Use of Opioids in Asphyxiated Term Neonates: Effects on Neuroimaging and Clinical Outcome

Abstract

Perinatal asphyxia is a common cause of neurologic morbidity in neonates who are born at term. Asphyxiated neonates are frequently treated with analgesic medications, including opioids, for pain and discomfort associated with their care. On the basis of previous laboratory studies suggesting that opioids may have neuroprotective effects, we conducted a retrospective review of medical records of 52 neonates who were admitted to our neonatal intensive care unit between 1995 and 2002 and had undergone magnetic resonance imaging (MRI) of the brain. Our review revealed that 33% of neonates received morphine or fentanyl. The neonates who received opioids also had experienced hypoxic/ischemic insults of greater magnitude as suggested by higher plasma lactate levels and lower 5-min Apgar scores. It is interesting that the MRI studies of neonates who were treated with opioids during the first week of life demonstrated significantly less brain injury in all regions studied. More important, follow-up studies of a subgroup of opioid-treated neonates whose MRI scans were obtained in the second postnatal week had better long-term neurologic outcomes. Our results suggest that the use of opioids in the first week of life after perinatal asphyxia have no significant long-term detrimental effects and may increase the brain's resistance to hypoxicischemic insults. Immediately after birth, asphyxiated neonates who are admitted to the neonatal intensive care unit (NICU) experience repetitive invasive and noninvasive procedures, such as endotracheal intubation, arterial line placement, i.v. catheterization, intramuscular injections, and endotracheal suctioning. Although necessary steps in the care of these neonates, such procedures result in pain and prolonged stress during a critical time associated with rapid brain growth and development (1). In addition to causing abnormalities in respiration, heart rate, and blood pressure (2), neonatal pain may alter neuronal and synaptic organization (3) and potentiate the effects of hypoxia (4). Animal studies show that exposure to untreated repetitive pain and stress results in prolonged firing of C-fibers, causing glutamate-induced N-methyl-D-aspartate (NMDA) receptor activation (5). This may augment hypoxia-induced glutamate release, an important mechanism that contributes to neuronal injury or death.Opioid analgesics such as morphine and fentanyl are administered to critically ill neonates in an effort to reduce pain and stress (6). The antinociceptive effects of these medications are mediated through a combined presynaptic and postsynaptic hyperpolarization, leading to reductions in the release of and sensitivity to endogenous mediators such as glutamate (7,8). These data suggest that opioids might confer neuroprotection by decreasing excitotoxicity through reductions in glutamate release, leading to greater overall reductions in neurologic damage. Cell culture studies indicate that both endogenous and exogenous opioids can protect cortical neurons from hypoxiainduced cell death (9,10) an...

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

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Systemic Hypothermia After Neonatal Encephalopathy: Outcomes of neo.nEURO.network RCT

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

“…Taddio et al 26 demonstrated that intravenous morphine was more effective than topical tetracaine for the management of pain associated with central line placement in neonates. Angeles et al 45 showed that opioid use in asphyxiated term neonates had a positive effect on the neuroimaging outcomes and clinical outcomes at 18 months.…”