Background: A recent out-of-hospital cardiac arrest (OHCA) clinical trial showed improved survival to hospital discharge (HD) with favorable neurologic function for patients with cardiac arrest of cardiac origin treated with active compression decompression cardiopulmonary resuscitation (CPR) plus an impedance threshold device (ACD + ICD) versus standard (S) CPR. The current analysis examined whether treatment with ACD + ITD is more effective than standard (S-CPR) for all cardiac arrests of non-traumatic origin, regardless of the etiology.Methods: This is a secondary analysis of data from a randomized, prospective, multicenter, intention-to-treat, OHCA clinical trial. Adults with presumed non-traumatic cardiac arrest were enrolled and followed for one year post arrest. The primary endpoint was survival to hospital discharge (HD) with favorable neurologic function (Modified Rankin Scale score <= 3).Results: Between October 2005 and July 2009, 2738 patients were enrolled (S-CPR = 1335; ACD + ITD = 1403). Survival to HD with favorable neurologic function was greater with ACD + ITD compared with S-CPR: 7.9% versus 5.7%, (OR 1.42, 95% CI 1.04, 1.95, p = 0.027). One-year survival was also greater: 7.9% versus 5.7%, (OR 1.43, 95% CI 1.04, 1.96, p = 0.026). Nearly all survivors in both groups had returned to their baseline neurological function by one year. Major adverse event rates were similar between groups.Conclusions: Treatment of out-of-hospital non-traumatic cardiac arrest patients with ACD + ITD resulted in a significant increase in survival to hospital discharge with favorable neurological function when compared with S-CPR. A significant increase survival rates was observed up to one year after arrest in subjects treated with ACD + ITD, regardless of the etiology of the cardiac arrest. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Background: We sought to identify the factors that were associated with higher incidence of VF and survival with good neurological function in the ResQ Trial patients that compared standard cardiopulmonary resuscitation (S-CPR) versus active compression decompression CPR with an inspiratory impedance threshold device (ACD+ITD) in patients with out of hospital cardiac arrest (OHCA). Methods: A retrospective analysis of a randomized multicenter clinical study of 1655 patients with OHCA. 88.3% (106/120) of the patients discharged with good neurological function [Modified Rankin Score (MRS)≤3] had a first recorded rhythm of ventricular fibrillation/pulseless ventricular tachycardia (VF). The first rhythm was recorded in 99.4% (1645/1655) of the cases about 9.5 minutes after 911 call, on average 3 minutes after the arrival of EMS on the scene and after CPR was performed for at least 2 minutes. Results: A total of 32.8% of the patients had VF as presenting rhythm and 42.8% received bystander CPR. Presence of bystander CPR was associated with a higher VF incidence only in the S-CPR group (40.8% versus 23.1% with no bystander, p=0.001) but survival was 7.6% versus 4.6% p=0.09. Presence or absence of bystander CPR let to similar VF incidence and survival in the ACD+ITD group 36.1% versus 33.9% and 9.0% versus 8.9% respectively, p>0.2. After propensity adjustment for witnessed arrest, age <67, gender, public location, bystander CPR lost significance. In the absence of bystander CPR, ACD+ITD significantly increased the incidence of first recorded VF compared to S-CPR from 106/459 (23.1%) to 164/484 (33.9%) [OR 1.71, 95% CI (1.27, 2.30), p<0.001], and in patients with VF, return of spontaneous circulation increased from 65/459 (14.2%) to 104/484 (21.5%) [OR 1.66, 95% CI (1.16, 2.37), p=0.004], leading to an overall doubling of survival with MRS≤3 from 21/455 (4.6%) to 43/482 (8.9%) [OR 2.02, 95% CI (1.15, 3.65), p=0.009]. After propensity adjustment ACD+ITD remained a significant predictor of an MRS≤3, (p= 0.02). Conclusions: VF was the most important predictor of survival with MRS≤3. In the absence of bystander CPR, ACD+ITD increased VF incidence as the first recorded rhythm and doubled survival to hospital discharge with MRS≤3 compared to S-CPR.

Background: A randomized multicenter clinical trial compared standard CPR (S-CPR) with active compression decompression CPR plus an inspiratory impedance threshold device (ACD+ITD) in patients with non-traumatic, out-of- hospital cardiac arrest (OHCA) from a presumed cardiac cause. Survival to hospital discharge (HD) with favorable neurologic function, defined as a modified Rankin Score (MRS) ≤3, and one year survival were greater in the ACD+ITD group. We evaluated the concordance of the primary endpoint, HD with MRS ≤3, with multiple secondary neurologic endpoints assessed at one year. Methods: A total of 813 patients were enrolled in the S-CPR group and 842 in the ACD+ITD group. MRS at HD, and Cerebral Performance Category (CPC), Overall Performance Category (OPC), Health Utilities Index (HUI) and Cognitive Abilities Screening Instrument (CASI) assessments were based on responses from consented survivors and known deaths at one year. Neurologic assessments were administered by research staff blinded to the CPR treatment. Survival data were available for 98% of subjects. Fisher’s Exact Test, Pearson Chi-Square test, Mann-Whitney U test, and t-test for Equality of Means were used, as applicable, for comparisons. All statistical tests were 2-sided and p-values < 0.05 were regarded as significant. Results: The MRS (≤3 vs. >3) neurological assessment at HD was highly predictive of whether or not a patient would be alive with favorable neurological function in both study groups, assessed using the CPC score (<3 vs. ≥3) at one year (98.0% observed agreement, kappa = 0.800, p < 0.001). Similar concordance was also shown with overall survival, OPC, HUI, CASI. Table shows data for MRS and CPC comparisons. Conclusion: Neurological status at the time of HD, as measured by MRS, is highly predictive of long-term neurological function at one year. This is the first time that the MRS at the time of HD has demonstrated the ability to predict long-term outcomes for patients with OHCA.

Background Federal regulation 21 § CFR 50.24 allows an initial waiver of informed consent (IC) for treatment of certain medical emergencies but requires the consent process be initiated at the earliest feasible opportunity. In a recent out-of-hospital cardiac arrest (OHCA) trial conducted under 21 § CFR 50.24, data from public records were collected which shed light on whether the willingness to provide subsequent IC was associated with study outcomes. We hypothesized that IC was less likely to be obtained in subjects with significantly compromised health status. Methods A post-hoc analysis was conducted using data from a NIH-funded randomized, controlled OHCA clinical trial comparing active compression decompression CPR plus an impedance threshold device (ACD+ITD) with standard CPR. The primary endpoint was survival to hospital discharge (HD) with favorable neurologic function [Modified Rankin Scale (MRS) score <3]. The status of the consent process was tabulated for all subjects who survived to hospital admission. Unadjusted Fisher’s exact test and associated odds ratios were used to compare the MRS at HD by IC status. Results Among a total study population of 1655 subjects, 457 survivors were admitted to the hospital, and 440 had known HD status (see table). Survival with a MRS≤3 was significantly higher in subjects where IC was given: 35.0% vs 4.1%, p < 0.001. Sixteen of the 17 cases with missing MRS outcomes were in the IC denied group. Even if all were considered to have favorable outcomes, the resulting rate (21.1%) was less than that seen among subjects with IC given (p = 0.015). Conclusion Subjects who denied IC were significantly less likely to have favorable outcome. These findings suggest that some resuscitation trials may unknowingly under-represent those subjects with the worst prognoses in a target study population despite pre-specified inclusion and exclusion criteria, due to the unwillingness or inability of the subjects or their families to provide IC.

Background—Active compression decompression cardiopulmonary resuscitation (ACD-CPR) plus a decrease in intrathoracic pressure during the decompression phase of CPR have been shown previously to result in improved hemodynamics when compared with standard CPR. We hypothesized that these interventions would increase survival rates with favorable neurologic function after out-of-hospital cardiac arrest (OOHCA) when compared with standard CPR. Methods—This prospective, randomized, open, blinded, multicenter trial evaluated the safety and effectiveness of ACD-CPR plus augmentation of negative intrathoracic pressure, achieved with an impedance threshold device (intervention), compared with standard CPR (control) in patients with non-traumatic OOHCA. The primary endpoint was survival to hospital discharge with favorable neurologic function, defined as a modified Rankin Scale (mRS) ≤3. Patients meeting final selection criteria (non-traumatic arrest, presumed cardiac etiology) were included in the primary intention-to-treat analysis. Findings—Of the 2470 provisionally enrolled patients, 817/2470 (33%) did not meet and 1653/2470 (67%) met the pre-specified final selection criteria. There were no significant Corresponding author: Tom P. Aufderheide, M.D., FACEP, FAHA, Professor of Emergency Medicine, Associate Chair of Research Affairs, Department of Emergency Medicine, 9200 W. Wisconsin Ave., Pavilion 1P, Milwaukee, Wisconsin 53226, 414-805-6452 (office phone), 414-805-6532 (fax), taufderh@mcw.edu. Clinical Trials registration number: NCT00189423 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Lancet. Author manuscript; available in PMC 2011 July 22. Published in final edited form as: Lancet. 2011 January 22; 377(9762): 301–311. doi:10.1016/S0140-6736(10)62103-4. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript differences in patient clinical profiles between the standard CPR (n=813) and the intervention (n=840) groups. Survival to hospital discharge with a mRS ≤3 was 5.8% (47/813) in the control group versus 8.9% (75/840) in the intervention group [p=0.019, OR 1.58 (CI= 1.07, 2.36)]. Overall, more patients survived to one year with intervention: 74/840 (8.8%) versus 48/813 (5.9%) (p=0.03), with similar cognitive skills, disability ratings, and quality of life indices in both groups. The overall major adverse event rate (secondary safety endpoint) was not significantly different between groups, but one category, pulmonary edema, was higher in the intervention group: 11.2% (94/840) versus 6.7% (62/813), p=0.015. Interpretation—Compared with standard CPR, treatment with 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 was significantly higher in the intervention group and there was a similar restoration of neurologic function in survivors in both groups.

Background Active compression-decompression cardiopulmonary resuscitation (CPR) with decreased intrathoracic pressure in the decompression phase can lead to improved haemodynamics compared with standard CPR. We aimed to assess effectiveness and safety of this intervention on survival with favourable neurological function after out-of-hospital cardiac arrest.Methods In our randomised trial of 46 emergency medical service agencies (serving 2.3 million people) in urban, suburban, and rural areas of the USA, we assessed outcomes for patients with out-of-hospital cardiac arrest according to Utstein guidelines. We provisionally enrolled patients to receive standard CPR or active compression-decompression CPR with augmented negative intrathoracic pressure (via an impedance-threshold device) with a computer-generated block randomisation weekly schedule in a one-to-one ratio. Adults (presumed age or age a:18 years) who had a nontraumatic arrest of presumed cardiac cause and met initial and final selection criteria received designated CPR and were included in the final analyses. The primary endpoint was survival to hospital discharge with favourable neurological function (modified Rankin scale score of <= 3). All investigators apart from initial rescuers were masked to treatment group assignment. This trial is registered with ClinicalTrials.gov, number NCT00189423.Findings 2470 provisionally enrolled patients were randomly allocated to treatment groups. 813 (68%) of 1201 patients assigned to the standard CPR group (controls) and 840 (66%) of 1269 assigned to intervention CPR received designated CPR and were included in the final analyses. 47 (6%) of 813 controls survived to hospital discharge with favourable neurological function compared with 75 (9%) of 840 patients in the intervention group (odds ratio 1.58, 95% CI 1.07-2.36; p=0.019]. 74 (9%) of 840 patients survived to 1 year in the intervention group compared with 48 (6%) of 813 controls (p=0.03), with equivalent cognitive skills, disability ratings, and emotional-psychological statuses in both groups. The overall major adverse event rate did not differ between groups, but more patients had pulmonary oedema in the intervention group (94 [11%] of 840) than did controls (62 [7%] of 813; p=0.015).Interpretation On the basis of our findings showing increased effectiveness and generalisability of the study intervention, active compression-decompression CPR with augmentation of negative intrathoracic pressure should be considered as an alternative to standard CPR to increase long-term survival after cardiac arrest.

Purpose: Active compression decompression cardiopulmonary resuscitation (ACD CPR) combined with an impedance threshold device (ITD) decreases intrathoracic pressure during the decompression phase of CPR, resulting in improved cardiac and cerebral perfusion. We hypothesized that ITD+ACD CPR would increase survival with good neurologic outcome in patients with out-of-hospital cardiac arrest (OHCA). Methods: This prospective, randomized multi-center trial evaluated adults with non-traumatic OHCA treated by emergency medical services in 7 United States study sites with a population of 2.3 million. Patients were randomized to ITD+ACD CPR (intervention) or standard CPR (control). The primary endpoint was survival to hospital discharge with good neurological function, determined by a modified Rankin Score (MRS) < 3. Secondary endpoints included major adverse events and 90-day neurological function, determined by a Cerebral Performance Category (CPC) of <2. Patients who met final criteria (non-traumatic arrest, presumed cardiac etiology) were included in the primary intention-to-treat analysis. Fisher's Exact Test was used to calculate statistical significance. Neurologic assessments and hospital chart reviews were performed by study staff blinded to CPR treatment assignment. Results: Of 2470 patients enrolled, randomized, and treated, 1653 patients met the final criteria. There were no significant differences in demographics, initial rhythms, bystander CPR, intervals to CPR, or adverse events between groups. A total of 75/840 (8.9%) in the intervention group versus 47/813 (5.8%) in the control survived to hospital discharge with a MRS < 3 [p = 0.015, OR 1.60 (CI = 1.08, 2.39)]. There were no significant adverse device events. Survival with good neurological function was higher in the intervention group 90 days after OHCA: 72/840 (8.6%) versus 47/813 (5.8%) [p = 0.029, OR 1.53 (CI = 1.03, 2.29)]. Conclusion: Compared with standard CPR, ITD+ACD CPR resulted in a >50% increase in survival with good neurologic function. These findings support the routine use of ITD+ACD CPR for treatment of OHCA.