Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial

Lancet. 2001 May 19;357(9268):1583-5. doi: 10.1016/S0140-6736(00)04726-7.


Background: During cardiopulmonary resuscitation (CPR), thrombolysis can help to stabilise patients with pulmonary embolism and myocardial infarction. Moreover, thrombolysis during CPR has beneficial effects on cerebral reperfusion after cardiac arrest. We investigated this new therapeutic approach in patients in whom conventional CPR had been unsuccessful.

Methods: We assessed, in a prospective study, patients undergoing CPR after out-of-hospital cardiac arrest for cardiological reasons in whom return of spontaneous circulation was not achieved within 15 min. According to the Ustein criteria, our control group consisted of patients who were assessed during 1 year. After this year patients were treated with a bolus of 5000 U of heparin and 50mg, over 2 min, of tissue-type plasminogen activator (rt-PA treated group). This intervention was repeated if return of spontaneous circulation was not achieved within the following 30 min. For controls only CPR was given.

Findings: Overall, 90 patients were included; heparin and rt-PA were given to 40 patients. There were no bleeding complications related to the CPR procedures. Of the rt-PA group, 68% (27) had return of spontaneous circulation and 58% (23) were admitted to a cardiac intensive care unit, compared with 44% (22; p=0.026) and 30% (15; p=0.009) of the controls, respectively. At 24 h after cardiac arrest a larger proportion of the rt-PA group than of the controls was alive (35% [14] vs 22% [11], p=0.171), and 15% (six) of rt-PA-treated patients and 8% (four) of controls could be discharged from hospital.

Interpretation: After initially unsuccessful out-of-hospital CPR, thrombolytic therapy combined with heparin is safe and might improve patient outcome. On the basis of our data a randomised controlled trial might be regarded as ethical.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiopulmonary Resuscitation / methods*
  • Drug Therapy, Combination
  • Emergency Medical Services
  • Female
  • Heart Arrest / drug therapy*
  • Heart Arrest / mortality
  • Heart Arrest / therapy
  • Heparin / administration & dosage*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / therapy
  • Probability
  • Prospective Studies
  • Pulmonary Embolism / mortality
  • Pulmonary Embolism / therapy
  • Reference Values
  • Statistics, Nonparametric
  • Survival Analysis
  • Thrombolytic Therapy / methods*
  • Tissue Plasminogen Activator / administration & dosage*
  • Treatment Failure
  • Treatment Outcome


  • Heparin
  • Tissue Plasminogen Activator