Elsevier

The Lancet

Volume 357, Issue 9268, 19 May 2001, Pages 1583-1585
The Lancet

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

https://doi.org/10.1016/S0140-6736(00)04726-7Get rights and content

Summary

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.

Introduction

The outlook of patients who have had out-of-hospital cardiac arrest is generally poor, and few specific treatments are available.1, 2

In about 50% to more than 70% of patients who had to be resuscitated after out-of-hospital cardiac arrest, either acute myocardial infarction or massive pulmonary embolism–and, thus, intravascular thrombosis–is the cause of the cardiocirculatory arrest.3, 4 Although cardiac arrest that is initiated by intracoronary thrombosis is quite different from pulmonary embolism, thrombolysis is an effective strategy in both.5, 6 However, thrombolytic therapy

during cardiopulmonary resuscitation (CPR) has traditionally been contraindicated because of the fear of severe bleeding complications associated with CPR procedures.

Findings from clinical case reports and small case series suggest that thrombolysis during CPR can contribute to haemodynamic stabilisation and long-term survival in patients with cardiac arrest after acute myocardial infarction or massive pulmonary embolism.7, 8, 9, 10, 11 Moreover, an unusual proportion of patients described in these reports survived long periods of cardiac arrest and CPR without any, or only minor, neurological deficits.7, 12 This survival might be attributable to the fact that, after cardiac arrest, reperfusion is associated with a striking and disseminated intravascular activation of blood coagulation without adequate activation of endogenous fibrinolysis and, thus, with intravascular clotting and fibrin formation.13, 14, 15 Therefore, thrombolysis during CPR, besides addressing the cause of acute myocardial infarction and pulmonary embolism, could also lead to a general improvement in microcirculatory flow, including cerebral reperfusion.14, 16 Experimental data indicate that thrombolysis during CPR improves early cerebral microcirculatory reperfusion,14, 17 and that thrombolytic agents directly affect cerebral tolerance to ischaemia.18 Therefore, our aim was to determine prospectively whether thrombolytic therapy is safe and effective after unsuccessful CPR out of hospital.

Section snippets

Patients

After institutional approval, we investigated in accordance with the Utstein Consensus Conference criteria,19 patients undergoing CPR after out-of-hospital cardiac arrest of cardiac aetiology in an area with advanced cardiac life-support service system staffed by doctors. The ethics committee approved the protocol for an intervention trial and deemed informed consent unnecessary. However, random assignment of unconscious patients was not approved for ethical and legal reasons. We obtained

Results

Overall, 90 patients were enrolled: 50 were controls, and 40 patients were given heparin combined with rt-PA. There were no differences between the two groups with respect to age, sex, number of cardiac arrests witnessed by bystanders, interval between alarm and arrival of advanced cardiac life-support unit, initial cardiac rhythm, duration of CPR in patients with return of spontaneous circulation, and number who had electrical defibrillation (table). Complications due to bleeding that required

Discussion

Our data show that, after initially unsuccessful out-of-hospital CPR thrombolytic therapy combined with heparin is feasible and safe. Thrombolytic therapy during CPR did not cause CPR-related bleeding complications. Additionally, this therapeutic strategy seems effective in improving outcome. The number of patients with return of spontaneous circulation and of those who could be admitted to a cardiac intensive-care unit was substantially higher in the rt-PA group. Hospital discharge rate was

References (31)

  • Guidelines for cardiopulmonary resuscitation and emergency cardiac care

    JAMA

    (1992)
  • PJ Kudenchuk et al.

    Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation

    N Engl J Med

    (1999)
  • T Silfvast

    Cause of death in unsuccessful prehospital resuscitation

    J Intern Med

    (1991)
  • CM Spaulding et al.

    Immediate coronary angiography in survivors of out-of-hospital cardiac arrest

    N Engl J Med

    (1997)
  • C Bode et al.

    Thrombolytic therapy in acute myocardial infarction‐selected recent developments

    Ann Hematol

    (1994)
  • Cited by (265)

    • Systemic thrombolysis for refractory cardiac arrest due to presumed myocardial infarction

      2021, American Journal of Emergency Medicine
      Citation Excerpt :

      The American Heart Association (AHA) stated fibrinolysis can be considered for cardiac arrest secondary to suspected or confirmed pulmonary embolism (PE), though not for undifferentiated refractory arrest [1,2]. Optimism for thrombolysis for OHCA from suspected acute myocardial infarction (AMI) abruptly halted after 2008 double blinded placebo controlled (DBPC) randomized controlled trial (RCT) reported futility and increased intracranial hemorrhage (ICH) [3-6]. Thereafter, the authors are not aware of further RCT in this topic.

    View all citing articles on Scopus
    View full text