Effect of morphine and pancuronium on the stress response in ventilated preterm infants

Quinn, Michael; Otoo, F.; Rushforth, J.A.; Dean, H. G.; Puntis, John; Wild, Jennifer; Levene, Malcolm I.

doi:10.1016/0378-3782(92)90073-p

Cited by 64 publications

(38 citation statements)

References 16 publications

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“…Two retrospective studies evaluated the longterm effects of sedation or analgesia in preterm infants hospitalized in the NICU. The first study (104) evaluated neurologic outcome at 5-6 y in survivors from two randomized controlled trials, investigating morphine use in the early 1990s (105,106). No differences occurred between infants exposed and nonexposed to morphine, although the rates of death or disability in both groups were high (in the range of 40% for both), corresponding to commonly reported clinical outcomes in the presurfactant era.…”

Section: Existing Human Data On Neurotoxicity Of Sedative Drugs Used mentioning

confidence: 99%

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

et al. 2010

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Recent advances in neonatal intensive care include and are partly attributable to growing attention for comfort and pain control in the term and preterm infant requiring intensive care. Limitation of painful procedures is certainly possible, but most critically ill infants require unavoidable painful or stressful procedures such as intubation, mechanical ventilation, or catheterization. Many analgesics (opioids and nonsteroidal anti-inflammatory drugs) and sedatives (benzodiazepines and other anesthetic agents) are available but their use varies considerably among units. This review summarizes current experimental knowledge on the effects of sedative and analgesic drugs on brain development and reviews clinical evidence that speaks for or against the use of common analgesic and sedative drugs in the NICU but avoids any discussion of anesthesia during surgery. Risk/benefit ratios of intermittent boluses or continuous infusions for the commonly used sedative and analgesic agents are discussed in the light of clinical and experimental studies. The limitations of extrapolating experimental results from animals to humans must be considered while making practical recommendations based on the currently available evidence.

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Section: Existing Human Data On Neurotoxicity Of Sedative Drugs Used mentioning

confidence: 99%

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

et al. 2010

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“…Nevertheless, even the smallest infant could metabolise morphine to M3G and M6G (birth weight 0.58 kg, M3G/morphine 0.19, M6G/morphine 0.07) and hepatic capacity was clearly not saturated by the infu sion rates used in this study (mean M3G/morphine and M6G/morphine ratios between dose regimens were not significantly differ ent). However, despite efforts to optimise morphine dosage regimens by ensuring ade quate plasma levels of morphine within 2 h, 25-30% of premature neonates continued to Tight' the ventilator [18]. Since the 3-and 6-glucuronide metabolites have opposing ef fects on respiratory effort, it is of interest that after 2-4 h of morphine infusion plasma lev els of M6G were virtually undetectable in pre mature neonates, irrespective of dose, where as M3G achieved about 20-30% of morphine plasma levels.…”

Section: Discussionmentioning

confidence: 99%

“…All infants were receiving morphine for analgesia and sedation, to aid synchronisation of their respiratory effort with that of the ventilator, during treatment for respiratory distress syndrome, apnoea or pneumonia. This practice is based on the observation that during intermittent posi tive pressure ventilation (IPPV) plasma catecholamine levels were lower in infants receiving sedation (mor phine) compared with those who were not sedated [18], Additional drugs used routinely during the treat ment of these babies included curosurf. ampicillin, gentamicin, pancuronium, vitamin K. dopamine, dobutamine and noradrenaline.…”

Section: Methodsmentioning

confidence: 99%

“…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. In view of the opposing pharmacological effects of M3G and M6G, this apparent inter subject variability in the extent of glucuroni dation to M3G or M6G may account for the marked variation in clinical response in pre mature neonates, particularly during the first 2-4 h of treatment [18]. This study examines the patency of the glucuronidation pathway and investigates developmental changes in plasma levels of the drug and its glucuronides in premature neonates (gestational age 25-34 weeks), who received morphine intravenously during the first 24 h of life (postnatal age <24 h at initiation of treatment).…”

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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“…Morphine given to preterm infants struggling against the ventilator reduced stress hormone levels [31] , but its sedative effect has not been proven in this group [23] .…”

Section: Sedation and Paralysismentioning

confidence: 99%

How Should We Manage Pain in Ventilated Neonates?

Menon

McIntosh

2008

Neonatology

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Newborn babies, even if extremely preterm, show responses to pain. The major stress responses seen with surgical pain are associated with serious adverse medical outcomes. There is an ethical imperative to consider pain relief in babies, despite the fact that they cannot verbalise their experience. Ventilator support, and accompanying treatments are described as distressing in adults, and are associated with an endocrine stress response in babies. Opiates have been shown to reduce physiological instability in sick newborn babies. Despite this, they have not been shown to reduce morbidity when given by infusion in ventilated infants, and in view of their serious side effects probably should not be used routinely in this way. It is logical and may be appropriate to give opiates peri-operatively and in babies likely to have severe pain (either from an underlying disease process such as necrotising enterocolitis, or during certain procedures). It is now accepted practice to use a potent analgesic/sedative for elective intubation and as cover for the treatment of retinopathy of prematurity. Topical anaesthetic creams reduce the pain response when used in anticipation of phlebotomy or vascular cannulation. Intra-oral sucrose is effective cover for procedures associated with mild to moderate distress, but its role in preterm infants is uncertain. Nursing interventions to reduce environmental stress, although commonly used, have not consistently been shown to be of benefit.

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Effect of morphine and pancuronium on the stress response in ventilated preterm infants

Cited by 64 publications

References 16 publications

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

Development of Morphine Glucuronidation in Premature Neonates

How Should We Manage Pain in Ventilated Neonates?

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