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Levobupivacaine absorption pharmacokinetics with and without epinephrine during TAP block: analysis of doses based on the associated risk of local anaesthetic toxicity

  • Pharmacokinetics and Disposition
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Cases of local anaesthetic systemic toxicity (LAST) periodically occur following transversus abdominal plane (TAP) blocks. The aim of this study was to characterize levobupivacaine absorption pharmacokinetics, with and without epinephrine, and estimate the risk of LAST, based on a previously reported toxic threshold.

Methods

Previously reported data from 11 volunteers receiving ultrasound-guided TAP blocks with and without epinephrine on two independent occasions were analysed. Serial venous concentrations were measured for 90 min. A pharmacokinetic analysis was performed using the NONMEM statistical programme. The use of epinephrine in the solution was included in the analysis of covariates. The associated risk of LAST symptoms associated with different levobupivacaine dose schemes with and without epinephrine was estimated in 1000 simulated subjects.

Results

A one-compartment first-order input and elimination model adequately fit the levobupivacaine data. Epinephrine prolonged the levobupivacaine absorption half-life {4.22 [95 % confidence interval (CI) 2.53–6.50] vs. 7.02 [95 % CI 3.74–14.1]; p < 0.05} and reduced its relative bioavailability (0.84; 95 % CI 0.72–0.97; p < 0.05) The derived model predicts that levobupivacaine dose schemes should be halved from 3 mg kg−1 body weight with epinephrine to 1.5 mg kg−1 without epinephrine to obtain a comparable risk of anaesthetic toxicity symptoms of approximately 0.1 %.

Conclusions

Our results strongly support the addition of epinephrine to the local anaesthetic solution, especially when doses of levobupivacaine of >1.5 mg kg−1 are required. Recommendations regarding the maximum allowable doses of local anaesthetics should consider population analysis to determine safer dosage ranges.

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Author contributions

PM wrote and planned the study, analysed the data and wrote the paper; AA wrote and planned the study and analysed the data; MAC wrote and planned the study and performed the research; GCE wrote and planned the study and performed the statistical analyses; LIC: wrote and planned the study, analysed the data and wrote the paper; FRA conceived the study, wrote and planned the study, analysed the data, and wrote the paper. All authors drafted and approved the final manuscript. The content is solely the responsibility of the authors.

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Authors and Affiliations

  1. División de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, 8330024, Santiago, Chile

    P. Miranda, M. A. Corvetto, Fernando R. Altermatt, A. Araneda, G. C. Echevarría & L. I. Cortínez

  2. Department of Anaesthesiology, New York University School of Medicine, New York, NY, USA

    G. C. Echevarría

Authors
  1. P. Miranda
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  2. M. A. Corvetto
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  3. Fernando R. Altermatt
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  4. A. Araneda
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  5. G. C. Echevarría
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  6. L. I. Cortínez
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Corresponding author

Correspondence to Fernando R. Altermatt.

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The authors have no conflicts of interest to declare.

Funding

This work was supported by a Research Fund, División de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile.

Additional information

ClinicalTrials.gov identifier: NCT01596998

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Miranda, P., Corvetto, M.A., Altermatt, F.R. et al. Levobupivacaine absorption pharmacokinetics with and without epinephrine during TAP block: analysis of doses based on the associated risk of local anaesthetic toxicity. Eur J Clin Pharmacol 72, 1221–1227 (2016). https://doi.org/10.1007/s00228-016-2086-1

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  • DOI: https://doi.org/10.1007/s00228-016-2086-1

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