High Serum Tumor Necrosis Factor Levels in the Early Post-Cardiac Arrest Period Are Associated with Poor Short-Term Survival in a Swine Model of Ventricular Fibrillation

Abstract

Most resuscitated victims of out-of-hospital cardiac arrest who survive to hospital expire due to the postresuscitation syndrome. This syndrome is characterized by a sepsis-like proinflammatory state. The objective of this investigation was to determine whether a relationship exists between the rise of tumor necrosis factor (TNF), a proinflammatory cytokine, following return of spontaneous circulation (ROSC), and early postarrest survival in a clinically relevant animal model of spontaneous ventricular fibrillation (VF). Mixed-breed Yorkshire swine (n = 20), weighing 39 ± 5 kg, were anesthetized and catheters placed in the right atrium and left ventricle/ascending aorta for continuous pressure monitoring. VF was induced by occluding the left anterior descending coronary artery with an angioplasty balloon. After 7 min of untreated VF, advanced life support resuscitation attempts were made for up to 20 min. Animals achieving ROSC were monitored for 3 h and fluid and pressor support was administered as needed. TNF levels were measured before VF and at 0, 15, and 30 min after ROSC using quantitative sandwich enzyme-linked immunosorbent assay. Twelve (60%) animals experienced early death, expiring during the 3 hour postarrest period (9 pulseless electrical activity, 2 VF, and 1 asystole). The TNF level at 15 min post-ROSC was significantly associated with death within the first 3 h post-ROSC with a univariate odds ratio of 1.4 [95% confidence interval (CI) 1.05-2.2, P = 0.01]. Using a cutoff TNF level of 525 pg/mL at 15 min post-ROSC had 100% negative predictive value (95% CI 0%-37%) and 67% positive predictive value (95% CI 35%-90%) for early death with a hazard ratio of 6.6 (95% CI 1.9-23.5). TNF increases shortly after ROSC and is predictive of early death. Early identification of resuscitated victims at greatest risk for hemodynamic collapse and recurrent arrest might facilitate the use of early hospital-based interventions to decrease the likelihood of a poor outcome.

Keywords: cardiac arrest; cytokines; post-cardiac arrest care; ventricular fibrillation.

FIG. 1.

Kaplan-Meier short-term survival estimate for 20 swine that achieved ROSC following resuscitation from ischemically- induced ventricular fibrillation. ROSC, return of spontaneous circulation.

FIG. 2.

Cox proportional hazards model comparing swine with a 15 min post-ROSC TNF level of ≥525 pg/mL with a TNF level of <525 pg/mL following resuscitation from ischemically induced ventricular fibrillation. TNF, tumor necrosis factor.