Effect of sustained inflation on pharmacokinetics and pharmacodynamics of endotracheal and supraglottic airway epinephrine in a neonatal piglet model.

BACKGROUND

During neonatal resuscitation, the preferred route is intravenous (IV) or intraosseous (IO) administration, while endotracheal (ETT) delivery is a temporary solution. Supraglottic airway (SGA) devices are an alternative route to ETT administration. We compared the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine administered via ETT and SGA, as well as the impact of a sustained inflation to enhance drug absorption by pushing the drug into the lung.

METHODS

Thirty newborn anesthetized normoxic piglets (1-4 days old, 1.7-2.4 kg) were randomized to receive 0.1 mg/kg epinephrine via ETT, SGA (top or bottom placement), or combined with SI. Hemodynamic parameters (heart rate [HR], mean arterial pressure [MAP], and carotid blood flow [CBF]) and plasma epinephrine concentrations were measured at baseline and 1-10 min post-administration.

RESULT: ETT administration resulted in significantly higher HR, CBF, MAP, and plasma epinephrine concentrations compared to SGA routes (all p < 0.05), with peak concentrations achieved within 2 min versus the delayed, lower peaks in the SGA groups. SI did not enhance PK/PD outcomes in either the ETT or SGA groups.

CONCLUSION

ETT administration resulted in significantly higher hemodynamic parameters compared to SGA, An SI did not enhance pharmacokinetic or pharmacodynamic outcomes in either the ETT or SGA groups.

IMPACT: Endotracheal (ETT) epinephrine administration produced significantly higher plasma concentrations and stronger hemodynamic responses than supraglottic airway (SGA) delivery in a newborn piglet model. This study is the first to directly compare pharmacokinetics and pharmacodynamics of epinephrine delivered via ETT versus multiple SGA positions, with and without sustained inflation (SI). SGA administration resulted in delayed and lower epinephrine absorption, indicating limited effectiveness for rapid drug delivery during neonatal resuscitation. Sustained inflation did not enhance drug absorption or hemodynamic response for either ETT or SGA routes, challenging assumptions that SI might improve pulmonary drug uptake.