These results demonstrated that treatment with ACD-CPR and enhancement of negative intrathoracic pressure during the decompression phase of CPR significantly increased survival to hospital discharge rates with favorable neurologic function by 53% relative to S-CPR after OOHCA of presumed cardiac etiology (P=0.019). Furthermore, a greater than 50% increase in overall survival rates was observed to one year in the intervention group compared with controls. Consistency of the intervention benefit was observed independent of gender, age, date of enrollment, or study site. Neurologic function, assessed by a number of cognitive, functional, and psychological indices, was similar between groups at 90 and 365 days after the OOHCA. Importantly, there was no increase in the number of patients with severe neurologic impairment. There were no differences in overall major adverse event rates between groups, though the incidence of pulmonary edema was increased by 50% in the device group, coexistent with the increase in survival with favorable neurologic function. In addition, the current findings strongly support the need for rapid deployment of all CPR interventions to maximize the benefits of CPR.
This investigation builds upon prior studies demonstrating that ACD-CPR and a means to lower intrathoracic pressure during the chest recoil phase transforms the chest into an active bellows to more effectively circulate blood during CPR to the heart and the brain and increase short term survival rates.7–12,15,16,26
The current study further demonstrated that it is practicable to teach and implement ACD-CPR and ITD skills in urban, suburban, and rural EMS environments. Given that the US study sites are similar in practice to most EMS systems in the US and that study devices have already been successfully integrated into emergency services at locations in the two largest European countries, this approach should be generalizable to any EMS system that follows current European Resuscitation Council or American Heart Association Guidelines.
In this study, the first statistically significant difference in clinical outcomes was observed at the time of hospital discharge; differences in ROSC and hospital admission rates were not statistically significant. Based upon preclinical and clinical studies demonstrating greater blood flow to the heart and brain with ACD CPR and augmentation of lower intrathoracic pressure (7, 10–12, 14, 26, 27,29), we speculate that improved cerebral perfusion during CPR in the intervention group resulted in reduced cerebral ischemia but that recovery and restoration of brain function may take more time than the recovery of cardiac function. These findings also support the hypothesis that better perfusion outside the hospital could result in better candidates for cardiac catheterization (more stable patients) in the intervention group, resulting in a trend towards higher cardiac catheterization rates.
This study has several limitations. First, EMS rescuers were not blinded to the CPR method. However, the primary outcome and subsequent neurologic assessments were blinded to intervention status, thus limiting potential bias to the extent feasible. Second, it was not possible to determine the relative contribution of ACD-CPR alone, the ITD alone, or the rescuer feedback elements including the timing lights, metronome, and force gauge to the positive study outcome. Animal and human data suggest that each component is essential to observe benefits with this combined approach.5,6,11,14,16,30
A potential limitation is that study enrollment was terminated early due to lack of funding and subsequent data could have either strengthened or weakened the primary findings. Finally, despite best efforts by the research team, some surviving patients refused to provide consent for further participation or release of data. Given the unique circumstances and limitations associated with obtaining informed consent under emergency circumstances, collection of follow-up data on 100% of patients remains a challenge for all such studies.
In conclusion, compared with standard CPR, ACD-CPR with augmentation of negative intrathoracic pressure resulted in significantly increased survival to hospital discharge with favorable neurological function. One year after OOHCA, survival rates with similar neurologic functionality were also significantly higher in the intervention group.
Research in Context: Four clinical trials that included a total of 644 patients, and also a single meta-analysis performed prior to the current clinical investigation provide strong support for the concept that ACD CPR with augmentation of negative intrathoracic pressure improves hemodynamics, short-term survival rates, and the potential for longer-term survival rates with favorable neurologic function (15–17, 29,30). These trials confirmed what had been observed in animal studies (7, 10–12, 14, 26, 27), that circulation is significantly enhanced with ACD CPR and augmentation of negative intrathoracic pressure. It has been previously observed that ACD CPR transforms the human chest into an active bellows: its use increased minute ventilation to 13.5 ± 5.5 L/min compared with 7.8±5.3 L/min observed with standard CPR (9). One important study on the mechanism of the combination of ACD CPR and the ITD demonstrated that ACD CPR by itself did not significantly reduce airway pressures during the decompression phase of CPR, as respiratory gases rushed into the lungs with each chest decompression (17). However, that same study showed that when used in combination with an ITD to impede inspiratory gases selectively during the recoil phase, ACD CPR significantly lowered intrathoracic pressures during chest decompression (17). Building upon this clinical foundation, the current investigation in 1653 patients treated with either standard CPR or the study intervention provides definitive evidence that ACD CPR with augmentation of negative intrathoracic pressure improves survival to hospital discharge with favorable neurologic function. Importantly, at one year following cardiac arrest, there was a continued 50% relative increase in survival in patients in the study intervention group. The neurologic function in survivors in both groups was similar one year after cardiac arrest. In addition, ACD CPR with augmentation of negative intrathoracic pressure was safe: with the exception of an increased incidence of pulmonary edema, which paralleled the 50% survival increase observed in the study intervention group, there were no other significant adverse events or adverse device events. There was no evidence that use of ACD CPR with augmentation of negative intrathoracic pressure increased the number of patients with significant neurological impairment. The current study also provides further support for the feasibility to teach and implement the use of ACD CPR with an ITD in variety of EMS environments.