title: Intramuscular versus Intraosseous Delivery of Nerve Agent Antidote Pralidoxime Chloride in Swine.
abstract: Exposure to nerve agents requires prompt treatment. We hypothesized that intraosseous (IO) injections of drug antidotes into the vascularized bone marrow will provide a more rapid and effective means to treat exposure to nerve agents than standard intramuscular (IM) injections. We compared the pharmacokinetics of IM and IO administration of pralidoxime chloride (2-PAM Cl) during normovolemia and hypovolemia, as well as their combined administration during normovolemia in swine.
  
  
  
  Ten normovolemic swine were randomly administered 2 mL, 660 mg 2-PAM Cl via the IM or IO route and monitored for 180 minutes. IM versus IO also was compared in 8 hypovolemic swine bled to a mean arterial pressure of 50 mmHg. In a combined group, an IO injection was administered followed by an IM injection 60 minutes later. Blood samples were collected at times over a 180-minute period to calculate standard pharmacokinetic variables to compare the 2 routes of administration.
  
  
  
  In the normovolemic swine, IM injection achieved therapeutic levels (4 μg/mL) in 2 minutes, whereas IO infusion achieved these levels in less than 15 seconds. 2-PAM-Cl concentrations fell below these levels at 60 minutes post-injection in both groups. In the hypovolemic swine, IM injection achieved therapeutic levels in 4 minutes compared to less than 15 seconds in the IO group. 2-PAM-Cl concentrations fell below therapeutic levels at 12 and 90 minutes post-injection in the IM and IO groups, respectively. In the combined IO-IM treatment, plasma levels remained above therapeutic levels for the entire experiment and had two concentration peaks that corresponded to IO and IM injections.
  
  
  
  The IO route for the delivery of 2-PAM Cl provides a significant time and high initial blood concentrations advantage compared to the IM route for the prehospital treatment of nerve agent exposure even under hypovolemic conditions. The initial concentration peak associated with IO, but not IM, may provide greater initial therapy at the most critical time.
authors.forename: Nabeel I
authors.initials: NI
authors.lastname: Uwaydah
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoskins
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Bruttig
authors.forename: Henry
authors.initials: H
authors.lastname: Farrar
authors.forename: Nick C
authors.initials: NC
authors.lastname: Copper
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Deyo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
authors.forename: George C
authors.initials: GC
authors.lastname: Kramer
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage*; D004333:Drug Administration Routes; D017148:Infusions, Intraosseous; D007273:Injections, Intramuscular; D000067397:Nerve Agents; D011220:Pralidoxime Compounds / Q000008:administration & dosage*; D011897:Random Allocation; D013552:Swine
chemical_list: D000931:Antidotes; D000067397:Nerve Agents; D011220:Pralidoxime Compounds; C028797:pralidoxime
keywords: hemorrhage shock; intraosseous; pharmacokinetics; pralidoxime chloride; swine