Variability in temperature control practices amongst the Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial.

AIM: Temperature control is a complex bundled intervention; the synergistic impact of each individual component is ill defined and underreported. Resultantly, the influence of parameter optimization on temperature control's overall neuroprotective effect remains poorly understood. To characterize variability in temperature control parameters and barriers to short pre-induction and induction times, we surveyed sites enrolling in an ongoing multicenter clinical trial. METHODS: This was a cross-sectional, survey study evaluating temperature control practices within the Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial (NCT04217551). A 23-question web-based survey (Qualtrics) was distributed to the site principal investigators by email. Respondents were asked about site practices pertaining to the use of temperature control, including the request to upload individual institutional protocols. Open-ended responses were analyzed qualitatively by categorizing responses into identified themes. To complement survey level data, records pertaining to the quality of temperature control were extracted from the ICECAP trial database. RESULTS: The survey response rate was 75% (n = 51) including 23.5% (n = 12) survey respondents who uploaded institutional protocols. Most sites reported having institutional protocols for temperature control (n = 41; 80%), including 62.5% (n = 32) who had separate protocols for initiation of temperature control in the emergency department (ED). Fewer sites had protocols specific to sedation or neuromuscular blockade (NMB) management (n = 35, 68.6%). Use of NMB during temperature control induction was variable; 61.7% (n = 29) of sites induced paralysis less than 20% of the time. While most institutional protocols (n = 11, 83.3%) commented on the importance of early initiation of temperature control, this was incongruent with the largest reported barrier, which was clinical nihilism regarding the importance of early temperature control initiation (n = 30, 62.5%). Within the ICECAP trial database, 1 in 2 patients were treated with NMB however, use of NMB and time to initiation of temperature control device varied widely between sites. CONCLUSION: Amongst ICECAP trial sites, there was significant variability in resources, methods, and barriers for early temperature control initiation. Defining and standardizing high-quality temperature control must be prioritized, as it may impact the interpretation of past and current clinical trial findings.

Impact of Time to Initiation of Targeted Temperature Management Among Patients with Out-of-Hospital Cardiac Arrest Undergoing Percutaneous Coronary Intervention.

Delays in initiation of targeted temperature management (TTM) have been observed in randomized trials evaluating immediate or delayed coronary angiography among survivors of ventricular tachycardia (VT) or ventricular fibrillation (VF) out-of-hospital cardiac arrest (OHCA), but whether delays are associated with adverse clinical outcomes is unknown. Resuscitated survivors of VT/VF OHCA who received TTM between April 2011 and June 2015 were identified and time to TTM initiation was described. The association between TTM initiation <2 versus ≥2 hours, neurologically favorable, and overall survival to hospital discharge was assessed. In a propensity-weighted analysis of 2954 patients, a significantly larger proportion of patients undergoing percutaneous coronary intervention (PCI) had TTM initiation ≥2 hours (48.6%) as compared to patients undergoing angiography (41.4%) or those who did not undergo a procedure (33.0%; p < 0.001 for all comparisons). In this cohort, the odds of neurologically favorable survival (odds ratios [OR]: 0.88, 95% confidence intervals [CI] = 0.75-1.02) and overall survival (OR: 0.92, 95% CI = 0.83-1.03) to hospital discharge were similar among ST-elevation myocardial infarction (STEMI) patients who underwent PCI with TTM initiation <2 versus ≥2 hours. Patients without STEMI who underwent PCI with TTM initiation ≥2 hours and did not have a "do not resuscitate" order or withdrawal of life-sustaining care had decreased odds of neurologically favorable survival to hospital discharge (OR: 0.45, 95% CI = 0.22-0.93) compared to TTM initiation <2 hours. PCI was associated with delays in TTM initiation ≥2 hours among resuscitated survivors of VT/VF OHCA. Delays in TTM initiation ≥2 hours were associated with decreased odds of neurologically favorable survival among patients without STEMI who underwent PCI.

Temperature Control Parameters Are Important: Earlier Preinduction Is Associated With Improved Outcomes Following Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: Temperature control trials in cardiac arrest patients have not reliably conferred neuroprotective benefit but have been limited by inconsistent treatment parameters. To evaluate the presence of a time dependent treatment effect, we assessed the association between preinduction time and clinical outcomes. METHODS: In this retrospective, single academic center study between 2014 and 2022, consecutive out-of-hospital cardiac arrest (OHCA) patients treated with temperature control were identified. Preinduction was defined as the time from hospital arrival to initiation of a closed-loop temperature feedback device [door to temperature control initiation time], and early door to temperature control device time was defined a priori as <3 hours. We assessed the association between good neurologic outcome (cerebral performance category 1 to 2) and door to temperature control device time using logistic regression. The proportion of patients who survived to hospital discharge was evaluated as a secondary outcome. A sensitivity analysis using inverse probability treatment weighting, created using a propensity score, was performed to minimize measurable confounding. RESULTS: Three hundred and forty-seven OHCA patients were included; the early door to temperature control device cohort included 75 (21.6%) patients with a median (interquartile range) door to temperature control device time of 2.50 (2.03 to 2.75) hours, whereas the late door to temperature control device cohort included 272 (78.4%) patients with a median (interquartile range) door to temperature control device time of 5.18 (4.19 to 6.41) hours. In the multivariable logistic regression model, early door to temperature control device time was associated with improved good neurologic outcome and survival before [adjusted odds ratio (OR) (95% confidence interval) 2.36 (1.16 to 4.81) and 3.02 (1.54 to 6.02)] and after [adjusted OR (95% confidence interval) 1.95 (1.19 to 3.79) and 2.14 (1.33 to 3.36)] inverse probability of treatment weighting, respectively. CONCLUSION: In our study of OHCA patients, a shorter preinduction time for temperature control was associated with improved good neurologic outcome and survival. This finding may indicate that early initiation in the emergency department will confer benefit. Our findings are hypothesis generating and need to be validated in future prospective trials.

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.

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).

Examining the Impact of Layperson Rescuer Gender on the Receipt of Bystander CPR for Women in Cardiac Arrest.

BACKGROUND: Women who suffer a witnessed out-of-hospital cardiac arrest receive bystander cardiopulmonary resuscitation (CPR) less often than men. To understand this phenomenon, we queried whether there are differences in deterrents to providing CPR based on the rescuer's gender. METHODS: Participants were surveyed using a national crowdsourcing platform. Participants ranked the following 5 previously identified themes as reasons: rescuers are afraid to injure or hurt women; rescuers might have a misconception that women do not suffer cardiac arrest; rescuers are afraid to be accused of sexual assault or sexual harassment; rescuers have a fear of touching women or that their touch might be inappropriate; and rescuers think that women are faking it or being overdramatic. Participants were adult US residents able to correctly define CPR. Participants ranked the themes if the rescuer was gender unidentified, a man, and a woman, in variable order. RESULTS: In November 2018, 520 surveys were completed. The respondents identified as 42.3% women, 74.2% White, 10.4% Black, and 6.7% Hispanic. Approximately half (48.1%) of the cohort knew how to perform CPR, but only 7.9% had ever performed CPR. When the rescuer was identified as a man, survey participants ranked fear of sexual assault or sexual harassment and fear of touching women or that the touch might be inappropriate as the top reasons (36.2% and 34.0% of responses, respectively). Conversely, when the rescuer was identified as a woman, survey respondents reported fear of hurting or injuring as the top reason (41.2%). CONCLUSIONS: Public perceptions as to why women receive less bystander CPR than men were different based on the gender of the rescuer. Participants reported that men rescuers would potentially be hindered by fears of accusations of sexual assault/harassment or inappropriate touch, while women rescuers would be deterred due to fears of causing physical injury.

Emotional distress, social support, and functional dependence predict readiness for hospital discharge in a prospective sample of cognitively intact cardiac arrest survivors.

AIM: To inform screening, referral and treatment initiatives, we tested the hypothesis that emotional distress, social support, functional dependence, and cognitive impairment within 72 hours prior to discharge predict readiness for discharge in awake and alert cardiac arrest (CA) survivors. METHODS: This was a secondary analysis of a prospective single-center cohort of CA survivors enrolled between 4/2021 and 9/2022. We quantified emotional distress using the Posttraumatic Stress Disorder Checklist-5 and PROMIS Emotional Distress - Anxiety and Depression Short Forms 4a; perceived social support using the ENRICHD Social Support Inventory; functional dependence using the modified Rankin Scale; and cognitive impairment using the Telephone Interview for Cognitive Status. Our primary outcome was readiness for discharge, measured using the Readiness for Hospital Discharge Scale. We used multivariable linear regression to test the independent association of each survivorship factor and readiness for discharge. RESULTS: We included 110 patients (64% male, 88% white, mean age 59 [standard deviation ± 13.1 years]). Emotional distress, functional dependence, and social support were independently associated with readiness for discharge (adjusted ß's [absolute value]: 0.25-0.30, all p < 0.05). CONCLUSIONS: Hospital systems should consider implementing routine in-hospital screening for emotional distress, social support, and functional dependence for CA survivors who are awake, alert and approaching hospital discharge, and prioritize brief in hospital treatment or post-discharge referrals.

2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

Cardiac arrest is common and deadly, affecting up to 700 000 people in the United States annually. Advanced cardiac life support measures are commonly used to improve outcomes. This "2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support" summarizes the most recent published evidence for and recommendations on the use of medications, temperature management, percutaneous coronary angiography, extracorporeal cardiopulmonary resuscitation, and seizure management in this population. We discuss the lack of data in recent cardiac arrest literature that limits our ability to evaluate diversity, equity, and inclusion in this population. Last, we consider how the cardiac arrest population may make up an important pool of organ donors for those awaiting organ transplantation.

The Latest in Resuscitation Research: Highlights From the 2022 American Heart Association's Resuscitation Science Symposium.

BACKGROUND: Every year the American Heart Association's Resuscitation Science Symposium (ReSS) brings together a community of international resuscitation science researchers focused on advancing cardiac arrest care. METHODS AND RESULTS: The American Heart Association's ReSS was held in Chicago, Illinois from November 4th to 6th, 2022. This annual narrative review summarizes ReSS programming, including awards, special sessions and scientific content organized by theme and plenary session. CONCLUSIONS: By exploring both the science of resuscitation and important related topics including survivorship, disparities, and community-focused programs, this meeting provided important resuscitation updates.

An investigation of temperature and fever burdens in patients with sepsis admitted from the emergency department to the hospital.

Aim: We sought to collect granular data on temperature burden to further explore existing conflicting information on the relationship between temperature alterations and outcomes in patients with sepsis requiring hospital admission. Methods: This was a prospective cohort study that enrolled a convenience sample of patients with sepsis or septic shock admitted to the hospital from the emergency department (ED). A "unit of temperature burden (UTB)" was defined as >1°C (1.8°F) above or below 37°C (98.6°F) for 1 min. Fever burden was defined as the number of UTBs >38°C (100.4°F). The primary objective was to calculate the fever burden in patients with sepsis during their ED stay. This was analyzed for patients who present to triage febrile or hypothermic and also for those who developed temperature abnormalities during their ED stay. The secondary objectives were correlating fever and hypothermia burden with in-hospital mortality, Systemic Inflammatory Response Syndrome (SIRS) criteria, and the quick Sequential (Sepsis-Associated) Organ Failure Assessment (qSOFA) score and identification of patients who may benefit from early implementation of targeted temperature management. Results: A total of 256 patients met the inclusion criteria. The mean age of patients was 60.1 ± 18.4 years; 46% were female and 29.6% were black. The median (interquartile range [IQR]) fever burden for the fever in triage cohort (n = 99) was 364.6 (174.3-716.8) UTB and for the no fever in triage cohort (n = 157) was 179.3 (80.9-374.0) UTB (p = 0.005). The two groups had similar in-hospital mortality (6.1 vs 8.3%; p = 0.5). The median fever burden for the fever anytime cohort was 303.8 (IQR 138.8-607.9) UTB and they had lower mortality than the no fever anytime cohort (4.7% vs 11.2%; p = 0.052). Patients with fever at triage had higher mean SIRS criteria than those without (2.8 vs 2.0; p < 0.001) while qSOFA points were similar (p = 0.199). A total of 27 patients had hypothermia during their ED stay and these patients were older with higher mean SIRS criteria. Conclusions: Patients with sepsis and septic shock have a significant temperature burden in the ED. When comparing patients who had fever at any time during their ED stay with those who never had a fever, a trend toward an inverse relationship between fever burden and mortality was found.

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.

Protective positive psychology factors and emotional distress after cardiac arrest.

BACKGROUND: There is a critical need to identify factors that can prevent emotional distress post-cardiac arrest (CA). CA survivors have previously described benefitting from utilizing positive psychology constructs (mindfulness, existential well-being, resilient coping, social support) to cope with distress. Here, we explored associations between positive psychology factors and emotional distress post-CA. METHODS: We recruited CA survivors treated from 4/2021-9/2022 at a single academic medical center. We assessed positive psychology factors (mindfulness [Cognitive and Affective Mindfulness Scale-Revised], existential well-being [Meaning in Life Questionnaire Presence of Meaning subscale], resilient coping [Brief Resilient Coping Scale], perceived social support [ENRICHD Social Support Inventory]) and emotional distress (posttraumatic stress [Posttraumatic Stress Checklist-5], anxiety and depression symptoms [PROMIS Emotional Distress - Anxiety and Depression Short Forms 4a]) just before discharge from the index hospitalization. We selected covariates for inclusion in our multivariable models based on an association with any emotional distress factor (p < 0.10). For our final, multivariable regression models, we individually tested the independent association of each positive psychology factor and emotional distress factor. RESULTS: We included 110 survivors (mean age 59 years, 64% male, 88% non-Hispanic White, 48% low income); 36.4% of survivors scored above the cut-off for at least one measure of emotional distress. In separate adjusted models, each positive psychology factor was independently associated with emotional distress (ß: -0.20 to -0.42, all p < 0.05). CONCLUSIONS: Higher levels of mindfulness, existential well-being, resilient coping, and perceived social support were each associated with less emotional distress. Future intervention development studies should consider these factors as potential treatment targets.

The relationship between mindfulness and enduring somatic threat severity in long-term cardiac arrest survivors.

BACKGROUND: Cardiac arrest (CA) survivors experience continuous exposures to potential traumas though chronic cognitive, physical and emotional sequelae and enduring somatic threats (ESTs) (i.e., recurring somatic traumatic reminders of the event). Sources of ESTs can include the daily sensation of an implantable cardioverter defibrillator (ICD), ICD-delivered shocks, pain from rescue compressions, fatigue, weakness, and changes in physical function. Mindfulness, defined as non-judgmental present-moment awareness, is a teachable skill that might help CA survivors cope with ESTs. Here we describe the severity of ESTs in a sample of long-term CA survivors and explore the cross-sectional relationship between mindfulness and severity of ESTs. METHODS: We analyzed survey data of long-term CA survivors who were members of the Sudden Cardiac Arrest Foundation (collected 10-11/2020). We assessed ESTs using 4 cardiac threat items from the Anxiety Sensitivity Index-revised (items range from 0 "very little" to 4 "very much") which we summed to create a score reflecting total EST burden (range 0-16). We assessed mindfulness using the Cognitive and Affective Mindfulness Scale-Revised. First, we summarized the distribution of EST scores. Second, we used linear regression to describe the relationship between mindfulness and EST severity adjusting for age, gender, time since arrest, COVID-19-related stress, and loss of income due to COVID. RESULTS: We included 145 CA survivors (mean age: 51 years, 52% male, 93.8% white, mean time since arrest: 6 years, 24.1% scored in the upper quarter of EST severity). Greater mindfulness (ß: -30, p = 0.002), older age (ß: -0.30, p = 0.01) and longer time since CA (ß: -0.23, p = 0.005) were associated with lower EST severity. Male sex was also associated with greater EST severity (ß: 0.21, p = 0.009). CONCLUSION: ESTs are common among CA survivors. Mindfulness may be a protective skill that CA survivors use to cope with ESTs. Future psychosocial interventions for the CA population should consider using mindfulness as a core skill to reduce ESTs.