Saturday, November 07, 2009

NHLBI CPR study halted

The ROC PRIMED trial, comparing different EMS protocols for cardiac arrest, was halted after data analysis showed no difference in outcomes. The two arms of the trial evaluated 1) an impedance threshold device attached to the airway and 2) two different durations of CPR applied before rhythm assessment and (when indicated) defibrillation. The NIH press release is a good example of the obfuscation that results in many attempts to make scientific findings palatable to the lay public. It reads in part (my emphasis):

Enrollment has ended early in a large, multicenter clinical trial comparing two distinct resuscitation strategies delivered by emergency medical service (EMS) providers to increase blood flow during cardiac arrest. The study's independent monitoring board and the National Heart, Lung, and Blood Institute (NHLBI), the lead sponsor of the study, stopped enrollment based on preliminary data suggesting that neither strategy significantly improved survival. One strategy compared different durations of manual cardiopulmonary resuscitation (CPR) by EMS providers before they assessed whether defibrillation was needed, and the other strategy tested the potential benefits and risks of an investigational device to maintain pressure in the chest during CPR.

The italicized portion of the above paragraph is deceptive. It omits background information from prior research suggesting that three minutes of compressions applied before assessment for defibrillation (as compared to no compressions) dramatically improves survival. (Background here, here and here). What was not known before was the optimal duration of compressions before defibrillation assessment. After these results, we know, as we did before, that for unwitnessed arrest compressions before assessment for defibrillation are beneficial, and we still don’t know the optimal duration.

The press release goes on, several paragraphs down:

"The ROC PRIMED study answers a long-standing question in the EMS community over whether it is better to defibrillate earlier or later when trying to resuscitate a patient," said Ian Stiell, M.D., professor and chair of the Department of Emergency Medicine at the University of Ottawa, senior scientist at the Ottawa Hospital Research Institute, and a principal investigator for the ROC PRIMED Analyze Early vs. Later protocol. "Both techniques appear to be equally beneficial."

Again, because it omits important background, the statement is confusing and deceptive. If the patient is in the electrical phase of resuscitation early is clearly better. If in the hemodynamic phase later is better---we just don’t know how much later. (For background on the importance of the physiologic phases of resuscitation consult this review).

The Steering Committee chair said this (my emphasis):

Myron Weisfeldt, M.D., ROC Steering Committee chair and director of the Department of Medicine at the Johns Hopkins University School of Medicine in Baltimore, added, "Questions like this one — which address the relative benefits of current medical practices — are an important example of comparative effectiveness research and, in this case, can help advance emergency medical care."

The press release does a poor job of reporting the primary research design and conditions but we have this clue:

The other principal strategy studied in ROC PRIMED was the timing of assessing the heart's rhythm to determine whether defibrillation is needed in relation to when CPR is started. For patients randomly assigned to the Analyze Early group, EMS providers were instructed to perform CPR until they were able to analyze the patient's heart rhythm (approximately 30 to 90 seconds). Patients in the Analyze Later group received CPR for at least three minutes before their heart rhythm was analyzed. When indicated, defibrillation was provided.

We’ll have to wait for official publication of the results, but it appears from this that there was considerable time variability in both arms. Some patients, we don’t know how many, actually got a minute and a half of compressions in the “short” arm. Patients in the long arm received “at least” three minutes. There’s probably an upper limit of optimal time. How long is too long? These questions illustrate a limitation of comparative effectiveness research (CER): experimental designs are inherently more complex than simple RCTs, and more variables are introduced. It’s anybody’s guess what was actually being compared in this study. It may be that the exact time is not critical, there being a range of optimal time. Equally plausible is the possibility that this study compared “too long” with “not long enough.” Because the design tweaks and time combinations that could be studied are virtually endless, CER is unlikely to give us a better answer than we already have from the work of Ewy and colleagues. What the CER agenda is likely to do is delay even longer the much needed guideline implementation of this important work. Medscape commentary here.

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