Laparoscopic cholecystectomy (LC) is now the gold standard in the management of symptomatic gallstone disease owing to its few advantages over open cholecystectomy such as smaller incisions, less postoperative pain, quicker recovery as well as a shortened hospital stay (1,2). Nonetheless, post operative pain especially during the initial few hours after an operation is a challenge that in most cases slows the recovery process and discharge (3).

Post-LC pain is multifactorial, with a combination of pneumoperitoneum, visceral manipulation, port-site injury, and enduring peritonal irritation (4). Multimodal analgesia is a way of attempting to act in different pain transmission pathways, and it is a proven technique to provide local anaesthetics directly into surgical sites to minimize the volume of nociceptive information (5,6). Bupivacaine is a long-lasting anaesthetic, which gives extensive analgesia upon intraperitoneal administration and port site pain management (7,8).

Previous studies have indicated mixed results concerning the efficacy of intraperitoneal administration of local anaesthetic in LC (9-12). This randomized controlled trial was undertaken to assess if intraoperative intraperitoneal and port-site infiltration of 0.25% bupivacaine plus standard analgesia would result in less postoperative pain and nausea than standard analgesia alone

Study design and setting: This was a prospective single-centre, randomized control trial study carried out at Rajarajeswari medical college and hospital, Bangalore, India, between July 1 and November 1, 2021.

Participants: Adults aged over 18 years old being scheduled with the elective LC due to symptomatic cholelithiasis which was confirmed with ultrasound were the eligible participants. Exclusion criteria were: emergency cholecystectomy, surgery to treat other causes, conversion to open cholecystectomy, pregnancy and those who withdrew before the 7-day follow-up.

Randomization and assignment: Sixty patients were randomized 1:1 by a computer generated randomization list. Allocation was blinded by being concealed in opaque envelopes, which were opened in the operating theatre following induction of anaesthesia.

Interventions: The study patients were treated with conventional analgesia and intraoperative infiltration with 16 mL 0.25% bupivacaine (8 mL sprayed into the gallbladder fossa into the peritoneum and 8 mL infiltrated subcutaneously on the four port sites), while only standard analgesia was given to the control group. The postoperative standard analgesia given in both groups was diclofenac 75 mg IM as required with the addition of tramadol 50 mg in case of unrelenting pain.

Outcomes: The main outcome was postoperative pain that was assessed on VAS scale for pain (scale of 1-10) at 1, 4, 6 hours, 12, 24 hours and 7 days after surgery. The secondary outcomes were postoperative nausea, vomiting, duration of the hospital stay, and any other adverse effects.

Statistical analysis: Fisher exact or chi-square were used to compare categorical variables and independent-samples t-test or Wilcoxon rank-sum test were used to compare continuous variables. The statistical significance of a p-value was determined as <0.05.

Our study had 53.3% female patients an 46.7% male patients. Of these, in the study group 17% male patients and 33% female patients were included.

The mean age of the study is 50.2 ± 15.0 years. Mean BMI of the study population is 27.6 ± 5.4 kg/m² and Nearly a fourth of patients were active smokers (23.8 %).

POST OPERATVIE ASSESSMENTS

Post op pain using VAS score

Severity of post operative nausea (VAS)

HOSPITAL STAY

There were no complications related to the use of bupivacaine used intraperitonelly recorded, like respiratory depression, paralytic ileus, etc.

In this prospective randomized controlled trial, use of intraoperative intraperitoneal administration and port-site infiltration of 0.25 % bupivacaine showed significant decrease in early postoperative pain and nausea that followed a laparoscopic cholecystectomy, when compared to standard analgesia. The significant improvement of pain levels was reported within the first 6 hours after surgery, where the highest pain intensity mostly appears in the immediate post-LC period (4,14).

The results of our study correlate with the findings achieved by Boddy et al. (5), who found that the largest effect of the use of local anaesthetic locally using an intraperitoneal route decreased the pain scores in the first 24 hours of using local anaesthetic in LC. Equally, Gupta et al. (4) recorded better analgesia when using intermittent delivery of wound catheter bupivacaine as compared to the placebo.

The use of a dual method, which we implemented, including intraperitoneal administration of the spray (galbladder fossa) and port-site infiltration has the advantage to cover visceral and somatic stages of postoperative pain. Alexander et al. (18) revealed that periportal infiltration reduced port-site pain by itself and Joris et al. (16) proved that intraperitoneal bupivacaine decreased visceral pain and referred shoulder pain. The combination scheme probably improved analgesia due to simultaneous action on both of the mechanisms.

The decrease of postoperative nausea with us is similar to the investigations conducted by Pasqualucci et al. (12) whose study revealed that pre-emptive intraperitoneal bupivacaine reduced pain as well as postoperative antiemetic requirement. The latter could be because of lubricating the visceral irritation and decreased opioid intake.

Study conducted by Lepner et al. (19), demonstrated little value of intraperitoneal local anaesthetic, they varied in their methodology, as they administered significantly lower doses and didn’t employ port-site infiltration. More volume and concurrent administration sites were more successful in our results.

Notably, within our cohort, the intervention was safe, and no complications related to use of bupivacaine were recorded. This is in line with the previous safety assessments, carried out by Kahokehr et al. (6), who concluded that there is no elevation in adverse incidents with the use of intraperitoneal local anaesthetic in abdominal surgery.

Our study strengths are the randomized procedure, comparable surgical and analgesic regimes used, the presence of both immediate and delayed pain measures, and assessment up to 7 days. Limitations included that this was a single-centre study, small sample size, and no double-blinding. Moreover, although results of pain and nausea were captured, the quantity of opioids used was captured in a qualitative form and not as an accurate cumulative dose which may suggest underestimation on total analgesic consumption variations.

The low-cost, safe, and effective mechanism of intraoperative intraperitoneal and port-site infiltration of 0.25% bupivacaine provides reduction in early postoperative pain and nausea that encompasses patients undergoing laparoscopic cholecystectomy. Doing so as a matter of routine can help the patient recover without a significant extension of the stay.

As it is safe, simple, and cheap, this technique may be introduced easily into high- or low-resource settings as a part of LC enhanced recovery protocols. Future studies need to be conducted using even larger multicentre RCTs that incorporate their analysis of cost-effectiveness and have extended follow-up to evaluate any effects on prolonged pain and the quality of life.

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