I IN NT TR RA AP PE ER RI IT TO ON NE EA AL L A AN ND D L LO OC CA AL L I IN NF FI IL LT TR RA AT TI IO ON N O OF F B BU UP PI IV VA AC CA AI IN NE E F FO OR R P PA AI IN N R RE EL LI IE EF F A AF FT TE ER R L LA AP PA AR RO OS SC CO OP PI IC C C CH HO OL LE EC CY YS ST TE EC CT TO OM MY Y

Abstract

Objective: To compare the effectiveness of intraperitoneal and local infiltration of bupivacaine on pain relief in postoperative period after laparoscopic cholecystectomy. Study Design: Randomized controlled trial. Place and Duration of Study: Combined Military Hospital Multan, from Jan to Dec 2014. Material and Methods: In this study, 72 adult patients of either gender with age between 20 to 60 years having symptomatic gallstones scheduled for elective laparoscopic cholecystectomy were divided into two groups. Patients in group A received intraperitoneal and local infiltration of bupivacaine at the end of surgery. Group B was administered placebo. Postoperatively, intensity of pain was recorded by using 10 points' Visual Analogue Score at 3, 9, 12, 24 hours. A p-value ≤0.05 was considered as statistically significant. Results: In group A, there were 27 male and 9 female patients while in group B, there were 22 male and 14 female patients. Mean age was 37.75 ± 12.49 years and 41.92 ± 12.73 years in groups A and B respectively. The mean postoperative pain score was 8.18 ± 1, 6.36 ± 0.98, 4.98 ± 1.11 and 3.89 ± 1.11 in group A & 8.72 ± 1.05, 6.91 ± 0.96, 5.92 ± 0.96 and 4.47 ± 1.05 in group B at 3, 9, 12 and 24 hours post operatively. The difference in mean pain scores was significant; 0.0286, 0.0188, 0.0001 and 0.0258 at 3, 9, 12 and 24 hours respectively. Conclusion: Intraperitoneal and local infiltration of 0.25% bupivacaine significantly reduces the intensity of postoperative pain and analgesic requirement in the early postsurgical hours following laparoscopic cholecystectomy.

Full text

Laparoscopic Cholecystectomy Pak Armed Forces Med J 2018; 68 (3): 510-14
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Abdul Jabbar, Muhammad Qasim Butt*, Irfan Qadir**, Kamran Rahim***, Salman Najam Sheen****
123 Medical Battalion Skardu Pakistan, *Military Hopital/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, **Combined
Military Hospital Multan Pakistan, ***Combined Military Hospital Kharian Pakistan, ****Combined Military Hospital Gilgit Pakistan
ABSTRACT
Objective: To compare the effectiveness of intraperitoneal and local infiltration of bupivacaine on pain relief in
postoperative period after laparoscopic cholecystectomy.
Study Design: Randomized controlled trial.
Place and Duration of Study: Combined Military Hospital Multan, from Jan to Dec 2014.
Material and Methods: In this study, 72 adult patients of either gender with age between 20 to 60 years having
symptomatic gallstones scheduled for elective laparoscopic cholecystectomy were divided into two groups.
Patients in group A received intraperitoneal and local infiltration of bupivacaine at the end of surgery. Group B
was administered placebo. Postoperatively, intensity of pain was recorded by using 10 points’ Visual Analogue
Score at 3, 9, 12, 24 hours. A p-value ≤0.05 was considered as statistically significant.
Results: In group A, there were 27 male and 9 female patients while in group B, there were 22 male and 14 female
patients. Mean age was 37.75 ± 12.49 years and 41.92 ± 12.73 years in groups A and B respectively. The mean
postoperative pain score was 8.18 ± 1, 6.36 ± 0.98, 4.98 ± 1.11 and 3.89 ± 1.11 in group A & 8.72 ± 1.05, 6.91 ± 0.96,
5.92 ± 0.96 and 4.47 ± 1.05 in group B at 3, 9, 12 and 24 hours post operatively. The difference in mean pain scores
was significant; 0.0286, 0.0188, 0.0001 and 0.0258 at 3, 9, 12 and 24 hours respectively.
Conclusion: Intraperitoneal and local infiltration of 0.25% bupivacaine significantly reduces the intensity of
postoperative pain and analgesic requirement in the early postsurgical hours following laparoscopic
cholecystectomy.
Keywords: Bupivacaine, Effectiveness, Intraperitoneal injection, Laparoscopic cholecystectomy, Periportal
injection, Postoperative pain.
INTRODUCTION
Laparoscopic cholecystectomy (LC) is now a
gold standard technique for the treatment of
gallstone disease. There are many advantages of
laparoscopic cholecystectomy against open
procedure which include reduced haemorrhage,
smaller incision, shortened recovery time, less
hospital stay and expenditure, reduced risk of
acquiring infections and blood loss. However,
these patients do experience postoperative pain
which may be transient or may last for 24 hours
upto 3 days. Besides pain, nausea and vomiting
are also common complications in early
postoperative hours1.
Wound infiltration with local anaesthetics
for postoperative pain relief is a routine practice
nowadays in many surgical procedures. Local
anaesthetic infiltration of wound is beneficial in
open abdominal surgery after minor procedures,
such as hernia repair. However, it has shown less
benefits in moderate to major procedures. As
laparoscopic surgery is a minimally invasive
technique and as it is associated with reduced
surgical trauma, wound infiltration of local
anaesthetics after laparoscopic surgery may
provide clinically significant relief from
postoperative pain in immediate postoperative
period2.
Administration of intraperitoneal and
periportal local anaesthetics employing
bupivacaine during surgery is used by many
clinicians to effectively decrease postoperative
pain. However, the studies have shown mixed
results. Therefore, this study was conducted to
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommon s.org/licenses/by/4.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Correspondence: Dr Abdul Jabbar, C/O Abdul Razzaque
Khaskheli, Fauji Foundation Higher Secondary School Tando
Pakistan (Email: abduljabbar.khaskheli@yahoo.com)
Received: 06 Mar 2017; revised received: 18 Mar 2017; accepted: 21 Mar
2017
Original Article
Open Access

Laparoscopic Cholecystectomy Pak Armed Forces Med J 2018; 68 (3): 510-14
511
study the role of bupivacaine in postoperative
pain management after laparoscopic
cholecystectomy.
MATERIAL AND METHODS
This was a randomized control trial
conducted at Combined Military Hospital
Multan, Pakistan for a period of 1 year from 1st
January 2014 to 31st December 2014. The sample
size was calculated based on the reported
effectiveness of intraperitoneal and local
infiltration of bupivacaine using Open Epi
software available online at http://www.
openepi.com/Sample Size.html. We assumed an
alpha error of 0.05 and applied an allocation ratio
of 1. A sample size of 36 participants in each
group was calculated to provide a 80% power in
detecting a difference in pain relief by 30%.
Seventy two adult patients of either gender
with age between 20 to 60 years having
symptomatic gallstones scheduled to undergo
elective laparoscopic cholecystectomy under
general anaesthesia were enrolled after seeking
approval from the hospital’s ethical committee
and after obtaining informed written consent
from the patients. Patients who had local
anaesthetic allergy; chronic pain for reasons
other than gall stones; been using opioids,
tranquilizers, steroids, NSAIDS or alcohol and
patients in whom laparoscopic cholecystectomy
had to be converted into open cholecystectomy
were excluded from the study. The sample size
was taken as such for convenience only.
Sampling technique was consecutive in nature.
Inclusion and exclusion criteria were strictly
followed to control bias. Ethical issues and
financial problems were properly addressed.
The patients were divided into two groups
by lottery method. At the end of surgery, group
A and B received 0.25% inj bupivacaine 10 ml and
placebo respectively. Postoperatively intensity of
pain was recorded by using 10 points visual
analogue score at 3, 9, 12, 24 hrs. Effectiveness
was labeled as positive when the frequency of
pain was less in patients treated with
intraperitoneal bupivacaine and periportal
injection of bupivacaine than those who did not
receive so.
Data were entered and analyzed using
SPSS version 21. At every assessment time,
the descriptive statistics of qualitative and
quantitative variables were calculated. For
quantitative variables i.e. age and pain score,
mean and standard deviation were calculated.
For qualitative variables i.e. gender and
effectiveness, frequency and percentage were
calculated. Student t-test was applied to compare
the mean postoperative pain scores and chi
square test was applied to compare effectiveness
of intraperitoneal and local infiltration of
bupivacaine in intervention and control groups.
Stratification was done on gender and age to see
the effect of these modifiers on outcome i.e.
effectiveness by applying chi square test or Fisher
exact test where appropriate. A p-value <0.05 was
considered significant.
RESULTS
In group A, there were 27 (75%) male and 9
(25%) female patients while in group B, there
were 22 (61%) male and 14 (39%) female patients.
Mean age was 37.75 ± 12.49 years and 41.92 ±
12.73 years in groups A and B respectively. The
mean postoperative pain score at 3, 9, 12 and 24
hours is shown in table-I.
In group A, the effectiveness was observed
in 15 (41.7%) patients and in 6 (16.7%) patients in
group B (p-value 0.035). The mean postoperative
pain score was 8.18 ± 1, 6.36 ± 0.98, 4.98 ± 1.11
and 3.89 ± 1.11 in group A & 8.72 ± 1.05, 6.91 ±
0.96, 5.92 ± 0.96 and 4.47 ± 1.05 in group B at 3, 9,
12 and 24 hours post operatively. The difference
in mean pain scores was significant; 0.0286,
0.0188, <0.0001 and 0.0258 at 3, 9, 12 and 24
hours respectively. No significant association of
effectiveness was observed with male gender
(p-value 0.088), female gender (p-value 0.108) and
age >38 years (p-value 0.181). Cross tabulations
are displayed in table-II.
DISCUSSION
Laparoscopic cholecystectomy surgery
was first introduced in late 1980s. After the

Laparoscopic Cholecystectomy Pak Armed Forces Med J 2018; 68 (3): 510-14
512
introduction of this new technique several studies
revealed an increase in cholecystectomy rates of
approximately 20%. As a consequence, even
small changes in indications for cholecystectomy
have major impact on health care costs. Since the
introduction of laparoscopic cholecystectomy,
many studies have discussed and high-lighted
the importance of adequate surgical technique in
order to improve the outcome and timing of
surgery. Comparisons to open cholecystectomy,
with or without minimal incision, have also been
highlighted2.
Open cholecystectomy has largely been
replaced by laparoscopic cholecystectomy which
has revolutionized the treatment of gall bladder
disease and is now gold standard treatment of
gall stones and the commonest operation
performed laparoscopically worldwide. Most
patients are being discharged the same day as
day caresurgery or on the first postoperative
day1. However in 17% to 41% of the patients, pain
is the main cause for staying overnight in the
hospital on the day of surgery3. Injectable
analgesics may be required for postoperative
pain in 58-70% of patients3. Postoperative pain
can be transient or may last for 24 hours up to 3
days.
Pain following LC is multifactorial in
etiology: 1) Pain arising from incision sites being
somatic pain 2) Pain from the gallbladder bed
being mainly visceral in nature 3) Shoulder pain
is mainly due to the residual CO2 irritating the
diaphragm4. Some studies report visceral pain to
be major component of early postoperative pain.
Others suggest that incisional sites play main
role in causing major component of the total
abdominal pain after that pneumoperitoneum
and then cholecystectomy. This sequence of pain
components is refuted by studies which report
that infiltration of trocar sites with local
anaesthetic does not provide significant local
analgesia. Most of the patients, ranging from
35% to 63% complain of shoulder pain after
laparoscopic procedures but the cause of that
type of pain is still not clear. Proposed
mechanisms consists of partial injury of the
phrenic nerve like neuropraxia, irritation of
diaphragmatic muscle because of stretching of
the fibers due to pneumoperitoneum and
peritoneal damage from chemical, ischemic or
traumatic injury. After 24-48 hours, most of
visceral and parietal pain subsides but shoulder
pain may remain problematic. In our study, we
sought to evaluate the efficacy of the total pain
control of the patient atvarious time intervals but
Table-I: Mean postoperative pain score.
Time
Group A
Group B
p-value
3 hours
8.18 ± 1
8.72 ± 1.05
0.0286
9 hours
6.36 ± 0.98
6.91 ± 0.96
0.0188
12 hours
4.89 ± 1.11
5.92 ± 0.96
<0.0001
24 hours
3.89 ± 1.11
4.47 ± 1.05
0.0258
Table-II: Comparison of pain relief in intervention and control groups by age and gender.
Variable
Group
Effectiveness
p-value
Yes
No
Male Gender
Bupivacaine
11
16
0.088
Control
4
18
Female Gender
Bupivacaine
4
5
0.108
Control
2
12
Age ≤38 years
Bupivacaine
9
9
0.041
Control
4
17
Age >38 years
Bupivacaine
6
12
0.181
Control
2
13

Laparoscopic Cholecystectomy Pak Armed Forces Med J 2018; 68 (3): 510-14
513
not the various types of pain and their various
intensities2.
Many ways have been used to decrease
postsurgical pain for example local anesthetic
infiltration, gasless technique, low pressure
pneumoperitoneum, saline washout and
instillation of a local anesthetic agent in the
subdiaphragmatic area4-6.
Instillation of a local anesthetic agent at
the trocar sites and in the subdiaphragmatic
region as a method for pain control has been
evaluated in many trials. In their systematic
review, Yari Ahn et al2 of usage of local
anaesthesia in LC in thirteen trials3-15 showed
intraperitoneal was beneficial in seven of nine
trials5-12. However, in their Cochrane database
review, Gurusamy et al13 included 12 randomized
controlled trials on use of intraperitoneal local
anaesthetics in patients undergoing elective
laparoscopic cholecystectomy. They found that
none of the trials reported good quality of life,
early return to normal activity, or early return to
work. The variations in proportion of patients
who were discharged as same day of surgery and
duration of hospital stay were imprecise in all the
trials of comparisons. There were few variations
in the pain scores on the visual analoguescale (1
to 10 cm) but these were neither consistent nor
robust to fixed effect versus random effects meta
analysis or sensitivity analysis.
Which local anaesthetic should be used
for local intraperitoneal instillation is also a
matter of debate. Ingelmo et al14 concluded that
Ropivacaine nebulization before or after surgery
reduced postoperative pain and reduced
morphine requirements. Khan el al15 concluded
that bupivacaine and lignocaine (lidocaine) are
both safe and equally effective at decreasing
postoperative pain after LC.
Karaaslan et al12 and Marks et al. showed
better control of postoperative pain with early
instillation of intraperitoneal local anaesthetics
compared with instillation at the end of the
surgery. Alkhamesi et al9 showed injected
intraperitoneal LA is less effective than
aerosolized LA. The timing, volume and way of
administration of drug are responsible for
difference in observations. Some authors believe
that most of the patients could not get enough
pain relief because of decreased contact time of
drug with surgical site due to intraperitoneal
influx. Ahmad et al16 applied a 2x3 inches
bupivacaine soaked surgical guaze at the gall
bladder bed for pain control and got better result
without significant complications because of
increased contact time of the drug.
Eight trials observed the effect of incisional
LA, including to which together with
intraperitoneal LA5,9,11,17-21. Out of these, only two
trials5,11 failed to give adequate benefit with
incisional LA and one9 of these infiltrated it after
surgery. Before giving incision LA was superior
to post-incisional administration19.
One of the main reason of using bupivacaine
intraperitoneally is to increase the concentration
of drug in plasma because peritoneum is good
systemic absorber. Raetzell et al22 reported an
increase of concentration of bupivacaine in
plasma exceeding the threshold value of 2mg/L
after intraperitoneal administration of 50ml
of 0.25% bupivacaine during laparoscopic
cholecystectomy. But the main drawback which
was found in these patients in the postoperative
period, was significant compromise of respiratory
function and recurrent episodes of hypoxemia
(SpO<92%). However in our study, we did not
calculate the exact concentration of bupivacaine
in plasma but not a single patient in our study,
reported with any respiratory, neurogenic or
cardiac problem in postoperative period, likely
due to administration of safest possible dose of
intraperitoneal bupivacaine.
Some authors have experimented with
addition of different agents to intra-peritoneal
bupivacaine regimen and study their effects on
pain relief. In their study Golubovic et al23
reported that intraperitoneal administration of
bupivacaine or tramadol or combined form of
both are effective procedure for control of pain
after laparoscopic cholecystectomy and they

Laparoscopic Cholecystectomy Pak Armed Forces Med J 2018; 68 (3): 510-14
514
decrease the usage of postoperative analgesic
and antiemetic medications significantly.
Upadaya et al24 compared the effectiveness
of intra-peritoneal bupivacaine (group I) versus
intravenous paracetamol (group II) and came to
the conclusion that post-operative pain, as
assessed by visual analog scale, was equivalent in
both groups at 1st and 4th hours. However VAS
was significantly raised in group I as compared to
group II at 8, 12 and 24 postoperative hour.
CONCLUSION
Intraperitoneal and local infiltration of
0.25% bupivacaine significantly reduces the
intensity of postoperative pain and analgesic
requirement in the early postsurgical hours
following laparoscopic cholecystectomy.
ACKNOWLEDGMENT
Sayed Mustansir Hussain Zaidi, for help
with statistical analysis (Head of statistics
Department, Liaquat National Hospital and
Medical College Karachi).
CONFLICT OF INTEREST
This study has no conflict of interest to
declare by any author.
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