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Is 0.375% bupivacaine safe in caudal anesthesia in neonates and young infants?

Cucchicaro et al. (1) recently reported single-dose caudal anesthesia in high-risk infants using 0.375% bupivacaine. We are concerned about their use of a relatively large dose of bupivacaine (3.75 mg/ kg) in their caudal solutions, which exceeds previously published guidelines (2,3) of 2.5 mg/kg in infants. The authors justify this dose by citing studies demonstrating serum levels below the reported toxic level of 4 g/mL using comparable doses (4,5). These studies were performed in children, not in neonates or young infants. Berde (3) has stated that convulsions can occur with serum concentrations as low as 2 g/mL. Mazoit et al. (6) reported that neonates and young infants have a significantly higher free fraction of caudally injected bupivacaine. This free fraction correlated inversely with low levels of -1 acid glycoprotein. None of these patients were tracheally intubated or mechanically ventilated. No episodes of hypoxemia were reported, but no mention was made of ETco2. The prematurity and medical conditions of these patients, coupled with surgical retraction, would make them prone to intraoperative hypercarbia, which could precipitate local anesthetic induced seizures should serum levels approach toxic levels. On the basis of these concerns, we caution readers to be judicious in their doses of bupivacaine for caudal blocks, especially in neonates.