Joshua C. Reynolds

Duration of Resuscitation Efforts and Functional Outcome After Out-of-Hospital Cardiac Arrest When Should We Change to Novel Therapies?

Background— Functionally favorable survival remains low after out-of-hospital cardiac arrest. When initial interventions fail to achieve the return of spontaneous circulation, they are repeated with little incremental benefit. Patients without rapid return of spontaneous circulation do not typically survive with good functional outcome. Novel approaches to out-of-hospital cardiac arrest have yielded functionally favorable survival in patients for whom traditional measures had failed, but the optimal transition point from traditional measures to novel therapies is ill defined. Our objective was to estimate the dynamic probability of survival and functional recovery as a function of resuscitation effort duration to identify this transition point. Methods and Results— Retrospective cohort study of a cardiac arrest database at a single site. We included 1014 adult (≥18 years) patients experiencing nontraumatic out-of-hospital cardiac arrest between 2005 and 2011, defined as receiving cardiopulmonary resuscitation or defibrillation from a professional provider. We stratified by functional outcome at hospital discharge (modified Rankin scale). Survival to hospital discharge was 11%, but only 6% had a modified Rankin scale of 0 to 3. Within 16.1 minutes of cardiopulmonary resuscitation, 89.7% (95% confidence interval, 80.3%–95.8%) of patients with good functional outcome had achieved return of spontaneous circulation, and the probability of good functional recovery fell to 1%. Adjusting for prehospital and inpatient covariates, cardiopulmonary resuscitation duration (minutes) is independently associated with favorable functional status at hospital discharge (odds ratio, 0.84; 95% confidence interval, 0.72–0.98; P=0.02). Conclusions— The probability of survival to hospital discharge with a modified Rankin scale of 0 to 3 declines rapidly with each minute of cardiopulmonary resuscitation. Novel strategies should be tested early after cardiac arrest rather than after the complete failure of traditional measures.

Part 3: Adult Basic Life Support and Automated External Defibrillation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

This review comprises the most extensive literature search and evidence evaluation to date on the most important international BLS interventions, diagnostics, and prognostic factors for cardiac arrest victims. It reemphasizes that the critical lifesaving steps of BLS are (1) prevention, (2) immediate recognition and activation of the emergency response system, (3) early high-quality CPR, and (4) rapid defibrillation for shockable rhythms. Highlights in prevention indicate the rational and judicious deployment of search-and-rescue operations in drowning victims and the importance of education on opioid-associated emergencies. Other 2015 highlights in recognition and activation include the critical role of dispatcher recognition and dispatch-assisted chest compressions, which has been demonstrated in multiple international jurisdictions with consistent improvements in cardiac arrest survival. Similar to the 2010 ILCOR BLS treatment recommendations, the importance of high quality was reemphasized across all measures of CPR quality: rate, depth, recoil, and minimal chest compression pauses, with a universal understanding that we all should be providing chest compressions to all victims of cardiac arrest. This review continued to focus on the interface of BLS sequencing and ensuring high-quality CPR with other important BLS interventions, such as ventilation and defibrillation. In addition, this consensus statement highlights the importance of EMS systems, which employ bundles of care focusing on providing high-quality chest compressions while extricating the patient from the scene to the next level of care. Highlights in defibrillation indicate the global importance of increasing the number of sites with public-access defibrillation programs. Whereas the 2010 ILCOR Consensus on Science provided important direction for the “what” in resuscitation (ie, what to do), the 2015 consensus has begun with the GRADE methodology to provide direction for the quality of resuscitation. We hope that resuscitation councils and other stakeholders will be able to translate this body of knowledge of international consensus statements to build their own effective resuscitation guidelines.

Part 4: Advanced life support

The International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support (ALS) Task Force performed detailed systematic reviews based on the recommendations of the Institute of Medicine of the National Academies1 and using the methodological approach proposed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group.2 Questions to be addressed (using the PICO [population, intervention, comparator, outcome] format)3 were prioritized by ALS Task Force members (by voting). Prioritization criteria included awareness of significant new data and new controversies or questions about practice. Questions about topics no longer relevant to contemporary practice or where little new research has occurred were given lower priority. The ALS Task Force prioritized 42 PICO questions for review. With the assistance of information specialists, a detailed search for relevant articles was performed in each of 3 online databases (PubMed, Embase, and the Cochrane Library). By using detailed inclusion and exclusion criteria, articles were screened for further evaluation. The reviewers for each question created a reconciled risk of bias assessment for each of the included studies, using state-of-the-art tools: Cochrane for randomized controlled trials (RCTs),4 Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 for studies of diagnostic accuracy,5 and GRADE for observational studies that inform both therapy and prognosis questions.6 GRADE evidence profile tables7 were then created to facilitate an evaluation of the evidence in support of each of the critical and important outcomes. The quality of the evidence (or confidence in the estimate of the effect) was categorized as high, moderate, low, or very low,8 based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and other considerations (including publication bias).9 These evidence profile tables were then used to create a …

Part 3: Adult Basic Life Support and Automated External Defibrillation

This Part of the 2015 International Consensus on Cardiopul monary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) Science With Treatment Recommendations (CoSTR) presents the consensus on science and treatment recommendations for adult basic life support (BLS) and automated external defibrillation (AED). After the publication of the 2010 CoSTR, the Adult BLS Task Force developed review questions in PICO (population, intervention, comparator, outcome) format.1 This resulted in the generation of 36 PICO questions for systematic reviews. The task force discussed the topics and then voted to prioritize the most important questions to be tackled in 2015. From the pool of 36 questions, 14 were rated low priority and were deferred from this round of evidence evaluation. Two new questions were submitted by task force members, and 1 was submitted via the public portal. Two of these (BLS 856 and BLS 891) were taken forward for evidence review. The third question (368: Foreign-Body Airway Obstruction) was deferred after a preliminary review of the evidence failed to identify compelling evidence that would alter the treatment recommendations made when the topic was last reviewed in 2005.2 Each task force performed a systematic review using detailed inclusion and exclusion criteria, based on the recommendations of the Institute of Medicine of the National Academies.3 With the assistance of information specialists, a detailed search for relevant articles was performed in each of 3 online databases (PubMed, Embase, and the Cochrane Library). Reviewers were unable to identify any relevant evidence for 3 questions (BLS 811, BLS 373, and BLS 348), and the evidence review was not completed in time for a further question (BLS 370). A revised PICO question was developed for the opioid question (BLS 891). The task force reviewed 23 PICO questions for the …

Comparing the prognosis of those with initial shockable and non-shockable rhythms with increasing durations of CPR: Informing minimum durations of resuscitation

AIM There is little data to inform the appropriate duration of resuscitation attempts for out-of-hospital cardiac arrest (OHCA). We assessed the relationship of elapsed duration since commencement of resuscitation and outcomes, highlighting differences between initial shockable and non-shockable rhythms. METHODS We examined consecutive adult non-traumatic EMS-treated OHCA in a single health region. We plotted the time-dependent accrual of patients with ROSC, as well as dynamic estimates of outcomes as a function of duration from commencement of professional resuscitation, and compared subgroups dichotomized by initial rhythm. Logistic regression tested the association between time-to-ROSC and outcomes. RESULTS Of 1627 adult EMS-treated cases of OHCA, 1617 patients were included; 14% survivors and 10% with favorable neurological outcomes. Time-to-ROSC (per minute increase) was independently associated with survival in those with initial shockable (aOR 0.95, 95% CI 0.92-0.97) and non-shockable (aOR 0.83; 95% CI 0.78-0.88) rhythms. Similar associations were seen with favorable neurologic outcome. The elapsed duration at which the probability of survival fell below 1% was 48 and 15 min in the shockable and non-shockable groups, respectively. Median time-to-termination of resuscitation was 36 and 26 min in the shockable and non-shockable groups, respectively. CONCLUSION The subgroup of initial shockable rhythms showed a less pronounced association of time-to-ROSC with outcomes, and demonstrated higher resilience for neurologically intact survival after prolonged periods of resuscitation. This data can guide minimum durations of resuscitation, however should not be considered as evidence for termination of resuscitation as survival in this cohort may have been improved with longer resuscitation attempts.

Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest: Implications for Prolonging or Terminating Resuscitation.

Background: Little evidence guides the appropriate duration of resuscitation in out-of-hospital cardiac arrest, and case features justifying longer or shorter durations are ill defined. We estimated the impact of resuscitation duration on the probability of favorable functional outcome in out-of-hospital cardiac arrest using a large, multicenter cohort. Methods: This was a secondary analysis of a North American, single-blind, multicenter, cluster-randomized, clinical trial (ROC-PRIMED [Resuscitation Outcomes Consortium Prehospital Resuscitation Using an Impedance Valve and Early Versus Delayed]) of consecutive adults with nontraumatic, emergency medical services–treated out-of-hospital cardiac arrest. Primary exposure was duration of resuscitation in minutes (onset of professional resuscitation to return of spontaneous circulation [ROSC] or termination of resuscitation). Primary outcome was survival to hospital discharge with favorable outcome (modified Rankin scale [mRS] score of 0–3). Subjects were additionally classified as survival with unfavorable outcome (mRS score of 4–5), ROSC without survival (mRS score of 6), or without ROSC. Subject accrual was plotted as a function of resuscitation duration, and the dynamic probability of favorable outcome at discharge was estimated for the whole cohort and subgroups. Adjusted logistic regression models tested the association between resuscitation duration and survival with favorable outcome. Results: The primary cohort included 11 368 subjects (median age, 69 years [interquartile range, 56–81 years]; 7121 men [62.6%]). Of these, 4023 (35.4%) achieved ROSC, 1232 (10.8%) survived to hospital discharge, and 905 (8.0%) had an mRS score of 0 to 3 at discharge. Distribution of cardiopulmonary resuscitation duration differed by outcome (P<0.00001). For cardiopulmonary resuscitation duration up to 37.0 minutes (95% confidence interval, 34.9–40.9 minutes), 99% with an eventual mRS score of 0 to 3 at discharge achieved ROSC. The dynamic probability of an mRS score of 0 to 3 at discharge declined over elapsed resuscitation duration, but subjects with initial shockable cardiac rhythm, witnessed cardiac arrest, and bystander cardiopulmonary resuscitation were more likely to survive with favorable outcome after prolonged efforts (30–40 minutes). After adjustment for prehospital (odds ratio, 0.93; 95% confidence interval, 0.92–0.95) and inpatient (odds ratio, 0.97; 95% confidence interval, 0.95–0.99) covariates, resuscitation duration was associated with survival to discharge with an mRS score of 0 to 3. Conclusions: Shorter resuscitation duration was associated with likelihood of favorable outcome at hospital discharge. Subjects with favorable case features were more likely to survive prolonged resuscitation up to 47 minutes. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00394706.

Effects of pre-arrest and intra-arrest hypothermia on ventricular fibrillation and resuscitation

BACKGROUND Hypothermia has been shown to improve survival and neurological outcomes for ventricular fibrillation (VF) cardiac arrest. The electrophysiological mechanisms of hypothermia are not well-understood, nor are the effects of beginning cooling during the resuscitation. METHODS AND RESULTS We hypothesized that inducing hypothermia prior to the onset of VF would slow the deleterious changes seen in the ECG during VF and that inducing hypothermia at the start of resuscitation would increase the rates of ROSC and short-term survival in a porcine model of prolonged VF. We randomly assigned 42 domestic swine (27.2+/-2.3 kg) to either pretreatment with hypothermia before induction of VF (PRE), normothermic resuscitation (NORM) or intra-resuscitation hypothermia (IRH). During anesthesia, animals were instrumented via femoral cutdown. Lead II ECG was recorded continuously. PRE animals were cooled before the induction of VF, with a rapid infusion of 4 degrees normal saline (30mL/kg). VF was induced electrically, left untreated for 8min, then mechanical CPR began. During CPR the NORM animals got 30mL/kg body-temperature saline and the IRH animals got 30mL/kg 4 degrees saline. In all groups first rescue shocks were delivered after 13min of VF. We calculated the VF scaling exponent (ScE) for the entire 8min period (compared using GEE). ROSC and survival were compared with Fishers exact test. Mean temperature in degrees C at the onset of VF was PRE=34.7 degrees (+/-0.8), NORM=37.8 (+/-0.9), and IRH=37.9 (+/-0.9). The ScE values over time were significantly lower after 8min in the PRE group (p=0.02). ROSC: PRE=10/14 (71%), NORM=6/14 (43%) and IRH=12/14 (86%); p for IRH vs. NORM=0.02. Survival: PRE=9/14 (64%), NORM=5/14 (36%), IRH 8/14 (57%). CONCLUSION Hypothermia slowed the decay of the ECG waveform during prolonged VF. IRH improved ROSC but not short-term survival compared to NORM. It is possible to rapidly induce mild hypothermia during CPR using an IV infusion of ice-cold saline.

Temperature Management After Cardiac Arrest

For more than a decade, mild induced hypothermia (32 °C-34 °C) has been standard of care for patients remaining comatose after resuscitation from out-of-hospital cardiac arrest with an initial shockable rhythm, and this has been extrapolated to survivors of cardiac arrest with initially nonshockable rhythms and to patients with in-hospital cardiac arrest. Two randomized trials published in 2002 reported a survival and neurological benefit with mild induced hypothermia. One recent randomized trial reported similar outcomes in patients treated with targeted temperature management at either 33 °C or 36 °C. In response to these new data, the International Liaison Committee on Resuscitation Advanced Life Support Task Force performed a systematic review to evaluate 3 key questions: (1) Should mild induced hypothermia (or some form of targeted temperature management) be used in comatose post-cardiac arrest patients? (2) If used, what is the ideal timing of the intervention? (3) If used, what is the ideal duration of the intervention? The task force used Grading of Recommendations Assessment, Development and Evaluation methodology to assess and summarize the evidence and to provide a consensus on science statement and treatment recommendations. The task force recommends targeted temperature management for adults with out-of-hospital cardiac arrest with an initial shockable rhythm at a constant temperature between 32 °C and 36 °C for at least 24 hours. Similar suggestions are made for out-of-hospital cardiac arrest with a nonshockable rhythm and in-hospital cardiac arrest. The task force recommends against prehospital cooling with rapid infusion of large volumes of cold intravenous fluid. Additional and specific recommendations are provided in the document.

Risk-adjusted outcome prediction with initial post-cardiac arrest illness severity: Implications for cardiac arrest survivors being considered for early invasive strategy

BACKGROUND Early CATH is recommended for cardiac arrest survivors with STEMI or suspicion for coronary ischemia. Comatose patients are at risk of death from neurologic injury irrespective of CATH, but post-procedural mortality data do not distinguish between causes of death. Pittsburgh Post Cardiac Arrest Category (PCAC) is a validated, early post-cardiac arrest illness severity score based on initial cardiopulmonary dysfunction and neurologic examination. We evaluated the association between early coronary angiography (CATH) and patient outcome after adjusting for initial post-cardiac arrest illness severity. METHODS Retrospective study of a prospective cardiac arrest database at a single site. We included 1011 adult survivors of non-traumatic in-hospital or out-of-hospital cardiac arrest from 2005 to 2012, then stratified by PCAC and immediate CATH. Logistic regression tested the association between immediate CATH and patient outcomes, adjusting for PCAC. RESULTS Overall, 273 (27%) received immediate CATH. Patients with immediate CATH had higher proportions of good outcome in all but the most severe stratum of illness severity (11% vs. 6%; p=0.11). The primary mode of death was neurologic for all but the least severe stratum. Adjusting for PCAC, immediate CATH was associated with favorable discharge disposition (OR 1.92; 95%CI 1.20, 3.07; p=0.006) and modified Rankin scale (OR 1.95; 95%CI 1.12, 3.38; p=0.02). CONCLUSIONS The benefit of CATH is less clear in the most severe stratum of illness, in which the high risk of mortality is primarily from neurologic causes. PCAC is a risk-stratification tool that provides pre-procedural risk-adjusted outcome prediction for post-cardiac arrest patients being evaluated for immediate CATH.

Relationship between Time-to-ROSC and Survival in Out-of-hospital Cardiac Arrest ECPR Candidates: When is the Best Time to Consider Transport to Hospital?

Abstract Objective: Extracorporeal cardiopulmonary resuscitation (ECPR) may improve outcomes for refractory out-of-hospital cardiac arrest (OHCA). Transport of intra-arrest patients to hospital however, may decrease CPR quality, potentially reducing survival for those who would have achieved return-of-spontaneous-circulation (ROSC) with further on-scene resuscitation. We examined time-to-ROSC and patient outcomes for the optimal time to consider transport. Methods: From a prospective registry of consecutive adult non-traumatic OHCAs, we identified a hypothetical ECPR-eligible cohort of EMS-treated patients with age ≤ 65, witnessed arrest, and bystander CPR or EMS arrival < 10 minutes. We assessed the relationship between time-to-ROSC and survival, and constructed a ROC curve to illustrate the ability of a pulseless state to predict non-survival with conventional resuscitation. Results: Of 6,571 EMS-treated cases, 1,206 were included with 27% surviving. Increasing time–to–ROSC (per minute) was negatively associated with survival (adjusted OR 0.91; 95%CI 0.89–0.93%). The yield of survivors per minute of resuscitation increased from commencement and started to decline in the 8th minute. Fifty percent and 90% of survivors had achieved ROSC by 8.0 and 24 min, respectively, at which times the probability of survival for those with initial shockable rhythms was 31% and 10%, and for non-shockable rhythms was 5.2% and 1.6%. The ROC curve illustrated that the 16th minute of resuscitation maximized sensitivity and specificity (AUC = 0.87, 95% CI 0.85–0.89). Conclusion: Transport for ECPR should be considered between 8 to 24 minutes of professional on-scene resuscitation, with 16 minutes balancing the risks and benefits of early and later transport. Earlier transport within this window may be preferred if high quality CPR can be maintained during transport and for those with initial non-shockable rhythms.