Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock.

BACKGROUND: Cardiogenic shock is associated with substantial morbidity and mortality. Although inotropic support is a mainstay of medical therapy for cardiogenic shock, little evidence exists to guide the selection of inotropic agents in clinical practice. METHODS: We randomly assigned patients with cardiogenic shock to receive milrinone or dobutamine in a double-blind fashion. The primary outcome was a composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke diagnosed by a neurologist, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite outcome. RESULTS: A total of 192 participants (96 in each group) were enrolled. The treatment groups did not differ significantly with respect to the primary outcome; a primary outcome event occurred in 47 participants (49%) in the milrinone group and in 52 participants (54%) in the dobutamine group (relative risk, 0.90; 95% confidence interval [CI], 0.69 to 1.19; P = 0.47). There were also no significant differences between the groups with respect to secondary outcomes, including in-hospital death (37% and 43% of the participants, respectively; relative risk, 0.85; 95% CI, 0.60 to 1.21), resuscitated cardiac arrest (7% and 9%; hazard ratio, 0.78; 95% CI, 0.29 to 2.07), receipt of mechanical circulatory support (12% and 15%; hazard ratio, 0.78; 95% CI, 0.36 to 1.71), or initiation of renal replacement therapy (22% and 17%; hazard ratio, 1.39; 95% CI, 0.73 to 2.67). CONCLUSIONS: In patients with cardiogenic shock, no significant difference between milrinone and dobutamine was found with respect to the primary composite outcome or important secondary outcomes. (Funded by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; ClinicalTrials.gov number, NCT03207165.).

Supraglottic Airway Versus Tracheal Intubation for Airway Management in Out-of-Hospital Cardiac Arrest: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVES: Given the uncertainty regarding the optimal approach for airway management for adult patients with out-of-hospital cardiac arrest (OHCA), we conducted a systematic review and meta-analysis to compare the use of supraglottic airways (SGAs) with tracheal intubation for initial airway management in OHCA. DATA SOURCES: We searched MEDLINE, PubMed, Embase, Cochrane Library, as well as unpublished sources, from inception to February 7, 2023. STUDY SELECTION: We included randomized controlled trials (RCTs) of adult OHCA patients randomized to SGA compared with tracheal intubation for initial prehospital airway management. DATA EXTRACTION: Reviewers screened abstracts, full texts, and extracted data independently and in duplicate. We pooled data using a random-effects model. We used the modified Cochrane risk of bias 2 tool and assessed certainty of evidence using the Grading Recommendations Assessment, Development, and Evaluation approach. We preregistered the protocol on PROSPERO (CRD42022342935). DATA SYNTHESIS: We included four RCTs ( n = 13,412 patients). Compared with tracheal intubation , SGA use probably increases return of spontaneous circulation (ROSC) (relative risk [RR] 1.09; 95% CI, 1.02-1.15; moderate certainty) and leads to a faster time to airway placement (mean difference 2.5 min less; 95% CI, 1.6-3.4 min less; high certainty). SGA use may have no effect on survival at longest follow-up (RR 1.06; 95% CI, 0.84-1.34; low certainty), has an uncertain effect on survival with good functional outcome (RR 1.11; 95% CI, 0.82-1.50; very low certainty), and may have no effect on risk of aspiration (RR 1.04; 95% CI, 0.94 to 1.16; low certainty). CONCLUSIONS: In adult patients with OHCA, compared with tracheal intubation, the use of SGA for initial airway management probably leads to more ROSC, and faster time to airway placement, but may have no effect on longer-term survival outcomes or aspiration events.

Pharmacological agents for procedural sedation and analgesia in the emergency department and intensive care unit: a systematic review and network meta-analysis of randomised trials.

BACKGROUND: We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications. METHODS: We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates. RESULTS: We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty). CONCLUSION: When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine.

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. METHODS: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. RESULTS: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. CONCLUSION: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

Inotrope versus placebo therapy in cardiogenic shock: Rationale and study design of the CAPITAL DOREMI2 trial.

BACKGROUND: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS. METHODS AND DESIGN: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge. IMPLICATION: This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients.

Predictors of Noninvasive Ventilation Failure in the Post-Extubation Period: A Systematic Review and Meta-Analysis.

OBJECTIVES: To identify factors associated with failure of noninvasive ventilation (NIV) in the post-extubation period. DATA SOURCES: We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to February 28, 2022. STUDY SELECTION: We included English language studies that provided predictors of post-extubation NIV failure necessitating reintubation. DATA EXTRACTION: Two authors conducted data abstraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios (ORs) mean difference (MD), respectively. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty. DATA SYNTHESIS: We included 25 studies ( n = 2,327). Illness-related factors associated with increased odds of post-extubation NIV failure were higher critical illness severity (OR, 3.56; 95% CI, 1.96-6.45; high certainty) and a diagnosis of pneumonia (OR, 6.16; 95% CI, 2.59-14.66; moderate certainty). Clinical and biochemical factors associated with moderate certainty of increased risk of NIV failure post-extubation include higher respiratory rate (MD, 1.54; 95% CI, 0.61-2.47), higher heart rate (MD, 4.46; 95% CI, 1.67-7.25), lower Pa o2 :F io2 (MD, -30.78; 95% CI, -50.02 to -11.54) 1-hour after NIV initiation, and higher rapid shallow breathing index (MD, 15.21; 95% CI, 12.04-18.38) prior to NIV start. Elevated body mass index was the only patient-related factor that may be associated with a protective effect (OR, 0.21; 95% CI, 0.09-0.52; moderate certainty) on post-extubation NIV failure. CONCLUSIONS: We identified several prognostic factors before and 1 hour after NIV initiation associated with increased risk of NIV failure in the post-extubation period. Well-designed prospective studies are required to confirm the prognostic importance of these factors to help further guide clinical decision-making.

Efficacy and safety of corticosteroids in cardiac arrest: a systematic review, meta-analysis and trial sequential analysis of randomized control trials.

BACKGROUND: Post-cardiac arrest, outcomes for most patients are poor, regardless of setting. Many patients who do achieve spontaneous return of circulation require vasopressor therapy to maintain organ perfusion. There is some evidence to support the use of corticosteroids in cardiac arrest. RESEARCH QUESTION: Assess the efficacy and safety of corticosteroids in patients following in- and out-of-hospital cardiac arrest. STUDY DESIGN AND METHODS: We searched databases CINAHL, EMBASE, LILACS, MEDLINE, Web of Science, CENTRAL, ClinicalTrails.gov, and ICTRP. We included randomized controlled trials (RCTs) that examined the efficacy and safety of corticosteroids, as compared to placebo or usual care in patients post-cardiac arrest. We pooled estimates of effect size using random effects meta-analysis and report relative risk (RR) with 95% confidence intervals (CIs). We assessed risk of bias (ROB) for the included trials using the modified Cochrane ROB tool and rated the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: We included 8 RCTs (n = 2213 patients). Corticosteroids administered post-cardiac arrest had an uncertain effect on mortality measured at the longest point of follow-up (RR 0.96, 95% CI 0.90-1.02, very low certainty, required information size not met using trial sequential analysis). Corticosteroids probably increase return of spontaneous circulation (ROSC) (RR 1.32, 95% CI 1.18-1.47, moderate certainty) and may increase the likelihood of survival with good functional outcome (RR 1.49, 95% CI 0.87-2.54, low certainty). Corticosteroids may decrease the risk of ventilator associated pneumonia (RR 0.76, 95% CI 0.46-1.09, low certainty), may increase renal failure (RR 1.29, 95% CI 0.84-1.99, low certainty), and have an uncertain effect on bleeding (RR 2.04, 95% CI 0.53-7.84, very low certainty) and peritonitis (RR 10.54, 95% CI 2.99-37.19, very low certainty). CONCLUSIONS: In patients during or after cardiac arrest, corticosteroids have an uncertain effect on mortality but probably increase ROSC and may increase the likelihood of survival with good functional outcome at hospital discharge. Corticosteroids may decrease ventilator associated pneumonia, may increase renal failure, and have an uncertain effect on bleeding and peritonitis. However, the pooled evidence examining these outcomes was sparse and imprecision contributed to low or very low certainty of evidence.

Intraoperative use of balanced crystalloids versus 0.9% saline: a systematic review and meta-analysis of randomised controlled studies.

BACKGROUND: The evidence regarding optimal crystalloid use in the perioperative period remains unclear. As the primary aim of this study, we sought to summarise the data from RCTs examining whether use of balanced crystalloids compared with 0.9% saline (saline) leads to differences in patient-important outcomes. METHODS: We searched Ovid MEDLINE, Embase, the Cochrane library, and Clinicaltrials.gov, from inception until December 15, 2022, and included RCTs that intraoperatively randomised adult participants to receive either balanced fluids or saline. We pooled data using a random-effects model and present risk ratios (RRs) or mean differences (MDs), along with 95% confidence intervals (CIs). We assessed individual study risk of bias using the modified Cochrane tool, and certainty of evidence using GRADE. RESULTS: Of 5959 citations, we included 38 RCTs (n=3776 patients). Pooled analysis showed that intraoperative use of balanced fluids compared with saline had an uncertain effect on postoperative mortality analysed at the longest point of follow-up (RR 1.51, 95% CI: 0.42-5.36) and postoperative need for renal replacement therapy (RR 0.95, 95% CI: 0.56-1.59), both very low certainty. Furthermore, use of balanced crystalloids probably leads to a higher postoperative serum pH (MD 0.05, 95% CI: 0.04-0.06), moderate certainty. CONCLUSIONS: Use of balanced crystalloids, compared with saline, in the perioperative setting has an uncertain effect on mortality and need for renal replacement therapy but probably improves postoperative acid-base status. Further research is needed to determine whether balanced crystalloid use affects patient-important outcomes. CLINICAL TRIAL REGISTRATION: CRD42022367593.

Efficacy and Safety of Low Molecular Weight Heparin Versus Unfractionated Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-analysis.

PURPOSE: Trauma patients are at high risk of VTE. We summarize the efficacy and safety of LMWH versus UFH for the prevention of VTE in trauma patients. METHODS: We searched 6 databases from inception through March 12, 2021. We included randomized controlled trials (RCTs) or observational studies comparing LMWH versus UFH for thromboprophylaxis in adult trauma patients. We pooled effect estimates across RCTs and observational studies separately, using random-effects model and inverse variance weighting. We assessed risk of bias using the Cochrane tool for RCTs and the Risk of Bias in Non-Randomized Studies (ROBINS)-I tool for observational studies and assessed certainty of findings using Grading of Recommendations, Assessment, Development and Evaluations methodology. RESULTS: We included 4 RCTs (879 patients) and 8 observational studies (306,747 patients). Based on pooled RCT data, compared to UFH, LMWH reduces deep vein thrombosis (RR 0.67, 95% CI 0.50 to 0.88, moderate certainty) and VTE (RR 0.68, 95% CI 0.51 to 0.90, moderate certainty). As compared to UFH, LMWH may reduce pulmonary embolism [adjusted odds ratio from pooled observational studies 0.56 (95% CI 0.50 to 0.62)] and mortality (adjusted odds ratio from pooled observational studies 0.54, 95% CI 0.45 to 0.65), though based on low certainty evidence. There was an uncertain effect on adverse events (RR from pooled RCTs 0.80, 95% CI 0.48 to 1.33, very low certainty) and heparin induced thrombocytopenia [RR from pooled RCTs 0.26 (95% CI 0.03 to 2.38, very low certainty)]. CONCLUSIONS: Among adult trauma patients, LMWH is superior to UFH for deep vein thrombosis and VTE prevention and may additionally reduce pulmonary embolism and mortality. The impact on adverse events and heparin induced thrombocytopenia is uncertain.

Prognostic factors for development of acute respiratory distress syndrome following traumatic injury: a systematic review and meta-analysis.

BACKGROUND: Our purpose was to summarise the prognostic associations between various clinical risk factors and development of acute respiratory distress syndrome (ARDS) following traumatic injury. METHODS: We conducted this review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) guidelines. We searched six databases from inception through December 2020. We included English language studies describing the clinical risk factors associated with development of post-traumatic ARDS, as defined by either the American-European Consensus Conference or Berlin definition. We pooled adjusted odds ratios for prognostic factors using the random effects method. We assessed risk of bias using the QUIPS (Quality in Prognosis Studies) tool and certainty of findings using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. RESULTS: We included 39 studies involving 5 350 927 patients. We identified the amount of crystalloid resuscitation as a potentially modifiable prognostic factor associated with development of post-traumatic ARDS (adjusted OR 1.19, 95% CI 1.15-1.24 for each additional litre of crystalloid administered within the first 6 h after injury; high certainty). Non-modifiable prognostic factors with a moderate or high certainty of association with post-traumatic ARDS included increasing age, non-Hispanic White race, blunt mechanism of injury, presence of head injury, pulmonary contusion or rib fracture and increasing chest injury severity. CONCLUSIONS: We identified one important modifiable factor, the amount of crystalloid resuscitation within the first 24 h of injury, and several non-modifiable factors associated with development of post-traumatic ARDS. This information should support the judicious use of crystalloid resuscitation in trauma patients and may inform development of risk stratification tools.

Transcatheter mitral valve repair for inotrope dependent cardiogenic shock - Design and rationale of the CAPITAL MINOS trial.

BACKGROUND: Functional mitral regurgitation (MR) is an important clinical consideration in patients with heart failure. Transcatheter edge-to-edge repair (TEER) has emerged as a useful therapeutic tool for patients with chronic heart failure, however the role of TEER in patients with cardiogenic shock (CS) and MR has not yet been studied in a randomized trial. The Transcatheter Mitral Valve Repair for Inotrope Dependent Cardiogenic Shock (CAPITAL MINOS) trial was therefore designed to determine if TEER improves clinical outcomes in the CS population. METHODS AND DESIGN: The CAPITAL MINOS trial is an open-label, multi-center randomized clinical trial comparing TEER to medical therapy in patients with CS and MR. A total of 144 patients with Society for Cardiovascular Angiography and Interventions (SCAI) class C or D CS and at least 3+ MR will be randomized in a 1:1 ratio to TEER or medical therapy alone. The primary outcome will be a composite of in-hospital all-cause mortality, cardiac transplantation, implantation of durable left ventricular assist device, or discharge on palliative inotropic therapy. Patients will be followed for the duration of their index hospitalization for the primary outcome. Secondary outcomes include 6 month mortality. IMPLICATIONS: The CAPITAL MINOS trial will determine whether TEER improves outcomes in patients with CS and MR and will be an important step in optimizing treatment for this high-risk patient population.

Prognostic Factors Associated With Development of Venous Thromboembolism in Critically Ill Patients-A Systematic Review and Meta-Analysis.

OBJECTIVE: To identify prognostic factors for the development of venous thromboembolism in the ICU. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to March 1, 2021. STUDY SELECTION: We included English-language studies describing prognostic factors associated with the development of venous thromboembolism among critically ill patients. DATA EXTRACTION: Two authors performed data extraction and risk-of-bias assessment. We pooled adjusted odds ratios and adjusted hazard ratios for prognostic factors using random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. DATA SYNTHESIS: We included 39 observational cohort studies involving 729,477 patients. Patient factors with high or moderate certainty of association with increased odds of venous thromboembolism include older age (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29 per 10 yr), obesity (adjusted odds ratio, 1.25; 95% CI, 1.18-1.32), active malignancy (adjusted odds ratio, 1.70; 95% CI, 1.18-2.44), history of venous thromboembolism (adjusted odds ratio, 4.77; 95% CI, 3.42-6.65), and history of recent surgery (adjusted odds ratio, 1.77; 95% CI, 1.26-2.47). ICU-specific factors with high or moderate certainty of association with increased risk of venous thromboembolism include sepsis (adjusted odds ratio, 1.41; 95% CI, 1.12-1.78), lack of pharmacologic venous thromboembolism prophylaxis (adjusted odds ratio, 1.80; 95% CI, 1.14-2.84), central venous catheter (adjusted odds ratio, 2.93; 95% CI, 1.98-4.34), invasive mechanical ventilation (adjusted odds ratio, 1.74; 95% CI, 1.36-2.24), and use of vasoactive medication (adjusted odds ratio, 1.86; 95% CI, 1.23-2.81). CONCLUSIONS: This meta-analysis provides quantitative summaries of the association between patient-specific and ICU-related prognostic factors and the risk of venous thromboembolism in the ICU. These findings provide the foundation for the development of a venous thromboembolism risk stratification tool for critically ill patients.

Mechanical circulatory support in the treatment of cardiogenic shock.

PURPOSE OF REVIEW: Cardiogenic shock is a condition that is characterized by end-organ hypoperfusion secondary to reduced cardiac output, and is associated with substantial mortality. The mainstay of therapy for cardiogenic shock is reversal of the underlying cause, and concomitant supportive care with vasoactive medications (vasopressors and inotropes). Patients who continue to deteriorate despite these measures may require mechanical circulatory support (MCS). Here, we review the devices available for MCS, and their associated benefits and risks. RECENT FINDINGS: Despite growing use worldwide, there is little randomized evidence supporting the routine use of any specific device for MCS in cardiogenic shock. A large randomized trial of the intra-aortic balloon pump did not demonstrate short- or long-term improvement in mortality. The TandemHeart and Impella devices which assist in left ventricular unloading have only been evaluated in small randomized trials, which showed an increase in adverse events without improvement in mortality. Finally, venoarterial extracorporeal membrane oxygenation (provides both circulatory and respiratory support) and is currently being evaluated in large randomized clinical trials. SUMMARY: Various devices for MCS in cardiogenic shock are available, but routine use is not supported by high-quality randomized evidence. Given the resources required for initiation of MCS, use of these treatments should be limited to centers experienced in advanced cardiac care, and future research should focus on what role (if any) these devices have in clinical practice.

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used extensively for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Reports early in the pandemic suggested that mortality in patients with COVID-19 receiving ECMO was comparable to non-COVID-19-related ARDS. However, subsequent reports suggested that mortality appeared to be increasing over time. Therefore, we conducted an updated systematic review and meta-analysis, to characterise changes in mortality over time and elucidate risk factors for poor outcomes. METHODS: We conducted a meta-analysis (CRD42021271202), searching MEDLINE, Embase, Cochrane, and Scopus databases, from 1 December 2019 to 26 January 2022, for studies reporting on mortality among adults with COVID-19 receiving ECMO. We also captured hospital and intensive care unit lengths of stay, duration of mechanical ventilation and ECMO, as well as complications of ECMO. We conducted random-effects meta-analyses, assessed risk of bias of included studies using the Joanna Briggs Institute checklist and evaluated certainty of pooled estimates using GRADE methodology. RESULTS: Of 4522 citations, we included 52 studies comprising 18,211 patients in the meta-analysis. The pooled mortality rate among patients with COVID-19 requiring ECMO was 48.8% (95% confidence interval 44.8-52.9%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 41.2%, 2nd half 2020: 46.4%, 1st half 2021: 62.0%, 2nd half 2021: 46.5%, interaction p value = 0.0014). Predictors of increased mortality included age, the time of final patient enrolment from 1 January 2020, and the proportion of patients receiving corticosteroids, and reduced duration of ECMO run. CONCLUSIONS: The mortality rate for patients receiving ECMO for COVID-19-related ARDS has increased as the pandemic has progressed. The reasons for this are likely multifactorial; however, as outcomes for these patients evolve, the decision to initiate ECMO should include the best contextual estimate of mortality at the time of ECMO initiation.

Increased Mortality and Costs Associated with Adverse Events in Intensive Care Unit Patients.

Background: Adverse events (AEs) are defined as unintended complications occurring to patients as a result of medical care. AEs are especially prevalent in the intensive care unit (ICU) setting and may lead to negative patient outcomes. Although many studies have examined the impact of AEs on patient outcomes, few have investigated their associated costs. Methods: The study population consisted of 17 173 adult patients (≥18 years of age) who were admitted to the ICU at The Ottawa Hospital (TOH) between 2011 and 2016. AEs were categorized using an established International Classification of Diseases 10th revision (ICD-10) patient safety indicators (PSI) system for AE detection. Logistic regression was performed to determine the association between AEs and in-hospital outcomes, including mortality. In addition, we constructed a generalized linear model to assess the independent association between AEs and total hospital costs. Results: Patients who experienced an AE had longer total hospital and ICU lengths of stay, required more invasive ICU interventions, had more complex discharge plans, and experienced higher rates of in-hospital mortality compared to those who did not experience an AE. Average total hospital costs and ICU-specific costs were higher among patients who experienced an AE ($72 718; $46 715) relative to their counterparts ($20 543; $16 217), but the per day cost was comparable in both groups. After controlling for age, sex, patient comorbidities, and illness severity, AEs were significantly associated with an increased odds of mortality (OR = 1.13, 95% CIs = 1.04, 1.22) and total average costs (Cost Ratio = 1.04, 95% CIs = 1.06, 1.08). The most impactful AE subtypes from a cost- and patient-perspective were hospital-acquired infections (HAI) and cardiac-related AEs. Conclusion: Incidence of AEs among ICU patients is associated with higher patient mortality and elevated costs. Specific causes of these AEs should be investigated, with further protocols and interventions developed to reduce their occurrence.

Development and evaluation of an evidence-based, theory-grounded online Clinical Frailty Scale tutorial.

INTRODUCTION: Frailty is a robust predictor of adverse outcomes in older people. Practice guidelines recommend routine screening for frailty; however, this does not occur regularly. The Clinical Frailty Scale (CFS) is a validated, feasible instrument that can be used in a variety of clinical settings and is associated with many adverse outcomes. Our objective was to develop and evaluate an online training module to guide frailty assessment using the CFS. METHODS: A multidisciplinary team of clinical experts developed an evidence-based, theory-grounded online training module for users who wished to perform frailty assessment using the CFS. The module was prospectively evaluated for user satisfaction, effectiveness and feasibility using a standardised questionnaire. Qualitative feedback was analysed with thematic analysis. RESULTS: Version 1 of the CFS module was used 627 times from 21 October 2019 to 24 March 2020. Satisfaction, effectiveness and feasibility of the module were positively rated (≥4/5 on a 5-point Likert scale n = 582 [93%], n = 507, [81%], n = 575, [91%], respectively). Qualitative feedback highlighted ease of use, likelihood of users to share the module with others and opportunities to increase multimedia content. CONCLUSION: An online tutorial, designed using evidence and theory to guide frailty assessment using the CFS, was positively rated by users. The module's content and structure was rated effective and feasible, and users were satisfied with, and likely to share, the module. Research evaluating the module's impact on the accuracy of frailty assessment is required.

Inotropes, vasopressors, and mechanical circulatory support for treatment of cardiogenic shock complicating myocardial infarction: a systematic review and network meta-analysis.

PURPOSE: To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction. SOURCE: We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality. PRINCIPAL FINDINGS: We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis. CONCLUSION: The results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding. STUDY REGISTRATION: Center for Open Science ( https://osf.io/ky2gr ); registered 10 November 2020.

RéSUMé: OBJECTIF: Comparer l'efficacité relative des thérapies de soutien (inotropes, vasopresseurs et assistance circulatoire mécanique [ACM]) chez les patients adultes atteints d'un choc cardiogénique compliquant un infarctus aigu du myocarde. SOURCES: Nous avons réalisé une revue systématique et une méta-analyse en réseau et effectué des recherches dans six bases de données depuis leur création jusqu'à décembre 2021 pour en tirer les études randomisées contrôlées (ERC). Nous avons évalué les inotropes, les vasopresseurs et les ACM dans des réseaux distincts. Deux réviseurs ont effectué la recherche, l'évaluation du texte intégral et l'extraction. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des résultats. Le critère d'évaluation d'intérêt était la mortalité toutes causes confondues à 30 jours. CONSTATATIONS PRINCIPALES: Nous avons inclus 17 ERC. Parmi les inotropes (sept ERC, 1145 patients), le lévosimendan a probablement réduit la mortalité par rapport au placebo (rapport de cotes [RC], 0,53; intervalle de confiance [IC] à 95 %, 0,33 à 0,87; certitude modérée), mais principalement en cas de choc de sévérité moindre. La milrinone (RC, 0,52; IC 95 %, 0,19 à 1,39; certitude faible) et la dobutamine (RC, 0,67, IC 95 %, 0,30 à 1,49; certitude faible) pourraient n'avoir aucun effet sur la mortalité par rapport au placebo. En ce qui concerne l'ACM (huit ERC, 856 patients), il pourrait n'y avoir aucun effet sur la mortalité avec un ballon intra-aortique (IABP) (RC, 0,94; IC 95 %, 0,69 à 1,28; certitude faible) ou un ACM percutané (ACMp) (RC, 0,96; IC 95 %, 0,47 à 1,98; certitude faible), par rapport à une stratégie sans ACM. L'utilisation d'un ballon intra-aortique était associée à moins de saignements majeurs par rapport à une ACMp. Nous n'avons trouvé que deux ERC évaluant les vasopresseurs, ce qui n'a pas fourni suffisamment de données pour la méta-analyse. CONCLUSION: Les résultats de cette revue systématique et de la méta-analyse en réseau indiquent que le lévosimendan réduit la mortalité par rapport au placebo chez les patients présentant un choc cardiogénique de faible gravité. Le ballon intra-aortique et l'ACMp n'ont eu aucun effet sur la mortalité par rapport à une stratégie sans ACM, mais l'ACMp était associée à des taux plus élevés de saignements majeurs. ENREGISTREMENT DE L'éTUDE: Center for Open Science ( https://osf.io/ky2gr ); enregistrée le 10 novembre 2020.

In COVID-19, tocilizumab reduces all-cause mortality at 28 d.

SOURCE CITATION: Ghosn L, Chaimani A, Evrenoglou T, et al. Interleukin-6 blocking agents for treating COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021;3:CD013881. 33734435.

Association of Extracorporeal Membrane Oxygenation With New Mental Health Diagnoses in Adult Survivors of Critical Illness.

Importance: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in critically ill patients, but little is known regarding long-term psychiatric sequelae among survivors after ECMO. Objective: To investigate the association between ECMO survivorship and postdischarge mental health diagnoses among adult survivors of critical illness. Design, Setting, and Participants: Population-based retrospective cohort study in Ontario, Canada, from April 1, 2010, through March 31, 2020. Adult patients (N=4462; age ≥18 years) admitted to the intensive care unit (ICU), and surviving to hospital discharge were included. Exposures: Receipt of ECMO. Main Outcomes and Measures: The primary outcome was a new mental health diagnosis (a composite of mood disorders, anxiety disorders, posttraumatic stress disorder; schizophrenia, other psychotic disorders; other mental health disorders; and social problems) following discharge. There were 8 secondary outcomes including incidence of substance misuse, deliberate self-harm, death by suicide, and individual components of the composite primary outcome. Patients were compared with ICU survivors not receiving ECMO using overlap propensity score-weighted cause-specific proportional hazard models. Results: Among 642 survivors who received ECMO (mean age, 50.7 years; 40.7% female), median length of follow-up was 730 days; among 3820 matched ICU survivors who did not receive ECMO (mean age, 51.0 years; 40.0% female), median length of follow-up was 1390 days. Incidence of new mental health conditions among survivors who received ECMO was 22.1 per 100-person years (95% confidence interval [CI] 19.5-25.1), and 14.5 per 100-person years (95% CI, 13.8-15.2) among non-ECMO ICU survivors (absolute rate difference of 7.6 per 100-person years [95% CI, 4.7-10.5]). Following propensity weighting, ECMO survivorship was significantly associated with an increased risk of new mental health diagnosis (hazard ratio [HR] 1.24 [95% CI, 1.01-1.52]). There were no significant differences between survivors who received ECMO vs ICU survivors who did not receive ECMO in substance misuse (1.6 [95% CI, 1.1 to 2.4] per 100 person-years vs 1.4 [95% CI, 1.2 to 1.6] per 100 person-years; absolute rate difference, 0.2 per 100 person-years [95% CI, -0.4 to 0.8]; HR, 0.86 [95% CI, 0.48 to 1.53]) or deliberate self-harm (0.4 [95% CI, 0.2 to 0.9] per 100 person-years vs 0.3 [95% CI, 0.2 to 0.3] per 100 person-years; absolute rate difference, 0.1 per 100 person-years [95% CI, -0.2 to 0.4]; HR, 0.68 [95% CI, 0.21 to 2.23]). There were fewer than 5 total cases of death by suicide in the entire cohort. Conclusions and Relevance: Among adult survivors of critical illness, receipt of ECMO, compared with ICU hospitalization without ECMO, was significantly associated with a modestly increased risk of new mental health diagnosis or social problem diagnosis after discharge. Further research is necessary to elucidate the potential mechanisms underlying this relationship.

Intracerebral Hemorrhage Incidence, Mortality, and Association With Oral Anticoagulation Use: A Population Study.

BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke associated with significant morbidity and mortality. Recent epidemiological data on incidence, mortality, and association with oral anticoagulation are needed. METHODS: Retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (April 1, 2009-March 30, 2019). We captured outcome data using linked health administrative databases. The primary outcome was mortality during hospitalization, as well as at 1 year following ICH. RESULTS: We included 20 738 patients with ICH. Mean (SD) age was 71.3 (15.1) years, and 52.6% of patients were male. Overall incidence of ICH throughout the study period was 19.1/100 000 person-years and did not markedly change over the study period. In-hospital and 1-year mortality were high (32.4% and 45.4%, respectively). Mortality at 2 years was 49.5%. Only 14.5% of patients were discharged home independently. Over the study period, both in-hospital and 1-year mortality reduced by 10.4% (37.5% to 27.1%, P<0.001) and 7.6% (50.0% to 42.4%, P<0.001), respectively. Use of oral anticoagulation was associated with both in-hospital mortality (adjusted odds ratio 1.37 [95% CI, 1.26-1.49]) and 1-year mortality (hazard ratio, 1.18 [95% CI, 1.12-1.25]) following ICH. CONCLUSIONS: Both short- and long-term mortality have decreased in the past decade. Most survivors from ICH are likely to be discharged to long-term care. Oral anticoagulation is associated with both short- and long-term mortality following ICH. These findings highlight the devastating nature of ICH, but also identify significant improvement in outcomes over time.