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The 90% effective dose of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal–epidural anesthesia in parturients with super obesity: an up-down sequential allocation study

La dose efficace à 90 % de bupivacaïne hyperbare intrathécale pour l’accouchement par césarienne sous péri-rachianesthésie combinée chez les personnes parturientes atteintes de super obésité : une étude d’allocation séquentielle en escalier

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Abstract

Purpose

To determine the 90% effective dose (ED90) of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal–epidural anesthesia (CSE) in parturients with super obesity (body mass index [BMI] ≥ 50 kg·m−2).

Methods

We enrolled parturients with BMI ≥ 50 kg·m−2 with term, singleton vertex pregnancies undergoing elective Cesarean delivery under CSE. An independent statistician generated the 0.75% hyperbaric bupivacaine dosing regimen in increments of 0.75 mg using a biased-coin up-down sequential allocation technique. This was combined with 15 μg fentanyl, 150 μg morphine, and normal saline to a volume of 2.05 mL. The initial and maximum doses were 9.75 mg and 12 mg, respectively. Participants, clinical team, and outcome assessors were blinded to the dose. The primary outcome was block success, defined as T6 block to pinprick within ten minutes and no intraoperative analgesic supplementation within 90 min of spinal injection. We determined the ED90 using logistic regression.

Results

We enrolled 45 parturients and included 42 in the analysis. All doses achieved a T6 level within ten minutes, and the primary outcome occurred in 0/1 (0%) of the 9.75-mg doses, 2/3 (67%) of the 10.5-mg doses, 21/27 (78%) of the 11.25-mg doses, and 11/11 (100%) of the 12-mg doses. The ED90 of hyperbaric bupivacaine was 11.56 mg (95% confidence interval, 11.16 to 11.99). Four parturients (9.5%) had sensory level higher than T2, but none was symptomatic or required general anesthesia.

Conclusion

The estimated ED90 of hyperbaric bupivacaine with fentanyl and morphine in parturients with super obesity undergoing Cesarean delivery under CSE was approximately 11.5 mg.

Study registration

ClinicalTrials.gov (NCT03781388); first submitted 18 December 2018.

Résumé

Objectif

Notre objectif était de déterminer la dose efficace à 90 % (DE90) de bupivacaïne hyperbare intrathécale pour l’accouchement par césarienne sous péri-rachianesthésie combinée (PRC) chez les personnes parturientes atteintes de super obésité (indice de masse corporelle [IMC] ≥ 50 kg·m−2).

Méthode

Nous avons recruté des personnes parturientes ayant un IMC ≥ 50 kg·m−2 présentant des grossesses uniques à terme, en présentation céphalique et bénéficiant d’un accouchement par césarienne programmée sous PRC. Un·e statisticien·ne indépendant·e a généré le schéma posologique de bupivacaïne hyperbare à 0,75 % par incréments de 0,75 mg à l’aide d’une technique d’allocation séquentielle en escalier. La bupivacaïne a été combinée à 15 μg de fentanyl, 150 μg de morphine et à une solution physiologique salée jusqu’à un volume de 2,05 mL. Les doses initiale et maximale étaient respectivement de 9,75 mg et 12 mg. Les participant·es, l’équipe clinique et les personnes évaluant les résultats n’avaient pas connaissance de la dose. Le critère d’évaluation principal était la réussite du bloc, définie comme un bloc à T6 à la piqûre dans les dix minutes et aucune supplémentation analgésique peropératoire dans les 90 minutes suivant l’injection rachidienne. Nous avons déterminé la DE90 à l’aide d’une méthode de régression logistique.

Résultats

Nous avons recruté 45 personnes parturientes et en avons inclus 42 dans l’analyse. Toutes les doses ont atteint le niveau T6 en dix minutes, et le critère d’évaluation principal a été obtenu pour 0/1 (0 %) des doses de 9,75 mg, 2/3 (67 %) des doses de 10,5 mg, 21/27 (78 %) des doses de 11,25 mg et 11/11 (100 %) des doses de 12 mg. La DE90 de bupivacaïne hyperbare était de 11,56 mg (intervalle de confiance à 95 %, 11,16 à 11,99). Quatre personnes parturientes (9,5 %) ont affiché un niveau sensoriel supérieur à T2, mais aucune n’était symptomatique ni n’a nécessité d’anesthésie générale.

Conclusion

La DE90 estimée de bupivacaïne hyperbare avec fentanyl et morphine chez les personnes parturientes hyperobèses bénéficiant d’une césarienne sous PRC était d’environ 11,5 mg.

Enregistrement de l'étude

ClinicalTrials.gov (NCT03781388); soumis pour la première fois le 18 décembre 2018.

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Author contributions

Ashraf S. Habib contributed to all aspects of this manuscript, including conception and design; acquisition, analysis, and interpretation of data; and drafting the article and revising it critically for intellectual content. Matthew Fuller contributed to the analysis of the data. Hon Sen Tan, Emily Barney, Olga Diomede, Riley Landreth, Trung Pham, Samantha Rubright, and Liliane Ernst contributed to the acquisition and interpretation of data and drafting of the article.

Acknowledgements

The authors acknowledge the contribution of the members of the Division of Women’s Anesthesia at Duke University Medical Center for their assistance with this study.

Disclosures

None.

Funding statement

Ashraf Habib has received research support from Pacira Biosciences, Haisco USA and Heron Therapeutics. He has also served on the Advisory Board for MDoloris, Vertex Pharmaceuticals, Merck and Heron Therapeutics.

Prior conference presentations

This study was presented in part at the 2023 Annual Meeting of the Society for Obstetric Anesthesia and Perinatology (3–7 May, New Orleans, LA, USA).

Editorial responsibility

This submission was handled by Dr. Ronald B. George, Associate Editor, Canadian Journal of Anesthesia/Journal canadien d’anesthésie.

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Authors and Affiliations

  1. Department of Women’s Anaesthesia, KK Women’s and Children’s Hospital, Singapore, Singapore

    Hon Sen Tan MD

  2. Department of Anesthesiology, Duke University Medical Center, Duke University, Durham, NC, USA

    Matthew E. Fuller MS & Emily Z. Barney MD

  3. Department of Anesthesiology and Perioperative Medicine, Maine Medical Center, Portland, OR, USA

    Olga I. Diomede MD

  4. Department of Anesthesiology, University of North Carolina, Chapel Hill, NC, USA

    Riley A. Landreth MD

  5. Associated Anesthesiologists Inc., Tulsa, OK, USA

    Trung Pham MD

  6. Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA

    Samantha M. Rubright MD

  7. Division of Women’s Anesthesia, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA

    Liliane Ernst MD & Ashraf S. Habib MBBCh, MSc, MHSc, FRCA

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  1. Hon Sen Tan MD
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  9. Ashraf S. Habib MBBCh, MSc, MHSc, FRCA
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Correspondence to Ashraf S. Habib MBBCh, MSc, MHSc, FRCA.

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Tan, H.S., Fuller, M.E., Barney, E.Z. et al. The 90% effective dose of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal–epidural anesthesia in parturients with super obesity: an up-down sequential allocation study. Can J Anesth/J Can Anesth 71, 570–578 (2024). https://doi.org/10.1007/s12630-024-02705-5

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