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
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.