Pharmacokinetics and systemic toxicity of local anesthetics in children

Abstract

toxicity is 2-3 µg/ml of total (protein bound and unbound) and 0.1-0.2 µg/ml of unbound bupivacaine, levobupivacaine and ropivacaine [1,2]. Notably, the intra-arterial concentration of unbound bupivacaine for inducing CNS toxicity is approximately 50 % of unbound ropivacaine, both of which are three-and four-fold higher, respectively, than the intravenous concentration [1]. Cumulative case reports and animal experiments have also shown that the systemic toxicity of levobupivacaine and ropivacaine is less than bupivacaine [3,4]. Infants are prone to develop CNS toxicity by bupivacaine at total and unbound concentrations lower than these values [5]. Although the threshold plasma concentration for cardiac toxicity is higher than for CNS, symptoms such as dysrhythmia and QRS widening due to decreased intraventricular conduction by long-acting local anesthetics may appear prior to any neurological manifestations in infants [6]. As neonates and infants have a higher heart rate than adults, the intensity of the block is also higher (use-dependent block) and they are more prone to the toxic effects of bupivacaine, levobupivacaine and ropivacaine than adults. Hypoxia, acidosis, hypothermia and electrolyte disorders increase cardiac toxicity [3]. Protein binding and dispositionAmide local anesthetics are predominantly bound to plasma alpha 1 -acid glycoprotein (AAG), and to a minor extent to albumin. The plasma concentration of AAG at birth is approximately 20-50 % of that in adults. During the first 6-9 months of life, it progressively increases to reach adult levels by the end of the first year [7] (Fig. 1a). Although the levels of albumin in neonates are also lower than in adults, its affinity to local anesthetics is approximately 5,000-10,000 times lower than AAG, suggesting that albumin

Erector spinae catheter for post-thoracotomy pain control in a premature neonate

“…Given the immature hepatic function in patients at this age, we believe that substituting this for the more commonly used aminoamide local anaesthetics may reduce these patients' risk of local anaesthetic toxicity. 9 We chose the infusion rate as it was published in several successful paediatric ESP catheter case reports, and it is a safe rate of chloroprocaine infusion. ESP catheter placement is feasible for premature neonates, and it provides effective intraoperative and postoperative analgesia for thoracotomy.…”

“…However, continuous ESP blocks may require large volume local anaesthetic infusions to be efficacious, which presents an additional challenge in this population due to immature hepatic metabolism and increased susceptibility to the cardiotoxic and neurotoxic effect of aminoamide local anaesthetics. 9 We present the novel management of a coagulopathic premature neonate undergoing thoracotomy for tracheoesophageal fistula (TEF) repair with a preoperatively placed ESP catheter with continuous intraoperative and postoperative chloroprocaine infusion.…”

“…However, continuous ESP blocks may require large volume local anaesthetic infusions to be efficacious, which presents an additional challenge in this population due to immature hepatic metabolism and increased susceptibility to the cardiotoxic and neurotoxic effect of aminoamide local anaesthetics. 9 …”

Exploring the transversus abdominis plane block in cesarean sections and the subsequent toxicity risk to neonates via breast milk

“…However, studies have demonstrated that despite the similarities in estimated half-time, bupivacaine when delivered via modalities, such as epidural or caudal injections, persists in the serum for longer in infants and children than adults. [1718] This is due in part to the fact that infants have lower levels of alpha-1-acid glycoprotein in their serum, which is the primary protein that binds to bupivacaine. This can result in a higher free concentration of bupivacaine, placing an infant at a higher risk for toxicity.…”

Eficacia analgésica y complicaciones a corto plazo de catéteres peridurales lumbares y torácicos en pacientes pediátricos: una evaluación retrospectiva

“…Esto permite administrar menores dosis de anestésicos locales, proporcionar una adecuada propagación del anestésico y disminuir el riesgo de TSAL. Esto último sería más relevante en lactantes y recién nacidos, en quienes las variaciones farmacocinéticas y farmacodinámicas los hacen más propensos a desarrollar TSAL con concentraciones más bajas de anestésicos locales (Oda, 2016).…”