Comparison of vasopressors versus placebo in beta blocker toxicity in a porcine model [abstract]
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Objective: Vasopressors (VP) are a standard treatment in shock. Pharmacotherapy with VP seems a logical approach to increase hemodyamic parameters and improve survival. Recent research on poison induced cardiogenic shock (PICS) suggests VP may be ineffective or even possibly harmful. We studied the effect of high-dose insulin (HDI) versus vasopressin and epinephrine (V/E) to treat beta-blocker toxicity in a porcine model. This study did not include a placebo group and therefore couldn't address how V/E therapy compared to placebo. We recently completed a HDI dose response study. The model and method for toxicity was identical in both studies. The objective is to determine if V/E vs placebo therapy increases mortality in PICS by comparing these two studies. Methods: Comparison of the mortality rate and cardiovascular parameters of the placebo group in the HDI dosing study to the V/E study group. Results: Mean arterial pressure (MAP) differed significantly between the V/E group and the placebo group (75.3 mm Hg vs 49 mm Hg; p 0.001). SVR was also statistically different between the V/E and placebo group (2046 vs 1263 dyne x sec/ cm 5 ; p 0.013). These effects would be expected per the pharmacological action of V/E. There was no statistical difference detected in cardiac output (2.55 vs 2.80 L/min/m 2 ; p 0.525). A striking difference in survival was observed between groups. All 5 pigs in the V/E study group died within 90 minutes. Only 2 out of 4 pigs given placebo died in the 360-minute study interval, with neither of these deaths occuring less than 220 mintues post-toxicity. A log-rank test showed a statistical difference in survival between the two cohorts ( x^2 = 7.5 on 1 df, p 0.0062). Conclusion: This comparison suggests VP may have an increased mortality as compared to placebo in PICS by beta-blocker. Further studies are warranted to define the benefit of VP in PICS.