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BMJ | 4 SEPTEMBER 2010 | VOLUME 341 499
PRACTICE
For the full versions of these articles see bmj.com
benefit and should not be given for this purpose.
The evidence for added calcium in the prevention of
hypertensive disorders is conflicting and confusing,
and more research is needed in this area.
Chronic hypertension
Preconception
• Tell women taking angiotensin converting enzyme
inhibitors and angiotensin II receptor blockers that
taking these drugs during pregnancy increases
the risk of congenital abnormalities, and that they
should discuss other antihypertensive treatments
with their healthcare professional if they are
planning pregnancy.
• Tell women taking chlorothiazide diuretics that
taking these drugs during pregnancy increases
the risk of congenital abnormalities and neonatal
GUIDELINES
Management of hypertensive disorders during pregnancy:
summary of NICE guidance
Cristina Visintin,1 Moira A Mugglestone,1 Muhammad Q Almerie,2 Leo M Nherera,1 David James,1
Stephen Walkinshaw,3 on behalf of the Guideline Development Group
1National Collaborating Centre for
Women’s and Children’s Health,
London W1T 2QA
2North Yorkshire and East Coast
Foundation School, Diana, Princess
of Wales Hospital, Grimsby
DN33 2BA
3Liverpool Women’s Hospital,
Liverpool L8 7SS
Correspondence to:
M A Mugglestone
mmugglestone@ncc-wch.org.uk
Cite this as: BMJ 2010;340:c2207
doi: 10.1136/bmj.c2207
This is one of a series of BMJ
summaries of new guidelines
based on the best available
evidence; they highlight
important recommendations for
clinical practice, especially where
uncertainty or controversy exists
Further information about the
guidance, a list of members of the
guideline development group,
and the supporting evidence
statements are in the full version
on bmj.com.
Why read this summary?
Hypertensive disorders of pregnancy cover a spectrum
of conditions, including chronic (pre-existing) hyperten-
sion, pre-eclampsia, and gestational hypertension (box
1). These conditions are associated with increased peri-
natal mortality and morbidity. Hypertensive disorders
cause one in 50 stillbirths in normal babies and 10% of
all preterm births. They contribute to a third of cases of
severe maternal morbidity.
1
Pre-eclampsia is one of the
most common causes of maternal death in the United
Kingdom.
2
This article summarises the most recent rec-
ommendations from the National Institute for Health and
Clinical Excellence (NICE) on how to manage hyperten-
sive disorders during pregnancy.3
Recommendations
NICE recommendations are based on systematic reviews
of best available evidence and explicit consideration of
cost eectiveness. When minimal evidence is available,
recommendations are based on the Guideline Develop-
ment Group’s experience and opinion of what constitutes
good practice. Evidence levels for the recommendations
are in the full version of this article on bmj.com.
Reducing the risk of hypertensive disorders in pregnancy
• Advise pregnant women of their risk of developing
hypertensive disorders during pregnancy (in
particular pre-eclampsia; see box 2) and of the
need to seek immediate advice from a healthcare
professional if they experience symptoms of pre-
eclampsia (severe headache; problems with vision,
such as blurring or flashing before the eyes; severe
pain just below the ribs; vomiting; sudden swelling
of face, hands, or feet).
• Advise women with at least one high risk factor for
pre-eclampsia or at least two moderate risk factors
for pre-eclampsia (box 2) to take 75 mg of aspirin
daily from 12 weeks until the birth of the baby.
• Although several drugs (nitric oxide donors,
progesterone, diuretics, and low molecular
weight heparin) and vitamin and nutrient
supplements (such as vitamin C, vitamin E, folic
acid, magnesium, fish oils, algal oils, and garlic)
have been studied as preventive treatments for
hypertensive disorders, these have not shown
Box 1 |
Definitions
Chronic hypertension: hypertension present at booking visit
or before 20 weeks’ gestation, or being treated at time of
referral to maternity services; can be primary or secondary
in aetiology
Clinically relevant proteinuria: more than 300 mg protein
in a 24 hour urine collection or more than 30 mg/mmol in a
spot urinary protein:creatinine sample
HELLP syndrome: haemolysis, elevated liver enzymes, and
low platelet count
Gestational hypertension: new hypertension presenting
after 20 weeks’ gestation without clinically relevant
proteinuria
Mild hypertension: diastolic blood pressure 90-99 mm Hg,
systolic blood pressure
140-149 mm Hg
Moderate hypertension: diastolic blood pressure 100-109
mm Hg, systolic blood pressure 150-159 mm Hg
Pre-eclampsia: new hypertension presenting after 20
weeks’ gestation with clinically relevant proteinuria
Severe hypertension: diastolic blood pressure 110 mm Hg
or greater, systolic blood pressure 160 mm Hg or greater
Severe pre-eclampsia: pre-eclampsia with severe
hypertension or with symptoms, biochemical
abnormalities, or haematological impairment (or any
combination thereof)
500 BMJ | 4 SEPTEMBER 2010 | VOLUME 341
PRACTICE
proteinuria, a recognised method of evaluating
completeness of the sample should be used.
Management of gestational hypertension
• Oer an integrated package of care covering
assessment in hospital by a healthcare professional
trained in managing hypertensive disorders;
possible hospital admission; treatment; and
monitoring of blood pressure, proteinuria, and
blood tests as indicated in table 1.
Management of pre-eclampsia
• Assess women with pre-eclampsia at each
consultation; assessment should be performed by a
healthcare professional trained in the management
of hypertensive disorders of pregnancy.
• Oer an integrated package of care covering
admission to hospital; treatment; and monitoring
of blood pressure, proteinuria, and blood tests as
indicated in table 2.
• Manage pregnancy conservatively (do not plan same
day delivery of the baby) until 34 weeks’ gestation.
• Consultant obstetric sta should document in the
woman’s notes maternal and fetal biochemical,
haematological, and clinical thresholds for birth
before 34 weeks’ gestation and write a plan for fetal
monitoring during birth.
Fetal monitoring
• In women with chronic hypertension, carry
out ultrasound assessment of fetal growth and
amniotic fluid volume and umbilical artery Doppler
velocimetry between 28 and 30 weeks’ gestation
and between 32 and 34 weeks’ gestation. If results
are normal, do not repeat after 34 weeks’ gestation,
unless clinically indicated.
• In women with mild or moderate gestational
hypertension diagnosed at less than 34 weeks’
gestation, carry out ultrasound assessment of fetal
growth and amniotic fluid volume and umbilical
artery Doppler velocimetry. If results are normal,
do not repeat after 34 weeks’ gestation, unless
clinically indicated.
• In women with severe gestational hypertension
or pre-eclampsia, carry out cardiotocography at
diagnosis. If conservative management is planned,
carry out ultrasound assessment of fetal growth and
amniotic fluid volume and umbilical artery Doppler
velocimetry at diagnosis; if results are normal,
do not repeat more than every two weeks. Do not
repeat cardiotocography more than weekly if results
of all fetal monitoring are normal.
Intrapartum care
• During labour, measure blood pressure hourly in
women with mild or moderate hypertension, and
continually in women with severe hypertension.
• Continue antenatal antihypertensive treatment
during labour.
• Determine the need for haematological and
biochemical tests during labour in women with mild
complications, and that they should discuss other
antihypertensive treatments with their healthcare
professional if they are planning pregnancy.
• Reassure women taking antihypertensive treatments
other than angiotensin converting enzyme
inhibitors, angiotensin II receptor blockers, or
chlorothiazide diuretics that the limited evidence
available has not shown an increased risk of
congenital malformation with such treatments.
Antenatal care
• Antihypertensive treatment should be oered but
be dependent on pre-existing treatment, side eect
profiles, and teratogenicity.
• If women taking angiotensin converting enzyme
inhibitors or angiotensin II receptor blockers
become pregnant, stop these drugs and oer
alternatives.
• Aim to keep blood pressure lower than 150/100 mm
Hg in pregnant women with uncomplicated chronic
hypertension but do not lower diastolic blood
pressure below 80 mm Hg.
• Schedule additional antenatal consultations on the
basis of the woman and her baby’s needs.
• Do not oer birth before 37 weeks’ gestation if
blood pressure is lower than 160/110 mm Hg, with
or without antihypertensive treatment.
New onset hypertension during pregnancy
Assessment of proteinuria
• To diagnose pre-eclampsia and distinguish it from
gestational hypertension, use an automated reagent
strip reading device or spot urinary protein:creatinine
ratio for estimating proteinuria in secondary care.
• If an automated reagent strip reading device is used
to detect proteinuria and a result of 1+ or more is
obtained, use a spot protein:creatinine ratio or 24
hour urine collection to quantify proteinuria.
• Diagnose clinically relevant proteinuria if the
urinary protein:creatinine ratio is greater than 30
mg/mmol or a validated 24 hour urine collection
shows greater than 300 mg protein.
• Where 24 hour urine collection is used to quantify
Box 2 |
Risk factors for pre-eclampsia
Moderate risk
Age 40 years or more
First pregnancy
Multiple pregnancy
Interval since last pregnancy of more than 10 years
Body mass index of 35 or more at presentation
Family history of pre-eclampsia
High risk
Chronic hypertension
Chronic kidney disease
Hypertensive disease during a previous pregnancy
Diabetes
Autoimmune disease
BMJ | 4 SEPTEMBER 2010 | VOLUME 341 501
PRACTICE
or moderate hypertension using the same criteria as
for the antenatal period (even if regional analgesia
is being considered).
• If low dose epidural analgesia or combined spinal
epidural analgesia is needed in women with severe
pre-eclampsia, do not preload with intravenous
fluids.
Medical management of severe hypertension or severe
pre-eclampsia in critical care
• The full guideline includes recommendations on
criteria for referral to critical care, management of
severe hypertension (including antihypertensive
treatment and blood pressure measurement),
anticonvulsants, corticosteroids (use
betamethasone for fetal lung maturation but do not
use betamethasone or dexamethasone for treatment
of HELLP syndrome (box 1)), and fluid balance and
volume expansion.
• Choose the mode of birth (induction of labour
or caesarean section) according to the clinical
circumstances and the woman’s preference.
Postnatal care and follow-up care
• The full guideline includes recommendations on
antihypertensive treatment and blood pressure
measurement in the postnatal period.
• Tell women that labetalol, nifedipine, enalapril,
captopril, atenolol, and metoprolol have no known
adverse eects on babies receiving breast milk.
• Tell women that there is insucient evidence on
the safety of angiotensin II receptor blockers,
amlodipine, and angiotensin converting enzyme
inhibitors other than enalapril and captopril in
babies receiving breast milk.
• Oer a medical review at the postnatal review (six to
eight weeks after the birth).
• At transfer to community care tell women who have
had gestational hypertension or pre-eclampsia that
they have an increased risk of these conditions
occurring in future pregnancies and an increased
risk of developing high blood pressure and its
complications in later life.
Overcoming barriers
Management of hypertensive disorders in pregnancy is
thought to vary considerably, with many practices reflec-
ting tradition rather than being evidence based. The rec-
ommendations and the supporting evidence should give
healthcare professionals confidence to reduce the fre-
quency of unnecessary tests and assessments in women
with mild or moderate disease, yet emphasise an escalat-
ing approach to care that is centred more on individual
women. The guidance may reduce interventions that
result in morbidity, such as preterm birth, and may better
target interventions that are likely to benefit the woman
and her baby. Such changes are more likely to be adopted
by clinicians, as are the many cost saving aspects of this
guidance. Informed dialogue is another powerful driver
of change: emphasising prevention, increasing informa-
tion for women themselves, and increasing awareness of
signs and symptoms from existing NICE guidance for rou-
tine antenatal care
4
should empower pregnant women to
have such dialogue with their healthcare professionals.
Contributors: CV and MAM wrote the initial draft of the article using
material produced collectively by the guideline development group and
revised the draft after receipt of comments from MQA, LMN, DJ, SW, and
the series editor. All authors approved the final version for publication.
MAM is guarantor.
Table 2
|
Management of pre-eclampsia
Management option
Degree of hypertension*
Mild hypertension Moderate hypertension Severe hypertension
Admit to hospital Yes Yes Yes
Treat No With oral labetalol as first line treatment to keep
diastolic blood pressure between 80 and 100 mm Hg,
and systolic blood pressure <150 mm Hg
With oral labetalol as first line treatment to keep diastolic
blood pressure between 80 and 100 mm Hg, and systolic
blood pressure <150 mm Hg
Measure blood pressure At least four times a day At least four times a day More than four times a day, depending on clinical
circumstances
Test for proteinuria Do not repeat measurement of proteinuria Do not repeat measurement of proteinuria Do not repeat measurement of proteinuria
Blood tests Monitor kidney function, electrolytes, full blood
count, transaminases, and bilirubin twice a week
Monitor kidney function, electrolytes, full blood count,
transaminases, and bilirubin three times a week
Monitor kidney function, electrolytes, full blood count,
transaminases, and bilirubin three times a week
*Mild hypertension is 140/90-149/99 mm Hg; moderate hypertension is 150/100-159/109 mm Hg; severe hypertension is ≥160/110 mm Hg.
Table 1
|
Management of gestational hypertension
Management
option
Degree of hypertension*
Mild hypertension Moderate hypertension Severe hypertension
Admit to hospital No No Yes (until blood pressure is ≤159/109 mm Hg)
Treat No With oral labetalol as first-line treatment to keep
diastolic blood pressure between 80 and 100 mm Hg,
and systolic blood pressure <150 mm Hg
With oral labetalol as first line treatment to keep diastolic
blood pressure between 80 and 100 mm Hg, and systolic
blood pressure <150 mm Hg
Measure blood pressure Not more than once a week At least twice a week At least four times a day
Test for proteinuria At each visit using automated reagent strip
reading device or urinary protein:creatinine ratio
At each visit using automated reagent strip reading
device or urinary protein:creatinine ratio
Daily using automated reagent strip reading device or
urinary protein:creatinine ratio
Blood tests Only those for routine antenatal care Test kidney function, electrolytes, full blood count,
transaminases, bilirubin; do not carry out further blood
tests if no proteinuria is seen at subsequent visits
At presentation and then weekly, test kidney function,
electrolytes, full blood count, transaminases, and
bilirubin
*Mild hypertension is 140/90-149/99 mm Hg; moderate hypertension is 150/100-159/109 mm Hg; severe hypertension is ≥160/110 mm Hg.
bmj.com archive
Previous articles in this
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502 BMJ | 4 SEPT EMBER 2010 | VOLUME 341
PRACTICE
Tiredness is a common presentation
in general practice, but how useful are
investigations, and what tests should be
done and how soon?
A 48 year old teacher with a two month history of continuing
tiredness visits her general practitioner. She has an unre-
markable medical history and no history of recent infection,
and she denies unusual stress. She has not lost any weight.
Clinical examination is normal with a blood pressure of
130/75 mm Hg, a regular pulse at 70 beats per minute, and
no lymphadenopathy.
The problem
Fatigue is a normal part of life, but it can also be a symp-
tom of disease, including serious illnesses. It is a common
complaint in primary care, exceeded only by complaints of
cough.1 Five to seven per cent of patients attending primary
care have a primary complaint of fatigue, with this propor-
tion being remarkably consistent across Western countries2-5
and over time.
4
The proportion of patients presenting with
fatigue as an additional complaint is nearly three times as
high.
3
6
Almost three quarters of consultations for fatigue are
isolated episodes, with no follow-up consultations on the
subject.5 This is presumably because most patients’ fatigue
improves,
7
especially if there is a time limited explanation,
such as a recent infection.89
It is not surprising, therefore, that general practitioners
perform investigations in only half of patients complain-
ing of fatigue10 and that few of these tests yield abnormal
results.1011 Even so, the high incidence of the fatigue com-
plaints means that laboratory tests for fatigue account for
almost 5% of the total number of laboratory tests ordered
by general practitioners.12
The likelihood of finding a diagnosis
A diagnosis is made in less than half of patients with fatigue;
furthermore, many of the diagnoses are descriptive, such as
stress, or are one of the many synonyms for fatigue itself.6
Patients understand that an underlying identifiable disease
may not be present,
6
though patients’ and doctors’ beliefs
are sometimes mismatched, with a higher proportion of doc-
tors than patients considering the particular problem to be
psychological.13
Precipitating factors for consultation can be stressful life
events (underlying about two thirds of fatigue complaints)—
for example, work disputes, family problems, bereavement,
or financial difficulties; or they can be illnesses such as
respiratory tract infections. Hypothyroidism and anaemia
are identified in under 3% of patients.
10
Other conditions,
such as Addison’s disease, renal failure, liver failure, carbon
monoxide poisoning, coeliac disease, pregnancy, domes-
tic abuse, and sleep apnoea are all rare, though each may
(rarely) present with fatigue as a predominant complaint.
Indeed, almost any condition can do so.
History and examination
After the initial history taking, ask questions about the main
organ systems, particularly about bleeding (menorrhagia,
gastrointestinal), gastrointestinal symptoms, urinary symp-
toms (including polyuria and polydipsia), quality and length
of sleep (sleep apnoea being characterised by episodes of
night-time breathlessness, daytime sleepiness, and often
snoring), recent infections, joint pains or swelling, and
mental health problems including concentration, motiva-
tion, stressful events, and mood. Review prescribed and over
the counter medications for iatrogenic fatigue and ask spe-
cifically about alcohol consumption. Examine the patient,
RATIONAL TESTING
Investigating fatigue in primary care
William Hamilton,1 2 Jessica Watson,3 Alison Round4
1Mount Pleasant Health Centre,
Exeter EX4 7BW
2Peninsula College of Medicine and
Dentistry, Exeter EX2 4SG
3Academic Unit of Primary Health
Care, Department of Community
Based Medicine, University of
Bristol, Bristol BS8 2AA
4Castle Place Practice, Tiverton
EX16 6NP
Correspondence to: W Hamilton
w.t.hamilton@btopenworld.com
Cite this as: BMJ 2010;341:c4259
doi: 10.1136/bmj.c4259
This series of occasional articles
provides an update on the best
use of key diagnostic tests in the
initial investigation of common or
important clinical presentations.
The series advisers are Steve
Atkin, professor, head of
department of academic
endocrinology, diabetes, and
metabolism, Hull York Medical
School; and Eric Kilpatrick,
honorary professor, department
of clinical biochemistry, Hull
Royal Infirmary, Hull York Medical
School.
LEARNING POINTS
Tiredness is a common complaint, reported in 5-7% of
general practice encounters
Investigations may exclude diagnosis and reassure
the patient, but they have a low rate of identifying any
underlying disease
Investigations are warranted in those who have not
recovered after one month or whose initial presentation is
atypical or is associated with “red flag” symptoms
Be alert for important but easily missed conditions
such as carbon monoxide poisoning, coeliac disease,
pregnancy, and sleep apnoea
Further evidence is needed to establish best practice in
the investigation of the tired patient
Funding: The National Collaborating Centre for Women’s and Children’s
Health was commissioned and funded by the National Institute for Health
and Clinical Excellence to write this summary.
Competing interests: All authors have completed the Unified Competing
Interest form at www.icmje.org/coi_disclosure.pdf (available on request
from the corresponding author) and declare that: (1) CV, MAM, LMN, and DJ
have support from the National Institute for Health and Clinical Excellence
for the submitted work; (2) They have no relationships with companies that
might have an interest in the submitted work; (3) Their spouses, partners,
and children have no financial relationships that may be relevant to the
submitted work; and (4) They have no non-financial interests that may be
relevant to the submitted work.
Provenance and peer review: Commissioned; not externally peer
reviewed.
1 Waterstone M, Bewley S, Wolfe C. Incidence and predictors
of severe obstetric morbidity: case-control study. BMJ
2001;322:1089-93.
2 Lyons G. Saving mothers’ lives: confidential enquiry into maternal
and child health 2003-5. Int J Obstet Anesth 2008;17:103-5.
3 National Institute for Health and Clinical Excellence. Hypertension
in pregnancy: the management of hypertensive disorders during
pregnancy (clinical guideline 107). 2010. www.nice.org.uk/CG107.
4 National Institute for Health and Clinical Excellence. Antenatal care:
routine care for the healthy pregnant woman (clinical guideline 62).
2008. www.nice.org.uk/CG062.
BMJ | 4 SEPTEMBER 2010 | VOLUME 341 503
PRACTICE
including urine analysis and blood pressure measurement.
Patients with Addison’s disease may have postural hypoten-
sion, as well as increased pigmentation.
What is the next investigation?
Rational investigation aims to allow most patients to forgo
testing and improve spontaneously, while identifying the
few patients with underlying disease reasonably quickly.
Younger patients are less likely to have underlying disease,
as are patients who consult frequently.1 10 Recent infection
or stressful events can justify deferral of testing. Time can
be a diagnostician as well as a healer, although it is prob-
ably advisable to oer a specific time for review rather than
a vague “return if you don’t improve.” Take action accord-
ingly when red flag symptoms or signs are detected; most
are obvious (box).
Investigations are warranted in those who have not
recovered at about four weeks,15 16 although they may
be warranted at presentation if this is atypical (an older
patient or a patient who consults infrequently)17 or if
clinical features suggest a diagnosis (such as polyuria
and polydipsia). Clinical intuition has also been shown
to have a useful role: the “art of general practice” is in
noting a slightly unusual presentation from knowledge
of the individual.18
First line investigations should be targeted at picking
up the relatively common diagnoses. Evidence from one
randomised trial suggests that a limited set of blood tests
(haemoglobin, erythrocyte sedimentation rate, glucose,
and thyroid stimulating hormone) is almost as useful diag-
nostically as a more extensive set of tests.
15
Whether mild
hyperglycaemia causes fatigue is not clear, but one study of
fatigue complaints in primary care found abnormalities of
blood glucose more often than anaemia or hypothyroidism.15
The National Institute for Health and Clinical Excellence also
Red flags*
•Weight loss
•Lymphadenopathy (such as a lymph node that is non-
tender, firm, hard, >2 cm in diameter, progressively
enlarging, supraclavicular, or axillary)
•Any other features of malignancy (such as haemoptysis,
dysphagia, rectal bleeding, breast lump, postmenopausal
bleeding)
•Focal neurological signs
•Features of inflammatory arthritis, vasculitis, or connective
tissue disease
•Features of cardiorespiratory disease
•Sleep apnoea
•*All the above are supported by narrative reviews from
cohort and/or case-control studies conducted in primary or
secondary care or are population based (sleep apnoea).14
Investigations requested after four weeks for patients who presented to their general practitioner with fatigue
Investigations
Proportion (%) of
patients for whom
test is requested12
Abnormality
rate (%)12
When to
consider test
Type of
evidence
Full blood count 74 12.0 Always Randomised trial evidence from
primary care15
Thyroid function tests 47 6.8 Always
Random glucose 19 Not known If symptoms suggest or if the
patient is obese
Erythrocyte sedimentation rate or
plasma viscosity
12 32.0 Always
C reactive protein Not known Not known If persistent infection is
suspected
Cohort studies in primary care21
Coeliac disease Not known Not known Second line or if any
gastrointestinal symptoms
Cohort studies in primary care22
Creatinine and electrolytes 23 10.9 Age >60 years or if other
symptoms such as itching or
polyuria14
Randomised trial evidence from
primary care15
Liver function tests 34 9.7 Age >60 years or with alcohol
excess or drug misuse14
Calcium Not known Not known If symptoms suggest
hypercalcaemia
Case reports
Ferritin 20 9.1 Women of childbearing age Randomised trial evidence from
primary care23
Glandular fever* Not known Not known Patients aged <40 years with
recent infection14
Cohort studies in primary care24
Depression screening tool, often
PHQ-925
Not known 1726 If symptoms suggest Cohort studies in primary care26
*The heterophil antibody (Monospot) test is the most appropriate test, though this may be negative in the first week of glandular fever. Epstein-Barr virus
IgM may be detectable at an earlier stage, but this is unlikely to be needed in the context of a fatigue complaint.
recommends testing for coeliac disease in people with per-
sistent fatigue, even when no other suggestive symptoms are
present.
19
Depending on the circumstances, additional first
line tests may be appropriate (table).
If first line tests are normal, a period of watchful wait-
ing can sensibly follow. If tiredness has persisted for three
months or if further suggestive symptoms have developed,
then a second line of testing is reasonable. If tiredness per-
sists for at least four months without a clear explanation,
a diagnosis of chronic fatigue syndrome should be consid-
ered.20 Referral may be indicated if the patient or doctor
continues to be concerned.
Outcome
In this case, as the patient has no red flag or suggestive
symptoms and no abnormal findings, the likely temporary
nature of the fatigue is discussed, together with some of the
bmj.com archive
Previous articles in this
series
ЖInvestigating mildly
abnormal serum
aminotransferase values
(
BMJ
2010;341:c4039)
ЖInvestigating
symmetrical polyarthritis
of recent origin
(
BMJ
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(
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2009;338:b912)
504 BMJ | 4 SEPTEMBER 2010 | VOLUME 341
PRACTICE
possible common precipitating factors. She is happy with a
plan to return after one month for routine blood tests (full
blood count, thyroid function tests, and erythrocyte sedi-
mentation rate and viscosity) if things have not improved.
In fact, she attends a couple of months later for a dierent
problem and comments that her fatigue has improved, prob-
ably as she has resolved a diculty at work.
Contributors: JW did the initial literature searches and WH wrote the first
draft. All authors critically revised subsequent drafts. WH is the guarantor.
Competing interests: None declared
Provenance and peer review: Commissioned; externally peer reviewed.
Patient consent not required (patient anonymised, dead, or hypothetical).
1 Okkes IM, Oskam SK, Lamberts H. The probability of specific
diagnoses for patients presenting with common symptoms to Dutch
family physicians. J Fam Pract 2002;51(1):31-6.
2 Cathebras PJ, Robbins JM, Kirmayer LJ, Hayton BC. Fatigue in primary
care: prevalence, psychiatric comorbidity, illness behavior, and
outcome. J Gen Intern Med 1992;7:276-86.
3 Cullen W, Kearney Y, Bury G. Prevalence of fatigue in general practice. Ir J
Med Sci 2002;171(1):10-2.
4 Gallagher AM, Thomas JM, Hamilton WT, White PD. Incidence of fatigue
symptoms and diagnoses presenting in UK primary care from 1990 to
2001. J R Soc Med 2004;97:571-5.
5 Kenter EG, Okkes IM, Oskam SK, Lamberts H. Tiredness in Dutch family
practice. Data on patients complaining of and/or diagnosed with
“tiredness.” Fam Pract 2003;20:434-40.
6 David A, Pelosi A, McDonald E, Stephens D, Ledger D, Rathbone R,
et al. Tired, weak, or in need of rest: fatigue among general practice
attenders. BMJ 1990;301:1199-202.
7 Kroenke K, Jackson JL. Outcome in general medical patients presenting
with common symptoms: a prospective study with a 2-week and a
3-month follow-up. Fam Pract 1998;15:398-403.
8 Hamilton WT, Gallagher AM, Thomas JM, White PD. The prognosis of
different fatigue diagnostic labels: a longitudinal survey. Fam Pract
2005;22:383-8.
9 Wessely S, Chalder T, Hirsch S, Pawlikowska T, Wallace P, Wright DJ.
Postinfectious fatigue: prospective cohort study in primary care. Lancet
1995;345:1333-8.
10 Gialamas A, Beilby JJ, Pratt NL, Henning R, Marley JE, Roddick JF.
Investigating tiredness in Australian general practice. Do pathology
tests help in diagnosis? Aust Fam Physician 2003;32:663-6.
11 Ridsdale L, Evans A, Jerrett W, Mandalia S, Osler K, Vora H.
Patients with fatigue in general practice: a prospective study. BMJ
1993;307:103-6.
12 Harrison M. Pathology testing in the tired patient—a rational
approach. Aust Fam Physician 2008;37:908-10.
13 Ridsdale L, Evans A, Jerrett W, Mandalia S, Osler K, Vora H. Patients
who consult with tiredness: frequency of consultation, perceived
causes of tiredness and its association with psychological distress.
Br J Gen Pract 1994;44:413-6.
14 NHS Clinical Knowledge Summaries. Tiredness/fatigue in adults—
management. www.cks.nhs.uk/tiredness_fatigue_in_adults
15 Koch H, van Bokhoven MA, ter Riet G, van Alphen-Jager JM, van der
Weijden T, Dinant GJ et al. Ordering blood tests for patients with
unexplained fatigue in general practice: what does it yield? Results
of the VAMPIRE trial. Br J Gen Pract 2009;59:e93-100.
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AN SWERS T O ENDG A M ES, p 511. For long answers go to the Edu cation channel on b mj.com
STATISTICAL QUESTION
Prevalence and incidence
a, b, c, and d are all true.
ON EXAMINATION QUIZ
Penicillins
Answers A, B, and C are all true,
whereas D and E are false.
ANATOMY QUIZ
Sagittal T2 weighted magnetic
resonance image of the brain
A Genu corpus callosum
B Lateral ventricle
C Pituitary stalk
D Splenium
E Quadrigeminal plate
CASE REPORT
Persistent cough and weight loss
1 Multidrug resistant tuberculosis is defined as M tuberculosis that is resistant to at least
rifampicin and isoniazid. Extensively drug resistant tuberculosis is defined as M tuberculosis
that is resistant to rifampicin, isoniazid, any fluoroquinolone, and at least one of the three
injectable second line agents (amikacin, kanamycin sulphate, and capreomycin). This patient
has extensively drug resistant tuberculosis.
2 The patient will require therapy with second line agents and admission to a negative pressure
room for infection control. She should also be referred to a tertiary centre experienced in the
management of drug resistant tuberculosis.
3 Public health services must be informed without delay. Cases of multidrug resistant or
extensively drug resistant tuberculosis warrant a formal case conference to identify issues
relating to patient isolation, contact tracing, and media liaison. Contacts at risk of infection need
to be identified and offered screening.
4 Cure rates for aggressively managed extensively drug resistant tuberculosis are 60% among
patients who do not have HIV.
5 The 2006 National Institute for Health and Clinical Excellence (NICE) guidelines identify six key
risk factors for drug resistance in the UK: a history of previous drug treatment for tuberculosis;
birth in a foreign country (particularly sub-Saharan Africa and the Indian subcontinent); HIV
infection; residence in London; age 25-44 years; and male gender.
6 Tests based on the polymerase chain reaction can be performed on sputum samples to detect
resistance mutations in three tuberculosis genes associated with resistance to rifampicin
(rpoB) and isoniazid (katG and inhA).
