Thrombolysis may be of benefit in patients with prolonged cardiac arrest
Date First Published:
April 15, 2002
Last Updated:
February 29, 2008
Report by:
Matt Baker, SpR accident and emergency (Basingstoke & North Hants Hospital)
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
Search Details:
(cardiac arrest/cardiopulmonary arrest/resuscitation AND thrombolysis/tpa/rtpa/tissue plasminogen activator/alteplase/tenecteplase)
Limited to clinical trials/randomised controlled trials/English
Limited to clinical trials/randomised controlled trials/English
Outcome:
42 studies of which 4 were relevant prospective trials
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Efficacy and safety of thrombolytic therapy after initially unsucessful cardiopulmonary resuscitation: a prospective clinical trial. Bottiger BW 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 | ||||
| Tissue Plasminogen activator in cardiac arrest with pulseless electrical activity. Riyad, B. 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)<br><br>Minor:0.9% for both groups (p=0.99) | ||||
| A pilot randomised trial of thrombolysis in cardiac arrest. (The TICA trial). Fatovich, D. 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 | ||||
| Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions. Bozeman, W. 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 |
Author Commentary:
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.
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:
- Bottiger BW et al.. Efficacy and safety of thrombolytic therapy after initially unsucessful cardiopulmonary resuscitation: a prospective clinical trial.
- Riyad, B. et al.. Tissue Plasminogen activator in cardiac arrest with pulseless electrical activity.
- Fatovich, D. et al.. A pilot randomised trial of thrombolysis in cardiac arrest. (The TICA trial).
- 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.