ORIGINALARTICLE

COMPARATIVE EVALUATION OF ANALGESIC OUTCOMES OF INTRAPERITONEAL VERSUS

SUBCUTANEOUS ADMINISTRATION OF BUPIVACAINE FOR LAPAROSCOPIC

CHOLECYSTECTOMY PATIENTS

Nimrah Iqbal¹, Waqas Anjum², Abdul Rehman³, Jawad Zahir⁴, Sahar Iqbal¹, Sundus Iqbal⁵

How to cite this article

ABSTRACT

OBJECTIVES

Iqbal N, Anjum W, Rehman A, Zahir

J, Iqbal S, Iqbal S. Comparative

Evaluation of Analgesic Outcomes of

Intraperitoneal Versus Subcutaneous

Administration of Bupivacaine for

Laparoscopic Cholecystectomy

This study aimed to compare the analgesic ecacy and recovery outcomes of

intraperitoneal versus subcutaneous administration of bupivacaine in patients

undergoing laparoscopic cholecystectomy.

METHODOLOGY

This was a comparative clinical study conducted at the Department of

Anesthesiology, Rawalpindi Medical University, and at Allied Hospitals. A

total of 86 ASA class I patients undergoing elective laparoscopic

cholecystectomy were divided into two groups: intraperitoneal bupivacaine

(n=43) and subcutaneous port-site inltration (n=43). Post-operative pain

was assessed using the Visual Analog Scale (VAS) at 1, 2, 4, 6, 12, and 24

hours. Time to rst rescue analgesia, total analgesic consumption, number of

rescue doses, recovery parameters, and complications were recorded.

Repeated measures ANOVA, independent sample t-test, and chi-square test

were applied, with p ≤ 0.05 considered statistically signicant.

RESULTS

Patients. J Gandhara Med Dent Sci.

81-86.

2026;13(3):

https://doi.org/10.37762/jgmds.13-3.893

Date of Submission: 13-03-2026

Date Revised:

Date Acceptance:

19-04-2026

23-04-2026

Assistant Professor, Department of

Anesthesiology, Rawalpindi Teaching

Hospital, Rawalpindi Medical University

Head of Department, Department of

Anesthesiology, Rawalpindi Teaching

Hospital, Rawalpindi Medical University

Intraperitoneal bupivacaine signicantly reduced post-operative VAS scores

at all time intervals (p < 0.001). Repeated-measures ANOVA demonstrated

signicant eects of time (p < 0.001) and group (p < 0.001), indicating

consistently lower pain scores in the intraperitoneal group. Time to rst rescue

analgesia was longer (211.1±44.1 vs 120.0±44.9 min), and total analgesic

consumption was lower (82.7±24.4 vs 125.4±21.1 mg) compared with

subcutaneous inltration (p < 0.001). Patients demonstrated earlier

ambulation, earlier oral intake, shorter hospital stay, and higher satisfaction

(p < 0.001). Shoulder tip pain was signicantly reduced (11.6% vs 46.5%),

while other complications were comparable between groups.

CONCLUSION

Intraperitoneal bupivacaine was associated with improved post-operative

analgesia, an enhanced recovery prole, and reduced shoulder tip pain,

without increasing complications, compared with subcutaneous inltration;

however, these ndings should be int erpreted cautiously due to the non-

randomized study design.

KEYWORDS: Laparoscopic Cholecystectomy, Pain, Analgesia, Anesthesia,

Outcomes

Associate Professor, Department of

Anesthesiology, Rawalpindi Medical

University

⁵Medical Ofcer, Department of General

Surgery, Rawalpindi Teaching Hospital

Correspondence

¹Nimrah Iqbal, Post Graduate Trainee,

Department of Anesthesiology,

Rawalpindi Teaching

Institute of

Hospital, Rawalpindi

Medical University

+92-335-0526611

drnimrahiqbal@gmail.com

operative analgesia is essential to facilitate early

mobilization, reduce opioid consumption, and improve

INTRODUCTION

overall recovery outcomes.⁴Various strategies have

been proposed, including systemic analgesics, regional

anesthesia techniques, and local anesthetic inltration.

Although port-site inltration is widely used due to its

simplicity and safety, it primarily targets somatic pain

and does not adequately address visceral and

diaphragmatic components. In contrast, intraperitoneal

instillation of local anesthetic directly acts on peritoneal

nociceptors and may reduce pneumoperitoneum-induced

irritation, thereby providing more comprehensive

analgesia.^5,6Bupivacaine, a long-acting amide local

anesthetic, is commonly used for post-operative pain

management due to its prolonged duration of action and

Laparoscopic cholecystectomy is the standard treatment

for symptomatic gallstone disease and is widely

preferred due to reduced tissue trauma, shorter recovery

time, and decreased hospital stay compared with open

surgery.^1,2Despite its minimally invasive nature, post-

operative pain remains a signicant clinical concern

affecting patient comfort, early mobilization, and

discharge readiness. Post-operative pain following

laparoscopic surgery is multifactorial, involving visceral

pain due to peritoneal stretching and gallbladder bed

manipulation, somatic pain from trocar incisions, and

referred shoulder tip pain caused by diaphragmatic

irritation and retained carbon dioxide.³Effective post-

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Comparative Evaluation of Analgesic Outcomes of Intraperitoneal Versus

favorable safety prole at recommended doses.⁷Several

Hospitals (Ref No. 688/IREF/RMU/2025 dated 26-11-

recent

studies

have

evaluated

intraperitoneal

2025). Written informed consent was obtained from all

participants. Condentiality was ensured through

anonymization, and the study was conducted in

accordance with the principles of the Declaration of

Helsinki. The sample size was calculated using a formula

for comparison of two means, assuming an expected

dierence in post-operative VAS score of 1.5 units with

a standard deviation of 2.0 based on previous literature,

at a 95% condence level and 80% power, resulting in a

total sample size of 86 patients (43 per group).⁸Inclusion

criteria comprised patients aged 18-65 years of either

gender, classied as ASA physical status I, undergoing

elective laparoscopic cholecystectomy, and willing to

participate. Exclusion criteria included hypersensitivity

to local anesthetics, ASA class II or higher, pregnancy,

chronic opioid use, psychiatric illness, conversion to

open surgery, or refusal to participate. Baseline

demographic and perioperative variables, including age,

gender, body mass index, duration of surgery, duration

of anesthesia, history of acute cholecystitis, and previous

abdominal surgery, were recorded. Post-operative pain

intensity was assessed using the Visual Analog Scale

(VAS; 0-10) at 1, 2, 4, 6, 12, and 24 hours. Observers

were trained prior to data collection to ensure

consistency in VAS assessment, although formal inter -

rater reliability was not statistically measured.

Intravenous tramadol (50 mg) was administered as

rescue analgesia when VAS ≥4. Tim e to rst rescue

analgesia, total analgesic consumption within 24 hours,

and number of rescue doses were documented. Recovery

parameters included sedation score, time to ambulation,

time to oral intake, duration of hospital stay, and patient

satisfaction score. Sedation was assessed using a 4-point

scale (1 = alert, 4 = deeply sedated), while patient

satisfaction was measured using a 5-point Likert scale (1

administration of local anesthetics in laparoscopic

surgeries; however, ndings regarding its superiority

over conventional techniques remain inconsistent.^8,9

Furthermore, most previous studies have relied on

limited statistical methods, and there is a lack of robust

analyses incorporating longitudinal pain assessment and

effect-size estimation, particularly in local populations.

Therefore, this study aimed to compare the analgesic

efcacy and post-operative recovery outcomes of

intraperitoneal versus subcutaneous administration of

bupivacaine in patients undergoing elective laparoscopic

cholecystectomy.

METHODOLOGY

This study was

prospective, non-randomized,

comparative clinical study conducted in the Department

of Anesthesiology, Rawalpindi Medical University and

Allied Hospitals, Rawalpindi, over a period of 2 months

from November 2025 to January 2026. Due to the non-

randomized allocation in routine clinical practice, the

study is observational, and causal inferences should be

interpreted with caution. Patients undergoing elective

laparoscopic cholecystectomy under general anesthesia

were followed and divided into two groups based on the

analgesic technique used in routine departmental

practice. Patients were allocated to two equal groups

based on the analgesia administered at the end of

surgery.

The

intraperitoneal

group

received

intraperitoneal instillation of bupivacaine, while the

subcutaneous group received port-site inltration of

bupivacaine. Allocation was based on routine anesthetic

practice

without

randomization

allocation

concealment, which may introduce selection bias and

confounding by indication. blinded observer

= very dissatised to 5 = very satised). Post-operative

complications within 24 hours, including shoulder tip

pain, nausea, vomiting, bradycardia, hypotension,

urinary retention, local anesthetic toxicity, and allergic

reactions, were recorded. Data were collected using a

structured pro forma by an anesthesia resident who was

not involved in administering the intervention. Three

consultant anesthesiologists reviewed the data collection

tool to ensure content validity. Confounding was

minimized through standardized anesthesia protocols,

consistent drug dosages, and uniform surgical

techniques; however, residual confounding cannot be

excluded due to the non-randomized design. Data were

analyzed using SPSS version 26 (IBM Corp., USA).

Quantitative variables were expressed as mean ±

standard deviation, and categorical variables as

performed post-operative assessment to reduce

assessment bias; however, patients and anesthesiologists

were not blinded, introducing a potential risk of

performance bias. All surgeries were performed using a

standardized four-port laparoscopic cholecystectomy

technique by experienced surgeons. General anesthesia

was induced using intravenous propofol (2 mg/kg),

fentanyl (2 µg/kg), and atracurium (0.5 mg/kg), followed

by endotracheal intubation and maintenance with

isourane in an oxygen-air mixture with intermittent

atracurium boluses. After surgery, patients in the

intraperitoneal group received 20 ml of 0.25%

bupivacaine injected into the gallbladder bed and the

subdiaphragmatic space, while those in the subcutaneous

group received 20 ml of 0.25% bupivacaine inltrated at

all trocar sites. No additional local anesthetic was

administered. Ethical approval was obtained from the

Institutional Research Forum and Research and Ethical

Committee of Rawalpindi Medical University and Allied

frequency and percentage.

repeated-measures

ANOVA was applied to assess dierences in VAS

clinically meaningful and sustained analgesic advantage.

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Comparative Evaluation of Analgesic Outcomes of Intraperitoneal Versus

The intraperitoneal group demonstrated signicantly dierent. Regression analysis showed the model was

scores over time between groups, with appropriate post

hoc analyses. An independent-samples t-test was used to

compare continuous variables, while chi-square or

Fisher's exact test was used for categorical variables.

Effect sizes and 95% condence intervals were

calculated where appropriate to enhance statistical

signicant (F = 18.82, p < 0.001, R² = 0.541). Group was

the only signicant predictor (β = 0.670, p < 0.001),

indicating that treatment type independently inuenced

pain outcomes. The intraperitoneal group consistently

demonstrated lower mean VAS scores at all

postoperative time points compared with the

subcutaneous group, indicating an improved and

sustained analgesic eect.

interpretation.

p-value ≤0.05 was considered

statistically signicant. The study was reported in

accordance with the TREND (Transparent Reporting of

Evaluations with Non-randomized Designs) guidelines.

Table 1: Baseline Characteristics of Patients (n = 86)

Variable

Intraper

itoneal

(n=43)

Subcutane Test statistic

ous (n=43)

value

RESULTS

Age (years)

BMI (kg/m²)

Duration of 60.2 ± 11.2

Surgery(min)

t(84) = -

t(84) =

38.9 ± 11.7 42.2 ± 12.9

1.245 0.217

0.017 0.986

0.175 0.862

The two groups were comparable with respect to

demographic and perioperative characteristics. There

was no statistically signicant dierence in age, BMI,

duration of surgery, duration of anesthesia, gender

distribution, presence of acute cholecystitis, or history of

previous abdominal surgery (p>0.05), indicating

baseline homogeneity between the groups. All patients

belonged to ASAclass I, ensuring comparable anesthetic

risk. Table 1 demonstrates that both groups were well

matched at baseline with no statistically signicant

dierences in demographic or clinical variables. This

minimizes confounding and strengthens the validity of

group comparisons. Repeated-measures ANOVA

showed a signicant eect of time on post-operative

pain (F = 129.35, p < 0.001, partial η² = 0.606),

indicating that pain decreased over time in both groups.

However, the interaction between time and group was

not signicant (F = 0.661, p = 0.653), suggesting that

both groups improved in a similar pattern. A highly

signicant group eect was observed (F = 361.82, p <

0.001, partial η² = 0.812), indicating consistently lower

pain scores in the intraperitoneal group. Although the

interaction between time and group was not statistically

signicant, the consistently lower VAS scores across all

time points in the intraperitoneal group indicate a

lower VAS scores at all time points (p < 0.001). The

mean dierence ranged from -1.39 to -1.74 with narrow

condence intervals, indicating strong statistical

precision. Eect size analysis showed very large eects

(Cohen's d = 1.55-2.12), conrming strong clinical

signicance. The intraperitoneal group showed

signicantly prolonged time rst to rescue analgesia and

reduced total analgesic consumption and rescue doses (p

< 0.001). These ndings indicate improved pain control

and reduced opioid requirement. The intraperitoneal

group showed signicantly better recovery outcomes,

including earlier ambulation, earlier oral intake, a shorter

hospital stay, and higher satisfaction (p < 0.001).

Shoulder tip pain was signicantly lower (χ² = 12.69, p

< 0.001) with a moderate eect size (Cramér’s V =

0.384). Other complications were not statistically

27.6 ± 3.22 27.6 ± 3.05

t(84) =-

60.6 ± 10.3

Duration of

Anesthesia

(min)

t(84) =

0.008 0.994

82.1 ± 11.3 82.1 ± 10.3

Male

(48.8%) 25 (58.1%) χ² = 0.748

(51.2%) 18 (41.9%)

0.387

Female

Acute

cholecystitis

surgery

0.12^—6

(16.3%) 13 (30.2%) χ² = 2.^—345

03 (7.0%) 5 (11.6%) χ² = 0.551

0.458

Table 2: Comparison of Post-operative Pain Scores (VAS) with

CI and Eect Size

Time Intraperitoneal Subcutane Mean

-value Eect

ous

(d)

Difference

Size

(95% CI)

1 hr 3.35 ± 0.93

2 hr 3.58 ± 0.91

4 hr 4.17 ± 0.83

6 hr 3.81 ± 0.88

12 hr 2.48 ± 0.97

24 hr 1.00 ± 0.85

4.74 ± 0.82 -1.39 (-1.77 <0.001 1.59

-1.02)

5.06 ± 0.72 -1.48 (-1.83 <0.001 1.80

-1.13)

5.72 ± 1.14 -1.55 (-1.98 <0.001 1.56

-1.12)

5.28 ± 0.95 -1.47 (-1.86 <0.001 1.60

1.07)

4.26 ± 1.02 -1.78 (-2.21 <0.001 1.79

-1.36)

2.74 ± 0.78 -1.74 (-2.09 <0.001 2.12

-1.39)

Table 3: Post-operative Analgesic Requirements

value

Variable

Intraperitoneal Subcutaneous Mean

Difference

Time to

211.1 ± 44.1

120.0 ± 44.9 +91.1

<0.001

rescue(min)

Total analges 82.7 ± 24.4

ia (mg)

125.4 ± 21.1 -42.7

Rescue doses 0.65 ± 0.61

1.81 ± 0.66

-1.16

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Comparative Evaluation of Analgesic Outcomes of Intraperitoneal Versus

Table 4: Recovery Outcomes and Complications

clinically interpretable assessment of analgesic

Variable

Intraperitoneal Subcutaneous Test

-value

effectiveness. Furthermore, repeated-measures ANOVA

demonstrated a signicant eect of time (p < 0.001).

However, a non-signicant interaction between time and

group (p = 0.653), indicating that although both groups

improved over time, the intraperitoneal group

consistently maintained lower pain scores across all time

points. The large eect sizes observed (Cohen's d >1.5)

indicate that the dierences are not only statistically

signicant but also clinically substantial. Although the

interaction between time and group was not statistically

signicant, the consistently lower VAS scores ac ross all

time points, supported by large eect sizes (Cohen's d =

Sedation

1.21 ± 0.56

1.35 ± 0.57

9.92 ± 1.85

0.256

<0.001

Ambulation 7.72 ± 2.01

(hrs)

Oral intake 6.47 ± 2.06

(hrs)

9.10 ± 1.99

25.6 ± 3.9

<0.001

Hospital

stay (hrs)

19.1 ± 3.4

Satisfaction 4.15 ± 0.66

3.10 ± 0.83

46.5%

Shoulder

11.6%

χ²=12.6 <0.001

pain

Nausea

Vomiting

Bradycardia 2.3%

Hypotension 2.3%

14.0%

9.3%

27.9%

20.9%

2.3%

χ²

0.112

0.132

1.000

χ²

Fisher

1.55-2.12), indicate

clinically meaningful and

7.0%

Fisher

0.616

sustained analgesic advantage. This nding aligns with

contemporary evidence suggesting that intraperitoneal

local anesthetics eectively target visceral pain by acting

on peritoneal nociceptors and reducing diaphragmatic

irritation. Similar ndings have been reported in recent

Table 5: Multivariate Regression Analysis (VAS at 24 hours)

p-value

Variable

Group

Age

Beta (β)

0.670

95% CI

1.08 – 2.09

<0.001

0.894

0.780

0.772

0.010

randomized

controlled

trials

and

systematic

BMI

-0.021

-0.022

reviews.^10,11,12,13The clinical relevance of enhanced pain

management is further supported by our ndings on

analgesic requirements. The intraperitoneal group

showed a signicantly longer time to rst rescue

analgesia and reduced total analgesic consumption and

number of rescue doses (Table 3). The magnitude of

reduction in analgesic requirement reects not only

statistical signicance but also clinical importance,

suggesting reduced opioid dependence and improved

patient comfort. These ndings are consistent with

previous studies demonstrating that intraperitoneal

administration reduces post-operative analgesic demand

by providing broader peritoneal coverage and

minimizing nociceptive transmission.^3,14,15In addition to

improved pain control, the intraperitoneal group

exhibited earlier ambulation, earlier oral intake, shorter

hospital stay, and higher patient satisfaction (Table 4).

These ndings are clinically signicant as they support

enhanced recovery pathways and align with modern

ERAS (Enhanced Recovery After Surgery) principles.

Recent evidence has similarly shown that improved

analgesia contributes to early mobilization, reduced

hospital stay, and better overall patient outcomes.^4,16

One important nding of this study was a signicant

reduction in shoulder tip pain in the intraperitoneal group

(Table 4). Shoulder tip pain following laparoscopic

surgery is primarily attributed to diaphragmatic irritation

due to residual carbon dioxide. The targeted delivery of

local anesthetic to the subdiaphragmatic region likely

explains the reduction observed in this study. This

nding is supported by previous studies demonstrating

that intraperitoneal interventions eectively reduce

referred shoulder pain by minimizing peritoneal

irritation and residual gas eects.^15,17,18,19The safety

prole of intraperitoneal bupivacaine in this study was

Surgery

duration

Total analgesia

0.089

0.408

Postoperative Pain Score (VAS)

Comparison Between Study Groups

Time after surgery (hours)

Intraperitoneal Mean VAS

Subcutaneous Mean VAS

Figure 1: Comparison of post-operative pain intensity (VAS

score) between intraperitoneal and subcutaneous bupivacaine

groups over 24 hours following laparoscopic cholecystectomy.

DISCUSSION

Intraperitoneal bupivacaine was found to be more

effective than subcutaneous (port-site) inltration in

patients undergoing laparoscopic cholecystectomy.

Despite comparable baseline characteristics (Table 1),

the intraperitoneal group demonstrated signicantly

lower VAS scores at all post-operative time points (1-24

hours), with the greatest difference observed in the early

post-operative phase (Table 2). Unlike many previous

studies that relied solely on simple comparative

statistics, the present study incorporates repeated-

measures ANOVA, eect size estimation, and

multivariate regression, providing a more robust and comparable to that of subcutaneous inltration. No cases

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Comparative Evaluation of Analgesic Outcomes of Intraperitoneal Versus

recovery and patient comfort.

of local anesthetic toxicity or allergic reactions were

observed, and other complications such as nausea,

vomiting, bradycardia, and hypotension were not

signicantly dierent between groups. These ndings

are consistent with recent systematic reviews conrming

that intraperitoneal local anesthetics are safe when used

within recommended dosage limits.^13,20A major strength

of this study is the use of advanced statistical methods,

including repeated-measures ANOVA, condence

intervals, eect size estimation, and multivariate

regression. The regression analysis demonstrated that

group allocation remained an independent predictor of

post-operative pain (p < 0.001), even after adjusting for

potential confounders, thereby strengthening the internal

validity of the ndings.

CONFLICT OF INTEREST: None

FUNDING SOURCES: None

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LIMITATIONS

This was a prospective, non-randomized study, and

allocation based on routine clinical practice, without

randomization or allocation concealment, introduces

potential selection bias and limits causal inference.

Although baseline comparability and regression

adjustment were performed, residual confounding

cannot be excluded. The study was conducted at a single

center with a relatively small sample size, limiting

generalizability. Post-operative pain assessment using

the Visual Analog Scale is subjective and influenced by

individual perception, despite observer training aimed at

minimizing variability. Additionally, formal inter-rater

reliability was not statistically assessed, which may

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CONCLUSION

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Intraperitoneal bupivacaine was associated with

signicantly improved postoperative analgesia and

recovery outcomes compared with subcutaneous

infiltration; however, these ndings should be

interpreted cautiously due to the non-randomized study

design. Patients in the intraperitoneal group experienced

lower pain scores at all post-operative time intervals,

delayed need for rescue analgesia, reduced total

analgesic consumption, and fewer rescue doses.

Improved recovery parameters, including earlier

ambulation, earlier oral intake, shorter hospital stay, and

higher patient satisfaction, were also observed, along

with a marked reduction in shoulder tip pain without

increased adverse eects. These ndings suggest that

intraperitoneal bupivacaine is a safe, effective, and

clinically benecial technique that may be incorporated

into routine post-operative pain management protocols

for elective laparoscopic cholecystectomy to enhance

https://doi.org/10.1002/14651858.CD007337.pub4

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postoperative pain: a systematic review and meta-analysis. BMC

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025-03105-y (PMID pending)

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14. Jingar H, et al. Levobupivacaine plus dexmedetomidine versus

AUTHORS CONTRIBUTION

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16. Hassan N, et al. Transversus abdominis plane block in

Nimrah Iqbal - Concept & Design; Data Acquisition; Data

Analysis/Interpretation; Drafting Manuscript; Supervision;

Final Approval

Waqas Anjum - Concept & Design; Data Acquisition; Data

Analysis/Interpretation; Drafting Manuscript; Final Approval

Abdul Rehman- Concept & Design; Data Acquisition; Drafting

Manuscript; Critical Revision; Final Approval

Jawad Zahir - Concept & Design; Data Acquisition; Drafting

Manuscript; Critical Revision; Final Approval

Sahar Iqbal - Concept & Design; Data Acquisition; Data

Analysis/Interpretation; Drafting Manuscript; Critical Revision;

Final Approval

Sundus Iqbal - Concept & Design; Data Acquisition; Data

Analysis/Interpretation; Drafting Manuscript; Critical Revision;

Final Approval

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