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