Clinical Trials

The clinical practice of resuscitation science is dependent on discoveries generated in the basic science and animal laboratory and then translated into clinical trials for application in humans. The successful implementation of prospective, randomized, controlled, clinical trials in the field of cardiac arrest remains challenging and continues to evolve. Funding for clinical trials of cardiac arrest is limited, and there are significant obstacles to performing such studies because of the inability to obtain informed consent under these emergency circumstances. The absence of reliable national statistics on cardiac arrest, evaluation of neurological outcome, and potential confounders such as post-resuscitation hospital-based care and quality of cardiopulmonary resuscitation (CPR) continue to challenge cardiac arrest clinical trials. Nonetheless, the immense public health burden of cardiac arrest is being recognized, appropriate public health initiatives to address the problem are being implemented, and the resuscitation research community is meeting this challenge

Implementing the 2005 American Heart Association guidelines, including use of the impedance threshold device, improves hospital discharge rate after in-hospital cardiac arrest

OBJECTIVE: To determine the impact of the 2005 American Heart Association cardiopulmonary resuscitation (CPR) guidelines, including use of an impedance threshold device (ITD), on survival after in-hospital cardiac arrest. METHODS: Two community hospitals that tracked outcomes after in-hospital cardiac arrest pooled and compared their hospital discharge rate before and after implementing the 2005 American Heart Association CPR guidelines (including ITD) in standardized protocols. In CPR we used the proper ventilation rate, allowed full chest-wall recoil, conducted continuous CPR following intubation, and used an ITD. We compared historical control data from a 12-month period at St Cloud Hospital, St Cloud, Minnesota, to data from a subsequent 18-month intervention phase. We compared historical control data from a 12-month period at St Dominic Hospital, Jackson, Mississippi to a subsequent 12-month intervention phase. 507 patients received CPR during the study period. Patient age and sex were similar in the control and intervention groups. RESULTS: The combined hospital discharge rate for patients with an in-hospital cardiac arrest was 17.5% in the control group (n=246 patients), which is similar to the national average, versus 28% in the intervention group (n=261 patients) (P=.006, odds ratio 1.83, 95% CI 1.17-2.88). The greatest benefit of the intervention was in patients with an initial rhythm of pulseless electrical activity: 14.4% versus 29.7% (P=.014, odds ratio 2.50, 95% CI 1.15, 5.58). Neurological function (as measured with the Cerebral Performance Category scale) in survivors at hospital discharge was similar between the groups. CONCLUSIONS: Implementation of improved ways to increase circulation during CPR increased the in-hospital discharge rate by 60%, compared to historical controls in 2 community hospitals. These data demonstrate that immediate care with improved means to circulate blood during CPR significantly reduces hospital mortality from inhospital sudden cardiac arrest

Higher resuscitation guideline adherence in paramedics with use of real-time ventilation feedback during simulated out-of-hospital cardiac arrest : a randomised controlled trial

To investigate whether real-time ventilation feedback would improve provider adherence to ventilation guidelines. Non-blinded randomised controlled simulation trial. One Emergency Medical Service trust in Copenhagen. 32 ambulance crews consisting of 64 on-duty basic or advanced life support paramedics from Copenhagen Emergency Medical Service. Participant exposure to real-time ventilation feedback during simulated out-of-hospital cardiac arrest. The primary outcome was ventilation quality, defined as ventilation guideline-adherence to ventilation rate (8-10 bpm) and tidal volume (500-600 ml) delivered simultaneously. The intervention group performed ventilations in adherence with ventilation guideline recommendations for 75.3% (Interquartile range (IQR) 66.2%-82.9%) of delivered ventilations, compared to 22.1% (IQR 0%-44.0%) provided by the control group. When controlling for participant covariates, adherence to ventilation guidelines was 44.7% higher in participants receiving ventilation feedback. Analysed separately, the intervention group performed a ventilation guideline-compliant rate in 97.4% (IQR 97.1%-100%) of delivered ventilations, versus 66.7% (IQR 40.9%-77.9%) for the control group. For tidal volume compliance, the intervention group reached 77.5% (IQR 64.9%-83.8%) of ventilations within target compared to 53.4% (IQR 8.4%-66.7%) delivered by the control group. Real-time ventilation feedback increased guideline compliance for both ventilation rate and tidal volume (combined and as individual parameters) in a simulated OHCA setting. Real-time feedback has the potential to improve manual ventilation quality and may allow providers to avoid harmful hyperventilation. [Abstract copyright: © 2021 The Authors.

Ventricular Tachyarrhythmias after Cardiac Arrest in Public versus at Home

Background The incidence of ventricular fibrillation or pulseless ventricular tachycardia as the first recorded rhythm after out-of-hospital cardiac arrest has unexpectedly declined. The success of bystander-deployed automated external defibrillators (AEDs) in public settings suggests that this may be the more common initial rhythm when outof-hospital cardiac arrest occurs in public. We conducted a study to determine whether the location of the arrest, the type of arrhythmia, and the probability of survival are associated. Methods Between 2005 and 2007, we conducted a prospective cohort study of out-of-hospital cardiac arrest in adults in 10 North American communities. We assessed the frequencies of ventricular fibrillation or pulseless ventricular tachycardia and of survival to hospital discharge for arrests at home as compared with arrests in public. Results Of 12,930 evaluated out-of-hospital cardiac arrests, 2042 occurred in public and 9564 at home. For cardiac arrests at home, the incidence of ventricular fibrillation or pulseless ventricular tachycardia was 25% when the arrest was witnessed by emergency-medical-services (EMS) personnel, 35% when it was witnessed by a bystander, and 36% when a bystander applied an AED. For cardiac arrests in public, the corresponding rates were 38%, 60%, and 79%. The adjusted odds ratio for initial ventricular fibrillation or pulseless ventricular tachycardia in public versus at home was 2.28 (95% confidence interval [CI], 1.96 to 2.66; P\u3c0.001) for bystanderwitnessed arrests and 4.48 (95% CI, 2.23 to 8.97; P\u3c0.001) for arrests in which bystanders applied AEDs. The rate of survival to hospital discharge was 34% for arrests in public settings with AEDs applied by bystanders versus 12% for arrests at home (adjusted odds ratio, 2.49; 95% CI, 1.03 to 5.99; P=0.04). Conclusions Regardless of whether out-of-hospital cardiac arrests are witnessed by EMS personnel or bystanders and whether AEDs are applied by bystanders, the proportion of arrests with initial ventricular fibrillation or pulseless ventricular tachycardia is much greater in public settings than at home. The incremental value of resuscitation strategies, such as the ready availability of an AED, may be related to the place where the arrest occurs. (Funded by the National Heart, Lung, and Blood Institute and others.

Early versus Later Rhythm Analysis in Patients with Out-of-Hospital Cardiac Arrest

Background In a departure from the previous strategy of immediate defibrillation, the 2005 resuscitation guidelines from the American Heart Association–International Liaison Committee on Resuscitation suggested that emergency medical service (EMS) personnel could provide 2 minutes of cardiopulmonary resuscitation (CPR) before the first analysis of cardiac rhythm. We compared the strategy of a brief period of CPR with early analysis of rhythm with the strategy of a longer period of CPR with delayed analysis of rhythm. Methods We conducted a cluster-randomized trial involving adults with out-of-hospital cardiac arrest at 10 Resuscitation Outcomes Consortium sites in the United States and Canada. Patients in the early-analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR and those in the later-analysis group were assigned to receive 180 seconds of CPR, before the initial electrocardiographic analysis. The primary outcome was survival to hospital discharge with satisfactory functional status (a modified Rankin scale score of ≤3, on a scale of 0 to 6, with higher scores indicating greater disability). Results We included 9933 patients, of whom 5290 were assigned to early analysis of cardiac rhythm and 4643 to later analysis. A total of 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the criteria for the primary outcome, with a cluster-adjusted difference of −0.2 percentage points (95% confidence interval, −1.1 to 0.7; P=0.59). Analyses of the data with adjustment for confounding factors, as well as subgroup analyses, also showed no survival benefit for either study group. Conclusions Among patients who had an out-of-hospital cardiac arrest, we found no difference in the outcomes with a brief period, as compared with a longer period, of EMS-administered CPR before the first analysis of cardiac rhythm. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.

International variation in survival after out-of-hospital cardiac arrest : A validation study of the Utstein template

Introduction: Out-of-hospital cardiac arrest (OHCA) survival varies greatly between communities. The Utstein template was developed and promulgated to improve the comparability of OHCA outcome reports, but it has undergone limited empiric validation. We sought to assess how much of the variation in OHCA survival between emergency medical services (EMS) across the globe is explained by differences in the Utstein factors. We also assessed how accurately the Utstein factors predict OHCA survival. Methods: We performed a retrospective analysis of patient-level prospectively collected data from 12 OHCA registries from 12 countries for the period 1 Jan 2006 through 31 Dec 2011. We used generalized linear mixed models to examine the variation in survival between EMS agencies (n = 232). Results: Twelve registries contributed 86,759 cases. Patient arrest characteristics, EMS treatment and patient outcomes varied across registries. Overall survival to hospital discharge was 10% (range, 6% to 22%). Overall survival with Cerebral Performance Category of 1 or 2 (available for 8/12 registries) was 8%(range, 2% to 20%). The area-under-the-curve for the Utstein model was 0.85 (Wald CI: 0.85-0.85). The Utstein factors explained 51% of the EMS agency variation in OHCA survival. Conclusions: The Utstein factors explained 51%. of the variation in survival to hospital discharge among multiple large geographically separate EMS agencies. This suggests that quality improvement and public health efforts should continue to target modifiable Utstein factors to improve OHCA survival. Further study is required to identify the reasons for the variation that is incompletely understood.Peer reviewe

A Trial of an Impedance Threshold Device in Out-of-Hospital Cardiac Arrest

Background The impedance threshold device (ITD) is designed to enhance venous return and cardiac output during cardiopulmonary resuscitation (CPR) by increasing the degree of negative intrathoracic pressure. Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest. Methods We compared the use of an active ITD with that of a sham ITD in patients with out-ofhospital cardiac arrest who underwent standard CPR at 10 sites in the United States and Canada. Patients, investigators, study coordinators, and all care providers were unaware of the treatment assignments. The primary outcome was survival to hospital discharge with satisfactory function (i.e., a score of ≤3 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating greater disability). Results Of 8718 patients included in the analysis, 4345 were randomly assigned to treatment with a sham ITD and 4373 to treatment with an active device. A total of 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 percentage points; 95% confidence interval, −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. Conclusions Use of the ITD did not significantly improve survival with satisfactory function among patients with out-of-hospital cardiac arrest receiving standard CPR. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.

Expanding Paramedicine in the Community (EPIC): study protocol for a randomized controlled trial

BACKGROUND: The incidence of chronic diseases, including diabetes mellitus (DM), heart failure (HF) and chronic obstructive pulmonary disease (COPD) is on the rise. The existing health care system must evolve to meet the growing needs of patients with these chronic diseases and reduce the strain on both acute care and hospital-based health care resources. Paramedics are an allied health care resource consisting of highly-trained practitioners who are comfortable working independently and in collaboration with other resources in the out-of-hospital setting. Expanding the paramedic’s scope of practice to include community-based care may decrease the utilization of acute care and hospital-based health care resources by patients with chronic disease. METHODS/DESIGN: This will be a pragmatic, randomized controlled trial comparing a community paramedic intervention to standard of care for patients with one of three chronic diseases. The objective of the trial is to determine whether community paramedics conducting regular home visits, including health assessments and evidence-based treatments, in partnership with primary care physicians and other community based resources, will decrease the rate of hospitalization and emergency department use for patients with DM, HF and COPD. The primary outcome measure will be the rate of hospitalization at one year. Secondary outcomes will include measures of health system utilization, overall health status, and cost-effectiveness of the intervention over the same time period. Outcome measures will be assessed using both Poisson regression and negative binomial regression analyses to assess the primary outcome. DISCUSSION: The results of this study will be used to inform decisions around the implementation of community paramedic programs. If successful in preventing hospitalizations, it has the ability to be scaled up to other regions, both nationally and internationally. The methods described in this paper will serve as a basis for future work related to this study. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02034045. Date: 9 January 2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1745-6215-15-473) contains supplementary material, which is available to authorized users