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Thrombolysis may be of benefit in patients with prolonged cardiac arrest

Three Part Question

In [patients who suffer (non traumatic) cardiac arrest] does [thrombolysis] improve [outcome]?

Clinical Scenario

A 60 year old patient with risk factors for ischaemic heart disease suffers a non traumatic out of hospital cardiac arrest. There is no return of cardiac output despite advance life support. You know that the majority of sudden cardiac arrests are thrombotic in origin and you wonder whether thrombolysis would be of benefit.

Search Strategy

Medline via the pubmed interface from 1950 to Sept '07
(cardiac arrest/cardiopulmonary arrest/resuscitation AND thrombolysis/tpa/rtpa/tissue plasminogen activator/alteplase/tenecteplase)
Limited to clinical trials/randomised controlled trials/English

Search Outcome

42 studies of which 4 were relevant prospective trials

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Bottiger et al
90 patients who suffered an out of hospital cardiac arrest, 1st year of study recruited 50 patients who were controls, 40 were recruited in the 2nd year who received heparin & rt-PA bolus (over 2 minutes) after 15 minutes of CPR if no ROSC at 30 minutes then drugs repeated.Prospective, non randomised control trialReturn of spontaneous circulation68% of intervention group versus 44% of control group (p=0.026, OR 2.65)Small numbers, not randomized or blinded. Waited 15 mins before intervention therefore potentially poor outlook group. Trial stopped after interim analysis showing improved early outcomes.
Admission to ITU58% of intervention group versus 30% of control group (p=0.009, OR 3.15)
Survival at 24 hours35% of intervention group versus 22% of control group (p=0.171)
Survival to discharge15% of intervention group versus 8% of control group
Bleeding related to CPRNone reported
Riyad et al,
233 patients who suffered an out of hospital PEA arrest of greater than 1 minute duration and no palpable pulse for greater than 3 minute during CPR. 117 received tpa infusion over 15 minutes. Heparin & aspirin at physician discretion for survivors.Prospective, randomized, double blind, placebo control.Return of spontaneous circulation21% of intervention group versus 23% of control group (p=0.85)Poor outcome group. Groups treated differently with regard to heparin & aspirin.
Survival to hospital admission6% of intervention group versus 5% of control (p=0.99)
Survival at 24 hours3% of intervention group versus 0% of control group
Length of hospital stay (median)0.4 days intervention group versus 0.5 days control.
HaemorrhageMajor:1.7% of intervention versus 0% of control (p=0.5)

Minor:0.9% for both groups (p=0.99)
Fatovich et al,
35 patients who suffered an out of hospital cardiac arrest, still arrested on arrival to ED. 19 received tenecteplaseProspective, randomized, double blind, placebo control.Return of spontaneous circulation42% intervention group versus 6% controlSmall numbers. 116 patients needed according to power calculation but stopped early due to funding difficulties. Groups different at baseline.
Survived to leave ED10% intervention versus 6% control
Survived to leave ICU5% intervention versus 6% control
Survival to discharge5% intervention versus 6% control
Bozeman et al,
163 patients who required resuscitation in the ED that was refractory to standard ACLS. 50 were given a single standard weight based dose of tenecteplase.Prospective, multicenter non randomised control trialReturn of spontaneous circulation26% of intervention group versus 12.4% of control (p=0.04)Enrolment based on case by case basis decided by physician. Selection bias.
Survival to ICU admission12% of intervention group versus none of control (p=0.0007)
Survival at 24 hours4% of intervention
Survival to discharge4% of intervention
Haemorrhage2% of interventional group


Thrombolysis in non traumatic cardiac arrest is based on the assumption that the underlying pathology is most likely to be thrombo-embolic in nature. Thrombolysis in cardiac arrest secondary to massive pulmonary embolism is now accepted practice. The literature contains a number of case reports and case series of patients receiving empiric thrombolysis for non traumatic cardiac arrest with promising results but suffer from the normal weaknesses of this kind of literature. Three of the four prospective trials show an improvement in early outcomes but this trend is not universally continued in terms of discharge to hospital. All of the prospective trials have significant weaknesses however including small numbers, trials finishing early and the larger of the trials not controlling for the use of heparin or aspirin.

Editor Comment

This update replaces a 2002 version by Dr Frampton and Dr Katharawoo, Poole Hospital, Dorset.

Clinical Bottom Line

In a patient who has suffered a non traumatic out of hospital cardiac arrest there is currently insufficient evidence to advocate thrombolysis for presumed coronary thrombosis.


  1. Bottiger BW et al. Efficacy and safety of thrombolytic therapy after initially unsucessful cardiopulmonary resuscitation: a prospective clinical trial. The Lancet 2001;357(9268):1583-5.
  2. Riyad, B. et al. Tissue Plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med 2002;346:1522-1528.
  3. Fatovich, D. et al. A pilot randomised trial of thrombolysis in cardiac arrest. (The TICA trial). Resuscitation 2004;61:309-313.
  4. Bozeman, W. et al. Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions. Resuscitation 2006;69:399-406.