Abstract 1778: Drug Administration in Animal Studies of Cardiac Arrest Does Not Reflect Human Clinical Experience
Introduction: To date, there is no evidence showing a benefit from any ACLS medication in out-of-hospital cardiac arrest (OOHCA) despite numerous animal models demonstrating superior survival rates with various medications. One explanation for the failure of animal studies to translate into successful human trials may be a difference in the time to first drug administration. Our previous work has shown the average time to first drug administration in randomized controlled clinical trials is 19 minutes.
Hypothesis: We hypothesized that the average time to drug administration in large animal experiments is substantially faster than in OOHCA clinical trials.
Methods: We performed a comprehensive literature review between January 1990 and May 2006 in MEDLINE using the following MeSH headings: Swine, Dogs, Resuscitation, Heart Arrest, EMS, EMT, Ambulance, Ventricular Fibrillation, Drug Therapy, and the names of all ACLS medications. All abstracts were reviewed and the following were excluded: non-peer reviewed, all without primary animal data, traumatic models, and those utilizing cardiopulmonary bypass. We used no language restriction. The data are reported as mean, ranges, and 95% confidence intervals. Mean time to first drug administration in animal laboratory studies and human clinical trials were compared with a t-test.
Results: We reviewed the abstracts of 331 studies and 197 full manuscripts. From these, we identified 120 papers that contained unique information on time to medication administration. The mean time to first drug administration in 2410 animals was 9.5 minutes (range 3.0–28.0; 95% CI around mean 2.76, 16.24). This is substantially less than the time reported in clinical trials (19.4 min, p < 0.001).
Conclusion: Faster drug delivery time in animal models of cardiac arrest may explain, in part, the failure of animal studies to successfully translate in the clinical arena.