthesia for
Cesarean delivery but does not improve neonatal
outcome. Can J Anesth 2002;49:588-99.
9. Heller AR, Zimmermann K, Seele K, Rossel T, Koch T, Litz
RJ. Modifying the baricity of local anesthetics for spinal
anesthesia by temperature adjustment – model
calculations. Anesthesiology 2006;105:346-53.
10. Horlocker TT, Wedel DJ. Density, specific gravity, and
baricity of spinal anesthetic solutions at body
temperature. Aneth Analg 1993;76:1015-8.
11. Lui ACP, Munhall RJ, Winnie AP, Selander D. Baricity and
the distribution of lidocaine in a spinal canal model. Can J
Anaesth 1991;38:522-6.
12. Hallworth SP, Fernando R, Columb MO, Stocks GM. The
effect of posture and baricity on the spread of intrathecal
bupivacaine for elective cesarean delivery. Anesth Analg
2005;100:1159-65.
13. Inglis A. Daniel M. McGrady E. Maternal position during
induction of spinal anaesthesia for caesarean section. A
comparison of right lateral and sitting positions.
Anaesthesia 1995;50:363-5.
14. Russell IF. Effect of posture during the induction of
subarachnoid analgesia for caesarean section. Right v. left
lateral. Br J Anaesth 1987;59:342-6.
15. Rees SGO, Thurlow JA, Gardner IC, Scrutton MJL,
Kinsella SM. Maternal cardiovascular consequences of
positioning after spinal anaesthesia for Caesarean section:
left 15o table tilt vs. left lateral. Anaesthesia 2002;57:15-20.
16. Hartley H, Seed PT, Ashworth H, Kubli M, O’Sullivan G,
Reynolds F. Effect of lateral versus supine wedged
position on development of spinal blockade and
hypotension. Int J Obstet Anaesth 2001;10:182-8.
17. Mendonca C, Griffiths J, Ateleanu B, Collis RE.
Hypotension following combined spinal-epidural
anaesthesia for Caesarean section. Left lateral position vs.
tilted supine position. Anaesthesia 2003;58:428-31.
18. Bucx MJ, Kroon JW, Stienstra R. Effect of speed of injection
on the maximal sensory level for spinal anesthesia using
plain bupivacaine 0.5% at room temperature. Reg Anesth
1993;18:326-7.
19. Simon L, Boulay G, Ziane AF, et al. Effect of injection rate
on hypotension associated with spinal anesthesia for
cesarean section. Int J Obstet Anesth 2000;9:10-4.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
31
20. Carrie LES. Spinal and/or epidural blockade for
Caesarean section. In: Reynolds F, ed. Epidural and Spinal
Blockade in Obstetrics. London: Bailliere Tindall, 1990;
139-50.
21. Stoneham MD, Eldridge J, Popat M, Russell R. Oxford
positioning technique improves haemodynamic stability
and predictability of block height of spinal anaesthesia for
elective caesarean section. Int J Obstet Anaesth
1999;8:242-8.
22. Dyer RA, Joubert IA. Low-dose spinal anaesthesia for
Caesarean section. Curr Opin Anaesthesiol 2004;17:301-8.
23. Ben-David B, Miller G, Gavriel R, Gurevitch A. low-dose
bupivacaine-fentanyl spinal anesthesia for cesarean
delivery. Reg Anesth Pain Med 2000;25:235-9.
24. Goy RWL, Sia ATH. Sensorimotor anesthesia and
hypotension after subarachnoid block: combined
spinal-epidural versus single-shot spinal technique.
Anesth Analg 2004;98:491-6.
25. Hamlyn EL, Douglass CA, Plaat F, Crowhurst JA, Stocks
GM. Low-dose sequential combined spinal-epidural: an
anaesthetic technique for caesarean section in patients
with significant cardiac disease. Int J Obstet Anesth
2005;14:355-61.
26. Crawford JS. Principles and practice of obstetric
anaesthesia. 5th Ed. Oxford: Blackwell Scientific, 1984:
286-7.
27. Jones SJ, Kinsella SM, Donald FA. Comparison of
measured and estimated angles of table tilt at Caesarean
section. Br J Anaesth 2003;90:86-7.
28. Kinsella SM, Whitwam JG, Spencer JAD. Aortic
compression by the uterus: identification with the
Finapress digital arterial pressure instrument. Br J Obstet
Gynaecol 1990;97:700-5.
29. Rout CC, Rocke DA, Gouws E. Leg elevation and
wrapping in the prevention of hypotension following
spinal anaesthesia for elective caesarean section.
Anaesthesia 1993;48:304-8.
30. Morgan PJ, Halpern SH, Tarshis J. The effects of an
increase of central blood volume before spinal anesthesia
for cesarean delivery: a qualitative systematic review.
Anesth Analg 2001;92:997-1005.
31. Burns SM, Cowan CM, Wilkes RG. Prevention and
management of hypotension during spinal anaesthesia
for elective Caesarean section: a survey of practice.
Anaesthesia 2001;56:794-8.
32. Dyer RA, Farina Z, Joubert IA, et al. Crystalloid preload
versus rapid crystalloid administration after induction of
spinal anaesthesia (coload) for elective caesarean section.
Anaesth Intens Care 2004;32:351-7.
33. Ayorinde BT, Buczkowski P, Brown J, et al. Evaluation of
pre-emptive intramuscular phenylephrine and ephedrine
for reduction of spinal anaesthesia-induced hypotension
during Caesarean section. Br J Anaesth 2001;86:372-6.
34. Ralston DH, Shnider SM, DeLorimier AA. Effects of
equipotent ephedrine, metaraminol, mephentermine, and
methoxamine on uterine blood flow in the pregnant ewe.
Anesthesiology 1974;40:354–70.
35. McGrath JM, Chestnut DH, Vincent RD, et al. Ephedrine
remains the vasopressor of choice for treatment of
hypotension during ritodrine infusion and epidural
anesthesia. Anesthesiology 1994;80:1073-81.
36. Ramanathan S, Grant GJ. Vasopressor therapy for
hypotension due to epidural anesthesia for caesarean
section. Acta Anaesthesiol Scand 1988;32:559-65.
37. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic
review of randomized controlled trials of ephedrine
versus phenylephrine for the management of hypotension
during spinal anesthesia for cesarean delivery. Anesth
Analg 2002;94:920-6.
38. Ngan Kee WD, Khaw KS, Ng FF. Lee BB. Prophylactic
phenylephrine infusion for preventing hypotension
during spinal anesthesia for cesarean delivery. Anesth
Analg 2004; 98:815-21.
39. Ngan Kee WD, Khaw KS, Ng FF. Comparison of
phenylephrine infusion regimens for maintaining
maternal blood pressure during spinal anaesthesia for
Caesarean section. Br J Anaesth 2004;92:469-74.
40. Erkinaro T, Kavasmaa T, Pakkila M, Acharya G,
Makikallio K, Alahuhta S, Rasanen J. Ephedrine and
phenylephrine for the treatment of maternal hypotension
in a chronic sheep model of increased placental vascular
resistance. Br J Anaesth 2006;96:231-7.
41. Datta S, Brown WU Jr. Acid-base status in diabetic
mothers and their infants following general or spinal
anesthesia for cesarean section. Anesthesiology
1977;47:272-6.
42. Vallejo MC, Ramanathan S. Should α-agonists be used as
first line management of spinal hypotension? (Editorial)
Int J Obstet Anaesth 2003;12:243-5.
43. Riley ET. Spinal anaesthesia for Caesarean delivery: keep
the pressure up and don’t spare the vasoconstrictors.
(Editorial) Br J Anaesth 2004;92:459-61.

Introduction
Medical simulation is an exercise designed to mimic a
real life situation in which the learner is given an
opportunity to reason through a clinical problem and
make diagnostic and treatment decisions in real time
without fear of patient compromise. It also refers to the
artificial representation of a complex real-world
process with sufficient fidelity to achieve a particular
objective, either for the purposes of training or
performance testing.
Simulator refers to a computerized mannikin with a
realistic cardiopulmonary system that interfaces with
standard equipment (monitors, intubation supplies,
etc.). High fidelity physiology and pharmacology
programs control the mannikin and mimic human
responses. It even has a “voice” to provide realistic
patient encounters.
The introduction of high fidelity simulation and its
associated training program into the medical training
has made an impact on safety aspects of patient health
care, especially in anaesthesiology.1
History
While simulation has been practiced from the early
times (as in the rehearsal of animal hunting activities or
preparing for warfare), the needs of World War II
greatly accelerated simulation technology for use of in
flight training.
The first recorded use of a medical simulator is that of a
32
Use of Medical Simulation in the Practice of Anaesthesia
mannikin created in the 17th Century by a Dr Gregoire
of Paris (Buck, 1991). He used a pelvis with skin
stretched across it to simulate an abdomen, and with
the help of a dead fetus explained assisted and
complicated deliveries to midwives.
In spite of this early start, medical simulators did not
really gain widespread use in the following centuries,
principally for reasons of cost, reluctance to adopt
new teaching methods, and scepticism that what was
learned from a simulator could be transferred to actual
practice.
All of these reasons are still relevant today, however the
combination of improved technology and increasing
pressures on educators have promoted simulation as
one option to address the problems associated with
traditional clinical skills teaching. With the availability
of inexpensive computer technology in recent years,
simulation technology has blossomed again. This is
especially in the field of medicine, where applications
range from scientific modeling to clinical performance
appraisal in the setting of crisis management.
In the last 10 years, simulation using high-fidelity
patient simulators for the purpose pf training
health-care professionals has grown and expanded
rapidly. There are now approximately 200 simulation
training centres operating internationally. Malaysia
currently has two such centres and one of them is the
University Malaya Simulation Centre that was opened
in 2001. Located in the Faculty of Medicine, it is
supported by a government grant and provides
multidisciplinary training for doctors and nurses at
both undergraduate and postgraduate levels.
Loo Wee Tze, MBBS(Malaya), M.Med (Anaes) UKM.
Department of Anaesthesia and Intensive Care, Hospital Kuala Lumpur.
Wang Chew Yin, MBChB (Birmingham), FRCA, FFARCS (Ireland), FAMM.
Department of Anaesthesiology and Intensive Care, Faculty of Medicine, University of Malaya.
Dr Loo Wee Tze is a Consultant Anaesthetist at Hospital Kuala Lumpur. His areas of interest include neuroanaesthesia and
simulation training. He is one of the key instructors of the Anaesthesia Crisis Resource Management (ACRM) course
conducted in University of Malaya.
Professor Dato’ Wang Chew Yin is Professor of Anaesthesiology, Head of Day Surgery Unit and Coordinator of Health Simula-
tion and Skills Training at University of Malaya. She regularly conducts the Anaesthesia Crisis Resource Management
(ACRM) courses and is regarded as the leading authority in medical simulation in the country.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
Type of simulators
Computer-based simulators used in medical
education fall into four general categories:
(1) Screen-based text simulators,
(2) Screen-based graphical simulators,
(3) Mannikin-based simulators,
(4) Virtual reality trainers.
The Virtual Anesthesiology Training Simulation
System from CAE/Eagle/MedSim (the name
reflects a series of corporate sales and takeovers) is a
modern anesthesiology simulator conceived for a
number of training applications, such as to train
anesthesiology residents, for practice with new
technology or instruments, for rehearsing anesthetic
emergencies, and possibly for future testing,
certification, or recertification of anesthesiologists. It
is also of potential use outside the operating room,
in situations like Critical Care Training and
Emergency Room Training.
This high level Human Patient Simulator (HPS)
consists of a lifelike patient mannikin; which
breathes spontaneously, has palpable pulses, heart
and lung sounds and responds appropriately to
stimuli such as electrical current from a
neuromuscular blockade monitor. It can also present
a wide range of responses such as arm motion,
eyelid open/closure, pupil dilatation/contraction,
and tongue and airway swelling. The mannikin can
be intubated and connected to life-support systems,
such a mechanical ventilators or intravenous cardiac
inotrope infusion pumps.2 A hybrid (mechanical and
mathematical) lung model allows the patient
mannikin to consume oxygen and produce carbon
dioxide. The HPS is able to recognise and respond to
a wide variety of pharmacological agents and
physiology events. The simulator can be
programmed to present a variety of medical
problems (e.g. mitral and aortic stenosis,
intracranial hypertension) and altered physiologic
states including cardio respiratory events such as
haemorrhage, anaphylaxis, pneumothorax, and
aspiration; and metabolic events, as well as a
difficult airway and equipment malfunction. Almost
any specialty can be accommodated, including
pediatrics and obstetrics.
33
MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
Figure 1
Figure 2
High Fidelity Simulator : SAM of UM
Teaching Crisis Management in Trauma Patient
Uses of medical simulation
In recent decades, the simulation technology has
been leading the change in new teaching
techniques. This change is evident in anaesthesia
education, where there is a shift from
structure-based curriculum to competence-based
curriculum. In the latter, accomplishments of preset
competencies determine the learning process.
Medical simulation – with its improved
computer-based programs, increasingly
sophisticated task trainers and simulator facilitators
– allows for new teaching methods that fulfill this
shift in education approach.
In anaesthesia, the major purpose of simulators is to
rehearse the management of both frequently

YEAR BOOK 2006/2007
34
YEAR BOOK 2006/2007
occurring and rare events during anaesthesia. The
principal objective of simulators is to provide the
highest transfer of skills from the training device to
the operation systems.
There are five essential elements of medical
simulation training which include curriculum,
training tools, performance evaluation, data
collection, and debriefing. Since the introduction of
the first fully interactive patient simulator in the
1960s, the health care industry has rapidly embraced
the use of medical simulators as a component of
medical training. Today, there are more than 40
virtual reality, graphical, mannikin-based and
screen-based simulators available for initial and
ongoing training of health care professionals.
How Can Simulation Improve Patient Safety?
Simulation offers methodical training, performance
assessment and refinement in practice; which may
indirectly improve patient safety. It acts as a platform
for the change in learning culture and improvement
in quality and risk management activities.
The following areas below underpin the contribution
of simulation towards improvement in patient safety
in anaesthesia.
1. Education
• Introduction to anaesthesia for medical students
• Introduction to anaesthesia for medical officers
2. Training
• Specific professional group - Training curriculum
focuses on skills & behaviours required for tasks
on the job
• Advanced airway management skills
• Anesthesia Crisis Resource Management
(ACRM)
3. Research
• A wide variety of research on human performance
in health care requires simulation
• “Educational research” & performance
assessment
• Clinical techniques (e.g. pediatric sedation)
• Human machine interaction
• Decision making
4. Risk Management
• Appropriate simulation training may reduce:
- The frequency of adverse clinical events
- The impact of clinical events that do occur
- The likelihood of litigation after an event
- A jury’s perception that the institution did not
take patient safety seriously
5. Performance Assessment
Simulation is a key research tool in human
performance because it provides:
• Reproducibility
• Controllability
• Criticality
all in a confidential environment with no risk to
patients
While application of simulation in the areas of
education, training and research has been well
established, more needs to be done for risk
management and performance assessment.2
Why has simulation become more popular as
a teaching and assessment tool?
In the past, health care professionals learnt on the job,
which some still believe is the best way to gain
experience. However, there are a number of barriers
to this type of traditional clinical teaching. These
include:
a) Humanitarian issues – practicing on patients is
not ethical. We have moved into an age of where
learning on patients is no longer acceptable if
there is an alternative.
b) There has been a decrease in the number of
inpatients, in part due to an increasing number of
day case patients and also the fact that chronic
conditions are being cared for in the community.
This has led to a decrease in exposure and access
of the trainees to ward patients.
c) The training time for postgraduate medical
education has decreased and will continue to
decrease further. With the implementation of new

35
MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
training schemes, experience cannot be built
upon over time as before.
d) Some situations are so rare that to gain experience
would take many lifetimes.
e) Legal/litigation issues. The possibility of
educational establishments being sued by
patients and ex-students for not teaching and
assessing clinical skills as laid down by the
regulatory bodies could arise.
f) Record keeping, reproducibility, assessment and
validity are issues all brought to the forefront
with clinical governance and revalidation.
Simulation is seen as away of addressing some of
these issues.
g) Students learn more effectively in a
non-threatening environment.
h) There is increasing emphasis on
multidisciplinary learning, and clinical skills
teaching is an ideal forum for this.
Is patient simulator ready for competence
testing?
Despite increasing use and popularity of simulation
in medical education, most professional societies,
medical associations, and licensing boards are
opposed to its use as a primary component of the
certification process. This hesitancy is partly because
it has been difficult to tie simulator outcomes to
real-life procedural outcomes. In short, there is a
paucity of data to support the validity, reliability, and
reproducibility of simulator training or its translation
into clinical practice.
How successful is the implementation of
simulator training in Malaysia?
The progression of simulator training program is still
slow in Malaysia, due to the lack of financial and
human resources, time, and validation of education
or evaluation model. Currently, the high fidelity
human patient simulators in Malaysia are used to run
programs such as advanced airway management,
advanced trauma care and anaesthetic crisis resource
management (ACRM). We conducted an evaluation
of simulation-based activities in University Malaya
Medical Centre and the results were very positive;
majority of the participants regarded the tool as
realistic and helped them to improve their skills in
anaesthesia with further training.3
What is in the future?
The high cost of purchase and maintenance of the
full-scale (FS) simulators compared to the
less-expensive training methods has created
controversy within the anaesthesia profession, with
cost-effectiveness being the main concern. At some
simulation centres, simulator training is compulsory
for anaesthesia trainees. In Denmark, all trainees are
expected to undergo a 3-day national compulsory
course in clinical decision making at the Simulation
Centre in Herlev.4,5 However, there is limited
evidence that people actually perform better and
learn faster or of change in patient outcome as a result
of patient simulation training. Weller et al 6 showed
that in a survey study of anaesthetists who had
attended a simulation-based course in anaesthesia
crisis management in the preceding year, the
respondents highly valued the course and perceived
a change in their practice as a result of the training.
The Simulation Centre in Bristol, England is now
conducting a study to examine whether simulation
training used in crisis management courses for
neonatal emergencies is more effective than standard
training in reducing perinatal mortality.
In short, the future of simulation in anaesthesia will
be influenced by its cost-effectiveness and the
validation of its effect on actual patient outcome.
Nevertheless, to quote Dr Gaba:
“ No industry in which human lives depend on the
skilled performance of responsible operators has
waited for unequivocal proof of the benefits of
simulation before embracing it… Neither should
anesthesiology.”
Gaba DM. Anesthesiology 76:491-494, 1992

36
YEAR BOOK 2006/2007
Reference
1. Gaba DM. Applications of Simulation in Anesthesiology.
2. Doyle D.J. Simulation in Medical Education: Focus on
Anesthesiology.. Available from: URL:
http://www.med-ed-online.org
3. Ringsted C, Østergaard D, Scherpbier A: Embracing the
new paradigm of assessment in residency training: An
assessment programme for first-year residency training in
anaesthesiology. Med Teach 2003; 25: 54–62
4. Østergaard, Doris MD. National Medical Simulation
training program in Denmark. Crit Care Med 2004;32(2):
S58-S60
5. Wang CY, Ng KP, Mohd Isa M, Mah Y, Ong G, Kaur R.
Human Patient Simulator: The Malaysian Experience.
13th World Congress of Anaesthesiologists 2004; abstract
S027.
6. Weller J, Wilson L, Robinson B. Survey of change in
practice following simulation-based training in crisis
management. Anaesthesia 2003;58(5): 471-473.

37
Propofol Infusion Syndrome
Propofol infusion syndrome
Propofol infusion syndrome (PRIS) is a constellation of
signs originally described in children but has since been
shown to occur in adults as well. First seen in critically
ill paediatric patients sedated with propofol, it has
since been described in adult neurosurgical intensive
care units as well as in anaesthesia. Up till 2006, 24
paediatric and 14 adult cases have been reported.1
In view that propofol is immensely popular and is
beginning to be used by non-anaesthesiologists, this
review article aims to describe the syndrome, explain
its suggested pathophysiology and possible treatment.
PRIS and the paediatric patient
In 1990, the death of a two-year-old child with croup
was reported in Denmark. The child was sedated in the
intensive care unit with propofol averaging
10mg/kg/hr over 4 days. The patient developed
hepatomegaly, heart failure and hypotension.
Unfortunately, as it was reported in an obscure paper,2
the mortality was not given much attention. It is now
recognized that this may have been the first mortality
reported due to PRIS.
It was not until two years later that mortality linked
to the use of propofol was reported in English.
Parke et al3 reported five cases of mortality in children
ranging from age of 4 weeks to 6 years who were
diagnosed with croup or bronchiolitis. These young
patients had received propofol infusions at 7 – 10
mg/kg/hr for between 66 to 115 hours. The features
were similar among the children – lipemia,
hepatomegaly, metabolic acidosis followed by
bradyarrhythmia and progressive cardiac failure.
This report prompted the manufacturer to warn
physicians, that propofol at the time, was not licensed
for use in the paediatric population.4,5 Confusion
reigned however, as the United States Food and Drug
Administration (US FDA) found no direct link to
paediatric deaths and instead urged the manufacturer
to “pursue pediatric indication”.6
Sporadic cases continued to be reported in the
literature. In 1998, Bray7 reported a series of 18 critically
ill paediatric patients who died after developing
similar features of bradycardia, asystole, metabolic
acidosis, lipemia, hepatomegaly and rhabdomyolysis.
This was followed by a warning from the US FDA itself
which halted a randomized controlled trial (RCT)
which showed that paediatric patients given propofol
sedation had higher death rates (9.5%) compared to
those who received other agents (3.8%). Unfortunately
the RCT was terminated and its results were not
published. The Canadian health authorities also issued
a warning that propofol was contraindicated in the
paediatric age group.
Despite these warnings, many disputed the existence of
PRIS.8,9 Despite the lack of large scale RCTs evaluating
the safety of the drug for procedural sedation or for the
induction and maintenance of general anaesthesia,10
propofol has been used in large paediatric centers with
no apparent untoward incidents.11 The United
Kingdom Committee on Safety of Medicines currently
states that propofol is contraindicated for sedation of
children aged 16 and below.12
PRIS in adults
The first recorded case of mortality in adults associated
with PRIS was reported in 2000.13 The patient was an
18-year-old man involved in a motor vehicle accident.
He sustained head and chest trauma, multiple
fractures, facial burns, multiple lacerations and
abrasions. He was sedated with propofol during
transport to hospital as well as in the emergency
department. Post operatively he was transferred to the
ICU and continued to receive propofol as an infusion.
On day 3, his creatine kinase (CK) level was elevated.
Although he did not have compartment syndrome, the
Thong Chwee Ling, MBBS (Malaya) Distinction, MMed (Anaes) UKM, AM (Mal)
Dr Thong Chwee Ling is a private anaesthesiologist practicing in Klang Valley and has been actively involved in various anaes-
thesia educational activities. She has wide areas of interest, with an inclination towards neuroanaesthesia and neurointensive
care.

YEAR BOOK 2006/2007
raised CK was attributed to extensive soft tissue
injuries and fractures. He was treated with diuretics
and alkalinisation of urine.
On day 5, he developed atrial fibrillation with rapid
ventricular response. His electrocardiogram (ECG)
showed intraventricular conduction block, a new left
axis deviation and possible anterolateral infarction.
This changed to left bundle branch block over 4
hours.
He developed progressive metabolic acidosis with
hyperkalaemia and rising methaemoglobinaemia
(13%). Global hypokinesia was demonstrated on
echocardiogram. He developed bradycardia and
hypotension unresponsive to atropine, epinephrine
and fluids. He subsequently went into pulseless
electrical activity and asystole.
Haemoglobin electrophoresis showed normal
level of methaemoglobinaemia. The
pseudomethaemoglobinaemia arose due to a lab error
in spectrophotometry due to high turbidity from a
hyperlipidaemic blood sample. The patient had
received a total dose of 530 mg/kg of propofol for 39
hours and 700 mg/kg for 59 hours.
In 2001, Cremer et al14 reported the first series of
adult deaths. Five patients with head injuries
inexplicably had fatal cardiac arrests in a
neurosurgical intensive care unit after introduction
of 2% propofol for sedation. This prompted a
retrospective analysis of head-injured patients aged
16 to 55 years admitted to the unit from 1996 to
1999 who were mechanically ventilated for more
than 48 hours. This unit practiced a head injury
protocol where patients had intracranial pressure
(ICP) monitoring, were moderately hyperventilated
based on jugular-venous oximetry and received
propofol sedation. Larger doses of propofol were
used to reduce cerebral metabolic requirements of
oxygen (CMRO2) and ICP.
Of the 67 cases analysed, 7 possible cases of PRIS were
identified. These patients had increasing need for
inotropic and vasopressor support 24-48 hours after
propofol was started. They received higher mean doses
of propofol compared to other cases, and all had
received more than 5mg/kg/hr of propofol for more
than 58 hours.
38
Based on their findings, Cremer et al calculated that the
crude odds ratio for occurrence of PRIS was 1.93 (95%
CI 1.12-3.32) per unit (mg/kg/hr) increase in mean
propofol use. PRIS did not occur in patients who
received less than 5 mg/kg/hr. The incidence was 17%
in those who received between 5 to 6 mg/kg/hr and
rose to 31% in those receiving more than 6mg/kg/hr of
propofol.
PRIS has been reported to occur when propofol was
used in large doses for even short periods of time for
anaesthesia as well.15,16
Pathophysiology of PRIS
The pathophysiology of PRIS is unclear, although it is
likely to be multifactorial. A number of priming factors
such as central nervous system activation in the
critically ill patient have been identified which puts the
patient at risk of PRIS. High dose propofol along with
supportive therapy such as catecholamines and
corticosteroids act as triggering factors.17
In animal models, propofol has been shown to
uncouple oxidative phosphorylation and energy
production in the mitochondria, hence impairing
oxygen utilization and inhibiting electron flow along
the electron transport chain.18,19 It antagonizes
β-adrenoceptors and calcium channel proteins causing
diminished cardiac contractility.20,21
In humans, muscle cytochrome oxidase deficiency was
demonstrated in one child who developed PRIS after
propofol sedation,22 while the muscle biopsy of
another child showed decreased complex IV activity
and low cytochrome oxidase ratio24. These are
suggestive of mitochondrial respiratory chain enzyme
deficiency.
In critically ill patients, catecholamine-mediated
lipolysis of adipose tissues produces free fatty acids
(FFA) which form the most important substrates for
production of energy. FFA undergo β-oxidation in the
mitochondria, a process which generates electrons
which are then transferred to the respiratory chain.
Wolf et al24 found evidence of impaired fatty acid
oxidation in a 2-year-old boy who had clinical features
of PRIS. The boy had raised plasma concentration of

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
39
malonyl carnitine and C5-acylcarnitine which
subsequently normalized following recovery. These
findings suggest that there were altered long-chain FFA
entry into the mitochondria caused by inhibition of
carnitine palmitoyl transferase I and uncoupling of
β-oxidation with the respiratory chain at complex II.
This results in failure of long-chain FFA entering the
mitochondria, while medium- and short-chain FFA
which freely cross the mitochondrial membranes could
not be utilized. This leads to an imbalance of energy
production and demand. An accumulation of
unutilized FFA also results, which have
pro-arrhythmogenic properties.25
Low carbohydrate supply is a risk factor for PRIS. The
body reverts to lipolysis to meet energy demands,
leading to further accumulation of FFA. Children are at
a higher risk due to low glycogen storage.26 Wolf et al27
reported the case of an 11-year-old child, who received
propofol for more than 5 days for treatment of epilepsy,
developing high C4-acylcarnitine levels associated
with low carbohydrate intake. Fat overload may also be
a contributory factor. A 10-year-old boy developed
PRIS after receiving a ketogenic diet, which contains
90% energy in the form of long-chain triglycerides, for
control of refractory epilepsy.28
An interesting relationship has been shown between
high catecholamine levels and propofol
pharmacokinetics in an animal study.29 As
catecholamines increase cardiac output, mean propofol
arterial concentration was linearly reduced, causing a
reversal of anaesthesia. This was attributed to
increased first-pass dilution and clearance of propofol
resulting from increased cardiac output. Propofol
antagonism of β-adrenoceptors20 may also contribute.
Catecholamine surges in acute neurological dysfunction
is well recognized and may cause increasing doses of
propofol usage to ensure adequate sedation. This
negative inotropic effects of propofol in turn drives
increased usage of catecholamines to maintain cardiac
output, resulting in a positive feedback mechanism and
progressive myocardial depression.
Possible treatments
The early cases of PRIS carried high mortality. With
increasing awareness, several possible treatments have
been suggested.
The first recorded survival was reported in 1992.30 The
patient was a 20-month-old child who developed
asystolic cardiac arrest after receiving propofol 5 – 10
mg/kg/hr for 56 hours. The patient
was successfully resuscitated and underwent
venovenous haemofiltration. Extracorporeal
membrane oxygenation (ECMO) was successfully used
to treat a 13-year-old male with PRIS.31
It has been suggested that stopping the propofol
infusion, institution of supportive measures and dialysis
are the cornerstone of management. Weaning patients
off catecholamine support and early nutrition to prevent
breakdown of fats may be useful, as evidenced by
Corbett et al’s32 success in the managing a head-injured
patient with PRIS. This patient had the propofol infusion
ceased, was weaned off his catecholamine support and
started on appropriate tube feeding. His renal function
which was initially impaired, improved after cessation
of propofol. He received metoprolol and captopril for
treatment of moderate to severe global left ventricular
dysfunction (ejection fraction 25 – 30%) and moderate
right ventricular dysfunction. The patient was
subsequently discharged home.
Despite progress being made, prevention is always
better than cure. It would be prudent to keep propofol
infusions at less than 5 mg/kg/hr for less than 48
hours. If higher doses are required, or sedation is
needed for longer periods of time, one should consider
the use of other sedative agents.
Conclusions
Propofol infusion syndrome is a rare occurrence which
carries a high mortality rate. More cases may be seen in
the future as the popularity of propofol as a sedative
and anaesthetic agent for short procedures increases. A
heightened awareness of PRIS and its presentation,
such as unexplained metabolic acidosis and myocardial
depression may uncover more cases, contribute to
earlier cessation of the drug and an improved outcome.
The pathophysiology of PRIS has not been fully
elucidated but the effects of propofol on free fatty acid
metabolism and mitochondrial respiratory chain and
its relationship with catecholamines contribute to the
occurrence of this syndrome. Treatment of this
syndrome is by stopping the infusion and providing
supportive therapy.

YEAR BOOK 2006/2007
40
References
1. Fudickar A, Bein B, Tonner PH. Propofol infusion
syndrome in anaesthesia and intensive care medicine.
Curr Opin Anaesthesiol 2006; 19: 404-10.
2. Notits fra Bivirkningsnaevnet. Propofol (Diprivan)
bivirkninger. Ugeskr Laeger 1990; 152: 1176.
3. Parke TJ, Stevens JF, Rice AS, Greenaway CL, Bray RJ,
Smith PJ et al. Metabolic acidosis and fatal myocardial
failure after propofol infusion in children: five case
reports. BMJ 1992; 305: 613-6.
4. Edwards KG. ‘Diprivan’ ICU sedation in children:
unlicensed use. Serious adverse events including
fatalities. Letter to doctors. Macclesfield, UK: ICI
Pharmaceuticals 1992 April 29.
5. Edwards KG, Arnold BDC. Propofol infusion in children
[Letter]. BMJ 1992; 305: 952.
6. FDA’s Anesthetic and Life Support Drugs Advisory
Committee. ICI’s Diprivan (propofol) anesthetic has no
direct link to pediatric deaths in ICUs, FDA advisory
committee finds; FDA asks ICI to pursue pediatric
indication. FDC Reports 1992; 54:14.
7. Bray RJ. Propofol infusion syndrome in children. Paediatr
Anaesth 1998; 8: 491-9.
8. Reed MD, Blumer JL. Propofol bashing: The time to stop is
now! Crit Care Med 1996; 24: 175-6.
9. Susla GM. Propofol toxicity in critically ill pediatric
patients: show us the proof. Crit Care Med 1998; 26:
1959-60.
10. Hatch DJ. Propofol infusion syndrome in children. Lancet
1999; 353: 1117-8.
11. Crawford MW, Dodgson BG, Holthy HHK, Roy WL.
Propofol syndrome in children. CMAJ 2003; 168(6): 669.
12. Committee on Safety of Medicines, Medicines Control
Agency. Propofol (Diprivan) infusion: sedation in children
aged 16 or younger contraindicted. Current problems in
Pharmacovigilance 2001; 27: 10.
13. Perrier ND, Baerga-Varela Y, Murray MJ. Death related to
propofol use in an adult patient. Crit Care Med 2000;
28(8): 3071-4.
14. Cremer OL, Moons KGM, Bouman EAC, Kruijswijk JE, de
Smet AMGA, Kalkman CJ. Long-term propofol infusion
and cardiac failure in adult head-injured patients. Lancet
2001; 357: 117-8.
15. Burrow BK, Johnson ME, Packer DL. Metabolic acidosis
associated with propofol in the absence of other causative
factors. Anesthesiology 2004 Jul; 101(1); 239-43.
16. Liolios A, Guerit JM, Scholtes JL, Raftopoulos C, Hantson
P. Propofol infusion syndrome associated with short-term
large-dose infusion during surgical anesthesia in an adult.
Anesth Analg 2005; 100: 1804-6.
17. Vasile B, Rasulo F, Candiani A, Latronico N. The
pathophysiology of propofol infusion syndrome: a simple
name for a complex syndrome. Intensive Care Med 2003;
29: 1417-25.
18. Branca D, Roberti MS, Lorenzin P, Vincenti E, Scutari G.
Influence of the anaesthetic 2,6 diisoprophylphenol on the
oxidative phosphorylation of isolated rat liver
mitochondria. Biochem Pharmacol 1991; 42: 87-90.
19. Schenkman KA, Yan S. Propofol impairment of
mitochondrial respiration in isolated perfused guinea pig
hearts determined by reflectance spectroscopy. Crit Care
Med 2000; 28: 172-7.
20. Zhou W, Fontenot HJ, Wang SN, Kennedy RH. Propofol
induced alterations in myocardial beta-adrenoceptor
binding and responsiveness. Anesth Analg 1999; 89: 604-8.
21. Zhou W, Fontenot HJ, Liu S, Kennedy RH. Modulation of
cardiac calcium channels by propofol. Anesthesiology
1997; 86: 670-5.
22. Cray SH, Robinson BH, Cox PN. Lactic acidemia and
bradyarrhythmia in a child sedated with propofol. Crit
Care Med 1998; 2089-92.
23. Mehta N, DeMunter C, Habibi P, Nadel S, Britto J.
Short-term propofol infusions in children. Lancet 1999;
354: 866-7.
24. Wolf A, Weir P, Segar P, Stone J, Shield J. Impaired fatty
acid oxidation in propofol infusion syndrome. Lancet
2001; 357: 606-7.
25. Jouven X, Charles MA, Desnos M, Ducimetiere P.
Circulating nonesterified fatty acid level as a predictive
risk factor for sudden death in the population. Circulation
2001; 104: 756-61.
26. Short TG, Young Y. Toxicity of intravenous anaesthetics.
Best Pract Res Clin Anaesthesiol 2003; 17: 77-89
27. Wolf AR, Potter F. Propofol infusion in children: when
does an anaesthetic tool become an intensive care liability?
Paediatr Anaesth 2004; 14: 435-8.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
41
28. Baumeister FA, Oberhoffer R, Liebhaber GM. Fatal
propofol infusion syndrome in association with ketogenic
diet. Neuropaediatrics 2004; 35: 250-2.
29. Myburgh JA, Upton RN, Grant C, Martinez A.
Epinephrine, norepinephrine and dopamine infusions
decrease propofol concentrations during continuous
propofol infusion in an ovine model. Intensive Care Med
2001; 27: 276-82.
30. Barclay K, Williams AJ, Major E. Propofol infusion in
children (Letter). BMJ 1992; 305: 953.
31. Culp KE, Augoustides JG, Ochroch AE, Milas BL. Clinical
management of cardiogenic shock associated with
prolonged propofol infusion. Anesth Analg 2004; 99:
221-6.
32. Corbett SM, Moore J, Rebuck JA, Rogers FB, Greene CM.
Survival of propofol infusion syndrome in a head-injured
patient. Crit Care Med 2006; 34(9): 2479-83.

42
Central Venous Oxygen Saturation: How To Use It
The aim of cardiovascular monitoring is to recognise
impending tissue hypoxia. Early recognition and
treatment of tissue hypoxia is important in the
management of the critically ill. If untreated, global
tissue hypoxia leads to anaerobic metabolism, lactate
production and oxygen debt. The magnitude and
duration of oxygen debt have been implicated in the
development of multi-system organ failure and
increased mortality. Unfortunately, the routine
continuous monitoring of the systemic blood
pressure, heart rate and central venous pressure is
unable to provide information about the imbalances
between whole body oxygen supply and demand in
these patients.
Measurement of mixed venous oxygen saturation
(SvO2) from the pulmonary artery has been
advocated as an indirect indicator of the adequacy of
tissue oxygenation. To enable measurement of this
parameter, pulmonary artery catheterisation is
necessary. Due to its inherent risks and lack of
convincing data of its usefulness, pulmonary artery
catheterisation is not routinely carried out as part of
the cardiovascular monitoring in the critically ill
patient.
Central venous catheterisation, an easier and safer
procedure, is frequently performed in the critically ill
patient. It is mainly used to monitor central venous
pressure and administer vasoactive drugs. In the late
1960s, Goldman studied the measurement of central
venous oxygen saturation (ScvO2) in patients with
myocardial infarction while Scheinman investigated
if the ScvO2 reflects changes in SvO2. Whether ScvO2
exactly mirrors SvO2, especially in the critically ill
patients, has always been a question. Rivers, in a
prospective randomised trial, demonstrated that
there was improved survival outcome with early
intervention directed by ScvO2 in patients with
severe sepsis and septic shock.1 Since then, there has
been a resurgence in interest in the measurement of
ScvO2 in critically ill patients.
Physiology of mixed venous oxygen
saturation (SvO2)
Calculation of O2 consumption (VO2) according to the
Fick principle is given as the product of cardiac output
(CO) and arteriovenous O2 content difference
(a-v[O2]).
VO2 = CO X a-v[O2]
a-v[O2] is the difference between arterial O2 content and
venous O2 content (CaO2 – CvO2)
Therefore VO2 = CO X ( CaO2 – CvO2 )
Rearranging the formula for O2 consumption
CvO2 = CaO2 – VO2
CO
O2 content ([O2]) is the sum of oxygen bound to
haemoglobin [product of haemoglobin concentration
(Hb) and O2 saturation (SO2)] and physically dissolved
oxygen [PO2].
[O2] = [Hb X 1.36 X SO2] + {[PO2 X 0.003]} -- negligible
Substituting O2 content in the formula for O2
consumption
CvO2 = CaO2 – VO2
CO
Hb X 1.36 X SvO2 = Hb X 1.36 X SaO2 – VO2
CO
SvO2 ≈ SaO2– VO2
CO
SvO2 indicates the balance between oxygen supply and
demand. SvO2 can be decreased when O2 supply does
not increase proportionately to an increased O2
demand. Thus fever, pain or stress may decrease SvO2
when the increase in whole-body O2 demand is not
matched by an appropriate increase in O2 delivery.
Tai Li Ling, M.Anaes (Malaya), EDIC.
Department of Anaesthesia and Intensive Care, Hospital Kuala Lumpur.
Dr Tai Li Ling is a Consultant Intensivist at Hospital Kuala Lumpur. One of the leading authorities in intensive care in Malay-
sia, she is involved in organizing various educational programs and sits in several audit and guidelines committees.

43
MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
Limits of mixed venous oxygen saturation (SvO2)2
SvO2 level Consequences
SvO2 > 75% Normal extraction
O2 supply > O2 demand
75% > SvO2 > 50% Compensatory extraction
Increasing O2 demand or decreasing O2 supply
50% > SvO2 > 30% Exhaustion of extraction
Beginning of lactic acidosis
O2 supply < O2 demand
30% > SvO2 > 25% Severe lactic acidosis
SvO2 < 25% Cellular death
SvO2 can also decrease due to a lower arterial O2
content or cardiac output, or both. Conditions causing
this drop in O2 delivery include anaemia, hypoxia,
hypovolemia or heart failure.
Can ScvO2 function as a surrogate for SvO2?
In healthy humans, the oxygen saturation in the
inferior vena cava is higher than in the superior vena
cava as the lower body extracts less O2 than the upper
body. The reason is many of the vascular circuits that
drain into the inferior vena cava use blood flow for
non-oxidative phosphorylation needs (e.g. renal and
hepatic blood flow).
Measurement of ScvO2 in the superior vena cava
reflects the degree of O2 extraction from the brain and
the upper part of the body. Since the pulmonary artery
contains a mixture of blood from both the superior as
well as the inferior vena cava, SvO2 in the pulmonary
artery is greater than ScvO2 in the superior vena cava.
In non-shock states, a good correlation between ScvO2
and SvO2 has been shown, with ScvO2 being less than
SvO2 by about 2 - 3%. If the tip of the central venous
catheter is located inside the right atrium, there is
mixing of blood from the inferior vena cava and
measurement of ScvO2 may be higher than if the tip is
located in the superior vena cava.
The difference between ScvO2 and SvO2 is not constant
and may be affected by changes in the regional blood
flow and oxygen supply to demand ratio. In shock
states, there is a consistent reversal of the relation
between ScvO2 and SvO2 where superior vena cava
ScvO2 is always greater than SvO2 with the difference
ranging from 5-18%. Redistribution of blood flow away
from the splanchnic, renal, and mesenteric bed toward
the cerebral and coronary circulation, including more
desaturated blood (< 30%) from the coronary sinus,
contributes to this observation. Thus, ScvO2
consistently overestimates the true SvO2 under shock
conditions and the changes of these two parameters
occur mostly in a parallel manner.
Measurements of ScvO2 and SvO2 are not equivalent
i.e. the absolute values differ. It had been shown in
animal studies that SvO2 and ScvO2 closely paralleled
each other in various pathologic states. However,
studies in humans had shown conflicting results.3, 4, 5
ScvO2 monitoring: continuous vs. intermittent
Central venous O2 saturation can be measured either
intermittently using central venous blood gas analysis
or continuously using fibreoptic oximetry catheters. It
is vital to measure central venous oxyhaemoglobin
saturation using oximetry if intermittent blood gas
analysis is used. ScvO2 computed from partial pressure
oxygen (PvO2) will not be accurate. The PvO2 range is
within the steep section of the oxyhaemoglobin
dissociation curve where a small change in PvO2 will
cause a significant change in ScvO2.
When using ScvO2 to make clinical decisions, it should
not be based on a single measurement, but rather on
trends of ScvO2 to detect an imbalance between oxygen
delivery and consumption. Continuous monitoring of
ScvO2 and SvO2 in the framework of haemodynamic

44
YEAR BOOK 2006/2007
goals and treatment algorithms has resulted in
improved patient outcome. However, it is unclear if
intermittent measurements of ScvO2 can substitute
continuous monitoring of ScvO2 in these algorithms.
Clinical uses of ScvO2 monitoring
Septic shock
Although the blood flow to the splanchnic region is
increased in septic shock, the lower ratio of O2 supply
to demand in the this region results in greater O2
desaturation from venous blood that drains into the
hepatic vein and inferior vena cava, respectively. On
the other hand, cerebral blood flow is maintained
causing the measurement of ScvO2 to be higher than
SvO2. On average ScvO2 exceeds SvO2 by 8% in
patients with septic shock.3
Rivers et al. demonstrated that using ScvO2 as a
resuscitation end-point in addition to mean arterial
pressure and central venous pressure provides
significant outcome benefit for patients with severe
sepsis and septic shock over standard therapy.1 Those
in the early goal-directed therapy group were
resuscitated to ScvO2 greater than 70% using
continuous ScvO2 monitoring.
While ScvO2 is an excellent tool in the early
resuscitation period of shock, there is still controversy
as to whether it is a suitable parameter for follow-up
therapy in the intensive care unit. Varpula et al. found
that the difference between these two oxygen
saturation parameters varies highly in the intensive
care unit treatment period and concluded that SvO2 is
not to be estimated on the basis of ScvO2.5
Heart failure and cardiogenic shock
Heart failure is characterised by a limited cardiac
output. To meet the needs during an increase in O2
demand, the O2 extraction in tissue is increased as
these patients are unable to sufficiently increase their
cardiac output. Therefore, in these patients, SvO2 is
tightly correlated with cardiac output and a drop in
SvO2 is a good and early marker of cardiac
deterioration, most commonly seen in acute heart
failure in acute myocardial infarction. Goldman et al.
found that ScvO2 less than 60% showed evidence of
heart failure, shock or both.
However patients with chronic heart failure may live
with SvO2 in the low range of 30 - 40% without
apparent tissue hypoxia, presumably because they
have adapted to higher O2 extraction. These patients
can increase their O2 consumption to a limited degree
because O2 extraction is close to its limits as is cardiac
output. Anders examined the use of lactic acid levels
and ScvO2 to stratify and treat patients with acutely
decompensated end-stage congestive heart failure who
presented to the emergency department.6 ScvO2 was
significantly lower in the high lactic-acid group than in
the normal lactic-acid group. There was a significant
prevalence of undetected cardiogenic shock with ScvO2
ranging from 26.4 to 36.8% in the presence of normal
vital signs.
Cardiac arrest
Patients with cardiac arrest routinely have ScvO2
values of 5-20% during cardiopulmonary resuscitation.
Those with return of spontaneous circulation had a
higher initial mean and maximal ScvO2 than did those
without.7 No patient attained return of spontaneous
circulation without reaching a ScvO2 of at least 30%. A
ScvO2 of greater than 72% was 100% predictive of
return of spontaneous circulation. However, a very
high ScvO2 (>80%) in the presence of a very low O2
delivery after successful CPR is also an unfavorable
predictor of outcome as it is indicates impairment of
tissue O2 utilisation probably due to a prolonged
cardiac arrest. Continuous ScvO2 monitoring can
provide an objective measure to confirm the adequacy
or inadequacy of cardiopulmonary resuscitation in
providing O2 delivery but its practicality is doubtful.
Trauma and haemorrhage
Scalea et al. had shown that patients presenting with
trauma and hemorrhage required additional
resuscitation or surgical procedures when ScvO2
remained less than 65% despite stable systemic blood
pressure, heart rate and central venous pressure.8
These patients had more serious injuries and
significantly larger estimated blood losses and required
more transfusions than those patients with ScvO2
saturation > 65%. They also demonstrated prolonged
cardiac dysfunctions and elevated lactate levels.
Major surgery
Pearse et al. measured ScvO2 besides cardiac index and
O2 delivery index in patients after major general
surgery and found that a ScvO2 cut-off value of 64.4%

45
MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
(sensitivity 67%, specificity 56%) could be used to
discriminate patients with a complicated or
uncomplicated post-operative course.9 The lowest
ScvO2 was independently associated with
post-operative complications. In the first hour after
surgery, significant reductions in ScvO2 were observed
but there were no significant changes in cardiac index
or oxygen delivery index during the same period.
Reduction in ScvO2 is due to increased post-operative
oxygen consumption from various factors e.g. pain,
emergence from anaesthesia and shivering.
Limitations of mixed and central venous
oxygen saturation for the assessment of
tissue oxygenation
Inadequate tissue oxygenation may exist despite
normal central and mixed venous oxygen saturations.
Normal or high ScvO2 and SvO2 do not rule out tissue
hypoxia in the organ or at regional level. Venous
oximetry can reflect the adequacy of tissue oxygenation
only if the tissue is still capable of extracting O2.
Venous oximetry should not be used alone in the
assessment of the cardiovascular system but in
combination with other haemodynamic parameters
and indicators of organ perfusion such as serum lactate
concentration and urine output.
Conclusion
Low values of SvO2 or ScvO2 indicate a mismatch
between O2 delivery and tissue O2 demand. ScvO2
values differ from SvO2 values and this difference
varies with cardiac output and regional O2
consumption. Much remains unknown about ScvO2.
Further work is needed to understand changes of
ScvO2 over time in assessing treatment and in different
types of patients.
References
1. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed
therapy in the treatment of severe sepsis and septic shock.
N Engl J Med 2001;345(19): 1368-77
2. Marx G, Reinhart K. Venous oximetry. Curr Opin Crit Care
2006;1 2:263–268.
3. Reinhart K, Kuhn HJ, Hartog C, Bredle DL. Continuous
central venous and pulmonary artery oxygen saturation
monitoring in the critically ill. Intensive Care Med
2004;30(8): 1572-8
4. Chawla LS, Zia H, Gutierrez G. Lack of equivalence
between central and mixed venous oxygen saturation.
Chest 2004;126:1891-96
5. Varpula M, Karlsson S, Ruokonen E. Mixed venous
oxygen saturation cannot be estimated by central venous
oxygen saturation in septic shock. Intensive Care Med
2006 (electronic reference http://dx.doi.org/10.1007
/s00134-006-0270-y)
6. Ander DS, Jaggi M, Rivers E, et al. Undetected cardiogenic
shock in patients with congestive heart failure presenting
to the emergency department. Am J Cardiol 1998;82(7):
888-91.
7. Rivers EP, Martin GB, Smithline H, et al.. The clinical
implications of continuous central venous oxygen
saturation during human CPR. Ann Emerg Med 1992; 21;
1094-1101
8. Scalea TM, Hartnett RW, Duncan AO, et al. Central
venous oxygen saturation: a useful clinical tool in trauma
patients. J Trauma 1990; 30:1539-43
9. Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM,
Bennett ED. Changes in central venous saturation after
major surgery, and association with outcome. Crit Care
2005;9(6):R694-9.
10. Bloos F, Reinhart K. Venous oximetry. Intensive Care Med
2005;31(7):911-13.
11. Rivers E, Ander DS, Powell D. Central venous oxygen
saturation monitoring in the critically ill patient. Curr
Opin Crit Care 2001;7;204-211

46
Invasive Haemodynamic Monitoring
Introduction
Invasive haemodynamic monitoring has
revolutionised critical care practice. Assessment and
interventions for critically ill patients have been
transformed by the appropriate acquisition of
haemodynamic data, the appropriate interpretation of
the data obtained, and the subsequent decision making
that alters therapeutic interventions. Invasive
haemodynamic monitoring provides a tool to monitor
cardiovascular physiology, to titrate interventions and
to evaluate the response to the therapies instituted. For
the results of haemodynamic monitoring to be utilized
effectively, the bedside clinician must have a solid
foundation in understanding the technical and
physiologic implications that can impact the values
obtained.
I will address the issues of invasive haemodynamic
monitoring under the following headings.
Measuring Cardiac Output
Measuring Oxygen Utilisation
Continuous Monitoring
Less Invasive Monitoring
Functional Haemodynamic Monitoring
1) Measuring Cardiac Output
In the early 1970’s when Drs Swan and Ganz brought
this valuable tool, Pulmonary Artery Catheter (PAC), to
assess intracardiac pressures, patients had to be
transported to the cardiac catheter lab to obtain these
measurements. Once the PAC becomes readily
available these parameters could be obtained at the
bedside and without the need for fluoroscopy. Early in
the clinical use of PAC the pressures and cardiac
determinations were the primary parameters obtained.
Yet despite it being available the concept still required
more than two decades to gain acceptability in the
routine practice of most clinicians.
Changes in haemodynamic monitoring over the past 10
years have followed two paths. First, there has been a
progressive decrease in invasive monitoring, most
notably a reduction in the use of the pulmonary artery
catheter because of a presumed lack of efficacy in its
use in the management of critically ill patients, with an
increased use of less monitoring requiring only
central venous and arterial catheterization to derive the
same data. Second, numerous clinical trials have
documented improved outcome and decreased costs
when early goal-directed protocolised therapies are
used in appropriate patient populations.
The problem facing the clinicians when trying to
evaluate the effectiveness of the PAC is an important
one that goes beyond PAC use. Unlike the introduction
of new medications, technologies are not required to
demonstrate an impact on patient outcome prior to
approval for use. Virtually none of the current
technologies, ranging from noninvasive blood pressure
monitoring to echocardiography, have been well
studied for their impact on patient outcome.
Monitoring and diagnostic technologies, of which the
PAC is a member, do not directly impact patient
outcomes. The outcome of the patient is based on the
clinician’s interpretation of the information provided
by the technology.
For PAC utilization to accurately measure cardiac
output (CO) using thermodilution technique there are
some specific assumptions that must be taken into
consideration.
• The bolus must be injected within 4 seconds;
• The amount of the solution must be accurate;
• The temperature of the injectate must be precisely
measured;
• The catheter must be properly placed within the
heart and pulmonary artery;
• The computer must have the appropriate
computation constant
Another factor that can result in non-reproducible
values is the timing of the injectate to the respiratory
cycle. CO can differ from inspiration to expiration.
Mohamed Hassan M Ariff, MBBS (Monash), FFARCSI, FAMM
Department of Anaesthesia and Intensive Care, National Heart Institute.
Dato’ Dr Mohamed Hassan M Ariff is the Head of Department of Anaesthesia and Intensive Care, National Heart Institute. A
leading authority in cardiothoracic anesthesia in the country, his areas of interest include cardiopulmonary perfusion, cardiac
assist devices and paediatric cardiac anaesthesia and perfusion.

47
MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
Determinations that are not within a 5% to 10% range
are frequently deleted from the series. Averaging
strategies can produce varied CO values. For
reproducibility rather than accuracy, potential
physiologic events are often deleted. Apart from the
inherent variables cited above, the PAC is not without
its detractors. In general there is a reduction in PAC
utilization over the past 10 years. The decisions usually
quoted for using less of invasive haemodynamic
monitoring by the PAC are
1) increased risk to the patient with PAC insertion
and placement
2) the ability to measure similar variables via other
less invasive techniques e.g. CVP,
echocardiography (TEE or TTE),
3) increased cost
4) inaccurate measurement and misuse of PAC
derived variables
5) incorrect interpretation and application
6) lack of proven benefit of PAC in the overall patient
management.
However if we look at each of the reasons cited, we see
that they can be countered.
1) The risks of PAC insertion is not much different
from that of a CVP catheter insertion (hemorrhage,
pneumothorax, large vessel damage, arrhythmias)
– the only specific PAC complication is pulmonary
artery rupture
2) Although CVP catheters can also give central
venous saturation as a surrogate (as mixed venous
saturation in PAC) and cardiac output (via other
means e.g. PiCCO derived), it does not give
pulmonary circulation data
3) In Malaysia cost consideration is indeed a factor to
decide, but the cost of a PAC has come down in
recent times
4) Inaccuracies of PAC measurement usually are seen
during measurements of PCWP and PAOP rather
than mixed venous saturation
5) Inaccuracies of interpretation and application can
be reduced with better education and
familiarization – it is more of user fault than
equipment fault
6) Most of the studies that examine PAC derived data
and patient outcome do not examine them with a
defined treatment plan. Hence lack of proof of
benefit does not equate to proof of lack of benefit.
One must also realize that there is no such thing as a
normal cardiac output, and accurate measures of
cardiac output are less important than measures of
cardiac output changes in response to treatment and
time. Thus if one wants to accurately define adequacy
of cardiac output then we must also measure whether
the oxygen delivery is adequate to match the oxygen
demand. Hence measures of mixed venous oxygen
are essential - whether one uses the PAC to obtain
mixed venous saturation or one uses the CVP to
obtain central venous oxygen as a surrogate of mixed
venous saturation.
2) Measuring Oxygen Utilisation
The primary clinical application of mixed venous
oxygen (SvO2) monitoring is the assessment of
tissue oxygenation. Tissue oxygenation is the key
parameter that is affected by changes in cardiac
output and blood pressure. Since SvO2 reflects the
balance between oxygen delivery and oxygen
consumption, SvO2 values are often tied to
assessments of the adequacy of haemodynamic
values. Questions such as ‘What blood pressure or
cardiac output is acceptable for a given patient?” can
be better evaluated through the use of SvO2.
The benefit of the SvO2 value is that it is a reflection
of the overall balance of oxygen delivery and
consumption. A normal SvO2 value-about .60 to
.75-indicates that the balance between oxygen
delivery and consumption is adequate. If the SvO2
drops below .60, then either oxygen delivery is
inadequate (as in low cardiac output states like
congestive heart failure) or oxygen consumption is
too high (as in respiratory failure). The lower the
SvO2 value, the more likely a problem exists in terms
of tissue oxygenation. SvO2 values in the .30 to .49
region have been associated with disruptions in the
ability to produce adenosine triphosphate (ATP).
Elevated SvO2 values also are potentially
dangerous, indicating an obstruction or
maldistribution of blood flow to tissues in which
cells are unable to use oxygen. In the case of either
obstruction or maldistribution, an SvO2 value over
.75 is an indicator of a threat to tissue oxygenation in
that tissues are either not using or not receiving
oxygen. Most of the hemoglobin (SvO2) is being
returned to the lungs without having oxygen
removed.

48
YEAR BOOK 2006/2007
If blood pressure (BP) is considered low (e.g. 80/50 mm
Hg) but the SvO2 is normal, then the blood pressure is
not likely to be harming tissue oxygenation. If the BP is
low and the SvO2 is low, then treatment of the blood
pressure is more important.
Central venous saturation (CeVOX) as a surrogate of
mixed venous saturation is becoming more utilized
especially when PAC utilization is not an option (e.g.
pediatrics, or unstable patients).
Using pulse oximetry (SpO2) and SvO2 is termed “dual
oximetry”. Oxygen extraction can be obtained by
simply subtracting SvO2 from SpO2. Certain monitors
either provide a pulse oximeter to obtain SpO2 or have
the capability to have the value slaved in. Once both
SpO2 and SvO2 are available, dual oximetry parameters
can be obtained and displayed.
3) Continuous Monitoring
Continuous Cardiac Output (CCO)
There are two clinically acceptable methods available
to measure CO: bolus thermodilution (BTD-CO) and
continuous cardiac output (CCO). The bolus method
only allows intermittent measurement of cardiac
output and introduces the potential for user variability.
With the intermittent method, an injectate temperature
cooler than blood temperature is used for the input
signal.
The introduction of continuous cardiac output
measurement allows for near real-time measurement of
blood flow and stroke volume. Since the process is
automated, it also reduces user variability. A modified
pulmonary artery catheter with a 10cm thermal
filament is used. The thermal filament is maintained in
the right ventricle and continuously transfers heat
directly into the blood according to a random pattern.
A temperature change (less than 0.04ºC) is detected
downstream on a thermistor at the distal tip of the
pulmonary artery catheter. A computer calculates CO
via a thermodilution washout curve. A digital CO is
displayed continuously on the CCO monitor and is
updated every 30 seconds to provide an average flow
over the previous 3 – 5 minutes. CCO requires no user
calibration procedures.
Advantages of CCO include the ability to continuously
measure blood flow (i.e. cardiac output) and detect
changes in cardiac output and stroke volume early and
eliminate clinician error due to improper injectate
solution, volume, and/or temperature. Fewer
erroneous data are obtained due to dysrhythmias or
respiration variation. Limitations of CCO include time
delays in the response of the CCO catheter, need for an
invasive catheter, and increased cost of the catheter.
CCO values are influenced by the same assumptions as
intermittent thermodilution determinations – there
must be forward flow; a steady baseline PA
temperature; adequate mixing of the blood and input
signal; and proper catheter placement. Many of the
technique- related potentials for error are eliminated,
such as amount of fluid injected, timing of the injectate,
proper injectate sensing, and computation constant.
Continuous Venous Saturation (Mixed and
Central)
The technology for continuous SvO2 monitoring has
been in place for over 20 years. Refinements in the
optical processing of reflected light has minimized
problems of accuracy. However, manufacturers still
recommend an in vivo calibration on a daily basis to
confirm accuracy of the device.
The continuous SvO2 monitoring pulmonary artery
catheter functions by using light-emitting diodes that
send light (specifically along the light spectrums of red
and infrared light) into the blood. This allows the
detection of oxygen-carrying hemoglobin
(oxyhemoglobin) and non-oxygen carrying
hemoglobin (deoxyhemoglobin) by comparing the
amount of red and infrared light that is reflected. Light
bounces off hemoglobin (among other things), and the
reflected light is analyzed by an optical module. The
ratio of red to infrared light that is reflected is a
function of how much oxyhemoglobin and
deoxyhemoglobin is present. Changes in hemoglobin
should be monitored. Continuous monitoring of
patient variables has provided the clinician with the
ability to observe adverse events in a more timely
fashion. Physiologic changes can be acted upon in
amore timely manner than with intermittent
assessment
In its ultimate form it continuously measures
temperature, heart rate, mixed venous O2 saturation
(SvO2), cardiac output, right ventricular ejection
fraction and end diastolic volume, central venous
pressure and pulmonary arterial pressure. When

49
MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
coupled with non-invasive pulse oximetry, it can also
give total oxygen delivery (DO2) and consumption
(VO2). These measures will be made more effective if
coupled with parallel measurements of tissue wellness
with other techniques.
Continuous CeVOX is also available in the market now
e.g. PreSep catheter by Edwards.
4) Less Invasive Haemodynamic Monitoring
Pulse Contour Analysis
The possibility of determining the CO using the
arterial pulse wave has intrigued both scientists and
clinicians for decades. Preliminary successes have
been achieved using techniques involving
determination of the area under the arterial pressure
curve, as well as other methods involving analyses of
various subtleties of the wave. The issue has been
quantifying the relationship between the amount of
blood flow and the pressure wave associated with it.
This relationship can vary widely from one individual
as clinical conditions change. Knowing this
relationship for an individual patient and
circumstance allows for the calculation of a constant
(K), which can be used for subsequent CO
assessments. Techniques using the arterial wave have
thus previously required initial calibration with
another method of CO assessment.
There are four devices that track stroke volume (SV) by
analysis of the arterial pressure waveform
- 1) the PiCCO monitor (Pulsion, Munich, Germany)
- 2) the LiDCO plus System (LiDCO, Cambridge,
UK)
- 3) the PRAM system (FIAB SpA, Florence, Italy)
- 4) the Vigileo system and Flo Trac System (Edwards
Lifesciences, USA)
PiCCO
The clinical validation studies for pulse contour were
done with the arterial catheter in the femoral
position. The accuracy of pulse contour seems to
lessen when the arterial waveform analysis is
obtained from a peripheral location. The PiCCO
system may only be used with a cannula placed in
the femoral or axillary artery. Kinking of the cannula
may necessitate recalibration or even replacement of
the arterial cannula followed by recalibration. As
circulatory compliance changes in response to
primary physiological changes or vasoactive drugs,
the morphology of the arterial waveform alters. This
is not problematic unless the pulse rate is
particularly irregular.
The PiCCO continuous cardiac output shows good
agreement with intermittent thermodilution of PAC,
requiring recalibration only during major changes in
systemic vascular resistance e.g. after phenylephrine
infusion. This system also gives additional values
over and above the conventional data obtained from
the PAC catheter. Global end diastolic volume
(GEDV) approximates intrathoracic blood volume
(ITBV) and extravascular lung water (EVLW) as a
surrogate for cardiac preload. ITBV and EVLW have
traditionally been measured by the double indicator
technique (thermodilution and indocyanine green)
via a pulmonary artery catheter. Using EVLW to
guide fluid management in medical intensive care
patients has been suggested to reduce the duration of
mechanical ventilation and length of stay in the ICU.
The ITBV has been suggested to be a better indicator
of cardiac preload than pulmonary artery occlusion
pressure (PAOP) and central venous pressure.
Lithium Dilution Cardiac Output (LiDCO)
A small dose of lithium chloride is injected via a
central or peripheral venous line; the resulting
arterial lithium concentration-time curve is recorded
by withdrawing blood past a lithium sensor attached
to the patient’s existing arterial line. In terms of
accuracy, clinical studies have demonstrated that the
LiDCO method is at least as accurate as
thermodilution over a wide range of cardiac outputs.
It is more reliable than conventional thermodilution
cardiac output measurement. The dose of lithium
needed (0.15 – 0.3 mmol for an average adult) is very
small and has no known pharmacological effect.
Recalibration is unnecessary for at least 8 hours. This
approach differs slightly from that of the PiCCOTM
system; LiDCO analyses the arterial waveform
throughout the cardiac cycle whereas PiCCOTM
utilizes only the area under the systolic portion of the
curve.
Only three studies in humans have been published in
peer-reviewed journals, two in cardiac surgical patients
and one in critically ill paediatric patients.

50
YEAR BOOK 2006/2007
Pressure Recording Analytical Method
(PRAM) System
The PRAM system is based on the physics of
perturbations. It analyses all of the arterial wave
using a collecting signal of 100Hz. The most
important points on the waveform are the diastolic
pressure, the systolic pressure and the point of
closure of the aortic valve. The SV is calculated from
the area under the curve in the interval between the
diastolic part of the curve and the dicrotic notch. In
this way the system is analysed individually and
does not require calibration to correct for
compliance. PRAM has already been validated in
cardiac surgery against the PAC.
Edwards Vigileo and Flo Trac System
The Edwards Vigileo system, using the FloTrac
sensor attached to arterial pressure tubing, needs no
such calibration and provides continuous CO
measurements from the arterial pressure wave.
The system consists of a sensor (FloTrac, Edwards
LLC) and a processing/display unit (Vigileo,
Edwards LLC). The processing unit applies a
proprietary algorithm to the digitized wave, and
reports CO, cardiac index, stroke volume , stroke
volume index and stroke volume variation (SVV).
The system calculates the arterial pressure using
arterial pulsatility (standard deviation of the
pressure wave over a 20-s interval), resistance and
compliance, according to the following general
equation:
Stroke volume = K x Pulsatility
where K is a constant quantifying arterial
compliance and vascular resistance, and pulsatility
is proportional to the standard deviation of the
arterial pressure wave over a 20-s interval. K is
derived from patient characteristics (gender, age,
height and weight) as well as waveform
characteristics (e.g., skewness and kurtosis of
individual waves). This calibration constant is
recalculated every 10 min. There was close
correlation between the algorithm and continuous
thermodilution CO.
This technology represents a highly innovative and
potentially significant advance in haemodynamic
assessment. The lack of necessity for calibration
with a more invasive method of CO assessment
provides for easy and expeditious use in a myriad of
clinical venues, including the emergency room,
cardiac care unit, operating room, trauma bay,
medical/surgical intensive care units and
intermediate care units.
This represents an advantage over the PiCCO
system, which requires a centrally placed arterial
catheter (femoral, axillary or long radial). To obtain
information about systemic vascular resistance, a
central venous catheter can be transduced and
interfaced with the Vigileo. This allows the clinician
to provide optimal fluid, vasodilator and inotropic
therapy without the need for pulmonary artery
catheterization.
The FloTrac Vigileo system also reports SVV. This is
the change in SV in one respiratory cycle. Patients
suffering hypovolemia exhibit an exaggerated SVV.
A large SVV (>10%) thus indicates that the patient is
likely to respond favorably to fluid administration.
If a central venous pressure catheter has been placed,
its signal can be interfaced with the Vigileo, allowing
for the calculation of systemic vascular resistance
(SVR) and SVR index (SVRI). When use with a central
venous oximetry catheter, the Vigileo also provides
continuous central venous oxygen saturation (ScvO2).
The Vigileo reports haemodynamic parameters at 20-s
intervals, performing its calculations on the most
recent 20s of data.
Potential weaknesses of the system include possible
inaccuracy in the presence of arterial wave artifact,
compromise of the arterial catheter, aortic
regurgitation, intense peripheral vasoconstriction
and irregular pulse.
Functional Haemodynamic Monitoring
Specific haemodynamic variables are commonly
measured and displayed at the bedside, and their
values are often used in clinical decision making.
However the utility of each variable as a single
absolute value is questionable. This gives rise to the
concept of functional haemodynamic monitoring. It
can either be viewed as a solitary value and
interpreted according to its value and patternwhich

51
MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
may be called static functional monitoring. It can
also be viewed to evaluate the effect of treatment
looking at trends of change, hence implying its
therapeutic application which can be looked as a
dynamic functional haemodynamic monitoring.
Although trends in specific variables over time are
useful in defining haemodynamic stability, their
rapid change in response to application of a therapy
has greater clinical utility. For example, an elevated
CVP implies right ventricle pressure overload, it
provides no information on the precise etiology.
Assessing preload adequacy is more definitive in
managing a patient with elevated CVP – e.g. volume
challenge with fluids or passive leg raising (similar
to a slight Trendelenberg position). Recent
monitoring devices have incorporated this as part of
their system e.g. SVV value in PiCCO and Flo Trac
system.
One must not only look at the effect of respiration or
ventilation on the CVP but one must also give close
attention to CVP waveform interpretation. Examples
are given.
Conclusion
The effectiveness of haemodynamic monitoring
depends both on available technology and on our
ability to diagnose and effectively treat the disease
processes for which it is used. Within this context
haemodynamic monitoring represents a functional
tool that may be used to derive estimates of
performance that may in turn direct treatment. It
must be stressed that no monitoring device, no
matter how accurate or complete, could be expected
to improve patient outcome, unless coupled to a
treatment that itself improves outcome.
Further reading
1. M Singer, E D Bennett. Invasive Haemodynamic
Monitoring in the United Kingdom. Chest 1989; 95 : 623
– 626.
2. M Singer. Cardiac Output 1998 (Review). Heart 1998;
79: 425 – 428.
3. M Pinsky. Haemodynamic Monitoring Over the Past 10
Years. Critical Care 2006; 10: 117.
4. D Prentice, T Aherns. Controversies in the Use of the
Pulmonary Artery Catheter (Haemodynamic
Monitoring). J of Cardiovasc Nursing 2001; 15(2):1-5.
5. S Tibby, I A Murdoch. Monitoring Cardiac Function in
the Intensive Care (Review). Arch Dis in Childhood
2003; 88(1):46 – 52.
6. J M Headley. Invasive Haemodynamic Monitoring:
Applying Advanced Technologies. Crit Care Nurs
Quart 1998; 21(3): 73 – 84.
7. M Pinsky, J L Vincent. Let Us Use the Pulmonary Artery
Catheter Correctly and Only When We Need It. Crit
Care Med 2005; 33(5): 1119 – 1122.
8. R L Reed. Mixed Venous Saturation as a “stand-alone”
Indicator of the Oxygen Extraction Ratio. Int Care 2004;
11(3): 103 – 108.
9. J D Edwards, R Mayall. Importance of the Sampling
Site of Mixed Venous Oxygen Saturation in Shock. Crit
Care Med 1998; 26(8): 1356 – 1360.
10. K Reinhart, H J Kuhn, D L Bredle. Continuous Central
Venous and Pilmonary Oxygen Saturation Monitoring
in the Critically Ill. Int Care Med 2004; 30: 1572 – 1578.
11. J C Cheney, S Derdak. Minimally Invasive
Haemodynamic Monitoring for the Intensivist: Current
and Emerging Technology (Review). Crit Care Med
2002; 30(10); 2338 – 2345.
12. 12)C Zollner, M Haller, M Weis, K Morstedt, P Lamm, E
Kliger, A E Goetz. Beat to Beat Measurement of Cardiac
Output by Intravascular Pulse Contour Analysis: a
Prospective criterion Standard Study in patients After
Cardiac Surgery. J Cardiothoracic Vasc Anesth 200;
14(2): 125 – 129.
13. G R Manecke. Edwards FloTrac Sensor and Vigileo
Monitor. Expert Rev Med Devices 2005; 2(5): 523 – 527.
14. R M Pearse, K Ikram, J Barry. Equipment Review: An
Appraisal of the LiDCOplus Method of Measuring
Cardiac Output. Crit Care 2004; 8(3):190 – 195.
15. S Romano, M Pistolesi. Assessment of Cardiac Output
from Systemic Arterial Pressure in Humans. Crit Care
Med 2002; 30(8): 1834 – 1841.

52
YEAR BOOK 2006/2007
16. S Scolletta, S M Romano, B Biagioli, G Capannini, P
Giomarelli. Pressure Recording Analytical Method
(PRAM) for Measurement of Cardiac Output During
VariousHaemodynamic States. Br J Anaes 2005; 95(2):
159 – 165.
17. M Pinsky, D Payen. Functional Haemodynamic
Monitoring. Crit Care 2005; 9(6): 566 – 572.
18. 18 )G Marx, T Cope, L McCrossan, S Swaraj, C Cowan,
S M Mostafa, R Wenstone, M Leuwer. Assessing Fluid
Responsiveness by Stroke Volume Variation in
Mechanically Ventilated Patients with Severe Sepsis.
Euro J Anaes 2004; 21: 132 – 138.

53
Triage In The Intensive Care Unit
The demand for beds in the intensive care unit in both
general hospitals and teaching hospitals in Malaysia
usually far exceeds their availability. A national survey
carried out from May to July 2005 on intensive care
beds in all hospitals in Malaysia,1 showed that the
number of ICU beds made up only 1.5% of the total
hospital beds i.e. 2.4 ICU beds per 100,000 population.
This figure is rather dismal when compared to
developed countries (United Kingdom 8.5, Germany
28.5, France 38.4, United States 30.5). A 3 year audit on
adult intensive care units2 further revealed that as
much as 56% of patients referred were denied
admission due to the non-availability of beds, resulting
in patients being mechanically ventilated in the general
wards and an increased in mortality (51.8%) of those
denied admission. The situation is expected to worsen
as our population expands and ages. In addition,
advances in medicine have led to more complicated
procedures and treatments, resulting in patients
needing admission to ICU for monitoring purposes.
The reasons for this shortfall in ICU beds in Malaysia
are unknown as no local studies have looked into this
shortage. We may speculate that the main reasons for
Malaysia are likely to be financial and manpower
shortage. It is impossible for a developing country like
Malaysia to match the United States where ICU
expenditure accounts for up to 13.3% of total hospital
costs, 4.2% of national expenditure and 0.56% of their
Gross Domestic Product. However, many other factors
may also play a role. Lack of pooling of resources
within and between hospitals, persistent admission of
patients with no hope of survival and delays in
discharging patients that no longer require intensive
care may all be contributory.3
As the demand for intensive care services outstrips the
availability, prioritizing patients who will benefit most
from intensive care has been at the forefront of
intensive care practice in recent years. ‘Triage’ as it is
known, is derived from the French word ‘trier’ which
means to put aside and was first practiced by the
French military in the 19th century. For triage to take
place, the patient has to be identified first (pre ICU
triage). Various medical factors like age, severity of
illness, diagnosis, quality of life and advance
directives have been used in the triage decision.
However, non medical factors like the availability of
beds, type of referral (patient, chart or telephone
review), time of triage, seniority of the ICU physician,
interpersonal relationships and financial gain can also
affect the triage decision.4 For pre ICU triage to be
effective, it is impossible to ignore the fact that ICU
beds can be blocked by patients who no longer require
intensive care (post ICU triage). This has led to the
development of intermediate or ‘step down’ units to
cater for this group of patients.
Age has been used to triage ICU patients, as it is a
simple and objective measure of life expectancy. The
average life expectancy has increased substantially
worldwide and by the year 2020, the male life
expectancy in Malaysia is predicted to rise to 75 years
while for females it is 78 years. It would be difficult to
set an arbitrary cut off point and ethically questionable
to exclude older patients on the basis of age alone. In a
survey of 600 ICU clinicians, only 12% stated that age
should limit ICU admission; most indicated that
quality of life, probability of survival, reversibility of
acute illness and co-morbidities were more important
considerations when triaging.5 In the Support
Prognostic Model, which was done to understand
prognosis and preference for outcomes and risks of
treatments, age was found to be only a minor
contributor towards predicting 180 day survival
compared to acute physiological changes and Glasgow
Coma Scale.6 In another study by Nicholas F on
influence of patient’s age on survival,7 although
mortality was found to be higher in the older age
group, this is because of a greater severity of illness in
the elderly, with age being only a minor component
contributing to excess mortality. A similar study
looking into the outcome of intensive care in the
elderly,8 showed that the number of organ system
failures was associated with increased ICU and 1 year
mortality while age was not.. Age was also found to
Toh Khay Wee, MBBS (London), FRCA, EDIC
Dr Toh Khay Wee is a Consultant in Anaesthesia and Intensive Care at Subang Jaya Medical Centre. His teaching
and research interests include ALS training, Early Warning Systems in Intensive Care and Assessment of Intra-
thecal Blockade.

YEAR BOOK 2006/2007
54
have little impact on 1-year survival in over 65 years of
age whereas severity of illness, length of stay, prior ICU
admission and respiratory failure were much better
predictors.9 Similarly in the Malaysian population, a 2
year review of ICU survivors and non-survivors in the
year 2003-2004,10 also revealed that age was not found
to be an independent risk factor for death. However,
Joynt studied 236 ICU refusals and showed that
patients above the age of 65 years were more likely to
be refused admission (OR 2.58 [1.69 – 3.94]).11 A similar
study by Sprung showed that the 92 ICU refusals were
older (OR 1.02 p 0.04).12 A study carried out in Israel on
survival in critically ill patients hospitalized in and out
of intensive care units under paucity of intensive care
beds showed that the ICU population had a
significantly much younger age group compared to the
other departments. 13 This is in contradiction to single
and multi centre studies carried out in France by
Garrouste-Orgeas that showed that age was not a factor
in ICU refusal.14 It would appear that the importance of
age as a triage tool is not uniform and can vary
depending on the centre. From these studies, it would
seem that the withdrawal of therapy and triage
decisions should not be solely or primarily based on
age alone.
In 1988, a consensus panel in the United Kingdom
stated that the ‘Selection for intensive care should be
based on broad concepts of prognosis derived from
statistical analysis of comparable cohorts of patients
backed up by sound clinical trials’. Twenty years later,
we all know that the applicable instruments are hardly
available. All the current severity of illness scoring
systems suffer from very low sensitivity (APACHE II
51%, MPM 11.7%, SAPS II 21.2%) although specificity is
better (APACHE II 85.4%, MPM 84.5%, SAPS II
96.8%)15,16 This means that a proportion of those who
are not expected to survive in fact survive, making
these scoring systems useless for predicting individual
patients’ outcomes. Furthermore only MPM0 has been
validated for immediate assessment and can be applied
at the time of ICU admission. All the other scoring
systems include variables of physiological abnormality
after a specified time in the ICU. In comparison, it has
been shown that physicians could better discriminate
survivors from non-survivors as measured by area
under the receiver operating characteristic curve (0.89
for physicians vs. 0.83 for APACHE II, p < 0.001).17
Although medical intensive care personnel were fairly
accurate discriminators, there was a tendency to
underestimate survival that was affected by the level of
training and forecasting accuracy.18 Albeit an
improvement in sensitivity, physicians’ estimates still
had a poor sensitivity of 24% (compared to the
sensitivity of MPM0 2%). If survival was combined
with poor functional outcome as an end point, there
was an improvement in sensitivity to 35%. The benefits
of combining an objective prognostic measure with a
physicians estimate can be seen in the SUPPORT trial6
in which a model was developed for predicting
180-day survival. In this study, the discriminatory
ability of the model was increased from 0.79 to 0.82
when the physician’s estimates were included. It would
appear that scoring systems used in conjunction with
the clinical judgment of the physician represent the best
tools we have at the moment.
Severity of illness has been used to identify those
patients who will benefit most from ICU care by
refusing care to those who are ‘too well’ and those who
are ‘too sick’ to benefit from intensive care. In practice,
it is difficult to identify these 2 groups of patients.
There is a tendency for ICUs to refuse admission with
increasing severity of illness as shown by Joynt and
Sprung using MPM (OR 1.0[0-0.33], 1.49[0.34-0.66],
2.4[0.66-1.0]) and APACHE II (OR 1.0[1-10], 3.3[11-20],
27.5[21+]) scoring respectively.11,12 Both studies also
showed excess in mortality most marked in those
patients in the middle range of severity of illness
refused intensive care. When appropriately referred
patients for intensive care were refused admission to
the ICU, there was a relative risk of death of 1.6
compared with a group of appropriately admitted
cases with medium APACHE II scores (11-20). This
would suggest that if these patients were admitted,
lives would be saved. However, it is this middle
territory of disease severity where there is a lack of
discriminatory tools available to identify those who
might benefit from ICU.
The diagnosis can also have an influence on the
triaging decision. Diagnosis affecting the
cardio-respiratory system (OR refusal 0.53), sepsis (OR
0.46) and chronic renal disease (OR 0.45) were
associated with admission in 2 studies.11, 4 However,
this in contrast to the study by Sprung which showed
that refusal was associated with the cardio respiratory
system (OR 1.7), sepsis (OR 2.4) and neurological
system (OR 1.4).12 Not surprisingly, the highest refusal
rates were associated with metastatic cancer (OR 5.82),

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
55
chronic respiratory diseases19 and diseases that are
expected to cause death in <1 year (OR 2.67).14 There
also appears to be a bias against medical patients
whereby surgical and postoperative patients were
more likely to be granted admission.11,12,14 One can
only speculate that surgical patients may derive greater
benefit from ICU as shown by a higher mortality
among medical patients compared to surgical
patients.12 Another point to note is that all these studies
were performed by anaesthetists who have a closer
working relationship to their surgical counterparts.
Quality of life measure as a triaging tool appears
attractive as it provides information on the previous
functional status of the patient and what can be
achieved with further intervention. Quality of life
measures like the Nottingham Health Profile and
Katz’s Activities of Daily Living require cooperative
and conscious patients which may not be applicable to
the critically sick. Refusals for ICU admission have
been associated with quality of life factors like ‘needing
help at home’ (p 0.02), resident in a long term care
facility (p 0.002) and dependency (p 0.002).4. This was
similar to the large multi centre French study that
found higher refusal rates in dependent and
institutionalised patients.14 A lower hospital mortality
was found in patients who were able to live at home
without any help (Hazard Ratio 0.440 0.28-.68)4 and
had no chronic health problems.13 Although functional
status is used as an indicator of quality of life, Wilson
and Cleary found that despite poor function in
activities of daily living,25 patients may actually
perceive good health status and overall happiness.
When examining quality of life 1 year after ICU
admission, Konopad26 found that even though patients
had lower levels of activity, these patients perceived
better overall health status. Furthermore, functional
status can change as 30% of patients with marked
limitations of function at admission demonstrated
improvement after 2 months. Most physicians agree
that the family should play an active role in decision
making but patients’ and families’ opinions were more
often obtained by ICU physicians when the patients
were physically capable of expressing their wishes.
This may mean that triaging physicians who deemed
ICU admission inadvisable may have been reluctant
to ask the families involved for their opinion.One
study in France24 even showed that only 79% of
patients would designate their spouse as their
surrogate decision maker. The question of the
patient surrogate may be very different in Malaysia
given the role of the extended family which can involve
more than one individual. On the issue of advanced
directives, one Scandinavian study showed that only
1% of ICU patients27 had advance directives. This
figure is probably much lower in Malaysia.
It is interesting to note that the way and to whom a
referral is made can also affect the triage decision.
Phone triage and patients with unknown cardio
respiratory function have been significantly associated
with admission compared to patient review by the
triaging physician.4,14 Furthermore, there is evidence to
show that senior ICU triaging physicians are more
likely to refuse ICU admission compared to their junior
counterparts.4,14 This could imply that experience is
vital in the triaging process whereby more senior staff
with prior experience is possibly better at identifying
situations where ICU admission is not necessary. It is
also comforting to note that physicians are reluctant to
deny ICU admission in the face of limited
information.4,14
One of the most common problems faced by the ICU
triaging physician is deciding who should go to ICU
when there is a lack or no beds in the ICU. Evidence
shows that there is a tendency to refuse admission (OR
3.2 p 0.02) when the unit is full.4,12,14 However, triaging
decisions during these times were not significantly
associated with an increased mortality with other
factors like APACHE II, medical status and diagnosis
positively correlating to mortality.12,20 There was also a
tendency for refusing patients who were referred out of
hours whilst patients referred in the day were more
likely to be admitted (OR refusal 0.52).14 These findings
are not surprising but the higher rate of refusals in the
night may indicate that a shortage of staff during those
periods may have an effect on the triaging decision.
The increasing need to improve triaging decisions led
to the development of the Medical Emergency Teams
(MET) in Australia and Critical Care Outreach Teams
(CCOT) in the United Kingdom in the 90’s. The
primary objective of these teams were to identify
critically ill patients earlier, avert ICU admission
through early and appropriate management,
improving outcome and to educate ward staff on
managing critically ill patients. Earlier studies were
promising with Schein showing a 50% reduction in
cardiac arrest after the introduction of the MET.28 A

YEAR BOOK 2006/2007
56
prospective controlled trial of the effect of the MET on
postoperative patients showed that there was a
significant relative risk reduction of 36% for
postoperative death, 44.4% for emergency ICU
admissions and reduction in duration of hospital stay
from 23.8 days to 19.8 days.21 In contrast, a recent
study on 20,000 patients in Australia did not show any
benefit of the MET on reducing the incidence of
cardiac arrest or death.29 A study carried out at the
University of Malaya showed that critically ill medical
inpatients at risk of death could be identified by the
Modified Early Warning Score. This may mean that
the MET may still have a role in triaging by allowing
critically ill patients to be highlighted earlier. This
allows the ICU physicians to make better assessments
of their patient in terms of patient preferences, pre
hospital quality of life and reversibility of their
current condition. This information may not have
otherwise been possible in an acutely sick and
deteriorating patient.
In order to standardize the process of triaging to fulfil
the 4 principles of medical ethics (beneficence, non
malificience, autonomy and distributive justice),
guidelines on triaging have been issued by the Society
of Critical Medicine in 1999.22 The guidelines put
forward several principles:
1) Admission criteria should only select those who
are likely to benefit from ICU care.
2) To use tools for assessing severity of illness and
prognosis of critically ill patients combined with
clinical judgment.
3) Admission to be based on several models utilizing
prioritisation, diagnosis and objective parameter
models.
4) ICU director should have authority and
responsibility to admit or discharge patients when
the ICU is full.
5) Triage policies should be written in advance.
6) Triage decisions should be made explicitly and
without bias (ethnic, social status, sexual
preference and financial status are not to
be considered)
7) Triage decision may be made without patient or
surrogate consent.
8) Religious or moral convictions may be the basis for
providing treatment provided the costs are not
borne by society and the provision does not
foreclose treatment to other patients.
9) Policies should be reviewed annually by a multi
professional team.
However, the society clearly states that these are only
guidelines and individual institutions need to create
their own criteria to meet their specific requirements.
A recent Scandinavian survey showed that only 8% of
intensivists were aware of published guidelines on
triaging.23 In order to show compliance with triaging
guidelines, a French study on 26 ICUs showed that on
average only 4 (range 0-8) out of 20 recommendations
were observed when patients were refused ICU
admission. The situation was even worse when there
was a full unit or if triaging was done over the
phone.19 Therefore it appears that guidelines are
difficult to put into practice in real life.
In Malaysia where there is a shortage of beds,
improving the efficiency of the ICU has become of
paramount importance. This can be achieved by
pooling of resources like having a central or regional
bed manager to identify available ICU beds in the
region. An early warning system should also be put
into place in the general wards to identify patients
who are at risk of deterioration. Physicians in the
ward need to issue and record “do not resuscitate”
(DNR) orders in the notes of terminally ill patients.
Withdrawal and withholding therapy should be
practiced. A set of local guidelines also needs to be
developed to meet the multi cultural and religious
needs of the Malaysian society.
For the foreseeable future, triage to ICU will continue
to be dealt with on an individual basis. None of the
current triaging tools in use have been shown to be
perfect and we are left with a combination of these
tools which are only useful for research and audit
purposes. Furthermore as more treatment options
become available, the triaging process may need to be
constantly re-evaluated. The wide variation among
individual physicians, which may compromise the
principle of distributive justice, needs to be addressed
and mutual principles need to be adopted. Hence,
subjective patient assessments with ethical guidance
will remain as the main determinant of ICU triage.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
57
References
1. Tai LL, Ng SH. A National Survey of Intensive Care
Resources in Malaysia. Nov 2005.
2. Tong MG,Tan CC. National Audit on Adult ICUs. 2005
Report.
3. Levin PD, Sprung CL. The Process of Intensive Care
Triage. Intensive Care Med 2001; 27: 1441-1445.
4. Garrouste-Orgeas M, Montuclard L, Timsit JF, Misset B,
Christias M, Carlet J. Triaging patients to the ICU: a pilot
study of factors influencing admission decisions and
patient outcomes. Intensive Care Med 2003; 29: 774-781.
5. Society of Critical Care Medicine: Attitudes of critical care
medicine professionals concerning distribution of
intensive care resources. Crit Care Med 1994; 22: 358-362.
6. Knaus WA, Harrell FE, Lynn J. The Support Prognostic
Model: Objective Estimates of Survival for Seriously Ill
Hospitalized Adults. Ann Intern Med 1995; 122(3):
191-203.
7. Nicolas F, Le Gall JR, Alperovitch A. Influence of patients’
age on survival, level of therapy and length of stay in
intensive care units. Intensive Care Med 1987; 13(1): 9-13.
8. Kass JE, Castriotta RJ, Malakoff F. Intensive care unit
outcome in the very elderly. Crit Care Med 1992; 20(12):
1666-71.
9. Rockwood K, Noseworthy TW, Gibney RT. One-year
outcome of elderly and young patients admitted to
intensive care units. Crit Care Med 1993; 21(5): 687-91.
10. SH Ng, LL Tai, CC Tan, MG Tong. National Audit on
Adult ICUs. 2004 Report
11. Joynt GM, Gomersall CD, Tan P. Prospective evaluation of
patients refused admission to an intensive care unit:
triage, futility and outcome. Intensive Care Med 2001; 27:
1459-1465.
12. Sprung CL, Geber D, Eidelman LA. Evaluation of triage
decisions for intensive care admission. Crit Care Med
1999; 27(6): 1073-1079.
13. Simchen E, Sprung CL, Galai N. Crit Care Med 2004;
32(8):1654-1661.
14. Garrouste-Orgeas M, Montuclard L, Timsit JF. Predictors
of intensive care unit refusal in French intensive care units:
A multiple centre study. Crit Care Med 2005; 33(4):
750-755.
15. Schafer JH, Maurer A, Jochimsen F. Outcome prediction
models on admission in a medical intensive care unit: do
they predict individual outcome. Crit Care Med 1990;
18(10): 1111-8.
16. Wong DT, Crofts SL, Gomez M. Evaluation of predictive
ability of APACHE II system and hospital outcome in
Canadian intensive care unit patients. Crit Care Med 1995;
23(7): 1177-83.
17. McClish DK, Powell SH. How well can physicians
estimate mortality in a medical intensive care unit.
Medical Decision Making. 1989; 9(2): 125-32.
18. Christensen C, Cottrell JJ, Murakami J. Forecasting
survival in the medical intensive care unit: a comparison
of clinical prognoses with formal estimates.Methods of
Information in Med 1993; 32(4): 302-8.
19. Azoulay E, Pochard F, Chevret S. Compliance with triage
to intensive care recommendations. Crit Care Med 2001;
29(11): 2132-2136.
20. Metcalfe MA, Sloggett A, McPherson K. Mortality among
appropriately referred patients refused admission to
intensive care units. Lancet 1997; 350: 7-12.
21. Bellomo R, Goldsmith D, Uchino S. Prospective controlled
trial of effect of medical emergency team on postoperative
morbidity and mortality rates. Crit Care Med 2004; 32(4):
916-921.
22. Society of Critical Care Medicine. Guidelines for ICU
Admission, Discharge and Triage. Crit Care Med 1999;
27(3): 633-638.
23. Taligren M, Klepstad P, Petersson J. Ethical issues in
intensive care-a survey among Scandinavian intensivists.
Acta Anaesthesiol Scand 2005; 49(8);1092-1100.
24. Azoulay E, Pochard F, Chevret S. Opinions about
surrogate decision designation: a population survey in
France. Crit Care Med 2003; 31: 1711-4
25. Wilson I, Cleary P. Linking clinical variables with
health-related quality of life: A conceptual model of
patient outcomes. JAMA 1995; 273: 59-65
26. Konopad E, Noseworthy TW, Johnston R: Quality of life
measures before and one year after admission to an
intensive care unit. Crit Care Med 1995; 23:1653-1659
27. Goodman MD, Tarnoff M, Slotman G. Effect of advance
directives on the management of elderly critically ill
patients. Crit Care Med 1998; 26: 701-4

YEAR BOOK 2006/2007
58
28. Schein R, Hazday N, Pena M, Ruben B, Sprung C. Clinical
antecedents to inhospital cardiopulmonary arrest. Chest
1990; 6:1338-92
29. MERIT study investigators. Introduction of the Medical
Emergency Team (MET) System: A cluster-randomised
controlled trial. Lancet 2005; 365: 2091-97
30. Toh KW, Tan PSK, Ong GSY, Kow SP. A Prospective Study
of Intervention by the Critical Care Outreach Team on
Outcome in Malaysian Medical In-Patients. 2nd National
Conference on Intensive Care Sep 2004; Free Paper

59
VAP: Everything You Want to Know
Ventilator-associated pneumonia or VAP is one of
the most dreaded yet common nosocomial
infections occurring in the critically ill.
VAP is defined as pneumonia occurring in patients
more than 48 hours after endotracheal intubation
and mechanical ventilation. It is commonly classified
as early onset if it develops during the first 4 days of
ventilation and late-onset if it develops at day 5 or
more of ventilation. Early-onset VAP is usually
associated with antibiotic-sensitive organisms and a
better outcome compared to late-onset VAP which is
associated with antibiotic-resistant organisms and a
higher mortality.
Epidemiology
The incidence of VAP in the majority of reports
varies between 8 and 28% and this is probably due
to the different diagnostic criteria defining VAP.
The oft-quoted overall prevalence of nosocomial
pneumonia by the European Prevalence of
Infection in Intensive Care or the EPIC study is
10%. Cook et al in their prospective cohort study
showed that although the cumulative risk of VAP
increased over time, the daily hazard rate
decreased after day 5 ie 3.3% at day 5, 2.3% at day
10 and 1.3% at day 15
The development of VAP leads to increased
duration of mechanical ventilation and this results
in prolonged ICU and hospital stay. A study by
Heyland showed that patients with VAP stayed an
average of 4.3 days longer in the ICU compared to
patients without VAP. This increase in the duration
of ICU as well as hospital stay would invariably
lead to rising health care costs.
The mortality attributable to VAP is difficult to
quantify, as there are many compounding factors
affecting the mortality of critically ill patients.
Reported crude mortality rates of VAP vary
between 24 to 50% and can reach up to 76% in
specific settings or when lung infection is caused
by high risk pathogens.
Risk factors
Multiple risk factors have been identified in the
development of VAP. Intubation is perhaps the
most significant risk factor and has shown to
increase the risk of nosocomial pneumonia by 6- to
21-fold. Other risk factors include reintubation and
unplanned extubation, severity of illness on
admission (APACHE II score > 16), acute and
chronic lung disease, excessive sedation, patients
admitted with trauma or burns, witnessed arrest
and aspiration and the use of paralytic agents.
Pathogenesis
The pathogenesis of VAP involves bacterial
colonization of the aerodigestive tract. Subsequent
aspiration of these contaminated secretions into the
lower airways is the main route by which the
bacteria invade the lower airways and cause VAP
Although less common, inhalation of pathogens
from contaminated aerosols and direct inoculation
of contaminated condensates from ventilator
tubings could also result in VAP
Some investigators have postulated that the
endotracheal tube of ventilated patients could
become colonized with the bacteria which is
encased in a biofilm. Subsequently embolization of
these bacteria into the alveoli during suctioning or
bronchoscopy may result in VAP.
Shanti Rudra Deva, MBBS, M. Anaes (Malaya), EDIC
Department of Anaesthesia and Intensive Care, Hospital Kuala Lumpur.
Dr Shanti Rudra Deva is a Consultant Intensivist at Hospital Kuala Lumpur. She is the national coordinator of the Basic
Assessment & Support in Intensive Care (BASIC) course. Her special interests are sedation in intensive care and ventilator
associated pneumonia.

YEAR BOOK 2006/2007
60
Prevention
Prevention is the cornerstone to decreasing the
incidence of VAP. General as well as specific infection
control measures should be put in place at all times in
the intensive care unit.
Perhaps the most important and effective general
infection control measure taken to prevent all
nosocomial infections is hand washing. Adequate hand
washing facilities and alcohol hand rubs help decrease
cross contamination of multidrug resistant organisms
between patients. Constant and continuous education
of health care workers on the epidemiology and
prevention of VAP is advocated. Zack et al have
showed that a formal education program on risk
factors on the development of VAP and correct
practices on the prevention of VAP directed at intensive
care nurses can decrease the incidence of VAP.
Specific preventive strategies are targeted at preventing
aspiration. Barring no contraindications, intubated
patients should be nursed in the semi recumbent
position. This is defined as elevation of the head of the
bed between 30 – 45 degrees. Endotracheal cuff
pressure should be monitored regularly ensuring cuff
pressure is kept between 25 – 30mmHg. Preventing
unplanned extubation as well as reintubation are other
important measures in preventing aspiration.
Use of special endotracheal tubes which allow
continuous aspiration of subglottic secretions has been
shown to decrease early onset pneumonia and is
recommended if available in patients who are going to
be ventilated for more than 4 days
Enteral feeding may similarly increase the risk of
aspiration. It is however preferred over parental
nutrition as it prevents intestinal villous atrophy and
may attenuate bacterial translocation. Caveats when
patients are enterally fed: prevent gastric over
distension, monitor and treat large gastric volumes and
lastly ensure patients are in the semi recumbent
position.
Intubation per se has been shown to increase the
incidence of VAP by manifold. Thus early liberation
from ventilation is warranted. Daily sedation vacation
and weaning protocols can decrease time spent on the
ventilator and hence decrease the incidence of VAP.
Similarly, non invasive ventilation should be used
whenever possible in selected patients with respiratory
failure.
Stress ulcer prophylaxis with H2 antagonist such as
ranitidine is advocated in the prevention. Despite
sucralfate showing a trend towards reduced VAP, its
use when compared to H2 antagonist has been shown
to have a slightly higher rate of clinically significant
gastric bleeding.
Routine change of ventilator circuits is not advocated
as the tubings become colonized as soon as they are
changed. What is more important is to prevent the
condensates that accumulate within the circuit tubings
from entering the endotracheal tube. Scheduled
drainage of these condensates is thus necessary to
prevent this.
Diagnosis
Diagnosing VAP accurately and early is neither easy
nor straightforward. It is however crucial as early and
appropriate antibiotics have been shown to decrease
morbidity and mortality.
The latest American Thoracic Society guidelines in
diagnosing VAP divide diagnostic strategy into a
clinical and bacteriological one, incorporating both
features in the final recommendation.
When the clinical approach is used, VAP may be
suspected if there is a new or progressive infiltrate on
the chest X-Ray with two of three clinical signs of
infection (fever, leucocytosis or leucopenia, purulent
secretions). Empiric antibiotic may be started based on
the above. The initial empiric antibiotic should be
based on the risk factors for specific pathogens as well
local patterns of antibiotic resistance and organism
prevalence. Sampling of the lower respiratory tract
secretions for culture and blood culture is
recommended prior to starting antibiotics.
To improve specificity in the clinical diagnosis of VAP,
the Clinical Pulmonary Infection Score or CPIS was
introduced by Pugin et al. This score had some
limitations as it included microbiological cultures to
diagnose VAP. Singh et al modified the CPIS using only
physiological and radiological parameters.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
61
A score of more than 6 was required to diagnose VAP.
Using the modified CPIS, patients with a low clinical
suspicion of VAP can be have their antibiotics safely
discontinued after 3 days.
The bacteriological approach to diagnose VAP uses
quantitative cultures of the lower respiratory tract
secretions ie endotracheal aspirates, bronchoalveolar
lavage (BAL) or protected specimen brush (PSB)
specimens. Growth above specific threshold is
required to diagnose and determine the causative
microorganism. Quantitative cultures are useful to
diagnose VAP in patients with low or equivocal
clinical suspicion of infection. However false negative
cultures is a possibility in patients who have recently
been started on antibiotics, especially in the preceding
24 hours
Below is a summary of the management strategies for
patients with suspected VAP
VAP suspected
Obtain a lower respiratory tract culture &
microscopy
Begin empiric antibiotic therapy
Days 2 &3: Check cultures and assess clinical response
Clinical improvement in 48 - 72 hours?
NO Yes
Cultures - Cultures + Cultures - Cultures +
Search for other
Pathogens, diagnosis,
Sites of infection
Adjust antibiotic.
Search for other
Pathogens, sites of
infection
Consider stopping
antibiotics
Continue treatment
De escalate if
possible

YEAR BOOK 2006/2007
62
Treatment
Appropriate antibiotic selection with adequate dosing
ensures a favorable outcome in patients with VAP.
Some patients are at high risk of developing VAP with
multidrug-resistant organisms. Risk factors to the
development of multidrug-resistant pathogens
include antimicrobial therapy in the preceding 90
days, current hospitalization of 5 days or more and the
presence of immunosuppressive disease or therapy.
Identifying these groups of patients is important to
ensure that the initial antibiotics target these
organisms.
Reducing the duration of treatment in patients with
VAP has led to good outcomes with more antibiotic
free days and less super infection. A large multi-center
trial showed that there was no difference in terms of
mortality, relapse or length of ICU stay in patients
treated with 8 or 15 days of antibiotics. In another
study, Singh and co-workers used the modified CPIS
to guide them on the duration of antibiotics with low
risk patients (CPIS 6 or less) having only 3 days of
antibiotics compared to the conventional 10 -14 days.
These patients had a better outcome when compared
to the conventional group.
Shortening the course of treatment to VAP appears to
limit cost and the potential for resistance while
preserving a clinically acceptable response. Another
aspect when treating VAP is de-escalation of
antibiotics. This practice is currently recommended to
ensure the culprit pathogen is treated yet at the same
time prevent superinfections and the emergence of
resistance strains
Conclusion
Preventing, diagnosing and treating VAP continues to
be a challenge to the intensivist. Great efforts should
be made to decrease the incidence of VAP as it
represents a major health care burden, increasing
morbidity and mortality of critically ill patients.
Preventing VAP should be made an important focus
for quality improvement and infection control in the
ICU
Further Reading
1. American Thoracic Society. Guidelines for the
management of adults with with
hospital-acquired, ventilator-associated, and
healthcare-associated pneumonia. Am J. Resp Crit
Care Med 2005;171: 388 – 416
2. Cook DJ, Walter SD, Cook RJ, Griffith LE et al.
Incidence and risk factors for Ventilator-associated
pneumonia in critically ill patients. Ann Intern
Med 1998; 129:440
3. Chastre J, Fagon JY. Ventilated – associated
pneumonia. Am J Resp Crit Care Med
2002;165:867-903
4. Singh N, Rogers P et al. Short course empiric
antibiotic therapy for patients with pulmonary
infiltrates in the intensive care unit: prospective
evaluation of the CPIS score as an early predictor
of outcome. Am J Resp Crit Care Med 2000;162:505
-511

63
Volatile Anaesthetics and Cardioprotection
There is evidence indicating that volatile anesthetics
protect the myocardium against reversible and
irreversible ischemic injury. Volatile agents reduce
arterial and coronary perfusion pressure, cause
dose-related depression of myocardial contractility,
produce coronary vasodilatation, affect
electrophysiologic function, and modify autonomic
nervous system activity to varying degrees. The
anti-ischemic effects of volatile anesthetics may
therefore be mediated, at least in part, by favorable
alterations in myocardial oxygen supply-demand
relations, preservation of energy-dependent cellular
functions, and increased coronary blood flow. It
seems unlikely however that changes in myocardial
metabolism and coronary perfusion caused by
volatile anesthetics are solely responsible for
protection against ischemic damage. Inhalational
anaesthetics given before ischaemia, in fact trigger
an endogenous cardioprotective mechanism known
as preconditioning. Even when administered after
ischaemia, volatile anaesthetics continue to provide
specific protection against reperfusion injury –
including after cardioplegic arrest.
Ischaemic Preconditioning
Ischaemic preconditioning (IPC) is a phenomenon in
which a short period of ischaemia protects against a
subsequent and more prolonged episode of
ischaemia.
During myocardial ischaemia, cardiac myocytes
demonstrate reduced contractility within a few
seconds and stop contracting within the first few
minutes. This 15-minute period of ischaemia,
however, induces numerous changes in the
non-contracting myocytes, including a marked
decrease in high-energy phosphates and the adenine
nucleotide pool, depletion of glycogen, accumulation
of lactate and H+ and mild intracellular edema
observed on ultrastructure. Once blood flow is
re-established, the myocytes eventually recover.
However if ischaemia continues for longer than 15
minutes, cellular necrosis will begin followed by the
process of apoptosis, which will occur even after
reperfusion if ischaemia is severe. In contrast, short
periods of transient myocardial ischaemia appear to
protect the heart from extensive damage during
subsequent longer periods of ischaemia. This
phenomenon was first described by Murry et al.1
Importantly, if the time between preconditioning and
prolonged ischaemia was longer than 2 hours, the
effect of preconditioning decreased.2 However, if this
period between the preconditioning ischaemia and
prolonged coronary artery occlusion was extended to
24 h, the IPC phenomenon was restored, indicating
the existence of an additional delayed
preconditioning effect, called the “second window”
of preconditioning.3
Anaesthetic Preconditioning
The administration of some anesthetics produces a
preconditioning-like effect, protecting the
myocardium from the effects of myocardial infarction
and myocardial dysfunction.
One has to distinguish between triggers, i.e.
mechanisms at the beginning of the signal
transduction cascade, and mediators, which finally
mediate cardioprotection during the long
infarct-inducing (index) ischaemia. It is hypothesized
Khoo Teik Hooi, MD (USM), M.Anaes (Malaya), FANZCA, AM (Mal).
Department of Anaesthesia and Intensive Care, Hospital Pulau Pinang.
Rafidah Atan, MBBS (Malaya), M.Anaes (Malaya), FANZCA, AM (Mal).
School of Medicine & Health Sciences, Monash University Malaysia.
Dr Khoo Teik Hooi is a Consultant Anaesthesiologist at Hospital Pulau Pinang. Her main interests are neuroanaesthesia and
medical education. She has been actively involved in basic sciences teaching for postgraduate anaesthesia.
Dr Rafidah Atan is a Lecturer with Monash University, at the newly established offshore medical school in Malaysia. Her main
interests include medical education, acute care and crisis management in anaesthesiology.

YEAR BOOK 2006/2007
64
that volatile anesthetics stimulate a trigger that
initiates a cascade of events leading to activation of
an end-effector that is responsible for resistance to
injury. To date, adenosine type 1 (A1) receptors,
protein kinase C (PKC), inhibitory guanine
nucleotide binding (Gi) proteins, reactive oxygen
species, and mitochondrial and sarcolemmal KATP
(mito KATP and sarc KATP, respectively) channels
have been shown to mediate anaesthetic
preconditioning (APC).4
KATP Channels
Mitochondrial adenosine triphosphate-sensitive
potassium (KATP) channels have been implicated as
the end-effector in this protective scheme, but
sarcolemmal KATP channels may also play a role.
KATP channels are heteromultimeric complexes
containing an inward-rectifying potassium (Kir)
channel and a sulfonylurea receptor (SUR). Opening
of KATP channels is an important step in the signal
transduction cascade of anaesthetic-induced
preconditioning. The administration of a
non-specific KATP channel-blocker, glibenclamide,
prior to the administration of the volatile
anaesthetics completely abolishes cardioprotection.
In vitro experiments suggest that volatile
anesthetics are capable of modifying KATP channel
activity. Isoflurane stimulates outward K+ current
through sarc KATP channels in isolated ventricular
myocytes during patch clamping. Volatile
anesthetics also reduced sarc KATP channel
sensitivity to inhibition by ATP, thereby increasing
open state probability.5
G Protein–coupled Receptors
Volatile anesthetics modulate KATP channel activity
through second messenger signaling. Overall, APC
seems to be associated with the activation of separate
receptor-mediated pathways that are mostly linked
to inhibitory G-protein (Gi), namely adenosine (A1,
A3), purinoceptors (P2Y), endothelin (ET1),
acetylcholine (M2), α1- and β-adrenergic, angiotensin
II (AT1), bradykinin (B2) and opioid (δ1, κ) receptors,
which couple to a highly complex network of
kinases.4
Protein Kinase C
Protein Kinase C (PKC) is an essential component of
the signaling pathways associated with preserving
cellular viability. The diverse PKC isoform family is a
large group of serine/threonine protein kinases that
are distinguished by variable regulatory domains and
cofactors and also display diverse tissue and species
distributions. Activation of G protein-coupled
receptors (e.g., A1, bradykinin, δ1 opioid) stimulate
PKC during IPC. Volatile anesthetics have also been
shown to stimulate PKC translocation and activity,
possibly by interacting with the regulatory domain of
the enzyme. Recent findings strongly suggest that
volatile anesthetic-induced PKC activation is
required to open KATP channels and produce
myocardial protection.4
Reactive Oxygen Species
Large quantities of reactive oxygen species (ROS) are
released during reperfusion of ischemic myocardium
that damage proteins responsible for intracellular
homeostasis, depress contractile function, and
produce membrane damage. Halothane, isoflurane,
and enflurane have been shown to attenuate the toxic
effects of ROS on left ventricular pressure
development in isolated hearts. The protective effects
of sevoflurane were associated with reduced
dityrosine formation, an indirect marker of ROS and
reactive nitrogen species. These results support the
hypothesis that volatile anesthetics reduce the release
of deleterious quantities of ROS associated with
coronary artery occlusion and reperfusion. Other
findings strongly suggest that a variety of
preconditioning stimuli; direct mito KATP channel
openers, opioids, and volatile anesthetics, stimulate a
small burst of ROS that initiate downstream signaling
events and produce protection from subsequent
ischemic injury. For example, pretreatment with low
concentrations of ROS have been shown to mimic the
beneficial actions of IPC. Free radical scavengers
administered before or during brief ischaemia
markedly attenuated the protective effect of the
preconditioning stimulus on infarct size.
Alternatively, different ROS may exert opposing
actions on mito KATP channel activity.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
65
Mitochondrial adenosine triphosphate–sensitive
potassium (KATP) channels have been implicated as the
end-effector in this protective scheme, but sarcolemmal
KATP channels may also play a role. Volatile anesthetics
signal through adenosine and opioid receptors,
modulate G proteins, stimulate protein kinase C (PKC)
and other intracellular kinases, or have direct effects on
mitochondria to generate reactive oxygen species (ROS)
that ultimately enhance KATP channel activity. Volatile
anesthetics may also directly facilitate KATP channel
opening.4
Mechanism of Cardioprotection
The protective effect of anaesthetic preconditioning is
mediated by opening mito KATP channel,6 which also
mediates the protective effect of ischaemic
preconditioning. Alteration of the mitochondrial
oxidation–reduction balance by mito KATP channel
opening may also act to promote cellular protection.
A similar cardioprotective effect was confirmed for
enflurane, isoflurane, sevoflurane and desflurane and
the noble gas xenon under a variety of experimental
conditions in vitro and in vivo; cardioprotection
against reperfusion damage was also maintained when
the heart was already protected against ischaemic
damage by cardioplegic solutions (see review by
Preckel7). The amount of cardioprotection in all these
studies was substantial, leading to an infarct size
reduction of about 50%. In addition, several specific
mechanisms could be identified: a direct action at the
myocardial cell against immediate damage by an
interaction with the ryanodine receptor of the
sarcoplasmic reticulum and an action against the
neutrophil mediated secondary damage.8 Han and
co-workers not only demonstrated that isoflurane
reduces the inhibitory effect of ATP on KATP channel
opening9 but also that the isoflurane metabolite
trifluoroacetic acid directly activates KATP channels. In
contrast, a study by Zaugg and co-workers found that
the administration of isoflurane or sevoflurane in
isolated rat cardiomyocytes did not increase the
open-state probability of mitochondrial KATP channels
directly, but that this effect depended on activation of
PKC.10 In one study, it was shown that the
cardioprotection induced by both volatile anaesthetics
did not depend on opening of sarc KATP channels.
In early preconditioning, the in vivo experiments
confirmed the results of previous in vitro studies that
opening of mitochondrial and/or sarcolemmal KATP
channels is a key mechanism of the signal transduction
cascade of pharmacologically induced preconditioning
by volatile anaesthetics. Activation of adenosine
receptors and inhibitory G-proteins trigger the
cardioprotection conferred by isoflurane-induced
preconditioning. Opening of stretch-activated channels
is also involved; administration of gadolinium (a
blocker of these channels) prior to isoflurane
administration also blocked the preconditioning effect.
Only two studies have investigated whether
isoflurane-induced early preconditioning is
dose-related. The data collected provided evidence that
the threshold for induction of preconditioning by a
30-minutes period of isoflurane inhalation is 0.25 MAC
in dogs. Protection was only dose-dependent in the
presence of a low coronary collateral blood flow. In
contrast, in a recent study by our laboratory we could
in fact show that lower doses of isoflurane increase
PKC-ε activation and decreased infarct size to a greater
extent than higher doses.
Isoflurane administration before myocardial ischaemia
also reduces contractile dysfunction (‘stunning’):
pharmacologically induced preconditioning against
stunning involves activation of adenosine-A1
receptors, PKC and KATP channels. In all of these
studies, KATP channel blockers were administered
before the preconditioning stimulus and not during the
index ischaemia. Therefore, these results suggest that
opening of KATP channels is not an end-effector
(mediator) of pharmacologically induced
preconditioning as previously thought,11 but rather
acts as a trigger, i.e. an early part of the signal
transduction pathway.
cell
membrane
Inhaled
anaesthetics
act here
Inhaled
anaesthetics
act here
mitochondria

YEAR BOOK 2006/2007
66
Xenon administered for 3 to 5 minutes before ischaemia
reperfusion in an in vivo rat model significantly
reduced the infarct size, and that this cardioprotection
was in fact mediated via an increased phosphorylation
and translocation of PKC-ε.
Roscoe and co-workers showed in isolated isolated
human atrial tissue that adenosine A1 receptor
activation and KATP channel opening is essential for
pharmacologically induced preconditioning by
isoflurane.12 In contrast, no protective effect was found
for halothane. In the same study, patch clamp
measurements did not demonstrate a direct effect for
either volatile anaesthetic on KATP channel-opening
probabilities. Desflurane preconditions human atrial
myocardium by activation of adenosine A1 receptors,
α- and β-adrenoceptors and mito KATP channels.13
Zaugg and co-workers demonstrated that
preconditioning induced by 10 minutes administration
of 2 MAC sevoflurane preserves myocardial and renal
function in patients undergoing coronary artery bypass
graft surgery under cardioplegic arrest and that PKC-δ
and -ε are activated and translocated in response to
sevoflurane in the human myocardium.14
In contrast to early preconditioning, the phenomenon
of late preconditioning, though less pronounced,
protection occurs 12±24 h after the initial
preconditioning stimulus and lasts for up to 72 h
(second window of protection or late/delayed
preconditioning). It was long thought not to be
mediated by volatile anaesthetics. Consistent with this
delayed type of protection, late preconditioning is
dependent on de novo synthesis of cardioprotective
proteins. In contrast to most classic or early
preconditioning models, late preconditioning
consistently protects against stunning.15 Opioids can
also stimulate late preconditioning in vivo.8
Intravenous anaesthetics have shown little evidence of
cardioprotection during ischaemia reperfusion
situations. Propofol, for example, is known as an
oxygen free radical scavenger and inhibits calcium
influx across plasma membranes, but does not improve
post-ischaemic myocardial function.16 Ketamine can
block this channel and prevent the cardioprotective
effect of ischaemic preconditioning at clinically
relevant concentrations. The effect is stereospecific for
the R(-)-isomer and does not occur with S(+)-ketamine.
Cardioprotection by late preconditioning is also
blocked by a single bolus dose of racemic ketamine, but
not by S(+) ketamine.17 Barbiturates may also block the
ATP regulated potassium channels, a blocking effect on
preconditioning may only occur at supratherapeutical
doses.18
Potential harmful mechanisms
Opening of the (mitochondrial) KATP channel is a
central mechanism in the signal transduction of
preconditioning. Both barbiturates and ketamine can
block KATP channels in isolated cells. While thiopental
appeared to be safe and did not block experimental
preconditioning at clinical doses,18 several studies
found that ketamine completely blocked the
cardioprotection of ischaemic preconditioning both in
vitro and in vivo; the effect was stereospecific for the
R(-)-isomer. A recent study from our laboratory
showed that lidocaine blocks ischaemic
preconditioning only when used at supratherapeutic
concentrations.19
While the clinical importance of these findings is still
unknown, it is probably safer to avoid racemic
ketamine in clinical settings where ischaemia
reperfusion is likely to occur. Sulphonylurea oral
anti-diabetics such as gliblenclamide can block the
KATP channel and prevent cardioprotection by
preconditioning. Recent evidence suggests that a
patient with type II diabetes and coronary artery
disease may profit from changing the treatment to
insulin (by having less ischaemia-induced myocardial
dysfunction).20
Clinical trials to prove clinical relevance
Evidence is now needed from clinical trials involving
actual patients with coronary artery disease
undergoing surgery to confirm that exposure to volatile
anaesthetics does offer cardioprotection. Although
animal studies have mostly succeeded in
demonstrating cardioprotection with volatile
anaesthetics, the same cannot be assumed to occur in
humans. In fact, two previous trials conducted in
coronary surgery, each involving more than 1000
patients had found no difference in terms of outcome,
including the incidence of myocardial ischaemia,
between intravenous and volatile anaesthetic

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
67
regimens.21,22 In view of recent interests in the
cardioprotective effects of volatile anaesthetics, some
trials are revisiting the topic.23
A review of the clinical studies conducted to date reveal
that these studies on anaesthetic preconditioning are
aimed at either of the following:
i) Finding evidence that the administration of volatile
anaesthetics result in preconditioning. This is
achieved by demonstrating an increase in the level
of markers of preconditioning.
ii) Demonstrating cardioprotective effects when
volatiles are included in the anaesthetic regimen as
indicated by:
• Improved ventricular function e.g. maintained
haemodynamic variables, reduced inotropic
requirements and normal measures of contractility
• Reduced incidence of dysrhythmias on reperfusion
• Reduced period of myocardial stunning and earlier
functional recovery
• Reduction in infarct size or prevention of infarct
• Reduced length of hospital or intensive care unit
stay
Ischaemic preconditioning and clinical
relevance
There is plenty of evidence suggesting the benefits of
ischaemic preconditioning, which is the counterpart of
anaesthetic preconditioning. Preinfarction angina, for
example is found to reduce the size of hypokinetic
segments on echocardiography and peak CKMB
levels.24 In a review of ischaemic preconditioning
written in 2006,25 Kloner summarised the following
findings regarding manifestations of preconditioning
in the human heart; ‘that repeat angioplasty balloon
inflations result in less chest pain, ST segment
elevation, and lactate production than upon an initial
inflation; that a second episode of ischemia induced by
exercise or pacing is associated with less chest pain, ST
segment change, and lactate production than a first
episode; that pre-infarct angina reduces infarct size and
is associated with better clinical outcome; that
intermittent aortic cross clamping preserves
myocardial ATP during coronary artery bypass
surgery; that certain preconditioning mimetic agents
can reduce ischemia during balloon inflation or
exercise testing in both an early preconditioning and
delayed fashion’. The preconditioning mimetic agents
referred to in this review include adenosine, adenosine
agonists, KATP channel/opener and nitrate-like agent
nicorandil, delta opioids, volatile anaesthetics and
nitroglycerin. This review also outlined various factors
that may result in attenuation or abolishment of
ischaemic preconditioning namely diabetes mellitus,
hyperglycaemia, certain oral hypoglycaemic agents
like glibenclamide (sulphonylureas),
hypercholesterolaemia and high cholesterol diet. For
the last factor, pravastatin apparently restores
ischaemic preconditioning even at a dose that did not
normalize serum cholesterol levels.
Anaesthetic preconditioning and clinical
relevance
It is rather disappointing that clinical studies on
anaesthetic preconditioning, on the other hand, fail to
mimic the almost unequivocal benefit seen in animal
studies or the convincing evidence from studies on
ischaemic preconditioning. There may be many reasons
for this failure. Complex considerations need to be
undertaken in reproducing the findings from animal
studies in that of real patients with coronary artery
disease undergoing surgery. Various designs were
devised to meet the obvious difficulties faced in
conducting such trials. The ischaemia must be induced
in a predictable, standardized and reproducible
manner. Exposures to volatile anaesthetics at a
standardized time, either pre-ischaemia,
post-ischaemia or throughout the anaesthetic period
are then studied to determine whether the exposure
will in fact prevent adverse outcomes. All this must be
done while also randomizing the subjects to different
interventions. These issues pose serious practical as
well as ethical problems and some would consider the
conduct of these studies as going against many things
accepted as good clinical practice. The interpretation of
the results must then take into account the fact that
factors such as surgical expertise, anaesthetic expertise,
haemodynamic strategies, to name a few, may also
interfere with outcome measurements.
As a result of the above difficulties, most clinical trials
on anaesthetic preconditioning were conducted in
patients undergoing cardiac surgery. In this setup, the
occurrence of ischaemia can be predicted and

YEAR BOOK 2006/2007
68
subsequent reperfusion is a routine part of the
procedure. Furthermore, compared to non-cardiac
surgery, complications can be more expediently dealt
with; elegant techniques of measurement of variables
such as contractility are possible and intensive
monitoring after surgery as well as measurements of
cardiac enzymes in the post operative period is
routinely done.
Although cardiac surgery provides the most ethical,
predictable and safe scenario for the conduct of such
studies, the actual relevance of the findings remain
questionable, as these are not the only group of
patients at risk where the occurrence of perioperative
ischaemia is concerned. It is reported that
perioperative ischaemia occurs in 18 to 74% of
patients with coronary artery disease undergoing non
cardiac surgery26. Most of these clinical trials also
involve the institution of cardiopulmonary bypass
(CPB), which in itself induces preconditioning.29 Any
proof of preconditioning or its beneficial effects must
ideally differentiate between that which is due to the
anaesthetic agent and preconditioning induced by the
institution of CPB. Furthermore, in cardiac surgery,
definitive treatment for the ischaemia is achieved at
the end of the surgery, which can certainly improve
patient outcome. This does not occur in patients with
ischaemic heart disease undergoing non cardiac
surgery, and the findings of studies in cardiac surgery
may not be suitably translated to them. From the
above discussion, it is evident that this latter group is
more likely to benefit, if anaesthetic preconditioning is
shown to improve outcome of perioperative
ischaemia.
Apart from the issue of differences in the target group
concerned, other issues like the timing and dosing of
such exposure need to be resolved if the information is
to be used in clinical practice. Review of the current
literature reveals that these clinical studies use rather
diversely different protocols, measure quite different
endpoints and produce different conclusions, leaving
readers wondering about the application of
anaesthetic preconditioning as well as the adequacy of
evidence to promote such management.
It is evident from animal and human studies that
study protocols mainly target three timings of
exposure to volatile anaesthetics:
1. Preconditioning protocols where the volatile
exposure occurs exclusively during the
preischaemic phase. Often this involves a washout
period prior to the ischaemic insult, so that the
volatile anaesthetic is exclusively present only
during the preconditioning phase. A large
proportion of earlier clinical studies were studying
this form of exposure.
2. Reperfusion protocols where volatile anaesthetics
are introduced only after the ischaemic insult has
occurred and during the reperfusion period. So far
these have been mainly conducted in animal
studies.
3. Protocols where exposure to volatile agents occur
throughout the anaesthetic, including both the
preischaemia and reperfusion period. These trials
involving patients are published as studies which
compare outcome between total intravenous
anaesthetic regimens and volatile incorporated
regimens. It indirectly challenges the long held
belief that the anaesthetic regimen has no bearing
on patient outcome.
With regard to outcome measures, some trials
involving patients were only aimed at determining if a
preconditioning phenomenon had in fact occurred on
exposure to volatile anaesthetics. These trials studied
levels of various markers of preconditioning such as
protein kinase C and tyrosine kinase. Some other trials
sought to compare differences in the extent of
ischaemic damage following ischaemia for which levels
of markers such as troponin T, troponin I, creatine
kinase-MB levels and degree of ST segment changes
were compared. Other outcomes of interests that have
been looked into include measurement of myocardial
function such as echocardiographic measurements of
contractility, intraventricular pressure measurements,
inotropic support requirements, cardiac index
measurements and rates of complications such as
arrhythmia. Recent clinical trials on anaesthetic
preconditioning have taken all this a step further by
looking at more definitive measures of patient outcome
such as hospital and intensive care unit (ICU) length of
stay and other measures of morbidity.
Preconditioning studies
In clinical trials involving preconditioning protocols
during coronary surgery, the index ischaemia is taken

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
69
to occur during aortic cross-clamping. Volatile
anaesthetics, in most instances, were introduced upon
commencement of CPB, just prior to aortic cross
clamping. This is usually followed by a period where
washout of the volatile is allowed to occur. The
volatile anaesthetic is therefore present only in the
preischaemia period.
A fair number of these studies report equivocal
findings between the experimental and the control
group. This may be contributed by another common
feature shared between many of these clinical studies
utilising preconditioning protocols; small sample size.
Most studies involve only around 20 subjects,
although some included more, up to 50 to 72 subjects.
It is therefore unclear if this lack of power contributes
to the lack of positive findings. Furthermore, even
with positive findings, there is an issue raised as to
whether the institution of CPB induces ischaemic
preconditioning in itself and this needs to be
differentiated from benefits due to anaesthetic
preconditioning conferred by the volatile agents.
The first of these preconditioning studies were
conducted by Belhomme et al in 1999 involving 20
patients.27 In this protocol, the treatment group was
exposed to isoflurane at 2.5 MAC for 5 minutes upon
institution of the CBP. A 10 minute washout period
then followed prior to aortic cross-clamping. The
findings of this study showed that although the
treatment group had an increase a marker of protein
kinase C activation (taken to indicate the occurrence
of preconditioning), there was no difference in
postoperative release of creatinine kinase MB and
troponin I compared to the control group.
In another study of 20 patients, an effort was made by
Pouzet et al to differentiate between preconditioning
conferred by the volatile anaesthetic and
preconditioning conferred by the institution of CPB
alone.28 In the treatment group, sevoflurane was
administered at 2.5 MAC during the first 10 minutes
of CPB whilst the control group received no exposure
to sevoflurane. The findings showed that two markers
of preconditioning studied were significantly
increased and occurred to a similar extent in both
groups and the authors concluded that there was no
evidence to indicate that exposure to volatiles resulted
in greater preconditioning. Furthermore, there was
again no difference in the level of Troponin I in both
groups. The sevoflurane group however, also showed
an increase in levels of a third marker, tyrosine
kinase. Although the authors did not make any
implications of the last finding, De Hert, in a
narrative review took this be indicative of greater
preconditioning in the sevoflurane group.29
Subsequent studies attempted to determine if
anaesthetic preconditioning resulted in improved
ventricular function. A study on 22 patients
conducted by Penta de Peppo et al30 found that
enflurane administered at 1.3% for 5 minutes
immediately before CPB enhanced left ventricular
function as indicated by measures of contractility
derived via echocardiography. There was again no
difference from the control group in terms of extent of
ischaemic damage as indicated by creatine kinase-MB
and troponin I levels.
Tomai et al studied 40 patients,31 the treatment group
of which received isoflurane at 1.5% for 15 minutes,
followed by a washout period of 10 minutes before
the start of CPB. The study found no difference
between the two groups with regard to postoperative
cardiac function and peak troponin I values except in
a subgroup of patients with ejection fraction less than
50%, where the release of troponin I levels 24 H
postoperatively were slightly lower in the treatment
group.
Administration of isoflurane 0.5-2.0% until start of
CPB resulted in better postoperative cardiac index
and a lesser degree of ST segment changes compared
to the control group in a study of 49 patients by
Haroun- Bizri.32 The incidence of reperfusion
arrhythmias were however similar in both groups.
And the largest of these preconditioning studies were
conducted by Julier et al, involving 72 patients, which
found that administration of sevoflurane 4% for the
first 10 minutes of CPB before aortic cross-clamping
resulted in a lower release of a biochemical marker
for myocardial contractile dysfunction (brain
natriuretic peptide) although again no differences
could be found in the occurrence of arrhythmias,
creatine kinase MB and cardiac troponin T release.33
Contrary to the findings of Haroun Bizri et al, this
study found no difference in perioperative ST
segment changes compared to the control group.

YEAR BOOK 2006/2007
70
From the analysis of these studies involving
preconditioning protocols, questions arise if the
variable findings occurred as a result of differences in
the type, concentrations and timing of administration
of the volatile agents used. It appears that consistency
is achieved in demonstrating that the phenomenon of
preconditioning also occurs in humans with exposure
to volatiles. However, there is lack of evidence to
indicate that when volatiles are administered
exclusively in the preischaemic period to humans,
reduced ischaemic damage and better myocardial
function results.
Volatile incorporated versus total intravenous
anaesthesia
Other clinical trials then attempted to compare
anaesthetic regimens incorporating volatile agents with
anaesthetic regimens which only involved intravenous
agents. In the treatment group of these studies,
exposure to volatile agents occur throughout the
anaesthetic, as opposed to the preconditioning
protocols discussed earlier where volatile exposure
only occur during the preischaemic period. In contrast
to preconditioning studies, these studies tend to report,
rather consistently, positive results supportive of
volatile incorporated anaesthetic regimens. Indirectly,
this approach also questions the previously held belief
that the choice of anaesthetic regimen has no bearing
on patient outcome.21,22
De Hert et al studied 20 patients comparing myocardial
function during and after coronary surgery between
two anaesthetic regimens, using sevoflurane and
propofol respectively.34 Better preserved cardiac
performance was observed in the sevoflurane group as
demonstrated by a pressure catheter placed in both the
left ventricle and the left atrium which measured both
contraction and relaxation response to increased
cardiac load. There was also less need for inotropic
support (dobutamine) during weaning from CPB for
the sevoflurane group. The plasma concentrations of
cardiac troponin I were also lower in this treatment
group.
The same group of researchers subsequently repeated
the study in a group of high risk patients (n=45), as
defined by elderly patients with three vessel disease
and ejection fraction of less than 50%, using desflurane,
sevoflurane and propofol respectively and found
similar protective effects, namely better preserved
cardiac function, less need for haemodynamic support
post CPB and less myocardial damage with both
volatile groups.35
In a correspondence published in 2003 in
Anaesthesiology, Van der Linden and a group of
researchers which also included De Hert, reported a
before and after analysis of the routine use of volatile
anaesthetics during anaesthesia for cardiac surgery.36
In this observational analysis, 107 patients underwent
coronary surgery in the ‘before’ period during which
the anaesthetic only involved usage of midazolam and
high dose sufentanil. This centre for coronary surgery
was then rebuilt, equipping the anaesthetic machine
and the CPB circuits with vaporizers and end tidal
anaesthetic concentration monitoring. A total of 91
patients subsequently underwent coronary surgery in
the ‘after ’ period, when the anaesthetic technique was
modified to using a lower dose of midazolam and
sufentanil but routinely including sevoflurane at 0.5 to
2.0%. During both time periods, the same surgical and
anaesthetic team performed all the procedures and
patient characteristics, medication, intraoperative data
and haemodynamic strategies were the same. The
findings of this observational analysis reported
consistently lower Troponin T levels, lower need for
inotropic support during weaning from CPB and lower
incidence of low cardiac index (as defined by the need
for inotropic support for cardiac index lower than 2.0 1
• min-1 • m2) for patients anaesthetized in the ‘after’
period with sevoflurane routinely included in the
anaesthetic regimen.
El Azab et al in a small trial of 20 patients comparing
sevoflurane with midazolam-sufentanil anaesthesia
found that sevoflurane anaesthesia resulted in
decreased levels of plasma tumor necrosis factor (TNF),
an ischaemia-reperfusion injury marker.37 Less patients
in the sevoflurane group needed inotropic support to
maintain haemodynamic stability and the length of
stay in the intensive care unit was significantly lower in
the sevoflurane group.
There is hitherto only one study which looked at the
cardioprotective effects of volatile agents in off pump
coronary surgery. Conzen et al demonstrated in a study
of 20 patients that sevoflurane anaesthesia resulted in
better cardiac function and reduced serum troponin I

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
71
levels although no significant effect on creatine
kinase-MB could be found.38 It was suggested that this
off-pump study, with the elimination of
preconditioning by CPB, can be better translated to
patients undergoing non cardiac surgery.
As was outlined in this section earlier, these studies
where exposure to volatile anaesthetics occur
throughout the pre and post-ischaemia period, showed
consistently positive findings in favour of a
volatile-incorporated anaesthetic.
Implications on outcome of patients
The final question of interest after demonstrating the
occurrence of anaesthetic preconditioning and
studying its effects on cardioprotection, is whether the
outcome of patients with coronary artery disease is
significantly improved if volatile anaesthetic regimens
are used during surgery.
De Hert again published another clinical trial, this time
including a larger sample of 320 patients.39 Four
fast-track anaesthetic protocols were compared, two
based on total intravenous regimen using propofol and
midazolam respectively and two based on volatile
anaesthetics namely sevoflurane and desflurane
respectively. The study found that both volatile
anaesthetic groups had shorter ICU and hospital length
of stay, less incidence of patients requiring ICU
admission for > 48 hours, lower levels of troponin I,
lower incidence of raised levels of troponin I > 4
ng/mL, lower need for inotropic support and less
incidence of prolonged need for inotropic support. The
four groups were similar in terms of duration of
postoperative ventilation, incidence of post operative
atrial arrhythmia, reintubation and pulmonary
oedema.
Conclusion
The findings of clinical trials in the latter period, where
volatile anaesthetics are used throughout the surgery
certainly seem encouraging and more supportive of the
cardioprotective effects of volatile agents. There is a
need to take a closer look at these findings especially in
the light of earlier studies which have found no added
benefit of using volatile anaesthetic regimens in
patients undergoing cardiac surgery.
Why is there a difference? Other questions one might
ask include: do different agents have differing effects
on preconditioning? Are some agents better than
others? Some trials have already looked into these and
there is suggestion that not all volatiles are created
equal.40 Clinical trials then need to look at patients with
coronary disease who undergo non-cardiac surgery,
while overcoming the greater challenges posed
considering all the factors that are against the conduct
of such studies. It would be, however, a worthwhile
effort as the anaesthetic specialty ultimately needs to
decide how this information can be utilized, especially
in patients undergoing non cardiac surgery. We also
need to look at what factors abolish these effects and
therefore to be avoided in patients with coronary
disease who come under our care. These factors have
been impressively studied by our cardiology
colleagues and may also apply to anaesthetic
preconditioning. For example, many of the trials on
anaesthetic preconditioning had excluded patients
under glibenclamide and theophylline, as these agents
are shown to abolish ischaemic preconditioning.
The medical fraternity as a whole is studying other
preconditioning mimetics, apart from volatiles, and
these agents may also be utilized by anaesthetists. The
effects of preconditioning on other tissues are also
being studied and there is possibility for us to tap into
these when considering protection of other organs such
as the kidney, brain and liver. In fact, anaesthetic
preconditioning affecting endothelial cells has been
shown to occur and may play a role in protection
against ischaemia-reperfusion injury in humans.41
Although the possibilities are indefinite, the prospects
of these are certainly exciting and we hope that this
quest to find better techniques that improve the
outcome of our patients will bear fruit in the near
future.

YEAR BOOK 2006/2007
72
References
1. Murry CE, Jennings RB, Reimer KA. Preconditioning with
ischemia: a delay of lethal cell injury in ischemic
myocardium. Circulation 1986;74:1124-36.
2. Murry CE, Richard VJ, Jennings RB, Reimer KA.
Myocardial protection is lost before contractile function
recovers from ischemic preconditioning. Am J Physiol
1991;260:H796-804.
3. Kuzuya T, Hoshida S, Yamashita N, et al. Delayed effects
of sublethal ischemia on the acquisition of tolerance to
ischemia. Circ Res 1993;72:1293-9.
4. Tanaka K, Ludwig LM, Kersten JR, Pagel PS, Warltier DC.
Mechanisms of Cardioprotection by Volatile Anesthetics.
Anesthesiology 2004;100:707-21
5. Han J, Kim E, Ho WK, Earm YE: Effects of volatile
anesthetic isoflurane on ATP-sensitive K+ channels in
rabbit ventricular myocytes. Biochem Biophys Res
Commun 1996;229:852–6
6. Kersten JR, Schmeling TJ, Pagel PS, Gross GJ, Warltier DC:
Isoflurane Mimics Ischemic Preconditioning via
Activation of K sub ATP Channels: Reduction of
Myocardial Infarct Size with An Acute Memory Phase.
Anesthesiology 1997;87:361-370,
7. Preckel B & Schlack W. In Vincent J Le (ed.) Effect of
Anesthetics on Ischemia-Reperfusion Injury of the Heart.
Berlin:Springer;2002:165-176.
8. Weber NC, Schlack W. The concept of anaesthetic-induced
cardioprotection: mechanisms of action. Best Practice &
Research Clinical Anaesthesiology 2005;19(3):429–443,
9. Han J, Kim E, Ho WK & Earm YE. Effects of volatile
anesthetic isoflurane on ATP-sensitive K+ Channels in
rabbit ventricular myocytes. Biochem. Biophys. Res.
Commun 1996;229:852–856.
10. Zaugg M, Lucchinetti E, Spahn DR et al. Volatile
anesthetics mimic cardiac preconditioning by priming the
activation of mitochondrial KATP channels via multiple
signaling pathways. Anesthesiology 2002;97:4–14
11. Kersten JR, Gross GJ, Pagel PS &Warltier DC. Activation of
adenosine triphosphate-regulated potassium channels:
mediation of cellular and organ protection.
Anesthesiology 1998;88:495–513.
12. Roscoe AK, Christensen JD, Lynch C 3rd. Isoflurane, but
not halothane, induces protection of human myocardium
via adenosine A1 receptors and adenosine
triphosphate-sensitive potassium channels.
Anesthesiology 2000;92:1692–1701.
13. Hanouz JL, Yvon A, Massetti M et al. Mechanisms of
desflurane-induced preconditioning in isolated human
right atria in vitro. Anesthesiology 2002;97:33–41.
14. Julier K, Da Silva R, Garcia C et al. Preconditioning by
sevoflurane decreases biochemical markers for
myocardial and renal dysfunction in coronary artery
bypass graft surgery: a double-blinded, placebo
controlled, multicenter study. Anesthesiology
2003;98:1315–1327.
15. Zaugg M, Lucchinetti E, Uecker M, et al. Anaesthetics and
cardiac preconditioning. Part I. Signalling and
cytoprotective mechanisms. Br J Anaesth 2003;91:551– 65.
16. Ross S, Munoz H, Piriou Vet al. A comparison of the effects
of fentanyl and propofol on left ventricular contractility
during myocardial stunning. Acta Anaesthesiol. Scand.
1998;42:23–31.
17. Mullenheim J, Frassdorf J, Preckel B, Thamer V, Schlack W.
Ketamine, but not S(+)-ketamine, blocks ischemic
preconditioning in rabbit hearts in vivo. Anesthesiology.
2001; 94(4): 630-6.
18. Mullenheim J, Molojavyi A, Preckel B, Thamer V, Schlack
W. Thiopentone does not block ischemic preconditioning
in the isolated rat heart. Can J Anaesth. 2001; 48(8): 784-9.
19. Barthel H, Ebel D, Mullenheim J et al. Effect of lidocaine
on ischaemic preconditioning in isolated rat heart. Br. J.
Anaesth. 2004; 93: 698–704.
20. Scognamiglio R, Avogaro A, Vigili de KS et al. Effects of
treatment with sulfonylurea drugs or insulin on
ischemia-induced myocardial dysfunction in type 2
diabetes. Diabetes 2002; 51: 808–812.
21. Slogoff S, Keats AS. Randomized trial of primary
anesthetic agents on outcome of coronary artery bypass
operations. Anesthesiology 989; 70:179–88
22. Tuman KJ, McCarthy RJ, Spiess BD, et al. Does choice of
anesthetic agent significantly affect outcome after
coronary artery surgery? Anesthesiology 1989; 70:189 –98
23. De Hert SG, Van der Linden PJ, Cromheecke S, et al.
Choice of primary anesthetic regimen can influence
intensive care unit length of stay after coronary surgery
with cardiopulmonarybypass. Anesthesiology 2004; 101: 9
–20.
24. Ottani F, Galvani M, Ferrini D, et al. Prodromal angina
limits infarct size: a role for ischemic preconditioning.
Circulation 1995;91:291–7.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
73
25. Kloner RA, Rezkalla SH. Preconditioning,
postconditioning and their application to clinical
cardiology. Cardiovasc Res. 2006;70(2):297-307.
26. Mangano DT. Perioperative cardiac morbidity.
Anesthesiology 1990;72:153– 84.
27. Belhomme D, Peynet J, Louzy M, et al. Evidence of
preconditioning by isoflurane in coronary artery bypass
graft surgery. Circulation 1999;100(suppl II):II-340-II4.
28. Pouzet B, Lecharny JB, Dehoux M, et al. Is there a place for
preconditioning during cardiac operations in humans?
AnnThorac Surg 2002;73:843– 8.
29. De Hert SG, Turani F, Mathur S, Stowe DF.
Cardioprotection with volatile anesthetics: mechanisms
and clinical implications. Anesth Analg.
2005;100(6):1584-93
30. Penta de Peppo A, Polisca P, Tomai F, et al. Recovery of
LVcontractility in man is enhanced by preischemic
administration of enflurane. Ann Thorac Surg
1999;68:112– 8.
31. Tomai F, De Paulis R, Penta de Peppo A, et al. Beneficial
impact of isoflurane during coronary bypass surgery on
troponin I release. G Ital Cardiol 1999;29:1007–14.
32. Haroun-Bizri S, Khoury SS, Chehab IR, et al. Does
isoflurane optimize myocardial protection during
cardiopulmonary bypass? J Cardiothorac Vasc Anesth
2001;15:418 –21.
33. Julier K, da Silva R, Varcia C, et al. Preconditioning by
sevoflurane decreases biochemical markers for
myocardial and renal dysfunction in coronary artery
bypass graft surgery: a doubleblinded placebo-controlled,
multicenter study. Anesthesiology 2003;98:1315–27.
34. De Hert S, ten Broecke P, Mertens E, et al. Sevoflurane but
not propofol preserves myocardial function in coronary
surgery patients. Anesthesiology 2002;97:42–9.
35. De Hert S, Cromheecke S, ten Broecke P, et al. Effects of
propofol, desflurane, and sevoflurane on recovery of
myocardial function after coronary surgery in elderly
high-risk patients. Anesthesiology 2003;99:314 –23.
36. Van der Linden P, Daper A, Trenchant A, De Hert S.
Cardioprotective effects of volatile anaesthetics in cardiac
surgery. Anesthesiology 2003;99:516 –7.
37. El Azab SR, Rosseel PM, De Lange JJ, et al. Effect of
sevoflurane on the ex vivo secretion of TNF-alpha during
and after coronary artery bypass surgery. Eur J
Anaesthesiol 2003;20:380–4.
38. Conzen PF, Fischer S, Detter C, Peter K. Sevoflurane
provides greater protection of the myocardium than
propofol in patients undergoing off-pump coronary
artery bypass surgery. Anesthesiology 2003;99:826
–33.
39. De Hert SG, Van der Linden PJ, Cromheecke S, et al.
Choice of primary anesthetic regimen can influence
intensive care unit length of stay after coronary
surgery with cardiopulmonary bypass.
Anesthesiology 2004;101:9 –20.
40. Roscoe A, Christensen J, Lynch C III. Isoflurane, but
not halothane, induces protection of human
myocardium via adenosine A1 receptors and
adenosine triphosphate-sensitive potassium
channels. Anesthesiology 2000;92:1692–701.
41. Lucchinetti E, Ambrosio S, Aguirre J, et al.
Sevoflurane inhalation at sedative concentrations
provides endothelial protection against
ischemia-reperfusion injury in humans.
Anesthesiology 2007;106(2):262-8.

74
Anaesthesia for Pituitary Tumor Surgery
Introduction
Pituitary tumors can be generally divided into two
groups: functioning pituitary tumors and
non-functioning pituitary tumors. They account for
10-15% of all intracranial neoplasms, with the majority
of pituitary tumours being non-functional
macroadenomas.1 Functioning pituitary adenomas
often present with symptoms of hormonal
hypersecretion, and although medical therapy is
available for most of these hyperfunctioning states, it is
not curative. As a result, transsphenoidal pituitary
surgery has become a commonly performed
neurosurgical procedure, posing unique challenges to
the anesthesiologist, due to distinct medical
co-morbidities associated with the various adenomas.2
Clinical Presentation
This can be attributed to both pressure effects on local
structures adjacent to the pituitary gland as well as
hormonal effects to distant organs. Most patients
present with symptoms and signs of visual field
defects, headaches, hormone hypersecretion and
hypopituitarism either alone or in combination. A
functioning pituitary tumor may present with
Cushing’s syndrome (adenocorticotropin), acromegaly
(growth hormone,GH) and hyperprolactinemia
(prolactin).
Non-functioning pituitary tumors which include
chromophobe adenoma, craniopharyngioma,
meningioma, aneurysm and rarely metastatic or
granulomatous lesions, are usually larger than
functioning ones because of delay in presentation.
Increased intracranial pressure and
panhypopituitarism are therefore common presenting
symptoms.3
Pituitary tumors can also be part of multiple endocrine
neoplasia type I which is a syndrome of GH-producing,
prolactin-producing or chromophobe adenomas of the
pituitary; primary hyperparathyroidism and
insulin-producing or gastrin-producing tumors of the
pancreas.4
Classification of pituitary tumor
Pituitary tumours may be classified according to the
size and extend of sellar involvement. The Hardy
Classification of pituitary tumor is as follows:5,
Grade I: Normal size sella, mild thinning of the
floor, less than 10mm in diameter,
microadenoma
Grade II: Sella enlarged but intact, no extrasellar
extension
Grade III: Localized erosion of sellar floor, extension
into sphenoid sinus or suprasellar space.
Grade IV: Diffuse erosion of the sellar floor.
“Phantom” sella, extension into sphenoid
sinus or suprasellar space.
Surgical treatment2
Except for prolactinomas, the first line treatment for
pituitary adenomas that hypersecrete or cause mass
effects is usually transsphenoidal surgery. This should
always be preceded by measurement of prolactin and
thyroxine levels and the patient should be covered with
Dr Lim Wee Leong, MD (UKM), M Med (UKM), FAMM
Department of Anaesthesia and Intensive Care, Hospital Sungai Buloh.
Loo Wee Tze, MBBS(Malaya), M.Med (Anaes) UKM.
Department of Anaesthesia and Intensive Care, Hospital Kuala Lumpur.
Dr Lim Wee Leong is the Head of Department of Anaesthesia and Intensive Care at Hospital Sungai Buloh. His areas of interest
include anaesthesia for neurosurgery and spine surgery. He also has a special interest in quality management in anaesthesia.
Dr Loo Wee Tze is a Consultant Anaesthetist at Hospital Kuala Lumpur. His areas of interest include neuroanaesthesia and
simulation training. He is one of the key instructors of the Anaesthesia Crisis Resource Management (ACRM) course conducted
in University of Malaya.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
75
either hydrocortisone or dexamethasone. The use of
endoscopic instruments and intraoperative
fluoroscopy are standard equipments for
transplenoidal surgery but with the introduction of
computerized real time, three dimensional image
processing, the efficacy of surgery is further enhanced.
This is particularly when local landmarks have been
lost or disturbed by previous explorations.
Transsphenoidal microsurgical excision is considered
the therapy of choice for all pituitary tumors without
marked extrasellar extension. Mortality associated
with this procedure is less than 1% and morbidity such
as carotid artery injury, visual loss, ophthalmoplegia is
rare. Other advantages include preservation of normal
pituitary function, lower incidence of permanent
diabetes insipidus, less blood loss and no external
scarring.6
The transfrontal approach is reserved for tumor of
uncertain diagnosis and those that extend into the
anterior and middle fossae. Morbidity and mortality is
higher compared to the previous technique.7
Treatment of craniopharyngiomas in young children is
controversial and range from attempts at total excision
to conservative surgery (cyst aspiration, ventricular
shunting) plus radiation.8
For micro-prolactinomas, long term treatment with
bromocriptine or an alternative dopamine agonist is
the most common treatment of choice. Surgery is rarely
curative for macroadenomas and often results in
hypopituitarism. Dopamine agonists are the treatment
of choice as serum prolactin return to normal in over
75% of patients and result in long term shrinkage of
most tumors.9
Pre-operative Evaluation and Anaesthetic
Concerns3
In preoperative assessment of patients presenting for
pituitary surgery, a detailed pulmonary and airway
assessment must be taken into account. Features of
acromegaly or cushingoid features suggest a potential
difficult airway due to large tongue in the former and
relative short neck with buffalo hump in the latter.
Thickening of the laryngeal and pharyngeal soft tissues
leading to a reduction in the size of the glottic opening,
hypertrophy of the periepiglottic folds and
macroglossia can all contribute to airway obstruction.
Fiberoptic intubation may be necessary, but may prove
difficult in these patients because of distorted anatomy
and resistance to advancement of the endotracheal
tube. An obstructive respiratory syndrome is observed
in 25% of female and 70% of male patients. Obstructive
sleep apnea (OSA) secondary to upper airway
obstruction can affect up to 70% of acromegalic
patients.10,11
Cardiac disease is a major cause of morbidity and
mortality in acromegalic patients. Electrocardiography
changes such as ST segment depression, T-wave
abnormalities, and conduction defects are common
while hypertension occurs in approximately 40% of
acromegalic patients. Left ventricular hypertrophy can
occur in the presence of systemic hypertension, but also
occurs in at least 50% of normotensive acromegalic
patients. Echocardiography reveals an increase in left
ventricular mass, stroke volume, cardiac output, and
isovolumic relaxation time. A poorly compliant left
ventricle and its accompanying need for high filling
pressures may be considered the hallmark of
acromegalic cardiomyopathy.
Visual field defect is due to direct pressure of the
tumour on the anterior chiasm leading to the classic
symptoms of bitemporal hemianopia.
In Cushing’s disease, the hypersecretion of
adrenocorticotropic hormone (corticotropin) stimulates
the adrenal gland to produce cortisol, androgens, and to
a lesser extent mineralocorticoids. The patients may
also be hypertensive, and have hirsutism, thin skin with
purple striae, easy bruising, acne, proximal muscle
weakness, osteoporosis, emotional lability, psychosis,
hypokalemic metabolic alkalosis, hyperpigmentation,
glucose intolerance, increased susceptibility to infection
and impaired wound healing.
Evaluation of
cardiovascular function, electrolytes and plasma
glucose are required. Cortisol release will be increased
during surgical stimulation. Skeletal muscle weakness
may affect the responses to muscle relaxants.
Stress-dose steroids will be required intraoperatively.
Diabetes mellitus can be seen in one third of patients
with Cushing’s disease and need to be controlled prior
to surgery.

YEAR BOOK 2006/2007
76
Premedication is rarely indicated in patients for
pituitary surgery unless the patient is anxious or
hypertensive. Patients with sleep apnea are usually not
premedicated so as to avoid further airway
compromise.
Endocrinologic consideration12
Before pituitary surgery, all patients with pituitary
disease should be subjected to a diagnostic test of
Hypothalamic-Pituitary Axis function. Hormonal
assay to be done include serum cortisol, serum GH
level, serum prolactin and serum thyroid stimulating
hormone, TSH. The decision regarding the
perioperative use of glucocorticoid cover depends on
the result of the preoperative screening test. There are
various intraoperative glucocorticoids replacement
regimes recommended for the perioperative period in
the presence of actual or potential anterior pituitary
insufficiency.
If the ACTH 1-24 (Synacthen) test is abnormal, then the
patient should be commenced on standard
maintenance doses of glucocorticoid (15-30 mg
hydrocortisone daily, depending on factors such as age,
sex, and body habitus) in the lead-up to surgery. These
patients should be treated perioperatively with 48
hours of supra-physiological glucocorticoid therapy,
with rapid dose reduction. A suggested dose regimen,
using hydrocortisone, is:
i) 50 mg every 8 h on day of surgery,
ii) 25 mg every 8 h on day one post-operatively, and
iii) 25 mg at 0800 h on day two post-operatively
Oral thyroid replacement is indicated in patients with
pan-hypopopituitarism.
Diabetes insipidus rarely occurs intra-operatively but is
not uncommon post-operatively. Therefore monitoring
urine volume, specific gravity and serum electrolytes is
necessary during intra-operative and post-operative
periods. Treatment should be considered if there is a
significant discrepancy in fluid intake and output, an
increasing serum sodium (above 145 mmol l-1), and
when excessive urine output significantly interferes
with sleep. Desmopressin (DDAVP) works quickly and
effectively without undesirable increases in arterial
blood pressure. An initial dose of 0.1 mg of DDAVP can
be administered orally or alternatively, if the patient is
unable to take oral medications, 1 µg of DDAVP can be
administered subcutaneously.
Conduct of Anaesthesia
These are usually elective procedures but occasionally
urgent transsphenoidal or transcranial surgery is
indicated to decompress the optic nerves and chiasm as
in the case of a haemorrhagic infraction of pituitary
tumor which may produce the signs and symptoms of
subarachnoid hemorrhage, sudden loss of
consciouness, meningeal symptoms, blindness,
ophthalmoplegia and panhypopituitarism.
Intraoperative anaesthetic technique13
The goals of anaesthesia are smooth induction, airway
control with endotracheal intubation and adequate
depth of anaesthesia to obtund sympathetic reflexes.
Anaesthetic techniques that can be used in the majority
of patients include the use of narcotics, inhalation or
total intravenous anaesthesia with muscle relaxants. It
is important that patients do not cough after reversal as
this may lead to CSF rhinorrhoea.
Intravenous induction is commonly used unless
difficult airway is suspected especially in acromegalic
patients. Total intravenous anaesthesia using propofol
has the advantages of providing anaesthesia with
lower blood pressure and better recovery profile;
otherwise general anaesthesia using inhalational agent,
air and oxygen is other alternative. Either a RAE tube
or armored tube can be used to secure the airway.
Standard intra-operative monitoring includes standard
ECG monitoring, pulse oximetry, ETCO2, NIBP, urine
output and core temperature. Invasive arterial pressure
monitoring is considered essential as we may need to
treat sudden surges in intraoperative blood pressure as
well as to manage troublesome intraoperative
bleeding. Central venous pressure monitoring will
facilitate the fluid replacement therapy in patients as
some may develop diabetes insipidus post-operatively.
Unless faced with technical problems, invasive
monitoring such as CVP and arterial pressure
monitoring is used routinely for our patients
undergoing pituitary surgery. Radial artery
cannulation is to be avoided in acromegalic patients
who show signs of carpel tunnel syndrome.

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
77
Intermittent doses of muscle relaxant technique are
usually adequate and should be titrated to a TOF count
of 0-1. For transsphenoidal approach technique, short
acting opiates such as fentanyl is usually adequate for
the pain relief in the majority of patients.
Patient Positioning and surgery
For transsplenoidal surgery, the patient is placed in a
semi-recumbent, reclining, or lawn-chair position, with
the operative site above the level of the heart to allow
for free drainage of blood from the region of the sella
and the sphenoid sinus. The patient is positioned in the
head-up position either rested on the horseshoe ring or
fixed by 3 pins.
The operative table will need to be positioned so that
the room can accommodate the fluoroscopic or image
guidance systems which will be used intraoperatively
to confirm the position and trajectory of the
transsphenoidal speculum.
Air embolism is rare if the gradient between the head
and operative field is 15 degrees or less. Excessive
bleeding from cavernous sinus may occur and may
need temporary or permanent packing of the sinus.
Postoperative ophthalmoplegia, facial anesthesia and
contralateral hemiparesis or hemiplegia my result from
direct pressure or vasospasm.
For removal of the lateral portions of tumors,
particularly those with suprasellar extension, the
surgeon may request for a valsalva maneuver to cause
the remaining tumor to prolapse into view.
Alternatively, the injection of 10 ml of air or saline via a
lumbar catheter often will deliver the remaining
suprasellar portion of the tumour into the sella.14
Bothersome bleeding during intrasellar exploration can
be effectively controlled with adequate local anesthetic
nitration of the nasal passages combined with
appropriate anaesthetic depth and in some instances
hypotension anaesthesia.
There is an incidence between 1 and 4% of CSF leak
when surgeons use the trans-splenoidal approach and
this may require a repair in a later stage. For treatment
of postoperative rhinorrhea, the placement of a
continuous closed system or intermittent CSF drainage
via a lumbar subarachnoid catheter may be considered
to allow the leak to seal. The lumbar catheter can either
be inserted as a prophylactic procedure prior to the
operation in the awake patient or postoperatively if
CSF leak is encountered intraoperatively.14
Post-operative Care
Patients should be instructed that mouth breathing will
be required in the postoperative period because of
bilateral nasal packs.
The incidence of PONV after transsphenoidal
procedures seems to be less frequent than that reported
for supra and infratentorial craniotomy.15 Nevertheless
it is important that any PONV need to be treated
aggressively as it may dislodge the fat graft placed
within the sella and sphenoid sinus.
Patients are usually extubated immediately after the
surgery and admitted to a high dependency unit for
post-operative care. Immediately post-anaesthetic
concerns include compromised airways (due to
bilateral nasal packing) or bleeding into airway.
Diabetes insipidus can set in quite early if not during
the surgery. Monitoring for visual field defects is
necessary as any worsening of visual field may indicate
compression to the chiasma due to bleeding or direct
surgical damage.
Follow up
Provided there are no postoperative complications,
glucocorticoid supplementation should be withdrawn
after 48 hours, and measurement of morning plasma
cortisol levels performed daily between day 3 and 5
postoperatively. Daily clinical assessment of the
patient, together with these cortisol results, will
determine the subsequent use of glucocorticoid
replacement therapy.
Frequency of follow up depends on the size of the
residual tumor, the presence or absence of residual
visual field defects, and the possibility of further
endocrine loss following radiotherapy.

78
YEAR BOOK 2006/2007
References
1. Levy A, Lightman SL. The pathogenesis of pituitary
adenomas. Clin Endocrinol 1993;38:559-70
2. Fortnightly Review: Diagnosis and management of
pituitary tumors. A Levy, S L Lightman. BMJ
1994;308:1087-91
3. Cortell JE, Smith DS, editors. Anaesthesia and
Neurosurgery 4th ed. Mosby; 2001:591-609.
4. O’ Brien T, O’Riordan DS, Gharib H, et al: Results of
treatment of pituitary disease in multiple endocrine
neoplasia, type I. Neurosurgery 1996;39:273-279
5. Hardy J.The transsphenoidal surgical approach to the
pituitary. Hospital Practice 1979;7:81-89
6. Ciric I, Ragin A, Baumgartner C, et al. Complications of
transsphenoidal surgery: results of a national survey,
review of the literature, and personal experience.
Neurosurgery 1997; 40:225-237
7. Hoffman LD, DeSilva M, Humprey RP, et al: Aggressive
surgical management of craniopharyngiomas in children.
J Neurosurg 1992;76:47-52
8. Carazzuti V, Fischer EG, Welch K, et al. Neurologic and
psychophysiological sequelae following different
treatments of craniopharyngioma in children. J Neurosurg
1983;59:409 – 417
9. Molitch ME: Medical treatment of prolactinomas.
Endocrinol Metab Clin North Am 1999;28:143–169
10. Piper JG, Dirks BA, Traynelis VC, VanGilder JC.
Perioperative Management and Surgical Outcome of the
Acromegalic Patient with Sleep Apnea. Neurosurgery
1995;36(1):70–75
11. Breivik H. Perianaesthetic management of patients with
endocrine disease Acta Anaesthesiologica Scandinavica
1996;40(2):1004-1015
12. Inder WJ, Hunt PJ. Glucocorticoid Replacement in
Pituitary Surgery: Guidelines for Perioperative
Assessment and Management. Journal of clinical
endocrinology and metabolism. 2002;87(6):2745-2750
13. Nemergut EC, Dumont AS, Barry UT, Laws ER.
Perioperative Management of Patients Undergoing
Transsphenoidal Pituitary Surgery. Anesth Analg
2005;101:1170 –81
14. Jane et al. Pituitary Surgery: Transsphenoidal Approach.
Neurosurgery 2002;51:435-444
15. Flynn BC, Nemergut EC. Postoperative Nausea and
Vomiting and Pain After Transsphenoidal Surgery: A
Review of 877 Patients Anesth Analg 2006;103:162–7

Pain is defined as unpleasant sensory, emotional
and/or motor perception resultant from actual or
potential tissue damage. It is considered as “the fifth
vital sign” by the new Joint Commission on Accreditation
of Healthcare Organization (JCAHO), which requires
healthcare professionals to address, assess and to treat
regularly in order to alleviate unnecessary suffering to
the patients of all age groups.1 However, pain remains
one of the most misunderstood, underdiagnosed and
hence undertreated complex clinical symptom
especially among the paediatric age groups. That the
experiencing of pain is basically subjective makes its
objective measurement extremely difficult.
Traditionally, healthcare professionals tend to believe
that young infants or neonates do not feel much pain.
This is attributed to a misconception that in this group
of patients, their nervous system is relatively immature
and therefore unable to perceive much nociception.
These myths have been proven to be inaccurate as
researchers have shown that the foetal central nervous
system is relatively well-developed in as early as the
26th week of gestation, with neurochemical and
anatomical capabilities of experiencing nociception. In
this respect, suboptimal pain treatment rendered to
premature babies and neonates may have implications
that extend beyond infancy, including hypersensitivity
to noxious stimuli in the later life.2
Paediatric patients are unique when it comes to pain
management. On one hand, they are exceptionally
sensitive to opioids owing to the fact that their central
nervous system, hepatic and renal functions are
relatively immature. On the other hand, their total
requirement of opioids may be higher than the adults
(in terms of per body weight requirement), which can
be attributed to their higher degree of extra-cellular
fluid compartment as well as volume of distribution.
Besides, it is also important to note that patients
presenting for repeated procedures may actually
require more analgesia for the same degree of painful
79
Contemporary Issues in Effective Paediatric
Pain Management
stimulus and this should be taken into consideration in
the planning of their pain management.
As paediatric patients traverse over various
developmental stages, it is important to take into
account their respective physiological, psychological
and emotional responses to pain perception while
formulating their pain management plan.
Identification of the presence and severity of pain in
these patients is a challenging endeavour and requires
experience as well as patience on the part of the
clinician. When dealing with pre-verbal age groups in
particular, their inability to convey the pain perception
often leaves interpretation of the level of pain
perplexing. A relatively inexperienced healthcare
provider or parent may sometimes mistake the
uncommon presentations of pain to non-noxious
manifestations such as hunger, wetting or fear of
unfamiliar surroundings, subsequently leading to
delayed or inadequate pain treatment. Hence, pain
assessment of paediatric patients should be undertaken
with techniques which are appropriate to their
developmental level. Members of the pain team need to
go down to the child’s level in order to gain an insight
into the child’s condition. For children who are unable
to communicate or are at age less than 3 years, they
should be assessed using the FLACC scale (appendix 1).
In contrast, the FACES pain rating scale as advocated
by Baker & Wong,1987 should be used for those aged 3
and above (appendix 2).
As for children who are able to use descriptory words
and understand well the concepts of rank and order,
methods of pain assessment such as the numerical
scale, colour scale or word scale can be utilized
instead.3 Whenever possible, all manners of
description of pain such as the location, duration,
character and intensity should be explored among the
older age groups as they often provide valuable
information that contributes to successful pain
management.
Wong Wai Hong, BSc (Med), MD (UKM), M Med(Anaes) UKM, AM (Mal)
Faculty of Medicine & Health Sciences, Universiti Putra Malaysia
Dr Wong Wai Hong is a Senior Lecturer and Anaesthesiologist at Universiti Putra Malaysia. His special interests are
paediatric anaesthesia and intensive care.

YEAR BOOK 2006/2007
The common pitfalls of paediatric pain management
include under dosing on the clinician’s part for fear of
adverse complications such as respiratory depression
and cardiovascular compromise, especially in
non-intubated children. The misconceived parental
worry of addiction and subsequent physical
dependence as well as the possible undesirable long
term effects of analgesics to their children do not help
either. All these often lead to a less aggressive approach
with subsequent administration of subtherapeutic
doses to the patients especially among the pre-verbal
age groups and neonates.4 Such undertreatment can be
circumvented by formulation of a comprehensive pain
management plan encompassing careful incremental
titration of analgesics and proper monitoring of the
patients. The development of institutional protocol
and guidelines will help to “safe-guard” the process of
pain management. In addition, healthcare
professionals should engage in continuous medical
education and alleviation of unfounded parental fears.
Nevertheless, the role of family members in the pain
management of patients should not be underestimated,
for they can assume active and important roles such as
early detection of untoward incidents or help in the
administration of analgesics in suitable conditions (e.g.
parent-controlled analgesia or parent monitored
analgesia).
In recent years, the multi-modal approach utilizing a
combination of techniques and/or medications has
gained popularity and been proven to achieve greater
success in pain management of paediatric patients.
This approach effectively modulates pain perception at
multiple levels. In addition, its advantage of avoiding
excessive dosage of any single analgesic is often
extolled.
It is imperative that the attending anaesthesiologist
formulate a suitable anaesthetic and pain management
plan in accordance to the patient’s needs as well as the
nature of the surgery. This would entail a
comprehensive pre-operative assessment and
preparation. Apart from conducting a thorough history
and physical examination, these preoperative visits by
the anaesthesiologist are helpful in establishing a
rapport with the patient and the parents as well as
alleviating their anxiety. Issues which may influence
the pain management plan such as co-morbid diseases,
surgical site, postoperative disposition and family
consent for pain management techniques should be
80
addressed and agreed upon during this preoperative
session. In view of the fact that children abhor needles
and its associated pain, inhalational induction should
be considered before embarking on obtaining
intravenous access. Alternatively, EMLA cream (Eutatic
Mixture of Local Anaesthetic) should be applied to
prospective venupuncture sites at least one hour
before-hand prior to sending to the operating theatre.
Besides sedative pre-medication, pre-emptive
analgesia such as oral paracetamol or NSAIDs
(Non-Steroidal Anti-Inflammatory Drugs) may be
prescribed as it would minimize subsequent
postoperative analgesic consumption as well as
improve time to first rescue analgesia post-operatively.
The presence of the parents or guardians in the
operating theatre on the day of surgery will help to
avoid unwarranted agitation of the patient prior to
induction of anaesthesia. This practice should be
encouraged in all cases, if possible. A balanced
anaesthesia approach which utilizes opioids, in
conjunction with inhalational agent administration
(with muscle relaxant as well in certain cases) remains
the much favoured technique. Other agents which aid
intra-operative analgesia such as ketamine, tramadol,
codeine and clonidine may be considered in selective
cases. However, some of these agents are not available
in our local setting.
By and large, young children who undergo day care
operations usually experience minor or manageable
post-operative pain. They can be treated with simple
paracetamol, regional, peripheral nerve blockade
and/or simple local infiltration. Conversely, for those
who are admitted electively and subjected to more
complex procedures, opioids should be administrated
judiciously and titrated to the needs of the patient
especially if nursed in a non-high dependency setting
post-operatively. In critically ill patients who remain
intubated post-operatively, opioid infusion provides
effective pain relief as well as decrease in sedation
needs in the ICU setting. In the normal ward setting,
patient-controlled analgesia with morphine (or
sometimes, parent or nurse-controlled analgesia) may
be considered for suitable patients if they can
understand and obey instructions well.5,6
In certain cases, intraoperative surgical pain can be
alleviated with central neuraxial blocks/analgesia
techniques such as epidural (either caudal, lumbar or

MALAYSIAN SOCIETY OF ANAESTHESIOLOGISTS
81
thoracic depending on the desired level of analgesia),
subarachnoid or plexus blockade. These techniques are
highly effective, coupled with relatively low
complication rates in experienced hands and are
widely practiced nowadays. The benefits of the
epidural analgesia may also be extended to the
post-operative period.
Apart from these factors, good surgical skills with
minimal tissues handling or damage and strict
perioperative infection control are pivotal,
considering the fact that uncomplicated wound
healing is usually associated with lesser pain
perception.
The therapeutic effects of the non-pharmacological
methods are essential and should not be
underestimated. Active participation and support
from ward nurses, physiotherapists, play therapists
and child psychologist are important as well in
ensuring effective pain alleviation.7 Maintenance of
good communication among members of a cohesive
team will eventually contribute to the improvement
and success of the overall pain management.
Quality assurance measures include proper database
and record-keeping, which should be handled by
dedicated staff. These audits are important in
streamlining pain management protocol and
guidelines for the benefit of the patients. The audits
will also ensure consistency in practices and
avoidance of unnecessary errors. Efforts should be
made to provide for sufficient funds for the purpose
of promoting continuous education as well as
equipment upgrading and purchases. All the
members of the pain management team should meet
on a regular basis to facilitate the smooth running of
team, tackle on-going problems, and provide
consultations and discussions on implementation of
new guidelines or protocols.
The advancement and refinement of paediatric
anaesthesia over the years has seen the effectiveness
of various pharmacological and
non-pharmacological methods of analgesia
established from research in paediatric patients
rather than mere extrapolation from studies on adult
patients. As the understanding of paediatric pain
improves, pain management has become an
indispensable and integral part of paediatric
anaesthesia. As such, continuous educational
programmes should be made freely available to
inculcate all healthcare professionals with a better
understanding of effective paediatric pain
management.
In summary, effective paediatric pain management is
an intergration of good understanding of paediatric
pain issues, quality assurance and continuous
education.
Reference
1) Ellis J, O’ Connor BV, Cappelli M, Goodman JT, Blouin R,
Reid CW. Pain in hsopitalized pediatric patients: How
are we doing? Clinical Journal of Pain. 2002; 18:262-269.
2) Anand KJ, Brown MJ, Causon RC. Can the human
neonate mount an endocrine and metabolic response to
surgery? J Pediatr Surg. 1985;20(1):41-48.
3) Amy LD, David CB, Marc HG. Pain assessment for
pediatric patients in the Emergency Department.
Pediatrics. 2006; 117(5):1511-1518.
4) Jan PH, Huda Huijer AS, Marcel A, Ruud JG. Are
children given insufficient pain-relieving medication
postoperatively? J of Advanced Nursing. 1998; 27(1):37.
5) Monitto CL, Greenberg RS, Kost-Byerly S, Wetzel R,
Billett C, Lebet RM, Yaster M. The safety and efficacy of
parent-/nurse-controlled analgesia in patients less than
six years of age. Anesth Analg. 2000; 91(3):573-579.
6) Tarja P, Katri VJ, Anna-Maija P. Parents’ roles in using
non-pharmacological methods in their child’s
postoperative pain alleviation. J of clinical nursing.
2002; 11(4):526.

YEAR BOOK 2006/2007
82
Appendix 1:
The FLACC is a behaviour pain assessment scale © University of Michigan Health System
- this is a behaviour scale that has been tested with children age 3 months to 7 years.
- each of the five categories (Faces, Legs, Activity, Cry, Consolability) is scored from 0-2 and the scores are
added to get a psychological status, anxiety and other environment factors.
Appendix 2:
- The Faces Pain Score, by Baker & Wong (1987).
- The pain team should be informed as soon as the score is ≥ 6 while in the ward.
FACE (0) (1) (2)
LEGS (0) (1) (2)
ACTIVITY (0) (1) (2)
CRY (0) (1) (2)
CONSOLABILITY (0) (1) (2)
no particular
expression or smile
occasional grimace
or frown
withdrawn disinterested
frequent to constant
frown, clenched jaw,
quivering chin
normal position or
relaxed
uneasy, restless, tense kicking, or legs
drawn up
lying quietly, normal
position, moves easily
squirming, shifting
back and forth, tense
arched, rigid or
jerking
no cry
(awake or asleep)
moans or whimpers,
occasionally complaint
crying steadily,
screams or sobs,
frequent complaints
content, relaxed reassured by occasional
touching, hugging or
“talking” to, distractible
difficult to console
or comfort