Introduction: Beneficial effects of the a-2 agonist clonidine have recently been reported in children both regarding its use during general anesthesia (Mkawa et al) and following epidural administration (Ivani et al). The pharmacokinetic and hemodynamic profile of clonidine after intravenous administration has also been found acceptable in pédiatrie patients (Lönnqvist et al). The aim of the current study was to determine the pharmacokinetic profile of clonidine after epidural administration in children. Methods: Following ethical committee approval and parental informed consent eight children (sex M/F: 4/4; age range: 1-9 y, weight range: 9-41 kg) undergoing ureteral reimplantation were included in the study. After induction of anesthesia and following endotracheal intubation an epidural puncture was performed at the L4-5 interspace (Portex 19 G Touhy needle, UK) followed by an epidural single bolus administration of bupivacaine 2 mg/kg (0.25 %) and clonidine 2 μg/kg. Non-invasive hemodynamic measurements as well as blood sampling for plasma clonidine levels were performed at 2, 5, 15, 30, 60 minutes and 3, 6, 10 hours following the epidural injection. Postoperative analgesia was assessed by the Hannallah-Broadman pain score (pain score < 6 defined as adequate analgesia; > 6 rescue paracetamol 20 mg/kg PR) and postoperative sedation was assessed by a previously reported sedation scale ' Plasma clonidine was analyzed by radio-immuno assay (Boehringer-rngelheim, Mainz, Germany). Results: Hemodynamic parameters remained stable during the study period. The mean time for postoperative analgesia and postoperative sedation were 924 minutes (range 120-1440) and 365 minutes (range 60-540), respectively. Plasma levels of clonidine are shown in the figure below. Peak plasma concentrations ranged 0.48-0.76 ng/ml and the time to maximum concentration (Tmax) ranged 45-180 minutes. Discussion: Absorption of clonidine from the epidural space was found to be slower in children compared to adults were very rapid absorption has been reported (Tmax 5-10 nun) 2. The absorption appears to have a two phase pattern with an early more rapid phase resulting in a "plateau" after approx. 30 minutes and a late phase causing maximum plasma levels at approx. (45-) 60-180 minutes. The clonidine administration was associated with stable hemodynanucs and prolonged postoperative analgesia. As expected sedation was observed during the early postoperative period.
Plasma levels of clonidine following epidural bolus administration (2 μg/kg) in children
Lampugnani E.;Jasonni V.;Mattioli G.;
1997-01-01
Abstract
Introduction: Beneficial effects of the a-2 agonist clonidine have recently been reported in children both regarding its use during general anesthesia (Mkawa et al) and following epidural administration (Ivani et al). The pharmacokinetic and hemodynamic profile of clonidine after intravenous administration has also been found acceptable in pédiatrie patients (Lönnqvist et al). The aim of the current study was to determine the pharmacokinetic profile of clonidine after epidural administration in children. Methods: Following ethical committee approval and parental informed consent eight children (sex M/F: 4/4; age range: 1-9 y, weight range: 9-41 kg) undergoing ureteral reimplantation were included in the study. After induction of anesthesia and following endotracheal intubation an epidural puncture was performed at the L4-5 interspace (Portex 19 G Touhy needle, UK) followed by an epidural single bolus administration of bupivacaine 2 mg/kg (0.25 %) and clonidine 2 μg/kg. Non-invasive hemodynamic measurements as well as blood sampling for plasma clonidine levels were performed at 2, 5, 15, 30, 60 minutes and 3, 6, 10 hours following the epidural injection. Postoperative analgesia was assessed by the Hannallah-Broadman pain score (pain score < 6 defined as adequate analgesia; > 6 rescue paracetamol 20 mg/kg PR) and postoperative sedation was assessed by a previously reported sedation scale ' Plasma clonidine was analyzed by radio-immuno assay (Boehringer-rngelheim, Mainz, Germany). Results: Hemodynamic parameters remained stable during the study period. The mean time for postoperative analgesia and postoperative sedation were 924 minutes (range 120-1440) and 365 minutes (range 60-540), respectively. Plasma levels of clonidine are shown in the figure below. Peak plasma concentrations ranged 0.48-0.76 ng/ml and the time to maximum concentration (Tmax) ranged 45-180 minutes. Discussion: Absorption of clonidine from the epidural space was found to be slower in children compared to adults were very rapid absorption has been reported (Tmax 5-10 nun) 2. The absorption appears to have a two phase pattern with an early more rapid phase resulting in a "plateau" after approx. 30 minutes and a late phase causing maximum plasma levels at approx. (45-) 60-180 minutes. The clonidine administration was associated with stable hemodynanucs and prolonged postoperative analgesia. As expected sedation was observed during the early postoperative period.
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