Plasma concentration was measured after rectal and nasogastric administration of paracetamol 15 mg/kg to 28 febrile children aged between 9 days to 7 years who had undergone cardiac surgery. After equivalent doses, rectal administration in neonates and children on the first postoperative day was found to produce plasma concentrations below the therapeutic range with higher concentrations after nasogastric paracetamol on the second postoperative day. There was less variance in plasma paracetamol concentrations in neonates. Both plasma elimination half life and area under the plasma concentration time curve were significantly increased in neonates after suppository dosing compared with older children. There was no difference in antipyretic effect between the two routes of administration, but this was much lower than that previously reported in febrile children.
Ninety boys, aged 13-53 months, undergoing repair of hypospadias, were allocated randomly to receive 0.8 ml kg-1 of one of three solutions into the caudal extradural space: group B received bupivacaine 2 mg kg-1, group T received tramadol 2 mg kg-1 in 0.9% saline and group BT a mixture of both. Postoperative pain was assessed hourly for 12 h after injection using a modified TPPPS pain score and additional analgesia was administered to those children whose pain scores were > 3/10. Nine patients (30%) in group T required additional analgesia within 1 h of surgery compared with only two (6.7%) and three (10%) patients in groups B and BT, respectively (P = 0.04). Mean duration before additional analgesia was required in the remaining patients was 9.3 (SD 3.0) h in group B, 10.7 (2.2) h in group T and 10.5 (2.0) h in group BT (P > 0.20). There were no significant differences between the groups in mean ventilatory frequency, sedation scores, incidence of emesis, facial flushing or pruritus. We conclude that caudal tramadol had a slow onset of action and that the addition of tramadol to bupivacaine, when both drugs were administered caudally, did not significantly prolong the duration of action of bupivacaine.
We have studied the pharmacokinetics of a single bolus dose of tramadol 2 mg kg-1 injected either i.v. or into the caudal epidural space in 14 healthy children, aged 1-12 yr, undergoing elective limb, urogenital or thoracic surgery. Serum concentrations of tramadol and its metabolite O-demethyl tramadol (MI) were measured in venous blood samples at various intervals up to 20 h by non-stereoselective gas chromatography with nitrogen-selective detection. All pharmacokinetic variables were evaluated using a non-compartmental model. After a single i.v. injection (n = 9), the mean elimination half-life of tramadol was 6.4 (SD 2.7) h, with a volume of distribution of 3.1 (1.1) litre kg-1 and total plasma clearance of 6.1 (2.5) ml kg-1 min-1. All of these pharmacokinetic variables were similar to those reported previously in adults. After caudal epidural administration (n = 5), mean elimination half-life was 3.7 (0.9) h, volume of distribution was 2.0 (0.4) litre kg-1 and total clearance was 6.6 (1.9) ml kg-1 min-1. The caudal/i.v. quotient of the AUC was 0.83, which confirms that there is extensive systemic absorption of tramadol after caudal administration. Serum concentrations of MI showed a time course typical of a metabolite after both modes of administration. Serum concentrations of MI after caudal administration were lower than those after i.v. injection.
Prolongation of the QT interval is associated with torsades de pointes (TdP), especially in children or young adults with long QT syndromes. Susceptibility to TdP arises from increased transmural dispersion of repolarization (TDR) across the myocardial wall. Several anesthetic drugs prolong the QT interval, but their effect on TDR is unknown. TDR can be measured on the electrocardiograph (ECG) as the time interval between the peak and end of the T wave (Tp-e). We investigated the effects of propofol and sevoflurane on the corrected QT (QTc) and Tp-e intervals in 50 unpremedicated ASA physical status I-II children, aged 1-16 yr, who were randomized to receive propofol (group P) or sevoflurane (group S). Twelve-lead ECGs were recorded preoperatively and intraoperatively. Sevoflurane significantly prolonged the preoperative QTc; propofol did not. Neither anesthetic had any significant effect on the preoperative Tp-e. Sevoflurane increases the duration of myocardial repolarization in children to a larger extent than does propofol, but as the dispersion of repolarization appears unaffected, the risk of TdP is likely to be minimal with either anesthetic.
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