Paracetamol Plus Tramadol Versus Fentanyl as Pre-emptive Analgesia for Enhanced Recovery after Day-Case Surgeries: A Randomised Controlled Trial

Abstract Background: Effective perioperative pain control is central to enhanced recovery after day-case surgery, yet the optimal pre-emptive analgesic strategy for ambulatory procedures remains debated. This trial compared pre-emptive intravenous paracetamol plus tramadol with pre-emptive intravenous fentanyl for enhanced recovery following day-case surgery. Methods: In this prospective, randomised controlled trial, 102 adult patients (ASA physical status I–II, aged 21–65 years, BMI 25–30 kg/m²) scheduled for elective day-case surgery lasting 1–2 hours were randomly allocated 1:1 to intravenous paracetamol (15 mg/kg) plus tramadol (1 mg/kg) (Group T, n=51) or intravenous fentanyl (1.5 µg/kg) (Group F, n=51) before induction of general anaesthesia. The primary outcome was the Enhanced Recovery Score (QoR-40), recorded 24 hours postoperatively. Secondary outcomes included postoperative VAS pain scores, time to first rescue analgesia, RASS scores, perioperative haemodynamics, hospital stay duration, and adverse events. Results: Baseline characteristics were comparable between groups. The Enhanced Recovery Score was significantly higher in Group T than Group F (188.06±4.29 vs 179.82±5.17; p=0.0001). Group T had lower VAS scores on arrival and at 1 hour (p<0.001), whereas Group F had lower VAS scores from 4 hours onward (p<0.001); despite this, Group T had a markedly longer time to first rescue analgesia (median 6 vs 1 hour; p<0.001). Group T showed deeper sedation on RASS immediately after extubation and on arrival to the PACU (p<0.001), with no difference by 20 minutes. Postoperative heart rate was higher in Group F (76.61±9.74 vs 72.73±7.76 beats/min; p=0.028); other haemodynamic parameters and hospital stay did not differ significantly. No other adverse events occurred; nausea and vomiting occurred at a low, similar rate in both groups. Conclusion: Pre-emptive paracetamol plus tramadol provided better early analgesia, markedly delayed the need for rescue analgesia, and was associated with a higher Enhanced Recovery Score than pre-emptive fentanyl in patients undergoing day-case surgery, despite higher pain scores from 4 hours onward and deeper early postoperative sedation. Both regimens showed a comparable safety profile. Trial registration: The trial was prospectively registered on 14 th of August 2023 on Clinicaltrials.gov (NCT05990686) prior to enrolment of the first participant.