A Systematic Review and Meta-Analysis of the Effect of Intraoperative Bupivacaine in Gynaecologic Surgery After 24 Hours or 9 Half-Lives

J Obstet Gynaecol Can. 2021 Nov;43(11):1279-1287. doi: 10.1016/j.jogc.2021.06.010. Epub 2021 Jul 19.


Objective: To review all high quality available evidence regarding the effect of intraoperative bupivacaine 24 hours (or 8.9 half-lives) after intraoperative administration at time of gynaecologic surgery and to ascertain whether a second mechanism of action, beyond the initial prevention of sodium channel depolarization and blockade of nerve impulses, may be occurring.

Data sources: We searched all major databases with an algorithm designed to include all randomized trials that used any form of local bupivacaine, regardless of dose or route of administration, at the time of any gynaecologic surgery and compared its use with saline placebo.

Results: As expected, we found that bupivacaine showed a significant improvement for all gynaecologic surgeries with respect to pain intensity at 6 hours after surgery when compared with a saline group (mean difference [MD] -1.28; 95% CI -1.96 to -0.61], P = 0.07). We also found a significant difference at 24 hours after surgery, giving evidence to the possibility of a second mechanism of action (MD -0.57; 95% CI -1.10 to -0.05], P = 0.01). Further subgroup analysis for pain levels at 24 hours showed significant decreases in pain for the laparoscopy (MD -0.74; 95% CI -0.93 to -0.54, P < 0.01) and laparotomy (MD -2.60; 95% CI -2.93 to -2.27, P < 0.01)) subgroups but not for the vaginal hysterectomy (MD 0.20; 95% CI -0.69 to 1.09, P = 0.66) or prolapse surgery (MD -0.11; 95% CI -0.41 to 0.19, P = 0.48) subgroups. There was no significant difference with respect to the length of hospital stay (MD -0.11; 95% CI -0.59 to 0.38, P = 0.67).

Conclusion: As expected, bupivacaine significantly reduced visual analog pain scores when compared with placebo at 6 hours after surgery, but also showed a significant difference at 24 hours after surgery, giving evidence of a second mechanism of action following the initial sodium channel blockade.

Keywords: Marcaine; anesthesia, local; bupivacaine; enhanced recovery after surgery; pain, ostoperativep; post-injury hypersensitivity.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anesthetics, Local
  • Bupivacaine*
  • Female
  • Gynecologic Surgical Procedures
  • Humans
  • Length of Stay
  • Pain, Postoperative* / drug therapy
  • Pain, Postoperative* / prevention & control


  • Anesthetics, Local
  • Bupivacaine