t-PA Infusion for Undifferentiated, Unresponsive PEA: Just Say No?

Abstract & Commentary

Source: Abu-Laban RB, et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med 2002;346:1522-1528.

Acute coronary thrombosis and pulmonary embolism (PE) are considered common causes of cardiac arrest. This randomized, double-blind, placebo-controlled trial was conducted to evaluate the effect of the administration of tissue plasminogen activator (t-PA) during cardiopulmonary resuscitation (CPR) in adults with undifferentiated pulseless electrical activity (PEA). Patients were eligible for inclusion if they were older than 16 years and had more than one minute of PEA that was unresponsive to initial therapy outside the hospital or in the emergency department. All patients underwent endotracheal intubation, received 100% oxygen, and were given 500 mL of normal saline and 1 mg of epinephrine intravenously.

Patients randomly were assigned to receive 100 mg of t-PA or placebo intravenously over a 15-minute period during CPR. The infusion was completed regardless of whether a pulse developed, and standard resuscitation efforts were continued for a minimum of 15 minutes after the infusion was completed. Further treatment was at the discretion of the CPR leader and the decision to administer heparin, aspirin, or both was at the discretion of the attending physician. The primary outcome was survival to hospital discharge.

A total of 1583 patients with cardiac arrest were treated; 756 had PEA, 289 were eligible, and 233 were enrolled (117 in the t-PA group and 116 in the placebo group). Baseline characteristics of the patients in the two groups were similar, and there were no significant differences between the groups with respect to variables predictive of survival, including the initial rhythm, witnessed collapse, and bystander performance of CPR.

One patient in the t-PA group survived to hospital discharge, compared to none in the placebo group (absolute difference between groups, 0.9; 95% CI, -2.6 to 4.8; p=0.99). There was return of spontaneous circulation in 21.4% in the t-PA group and 23.3% in the placebo group (absolute difference between groups, -1.9; 95% CI, -12.6—8.8; p=0.85). Autopsies were done in 42 patients (18%), with death attributed to a cardiovascular cause in 25 patients (59.5%), hemorrhage in four patients (9.5%), and PE in one patient (2.4%); the remainder were attributed to miscellaneous conditions.

Commentary by Stephanie B. Abbuhl, MD, FACEP

Up until this point, there had been no randomized, controlled trial to evaluate the potential effects of a thrombolytic agent in cardiac arrest, despite several small studies (case reports and case series) suggesting a promising role.1 Unfortunately, in an answer to this call, this methodologically sound study by Abu-Laden and colleagues found no evidence of a beneficial effect of t-PA in patients with cardiac arrest and PEA of unknown cause.

There are some limitations to the study that should be noted. The median time from the collapse of the patient to the time of the infusion was 35 minutes, and it is possible that earlier administration of t-PA could have led to different results. It also is possible that a bolus fibrinolytic agent (not available when the study was designed), as opposed to a 15-minute infusion, might have made a difference in the outcome of the thrombolytic group.

Despite these limitations, the fundamental question of the use of thrombolytics in undifferentiated PEA patients has been dealt a significant blow. With the number of subjects used in the two groups, the 95% confidence intervals reliably exclude a t-PA-related increase in the rate of survival to hospital discharge of more than 4.8%. It remains possible that t-PA could have a small effect, but a much larger study would be needed to detect this.

The use of t-PA or another thrombolytic agent in specific subgroups remains unclear and in need of further study. In a recent review, the authors examine the literature where thrombolytic agents have been associated with remarkably successful outcomes, and point out that over half the cases were in patients with strongly suspected PE.1 Based on the small number of autopsies done in this study (18%), it is hard to generalize about the true number of PEs that are the cause of PEA, but only a single PE among the autopsies was somewhat surprising. The use of t-PA in patients with PEA and a high suspicion for PE should continue to be considered.

Dr. Abbuhl, Medical Director, Department of Emergency Medicine, The Hospital of the University of Pennsylvania; Associate Professor of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.

Reference

1. Newman DH, et al. Cardiac arrest and the role of thrombolytic agents. Ann Emerg Med 2000;35:472-480.