Superiority of preemptive analgesia with intraperitoneal instillation of bupivacaine before rather than after the creation of pneumoperitoneum for laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled study

Background: This study aimed to evaluate the optimal timing of preemptive analgesia with bupivacaine peritoneal instillation in a prospective, randomized, double-blind, placebo-controlled trial. Methods: In this study, 120 patients qualified for laparoscopic cholecystectomy were randomized to four groups. Group A received 2 mg/kg of bupivacaine in 200 ml of normal saline before creation of pneumoperitoneum. Group B received 2 mg/kg of bupivacaine in 200 ml of normal saline after creation of pneumoperitoneum. Group C received 200 ml of normal saline before creation of pneumoperitoneum. Group D received 200 ml of normal saline after creation of pneumoperitoneum. Local wound infiltration with bupivacaine was used before skin incisions. The primary end points of the study were postoperative pain intensity on a visual analog scale and incidence of shoulder tip pain. The secondary end points included the latency of nurse-controlled analgesia activation, the analgesia request rate, and analgesic consumption. Results: Significantly lower visual analog scores were observed in group A versus groups C and B versus group D during the initial 48 and 24 h, respectively. The patients in group A versus group B reported significantly lower pain at 4 h (p < 0.001) and 8 h (p = 0.003) postoperatively, but the difference was not significant after 12, 24, and 48 h. None of the group A patients reported shoulder tip pain, whereas it was reported by 3 patients in group B, 6 patients in group C, and 7 patients in group D (p < 0.01). The latency of nurse-controlled analgesia activation was 426.8 +/- 57.2 min in group A, as compared with 307 +/- 39.8 min in group B, 109.3 +/- 51 min in group C, and 109 +/- 46.5 min in group D (p < 0.001). A significantly lower analgesia request rate was observed in group A versus C, as compared with group B versus D, throughout the entire study period (p < 0.05). Conclusions: Preemptive analgesia with bupivacaine peritoneal instillation is much more effective for pain relief if used before creation of pneumoperitoneum. Although the effect of bupivacaine peritoneal instillation is also noticeable when used after creation of pneumoperitoneum, it confers significantly lower benefits.