Experimental paperAssociation of delay to first intervention with return of spontaneous circulation in a swine model of cardiac arrest☆,☆☆
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.
References (36)
- et al.
Magnesium in cardiac arrest (the magic trial)
Resuscitation
(1997) - et al.
Differential effects of out-of-hospital interventions on short and long-term survival after cardiopulmonary arrest
Resuscitation
(2005) - et al.
An experimental algorithm versus standard advanced cardiac life support in a swine model of out-of-hospital cardiac arrest
Ann Emerg Med
(1993) - et al.
Use of a cardiocerebral-protective drug cocktail prior to countershock in a porcine model of prolonged ventricular fibrillation
Resuscitation
(2001) - et al.
Splanchnic and renal blood flow after cardiopulmonary resuscitation with epinephrine and vasopressin in pigs
Resuscitation
(1998) - et al.
Synergistic effects of a vasopressin plus epinephrine during cardiopulmonary resuscitation
Resuscitation
(1997) - et al.
Factors associated with an increased chance of survival among patients suffering from an out-of-hospital cardiac arrest in a national perspective in Sweden
Am Heart J
(2005) - et al.
A randomized comparison of manual, mechanical and high-impulse chest compression in a porcine model of prolonged ventricular fibrillation
Resuscitation
(2006) - et al.
Dynamic nature of electrocardiographic waveform predicts rescue shock outcome in porcine ventricular fibrillation
Ann Emerg Med
(2003) - et al.
Optimum defibrillation intervals for maximum out-of-hospital cardiac arrest survival rates
Ann Emerg Med
(2003)
Predicting survival from out-of-hospital cardiac arrest: a graphic model
Ann Emerg Med
Cardiac arrest and resuscitation: a tale of 29 cities
Ann Emerg Med
Post-resuscitation hemodynamics and relationship to duration of ventricular fibrillation
Prehospital Emerg Care
Quality of BLS decreases with increasing resuscitation complexity
Resuscitation
Cardiac arrest survival as a function of ambulance deployment strategy in a large urban emergency medical services system
Resuscitation
Advanced cardiac life support in out-of-hospital cardiac arrest
N Engl J Med
Treatment of prolonged ventricular fibrillation. Immediate countershock versus high-dose epinephrine and CPR preceding countershock
Circulation
Combination pharmacotherapy with delayed countershock vs. standard advanced cardiac life support after prolonged ventricular fibrillation
Prehospital Emerg Care
Cited by (0)
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Presented at the Society for Academic Emergency Medicine, San Francisco, CA, 20 May 2006 by Dr. Jon C. Rittenberger.
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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.