Pharmacokinetics and haemodynamic response after an intravenous bolus injection of clonidine in children

Abstract

SummaryThe pharmacokinetics and haemodynamic response after an intravenous bolus injection of clonidine (2.5 μg·kg−1) were investigated in paediatric patients. Plasma levels of clonidine were determined by radioimmunoassay in eight ASA 1 paediatric patients (age: 33 months (SD 13), weight: 15.1 kg (SD 3.4), body surface area: 0.625 m2 (SD 0.109)). A considerably shorter terminal half‐life (mean 6.13 h (SD 1.33), harmonic mean: 5.55 h, 95% confidence interval 4.60–7.63), a smaller distribution volume (0.96 1·kg−1 (SD 0.43)) and a higher total body clearance (4.85 ml·kg−1 min−1 (SD 1.00)) were found in comparison with previously reported adult studies. The haemodynamic response was investigated during isoflurane anaesthesia in twelve ASA 1 children (age: 31 months (SD 11), weight: 14.4 kg (SD 3.1)) premedicated with rectal midazolam and atropine. A significant reduction in mean arterial blood pressure (MABP) was observed (P= 0.0032). The MABP was found to be reduced by 26.3% (SD 13.6) compared with baseline and the time for 75% of the expected blood pressure reduction to occur was 21.3 min (SD 25.6). A consistent finding in all patients was a harmonic undulation of the blood pressure implying a dampened sine wave response. A small but significant decrease in heart rate (127 bpm (SD 19) vs 119 bpm (SD 20), P= 0.006) was observed immediately after injection following which the heart rate gradually returned to the previous baseline. The observed changes in heart rate and blood pressure responses were of a moderate magnitude. The use of clonidine as a premedicant or adjunct to general anaesthesia in children appears to be appropriate from both a pharmacokinetic and haemodynamic standpoint.