Advanced Cardiac Life Support Medications for Cardiac Arrest

No benefit found

Benefits in NNT

None were helped
100% saw no benefit

Harms in NNT

None were identifiably harmed*
0% were identifiably harmed*
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Efficacy Endpoints


Harm Endpoints



Hundreds of thousands of individuals suffer sudden cardiac arrest (SCA) each year in the United States and abroad. Advanced Cardiac Life Support (ACLS) is an algorithm-based set of recommendations and instructions assembled by the American Heart Association for the management of this condition. While rapid defibrillation appears highly effective for SCA, the role of intravenous agents is unproven.

This review examined the utility of the ACLS algorithms in the only two high quality trials to test them. The first used historical controls during the ‘phase-in’ of an ACLS system to an existing rapid-defibrillation-and-CPR-only system. Despite the pitfalls and biases inherent to this design, which tend to favor a treatment effect, ACLS failed to produce a change in survival though it did lead to more intensive care unit admissions.

The second study randomized 851 nontraumatic cardiac arrest patients to receive treatment with or without intravenous access using ACLS algorithms. There was no difference in mortality, the primary outcome. Some have argued that the 1.3% nonsignificant difference may represent a potential benefit, which assumes that a trial of 851 subjects was inadequately powered. This remains unproved and, if correct, suggests a very small hypothetical effect.

The harms and costs of ACLS are not typically visible in such studies. It is important to note that first, because patients are pulseless (dead) at the moment of enrollment, any intervention that does not produce an improvement should be seen as an opportunity cost if other approaches are available. For instance non-ACLS based approaches including those based on physician judgment rather than undifferentiated algorithms, are commonly eschewed in favor of ACLS, despite the apparently established futility of ACLS. Second, ACLS tends to increase intensive care unit admissions and generate substantial resource utilization (both during resuscitation and in the implementation of post-resuscitation care), in the absence of a detectable benefit. In the two studies above there was an additional 5 to 10% absolute increase in intensive care admissions in the group receiving intravenous, ACLS-based medications.


*One of the above studies uses a before/after historical controls design in a Canadian milieu, and the second is in a single Norwegian emergency medical services setting. Despite their being the best available evidence, the data are limited and the external validity of these data is therefore unclear.

While all of these trials refer to out-of-hospital cardiac arrest, there have not been any in-hopsital cardiac arrest trials showing benefit, and there have been a handful of observational studies suggesting possible harm from ACLS medications.


David Newman, MD


August 19, 2010