Plasma concentrations of bupivacaine after combined spinal epidural anaesthesia in infants and neonates

Abstract

The unbound and bound plasma concentration of bupivacaine in 50 infants less than 55 weeks postconceptual age was determined following combined spinal and epidural anaesthesia (csea). Plasma concentrations were determined at 15-min intervals up to 60 min postspinal anaesthesia. Maximum plasma bupivacaine levels were recorded between 45 and 60 min post CseA. Total plasma concentrations above a toxic threshold level of 4 microg.ml(-1) were recorded in 4% of patients and above 2.5 microg.ml(-1) in 10% of patients. Unbound bupivacaine levels were greater than a presumed toxic level of 0.25 microg.ml(-1) in 16% of cases and above 0.3 microg. ml(-1) in 14% of cases. A wide range of protein binding was measured (varying from 53.8-98.2%) and could not be correlated with standard indicators of local anaesthetic binding. Two neonates had brief apnoeas in the immediate perioperative phase but no adverse cardiac or central nervous system events attributable to the performance of Csea were demonstrated.

Concentração plasmática de ropivacaína durante anestesia peridural lombar em crianças

“…Provavelmente a boa estabilidade cárdiopulmonar observada no nosso estudo seja devido à concentração plasmática estar bem abaixo da encontrada no estudo feito em ratos, que foi 6 µg.ml -1 para bupivacaína e 13 µg.ml -1 para ropivacaína. O nível plasmático que oferece segurança é de 3 µg.ml -1 para ambos os agentes bupivacaína e ropivacaína 13,14 . Há relato de aparecimento de sinais e sintomas de toxicidade, em voluntários sadios, após infusão venosa de bupivacaína e ropivacaína, com níveis plasmáticos de ambas as drogas entre 1 e 2 µg.ml .…”

“…I t i s p o s s i b l e t h a t t h e g o o d cardiopulmonary stability observed in our study has been due to plasma concentrations for below that found in the study with rats, which was 6 µg.ml -1 for bupivacaine and 13 µg.ml -1 for ropivacaine. Safe plasma level is 3 µg.ml -1 for both agents 13,14 . There is a report on toxicity signs and symptoms in healthy volunteers after bupivacaine and ropivacaine intravenous infusion with plasma levels between 1 and 2 µg.ml .…”

“…Com relação às crianças, os parâmetros farmacocinéticos têm sido calculados para diferentes grupos etários submetidos à infusão contínua por via peridural 7 . O objetivo desse estudo é avaliar as concentrações sangüí-neas que podem ser atingidas quando a ropivacaína e a bupivacaína são administradas em bolus, por via peridural lombar em crianças, sendo o bloqueio eficaz, relacionando-se os valores encontrados àqueles descritos como níveis de segurança 13,14 . 15 .…”

“…In children, pharmacokinetic parameters have been calculated for different age groups after epidural continuous infusion 7 . The purpose of this study was to evaluate plasma concentrations reached with bolus lumbar epidural ropivacaine or bupivacaine in children after successful blocks, correlating them to values described as safe in the literature 13,14 .…”

Pharmacokinetics and systemic toxicity of local anesthetics in children

“…These results suggest that the plasma concentrations of both bupivacaine and levobupivacaine after spinal anesthesia are below the toxic level. However, the total plasma concentration of bupivacaine exceeded 2.5 µg/ml with unbound fraction >0.25 µg/ ml in neonates after a supplemental epidural dose of 1.25 mg/kg of 0.25 % bupivacaine following spinal anesthesia with 1 mg/kg of 0.5 % bupivacaine [24], suggesting the possibility of inducing systemic toxicity after spinal epidural anesthesia.…”