Myocardial infarction and pulmonary embolism account for approximately 70% of out of hospital cardiac arrests. Cardiac arrest itself activates systemic coagulation hence thrombolytic therapy delivered during cardiopulmonary resuscitation can dissolve intravascular blood clots and has beneficial effects on microcirculatory reperfusion, improving survival and neurological recovery.
This prospective multi-centre randomised controlled trial aimed to evaluate whether the use of tenecteplase during cardiopulmonary resuscitation improved survival in adults with witnessed out of hospital arrest of presumed cardiac origin. In order to be eligible basic or advanced cardiac life support had to be initiated within 10 minutes of collapse. The primary end-point was 30 day survival with secondary end-points being hospital admission, return of spontaneous circulation, 24 hour survival, survival to hospital discharge and neurologic outcome.
Following blinded review of data from the first 443 patients the trial data and safety monitoring board recommended that enrolment of asystolic patients was discontinued due to low survival and the protocol was amended accordingly. Subsequently the trial enrolment was terminated prematurely on grounds of futility after enrolling 1050 patients – 525 received tenecteplase and 525 placebo. No significant difference in the primary end-points between tenecteplase and placebo respectively was detected (14.7% vs 17.0%, p = 0.36, relative risk 0.87, 95% CI 0.65-1.15); or in the secondary end-points of hospital admission (53.5% vs 55%, p = 0.67), return of spontaneous circulation (55% vs 54.6%, p = 0.96), 24 hour survival (30.6% vs 33.3%, p = 0.39), survival to hospital discharge (15.1% vs 17.5%, p = 0.33) or neurological outcome (p = 0.69). More intracranial haemorrhage was seen in the tenecteplase arm.
Previous studies of thrombolytic therapy administered during cardiopulmonary resuscitation have suggested that there may be a benefit. Whilst thrombolytic therapy dissolves intravascular thrombus, delivery may be hampered during cardiac arrest sue to the restricted perfusion of vital organs. Whilst this study failed to show a benefit for tenecteplase, another study performed retrospectively has shown excellent survival in patients with myocardial infarction who received lytic agents following return of spontaneous circulation. Further research is needed in this challenging area to identify the most appropriate therapeutic strategy.
- Bottiger BW, Arntz HR, Chamberlain DA etal. Thrombolysis during Resuscitation for Out-of-Hospital Cardiac Arrest. N Engl J Med 2008;359:2651-62