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.).

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.

Black representation in critical care randomized controlled trials: a meta-epidemiological study.

PURPOSE: The under-representation of Black people within critical care research limits the generalizability of randomized controlled trials (RCTs). This meta-epidemiologic study investigated the proportionate representation of Black people enrolled at USA and Canadian study sites from high impact critical care RCTs. SOURCE: We searched for critical care RCTs published in general medicine and intensive care unit (ICU) journals between 1 January 2016 and 31 December 2020. We included RCTs that enrolled critically ill adults at USA or Canadian sites and provided race-based demographic data by study site. We compared study-based racial demographics with site-level city-based demographics and pooled representation of Black people across studies, cities, and centres using a random effects model. We used meta-regression to explore the impact of the following variables on Black representation in critical care RCTs: country, drug intervention, consent model, number of centres, funding, study site city, and year of publication. PRINCIPAL FINDINGS: We included 21 eligible RCTs. Of these, 17 enrolled at only USA sites, two at only Canadian sites, and two at both USA and Canadian sites. Black people were under-represented in critical care RCTs by 6% compared with population-based city demographics (95% confidence interval, 1 to 11). Using meta-regression, after controlling for pertinent variables, the country of the study site was the only significant source of heterogeneity (P = 0.02). CONCLUSION: Black people are under-represented in critical care RCTs compared with site-level city-based demographics. Interventions are required to ensure adequate Black representation in critical care RCTs at both USA and Canadian study sites. Further research is needed to investigate the factors contributing to Black under-representation in critical care RCTs.

RéSUMé: OBJECTIF: La sous-représentation des personnes noires dans la recherche en soins intensifs limite la généralisabilité des études randomisées contrôlées (ERC). Cette étude méta-épidémiologique a examiné la représentation proportionnelle des personnes noires inscrites aux sites américains et canadiens d'ERC à fort impact réalisées en soins intensifs. SOURCES: Nous avons recherché des ERC en soins intensifs publiées dans des revues de médecine générale et de soins intensifs (USI) entre le 1er janvier 2016 et le 31 décembre 2020. Nous avons inclus des ERC qui ont recruté des adultes gravement malades dans des sites américains ou canadiens et fourni des données démographiques basées sur la race par site d'étude. Nous avons comparé les données démographiques raciales de chaque étude aux données démographiques de la ville du site d'étude et regroupé la représentation des personnes noires dans les études, les villes et les centres en utilisant un modèle à effets aléatoires. Nous avons utilisé la méta-régression pour explorer l'impact des variables suivantes sur la représentation des personnes noires dans les ERC en soins intensifs : pays, intervention médicamenteuse, modèle de consentement, nombre de centres, financement, ville du site d'étude et année de publication. CONSTATATIONS PRINCIPALES: Nous avons inclus 21 ERC éligibles. De ce nombre, 17 ont recruté des patient·es uniquement dans des sites américains, deux dans des sites canadiens seulement et deux aux États-Unis et au Canada. Les personnes noires étaient sous-représentées dans les ERC en soins intensifs de 6 % par rapport à la population démographique des villes (intervalle de confiance à 95 %, 1 à 11). En utilisant la méta-régression, après avoir tenu compte des variables pertinentes, le pays du site d'étude était la seule source significative d'hétérogénéité (P = 0,02). CONCLUSION: Les personnes noires sont sous-représentées dans les ERC en soins intensifs par rapport aux données démographiques des villes. Des interventions sont nécessaires pour assurer une représentation adéquate des personnes noires dans les ERC en soins intensifs dans les sites d'étude américains et canadiens. D'autres recherches sont nécessaires pour étudier les facteurs contribuant à la sous-représentation des personnes noires dans les ERC en soins intensifs.

Association of age with death and withdrawal of life-sustaining therapy after severe traumatic brain injury.

BACKGROUND: Compared to younger age, older age (≥ 65 yr) is associated with worse outcomes after severe traumatic brain injury (TBI). We sought to describe the association of older age with in-hospital death and aggressiveness of intervention. METHODS: We conducted a retrospective cohort study of adult (age ≥ 16 yr) patients with severe TBI admitted to a single academic tertiary care neurotrauma centre between January 2014 and December 2015. We collected data through chart review as well as from our institutional administrative database. We provided descriptive statistics and used multivariable logistic regression to evaluate the independent association of age with the primary outcome, in-hospital death. The secondary outcome was early withdrawal of life-sustaining therapy. RESULTS: There were 126 adult patients (median age 67 yr [Q1-Q3, 33-80 yr]) with severe TBI during the study period who met our eligibility criteria. The most common mechanism was high-velocity blunt injury (55 patients [43.6%]). The median Marshall score was 4 (Q1-Q3, 2-6), and the median Injury Severity Score was 26 (Q1-Q3, 25-35). After controlling for confounders including clinical frailty, pre-existing comorbidity, injury severity, Marshall score and neurologic examination at admission, we observed that older patients were more likely than younger patients to die in hospital (odds ratio 5.10, 95% confidence interval 1.65-15.78). Older patients were also more likely to experience early withdrawal of life-sustaining therapy and less likely to receive invasive interventions. CONCLUSION: After controlling for confounding factors relevant to older patients, we observed that age was an important and independent predictor of in-hospital death and early withdrawal of life-sustaining therapy. The mechanism by which age influences clinical decision-making independent of global and neurologic injury severity, clinical frailty and comorbidities remains unclear.

The role of low-carbohydrate diets in the intensive care unit.

Low-carbohydrate, high-fat (LCHF) nutrition therapy is characterized by carbohydrates comprising <26% of the daily caloric intake and a higher proportion of fat. LCHF therapies reduce exogenous glucose load, improve glycemic control, decrease inflammation, and improve clinical outcomes such as respiratory function. Given the altered metabolism in critically ill patients, LCHF nutrition therapy may be especially beneficial as it enables the conservation of protein and glucose for metabolic roles beyond energy use. In critical illness, LCHF diets have the potential to reduce hyperglycemia, improve ventilation, decrease hospital length of stay and reduce hospital costs. The purpose of this commentary piece is to describe LCHF nutrition therapy, summarize its impact on health outcomes, and discuss its role in the intensive care unit (ICU). Additional research on the effects of LCHF nutrition therapy on critically ill patients is warranted, including a focus on COVID-19.

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.

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.

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.

Virtual home-based palliative care during COVID-19: A qualitative exploration of the patient, caregiver, and healthcare provider experience.

BACKGROUND: Due to the COVID-19 pandemic, many community palliative healthcare providers shifted from providing care in a patient's home to providing almost exclusively virtual palliative care, or a combination of in-person and virtual care. Research on virtual palliative care is thus needed to provide evidence-based recommendations aiming to enhance the delivery of palliative care during and beyond the pandemic. AIM: To explore the experiences and perceptions of community palliative care providers, patients and caregivers who delivered or received virtual palliative care as a component of home-based palliative care during the COVID-19 pandemic. DESIGN: Qualitative study using phone and video-based semi-structured interviews. Data were analyzed using thematic analysis. SETTING/PARTICIPANTS: A total of 37 participants, including community palliative care patients/caregivers (n = 19) and healthcare providers (n = 18) recruited from sites in Ottawa and Toronto, Ontario, Canada. RESULTS: Overall, participants preferred in-person palliative care compared to virtual care, but suggested virtual care could be a useful supplement to in-person care. The findings are presented in three main themes: (1) Impact of COVID-19 pandemic on community palliative care services; (2) Factors influencing transition from exclusively virtual model of care back to a blended model of care; and (3) Recommended uses and implementation of virtual palliative care. CONCLUSIONS: Incorporating virtual palliative care into healthcare provider practice models (blended care models) may be the ideal model of care and standard practice moving forward beyond the COVID-19 pandemic, which has important implications toward organization and delivery of community palliative care services and funding of healthcare providers.

"Everything has been tried and his heart can't recover ": A Descriptive Review of "Do Everything!" in the Archive of Ontario Consent and Capacity Board.

BACKGROUND: In end-of-life situations, the phrase "do everything" is sometimes invoked by physicians, patients, or substitute decision-makers (SDM), though its meaning is ambiguous. We examined instances of the phrase "do everything" in the archive of the Ontario Consent and Capacity Board (CCB) in Canada, a tribunal with judicial authority to adjudicate physician-patient conflicts in order to explore its potential meanings. METHODS: We systematically searched the CCB's online public archive from its inception to 2018 for any references to "do everything" in the context of critical care medicine and end-of-life care. Two independent assessors reviewed decisions, collected characteristics, and identified key themes. RESULTS: Of 598 cases in the archive, 41 referred to "do everything" in end-of-life situations. The phrase was overwhelmingly invoked by SDMs (38/41, 93%), typically to advocate for life-prolonging measures that contradicted physician advice. Physicians generally related "doing everything" to describe the interventions they had already performed (3/41, 7%), using it to recommend focusing on patients' quality of life. SDMs were generally reluctant to accept death, whereas physicians found prolonging life at all costs to be morally distressing. The CCB did not interpret appeals to "do everything" legally but followed existing laws by deferring to patients' prior wishes whenever known, or to concepts of "best interests" when not. The CCB generally recommended against life-prolonging measures in these cases (26/41, 63%), focusing on patients' "well-being" and "best interests." CONCLUSIONS: In this unique sample of cases involving conflict surrounding resuscitation and end-of-life care, references to "do everything" highlighted conflicts over quantity versus quality of life. These appeals were associated with signs of cognitive distress on the behalf of SDMs who were facing the prospect of a patient's death, whereas physicians identified moral distress related to the prolongation of patients' suffering through their use of life-sustaining interventions. This divergence in perspectives on death versus suffering was consistently the locus of conflict. These findings support the importance of tools such as the Serious Illness Conversation Guide that can be used by physicians to direct conversations on the patients' goals, wishes, trade-offs, and to recommend a treatment plan that may include palliative care. TRIAL REGISTRATION: Not applicable.

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.

Can Early Warning Systems Enhance Detection of High Risk Patients by Rapid Response Teams?

PURPOSE: We sought to evaluate if incorporating an early warning system (EWS), the Visensia Safety Index (VSI) and the National Early Warning Systems 2 (NEWS2), may lead to earlier identification of rapid response team (RRT) patients. METHODS: This was a retrospective study (2015-2018) of patients experiencing RRT activation within a tertiary care network. We evaluated the proportion of patients with an EWS alert prior to RRT activation and their associated outcomes (primary: hospital mortality). RESULTS: There were 6,346 RRT activations over the study period. Of these, 2042 (50.8%) patients would have had a VSI alert prior to RRT activation, with a median advanced time of 3.6 (IQR 0.5-12.8) hours, compared to 2351 (58.4%) patients and 9.8 (IQR 2.0-18.7) hours for NEWS2. Patients with a potential alert prior to RRT activation had an increased odds of mortality for both VSI (OR 1.2, 95%CI 1.1-1.3) and NEWS2 (OR 2.7, 95% CI 2.4-3.1). Prognostic accuracy for hospital mortality was similar between groups. CONCLUSION: Utilization of an EWS by an RRT has potential to provide earlier recognition of deterioration and mortality risk among hospitalized inpatients.

Costs and Outcomes of Patients Admitted to the Intensive Care Unit With Cancer.

INTRODUCTION: Cancer is associated with significant health-care expenditure, but few studies have examined the cost of patients with cancer in the intensive care unit (ICU). We aimed to describe the costs and outcomes of patients admitted to the ICU with cancer. METHODS: We conducted a retrospective cohort study of patients admitted between 2011 and 2016 to 2 tertiary-care ICUs. We included patients with a cancer-related most responsible diagnosis using International Classification of Disease, 10th Revision, Canada codes. We compared costs and outcomes of patients having cancer with noncancer controls matched for age, sex, and Elixhauser comorbidity score. We used logistic regression to determine predictors of mortality among patients with cancer. RESULTS: There were 1022 patients with cancer during the study period. Mean age was 63.2 years and 577 (56.5%) were male. Inhospital mortality for all patients with cancer was 24.0%. Total cost per patient was higher for patients with cancer compared to noncancer patients (CAD$57 084 vs CAD$40 730; P < .001) but there were no differences in the cost per day (CAD$2868 vs CAD$2887; P = .76) or ICU cost (CAD$30 495 vs CAD$29 382; P = .42). Among patients with cancer, the cost per day was higher for nonsurvivors (CAD$3477 vs CAD$2677; P < .001). Liver disease (odds ratio [OR]: 2.96; 95% confidence interval [CI]: 1.22-7.81), mechanical ventilation (OR: 1.73; 95% CI: 1.25-2.39), hematologic malignancy (OR: 3.88; 95% CI: 2.31-6.54), and unknown primary site (OR: 2.13; 95% CI: 1.36-3.35) were independently associated with mortality in patients with cancer. CONCLUSION: Patients admitted to the ICU with cancer did not differ in cost per day, ICU cost, or mortality compared to matched noncancer controls. Among patients with cancer, nonsurvivors had significantly higher cost per day compared to survivors. Hematologic and unknown primaries, liver disease, and mechanical ventilation were independently associated with mortality in patients with cancer.

Frailty Is Associated With Decreased Time Spent at Home After Critical Illness: A Population-Based Study.

BACKGROUND: Frailty is characterized by vulnerability to stressors due to an accumulation of multiple functional deficits. Frailty is increasingly recognized as a risk factor for accelerated functional decline, increasing dependency, and risk of mortality. The objective of this study was to examine the association of frailty, at the time of critical care admission, with days alive at home and health care costs post-discharge. METHODS: This retrospective cohort study used linked administrative data (2010-2016) in Ontario, Canada. We identified all patients admitted at the intensive care unit (ICU), aged 19 years and above, assessed using the Resident Assessment Instrument for Home Care (RAI-HC), within 6 months prior to index hospitalization including an ICU stay. Patients were stratified as robust, pre-frail, or frail based on a validated Frailty Index. The primary outcome was days alive at home in the year after admission. Secondary outcomes included mortality, health care-associated costs, ICU interventions, long-term care admissions, and hospital readmissions. RESULTS: Frail patients spent significantly fewer days at home within 1 year of index hospitalization (mean 159 days vs 223 days in robust cohort, P < .001). Mortality was higher among frail patients at 1 year (59.6% in the frail cohort vs 45.9% in robust patients; odds ratio for death 1.59 [1.49-1.69]). Frail patients also had higher rates of long-term care admission within 1 year (30.1% vs 10.6% in robust patients). Total health care-associated costs per person alive were $30 450 higher the year after admission in the frail cohort. CONCLUSIONS: Frailty prior to ICU admission among patients who were eligible for RAI-HC assessment was associated with higher mortality and fewer days spent at home following admission. Frail patients had markedly higher rates of long-term care admission and increased costs per life saved following critical illness. These findings add to the discussion of risk-benefit trade-offs for ICU admission.

Preadmission Antiplatelet Use and Associated Outcomes and Costs Among ICU Patients With Intracranial Hemorrhage.

INTRODUCTION: Patients with intracranial hemorrhage (including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic hemorrhage) are commonly admitted to the intensive care unit (ICU). Although indications for oral antiplatelet agents are increasing, the impact of preadmission use on outcomes in patients with intracranial hemorrhage admitted to the ICU is unknown. We sought to evaluate the association between preadmission oral antiplatelet use, in-hospital mortality, resource utilization, and costs among ICU patients with intracranial hemorrhage. METHODS: We retrospectively analyzed a prospectively collected registry (2011-2016) and included consecutive adult patients from 2 hospitals admitted to ICU with intracranial hemorrhage. Patients were categorized on the basis of preadmission oral antiplatelet use. We excluded patients with preadmission anticoagulant use. The primary outcome was in-hospital mortality and was analyzed using a multivariable logistic regression model. Contributors to total hospital cost were analyzed using a generalized linear model with log link and gamma distribution. RESULTS: Of 720 included patients with intracranial hemorrhage, 107 (14.9%) had been using an oral antiplatelet agent at the time of ICU admission. Oral antiplatelet use was not associated with in-hospital mortality (adjusted odds ratio: 1.31 [95% confidence interval [CI]: 0.93-2.22]). Evaluation of total costs also revealed no association with oral antiplatelet use (adjusted ratio of means [aROM]: 0.92 [95% CI: 0.82-1.02, P = .10]). Total cost among patients with intracranial hemorrhage was driven by illness severity (aROM: 1.96 [95% CI: 1.94-1.98], P < .001), increasing ICU length of stay (aROM: 1.05 [95% CI: 1.05-1.06], P < .001), and use of invasive mechanical ventilation (aROM: 1.76 [95% CI: 1.68-1.86], P < .001). CONCLUSIONS: Among ICU patients admitted with intracranial hemorrhage, preadmission oral antiplatelet use was not associated with increased in-hospital mortality or hospital costs. These findings have important prognostic implications for clinicians who care for patients with intracranial hemorrhage.

Outcomes and Resource Utilization Among Patients Admitted to the Intensive Care Unit Following Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a common condition, accounting for a significant number of intensive care unit (ICU) admissions. However, little is known about outcomes and costs among ICU patients admitted with acute exacerbations of COPD (AECOPD). We studied predictors of inhospital mortality and costs of ICU admissions for AECOPD. METHODS: Data were obtained from a prospectively maintained registry from 2 ICUs from 2011 to 2016, including adult patients (age ≥ 18) with an ICU discharge diagnosis of AECOPD. The primary outcome was hospital mortality. Secondary outcomes included ICU length of stay, resource utilization, total hospital costs, and cost per survivor. RESULTS: We included 390 patients, of which 27.2% died in hospital. Independent predictors of inhospital mortality included age (odds ratio [OR]: 1.95, CI: 1.58-2.67) and the presence of clinical frailty (OR: 4.12, CI: 2.26-6.95). The mean total hospital costs were Can$35 059, with a cost per survivor of Can$48 191. Factors associated with increased cost included transfer from an inpatient setting, severity of illness, and previous ICU admission. CONCLUSIONS: Approximately a quarter of patients admitted to ICU with AECOPD died during hospitalization, and these patients accrued significant costs. This study identifies important factors associated with poor outcome in this at-risk population, which has value in risk stratification and patient or family discussions addressing goals of care.

Characteristics and resource utilization of high-cost users in the intensive care unit: a population-based cohort study.

BACKGROUND: Healthcare expenditure within the intensive care unit (ICU) is costly. A cost reduction strategy may be to target patients accounting for a disproportionate amount of healthcare spending, or high-cost users. This study aims to describe high-cost users in the ICU, including health outcomes and cost patterns. METHODS: We conducted a population-based retrospective cohort study of patients with ICU admissions in Ontario from 2011 to 2018. Patients with total healthcare costs in the year following ICU admission (including the admission itself) in the upper 10th percentile were defined as high-cost users. We compared characteristics and outcomes including length of stay, mortality, disposition, and costs between groups. RESULTS: Among 370,061 patients included, 37,006 were high-cost users. High-cost users were 64.2 years old, 58.3% male, and had more comorbidities (41.2% had ≥3) when likened to non-high cost users (66.1 years old, 57.2% male, 27.9% had ≥3 comorbidities). ICU length of stay was four times greater for high-cost users compared to non-high cost users (22.4 days, 95% confidence interval [CI] 22.0-22.7 days vs. 5.56 days, 95% CI 5.54-5.57 days). High-cost users had lower in-hospital mortality (10.0% vs.14.2%), but increased dispositioning outside of home (77.4% vs. 42.2%) compared to non-high-cost users. Total healthcare costs were five-fold higher for high-cost users ($238,231, 95% CI $237,020-$239,442) compared to non-high-cost users ($45,155, 95% CI $45,046-$45,264). High-cost users accounted for 37.0% of total healthcare costs. CONCLUSION: High-cost users have increased length of stay, lower in-hospital mortality, and higher total healthcare costs when compared to non-high-cost users. Further studies into cost patterns and predictors of high-cost users are necessary to identify methods of decreasing healthcare expenditure.