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



      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.


      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).


      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.



      Examiner toutes les données probantes de haute qualité disponibles concernant l'effet de la bupivacaïne 24 heures (ou 8,9 demi-vies) après son administration peropératoire pendant une intervention chirurgicale gynécologique et vérifier si un deuxième mode d'action se produit, au-delà de la prévention initiale de l'ouverture des canaux sodiques par dépolarisation et du bloc de l'impulsion.

      Sources de données

      Nous avons fait des recherches dans toutes les grandes bases de données à l'aide d'un algorithme conçu pour inclure tous les essais randomisés qui ont utilisé n'importe quelle forme de bupivacaïne locale, quelle que soit la dose ou la voie d'administration, pendant une intervention chirurgicale gynécologique et qui ont comparé son utilisation avec un placebo de solution saline.


      Comme attendu, nous avons constaté que la bupivacaïne permettait d'obtenir une amélioration significative pour toutes les interventions chirurgicales gynécologiques en ce qui concerne l'intensité de la douleur 6 heures après l'intervention comparativement au groupe de la solution saline (différence moyenne [DM] : -1,28; IC à 95 % : -1,96 à -0,61, p = 0,07). Nous avons également constaté une différence significative 24 heures après l'intervention, ce qui indique la possibilité d'un deuxième mode d'action (DM : -0,57; IC à 95 % : -1,10 à -0,05, p = 0,01). Une autre analyse de sous-groupe des intensités de douleur à 24 heures indique une diminution significative de la douleur pour les sous-groupes de la laparoscopie (DM : -0,74; IC à 95 % : -0,93 à -0,54, p < 0,01) et de la laparotomie (DM : -2,60; IC à 95 % : -2,93 à -2,27, p < 0,01), mais pas pour ceux de l'hystérectomie vaginale (DM : 0,20; IC à 95 % : -0,69 à 1,09, p = 0,66) et de la réparation d'un prolapsus (DM : -0,11; IC à 95 % : -0,41 à 0,19, p = 0,48). Aucune différence significative n'a été observée quant à la durée d'hospitalisation (DM : -0,11; IC à 95 % : -0,59 à 0,38, p = 0,67).


      Comme attendu, la bupivacaïne a significativement réduit les scores visuels analogiques de la douleur comparativement au placebo 6 heures après l'intervention, mais elle a également montré une différence significative 24 heures après l'intervention, ce qui laisse croire à un deuxième mode d'action après le bloc des canaux sodiques.


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        • Zhou S
        • Huang G
        • Chen G
        Synthesis and biological activities of local anesthetics.
        RSC Advances. 2019; 9: 41173-41191
        • Bentsianov SD
        • Brandi K
        • Chen P
        • et al.
        A pilot study to understand the adolescent pain experience during contraceptive implant insertion.
        J Ped Adolesc Gynecol. 2021; 34: 522-524
        • Limwatanapan N
        • Chalapati W
        • Songthamwat S
        • et al.
        Lidocaine spray versus paracervical block during loop electrosurgical excision procedure: a randomized trial.
        J Low Genit Tract Dis. 2018; 22: 38-41
        • Uustal E
        Pre-emptive digitally guided pudendal block after posterior vaginal repair.
        Int Urogynecol J. 2020; : 1-7
        • Chang H
        • Rimel BJ
        • Li AJ
        • et al.
        Ultrasound guided transversus abdominis plane (TAP) block utilization in multimodal pain management after open gynecologic surgery.
        Gynecol Oncol Rep. 2018; 26: 75-77
        • Suner ZC
        • Kalayci D
        • Sen O
        • et al.
        Postoperative analgesia after total abdominal hysterectomy: is the transversus abdominis plane block effective?.
        Niger J Clin Pract. 2019; 22: 478
        • Braxton EG
        • Vilasagar S
        Laparoscopic transversus abdominis plane block in minimally invasive gynecologic surgery.
        J Minim Inv Gynecol. 2020; 27: S19
        • Williams LK
        • Weber JM
        • Pieper C
        • et al.
        Lidocaine–prilocaine cream compared with injected lidocaine for vulvar biopsy: a randomized controlled trial.
        Obstet Gynecol. 2020; 135: 311-318
        • Foo I
        • Macfarlane AJ
        • Srivastava D
        • et al.
        The use of intravenous lidocaine for postoperative pain and recovery: international consensus statement on efficacy and safety.
        Anaesthesia. 2021; 76: 238-250
        • Dunn LK
        • Durieux ME
        Perioperative use of intravenous lidocaine.
        Anesthesiology. 2017; 126: 729-737
        • Masic D
        • Liang E
        • Long C
        • et al.
        Intravenous lidocaine for acute pain: a systematic review.
        Pharmacotherapy. 2018; 38: 1250-1259
        • Uta D
        • Koga K
        • Furue H
        • et al.
        L-bupivacaine inhibition of nociceptive transmission in rat peripheral and dorsal horn neurons.
        Anesthesiology. 2021; 134: 88-102
        • El Beheiry H
        Local anesthetics.
        Pharmacology in clinical neurosciences. Springer, Singapore2020: 95-102
        • Liu H
        • Brown M
        • Sun L
        • et al.
        Complications and liability related to regional and neuraxial anesthesia.
        Best Pract Res Clin Anaesthesiol. 2019; 33: 487-497
        • Rajguru AY
        • Basha MK
        • Sravya YL
        • et al.
        Comparison of levobupivacaine and lidocaine for post-operative analgesia following tympanoplasty.
        J Evol Med Dent Sci. 2020; 9: 3029-3033
        • Woolf CJ
        Evidence for a central component of post-injury pain hypersensitivity.
        Nature. 1983; 306: 686-688
        • Sandkühler J
        Making the link from “central sensitization” to clinical pain.
        Landmark Papers in Pain: Seminal Papers in Pain with Expert Commentaries. 2018 Jul; 18: 47
        • Meacham K
        • Shepherd A
        • Mohapatra DP
        • et al.
        Neuropathic pain: central vs. peripheral mechanisms.
        Curr Pain Headache Rep. 2017; 21: 28
        • Shlaifer A
        • Sharfman ZT
        • Martin HD
        • et al.
        Preemptive analgesia in hip arthroscopy: a randomized controlled trial of preemptive periacetabular or intra-articular bupivacaine in addition to postoperative intra-articular bupivacaine.
        Arthroscopy. 2017; 33: 118-124
        • Moher D
        • Liberati A
        • Tetzlaff J
        • et al.
        Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement (Chinese edition).
        J Chinese Integrative Med. 2009; 7: 889-896
        • Higgins JPT
        • Green S
        Cochrane handbook for systematic reviews of interventions: Cochrane book series.
        Wiley, Hoboken, New Jersey2008 (Version 5)
        • Higgins JPT
        • Thompson SG
        • Deeks JJ
        • et al.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Higgins JP
        • Altman DG
        Assessing risk of bias in included studies.
        Cochrane handbook for systematic reviews of interventions: Cochrane book series. Wiley, Hoboken, New Jersey2008
        • Arden D
        • Seifert E
        • et al.
        Intraperitoneal Instillation of Bupivacaine for Reduction of Postoperative Pain After Laparoscopic Hysterectomy: A Double-Blind Randomized Controlled Trial.
        J Minim Invasive Gynecol. 2013; 20: 620-626
        • Marks JL
        • Ata B
        • Tulandi T
        Systematic review and metaanalysis of intraperitoneal instillation of local anesthetics for reduction of pain after gynecologic laparoscopy.
        J Minim Inv Gynecol. 2012; 19: 545-553
        • Katz J
        • Melzack R
        Measurement of pain.
        Surg Clin North Am. 1999; 79: 231-252