Respiratory Sensitivity of the Newborn Infant to Meperidine and Morphine

Way, Walter L.; Costley, E. C.; Way, E. Leong

doi:10.1097/00132586-196608000-00034

Cited by 12 publications

(16 citation statements)

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“…Volume of distribution (V) changes and their relation to age that occur as a consequence of body composition changes can be described using quantitative functions similar to those used for clearance maturation. Clarification of these changes has debunked myths such as respiratory drive sensitivity in neonates given morphine that is attributable to the leaky blood-brain barrier [64]. Morphine volume of distribution is reduced in neonates and increases exponentially with a maturation half-life of 26 days from 83 l per 70 kg at birth [17].…”

Section: Volume Of Distributionmentioning

confidence: 99%

Population clinical pharmacology of children: modelling covariate effects

Allegaert²,

2006

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Section: Volume Of Distributionmentioning

confidence: 99%

Population clinical pharmacology of children: modelling covariate effects

Allegaert²,

2006

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“…Volume of distribution at steady-state (V,,) was calculated by moment analysis corrected for input by way of a constant rate infusionz3: (1) in which k, is the infusion rate, T is the infusion time, and k,T is the administered dose.…”

Section: Appendixmentioning

confidence: 99%

“…One patient (patient 4) received indomethacin for successful closure of the patent ductus arteriosus. Eight infants (patients1,3,4,5,7,8,12, and 17) had neonatal hyperbilirubinemia that was successfully treated with phototherapy. Exchange transfusion was not necessary in any infant.…”

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confidence: 99%

Pharmacokinetic-pharmacodynamic relationships of morphine in neonates

Chay

Duffy

Walker

1992

Clin Pharmacol Ther

130

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Morphine pharmacokinetics and pharmacodynamics (analgesia and sedation) were evaluated after continuous intravenous infusion of morphine in 19 neonates, both preterm and term, whose lungs were ventilated to relieve respiratory distress. Elimination half-life, total plasma clearance, and volume of distribution (mean +/- SD) were 9.6 +/- 3.0 hours, 2.55 +/- 1.65 ml/min/kg (area analysis) or 2.09 +/- 1.19 ml/min/kg (steady-state data), and 2.05 +/- 1.05 L/kg, respectively, and were not significantly different in preterm and term neonates. In neonates with adverse effects of morphine, the plasma clearance was decreased twofold. Mean morphine concentration required to produce adequate sedation in 50% of patients was found to be 125 ng/ml, but concentrations above 300 ng/ml may be associated with adverse effects of morphine. Morphine-6-glucuronide was not detected in the plasma of any neonate, which may explain why neonates require high plasma concentrations of unchanged morphine for sedation.

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“…Finally, the respiratory centres of newborns are extremely sensitive towards opioids (Way et al 1965). This must be considered when using opioids during labour and it is also the explanation for the fact that neonatal apnoea episodes are significantly associated with exposure to opioids in breast milk (Naumburg & Meny 1988).…”

Section: Respiratory Depressionmentioning

confidence: 99%

Adverse Effects of Systemic Opioid Analgesics

Schug¹,

Zech²,

Grond³

1992

Drug Safety

143

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Adverse effects of opioids are multiple. They are most often receptor-mediated and inseparable from their desired effects. The most severe mishaps with opioids are related to their respiratory depressant effect, which is widely influenced by factors such as pain, previous opioid experience and awareness. Other relevant central nervous system effects of opioids include cough suppression, nausea and vomiting, rigidity, pruritus and miosis. The cardiovascular adverse effects of opioids are mainly related to histamine release and differ widely between agonists and agonist-antagonists. Gastrointestinal effects such as constipation, reflux and spasms of the bile duct are well described. Adverse effects on endocrine, immunological and haematological functions are possible, while allergic reactions are extremely rare. The adverse effects of long term use are overestimated. Systemic toxicity is negligible and development of tolerance is minimal while treating pain. In the clinical setting of pain control, addiction and withdrawal do not pose significant problems. Nevertheless, the possible effects of opioids on the unborn child should always be considered. Overall, opioids show a good record of safety. Their use should not be unduly limited by unfounded fears of adverse effects, but these effects should be avoided by anticipation and prevention.

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Respiratory Sensitivity of the Newborn Infant to Meperidine and Morphine

Cited by 12 publications

References 0 publications

Population clinical pharmacology of children: modelling covariate effects

Population clinical pharmacology of children: modelling covariate effects

Pharmacokinetic-pharmacodynamic relationships of morphine in neonates

Adverse Effects of Systemic Opioid Analgesics

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