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The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials. [ABSTRACT FROM AUTHOR]

(1) Background: Thiamine is an important cofactor for multiple metabolic processes. Its role in cancer has been debated for years. Our aim is to determine if thiamine can convert the cellular metabolic state of breast cancer cells from anaerobic to aerobic, thus reducing their growth. (2) Methods: Breast cancer (MCF7) and non-tumorigenic (MCF10A) cell lines were treated with various doses of thiamine and assessed for changes in cell growth. The mechanism of this relationship was identified through the measurement of enzymatic activity and metabolic changes. (3) Results: A high dose of thiamine reduced cell proliferation in MCF7 (63% decrease, p < 0.0001), but didn’t affect apoptosis and the cell-cycle profile. Thiamine had a number of effects in MCF7; it (1) reduced extracellular lactate levels in growth media, (2) increased cellular pyruvate dehydrogenase (PDH) activities and the baseline and maximum cellular oxygen consumption rates, and (3) decreased non-glycolytic acidification, glycolysis, and glycolytic capacity. MCF10A cells preferred mitochondrial respiration instead of glycolysis. In contrast, MCF7 cells were more resistant to mitochondrial respiration, which may explain the inhibitory effect of thiamine on their proliferation. (4) Conclusions: The treatment of MCF7 breast cancer cells with 1 μg/mL and 2 μg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells. [ABSTRACT FROM AUTHOR]

Aim: To conduct a prognostic factor systematic review on point-of-care echocardiography during cardiac arrest to predict clinical outcomes in adults with non-traumatic cardiac arrest in any setting.Methods: We conducted this review per PRISMA guidelines and registered with PROSPERO (ID pending). We searched Medline, EMBASE, Web of Science, CINAHL, and the Cochrane Library on September 6, 2019. Two investigators screened titles and abstracts, extracted data, and assessed risks of bias using the Quality in Prognosis Studies (QUIPS) template. We estimated prognostic test performance (sensitivity and specificity) and measures of association (odds ratio). Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology evaluated the certainty of evidence.Results: In total, 15 studies were included. We found wide variation across studies in the definition of 'cardiac motion' and timing of sonographic assessment. Most studies were hindered by high risks of bias from prognostic factor measurement, outcome measurement, and lack of adjustment for other prognostic factors. Ultimately, heterogeneity and risk of bias precluded meta-analyses. We tabulated ranges of prognostic test performance and measures of association for 5 different combinations of definitions of 'cardiac motion' and sonographic timing, as well as other miscellaneous sonographic findings. Overall certainty of this evidence is very low.Conclusions: The evidence for using point-of-care echocardiography as a prognostic tool for clinical outcomes during cardiac arrest is of very low certainty and is hampered by multiple risks of bias. No sonographic finding had sufficient and/or consistent sensitivity for any clinical outcome to be used as sole criterion to terminate resuscitation. [ABSTRACT FROM AUTHOR]

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest. [ABSTRACT FROM AUTHOR]

Importance: In-hospital cardiac arrest is common and associated with a high mortality rate. Despite this, in-hospital cardiac arrest has received little attention compared with other high-risk cardiovascular conditions, such as stroke, myocardial infarction, and out-of-hospital cardiac arrest.Observations: In-hospital cardiac arrest occurs in over 290 000 adults each year in the United States. Cohort data from the United States indicate that the mean age of patients with in-hospital cardiac arrest is 66 years, 58% are men, and the presenting rhythm is most often (81%) nonshockable (ie, asystole or pulseless electrical activity). The cause of the cardiac arrest is most often cardiac (50%-60%), followed by respiratory insufficiency (15%-40%). Efforts to prevent in-hospital cardiac arrest require both a system for identifying deteriorating patients and an appropriate interventional response (eg, rapid response teams). The key elements of treatment during cardiac arrest include chest compressions, ventilation, early defibrillation, when applicable, and immediate attention to potentially reversible causes, such as hyperkalemia or hypoxia. There is limited evidence to support more advanced treatments. Post-cardiac arrest care is focused on identification and treatment of the underlying cause, hemodynamic and respiratory support, and potentially employing neuroprotective strategies (eg, targeted temperature management). Although multiple individual factors are associated with outcomes (eg, age, initial rhythm, duration of the cardiac arrest), a multifaceted approach considering both potential for neurological recovery and ongoing multiorgan failure is warranted for prognostication and clinical decision-making in the post-cardiac arrest period. Withdrawal of care in the absence of definite prognostic signs both during and after cardiac arrest should be avoided. Hospitals are encouraged to participate in national quality-improvement initiatives.Conclusions and Relevance: An estimated 290 000 in-hospital cardiac arrests occur each year in the United States. However, there is limited evidence to support clinical decision making. An increased awareness with regard to optimizing clinical care and new research might improve outcomes. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine whether the provision of corticosteroids improves time to shock reversal and outcomes in patients with post-cardiac arrest shock.Methods: We conducted a randomized, double-blind trial of post-cardiac arrest patients in shock, defined as vasopressor support for a minimum of 1 hour. Patients were randomized to intravenous hydrocortisone 100 mg or placebo every 8 hours for 7 days or until shock reversal. The primary endpoint was time to shock reversal.Results: Fifty patients were included with 25 in each group. There was no difference in time to shock reversal between groups (hazard ratio: 0.83 [95% CI: 0.40-1.75], p = 0.63). We found no difference in secondary outcomes including shock reversal (52% vs. 60%, p = 0.57), good neurological outcome (24% vs. 32%, p = 0.53) or survival to discharge (28% vs. 36%, p = 0.54) between the hydrocortisone and placebo groups. Of the patients with a baseline cortisol < 15 ug/dL, 100% (6/6) in the hydrocortisone group achieved shock reversal compared to 33% (1/3) in the placebo group (p = 0.08). All patients in the placebo group died (100%; 3/3) whereas 50% (3/6) died in the hydrocortisone group (p = 0.43).Conclusions: In a population of cardiac arrest patients with vasopressor-dependent shock, treatment with hydrocortisone did not improve time to shock reversal, rate of shock reversal, or clinical outcomes when compared to placebo.Clinical Trial Registration: Clinicaltrials.gov: NCT00676585, registration date: May 9, 2008. [ABSTRACT FROM AUTHOR]

A response to a letter to the editor on epinephrine administration and pediatric in-hospital cardiac arrest is presented.

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. [ABSTRACT FROM AUTHOR]

Introduction: We previously found decreased levels of Coenzyme Q10 (CoQ10) in patients with septic shock. The objective of the current study was to assess whether the provision of exogenous ubiquinol (the reduced form of CoQ10) could increase plasma CoQ10 levels and improve mitochondrial function.Methods: We performed a randomized, double-blind, pilot trial at a single, tertiary care hospital. Adults (age ≥18 years) with severe sepsis or septic shock between November 2012 and January 2014 were included. Patients received 200 mg enteral ubiquinol or placebo twice a day for up to seven days. Blood draws were obtained at baseline (0 h), 12, 24, 48, and 72 h. The primary outcome of the study was change in plasma CoQ10 parameters (total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10). Secondary outcomes included assessment of: 1) vascular endothelial biomarkers, 2) inflammatory biomarkers, 3) biomarkers related to mitochondrial injury including cytochrome c levels, and 4) clinical outcomes. CoQ10 levels and biomarkers were compared between groups using repeated measures models.Results: We enrolled 38 patients: 19 in the CoQ10 group and 19 in the placebo group. The mean patient age was 62 ± 16 years and 47% were female. Baseline characteristics and CoQ10 levels were similar for both groups. There was a significant increase in total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10 in the ubiquinol group compared to the placebo group. We found no difference between the two groups in any of the secondary outcomes.Conclusions: In this pilot trial we showed that plasma CoQ10 levels could be increased in patients with severe sepsis or septic shock, with the administration of oral ubiquinol. Further research is needed to address whether ubiquinol administration can result in improved clinical outcomes in this patient population.Trial Registration: Clinicaltrials.gov identifier NCT01948063. Registered on 18 February 2013. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that relative adrenal insufficiency is prevalent in post-arrest patients and associated with worse outcome. Whether the provision of steroids improves time to shock reversal and outcomes in post-cardiac arrest shock remains unknown. Methods: We conducted a prospective, randomized, double-blinded trial of post-cardiac arrest patients in shock, defined as need for vasopressor support for a minimum of 1 hour. Patients were randomized to receive hydrocortisone 100 mg IV or placebo every 8 hours for 7 days or until shock reversal. The primary endpoint was time to shock reversal. We classified death as a competing risk event and used the estimated cumulative incidence functions (CIF) which were derived from the estimation of the Fine-Gray competing risk model. A pre-planned analysis of patients with adrenal insufficiency based on low baseline cortisol (<15 ug/dl) and failure to respond to the ACTH stimulation test was performed. Results: Fifty patients were included with 25 in each group (steroid or placebo). Baseline characteristics were similar between groups. There was no difference in the primary outcome of time to shock reversal between groups (hazard ratio: 0.83 [95%CI: 0.40 - 1.75], p = 0.63). We found no difference in secondary outcomes including shock reversal (52% vs. 60%, p = 0.57), good neurological outcome (24% vs. 32%, p = 0.53) or survival to discharge (28% vs. 36%, p = 0.54) between hydrocortisone and placebo groups. Of the patients with a baseline cortisol <15 ug/dl, 100% (6/6) in the steroid group achieved shock reversal compared to 33% (1/3) in the placebo group (p = 0.08). All in the placebo group died 100% (3/3) whereas 50% (3/6) died in the steroid group (p=0.43). There were no differences among those who did not respond to an ACTH stimulation test. Conclusion: In the overall population of cardiac arrest patients with vasopressor-dependent shock, treatment with hydrocortisone did not improve time to shock reversal (primary outcome), rate of shock reversal, or clinical outcomes when compared to placebo. In the subgroup with relative adrenal insufficiency defined by baseline cortisol <15 ug/dl, there was a trend toward increased rate of shock reversal in the hydrocortisone group. [ABSTRACT FROM AUTHOR]

Aims: Prior investigation has found that mechanical ventilation with lower tidal volumes (Vt) following out-of-hospital cardiac arrest is associated with better neurologic outcomes. The relationship between Vt and neurologic outcome following in-hospital cardiac arrest (IHCA) has not previously been explored. In the present study, we investigate the association between Vt and neurologic outcome following IHCA.Methods: This was an observational study using a prospectively collected database of IHCA patients at a tertiary care hospital in the United States. The relationship between time-weighted average Vt per predicted body weight (PBW) over the first 6- and 48 h after cardiac arrest and neurologic outcome were assessed using propensity-score adjusted logistic regression.Measurements and Main Results: Of 185 IHCA patients who received invasive mechanical ventilation within 6 h of return of spontaneous circulation (ROSC), the average Vt over the first 6 h was 7.7 ± 2.0 ml/kg and 68 (36.8%) patients received an average Vt > 8.0 ml/kg. Of 121 patients who received mechanical ventilation for at least 48 h post-ROSC, the average Vt was 7.6 ± 1.5 ml/kg and 46 (38.0%) patients received an average Vt > 8.0 ml/kg. There was no relationship between Vt/PBW over the first 6- or 48 h post-ROSC and neurologic outcome (OR 0.99; 95%CI 0.84-1.16; p = 0.89; OR 1.03; 95%CI 0.78-1.37; p = 0.83 respectively).Conclusions: This study did not identify a relationship between Vt and neurologic outcome following IHCA. This contrasts with results in OHCA, where higher Vt has been associated with worse neurologic outcome. Additional investigation is needed with respect to other potential benefits of low-Vt post IHCA. [ABSTRACT FROM AUTHOR]

The article focuses on a retrospective analysis of a large in-hospital data registry conducted to examine the effect of the timing of administration of epinephrine on patients who experience cardiac arrest with a non-shockable rhythm in hospital. Topics covered include the participants and setting of the study, the design, size and duration of the research and its main results. Offered as well are the bias, confounding and other reasons for caution for future studies.

An abstract of the article "Patient Perceptions of Bedside Teaching Rounds" by Joseph F. Majdan et al. is presented.

Background: Small‐bore chest tube (SBCT) placement via modified Seldinger technique is a commonly performed invasive procedure for treatment of pleural effusion and pneumothorax. When performed suboptimally, it may lead to serious complications. Validated checklists are central to teaching and assessing procedural skills and may result in improved health care quality. In this paper, we describe the development and content validation of a SBCT placement checklist. Methods: A literature review across multiple medical databases and seminal textbooks was performed to identify all publications describing procedural steps involved in SBCT placement. No studies were identified that involved systematic development of a checklist for this purpose. After the first iteration of a comprehensive checklist (CAPS) based on literature review was developed, the modified Delphi technique involving a panel of nine multidisciplinary experts was used to modify it and establish its content validity. Results: After four Delphi rounds, the mean expert‐rated Likert score across all checklist items was 6.85 ± 0.68 (out of 7). The final, 31‐item checklist had a high internal consistency (Cronbach's alpha = 0.846) with 95% of the responses (by nine experts across 31 checklist items) being a numerical score of 6 or 7. Conclusions: This study reports the development and content validity of a comprehensive checklist for teaching and assessing SBCT placement. For purposes of demonstrating construct validity, this checklist should next be studied in the simulation and clinical setting. [ABSTRACT FROM AUTHOR]

The article examines the relationship between home modifications and the occurrence of injurious falls in the homes of wheelchair users in the U.S. The presence of any indoor home modification was linked with a lower prevalence of falls involving injury. Home improvements that facilitate independence and that make it easier to move around should be considered a basic need for people with disabilities. From a public health perspective, both safety and access would be more facilitated if home improvements became a reimbursable expense under Medicare, Medicaid, and other health insurers.

This study explored children's experiences of participating in one-to-one physical training programs to identify how programs can best promote physical activity participation for children with cerebral palsy. A qualitative descriptive design with self-determination theory was used. Semistructured interviews were conducted with 6 children with cerebral palsy, age 8–14 years, who participated in a fundamental-movement-skills or lower-limb strength-training program. A hybrid approach of deductive and inductive analysis was used. Four themes developed: World around me (i.e., social/physical environments), Made for me (i.e., individualizing programs), Teach me how (i.e., teaching strategies facilitated skill learning), and I know me (i.e., sense of self). Results include recommendations for delivery of physical training programs. Using an individualized approach in a structured one-to-one program that employs skill-teaching strategies and self-reflection opportunities may provide a foundation to increase physical activity participation, related self-confidence, and desire to participate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Rising MCS Use: Durable mechanical circulatory support devices are becoming more common in acute resuscitation scenarios. • Knowledge Gap: Limited evidence exists on handling acute impaired perfusion in patients with MCS devices. • Review Insight: This scoping review explores resuscitation practices for MCS-supported patients and may guide international standards. There is an increasing prevalence of durable mechanical circulatory supported patients in both the in-and-out of hospital communities. The scientific literature regarding the approach to patients supported by durable mechanical circulatory devices who suffer acutely impaired perfusion has not been well explored. The International Liaison Committee on Resuscitation Advanced, Basic, and Pediatric Life Support Task Forces conducted a scoping review of the literature using a population, context, and concept framework. A total of 32 publications that included patients who were receiving durable mechanical circulatory support and required acute resuscitation were identified. Most of the identified studies were case reports or small case series. Of these, 11 (34.4%) included patients who received chest compressions. A number of studies reported upon delays in the application of chest compressions resulting from complexity due to the expected pulselessness in some patients with continuous flow left-ventricular assist devices as well as from concern regarding potential dislodgement of the mechanical circulatory support device. Three observational studies identified worse outcomes in durable mechanical circulatory support receiving patients with cardiac arrest and acutely impaired perfusion who received chest compressions as compared to those who did not, however those studies were at high risk of bias. Of 226 patients across 11 studies and two published scientific abstracts who sustained cardiac arrest while supported by durable MCS and underwent chest compressions, there were no reported instances of device dislodgement and 71 (31.4%) patients had favorable outcomes. There is a scarcity of evidence to inform the resuscitation of patients with durable mechanical circulatory support (MCS) experiencing acute impairment in perfusion and cardiac arrest. Reports indicate that delays in resuscitation often stem from rescuers' uncertainty about the safety of administering chest compressions. Notably, no instances of device dislodgement have been documented following chest compressions, suggesting that the risk of harm from timely CPR in these patients is minimal. [ABSTRACT FROM AUTHOR]

BACKGROUND: High‐risk neuroblastoma patients with end‐induction residual disease commonly receive post‐induction therapy in an effort to increase survival by improving the response before autologous stem cell transplantation (ASCT). The authors conducted a multicenter, retrospective study to investigate the efficacy of this approach. METHODS: Patients diagnosed between 2008 and 2018 without progressive disease with a partial response or worse at end‐induction were stratified according to the post‐induction treatment: 1) no additional therapy before ASCT (cohort 1), 2) post‐induction "bridge" therapy before ASCT (cohort 2), and 3) post‐induction therapy without ASCT (cohort 3). χ2 tests were used to compare patient characteristics. Three‐year event‐free survival (EFS) and overall survival (OS) were estimated by the Kaplan‐Meier method and survival curves were compared by log‐rank test. RESULTS: The study cohort consisted of 201 patients: cohort 1 (n = 123), cohort 2 (n = 51), and cohort 3 (n = 27). Although the end‐induction response was better for cohort 1 than cohorts 2 and 3, the outcomes for cohorts 1 and 2 were not significantly different (P =.77 for EFS and P =.85 for OS). Inferior outcomes were observed for cohort 3 (P <.001 for EFS and P =.06 for OS). Among patients with end‐induction stable metastatic disease, 3‐year EFS was significantly improved for cohort 2 versus cohort 1 (P =.04). Cohort 3 patients with a complete response at metastatic sites after post‐induction therapy had significantly better 3‐year EFS than those with residual metastatic disease (P =.01). CONCLUSIONS: Prospective studies to confirm the benefits of bridge treatment and the prognostic significance of metastatic response observed in this study are warranted. [ABSTRACT FROM AUTHOR]

Objective: Acute respiratory distress syndrome (ARDS) after out-of-hospital cardiac arrest is common and associated with worse outcomes. In the hospital setting, there are many potential risk factors for post-arrest ARDS, such as aspiration, sepsis, and shock. ARDS after in-hospital cardiac arrest (IHCA) has not been characterized.Methods: We performed a single-center retrospective study of adult patients admitted to the hospital between 2014-2018 who suffered an IHCA, achieved return of spontaneous circulation (ROSC), and were either already intubated at the time of arrest or within 2 hours of ROSC. Post-IHCA ARDS was defined as meeting the Berlin criteria in the first 3 days following ROSC. Outcomes included alive-and-ventilator free days across 28 days, hospital length-of-stay, hospital mortality, and hospital disposition.Results: Of 203 patients included, 146 (71.9%) developed ARDS. In unadjusted analysis, patients with ARDS had fewer alive-and-ventilator-free days over 28 days with a median of 1 (IQR: 0, 21) day, compared to 18 (IQR: 0, 25) days in patients without ARDS (p = 0.03). However, this association was not significant after multivariate adjustment. There was also a non-significant longer hospital length-of-stay (15 [IQR: 7, 26] vs 10 [IQR: 7, 22] days, p = 0.25; median adjusted increase in ARDS patients: 3 [95% CI: -2 to 8] days, p = 0.27) and higher hospital mortality (53% vs 44%, p = 0.26; aOR 1.6 [95% CI: 0.8-2.9], p = 0.17) in the ARDS group.Conclusion: Among IHCA patients, almost three-quarters developed ARDS within 3 days of ROSC. As in out of hospital cardiac arrest, post-IHCA ARDS is common. [ABSTRACT FROM AUTHOR]

To examine factors associated with distressing social decline and withdrawal during the COVID-19 pandemic for home care recipients. Retrospective cohort. Home care recipients age 18 years or older in Ontario, Canada without severe cognitive impairment with an assessment and follow-up between September 1, 2018 and August 31, 2020. Data were collected using the interRAI home care. Outcomes of interest were distressing decline in social participation and social withdrawal. Independent variables were entered into multivariable longitudinal generalized estimating equations. Interaction terms with the pandemic were tested. Those significant at P <.01 were retained in final models and reported as odds ratios (ORs), 95% confidence intervals (CIs). We compared 26,492 and 19,126 home care recipients before and during the pandemic, respectively. The pandemic was associated with greater odds of experiencing distressing social decline (OR 1.28, 95% CI 1.22‒1.34) and withdrawal (OR 1.09, 95% CI 1.04‒1.15). Living alone (OR 1.13, 95% CI 1.05‒1.22), frailty (OR 3.21, 95% CI 2.76‒3.73), health instability (OR 2.22, 95% CI 2.02‒2.44), and depression (OR 2.14, 95% CI 2.01‒2.29) increased the odds of distressing social decline. Older age (OR 0.71, 95% CI 0.65‒0.77), functional impairment (OR 0.58, 95% CI 0.51‒0.67), and receiving caregiving (OR 0.73, 95% CI 0.67‒0.79) decreased the odds. Home care recipients with mild/moderate dementia were less likely to experience distressing social decline during the pandemic. Those who lived alone were more likely. Frailty (OR 9.49, 95% CI 7.69‒11.71) and depression (OR 2.76, 95% CI 2.55‒3.00) increased the odds of social withdrawal. Functional impairment (OR 0.32, 95% CI 0.27‒0.39), congestive heart failure (OR 0.77, 95% CI 0.70‒0.84), and receiving caregiving (OR 0.50, 95% CI 0.46‒0.55) decreased the odds. Home care recipients age 18‒64 years and older than 75 years were less likely to experience social withdrawal during the pandemic. Social support interventions should focus on supporting those living alone, with frailty, health instability, or depression. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Survival after cardiac arrest (CA) is limited by the profound neurologic insult from ischemia–reperfusion injury. Therapeutic options are limited. Previous data suggest a benefit of coenzyme Q10 (CoQ10) in post-arrest patients. We hypothesized that plasma CoQ10 levels would be low after CA and associated with poorer outcomes. Methods: Prospective observational study of post-arrest patients presenting to a tertiary care center. CoQ10 levels were drawn 24h after return of spontaneous circulation (ROSC) and compared to healthy controls. Levels of inflammatory cytokines and biomarkers were analyzed. Primary endpoints were survival to discharge and neurologic status at time of discharge. Results: 23 CA subjects and 16 healthy controls were enrolled. CoQ10 levels in CA patients (0.28μmolL−1, inter-quartile range (IQR): 0.22–0.39) were significantly lower than in controls (0.75μmolL−1, IQR: 0.61–1.08, p <0.0001). The mean CoQ10 level in CA patients who died was significantly lower than in those who survived (0.27 vs 0.47μmolL−1, p =0.007). There was a significant difference in median CoQ10 level between patients with a good vs poor neurological outcome (0.49μmolL−1, IQR: 0.30–0.67 vs 0.27μmolL−1, IQR: 0.21–0.30, p =0.02). CoQ10 was a statistically significant predictor of poor neurologic outcome (adjusted p =0.02) and in-hospital mortality (adjusted p =0.026). Conclusion: CoQ10 levels are low in human subjects with ROSC after cardiac arrest as compared to healthy controls. CoQ10 levels were lower in those who died, as well as in those with a poor neurologic outcome. [Copyright &y& Elsevier]

To construct a data tool, the Residential History File (RHF), that summarizes information from Medicare claims and nursing home (NH) Minimum Data Set (MDS) assessments to track people through health care locations, including non-Medicare-paid NH stays. Online Survey of Certification and Reporting (OSCAR) data for 202 free-standing NHs, Medicare Denominator, claims (parts A and B), and MDS assessments for 60,984 people who were present in one of these NHs in 2006. The algorithm creating the RHF is outlined and the RHF for the study data are used to describe place of death. The identification of residents in NHs is compared with the reports in OSCAR and part B claims. The RHF correctly identified 84.8 percent of part B claims with place-of-service in NH, and it identified 18.3 less residents on average than reported in the OSCAR on the day of the survey. The RHF indicated that 17.5 percent non-Medicare NH decedents were transferred to the hospital to die versus 45.6 percent skilled nursing facility decedents. The population-based design of the RHF makes it possible to conduct policy-relevant research to examine the variation in the rate and type of health care transitions across the United States. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the frequency distributions and interrater reliability of individual items of the interRAI Acute Care instrument. DESIGN: Observational study of a representative sample of older inpatients; duplicate assessments conducted on a subsample by independent assessors to examine interrater reliability. SETTING: Acute medical, acute geriatric and orthopedic units in 13 hospitals in nine countries. PARTICIPANTS: Five hundred thirty-three patients aged 70 and older (mean age 82.4, range 70–102) with an anticipated stay of 48 hours or longer of whom 161 received duplicate assessments. MEASUREMENTS: Sixty-two clinical items across 11 domains. Premorbid (3-day observation period before onset of the acute illness) and admission (the first 24 hours of hospital stay) assessments were conducted. RESULTS: The frequency of deficits exceeded 30% for most items, ranging from 1% for physically abusive behavior to 86% for the need for support in activities of daily living after discharge. Common deficits were in cognitive skills for daily decision-making (38% premorbid, 54% at admission), personal hygiene (37%, 65%), and walking (39%, 71%). Interrater reliability was substantial in the premorbid period (average κ=0.61) and admission period (average κ=0.66). Of the 69 items tested, less than moderate agreement (κ<0.4) was recorded for six (9%), moderate agreement (κ=0.41–0.6) for 14 (20%), substantial agreement (κ=0.61–0.8) for 40 (58%), and almost perfect agreement (κ>0.8) for nine (13%). CONCLUSION: Initial assessment of the psychometric properties of the interRAI Acute Care instrument provided evidence that item selection and interrater reliability are appropriate for clinical application. Further studies are required to examine the validity of embedded scales, diagnostic algorithms, and clinical protocols. [ABSTRACT FROM AUTHOR]

Background: Thiamine supplementation is recommended for patients with alcohol use disorder (AUD). The authors hypothesize that critically ill patients with AUD are commonly not given thiamine supplementation.Objective: To describe thiamine supplementation incidence in patients with AUD and various critical illnesses (alcohol withdrawal, septic shock, traumatic brain injury [TBI], and diabetic ketoacidosis [DKA]) in the United States.Design: Retrospective observational study.Setting: Cerner Health Facts database.Patients: Adult patients with a diagnosis of AUD who were admitted to the intensive care unit with alcohol withdrawal, septic shock, TBI, or DKA between 2010 and 2017.Measurements: Incidence and predicted probability of thiamine supplementation in alcohol withdrawal and other critical illnesses.Results: The study included 14 998 patients with AUD. Mean age was 52.2 years, 77% of participants were male, and in-hospital mortality was 9%. Overall, 7689 patients (51%) received thiamine supplementation. The incidence of thiamine supplementation was 59% for alcohol withdrawal, 26% for septic shock, 41% for TBI, and 24% for DKA. Most of those receiving thiamine (n = 3957 [52%]) received it within 12 hours of presentation in the emergency department. The predominant route of thiamine administration was enteral (n = 3119 [41%]).Limitation: Specific dosing and duration were not completely captured.Conclusion: Thiamine supplementation was not provided to almost half of all patients with AUD, raising a quality-of-care issue for this cohort. Supplementation was numerically less frequent in patients with septic shock, DKA, or TBI than in those with alcohol withdrawal. These data will be important for the design of quality improvement studies in critically ill patients with AUD.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Investigates the interplay of human and technological assistance on the use of mobility equipment by older adults. Formal and informal care services from family members; Cost-effectiveness and community-based care; Substitutability of mobility equipment for human help; Factors affecting the regressing use of mobility equipment.

Background: Widespread reports suggest the characteristics and disease course of coronavirus disease 2019 (COVID-19) and influenza differ, yet detailed comparisons of their clinical manifestations are lacking.Objective: Comparison of the epidemiology and clinical characteristics of COVID-19 patients during the pandemic with those of influenza patients in previous influenza seasons at the same hospital DESIGN: Admission rates, clinical measurements, and clinical outcomes from confirmed COVID-19 cases between March 1 and April 30, 2020, were compared with those from confirmed influenza cases in the previous five influenza seasons (8 months each) beginning September 1, 2014.Setting: Large tertiary care teaching hospital in Boston, MA PARTICIPANTS: Laboratory-confirmed COVID-19 and influenza inpatients MEASUREMENTS: Patient demographics and medical history, mortality, incidence and duration of mechanical ventilation, incidences of vasopressor support and renal replacement therapy, and hospital and intensive care admissions.Results: Data was abstracted from medical records of 1052 influenza patients and 582 COVID-19 patients. An average of 210 hospital admissions for influenza occurred per 8-month season compared to 582 COVID-19 admissions over 2 months. The median weekly number of COVID-19 patients requiring mechanical ventilation was 17 (IQR: 4, 34) compared to a weekly median of 1 (IQR: 0, 2) influenza patient (p=0.001). COVID-19 patients were significantly more likely to require mechanical ventilation (31% vs 8%) and had significantly higher mortality (20% vs. 3%; p<0.001 for all). Relatively more COVID-19 patients on mechanical ventilation lacked pre-existing conditions compared with mechanically ventilated influenza patients (25% vs 4%, p<0.001). Pneumonia/ARDS secondary to the virus was the predominant cause of mechanical ventilation in COVID-19 patients (94%) as opposed to influenza (56%).Limitation: This is a single-center study which could limit generalization.Conclusion: COVID-19 resulted in more weekly hospitalizations, higher morbidity, and higher mortality than influenza at the same hospital. [ABSTRACT FROM AUTHOR]

Acute pancreatitis is a common disease which, in its severe form, is associated with significant morbidity and mortality. Currently, there is no specific therapy known to attenuate organ failure in severe pancreatitis and treatment consists primarily of supportive care. Corticosteroids have been shown to be beneficial in disease processes associated with systemic inflammation and could potentially improve outcomes in severe acute pancreatitis. The Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) trial is a multi-centre, double-blind, randomized, placebo-controlled clinical trial that aims to determine the impact of corticosteroids versus placebo on organ injury in patients with severe acute pancreatitis. Patients are randomized to receive 100 mg of hydrocortisone parenterally versus matching placebo every 8 h for 3 days. Clinical and laboratory data are collected at the time of study enrollment, at 24, 48 and 72 h. The primary end-point for the trial is the difference in 72-h change in the Sequential Organ Failure Assessment (SOFA) score between hydrocortisone and placebo groups. Additional key secondary outcomes include ventilator free days and 28-day mortality. This study will add to the evidence base in the treatment of severe acute pancreatitis. The results will inform clinical practice and future studies in the field. Trial registration number The trial is registered on clinicaltrials.gov (NCT05160506). It was posted on December 16th, 2021. The study protocol was approved by the Beth Israel Deaconess Medical Center Committee on Clinical Investigation (CCI) (protocol 2021 P-000803). [ABSTRACT FROM AUTHOR]

Introduction: Ubiquinol (reduced coenzyme Q10) is essential for adequate aerobic metabolism. The objective of this trial was to determine whether ubiquinol administration in patients resuscitated from cardiac arrest could increase physiological coenzyme Q10 levels, improve oxygen consumption, and reduce neurological biomarkers of injury.Materials and Methods: This was a randomized, double-blind, placebo-controlled trial in patients successfully resuscitated from cardiac arrest. Patients were randomized to receive enteral ubiquinol (300 mg) or placebo every 12 h for up to 7 days. The primary endpoint was total coenzyme Q10 plasma levels at 24 h after enrollment. Secondary endpoints included neuron specific enolase, S100B, lactate, cellular and global oxygen consumption, neurological status, and in-hospital mortality.Results: Forty-three patients were included in the modified intention-to-treat analysis. Median coenzyme Q10 levels were significantly higher in the ubiquinol group as compared to the placebo group at 24 h (441 [IQR, 215-510] ηg/mL vs. 113 [IQR, 94-208] ηg/mL, P < 0.001). Similar results were observed at 48 and 72 h. There were no differences between the two groups in any of the secondary endpoints. Median neuron specific enolase levels were not different between the two groups at 24 h (16.8 [IQR, 9.5-19.8] ηg/mL vs. 8.2 [IQR, 4.3-19.1] ηg/mL, P = 0.61).Conclusions: Administration of enteral ubiquinol increased plasma coenzyme Q10 levels in post-cardiac arrest patients as compared to placebo. There were no differences in neurological biomarkers and oxygen consumption between the two groups. [ABSTRACT FROM AUTHOR]

Aim: Guidance on post-cardiac arrest prognostication is largely based on data from out-of-hospital cardiac arrest (OHCA), despite clear differences between the OHCA and in-hospital cardiac arrest (IHCA) populations. Early prediction of mortality after IHCA would be useful to help make decisions about post-arrest care. We evaluated the ability of lactate and need for vasopressors after IHCA to predict hospital mortality.Methods: Single center retrospective observational study of adult IHCA patients who achieved sustained return of spontaneous circulation (ROSC), required mechanical ventilation peri-arrest and had a lactate checked within 2 h after ROSC. We evaluated the association of post-ROSC lactate and need for vasopressors with mortality using multivariate logistic regression.Results: A total of 364 patients were included. Patients who received vasopressors within 3 h after ROSC had significantly higher mortality compared to patients who did not receive vasopressors (58% vs. 43%, p = 0.03). Elevated lactate level was associated with mortality (44% if lactate <5 mmol/L, 58% if lactate 5-10 mmol/L, and 73% if lactate >10 mmol/L, p < 0.01). A multivariable model with lactate group and post-ROSC vasopressor use as predictors demonstrated moderate discrimination (AUC 0.64 [95%CI:0.59-0.70]). Including other variables, the most parsimonious model included lactate, age, body mass index, race, and history of arrhythmia, cancer and/or liver disease (AUC 0.70 [95% CI: 0.64-0.75]).Conclusion: Post-ROSC lactate and need for vasopressors may be helpful in stratifying mortality risk in patients requiring mechanical ventilation after IHCA. [ABSTRACT FROM AUTHOR]

Importance: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.Objective: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock.Design, Setting, and Participants: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019.Interventions: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102).Main Outcomes and Measures: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses.Results: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively).Conclusions and Relevance: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock.Trial Registration: ClinicalTrials.gov Identifier: NCT03389555. [ABSTRACT FROM AUTHOR]

Aim: To perform a systematic review and meta-analysis of the literature on oxygenation and ventilation targets after successful resuscitation from cardiac arrest in order to inform an update of international guidelines.Methods: The review was performed according to PRISMA and registered on PROSPERO (ID: X). Medline, EMBASE, and the Cochrane Library were searched on August 22, 2019. The population included both adult and pediatric patients with cardiac arrest. Two investigators reviewed abstracts, extracted data, and assessed the risk of bias. Meta-analyses were performed for studies without excessive bias. Certainty of evidence was evaluated using GRADE.Results: We included 7 trials and 36 observational studies comparing oxygenation or ventilation targets. Most of the trials and observational studies included adults with out-of-hospital cardiac arrest. There were 6 observational studies in children. Bias for trials ranged from low to high risk, with group imbalances and blinding being primary concerns. Bias for observational studies was rated as serious or critical risk with confounding and exposure classification being primary sources of bias. Meta-analyses including two trials comparing low vs high oxygen therapy and two trials comparing hypercapnia vs no hypercapnia were inconclusive. Point estimates of individual studies generally favored normoxemia and normocapnia over hyper- or hypoxemia and hyper- or hypocapnia.Conclusions: We identified a large number of studies related to oxygenation and ventilation targets in cardiac arrest. The majority of studies did not reach statistical significance and were limited by excessive risk of bias. Point estimates of individual studies generally favored normoxemia and normocapnia. [ABSTRACT FROM AUTHOR]

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research. [ABSTRACT FROM AUTHOR]

While survival after in-hospital cardiac arrest (IHCA) has improved in recent years, it remains unknown whether this trend primarily applies to younger IHCA victims. The aim of this study was to assess trends in survival to hospital discharge after adult IHCA across age groups from 2000 to 2016. This is an observational study of IHCA patients included in the Get With The Guidelines®-Resuscitation registry between 2000 and 2016. The primary outcome was survival to hospital discharge. Patients were stratified into five age groups: <50 years, 50–59 years, 60–69 years, 70–79 years, and ≥80 years. Generalized linear regression was used to obtain absolute survival rates over time. A total of 234,767 IHCA patients were included. The absolute increase in survival per calendar year was 0.8% (95% CI 0.7–1.0%, p < 0.001) for patients younger than 50 years, 0.6% (95% CI 0.4–0.7%, p < 0.001) for patients between 50 and 59 years, 0.5% (95% CI 0.4–0.6%, p < 0.001) for patients between 60 and 69 years, 0.5% (95% CI 0.4–0.6%, p < 0.001) for patients between 70 and 79 years, and 0.5% (95% CI 0.4–0.6%, p < 0.001) for patients older than 80 years. We observed a significant interaction between calendar year and age group (p < 0.001), indicating that the rate of improvement in survival over time was significantly different between age groups. For patients with IHCA, rates of survival to discharge have improved significantly from 2000 to 2016 across all age groups. [ABSTRACT FROM AUTHOR]

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research. [ABSTRACT FROM AUTHOR]

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research. [ABSTRACT FROM AUTHOR]

Aim: To systematically review the literature on the use of vasopressors during adult cardiac arrest to inform an update of international guidelines.Methods: PRISMA guidelines were followed. We searched Medline, Embase, Web of Science, CINAHL, and the Cochrane Library for controlled trials and observational studies. The population included adults with cardiac arrest in any setting. Pairs of investigators reviewed studies for relevance, extracted data, and assessed the risk of bias for individual studies. Certainty of evidence was evaluated using GRADE for controlled trials and meta-analyses were performed when at least two studies could be pooled.Results: We included 15 controlled trials and 67 observational studies. The majority of studies included out-of-hospital cardiac arrest only. Meta-analyses were performed for two controlled trials comparing epinephrine to placebo, three comparing vasopressin to epinephrine, and three comparing epinephrine plus vasopressin to epinephrine only. All controlled trials ranged between low to some concern in risk of bias. The certainty of evidence ranged from very low to high. Risk of bias for observational studies was generally critical or serious, largely due to confounding and selection bias.Conclusions: Controlled trial data suggest that epinephrine improves return of spontaneous circulation, survival to hospital discharge, and 3-month survival in out-of-hospital cardiac arrest. The improvement in short-term outcomes appeared more pronounced for non-shockable rhythms. Differences in long-term neurological outcome did not reach statistical significance, although there was a signal toward improved outcomes. Controlled trial data indicated no benefit from vasopressin with or without epinephrine compared to epinephrine only. [ABSTRACT FROM AUTHOR]