Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the United States. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 hours of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient reported quality of life measures. Discussion: In-vitro and in-vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration: ClinicalTrials.gov (NCT04217551, 2019-12-30).

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

Pediatric Out-of-Hospital Cardiac Arrest: The Role of the Telecommunicator in Recognition of Cardiac Arrest and Delivery of Bystander Cardiopulmonary Resuscitation.

BACKGROUND: Telecommunicator CPR (T-CPR), whereby emergency dispatch facilitates cardiac arrest recognition and coaches CPR over the telephone, is an important strategy to increase early recognition and bystander CPR in adult out-of-hospital cardiac arrest (OHCA). Little is known about this treatment strategy in the pediatric population. We investigated the role of T-CPR and related performance among pediatric OHCA. METHODS AND RESULTS: This study was a retrospective cohort investigation of OHCA among individuals <18 years in King County, Washington, from April 1, 2013, to December 31, 2019. We reviewed the 911 audio recordings to determine if and how bystander CPR was delivered (unassisted or T-CPR), key time intervals in recognition of arrest, and key components of T-CPR delivery. Of the 185 eligible pediatric OHCAs, 23% (n=43) had bystander CPR initiated unassisted, 59% (n=109) required T-CPR, and 18% (n=33) did not receive CPR before emergency medical services arrival. Among all cases, cardiac arrest was recognized by the telecommunicator in 89% (n=165). Among those receiving T-CPR, the median (interquartile range) interval from start of call to OHCA recognition was 59 seconds (38-87) and first CPR intervention was 115 seconds (94-162). When stratified by age (≤8 versus >8), the older age group was less likely to receive CPR before emergency medical services arrival (88% versus 69%, P=0.002). For those receiving T-CPR, bystanders spent a median of 207 seconds (133-270) performing CPR. The median compression rate was 93 per minute (82-107) among those receiving T-CPR. CONCLUSIONS: T-CPR is an important strategy to increase early recognition and early CPR among pediatric OHCA.

Risk Prediction in Male Adolescents With Congenital Long QT Syndrome: Implications for Sex-Specific Risk Stratification in Potassium Channel-Mediated Long QT Syndrome.

BACKGROUND: Sex-specific risk management may improve outcomes in congenital long QT syndrome (LQTS). We recently developed a prediction score for cardiac events (CEs) and life-threatening events (LTEs) in postadolescent women with LQTS. In the present study, we aimed to develop personalized risk estimates for the burden of CEs and LTEs in male adolescents with potassium channel-mediated LQTS. METHODS AND RESULTS: The prognostic model was derived from the LQTS Registry headquartered in Rochester, NY, comprising 611 LQT1 or LQT2 male adolescents from age 10 through 20 years, using the following variables: genotype/mutation location, QTc-specific thresholds, history of syncope, and ß-blocker therapy. Anderson-Gill modeling was performed for the end point of CE burden (total number of syncope, aborted cardiac arrest, and appropriate defibrillator shocks). The applicability of the CE prediction model was tested for the end point of the first LTE (excluding syncope and adding sudden cardiac death) using Cox modeling. A total of 270 CEs occurred during follow-up. The genotype-phenotype risk prediction model identified low-, intermediate-, and high-risk groups, comprising 74%, 14%, and 12% of the study population, respectively. Compared with the low-risk group, high-risk male subjects experienced a pronounced 5.2-fold increased risk of recurrent CEs (P<0.001), whereas intermediate-risk patients had a 2.1-fold (P=0.004) increased risk . At age 20 years, the low-, intermediate-, and high-risk adolescent male patients had on average 0.3, 0.6, and 1.4 CEs per person, respectively. Corresponding 10-year adjusted probabilities for a first LTE were 2%, 6%, and 8%. CONCLUSIONS: Personalized genotype-phenotype risk estimates can be used to guide sex-specific management in male adolescents with potassium channel-mediated LQTS.

Bag-Valve-Mask Ventilation and Survival From Out-of-Hospital Cardiac Arrest: A Multicenter Study.

BACKGROUND: Few studies have measured ventilation during early cardiopulmonary resuscitation (CPR) before advanced airway placement. Resuscitation guidelines recommend pauses after every 30 chest compressions to deliver ventilations. The effectiveness of bag-valve-mask ventilation delivered during the pause in chest compressions is unknown. We sought to determine: (1) the incidence of lung inflation with bag-valve-mask ventilation during 30:2 CPR; and (2) the association of ventilation with outcomes after out-of-hospital cardiac arrest. METHODS: We studied patients with out-of-hospital cardiac arrest from 6 sites of the Resuscitation Outcomes Consortium CCC study (Trial of Continuous Compressions versus Standard CPR in Patients with Out-of-Hospital Cardiac Arrest). We analyzed patients assigned to the 30:2 CPR arm with ≥2 minutes of thoracic bioimpedance signal recorded with a cardiac defibrillator/monitor. Detectable ventilation waveforms were defined as having a bioimpedance amplitude ≥0.5 Ω (corresponding to ≥250 mL VT) and a duration ≥1 s. We defined a chest compression pause as a 3- to 15-s break in chest compressions. We compared the incidence of ventilation and outcomes in 2 groups: patients with ventilation waveforms in <50% of pauses (group 1) versus those with waveforms in ≥50% of pauses (group 2). RESULTS: Among 1976 patients, the mean age was 65 years; 66% were male. From the start of chest compressions until advanced airway placement, mean±SD duration of 30:2 CPR was 9.8±4.9 minutes. During this period, we identified 26 861 pauses in chest compressions; 60% of patients had ventilation waveforms in <50% of pauses (group 1, n=1177), and 40% had waveforms in ≥50% of pauses (group 2, n=799). Group 1 had a median of 12 pauses and 2 ventilations per patient versus group 2, which had 12 pauses and 12 ventilations per patient. Group 2 had higher rates of prehospital return of spontaneous circulation (40.7% versus 25.2%; P<0.0001), survival to hospital discharge (13.5% versus 4.1%; P<0.0001), and survival with favorable neurological outcome (10.6% versus 2.4%; P<0.0001). These associations persisted after adjustment for confounders. CONCLUSIONS: In this study, lung inflation occurred infrequently with bag-valve-mask ventilation during 30:2 CPR. Lung inflation in ≥50% of pauses was associated with improved return of spontaneous circulation, survival, and survival with favorable neurological outcome.

Acute SARS-CoV-2 Infection and Incidence and Outcomes of Out-of-Hospital Cardiac Arrest.

Importance: Little is known about how COVID-19 affects the incidence or outcomes of out-of-hospital cardiac arrest (OHCA), and it is possible that more generalized factors beyond SARS-CoV-2 infection are primarily responsible for changes in OHCA incidence and outcome. Objective: To assess whether COVID-19 is associated with OHCA incidence and outcomes. Design, Setting, and Participants: This retrospective cohort study was conducted in Seattle and King County, Washington. Participants included persons aged 18 years or older with nontraumatic OHCA attended by emergency medical services (EMS) between January 1, 2018, and December 31, 2021. Data analysis was performed from November 2022 to March 2023. Exposures: Prepandemic (2018-2019) and pandemic (2020-2021) periods and SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcomes were OHCA incidence and patient outcomes (ie, survival to hospital discharge). Mediation analysis was used to determine the percentage change in OHCA incidence and outcomes between prepandemic and pandemic periods that was attributable to acute SARS-CoV-2 infection vs conventional Utstein elements related to OHCA circumstances (ie, witness status and OHCA location) and resuscitation care (ie, bystander cardiopulmonary resuscitation, early defibrillation, and EMS response intervals). Results: There were a total of 13 081 patients with OHCA (7102 dead upon EMS arrival and 5979 EMS treated). Among EMS-treated patients, the median (IQR) age was 64.0 (51.0-75.0) years, 3864 (64.6%) were male, and 1027 (17.2%) survived to hospital discharge. The total number of patients with OHCA increased by 19.0% (from 5963 in the prepandemic period to 7118 in the pandemic period), corresponding to an incidence increase from 168.8 to 195.3 events per 100 000 person-years. Of EMS-treated patients with OHCA during the pandemic period, 194 (6.2%) were acutely infected with SARS-CoV-2 compared with 7 of 191 EMS-attended but untreated patients with OHCA (3.7%). In time-series correlation analysis, there was a positive correlation between community SARS-CoV-2 incidence and overall OHCA incidence (r = 0.27; P = .01), as well as OHCA incidence with acute SARS-CoV-2 infection (r = 0.43; P < .001). The survival rate during the pandemic period was lower than that in the prepandemic period (483 patients [15.4%] vs 544 patients [19.2%]). During the pandemic, those with OHCA and acute SARS-CoV-2 infection had lower likelihood of survival compared with those without acute infection (12 patients [6.2%] vs 471 patients [16.0%]). SARS-CoV-2 infection itself accounted for 18.5% of the pandemic survival decline, whereas Utstein elements mediated 68.2% of the survival decline. Conclusions and Relevance: In this cohort study of COVID-19 and OHCA, a substantial proportion of the higher OHCA incidence and lower survival during the pandemic was not directly due to SARS-CoV-2 infection but indirect factors that challenged OHCA prevention and treatment.

Temperature Management for Comatose Adult Survivors of Cardiac Arrest: A Science Advisory From the American Heart Association.

Targeted temperature management has been a cornerstone of post-cardiac arrest care for patients remaining unresponsive after return of spontaneous circulation since the initial trials in 2002 found that mild therapeutic hypothermia improves neurological outcome. The suggested temperature range expanded in 2015 in response to a large trial finding that outcomes were not better with treatment at 33° C compared with 36° C. In 2021, another large trial was published in which outcomes with temperature control at 33° C were not better than those of patients treated with a strategy of strict normothermia. On the basis of these new data, the International Liaison Committee on Resuscitation and other organizations have altered their treatment recommendations for temperature management after cardiac arrest. The new American Heart Association guidelines on this topic will be introduced in a 2023 focused update. To provide guidance to clinicians while this focused update is forthcoming, the American Heart Association's Emergency Cardiovascular Care Committee convened a writing group to review the TTM2 trial (Hypothermia Versus Normothermia After Out-of-Hospital Cardiac Arrest) in the context of other recent evidence and to present an opinion on how this trial may influence clinical practice. This science advisory was informed by review of the TTM2 trial, consideration of other recent influential studies, and discussion between cardiac arrest experts in the fields of cardiology, critical care, emergency medicine, and neurology. Conclusions presented in this advisory statement do not replace current guidelines but are intended to provide an expert opinion on novel literature that will be incorporated into future guidelines and suggest the opportunity for reassessment of current clinical practice.

Genetic variant annotation scores in congenital long QT syndrome.

BACKGROUND: Congenital Long QT Syndrome (LQTS) is a hereditary arrhythmic disorder. We aimed to assess the performance of current genetic variant annotation scores among LQTS patients and their predictive impact. METHODS: We evaluated 2025 patients with unique mutations for LQT1-LQT3. A patient-specific score was calculated for each of four established genetic variant annotation algorithms: CADD, SIFT, REVEL, and PolyPhen-2. The scores were tested for the identification of LQTS and their predictive performance for cardiac events (CE) and life-threatening events (LTE) and then compared with the predictive performance of LQTS categorization based on mutation location/function. Score performance was tested using Harrell's C-index. RESULTS: A total of 917 subjects were classified as LQT1, 838 as LQT2, and 270 as LQT3. The identification of a pathogenic variant occurred in 99% with CADD, 92% with SIFT, 100% with REVEL, and 86% with PolyPhen-2. However, none of the genetic scores correlated with the risk of CE (Harrell's C-index: CADD = 0.50, SIFT = 0.51, REVEL = 0.50, and PolyPhen-2 = 0.52) or LTE (Harrell's C-index: CADD = 0.50, SIFT = 0.53, REVEL = 0.54, and PolyPhen-2 = 0.52). In contrast, high-risk mutation categorization based on location/function was a powerful independent predictor of CE (HR = 1.88; p < .001) and LTE (HR = 1.89, p < .001). CONCLUSION: In congenital LQTS patients, well-established algorithms (CADD, SIFT, REVEL, and PolyPhen-2) were able to identify the majority of the causal variants as pathogenic. However, the scores did not predict clinical outcomes. These results indicate that mutation location/functional assays are essential for accurate interpretation of the risk associated with LQTS mutations.

THE COMPENSATORY RESERVE INDEX FOR PREDICTING HEMORRHAGIC SHOCK IN PREHOSPITAL TRAUMA.

ABSTRACT: Background: The compensatory reserve index (CRI) is a noninvasive, continuous measure designed to detect intravascular volume loss. CRI is derived from the pulse oximetry waveform and reflects the proportion of physiologic reserve remaining before clinical hemodynamic decompensation. Methods: In this prospective, observational, prehospital cohort study, we measured CRI in injured patients transported by emergency medical services (EMS) to a single Level I trauma center. We determined whether the rolling average of CRI values over 60 s (CRI trend [CRI-T]) predicts in-hospital diagnosis of hemorrhagic shock, defined as blood product administration in the prehospital setting or within 4 h of hospital arrival. We hypothesized that lower CRI-T values would be associated with an increased likelihood of hemorrhagic shock and better predict hemorrhagic shock than prehospital vital signs. Results: Prehospital CRI was collected on 696 adult trauma patients, 21% of whom met our definition of hemorrhagic shock. The minimum CRI-T was 0.14 (interquartile range [IQR], 0.08-0.31) in those with hemorrhagic shock and 0.31 (IQR 0.15-0.50) in those without ( P = <0.0001). The positive likelihood ratio of a CRI-T value <0.2 predicting hemorrhagic shock was 1.85 (95% confidence interval [CI], 1.55-2.22). The area under the ROC curve (AUC) for the minimum CRI-T predicting hemorrhagic shock was 0.65 (95% CI, 0.60-0.70), which outperformed initial prehospital HR (0.56; 95% CI, 0.50-0.62) but underperformed EMS systolic blood pressure and shock index (0.74; 95% CI, 0.70-0.79 and 0.72; 95% CI, 0.67-0.77, respectively). Conclusions: Low prehospital CRI-T predicts blood product transfusion by EMS or within 4 hours of hospital arrival but is less prognostic than EMS blood pressure or shock index. The evaluated version of CRI may be useful in an austere setting at identifying injured patients that require the most significant medical resources. CRI may be improved with noise filtering to attenuate the effects of vibration and patient movement.

Head-to-pelvis CT imaging after sudden cardiac arrest: Current status and future directions.

Causes for sudden circulatory arrest (SCA) can vary widely making early treatment and triage decisions challenging. Additionally, cardiopulmonary resuscitation (CPR), while a life-saving link in the chain of survival, can be associated with traumatic injuries. Computed tomography (CT) can identify many causes of SCA as well as its sequelae. However, the diagnostic and therapeutic impact of CT in survivors of SCA has not been reviewed to date. This general review outlines the rationale and potential applications of focused head, chest, and abdomen/pelvis CT as well as comprehensive head-to-pelvis CT imaging after SCA. CT has a diagnostic yield approaching 30% to identify causes of SCA while the addition of ECG-gated chest CT provides further information about coronary anatomy and cardiac function. Risks of CT include radiation exposure, contrast-induced kidney injury, and incidental findings. This review's findings suggest that routine head-to-pelvis CT can yield clinically actional findings with the potential to improve clinical outcome after SCA that merits further investigation.

Prediction of Shock-Refractory Ventricular Fibrillation During Resuscitation of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Out-of-hospital cardiac arrest due to shock-refractory ventricular fibrillation (VF) is associated with relatively poor survival. The ability to predict refractory VF (requiring ≥3 shocks) in advance of repeated shock failure could enable preemptive targeted interventions aimed at improving outcome, such as earlier administration of antiarrhythmics, reconsideration of epinephrine use or dosage, changes in shock delivery strategy, or expedited invasive treatments. METHODS: We conducted a cohort study of VF out-of-hospital cardiac arrest to develop an ECG-based algorithm to predict patients with refractory VF. Patients with available defibrillator recordings were randomized 80%/20% into training/test groups. A random forest classifier applied to 3-s ECG segments immediately before and 1 minute after the initial shock during cardiopulmonary resuscitation was used to predict the need for ≥3 shocks based on singular value decompositions of ECG wavelet transforms. Performance was quantified by area under the receiver operating characteristic curve. RESULTS: Of 1376 patients with VF out-of-hospital cardiac arrest, 311 (23%) were female, 864 (63%) experienced refractory VF, and 591 (43%) achieved functional neurological survival. Total shock count was associated with decreasing likelihood of functional neurological survival, with a relative risk of 0.95 (95% CI, 0.93-0.97) for each successive shock (P<0.001). In the 275 test patients, the area under the receiver operating characteristic curve for predicting refractory VF was 0.85 (95% CI, 0.79-0.89), with specificity of 91%, sensitivity of 63%, and a positive likelihood ratio of 6.7. CONCLUSIONS: A machine learning algorithm using ECGs surrounding the initial shock predicts patients likely to experience refractory VF, and could enable rescuers to preemptively target interventions to potentially improve resuscitation outcome.

Age, sex, and survival following ventricular fibrillation cardiac arrest: A mechanistic evaluation of the ECG waveform.

BACKGROUND: Studies of outcome differences by sex in out-of-hospital cardiac arrest (OHCA) have produced mixed results that may depend on age, a potential surrogate for menopausal status. OBJECTIVE: We used quantitative measures of ventricular fibrillation (VF) waveforms - indicators of the myocardium's physiology - to assess whether survival differences according to sex and age group may be mediated via a biologic mechanism. METHODS: We conducted a cohort study of VF-OHCA in a metropolitan EMS system. We used multivariable logistic regression to assess the association of survival to hospital discharge with sex and age group (<55, ≥55 years). We determined the proportion of outcome difference mediated by VF waveform measures: VitalityScore and amplitude spectrum area (AMSA). RESULTS: Among 1526 VF-OHCA patients, the average age was 62 years, and 29% were female. Overall, younger women were more likely to survive than younger men (survival 67% vs 54%, p = 0.02), while survival among older women and older men did not differ (40% vs 44%, p = 0.3). Adjusting for Utstein characteristics, women <55 compared to men <55 had greater odds of survival to hospital discharge (OR = 1.93, 95% CI 1.23-3.09), an association not observed between the ≥55 groups. Waveform measures were more favorable among women and mediated some of the beneficial association between female sex and survival among those <55 years: 47% for VitalityScore and 25% for AMSA. CONCLUSIONS: Women <55 years were more likely to survive than men <55 years following VF-OHCA. The biologic mechanism represented by VF waveform mediated some, though not all, of the outcome difference.

Association between bystander physical limitations, delays in chest compression during telecommunicator-assisted cardiopulmonary resuscitation, and outcome after out-of-hospital cardiac arrest.

BACKGROUND: Promptly initiated bystander cardiopulmonary resuscitation (CPR) improves survival from out-of-hospital cardiac arrest (OHCA). Many OHCA patients require repositioning to a firm surface. We examined the association between repositioning, chest compression (CC) delay, and patient outcomes. METHODS: We used a quality improvement registry from review of 9-1-1 dispatch audio recordings of OHCA among adults eligible for telecommunicator-assisted CPR (T-CPR) between 2013 and 2021. OHCA was categorized into 3 groups: CC not delayed, CC delayed due to bystander physical limitations to reposition the patient, or CC delayed for other (non-physical) reasons. The primary outcome was the repositioning interval, defined as the interval between the start of positioning instructions and CC onset. We used logistic regression to assess the odds ratio of survival according to CPR group, adjusting for potential confounders. RESULTS: Of the 3,482 OHCA patients eligible for T-CPR, CPR was not delayed in 1,223 (35%), delayed due to repositioning in 1,413 (41%), and delayed for other reasons in 846 (24%). The repositioning interval was longest for the physical limitation delay group (137 secs, IQR-148) compared to the other delay group (81 secs, IQR-70) and the no delay group (51 secs, IQR-32) (p < 0.001). Unadjusted survival was lowest in the physical limitation delay group (11%) versus the no delay (17%) and other delay (19%) groups and persisted after adjustment (p = 0.009). CONCLUSION: Bystander physical limitations are a common barrier to repositioning patients to begin CPR and are associated with lower likelihood of receiving CPR, longer times to begin CC, and lower survival.

Diagnostic yield, safety, and outcomes of Head-to-pelvis sudden death CT imaging in post arrest care: The CT FIRST cohort study.

AIM: Our aim was to test whether a head-to-pelvis CT scan improves diagnostic yield and speed to identify causes for out of hospital circulatory arrest (OHCA). METHODS: CT FIRST was a prospective observational pre-/post-cohort study of patients successfully resuscitated from OHCA. Inclusion criteria included unknown cause for arrest, age >18 years, stability to undergo CT, and no known cardiomyopathy or obstructive coronary artery disease. A head-to-pelvis sudden death CT (SDCT) scan within 6 hours of hospital arrival was added to the standard of care for patients resuscitated from OHCA (post-cohort) and compared to standard of care (SOC) alone (pre-cohort). The primary outcome was SDCT diagnostic yield. Secondary outcomes included time to identifying OHCA cause and time-critical diagnoses, SDCT safety, and survival to hospital discharge. RESULTS: Baseline characteristics between the SDCT (N = 104) and the SOC (N = 143) cohorts were similar. CT scans (either head, chest, and/or abdomen) were ordered in 74 (52%) of SOC patients. Adding SDCT scanning identified 92% of causes for arrest compared to 75% (SOC-cohort; p value < 0.001) and reduced the time to diagnosis by 78% (SDCT 3.1 hours, SOC alone 14.1 hours, p < 0.0001). Identification of critical diagnoses was similar between cohorts, but SDCT reduced delayed (>6 hours) identification of critical diagnoses by 81% (p < 0.001). SDCT safety endpoints were similar including acute kidney injury. Patient survival to discharge was similar between cohorts. DISCUSSION: SDCT scanning early after OHCA resuscitation safely improved the efficiency and diagnostic yield for causes of arrest compared to the standard of care alone. CLINICAL TRIALS NUMBER: NCT03111043.

Instantaneous amplitude: Association of ventricular fibrillation waveform measures at time of shock with outcome in out-of-hospital cardiac arrest.

BACKGROUND: Prompt defibrillation is key to successful resuscitation from ventricular fibrillation out-of-hospital cardiac arrest (VF-OHCA). Preliminary evidence suggests that the timing of shock relative to the amplitude of the VF ECG waveform may affect the likelihood of resuscitation. We investigated whether the VF waveform amplitude at the time of shock (instantaneous amplitude) predicts outcome independent of other validated waveform measures. METHODS: We conducted a retrospective study of VF-OHCA patients ≥18 old. We evaluated three VF waveform measures for each shock: instantaneous amplitude at the time of shock, and maximum amplitude and amplitude spectrum area (AMSA) over a 3-s window preceding the shock. Linear mixed-effects modeling was used to determine whether instantaneous amplitude was associated with shock-specific return of organized rhythm (ROR) or return of spontaneous circulation (ROSC) independent of maximum amplitude or AMSA. RESULTS: The 566 eligible patients received 1513 shocks, resulting in ROR of 62.0% (938/1513) and ROSC of 22.3% (337/1513). In unadjusted regression, an interquartile increase in instantaneous amplitude was associated with ROR (Odds ratio [OR] [95% confidence interval] = 1.27 [1.11-1.45]) and ROSC (OR = 1.27 [1.14-1.42]). However, instantaneous amplitude was not associated with ROR (OR = 1.13 [0.97-1.30]) after accounting for maximum amplitude, nor with ROR (OR = 1.00 [0.87-1.15]) or ROSC (OR = 1.05 [0.93-1.18]) after accounting for AMSA. By contrast, AMSA and maximum amplitude remained independently associated with ROR and ROSC. CONCLUSIONS: We did not observe an independent association between instantaneous amplitude and shock-specific outcomes. Efforts to time shock to the maximal amplitude of the VF waveform are unlikely to affect resuscitation outcome.

Scoping review of echocardiographic parameters associated with diagnosis and prognosis after resuscitated sudden cardiac arrest.

AIM: Current international guidelines recommend early echocardiography after resuscitated sudden death despite limited data. Our aim was to analyze published data on early post-resuscitation echocardiography to identify cardiac causes of sudden death and prognostic implications. METHODS: We reviewed MEDLINE, EMBASE, and CENTRAL databases to December 2021 for echocardiographic studies of adult patients after resuscitation from non-traumatic sudden death. Studies were included if echocardiography was performed <48 hours after resuscitation and reported (1) diagnostic accuracy to detect cardiac etiologies of sudden death or (2) prognostic outcomes. Diagnostic endpoints were associations of regional wall motion abnormalities (RWMA), ventricular function, and structural abnormalities with cardiac etiologies of arrest. Prognostic endpoints were associations of echocardiographic findings with survival to hospital discharge and favorable neurological outcome. RESULTS: Of 2877 articles screened, 16 (0.6%) studies met inclusion criteria, comprising 2035 patients. Two of six studies formally reported diagnostic accuracy for echocardiography identifying cardiac etiology of arrest; RWMA (in 5 of 6 studies) were associated with presumed cardiac ischemia in 17-89% of cases. Among 12 prognostic studies, there was no association of reduced left ventricular ejection fraction with hospital survival (v10) or favorable neurologic status (n = 5). Echocardiographic high mitral E/e' ratio (n = 1) and right ventricular systolic dysfunction (n = 2) were associated with poor survival. CONCLUSION: This scoping review highlights the limited data on early echocardiography in providing etiology of arrest and prognostic information after resuscitated sudden death. Further research is needed to refine the clinical application of early echocardiographic findings in post arrest care.

Continuous assessment of ventricular fibrillation prognostic status during CPR: Implications for resuscitation.

BACKGROUND: Ventricular fibrillation (VF) waveform measures reflect myocardial physiologic status. Continuous assessment of VF prognosis using such measures could guide resuscitation, but has not been possible due to CPR artifact in the ECG. A recently-validated VF measure (termed VitalityScore), which estimates the probability (0-100%) of return-of-rhythm (ROR) after shock, can assess VF during CPR, suggesting potential for continuous application during resuscitation. OBJECTIVE: We evaluated VF using VitalityScore to characterize VF prognostic status continuously during resuscitation. METHODS: We characterized VF using VitalityScore during 60 seconds of CPR and 10 seconds of subsequent pre-shock CPR interruption in patients with out-of-hospital VF arrest. VitalityScore utility was quantified using area under the receiver operating characteristic curve (AUC). VitalityScore trends over time were estimated using mixed-effects models, and associations between trends and ROR were evaluated using logistic models. A sensitivity analysis characterized VF during protracted (100-second) periods of CPR. RESULTS: We evaluated 724 VF episodes among 434 patients. After an initial decline from 0-8 seconds following VF onset, VitalityScore increased slightly during CPR from 8-60 seconds (slope: 0.18%/min). During the first 10 seconds of subsequent pre-shock CPR interruption, VitalityScore declined (slope: -14%/min). VitalityScore predicted ROR throughout CPR with AUCs 0.73-0.75. Individual VitalityScore trends during 8-60 seconds of CPR were marginally associated with subsequent ROR (adjusted odds ratio for interquartile slope change (OR) = 1.10, p = 0.21), and became significant with protracted (100 seconds) CPR duration (OR = 1.28, p = 0.006). CONCLUSION: VF prognostic status can be continuously evaluated during resuscitation, a development that could translate to patient-specific resuscitation strategies.

Analysis of Epinephrine Dose, Targeted Temperature Management, and Neurologic and Survival Outcomes Among Adults With Out-of-Hospital Cardiac Arrest.

Importance: Epinephrine improves return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA). These beneficial cardiac effects do not directly translate to better neurologic outcomes, possibly because of epinephrine-induced microvascular effects that produce critical brain ischemia. Objective: To examine whether targeted temperature management (TTM) modifies the adverse association between increasing prehospital epinephrine dose and neurologically favorable survival. Design, Setting, and Participants: This retrospective cohort study assessed 14 612 adults from Seattle and King County, Washington, with nontraumatic OHCA between January 1, 2008, and December 31, 2018, and included those who achieved return of spontaneous circulation and were unconscious at hospital admission. Data analysis was performed from April 2021 to May 2022. Exposures: Epinephrine dose and TTM during prehospital resuscitation. Main Outcomes and Measures: Favorable neurologic survival (Cerebral Performance Category [CPC] 1 or 2) and survival to hospital discharge. Results: Of the 14 612 assessed adults, 5253 (median age, 63 years; IQR, 51-74 years; 3460 [65.8%] male) were eligible for the study. The median epinephrine dose was 2.0 mg (IQR, 1.0-3.0 mg); 3052 patients (58.1%) received TTM. In all, 1889 patients (36.0%) survived with CPC 1 to 2, and 2177 (41.4%) survived to discharge. Increasing doses of epinephrine were associated with a decreasing likelihood of CPC 1 to 2 (odds ratio [OR], 0.46; 95% CI 0.42-0.50 for each additional milligram of epinephrine) and survival (OR, 0.47; 95% CI, 0.43-0.51). The dose-dependent epinephrine association was modified by TTM. After adjusting for Utstein covariates, TTM was associated with a relative stepwise improvement in odds of CPC 1 to 2 (interaction OR, 1.36; 95% CI, 1.22-1.51) and survival (interaction OR, 1.37; 95% CI, 1.24-1.51). A significant interaction was also observed when the analysis was stratified according to initial rhythm among shockable OHCA and nonshockable OHCA (shockable interaction OR, 1.20; 95% CI, 1.04-1.39; and nonshockable interaction OR, 1.24, 95% CI, 1.07-1.45). Conclusions and Relevance: This cohort study found an interaction between TTM and epinephrine dose such that the beneficial association of TTM increased with increasing epinephrine dose, suggesting that TTM may attenuate the adverse effects of higher-dose epinephrine.

A method for continuous rhythm classification and early detection of ventricular fibrillation during CPR.

AIM: We developed a method which continuously classifies the ECG rhythm during CPR in order to guide clinical care. METHODS: We conducted a retrospective study of 432 patients treated following out-of-hospital cardiac arrest. Continuous ECG sequences from two-minute CPR cycles were extracted from defibrillator recordings and further divided into five-second clips. We developed an algorithm using wavelet analysis, hidden semi-Markov modeling, and random forest classification. The algorithm classifies individual clips as asystole, organized rhythm, ventricular fibrillation, or Inconclusive while integrating information from previous clips. Classifications were compared to manual annotations to estimate accuracy in an independent validation dataset. Continuous sequences were classified as shockable, non-shockable, or Inconclusive; classifications were used to compute shock sensitivity and specificity. RESULTS: Of 432 patient-cases, 290 were used for development and 142 for validation. In the 12,294 validation ECG clips during CPR, accuracies were 0.88 (95% CI 0.85-0.91) for asystole, 0.98 (95% CI 0.98-0.99) for organized rhythm, and 0.97 (95% CI 0.96-0.97) for ventricular fibrillation, with 43% classified as Inconclusive. Of 457 continuous sequences, shock sensitivity was 0.90 (95% CI 0.86-0.93), shock specificity was 0.98 (95% CI 0.93-0.99), and 7% were Inconclusive. Median delay to ventricular fibrillation recognition was 10 (IQR 5-32) seconds. CONCLUSION: A novel algorithm continuously classified the primary resuscitation rhythms-asystole, organized rhythms, and ventricular fibrillation-with 88-98% accuracy, enabling accurate shock advisory guidance during most two-minute CPR cycles. Additional investigation is required to understand how algorithm implementation could affect rescuer actions and clinical outcomes.