Opioid-free versus opioid based anaesthesia for laparoscopic cholecystectomy- a randomized clinical trial.

Abstract

 AIM To compare the effect of Opioid-free multimodal analgesic regimen over conventional general anesthesia with opioids for post operative pain relief in patients posted for laparoscopic cholecystectomy.  BACKGROUND Laparoscopic cholecystectomy is the standard surgical procedure for cholelithiasis and Gall stone diseases. Although this procedure is thought to be generally painless and require a shorter hospital stay, they can nonetheless result in significant Pain, particularly in the first four hours after procedure. Opioids have been the primary mode of analgesia in the perioperative period with a number of associated side effects like delirium, constipation, nausea, vomiting, sedation, physical dependence, muscle rigidity, tolerance, respiratory depression etc. The preference of Multimodal opioid-free analgesia over opioids have been seen to be associated with intraoperative hemodynamical stability, early return of the bowel function, earlier mobilization of the patient, reduced length of hospital stay along with reduce in the severity of postoperative pain thereby reducing risk of chronic postoperative pain.  METHODOLOGY Informed consent was taken before the surgery. Patients kept nil by mouth 6 hours prior surgery. 10 | P a g e Docusign Envelope ID: 8F437D08-9D11-4DD8-B075-F17F1CE04AE6 All the patients were educated on Visual Analogue Scale and its scoring system. They were evaluated with a detailed history, general and systemic examinations in the preoperative room. Airway assessment and systemic examinations were done. Randomization was done and patients in the study were assigned into two Groups viz., Group A- Opioid free Anaesthesia and Group B - Conventional opioid group. In the preoperative room, Preloading was done with IV crystalloids 10ml/kg. IV Dexamethasone 8 mg was administered to all patients. Baseline parameters were monitored and Group A patients were administered IV paracetamol 15 mg/kg preoperatively. Patients in both the groups were pre oxygenated with 100% O2 for 3 min and then premedicated. Induction was done using IV propofol 2.5mg/kg until the endpoint of loss of eyelash reflex is obtained, along with Lignocaine 1.5 mg/kg (bolus dose) and 1.5mg/kg of succinyl Choline. Endotracheal intubation was done, Atracurium 0.5 mg/kg was administered as loading dose and then in incremental doses as needed along with Nitrous oxide, oxygen and sevoflurane 1%. Additionally, During the maintenance phase, Group A patients received Lidocaine 1.5mg/kg as slow intravenous infusion for an hour and Magnesium 2 g (bolus dose) over 10-15 minutes. Pre-incisional infiltration using 20 ml of 0.25% Bupivacaine (5 ml in each port) and intraperitoneal instillation of 20 ml of 0.25% Bupivacaine was given in the gall bladder bed, after gall bladder has been taken out. In the conventional Opioid group, a similar induction protocol was followed, along with 2 mcg/kg bolus dose of Fentanyl was given and later 0.5mcg/kg IV fentanyl to reduce the intraoperative rise of blood pressure. Intra-abdominal pressure was maintained between 12-15 mmHg during 11 | P a g e Docusign Envelope ID: 8F437D08-9D11-4DD8-B075-F17F1CE04AE6 pneumoperitoneum, and end-tidal CO₂ was kept below 35 mmHg. Intraoperative hemodynamic parameters were recorded. Residual neuromuscular blockade was reversed with IV neostigmine 2.5mg and IV Glycopyrrolate 0.5mg and tracheal extubation was done, after meeting the extubation criteria. At the end of surgery, all the patients received 1g paracetamol intravenously. Postoperatively, pain scores were assessed at 0, 2, 4, 6, 12, and 24 hours using the Visual Analogue Scale (VAS). Rescue analgesia with IV paracetamol was provided for VAS >4, and tramadol was administered for severe pain (VAS 8-10). The primary outcomes included postoperative pain scores, total analgesic consumption and the time to first analgesic request.  RESULTS Demographic Characteristics:  The mean age of patients (years) in Group A (OFA) was 46.21 ± 15.497 years, while in conventional opioid group, it was 41.09 ± 13.957 years. The difference was not statistically significant, ensuring comparability between the groups.  The mean weight of patients in Group A was 68.62 ± 13.298 kg, while in Group B, it was 63.32 ± 12.579 kg. This difference was also not statistically significant (p = 0.096). Intraoperative Hemodynamic Stability:  The mean systolic blood pressure (SBP) was higher in Group A (123.65 ± 5.672 mmHg) compared to Group B (119.50 ± 5.720 mmHg) 12 | P a g e Docusign Envelope ID: 8F437D08-9D11-4DD8-B075-F17F1CE04AE6  No significant differences were observed in diastolic blood pressure (DBP), heart rate (HR), or mean arterial pressure (MAP) between the two groups (p > 0.05), suggesting comparable intraoperative hemodynamic stability. Postoperative Pain (VAS Score Comparison): At 0, 2, 4, and 24 hours postoperatively, the OFA group demonstrated significantly lower pain scores compared to the conventional group (p < 0.05), indicating superior early postoperative pain control. Duration of Analgesia: The mean duration of analgesia was significantly longer in the OFA group (11.35 ± 7.639 hours) compared to the Opioid group (4.26 ± 2.050 hours) (p < 0.001). This indicates prolonged postoperative pain relief in patients receiving opioid-free anesthesia. Postoperative Analgesic Consumption:  A higher percentage of patients in the OFA group (24%) did not require postoperative analgesics, whereas all patients in the Opioid group required pain management.  A greater proportion of patients in the OFA group (71%) required only a single dose of paracetamol, compared to the opioid group. 13 | P a g e Docusign Envelope ID: 8F437D08-9D11-4DD8-B075-F17F1CE04AE6  None of the patients in the OFA group required combination of paracetamol and tramadol 50 mg, whereas 21% of patients in the conventional group required the additional opioid analgesia for pain relief. Postoperative Adverse Effects:  The incidence of nausea and vomiting was higher in the conventional opioid group (n=5) compared to the OFA group (n=0), though this difference did not reach statistical significance (p = 0.053).  Shoulder tip pain, commonly associated with residual carbon dioxide, was significantly more prevalent in the Opioid group than the OFA group. (p = 0.0115).  Other adverse effects, such as generalized pruritus and shivering, were reported only in the conventional opioid anesthesia group but were not statistically significant. • CONCLUSION Opioid-free anesthesia provided effective postoperative pain relief, reduced analgesic requirements, and lowered adverse effects when compared to the conventional opioid-based anesthesia. This multimodal opioid-free approach may offer a safer alternative for pain management in laparoscopic cholecystectomies.