Clinical Trials in CPR

Out-of-hospital cardiac arrest is a common and lethal problem, with an estimated 330,000 deaths each year in North America alone. Even in those cases where help arrives in a timely fashion, outcomes remain dismal with estimates of survival to hospital discharge ranging from 3.0% to 16.3%.  Compounding the situation is the difficulty associated with conducting high quality research in the setting of cardiac arrest, therefore many therapies and guidelines are based on evidence of variable quality and expert consensus only.  Two recently published trials using overlapping patient cohorts attempt to ameliorate this situation by conducting large population based trials to guide best practice.

In the first of these the authors examined whether the recent change in guidelines to recommend a 2 minute period of cardiopulmonary resuscitation (CPR) before rhythm analysis provides a benefit over brief CPR and early analysis. A total of 9933 patients were studied of whom 5290 were assigned to early analysis and 4643 to later analysis.  The primary outcome was survival to hospital discharge with satisfactory functional status (a modified Rankin scale score of ≤3).  In total 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the primary outcome, with a cluster-adjusted difference of -0.2 percentage points (95% CI, -1.1 to 0.7; P=0.59) demonstrating equipoise between the two strategies. Analyses of the data with adjustment for confounding factors, as well as subgroup analyses, also showed no survival benefit for either study group.

In the second study, the authors examined an impedance threshold device (ITD) which is designed to enhance venous return and cardiac output during CPR by increasing the degree of negative intrathoracic pressure and has been shown to be efficacious in animal studies.  In this case recruiting 8718 patients, 4345 were randomly assigned to treatment with a sham ITD and 4373 to an active device with the primary end-point being identical to that in the first study. This time 260 patients (6.0%) in the sham-ITD group and 254 patients (5.8%) in the active-ITD group met the primary outcome (risk difference adjusted for sequential monitoring, -0.1 % points; 95% CI, -1.1 to 0.8; P=0.71).  There were also no significant differences in the secondary outcomes, including rates of return of spontaneous circulation on arrival at the emergency department, survival to hospital admission, and survival to hospital discharge.


Among patients with out-of-hospital cardiac arrest neither a delayed versus early rhythm analysis strategy, nor the use of an impedance threshold device, improved survival to hospital discharge with satisfactory functional status.  Despite these disappointing outcomes, these studies provide high quality evidence to shape future resuscitation guidelines.

  • Aufderheide TP, Nichol G, Rea TD, Brown SP, Leroux BG, Pepe PE, Kudenchuk PJ, Christenson J, Daya MR, Dorian P, Callaway CW, Idris AH, Andrusiek D, Stephens SW, Hostler D, Davis DP, Dunford JV, Pirrallo RG, Stiell IG, Clement CM, Craig A, Van Ottingham L, Schmidt TA, Wang HE, Weisfeldt ML, Ornato JP, Sopko G; Resuscitation Outcomes Consortium (ROC) Investigators.  A trial of an impedance threshold device in out-of-hospital cardiac arrest.  N Engl J Med. 2011 Sep 1;365(9):798-806.
  • Stiell IG, Nichol G, Leroux BG, Rea TD, Ornato JP, Powell J, Christenson J, Callaway CW, Kudenchuk PJ, Aufderheide TP, Idris AH, Daya MR, Wang HE, Morrison LJ, Davis D, Andrusiek D, Stephens S, Cheskes S, Schmicker RH, Fowler R, Vaillancourt C, Hostler D, Zive D, Pirrallo RG, Vilke GM, Sopko G, Weisfeldt M; ROC Investigators.  Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest.  N Engl J Med. 2011 Sep 1;365(9):787-97.

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