Breathing and temperature control disrupted by morphine and stabilized by clonidine in neonatal rats

Background: Sedative-analgesics are often given to newborn infants and are known to affect many components of the autonomic nervous system. While morphine is most frequently used, α-2 adrenergic receptor agonists are being increasingly used in this population. Alpha-2 adrenergic receptors agonists also have anti-shivering properties which may make it a desirable drug to give to infants undergoing therapeutic hypothermia. The aim of this study was to systematically compare two different classes of sedative-analgesics, morphine, a μ-opioid receptor agonist, and clonidine an α-2 adrenergic receptor agonist on breathing, metabolism and core body temperature (CBT) in neonatal rodents. Methods: Breathing parameters, oxygen consumption (VO₂) and carbon dioxide production (VCO₂), were measured prior to, 10 and 90min after intraperitoneal (IP) administration of morphine (2, 10 or 20mg/kg), clonidine (40, 200 or 400μg/kg), or saline in Sprague-Dawley rat pups at postnatal day 7 (p7) while continuously monitoring CBT. Results: Morphine reduced the respiratory rate, VO₂ and VCO₂ greater than clonidine at all dosages used (p<0.05, morphine vs. clonidine, for all metabolic and respiratory parameters). Furthermore, morphine induced prolonged respiratory pauses, which were not observed in animals treated with clonidine or saline. Morphine caused hypothermia which was dose dependent, while clonidine stabilized CBT in comparison to saline treated animals (p<0.0001). Conclusion: In the newborn rat, morphine causes profound respiratory depression and hypothermia while clonidine causes minimal respiratory depression and stabilizes CBT. All together, we suggest that clonidine promotes autonomic stability and may be a desirable agent to use in infants being treated with therapeutic hypothermia.