Pharmacokinetic modelling and simulation for prolonged infusion of levobupivacaine with or without epinephrine in transversus abdominis plane and erector spinae plane blocks: a randomised controlled trial and analysis of pooled data

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dc.catalogadorjca
dc.contributor.authorAraneda, Andrea
dc.contributor.authorDe La Cuadra Fontaine, Juan Carlos
dc.contributor.authorCorvetto Aqueveque, Marcia Antonia
dc.contributor.authorBalde Sepúlveda, Detlef Peter Mario
dc.contributor.authorDe La Fuente Sanhueza, Rene Francisco
dc.contributor.authorIbacache Figueroa, Mauricio Enrique
dc.contributor.authorContreras, Víctor
dc.contributor.authorSolari Gajardo, Sandra
dc.contributor.authorCortinez Fernández, Luis Ignacio
dc.date.accessioned2025-07-22T19:34:19Z
dc.date.available2025-07-22T19:34:19Z
dc.date.issued2025
dc.description.abstractBackground: Interfacial blocks often require large volumes of local anaesthetic, raising concerns about systemic absorption and potential toxicity. This study examined the pharmacokinetics of levobupivacaine with and without epinephrine during thoracic erector spinae plane (ESP) or transversus abdominis plane (TAP) blocks, simulating reported 48-h dosing regimens to evaluate safety. Methods: Data from three studies were analysed. Study 1 included 38 patients receiving an ESP block before video-assisted thoracoscopy, whereas Study 2 analysed published data on TAP blocks. Both studies used 20 ml of levobupivacaine 0.25% with or without epinephrine (5 μg ml−1), measuring arterial concentrations over 90 min. Study 3 involved intravenous bupivacaine administration in 10 healthy volunteers. Pharmacokinetic analysis used NONMEM software, with significance set at P<0.05. Results: We analysed 258 ESP samples, 150 TAP samples, and 190 bupivacaine i.v. samples. A one-compartment model described the data, with a mean distribution volume of 41.9 L (coefficient of variation, 47%) and clearance rate of 0.288 L min−1 (coefficient of variation, 38%). Epinephrine reduced bioavailability (54.3% vs 32.8%) and prolonged absorption half-life (0.84 min vs 1.55 min; P<0.05). Simulated doses of 50 mg plus 300 mg per 24 h over 48 h remained below toxic thresholds. Conclusions: Similar dosing regimens for ESP and TAP blocks are supported by this pharmacokinetic analysis, with epinephrine effectively reducing systemic drug concentrations by prolonging absorption half-life and lowering bioavailability. The findings suggest that extended 300 mg per 24 h dosing for 48 h is likely to be safe. Further studies in broader patient populations are warranted to evaluate safety.
dc.format.extent8 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.bja.2025.05.047
dc.identifier.urihttps://doi.org/10.1016/j.bja.2025.05.047
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/104991
dc.information.autorucEscuela de Medicina; De La Cuadra Fontaine, Juan Carlos; 0000-0002-3868-0764; 58562
dc.information.autorucEscuela de Medicina; Corvetto Aqueveque, Marcia Antonia; 0000-0003-4688-0210; 146036
dc.information.autorucEscuela de Medicina; Balde Sepúlveda, Detlef Peter Mario; S/I; 172128
dc.information.autorucEscuela de Medicina; De La Fuente Sanhueza, Rene Francisco; 0000-0001-7187-3405; 102089
dc.information.autorucEscuela de Medicina; Ibacache Figueroa, Mauricio Enrique; S/I; 817
dc.information.autorucEscuela de Medicina; Solari Gajardo, Sandra; 0000-0002-3185-4717; 1871
dc.information.autorucEscuela de Medicina; Cortinez Fernández, Luis Ignacio; 0000-0001-8544-8768; 79356
dc.language.isoen
dc.nota.accesocontenido parcial
dc.rightsacceso restringido
dc.subjectErector spinae plane block
dc.subjectInterfacial block
dc.subjectLocal anaesthetic
dc.subjectPharmacokinetic modelling
dc.subjectRegional anaesthesia
dc.subjectSystemic toxicity
dc.subjectTransversus abdominis plane block
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePharmacokinetic modelling and simulation for prolonged infusion of levobupivacaine with or without epinephrine in transversus abdominis plane and erector spinae plane blocks: a randomised controlled trial and analysis of pooled data
dc.typeartículo
sipa.codpersvinculados58562
sipa.codpersvinculados146036
sipa.codpersvinculados172128
sipa.codpersvinculados102089
sipa.codpersvinculados817
sipa.codpersvinculados1871
sipa.codpersvinculados79356
sipa.trazabilidadORCID;2025-07-21
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