Dose-Related Pharmacokinetic and Pharmacodynamic Effects of Intramuscular Epinephrine in Healthy Neonatal Piglets

健康新生仔猪肌注肾上腺素的剂量相关药代动力学和药效学效应

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Abstract

BACKGROUND: Epinephrine is currently the only vasopressor recommended during neonatal cardiopulmonary resuscitation (CPR). Rapid vasopressor administration is critical during CPR; however, establishing vascular access can take several minutes and requires extensive skills and/or training. The intramuscular (IM) route provides rapid drug administration and does not require special skills, training, or equipment. We aimed to compare various doses of IM epinephrine to intravascular (IV) epinephrine in a healthy neonatal piglet model. METHOD: Fifteen newborn piglets (1-3 days of age) underwent anesthesia, intubation via a tracheostomy, and randomization to 0.02 mg/kg IM epinephrine, 0.1 mg/kg IM epinephrine, or 0.02 mg/kg IV epinephrine. Hemodynamic and cardiac function parameters were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the experiment for pharmacokinetic and pharmacodynamic analysis. RESULTS: Dose-dependent changes in hemodynamic and cardiac function parameters were observed following IM epinephrine administration. Greater changes were observed with 0.1 mg/kg IM epinephrine, while there were little to no changes with 0.02 mg/kg IM epinephrine. Pharmacokinetic parameters were not different between 0.02 mg/kg IV epinephrine or 0.1 mg/kg IM epinephrine. CONCLUSIONS: IM epinephrine dose of 0.1 mg/kg was more effective in producing systemic hemodynamic and cardiac function changes compared to the lower IM dose 0.02 mg/kg.

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