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Blood pressure is severely reduced in patients in cardiac arrest receiving standard cardiopulmonary resuscitation (CPR). Although active compression-decompression (ACD) CPR improves acute hemodynamic parameters, arterial pressures remain suboptimal with this technique. We performed ACD CPR in patients with a new inspiratory threshold valve (ITV) to determine whether lowering intrathoracic pressures during the “relaxation” phase of ACD CPR would enhance venous blood return and overall CPR efficiency.This prospective, randomized, blinded trial was performed in prehospital mobile intensive care units in Paris, France. Patients in nontraumatic cardiac arrest received ACD CPR plus the ITV or ACD CPR alone for 30 minutes during advanced cardiac life support. End tidal CO2 (ETCO2), diastolic blood pressure (DAP) and coronary perfusion pressure, and time to return of spontaneous circulation (ROSC) were measured. Groups were similar with respect to age, gender, and initial rhythm. Mean maximal ETCO2, coronary perfusion pressure, and DAP values, respectively (in mm Hg), were 13.1±0.9, 25.0±1.4, and 36.5±1.5 with ACD CPR alone versus 19.1±1.0, 43.3±1.6, and 56.4±1.7 with ACD plus valve (P <0.001 between groups). ROSC was observed in 2 of 10 patients with ACD CPR alone after 26.5±0.7 minutes versus 4 of 11 patients with ACD CPR plus ITV after 19.8±2.8 minutes (P <0.05 for time from intubation to ROSC).Use of an inspiratory resistance valve in patients in cardiac arrest receiving ACD CPR increases the efficiency of CPR, leading to diastolic arterial pressures of >50 mm Hg. The long-term benefits of this new CPR technology are under investigation.