Fibrinolytic Therapy after Unsuccessful CPR

Abstract & Commentary

Source: Bottiger BW, et al. Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: A prospective clinical trial. Lancet 2001;357: 1583-1585.

Despite recent advances in emergency cardiac care, survival from out-of-hospital cardiac arrest remains dismally low. Studies suggest many sudden arrests in the field are attributable to associated vascular thrombosis, primarily acute myocardial infarction (AMI), or massive pulmonary embolism (PE).1 While cardiopulmonary resuscitation (CPR) efforts once were a contraindication to fibrinolytic (i.e., thrombolytic) therapy, there has been renewed interest in such treatment for cardiac arrest.

This European study evaluated the safety and utility of fibrinolytic therapy for out-of-hospital cardiac arrest. The authors postulate that fibrinolytics may be beneficial in this setting by treating the vascular thrombosis (AMI or PE) precipitating cardiac arrest, improving microcirculatory cardiac and cerebral blood flow, and addressing the coagulation abnormalities (such as disseminated intravascular coagulation) associated with cardiac arrest and its aftermath.

The investigators performed a prospective interventional trial on 40 cardiac arrest patients with no return of spontaneous circulation (ROSC) after 15 minutes of resuscitation. Patients received both heparin (5000 U) and recombinant tissue-plasminogen activator (rt-PA, 50 mg) intravenously (with a repeat dose if there was no ROSC within the following 30 minutes). Investigators studied resuscitation-related bleeding complications, ROSC, admission to a cardiac care unit, survival at 24 hours, and hospital discharge. Subjects were compared to 50 historical controls: patients who had suffered field cardiac arrest during the prior year and received only standard resuscitation measures.

Arrest victims who received fibrinolytics had a higher rate of ROSC (68% vs 44%, P = 0.0026) and admission to a cardiac care unit (58% vs 30%, P = 0.0009) compared to historical controls. Compared with standard resuscitation, the odds ratio for ROSC was 2.65 (95% CI; 1.11-6.25) and for admission 3.15 (1.32-7.69). There was a trend toward improved survival at 24 hours (35% vs 22%) and hospital discharge (15% vs 8%), but these findings were not statistically significant. There were no resuscitation-related bleeding complications in either group. The authors did report upper GI bleeding that required transfusion in two patients with fibrinolysis.

Based on these findings, the authors conclude that fibrinolytic therapy for out-of-hospital cardiac arrest is both safe and feasible. The authors believe a larger, randomized study is now warranted on the utility of fibrinolytics for cardiac arrest.

Comment by Theodore C. Chan, MD, FACEP

This investigation adds to other small studies, primarily case series, suggesting that fibrinolytic therapy is both safe and efficacious in the setting of cardiac arrest.2,3 This particular study was restricted to those victims likely to have a poor outcome; that is, those in whom 15 minutes of resuscitation was unsuccessful. In addition, patients in whom asystole was the initial cardiac rhythm (i.e., those with the lowest chance of survival) were included and comprised more than one-half the study population. Accordingly, the improvements in ROSC and admission are notable. Moreover, there was a trend toward improved survival (at 24 hours and discharge), though this finding was not statistically significant, possibly due to the small number of patients.

It is important to note that this investigation was conducted in Europe, where physicians often staff ambulances. In this study, the authors note that the "emergency doctor was aware of inclusion and exclusion criteria and enrolled appropriate patients" in the field. Thus, this study may not be directly applicable to areas in which physicians do not serve as field personnel. The investigators used one-half the standard AMI rt-PA dose with heparin and repeated the dose if there was no ROSC after 30 minutes. As work on fibrinolytics in this setting has just begun, the safest and most efficacious regimen has yet to be determined. In addition, the role of other agents, such as glycoprotein IIbIIIa inhibitors, has yet to be explored.

The investigators acknowledge that their non-randomized study is too small to make definitive conclusions and suggest their study lays the groundwork for a larger, randomized study. Despite the difficulty these days with performing randomized, clinical studies in emergency care and resuscitation (particularly with respect to informed consent), the need for such a study investigating the role of fibrinolytics in cardiac arrest is clear.


1. Silfvast T. Cause of death in unsuccessful prehospital resuscitation. J Intern Med 1991;229:331-335.

2. Bottiger BW. Thrombolysis during cardiopulmonary resuscitation. Fibrinolysis 1997;11(Suppl 2):93-100.

3. Tiffany PA, et al. Bolus thrombolytic infusions during CPR for patients with refractory arrest rhythms: Outcome of a case series. Ann Emerg Med 1998;31:124-126.