Comparison of Intra-Peritoneal Instillation of Bupivacaine and Morphine Hydrochloride versus Bupivacaine and Magnesium Sulfate for Post-Operative Pain Relief after Laparoscopic Cholecystectomy, A Randomized Double-Blind Comparison Study
Publication Type
Original research


Surgical and laparoscopic techniques are two different methods for

the removal of gall bladder. Today, laparoscopic cholecystectomy is a preferred

method for short-term hospitalization and early return to function related to

minimal invasive surgical technique. However, patients still complain of significant

postoperative pain, secondary inflammation of the diaphragm and the nociceptive

genus of the annoying membrane's peritoneum.

Multimodal analgesia is necessary for managing pain after laparoscopic

cholecystectomy. Magnesium sulfate is a new emerging medication for the

management of acute pain. There are no previous reports to compare the analgesic

effect of intraperitoneal instillation of bupivacaine plus morphine hydrochloride

and bupivacaine plus magnesium sulfate for postoperative pain after laparoscopic



The purpose of this study is to compare the analgesic effect of intraperitoneal

instillation of bupivacaine plus morphine hydrochloride versus bupivacaine plus

magnesium sulfate in patients undergoing laparoscopic cholecystectomy under

general anesthesia for better pain relief and less opioid consumption during the

first 24 hours.


Following the approval of the Institutional Review Board of An-Najah

National University and written informed consent from patients undergoing

laparoscopic cholecystectomy, hundred patients between 18 and 60 years old,

American Society of Anesthesiologist (ASA) Grades I and II, were randomized to

one of the following groups by the sealed envelope: (Mo group) (n=50) receiving

intraperitoneal instillation of 30 ml 0.25% bupivacaine and 3 mg morphine and

(Mg group) (n=50) receiving intraperitoneal instillation of 0.25% bupivacaine plus

50 mg/kg magnesium sulfate to a total volume of 30 ml. Medications were given

after peritoneal wash and suctioning through intraperitoneal instillation. A drug

solution is prepared by a doctor who does not participate in the study. All patients

received the same anesthesia method, general anesthesia was administered.

The induction protocol was standard for all patients. Patients were monitored for

electrocardiogram (ECG), heart rate, blood oxygenation (SpO


%) and noninvasive

blood pressure (NIBP). Postoperative pain was evaluated using visual analog

scale (pain score of 0-10). The participants were evaluated for 24 hours after the

operation with the registration of abdominal pain. The postoperative pain outcome

was reported at 0 and 30 min, 1, 4, 8, 12, 16 and 24 hours. The cut-off value for

VAS is 4 for indication of rescue medication. At VAS ≥ 4, rescue analgesics were

administered on request (20 mg of pethidine) intravenously in Post Anesthetic

Care Unit (PACU) and 50 mg intramuscularly in the surgical ward


Patients' characteristics of age, gender and BMI were comparable in the

two groups. There was no significant difference between the groups regarding the

duration of the surgery. The demographic parameters (age, gender and BMI) have

no effect on the mean of VAS (p value>0.05). There are significant differences

between Mo and Mg groups in the total VAS score (p value<0.05). In the Mo group,

the mean of total VAS (2.09) was significantly lower than the mean of total VAS in

the Mg group (2.71); which means that patients in the Mo group had significantly

less intensity of pain than patients in the Mg group (p=0.006).

There is a significant difference between the number (percent) of patients

complaining of moderate to severe postoperative pain in Mo group 15/50 (30%)

compared to Mg group 25/50 (50%) (p=0.0423). When estimating the size of

the treatment effect of morphine hydrochloride plus bupivacaine, found that

the relative risk reduction of moderate to severe pain postoperatively is 0.40.

There is also a significant difference between the number (percent) of patients

complained of drowsiness in Mo Group 7/50 (14%) compared to Mg group 18/50

(36%) (p=0.0115). There are no significant differences between the two study

groups regarding nausea, vomiting, dizziness and urinary retention.

Patients in Mo group consume less rescue analgesic dose M (± SD) (64.29

mg+22.04) compared to patients in Mg group M (± SD) (74.40 mg+25.67) without

significant relationship between both doses (p-value=0.163). Blood pressure,

heart rate and oxygen saturation were examined as hemodynamic parameters.

The result showed that no significant relationship between these parameters and

VAS (p-value>0.05).


Intraperitoneal instillation of combination of bupivacaine with

morphine hydrochloride is superior to bupivacaine plus magnesium sulfate to

reduce the intensity and incidence of postoperative pain in patients undergoing

laparoscopic cholecystectomy surgery without significant increase of side effects.

This peripheral effect of opioid provides a new approach to pain relief that can

have major clinical benefits.


Based on the results of this study, it is recommended

to consider the intraperitoneal instillation of morphine hydrochloride with

bupivacaine as a standard application for laparoscopic cholecystectomy surgery

to reduce postoperative pain.


Bupivacaine; Intra-peritoneal instillation; Laparoscopic

cholecystectomy; Magnesium sulphate; Morphine hydrochloride; Rescue

analgesia; Post-operative pain.


International Journal of Anesthesiology & Pain Medicine
iMedPub Journals
Publisher Country
United Kingdom
Publication Type
Both (Printed and Online)