◊ BACKGROUND:
Caudal administration of levobupivacaine (2.5 mg/kg) in children is used frequently in some hospitals. However, no reports of levobupivacaine concentrations have been published with this dosing scheme. We report the results of a study on the pharmacokinetics of levobupivacaine (2.5 mg/kg) after caudal administration in children younger than 3 yr.

◊ METHODS:
Ten children, aged 1-36 mo and scheduled for subumbilical surgery were studied under sevoflurane anesthesia. After caudal injection of 0.25% levobupivacaine (2.5 mg/kg), serial venous blood samples were taken for 3 h to measure total plasma concentration levels of levobupivacaine. Median (range) levobupivacaine Cmax and Tmax measured were 1.48 (0.62-2.40) microg/mL and 37 (10-60) min. The highest individual Cmax was observed in a 1-mo-old infant 30 min after caudal block.

◊ CONCLUSIONS:
The highest Cmax reached in this study was close to the toxic threshold of adult patients. Although no adverse events have been reported, care must be taken, especially in small infants, after caudal administration of levobupivacaine (2.5 mg/kg).

◊ Reviewed by A. Gupta, MD, PhD, FRCA
Associate Professor, Dept. of Anesthesiology and Intensive Care,
University Hospital, Örebro, Sweden

The study is simple in design and elegantly done, the aim being to determine the risk of toxic concentrations of levobupivacaine 2.5 mg/kg when injected caudally in children aged 1 – 36 months. Serial measurement of total plasma concentrations of levobupivacaine showed a wide variation in maximum concentration (Cmax 0.62-2.40 µg/mL) and time to maximum concentration (Tmax 10-60 min). The reason for this variation was unknown but the authors referred to previous studies where variation was similar. They state that no adverse (toxic) effect of the local anaesthetic was seen in any of the children but that care should be taken, specifically in small children where the maximum concentrations of levobupivacaine 2.5 mg/kg may approach concentrations known to be toxic in adults.

The first question that naturally arises is whether there is a real advantage of injecting 2.5 mg/kg levobupivacaine caudally compared to lower doses. Yao et al (Anaesthesia 2009;64:23-6) showed that the optimum dose of levobupivacaine for caudal analgesia in children is 1.5 mg/kg and therefore, there appears to be no reason to use 2.5 mg/kg. The correct approach should be to use the lowest doses of LA that provide adequate analgesia.

The next question is whether the large inter-individual variation in the maximum concentration of levobupivacaine could be explained by the variation of age (1 month – 36 months). In neonates and infants, the blood volume is centripetally distributed so that it is likely that the epidural space is proportionately more perfused with blood as compared to older children where blood distribution increasingly becomes centrifugal. A more rapid absorption of the LA through a highly perfused epidural space may lead to higher plasma concentration in neonates.

As the authors correctly point out, it is not the total plasma concentration of LA that is relevant to its toxicity, but the free concentration. The latter depends on the plasma level of α1-acid glycoprotein which, in the present study, was not measured. Therefore, although the concentration of levobupivacaine in the individual patient may have been high, the free concentration may have been not and consequently no evidence of toxicity was seen. This, however, remains hypothetical and in future studies, it is important to report free rather than total plasma concentrations.

Finally, since Tmax was 10-60 min and the caudal block was performed soon after induction of anaesthesia, it is likely that potential toxic symptoms would have occurred at a time when the child was still asleep under the effect of the anaesthetic. Therefore, it is incorrect to state “no child had signs or symptoms suggesting toxicity to LA”.

Having said this, I think that the authors performed a good study. What we can learn is that the dose of levobupivacaine should probably not exceed 2 mg/kg and in most cases, even 1.5 mg/kg may be adequate.