Elsevier

Resuscitation

Volume 73, Issue 1, April 2007, Pages 154-160
Resuscitation

Experimental paper
Association of delay to first intervention with return of spontaneous circulation in a swine model of cardiac arrest,☆☆

https://doi.org/10.1016/j.resuscitation.2006.07.029Get rights and content

Summary

Objective

No single drug improves survival after cardiac arrest, despite success in animal studies. We sought to determine the duration of circulatory arrest after which maximal drug treatment and a rescue shock would fail to achieve return of spontaneous circulation (ROSC).

Design/subjects

Retrospective analysis of 271 swine (20–30 kg) resuscitation attempts during ventricular fibrillation. Protocols were divided into five categories: immediate countershock, cardiopulmonary resuscitation (CPR) with standard-dose drugs, CPR alone, CPR and high-dose epinephrine (CPR + HDE) (0.1 mg/kg), and CPR with a drug cocktail (CPR + DC) of propanolol (1 mg), epinephrine (adrenaline) (0.1 mg/kg) and vasopressin (40 IU). Time to first CPR, time to first drug administration, time to first shock, and protocol were examined as predictors of ROSC using logistic regression with Hosmer–Lemeshow test of fit. Probability of ROSC was calculated from logistic curves.

Main results

ROSC occurred in 119 of the 271 swine (44%). Time to first drug and the CPR + DC group were predictors of ROSC. Time to first CPR, the CPR + DC group, and the CPR + HDE group were also predictors of ROSC. Time to first rescue shock, the CPR + DC group, and the CPR + HDE groups were predictors of ROSC. In the CPR + DC group, 50% ROSC occurred at a first CPR time of 13.4 min, first drug time of 14.1 min and first rescue shock time of 17.5 min.

Conclusions

Pre-shock delivery of CPR + DC increases the likelihood of ROSC, and reaches 50% with a time of drug delivery of 14.1 min. ROSC rates of 50% may be achievable using an optimized resuscitation in experimental CPR.

Introduction

To date, no drug has been shown to increase survival after cardiac arrest in humans.1, 2, 3 This finding is surprising given the extensive animal lab data indicating that various vasoactive medications are essential for successful resuscitation.4, 5, 6, 7, 8, 9, 10, 11, 12 One reason postulated is that first medication administration in out-of-hospital cardiac arrest (OOHCA) occurs approximately 18 min after emergency medical services (EMS) dispatch.13 In a bystander-witnessed cardiac arrest (the best-case scenario) earlier authors have estimated the pre-dispatch interval to range between 1 and 4 min.1, 14, 15, 16, 17, 18 This estimate is likely to underestimate the actual duration of cardiac arrest prior to EMS arrival and medication administration. Thus, medication administration frequently occurs in the “metabolic phase” of cardiac arrest, potentially limiting any benefit.19

We hypothesized that in a ventricular fibrillation model with optimal lab conditions and maximal drug treatment: (1) the first drug administration must occur within 15 min of circulatory arrest for return of spontaneous circulation (ROSC) to occur, and (2) that regardless of prior therapy, a rescue shock will restore a pulse in <30% of animals if delivered larger than 15 min after circulatory arrest.

Section snippets

Materials and methods

We completed a retrospective data analysis of all animals resuscitated between January 1993 and February 2005.5, 6, 9, 20, 21, 22, 23, 24 Our lab uses young mixed-breed domestic swine of either sex, weighing between 20 kg and 30 kg. The swine are approximately 4 months of age and our supplier has remained the same during the course of these experiments. Animal preparation methods have been previously described in detail and have remained consistent over the past 12 years, except as outlined below.

Results

Two hundred and seventy-one swine were included in the analyses. The numbers of swine in each group are depicted in Figure 1. ROSC occurred in 119 of the 271 (44%) swine. In the time to first shock analysis (N = 271), time to first rescue shock (β = −0.34, 95% CI [−0.45, −0.23]), the CPR + DC group (β = 4.27, 95% CI [3.23, 5.31]), and the CPR + HDE groups (β = 2.82, 95% CI [1.82, 3.81]) were predictors of ROSC (Hosmer–Lemeshow value = 0.05).

In the time to first CPR analysis (N = 158), time to first CPR (β = 

Discussion

Prior authors have attempted to model, either mathematically or theoretically, the probability of survival for patients suffering OOHCA.25, 26, 27 To our knowledge, this is the first study to utilize animal data to generate probability of ROSC curves. Our analysis has shown that ROSC is possible after 15 min of untreated VF using an optimal resuscitation. Moreover, a rescue shock delivered at 17.5 min following an optimal resuscitation could yield a >50% probability of ROSC in this model.

The

Conclusions

In this animal model of prolonged ventricular fibrillation, pre-shock delivery of CPR with a drug cocktail increases the likelihood of ROSC, and reaches 50% with first drug delivery of 14.1 min. ROSC in the swine model, therefore, has face validity as a model for human cardiac arrest. ROSC rates of 50% might be achieved using an optimized resuscitation if delivered in a timely fashion.

Conflict of interest

None.

Acknowledgements

Dr. Rittenberger and Dr. Menegazzi are supported by the Clinical Skills Training Core of the Resuscitation Outcomes Consortium through the National Heart, Lung and Blood Institute 5U01 HL077871-02. Dr. Callaway is supported through the Resuscitation Outcomes Consortium through National Heart, Lung and Blood Institute 5U01 HL077871-02.

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  • Cited by (0)

    Presented at the Society for Academic Emergency Medicine, San Francisco, CA, 20 May 2006 by Dr. Jon C. Rittenberger.

    ☆☆

    A Spanish translated version of the summary of this article appears as Appendix in the final online version at 10.1016/j.resuscitation.2006.07.029.

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