The pharmacokinetics of intraosseous atropine in hypovolemic swine
DOI:
https://doi.org/10.5055/ajdm.2015.0204Keywords:
intraosseous, intramuscular, atropine, nerve agent, shock, pharmacokineticsAbstract
Objective: Compare the pharmacokinetics of atropine administered via the intravenous (IV), intramuscular (IM), and intraosseous (IO) routes in a normovolemic and hypovolemic swine model.
Design: Prospective, between subjects, experimental study.
Setting: Vivarium.
Subjects: Yorkshire-cross swine (N = 36).
Intervention: Atropine was administered via IV, IM, or IO routes to normovolemic and hypovolemic swine. Blood samples were drawn at regular intervals after atropine administration and analyzed for plasma atropine concentration. Pharmacokinetic parameters were obtained from modeling the plasma concentrations.
Main outcome measurements: Pharmacokinetic parameters, maximum concentration (Cmax) and time to maximum concentration (Tmax).
Results: The IV and IO groups in both the normovolemic and hypovolemic models reached peak plasma concentration immediately and had a very rapid distribution phase with no apparent absorption phase for the IO groups. Peak plasma concentration and time to reach peak concentration were both significantly lower for the IM groups. There was a significant increase in absorption time with IM administration in the hypovolemic model compared to the normovolemic model.
Conclusion: The IO route is an effective method of administering atropine and is comparable to the IV route even under conditions of significant hemorrhage. Therapeutic levels of atropine may be delayed and possibly difficult to obtain via IM injection in the presence of hypovolemic shock.
References
Hurst G, Tuorinsky S, Madsen J, et al. (eds.): Medical Management of Chemical Casualties Handbook, 4th ed. Aberdeen Proving Grounds, MD: US Army Medical Research Institute for Chemical Defense, 2007.
Huebner KD, Arnold JL: CBRNE—Nerve agents, G-series—Tabun, sarin, soman. Medscape. Available at http://emedicine.medscape.com/article/831648-overview. Accessed September 21, 2015.
Buxton ILO, Benet LZ: Pharmacokinetics: The dynamics of drug absorption, distribution, metabolism, and elimination. In Brunton L, Lazo J, Parker K (eds.): Goodman and Gillman’s Pharmacological Basis of Therapeutics, 12th ed. China: McGraw-Hill, 2011: 22-23.
Sidell FR, Markis JE, Groff W, et al.: Enhancement of drug absorption after administration by an automatic injector. J Pharmacokinet
Biopharm. 1974; 2(3): 197-210.
Rowland M, Tozer T: Clinical Pharmacokinetics: Concepts and Applications, 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 1995.
Murray DB, Eddelston M, Thomas S, et al.: Rapid and complete bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning in minipigs after intraosseous administration. Ann Emerg Med. 2012; 60(4): 424-430.
Vardi A, Berkenstadt H, Levin I, et al.: Intraosseous vascular access in the treatment of chemical warfare casualties assessed by advanced simulation: proposed alteration of treatment protocol. Anesth Analg. 2004; 98(6): 1753-1758.
Martini WZ, Cortez DS, Dubick MA, et al.: Thromboelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. J Trauma. 2008; 65(3): 535-543.
Egan TD, Kuramkote S, Gong G, et al.: Fentanyl pharmacokinetics in hemorrhagic shock: A porcine model. Anesthesiology. 1999; 91(1): 156-166.
Friedl KE, Hannan CJ Jr, Schadler PW, et al.: Atropine absorption after intramuscular administration with 2-pralidoxime chloride by two automatic injector devices. J Pharm Sci. 1989; 78(9): 728-731.
Newmark J: (2004) The birth of nerve agent warfare lessons from Syed Abbas Foroutan. Neurology. 2004; 62(9): 1590-1596.
Published
How to Cite
Issue
Section
License
Copyright 2007-2023, Weston Medical Publishing, LLC
All Rights Reserved
