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September 2010

Critical Care

Reviewer Name:        Charles-Edouard Luyt                                              

Background and Overview

Article Title/Citation

CPR with chest compression alone or with rescue breathing.

Rea TD, Fahrenbruch C, Culley L, Donohoe RT, Hambly C, Innes J, Bloomingdale M, Subido C, Romines S, Eisenberg MS. N Engl J Med 2010;363:423-433.

Study objectives/purpose

To compare outcomes of patients with out-of-hospital cardiac arrest treated by dispatcher-assisted cardiopulmonary resuscitation (CPR), according to the instructions given by the dispatcher (chest compression alone or chest compression plus rescue breathing). The hypothesis was that instruction consisting of chest compression alone may lead to higher survival rates than instructions consisting of chest compression plus rescue breathing.

Brief background

In cardiac arrest, chest compression alone may be more efficient than chest compression associated with rescue breathing because interruption of chest compression decreases coronary and cerebral blood flows. Moreover, it may be more acceptable for bystanders than associated with mouth-to-mouth rescue breathing. In animal models, survival is improved with chest compression alone when the primary cause of the arrest is cardiac, whereas survival is decrease when the primary cause of the arrest is respiratory. To date, only one randomized study has compared the two strategies (chest compression alone vs. chest compression plus rescue breathing) and the results showed a non-significant higher survival rate in patients with chest compression alone (14.6% vs.10.4%).

Funding source of study

Funded by the Laerdal Foundation for Acute Medicine and the Medic One Foundation


Study design and methodology

Multicenter, randomized trial.
Randomization without consent via sealed enveloped. Survivors were subsequently informed of their participation. Randomization was stratified by blocks of 10.
Two study groups: patients with out-of-hospital cardiac arrest resuscitated by the caller with chest compression alone, and patients with out-of-hospital cardiac arrest resuscitated by the caller with chest compression plus rescue breathing.
The study took place at three sites: the King County Emergency Medical Service (EMS) and the Thurston county EMS (both in Washington state), and the London Ambulance Service (in England).
Enrollment took place between June 2004 and April 2009.

Patient selection and enrollment (inclusion and exclusion criteria, Sample size, power)

Patients for whom a bystander called 911 for cardiac arrest were considered for eligibility. Patients were eligible if they were unconscious, not breathing normally and not receiving CPR by a bystander. The randomization was performed by the dispatcher if the bystander agreed to undertake CPR.
Excluded patients were cardiac arrest due to trauma, drowning or asphyxiation, patients younger than 18, patients receiving CPR at the time of randomization and patients with do-not-resuscitate status. Patients who were deemed not to be in arrest at the arrival of the EMS team, and patients who had a confirmed arrest but were found to have signs of irreversible death were excluded after randomization.
The trial was designed to detect an absolute difference of 3.5% in the survival rates between the 2 groups (in favor of chest compression alone), with a two-sided alpha level of 0.05 and a power of 80%.


In the chest compression alone arm, callers were instructed by the dispatcher to perform chest compression alone (1 cycle of 50 compressions, checking for signs of life, then continue CPR if warranted).
In the chest compression plus rescue breathing arm, callers were instructed by the dispatcher to perform cycles of 2 rescue breaths followed by 15 chest compressions, and to repeat this cycle of 2:15.

Outcomes/endpoints being measured

Primary outcome was survival to hospital discharge.
Secondary outcomes were return of spontaneous circulation (ROSC) and favorable neurologic status at the time of hospital discharge (defined as a Cerebral Performance Category (CPC) of 1 or 2). Because one site (London) did not assess neurologic status at discharge, this outcome was restricted to the two other sites.

Statistical analysis

Characteristics and outcomes of the two groups were compared with the chi-square statistic, t-test or Mann–Whitney U test, as appropriate.
Results were analyzed in an intention-to-treat analysis. A second analysis was performed in patients receiving effective chest compressions.   
Four prespecified subgroups analyses were also performed: according to the underlying cause of arrest, the arrest rhythm, witness status of the arrest (yes/no), and EMS response interval among witnessed arrests (≤6 min or >6 min). Those analyses were performed with the Breslow–Day test for homogeneity to determine whether the intervention differed according to subgroups status.


Enrollment & baseline characteristics

Among the 5525 patients for whom a randomization envelope was opened, 1941 were included in the study. The two most common reasons for exclusion were that patients did not have cardiac arrest, or had signs of irreversible death at time of EMS team arrival.
Baseline characteristics were similar between the two groups (values given thereafter are rounded); patients were predominantly males (65%) with a mean age of 63. The cause of the arrest was cardiac origin in 70% of the patients, and a shockable rhythm was found in one third of the patients. The average time to initial EMS response was 6.5 min. The neurologic status was evaluated in 1286/1941 patients.

Summary of primary & secondary outcomes

Survival to hospital discharge was similar between the two groups: 12.5% for chest compression alone vs. 11.0% for chest compression plus rescue breathing (p=0.31). This trend was larger but still not significant in the 1481 patients receiving effective chest compression (11.9% vs. 9.9%, p=0.22). ROSC and favorable neurologic outcome at discharge (in the 1286 patients evaluated) in the chest compression alone and chest compression plus rescue breathing were not different (34.8% vs. 31.4%, p=0.12 and 14.4% vs. 11.5%, p =0.13, respectively).
None of the subgroups analyses showed a difference in survival to hospital discharge, whereas ROSC was significantly higher in the chest compression alone arm in the subgroup of patients with a cardiac cause (p=0.005), and in patients with a shockable rhythm (p=0.03). Favorable neurologic outcome was higher in the patients whose cause of arrest was cardiac.

Author’s Discussion and Conclusions

Brief summary of authors’ main discussion points

Rescue breathing could be deleterious in specific populations (arrest of cardiac origin), and this point should be further explored. Authors’ limitations: Results are not applicable to health professionals and to bystanders who have been previously trained. Neurologic status at discharge was not evaluated in one third of the patients. In the subgroups analyses, 5% of comparisons could be statistically significant simply by chance. Finally, the study has insufficient power to detect clinically important differences (study would need 4200 patients to have 80% power to demonstrate a difference).

Author’s conclusions

In patients with cardiac arrest, a strategy based on dispatcher instructions with chest compressions alone by a bystander did not increase survival, when compared to a strategy based on chest compression plus rescue breathing.

Reviewer’s Discussion and Conclusions

Study strengths:

Cardiac arrest is an important public health problem.
Large multicenter study, in 2 different countries with different emergency medical systems.
Rigorous protocol, with a high rate of adherence (roughly 80% of the population received the instructions provided by the dispatcher).

Study limits, weakness, (potential for bias, etc):

No data on the percentage of patients not included (5525 randomized, but how many were eligible?)
Instructions for resuscitation were a ratio of 2 breaths for 15 chest compressions in the first part of the trial, which are not the current recommendations. Because the interruption for rescue breathing may be detrimental, a protocol based on current recommendations (ratio 30:2) may have given different results.
Results are validated for non-healthcare professional bystanders. Whether chest compression alone is associated with better, worse or same outcome than chest compression plus rescue breathing when the bystander is trained remains to be determined.
No data on the use of automatic external defibrillators in this study.

Applicability & impact on healthcare providers

Chest compression alone is easier to teach and to perform. It is more acceptable for people than associated with mouth-to-mouth rescue breathing, thus it can increase the rate of bystander resuscitation attempt. Moreover, such a protocol can be easily implemented in all EMS.

Additional comments (if applicable)

Another study was published in the same issue: 1276 patients with witnessed out-of-hospital cardiac arrest were randomized to receive compression-only CPR or standard CPR. The rate of 30-day survival was similar in the two groups, 8.7% vs. 7%, respectively.

Conclusions and recommendations

In out-of-hospital cardiac arrest, mortality rate and neurologic outcome are the same when the first rescuer performed chest compression alone, as compared to chest compression plus rescue breathing. Chest compression alone by a non-healthcare professional bystander should be recommended.