Morphine metabolism in acutely ill preterm newborn infants

Bhat, Rama; Abu-Harb, Mohamad; Chari, Gopal; Gulati, Anil

doi:10.1016/s0022-3476(05)80251-3

Cited by 54 publications

(30 citation statements)

References 9 publications

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“…In contrast with recent reports which sug gest that the capacity of preterm infants to metabolise morphine by glucuronidation is extremely variable [9], or that neonates are unable to form M6G due to immaturity of hepatic glucuronidation [17], the present study provides unequivocal evidence that morphine is metabolised to both M3G and M6G, thus confirming UDPGT activity for conjugation of morphine at the 3-and 6-posi tions in preterm neonates [10]. Although only morphine and its main metabolite (M3G) could be detected after a 2-hour loading infu sion (M3G achieved about 20% of morphine plasma concentrations), we were able to mea sure plasma concentrations of morphine, M3G and M6G in all samples obtained fol lowing 24 h of continuous infusion (M3G and M6G achieved 80% and 25% of morphine plasma concentrations, respectively).…”

Section: Discussioncontrasting

confidence: 75%

“…Developmental changes in the half-life [7,8,11] and plasma clearance of morphine [7,8] in premature neonates support this view, but provide no indication of changes in the rela tive plasma levels of M3G and M6G during maturation of the metabolic and excretory mechanisms. A recent study by Bhat et al [9] noted marked variability in the presence of either metabolite in plasma or urine from pre term newborns who received a single intrave nous dose of morphine. In another recently published study, Chay et al [17] reported plasma levels of morphine and M3G, but were unable to detect M6G, in preterm in fants receiving the drug as a continuous infu sion.…”

Section: Introductionmentioning

confidence: 99%

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Development of Morphine Glucuronidation in Premature Neonates

Hartley

Green²,

Mw³

et al. 1994

Neonatology

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In premature neonates (25–34 weeks gestation) who were given morphine intravenously during the first 24 h of life, only morphine, and morphine-3-glucuronide (M3G) were detected in plasma obtained after a 2-hour loading infusion, but morphine-6-glucuronide (M6G) could also be quantified following 24 h of continuous infusion. M3G/morphine and M6G/morphine plasma concentration ratios increased significantly with increasing birth weight. However, the M6G/M3G plasma concentration ratio decreased with increasing birth weight (and gestational age), thus providing the first indication in vivo of the differential development of uridinediphosphate glucuronosyltransferases in humans.

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Section: Discussioncontrasting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Development of Morphine Glucuronidation in Premature Neonates

Hartley

Green²,

Mw³

et al. 1994

Neonatology

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“…38,39 Morphine causes some histamine release and may lead to several side effects as a result. 29 For those infants on fluid restriction for patent ductus arteriosus (PDA) and those on diuretics, morphine will produce some degree of hypotension.…”

Section: Morphinementioning

confidence: 99%

Pharmacological approaches to the management of pain in the neonatal intensive care unit

Anand

2007

J Perinatol

103

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Effective and consistent management of neonatal pain remains a controversial issue.Premature infants are repeatedly subjected to painful tests and procedures or suffer painful conditions when they are most vulnerable. With different mechanisms transducing various types of pain the practice of 'one-drug fits all' becomes questionable.Clinicians must use the latest non-pharmacologic and pharmacologic therapies for effective management of neonatal pain, distress, or agitation. Pharmacologic strategies for dealing with neonatal pain in the neonatal intensive care unit are described. Opioid therapy, once considered the mainstay for neonatal analgesia, may not be as effective as previously thought. Morphine infusions do not alter the neurological outcomes of preterm neonates and may not be effective against acute pain. Alternative approaches with methadone, ketamine, or local anesthetics should be considered. Clinicians must understand the contextual circumstances underlying pain in individual neonates and tailor therapy accordingly, using the most current evidence related to neonatal pain assessment and management.

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“…Opioids can be given either intermittently or as a continuous drip. Pharmacokinetics and metabolism of these drugs are well studied 4,5 but their impact on long-term outcome has not been reported in term infants. Infact, no RCTs are available in term infants to support its routine use.…”

Section: General Managementmentioning

confidence: 99%

Pharmacotherapy for meconium aspiration

Asad

Bhat

2008

J Perinatol

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In this article we have attempted to review the current pharmacological treatment options for infants with meconium aspiration syndrome with or without persistent pulmonary hypertension. These treatments include ventilatory support, surfactant treatment and inhaled nitric oxide (INO), in addition to older and newer pharmacological treatments. These include sedatives, muscle relaxants, alkali infusion, antibiotics and the newer vasodilators. Many aspects of treatment, including ventilatory care, surfactant treatment and the use of INO, are reviewed in great detail in this issue. On the other hand, many newer pharmacological modalities of treatment described here have not been evaluated with randomized control trials. We have given an overview of these emerging therapies.

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Morphine metabolism in acutely ill preterm newborn infants

Cited by 54 publications

References 9 publications

Development of Morphine Glucuronidation in Premature Neonates

Development of Morphine Glucuronidation in Premature Neonates

Pharmacological approaches to the management of pain in the neonatal intensive care unit

Pharmacotherapy for meconium aspiration

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