title: The Resuscitative and Pharmacokinetic Effects of Humeral Intraosseous Vasopressin in a Swine Model of Ventricular Fibrillation.
abstract: Introduction The American Heart Association (AHA; Dallas, Texas USA) and European Resuscitation Council (Niel, Belgium) cardiac arrest (CA) guidelines recommend the intraosseous (IO) route when intravenous (IV) access cannot be obtained. Vasopressin has been used as an alternative to epinephrine to treat ventricular fibrillation (VF). Hypothesis/Problem Limited data exist on the pharmacokinetics and resuscitative effects of vasopressin administered by the humeral IO (HIO) route for treatment of VF. The purpose of this study was to evaluate the effects of HIO and IV vasopressin, on the occurrence, odds, and time of return of spontaneous circulation (ROSC) and pharmacokinetic measures in a swine model of VF.
  
  
  METHODS
  Twenty-seven Yorkshire-cross swine (60 to 80 kg) were assigned randomly to three groups: HIO (n=9), IV (n=9), and a control group (n=9). Ventricular fibrillation was induced and untreated for two minutes. Chest compressions began at two minutes post-arrest and vasopressin (40 U) administered at four minutes post-arrest. Serial blood specimens were collected for four minutes, then the swine were resuscitated until ROSC or 29 post-arrest minutes elapsed.
  
  
  RESULTS
  Fisher's Exact test determined ROSC was significantly higher in the HIO 5/7 (71.5%) and IV 8/11 (72.7%) groups compared to the control 0/9 (0.0%; P=.001). Odds ratios of ROSC indicated no significant difference between the treatment groups (P=.68) but significant differences between the HIO and control, and the IV and control groups (P=.03 and .01, respectively). Analysis of Variance (ANOVA) indicated the mean time to ROSC for HIO and IV was 621.20 seconds (SD=204.21 seconds) and 554.50 seconds (SD=213.96 seconds), respectively, with no significant difference between the groups (U=11; P=.22). Multivariate Analysis of Variance (MANOVA) revealed the maximum plasma concentration (Cmax) and time to maximum concentration (Tmax) of vasopressin in the HIO and IV groups was 71753.9 pg/mL (SD=26744.58 pg/mL) and 61853.7 pg/mL (SD=22745.04 pg/mL); 111.42 seconds (SD=51.3 seconds) and 114.55 seconds (SD=55.02 seconds), respectively. Repeated measures ANOVA indicated no significant difference in plasma vasopressin concentrations between the treatment groups over four minutes (P=.48).
  
  
  CONCLUSIONS
  The HIO route delivered vasopressin effectively in a swine model of VF. Occurrence, time, and odds of ROSC, as well as pharmacokinetic measurements of HIO vasopressin, were comparable to IV. Burgert JM , Johnson AD , Garcia-Blanco J , Fulton LV , Loughren MJ . The resuscitative and pharmacokinetic effects of humeral intraosseous vasopressin in a swine model of ventricular fibrillation. Prehosp Disaster Med. 2017;32(3):305-310.
authors.affiliation: 1The Geneva Foundation for Military Medical Research,Tacoma,WashingtonUSA.
authors.forename: James M
authors.identifier: http://orcid.org/0000-0001-8346-6196
authors.initials: JM
authors.lastname: Burgert
authors.affiliation: 1The Geneva Foundation for Military Medical Research,Tacoma,WashingtonUSA.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Johnson
authors.affiliation: 1The Geneva Foundation for Military Medical Research,Tacoma,WashingtonUSA.
authors.forename: Jose
authors.initials: J
authors.lastname: Garcia-Blanco
authors.affiliation: 4Rawls College of Business & Center for Health Innovation,Education & Research,Texas Tech University,Lubbock,TexasUSA.
authors.forename: Lawrence V
authors.initials: LV
authors.lastname: Fulton
authors.affiliation: 5Department of Anesthesia,Madigan Army Medical Center,Fort Lewis,WashingtonUSA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Loughren
mesh_terms: D000818:Animals; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D017148:Infusions, Intraosseous; D007262:Infusions, Intravenous; D008297:Male; D013552:Swine; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014667:Vasopressins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D014662:Vasoconstrictor Agents; D014667:Vasopressins
keywords:  AHA American Heart Association;  ANOVA Analysis of Variance;  CA cardiac arrest;  CPR cardiopulmonary resuscitation;  Cmax maximum plasma concentration;  DBP diastolic blood pressure;  ECG electrocardiography;  ETCO2 end-tidal capnography;  HIO humeral intraosseous;  HR heart rate;  IO intraosseous;  IV intravenous;  MANOVA Multivariate Analysis of Variance;  MAP mean arterial pressure;  ROSC return of spontaneous circulation;  SBP systolic blood pressure;  SpO2 oxygen saturation;  TIO tibial intraosseous;  Tmax time to maximum concentration;  VF ventricular fibrillation; ROSC; cardiac arrest; intraosseous; resuscitation; vasopressin