January 18th, 2011
Study Supports a New Enhanced Form of CPR
Larry Husten, PHD
A study published in the Lancet lends support to a new form of CPR that uses a combination of two devices to provide three times more blood flow to the heart and brain than standard CPR. The first device is a small suction cup on the patient’s chest used to actively lift the chest and perform what is called active compression-decompression CPR. The second is an impedance-threshold device that uses a mask or tube to prevent passive air entry into the lungs.
The authors compared more than 1600 patients with cardiac arrest randomized to standard or enhanced CPR. Survival to hospital discharge with favorable neurological function occurred in 6% of patients receiving standard CPR and 9% of patients receiving enhanced CPR. Survival at one year was the same as the primary endpoint: 6% and 9%. The authors write that “for the first time” they “have shown that a new method of CPR increases hospital-discharge rates and 1-year survival, which are both associated with good neurological outcomes, by nearly 50%, compared with the current standard of care, closed-chest manual CPR.”
In an accompanying comment, Peter Nagele writes that it is too early to recommend widespread use of the device for out-of-hospital cardiac arrest, based on a lack of independent replication of the results and possible bias in the trial because of the the open use of the devices.
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Over the past several decades, many had thought that efforts to improve out-of-hospital cardiac arrest survival would be futile. The randomized trial by these authors suggest that a promising new CPR method may improve relevant patient outcomes. They found that the combination of active compression-decompression CPR, coupled with an impedance-threshold device, improved absolute survival rates with favorable neurological outcomes by 3%.
While, on the surface, this is indeed ground-breaking science, several unanswered questions remain.
1)A recent pooled meta-analysis of 3 randomized trials (Lancet 2010;376:1552-7) found that chest compression only CPR, compared with standard CPR (which was used in this trial), improved absolute rates of survival to discharge by 2.4% (95% CI: 0.1% – 4.9%)–a similar absolute gain in survival. Therefore, it is unclear whether active compression-decompression CPR with an impedance device has incremental survival gains over chest compression only CPR. Answering this would have important consequences for survival outcomes, as well as cost-effectiveness studies of the active compression-decompression device with impedance threshold.
2) The potential for bias in this randomized trial does exist. This is because patients (and potentially the nurses assessing the primary outcome) were not blinded to the mode of CPR used. Moreover, the primary end point was not assessed in 8.1% (8 of 87) of patients surviving to discharge in the placebo arm, but only 1.9% (2 of 106 survivors) of the intervention arm. Since the overwhelming majority of those surviving to discharge in both groups had a favorable neurological status (the primary outcome), and as the p-value for the primary outcome was borderline significant at 0.04, differential missing data between the 2 groups could lead to bias, and no sensitivity analyses were provided to explore the impact of missing data for the primary outcome. This is particularly noteworthy, as longer-term neurological outcomes at 90 days and at 365 days did not differ between the 2 treatment arms.
3) Finally, although survival at 1-year was higher in the intervention arm (p=0.03), this secondary end point was not adjusted for multiple comparisons. There were at least 5 secondary end points involving survival and 4 involving health status; thus, a conservative estimate would suggest a more restricted p-value of <0.01, which would make this end point not statistically significant. At best, the findings of 1-year survival should be considered exploratory.
Despite these limitations and the need for further confirmation of this trial's results, this study provides yet more hope that progress is likely occurring in out-of-hospital resuscitation and that lives may indeed be saved.
Competing interests pertaining specifically to this post, comment, or both:
None
This randomized trial is the first to report that a field intervention is associated with a significant improvement in neurologic status at discharge after out-of-hospital cardiac arrest. However, careful review of the trial report available on clinicaltrials.gov suggests that the trial began as a three arm trial, then dropped an arm after recruitment began. What happened to those patients? Outcomes are not reported on this group in the Lancet publication. More importantly, the statistics do not appear to account for this change in design.
Moreover the study intervention included a mechanical device to improve compressions. The study was not masked to treatment allocation. It seems plausible that better CPR may have been performed in the intervention group than in the control group. Unfortunately, detailed CPR process data was not collected on patients in the control or intervention group, so we will never now whether this is the case. Interestingly the treatment benefit reported in this trial is similar to that observed in unblinded vs. unblinded trials (Bero, PLOS Medicine, 2007).
Another concern is that >30% of patients were excluded after randomization, mainly because they were presumed to have cardiac arrest of non-cardiac etiology. There is a two-fold variation in the reported proportion of cardiac arrests that are of non-cardiac etiology(Kuisma, Eur Heart J, 1997; Drory, Am J Cardiol, 1991) and poor agreement in attributing the cause of heart failure deaths.(Ziesche, J Card Fail, 1995) In addition, information from a 12-lead electrocardiogram (ECG) and history does not always identify which patients among those resuscitated from OHCA have significant lesions at the time of emergency catheterization.(Spaulding, NEJM 1997) For these reasons, restricting analysis to arrests of cardiac etiology was not recommended by the authors of the most recent Utstein template.(Jacobs, Circulation, 2004) Moreover, since ascertainment of cardiac etiology is enhanced by acquisition of information in hospital, it is plausible that restricting analysis to patients with an arrest of cardiac etiology would preferentially exclude patients from the analysis who die in the field and thereby bias the estimate of treatment effect.
Finally, participating EMS providers were trained every 6 months, which is more frequent than cardiac resuscitation training is performed in most agencies. Greater adherence/compliance with protocol is associated with greater survival after cardiac arrest.(Bobrow, JAMA, 2008). Thus it seems plausible that some of the treatment benefit observed in this trial may be due to a Hawthorne effect. However the lack of relationship between date of treatment and outcome (Figures 4 and 5) suggests that this is unlikely to be the case.
We should await publication of a large randomized trial of an active vs. sham impedance threshold device before we determine whether devices intended to decrease intrathoracic pressure and improve hemodynamics should be considered as an alternative to standard CPR to increase long-term survival after cardiac arrest.
Competing interests pertaining specifically to this post, comment, or both:
Medical Director and Co Principal Investigator of Resuscitation Outcomes Consortium Coordinating Center