Clinical pharmacokinetics and pharmacodynamics of opioid analgesics in infants and children.
ABSTRACT Pain in childhood has not always been managed as actively as that in adults because of the limited amount of research available to provide guidelines for the management of paediatric pain. However, for many years now the pharmacokinetics and pharmacodynamics of opioid analgesics in infants and children have been studied intensively. Morphine is the standard for opioid analgesics and its pharmacology is the best studied in paediatric patients. During the neonatal period, the volume of distribution (Vd) appears to be smaller in neonates than in adults, but adult values are reached soon after the neonatal period. Although morphine is absorbed both orally and rectally, there is little information on the pharmacokinetics of morphine administered by these routes. The bioavailability of morphine after rectal administration appears to be highly variable. For all the opioid analgesics studied, the elimination of the opioids is slower in neonates than in adults. However, the rate of elimination usually reaches and even exceeds adult values within the first year of life. The high rate of drug metabolism means higher dosage requirements. In regard to the pharmacodynamics of opioid analgesics, infants and children do not appear to be more sensitive to the effects of opioids than adults. Thus, except for the neonatal period, the pharmacokinetics and pharmacodynamics of opioid analgesics are not markedly different from those of adults, and the risk of using opioids in infants and children is not higher.
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ABSTRACT: Oxycodone chloride (0.07 mg kg-1) was given by intravenous bolus to nine young adult surgical patients on the first postoperative day. Plasma was sampled for up to 12 h. Mean values of t1/2z, CL and Vss were 222 min, 0.78 l min-1 and 2.60 l kg-1, respectively. The concentrations of the metabolite noroxycodone was also measured. The mean AUC(0,12) ratio of noroxycodone to oxycodone was 0.33. Oxymorphone was not detected.British Journal of Clinical Pharmacology 11/1991; 32(4):516-8. · 3.58 Impact Factor
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ABSTRACT: We have analyzed several sedation techniques for paediatric cardiac catheterization which offer stable conditions for a few hours investigation, and maintain spontaneous breathing. In the present study, after premedication with oral flunitrazepam 0.1 mg.kg-1, 14 children aged 1-17 mo were sedated with an individually titrated alfentanil infusion. Every patient was sedated to a level which produced no reaction to pain or any discomfort. The induction dose and the maintenance requirement of alfentanil were 24 +/- 8 micrograms.kg-1 and 32 +/- 8 micrograms.kg-1.hr-1 (mean +/- SD), respectively. These doses were less in cyanotic than in acyanotic patients: 21 +/- 6 vs 28 +/- 8 micrograms.kg-1 and 29 +/- 10 vs 34 +/- 3 micrograms.kg-1.hr-1, respectively (P less than 0.05). The mean plasma concentration of alfentanil during maintenance of sedation was 79 +/- 23 ng.ml-1. Ventilation of two children was assisted for a short time after an incremental bolus of alfentanil. It is concluded that an alfentanil infusion technique with close monitoring of breathing is a practical sedation method for paediatric cardiac catheterization.Canadian Journal of Anaesthesia 12/1991; 38(8):980-4. · 2.13 Impact Factor
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ABSTRACT: The use of an alfentanil infusion as a supplement to a nitrous oxide-halothane anesthetic and the pharmacokinetics of alfentanil were evaluated in infants and children undergoing surgery for correction of congenital heart defects. Eleven patients, six infants and five children, were studied. Anesthesia was induced with nitrous oxide-halothane and pancuronium, 0.15 mg/kg. After intubation, anesthesia was maintained with nitrous oxide-oxygen and halothane to a maximum inspired concentration of 0.6%. After administration of atropine, 20 micrograms/kg, alfentanil, 20 micrograms/kg, was given, followed by a continuous infusion of 1 microgram/kg/min, which was stopped after closure of the sternum. Supplemental boluses of alfentanil, 5 micrograms/kg, were given when, during surgery, blood pressure and/or heart rate increased more than 20% above control values. At the end of surgery, after antagonism of residual neuromuscular blockade, the patients were extubated. Arterial blood samples were collected at regular intervals during surgery and for six hours thereafter for determination of alfentanil plasma concentrations by gas chromatography. Pharmacokinetic data were calculated using the method of residuals and noncompartmental moment analysis. Although atropine was administered, heart rate decreased significantly (2.5% to 15%) in all infants after administration of alfentanil. In the older children, blood pressure decreased 10% to 35%. In the period before bypass, three infants and four children needed supplemental boluses of alfentanil. During and after bypass, anesthesia was adequate. All patients could be extubed within 34 minutes of stopping the alfentanil infusion. Naloxone was not required in any patient, and postoperative respiratory depression did not occur. In the infants and children, total plasma clearance was 8.2 +/- 2.2 mL/kg/min and 6.3 +/- 0.8 mL/kg/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)Journal of Cardiothoracic Anesthesia 03/1988; 2(1):12-7.