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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 2001 Germany	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 trial	Return of spontaneous circulation	68% 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 ITU	58% of intervention group versus 30% of control group (p=0.009, OR 3.15)
			Survival at 24 hours	35% of intervention group versus 22% of control group (p=0.171)
			Survival to discharge	15% of intervention group versus 8% of control group
			Bleeding related to CPR	None reported
Riyad et al, 2002, Canada	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 circulation	21% 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 admission	6% of intervention group versus 5% of control (p=0.99)
			Survival at 24 hours	3% of intervention group versus 0% of control group
			Length of hospital stay (median)	0.4 days intervention group versus 0.5 days control.
			Haemorrhage	Major:1.7% of intervention versus 0% of control (p=0.5) Minor:0.9% for both groups (p=0.99)
Fatovich et al, 2004, Australia	35 patients who suffered an out of hospital cardiac arrest, still arrested on arrival to ED. 19 received tenecteplase	Prospective, randomized, double blind, placebo control.	Return of spontaneous circulation	42% intervention group versus 6% control	Small numbers. 116 patients needed according to power calculation but stopped early due to funding difficulties. Groups different at baseline.
			Survived to leave ED	10% intervention versus 6% control
			Survived to leave ICU	5% intervention versus 6% control
			Survival to discharge	5% intervention versus 6% control
Bozeman et al, 2006, America	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 trial	Return of spontaneous circulation	26% 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 admission	12% of intervention group versus none of control (p=0.0007)
			Survival at 24 hours	4% of intervention
			Survival to discharge	4% of intervention
			Haemorrhage	2% of interventional group

Comment(s)

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.

References

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.