Pharmacokinetics of IM, IV, and IO Atropine in Normovolemic and Hypovolemic Swine

Introduction: Chemical warfare specifically nerve agents continue to be a major threat. Standard treatment includes IM atropine because of difficulty in obtaining IV access. Absorption of atropine from the muscle is dependant on blood flow and may be slow and inconsistent, particularly when the casualty is in shock. IO administration may provide rapid therapeutic levels of atropine equivalent to IV administration even when the patient is in shock.  This study proposes to identify the impact of hypovolemic shock on the absorption of IM atropine and determine if IO administration is an acceptable alternative. 

Design: The proposed study is a prospective, experimental, between subjects design investigating the pharmacokinetics: peak concentration (Cmax), time to peak concentration (Tmax) and area under the concentration time curve (AUC) of single dose atropine administered via the IO, IV, and IM routes in a normovolemic and hypovolemic pig model.

Research Questions:

To meet these aims, the following research questions were generated and will guide the study:

1. Is there a statistically significant difference in the pharmacokinetics between IO, IV, and IM administration of atropine in a normovolemic pig model?

2. Is there a statistically significant difference in the pharmacokinetics between IO, IV, and IM administration of atropine in a hypovolemic pig model?

3. Is there a statistically significant difference in the pharmacokinetics between IO, IV, and IM administration of atropine in a normovolemic compared to a hypovolemic pig model? Specifically, is there a change in the rate and extent of absorption after IM injection?

Analysis:  A repeated analysis of variance (RANOVA) will be used to determine if there are statistically significant differences in the in the groups relative to the pharmacokinetic parameters. If there are statistically significant differences, a Tukey post-hoc test will be used to determine where the significant difference lies.

Implications for Military Nursing: This study will clearly address several of the priorities of research as mandated by TSNRP: evidenced-based practice, healthcare needs arising from war, military clinical practice, and military response in emergent situations.  The aims and findings of this study directly impact military deployment health.

Final Report is available on NTRL: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB2017101...