title: Blinded Evaluation of Combination Drug Therapy for Prolonged Ventricular Fibrillation Using a Swine Model of Sudden Cardiac Arrest.
abstract: Despite experimental evidence supporting the use of resuscitation drugs in the treatment of sudden cardiac arrest (CA), there are no good human clinical data to support the decades-old practice of giving these medications during out-of-hospital CA resuscitation. We hypothesized that the lack of efficacy in clinical practice in ventricular fibrillation (VF) is the failure-based manner in which resuscitation drugs have historically been administered (one at a time interspersed with chest compressions and a defibrillation attempt, giving the next only if the previous one was ineffective). The aim of this study was to determine if giving and circulating a combination of commonly available, historically used resuscitation drugs together, prior to the first defibrillation attempt after prolonged VF, might improve short-term outcomes compared with the failure-based serial drug approach used in the past. We used a well-established swine model of sudden prolonged untreated VF. Animals were randomized to receive epinephrine (0.01 mg/kg), vasopressin (0.5 U/kg), amiodarone (4 mg/kg), and sodium bicarbonate (1.0 mEq/kg) in series (SERIES group [n = 53]) or a combination of epinephrine (0.01 mg/kg), vasopressin (0.5 U/kg), amiodarone (4 mg/kg), sodium bicarbonate (1.0 mEq/kg), and metoprolol (0.2 mg/kg) (COCKTAIL group) delivered in rapid succession at the beginning of the attempted resuscitation (n = 27). Data were analyzed descriptively. Baseline characteristics and chemistries between the two groups were the same. Termination of VF was statistically similar in the two groups: 88.7% (47/53) versus 85.2% (23/27) p = 0.66, with an adjusted relative risk ratio (RRR) of 0.94 (0.37, 1.15). However, ROSC was higher in the SERIES group (56.6% [30/53] versus 22.2% [6/27], adjusted RRR = 2.83; [1.16, 3.84] p = 0.029) as was 20-minute survival (52.8% [28/53] versus 18.5% [5/27], adjusted RRR = 3.15 [1.14, 4.54] p = 0.032). The combination of drugs studied, at these dosages, inexplicably worsened short-term outcomes after prolonged untreated VF.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mader
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Coute
authors.forename: Adam R
authors.initials: AR
authors.lastname: Kellogg
authors.forename: Brian H
authors.initials: BH
authors.lastname: Nathanson
mesh_terms: D000818:Animals; D016757:Death, Sudden, Cardiac; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D023421:Models, Animal; D011897:Random Allocation; D012151:Resuscitation; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*
keywords: cardiac arrest; cardiopulmonary resuscitation; drug therapy