Critically Ill Older Adults' Representation in Intervention Trials: A Systematic Review.

OBJECTIVES: Older adults may be under-represented in critical care research, and results may not apply to this specific population. Our primary objective was to evaluate the prevalence of inclusion of older adults across critical care trials focused on common ICU conditions or interventions. Our secondary objective was to evaluate whether older age was used as a stratification variable for randomization or outcome analysis. DESIGN SETTING AND SUBJECTS: We performed a systematic review of previously published systematic reviews of randomized controlled trials (RCTs) in critical care. We searched PubMed, Ovid, CENTRAL, and Cochrane from 2009 to 2022. Systematic reviews of any interventions across five topics: acute respiratory distress syndrome (ARDS), sepsis/shock, nutrition, sedation, and mobilization were eligible. MAIN RESULTS: We identified 216 systematic reviews and included a total of 253 RCTs and 113,090 patients. We extracted baseline characteristics and the reported proportion of older adults. We assessed whether any upper age limit was an exclusion criterion for trials, whether age was used for stratification during randomization or data analysis, and if age-specific subgroup analysis was present. The most prevalent topic was sepsis (78 trials, 31%), followed by nutrition (62 trials, 25%), ARDS (39 trials, 15%), mobilization (38 trials, 15%), and sedation (36 trials, 14%). Eighteen trials (7%) had exclusion criteria based on older age. Age distribution with information on older adults prevalence was given in six trials (2%). Age was considered in the analysis of ten trials (5%) using analytic methods to evaluate the outcome stratified by age. Conclusions: In this systematic review, the proportion of older critically ill patients is undetermined, and it is unclear how age is or is not an effect modifier or to what extent the results are valid for older adult groups. Reporting age is important to guide clinicians in personalizing care. These results highlight the importance of incorporating older critically ill patients in future trials to ensure the results are generalizable to this growing population.

Incidence of venous thromboembolic disease and risk of bleeding in critically ill patients with hematologic malignancies: A retrospective study.

OBJECTIVE: Our objectives were to describe the use of thromboprophylaxis and the incidence of VTE/bleeding in critically ill patients with hematologic malignancies (HM). DESIGN: Retrospective cohort study (2014-2022). SETTING: Medic-Surgical Intensive Care Unit (ICU) in a tertiary care academic center. PATIENTS: Adult patients admitted to ICU with a concomitant diagnosis of a hematological malignancy. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We analyzed demographic data, use of thromboprophylaxis and secondary outcomes that included incidence of VTE (venous thromboembolism), bleeding, mortality, severity scores and organ support. We applied a multivariable logistic regression model to examine the risk of thrombosis in the ICU. RESULTS: We included 862 ICU admissions (813 unique patients). Thromboprophylaxis was given during 65% of admissions (LMWH 14%, UFH 8%, and SCDs 43%); in 21% it was contraindicated due to thrombocytopenia; 14% of cases lacked documentation on prophylaxis. There were 38 unique incident cases of VTE (27 DVT, 11 PE), constituting 4.4% of ICU episodes. Most of VTE cases happened in patients with various degrees of thrombocytopenia. In the multivariable analysis, SOFA score on the first ICU day was independently associated (OR 0.85, 95% CI 0.76-0.96) with the risk of VTE. Bleeding occurred in 7.2% (minor) and 14.4% (major) of episodes; most frequent sites being CNS, abdomen/GI and pulmonary. CONCLUSIONS: In this cohort of critically ill patients with HM, there was considerable variability in the utilization of DVT prophylaxis, with predominant use of SCDs. The incidence of VTE was 4.4% and major bleeding 14%. CLINICAL TRIAL REGISTRATION: NCT05396157. Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study (https://clinicaltrials.gov/).

Association between arterial oxygen and mortality across critically ill patients with hematologic malignancies: results from an international collaborative network.

PURPOSE: Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies. METHODS: Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality. RESULTS: 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]). CONCLUSION: In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

Age and associated outcomes among patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory failure: analysis of the Extracorporeal Life Support Organization registry.

PURPOSE: Venovenous extracorporeal membrane oxygenation (VV-ECMO) can be used to support patients with refractory acute respiratory failure, though guidance on patient selection is lacking. While age is commonly utilized as a factor in establishing the potential VV-ECMO candidacy of these patients, little is known regarding its association with outcome. We studied the association between increasing patient age and outcomes among patients with acute respiratory failure receiving VV-ECMO. METHODS: In this registry-based cohort study, we used individual patient data from 144 centres. We included adult patients (≥ 18 years of age) receiving VV-ECMO from 2017 to 2022. The primary outcome was hospital mortality. Secondary outcomes included a composite of complications following initiation of VV-ECMO. We conducted Bayesian analyses to estimate the association between chronological age and outcomes. RESULTS: We included 27,811 patients receiving VV-ECMO. Of these, 11,533 (41.5%) died in hospital. For the analysis conducted using weakly informed priors, and as compared to the reference category of age 18-29, the age brackets of 30-39 (odds ratio [OR] 1.17, 95% credible interval [CrI] 1.06-1.31), 40-49 (OR 1.65, 95% CrI 1.49-1.82), 50-59 (OR 2.39, 95% CrI 2.16-2.61), 60-69 (OR 3.29, 95% CrI 2.97-3.67), 70-79 (OR 4.57, 95% CrI 3.90-5.37), and ≥ 80 (OR 8.08, 95% CrI 4.85-13.74) were independently associated with increasing hospital mortality. Similar results were found between increasing age and post-ECMO complications. CONCLUSIONS: Among patients receiving VV-ECMO for acute respiratory failure, increasing age is significantly associated with poorer outcomes, and this association emerges as early as 30 years of age.

Venous thromboembolism in critically ill adult patients with hematologic malignancy: a population-based cohort study.

PURPOSE: The aim of this study was to describe the incidence of venous thromboembolism (VTE) and major bleeding among hospitalized patients with hematologic malignancy, assessing its association with critical illness and other baseline characteristics. METHODS: We conducted a population-based cohort study of hospitalized adults with a new diagnosis of hematologic malignancy in Ontario, Canada, between 2006 and 2017. The primary outcome was VTE (pulmonary embolism or deep venous thrombosis). Secondary outcomes were major bleeding and in-hospital mortality. We compared the incidence of VTE between intensive care unit (ICU) and non-ICU patients and described the association of other baseline characteristics and VTE. RESULTS: Among 76,803 eligible patients (mean age 67 years [standard deviation, SD, 15]), 20,524 had at least one ICU admission. The incidence of VTE was 3.7% in ICU patients compared to 1.2% in non-ICU patients (odds ratio [OR] 3.08; 95% confidence interval [CI] 2.77-3.42). The incidence of major bleeding was 7.6% and 2.4% (OR 3.33; 95% CI 3.09-3.58), respectively. The association of critical illness and VTE remained significant after adjusting for potential confounders (OR 2.92; 95% CI 2.62-3.25). We observed a higher incidence of VTE among specific subtypes of hematologic malignancy and patients with prior VTE (OR 6.64; 95% CI 5.42-8.14). Admission more than 1 year after diagnosis of hematologic malignancy (OR 0.64; 95% CI 0.56-0.74) and platelet count ≤ 50 × 109/L at the time of hospitalization (OR 0.63; 95% CI 0.48-0.84) were associated with a lower incidence of VTE. CONCLUSION: Among patients with hematologic malignancy, critical illness and certain baseline characteristics were associated with a higher incidence of VTE.

Ketamine sedation in the intensive care unit: a survey of Canadian intensivists.

PURPOSE: We sought to understand the beliefs and practices of Canadian intensivists regarding their use of ketamine as a sedative in critically ill patients and to gauge their interest in a randomized controlled trial (RCT) examining its use in the intensive care unit (ICU). METHODS: We designed and validated an electronic self-administered survey examining the use of ketamine as a sedative infusion for ICU patients. We surveyed 400 physician members of the Canadian Critical Care Society (CCCS) via email between February and April 2022 and sent three reminders at two-week intervals. The survey was redistributed in January 2023 to improve the response rate. RESULTS: We received 87/400 (22%) completed questionnaires. Most respondents reported they rarely use ketamine as a continuous infusion for sedation or analgesia in the ICU (52/87, 58%). Physicians reported the following conditions would make them more likely to use ketamine: asthma exacerbation (73/87, 82%), tolerance to opioids (68/87, 77%), status epilepticus (44/87, 50%), and severe acute respiratory distress syndrome (33/87, 38%). Concern for side-effects that limited respondents' use of ketamine include adverse psychotropic effects (61/87, 69%) and delirium (47/87, 53%). The majority of respondents agreed there is need for an RCT to evaluate ketamine as a sedative infusion in the ICU (62/87, 71%). CONCLUSION: This survey of Canadian intensivists illustrates that use of ketamine as a continuous infusion for sedation is limited, and is at least partly driven by concerns of adverse psychotropic effects. Canadian physicians endorse the need for a trial investigating the safety and efficacy of ketamine as a sedative for critically ill patients.

RéSUMé: OBJECTIF: Nous avons cherché à comprendre les croyances et les pratiques des intensivistes pratiquant au Canada concernant leur utilisation de la kétamine comme sédatif chez la patientèle gravement malade et à évaluer leur intérêt pour une étude randomisée contrôlée (ERC) examinant son utilisation à l'unité de soins intensifs (USI). MéTHODE: Nous avons mis au point et validé un sondage électronique auto-administré examinant l'utilisation de la kétamine comme perfusion sédative pour les patient·es aux soins intensifs. Nous avons envoyé le sondage à 400 médecins membres de la Société canadienne de soins intensifs (SCCC) par courriel entre février et avril 2022 et envoyé trois rappels à intervalles de deux semaines. Le sondage a été redistribué en janvier 2023 afin d'améliorer le taux de réponse. RéSULTATS: Nous avons reçu 87 questionnaires remplis sur 400 (22 %). La plupart des personnes répondantes ont déclaré qu'elles utilisaient rarement la kétamine en perfusion continue pour la sédation ou l'analgésie à l'USI (52/87, 58 %). Les médecins ont déclaré que les conditions suivantes les rendraient plus susceptibles d'utiliser de la kétamine : une exacerbation de l'asthme (73/87, 82 %), une tolérance aux opioïdes (68/87, 77 %), un état de mal épileptique (44/87, 50 %) et un syndrome de détresse respiratoire aigu (33/87, 38 %). Les inquiétudes quant aux effets secondaires qui ont limité l'utilisation de la kétamine par les répondant·es comprennent les effets psychotropes indésirables (61/87, 69 %) et le delirium (47/87, 53 %). La majorité des personnes répondantes étaient d'accord qu'une ERC est nécessaire pour évaluer la kétamine en tant que perfusion sédative à l'USI (62/87, 71 %). CONCLUSION: Cette enquête menée auprès d'intensivistes au Canada montre que l'utilisation de la kétamine comme perfusion continue pour la sédation est limitée, au moins en partie en raison d'inquiétudes liées aux effets psychotropes indésirables. Les médecins pratiquant au Canada reconnaissent la nécessité d'une étude sur l'innocuité et l'efficacité de la kétamine comme sédatif pour la patientèle gravement malade.

An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Age and associated outcomes among patients receiving venoarterial extracorporeal membrane oxygenation-analysis of the Extracorporeal Life Support Organization registry.

PURPOSE: Venoarterial extracorporeal membrane oxygenation (V-A ECMO) can be used to support severely ill patients with cardiogenic shock. While age is commonly used in patient selection, little is known regarding its association with outcomes in this population. We sought to evaluate the association between increasing age and outcomes following V-A ECMO. METHODS: We used individual-level patient data from 440 centers in the international Extracorporeal Life Support Organization registry. We included all adult patients receiving V-A ECMO from 2017 to 2019. The primary outcome was hospital mortality. Secondary outcomes included a composite of complications following initiation of V-A ECMO. We conducted Bayesian analyses of the relationship between increasing age and outcomes of interest. RESULTS: We included 15,172 patients receiving V-A ECMO. Of these, 8172 (53.9%) died in hospital. For the analysis conducted using weakly informed priors, and as compared to the reference category of age 18-29, the age bracket of 30-39 (odds ratio [OR] 0.94, 95% credible interval [CrI] 0.79-1.10) was not associated with hospital mortality, but age brackets 40-49 (odds ratio [OR] 1.26, 95% CrI: 1.08-1.47), 50-59 (OR 1.78, 95% CrI: 1.55-2.06), 60-69 (OR 2.24, 95% CrI: 1.94-2.59), 70-79 (OR 2.90, 95% CrI: 2.49-3.39) and ≥ 80 (OR 4.02, 95% CrI: 3.13-5.20) were independently associated with increasing hospital mortality. Similar results were found in the analysis conducted with an informative prior, as well as between increasing age and post-ECMO complications. CONCLUSIONS: Among patients receiving V-A ECMO for cardiogenic shock, increasing age is strongly associated with increasing odds of death and complications, and this association emerges as early as 40 years of age.

Using the Hospital Frailty Risk Score to assess mortality risk in older medical patients admitted to the intensive care unit.

BACKGROUND: Prognostic information at the time of hospital discharge can help guide goals-of-care discussions for future care. We sought to assess the association between the Hospital Frailty Risk Score (HFRS), which may highlight patients' risk of adverse outcomes at the time of hospital discharge, and in-hospital death among patients admitted to the intensive care unit (ICU) within 12 months of a previous hospital discharge. METHODS: We conducted a multicentre retrospective cohort study that included patients aged 75 years or older admitted at least twice over a 12-month period to the general medicine service at 7 academic centres and large community-based teaching hospitals in Toronto and Mississauga, Ontario, Canada, from Apr. 1, 2010, to Dec. 31, 2019. The HFRS (categorized as low, moderate or high frailty risk) was calculated at the time of discharge from the first hospital admission. Outcomes included ICU admission and death during the second hospital admission. RESULTS: The cohort included 22 178 patients, of whom 1767 (8.0%) were categorized as having high frailty risk, 9464 (42.7%) as having moderate frailty risk, and 10 947 (49.4%) as having low frailty risk. One hundred patients (5.7%) with high frailty risk were admitted to the ICU, compared to 566 (6.0%) of those with moderate risk and 790 (7.2%) of those with low risk. After adjustment for age, sex, hospital, day of admission, time of admission and Laboratory-based Acute Physiology Score, the odds of ICU admission were not significantly different for patients with high (adjusted odds ratio [OR] 0.99, 95% confidence interval [CI] 0.78 to 1.23) or moderate (adjusted OR 0.97, 95% CI 0.86 to 1.09) frailty risk compared to those with low frailty risk. Among patients admitted to the ICU, 75 (75.0%) of those with high frailty risk died, compared to 317 (56.0%) of those with moderate risk and 416 (52.7%) of those with low risk. After multivariable adjustment, the risk of death after ICU admission was higher for patients with high frailty risk than for those with low frailty risk (adjusted OR 2.86, 95% CI 1.77 to 4.77). INTERPRETATION: Among patients readmitted to hospital within 12 months, patients with high frailty risk were similarly likely as those with lower frailty risk to be admitted to the ICU but were more likely to die if admitted to ICU. The HFRS at hospital discharge can inform prognosis, which can help guide discussions for preferences for ICU care during future hospital stays.

ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies.

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

Liberation From Venovenous Extracorporeal Membrane Oxygenation for Respiratory Failure: A Scoping Review.

BACKGROUND: Safe and timely liberation from venovenous extracorporeal membrane oxygenation (ECMO) would be expected to reduce the duration of ECMO, the risk of complications, and costs. However, how to liberate patients from venovenous ECMO effectively remains understudied. RESEARCH QUESTION: What is the current state of the evidence on liberation from venovenous ECMO? STUDY DESIGN AND METHODS: We systematically searched for relevant publications on liberation from venovenous ECMO in Medline and EMBASE. Citations were included if the manuscripts provided any of the following: criteria for readiness for liberation, a liberation protocol, or a definition of successful decannulation or decannulation failure. We included randomized trials, observational trials, narrative reviews, guidelines, editorials, and commentaries. We excluded single case reports and citations where the full text was unavailable. RESULTS: We screened 1,467 citations to identify 39 key publications on liberation from venovenous ECMO. We then summarized the data into five main topics: current strategies used for liberation, criteria used to define readiness for liberation, conducting liberation trials, criteria used to proceed with decannulation, and parameters used to predict decannulation outcomes. INTERPRETATION: Practices on liberation from venovenous ECMO are heterogeneous and are influenced strongly by clinician preference. Additional research on liberation thresholds is needed to define optimal liberation strategies and to close existing knowledge gaps in essential topics on liberation from venovenous ECMO.

Resuscitation outcomes in patients with cancer: experience in a large urban cancer centre.

PURPOSE: Hospitalized patients with cancer who experience cardiopulmonary arrest have historically low survival rates. This retrospective cohort study describes outcomes of patients at a large Canadian cancer centre who had a "code medical emergency" activated, and the use of pragmatic criteria to identify patients with poor survival following resuscitation. METHODS: We included hospitalized patients with cancer who had a "code blue" activated between January 2007 and December 2018. Our primary outcome was intensive care unit (ICU) mortality. We developed pragmatic criteria to identify patients with "poor prognosis" for survival from cardiopulmonary resuscitation (CPR) based on disease status and candidacy for further cancer treatment. We used descriptive statistics to analyze the outcomes of poor prognosis patients. RESULTS: Two hundred and twenty-five patients had a code blue activated. The median age was 61 yr, 52% were male, and 48% had a solid tumour. Overall, 173/225 (77%) patients survived the code blue; 164 were admitted to the ICU, where 49% (81/164) died; 31% survived to hospital discharge; and 16% (n = 27) were alive at one year. One hundred and twenty out of 225 (53%) required chest compressions; spontaneous circulation returned in 61% (73/120), and 12% (14/120) survived to hospital discharge. Patients meeting "poor prognosis" criteria (114, 51%) were more likely to die in the ICU (64% vs 35%; P < 0.001) or in hospital (86% vs 59%; P < 0.001), and more often had goals-of-care discussions prior to the code blue (46% vs 7%; P < 0.001). At one year, only 2% of poor prognosis patients were alive, compared with 24% of patients who did not meet any poor prognosis criteria. CONCLUSION: Hospitalized patients with cancer requiring CPR have poor hospital and long-term outcomes. The proposed set of pragmatic criteria may be useful to identify patients unlikely to benefit from CPR and life support, to trigger early goals of care discussions, and to avoid potentially goal-discordant interventions.

RéSUMé: OBJECTIF: Les patient·es hospitalisé·es atteint·es d'un cancer qui subissent un arrêt cardiorespiratoire ont des taux de survie historiquement bas. Cette étude de cohorte rétrospective décrit les issues des patient·es d'un grand centre canadien de cancérologie pour qui un « code d'urgence médicale ¼ a été activé et l'utilisation de critères pragmatiques pour identifier les patient·es ayant une faible survie après réanimation. MéTHODE: Nous avons inclus les personnes hospitalisées atteintes d'un cancer pour qui un « code bleu ¼ avait été activé entre janvier 2007 et décembre 2018. Notre critère d'évaluation principal était la mortalité à l'unité de soins intensifs (USI). Nous avons développé des critères pragmatiques pour identifier les personnes ayant un « mauvais pronostic ¼ de survie à la réanimation cardiorespiratoire (RCR) en fonction de l'état de la maladie et de leur éligibilité à un traitement ultérieur contre le cancer. Nous avons utilisé des statistiques descriptives pour analyser les issues des patient·es ayant un mauvais pronostic. RéSULTATS: Un code bleu a été activé pour deux cent vingt-cinq patient·es. L'âge médian était de 61 ans, 52 % étaient des hommes et 48 % avaient une tumeur solide. Dans l'ensemble, 173/225 (77 %) patient·es ont survécu au code bleu; 164 ont été admis·es aux soins intensifs, où 49 % (81/164) sont décédé·es; 31 % ont survécu jusqu'à leur congé de l'hôpital; et 16 % (n = 27) étaient en vie après un an. Cent vingt sur 225 (53 %) ont nécessité des compressions thoraciques; la circulation spontanée est revenue chez 61 % (73/120), et 12 % (14/120) ont survécu jusqu'à leur congé de l'hôpital. Les patient·es répondant aux critères de « mauvais pronostic ¼ (114, 51 %) étaient plus susceptibles de mourir à l'USI (64 % vs 35 %; P < 0,001) ou à l'hôpital (86 % vs 59 %; P < 0,001) et avaient plus souvent eu des discussions sur les objectifs de soins avant l'activation du code bleu (46 % vs 7 %; P < 0,001). À un an, seulement 2 % des patient·es ayant un mauvais pronostic étaient en vie, contre 24 % des patient·es qui ne présentaient aucun critère de mauvais pronostic. CONCLUSION: Les personnes hospitalisées atteintes d'un cancer nécessitant une RCR ont de mauvaises issues intra-hospitalières et à plus long terme. L'ensemble de critères pragmatiques proposé peut être utile pour identifier la patientèle peu susceptible de bénéficier de la RCR et du maintien des fonctions vitales, pour amorcer rapidement des discussions sur les objectifs de soins et pour éviter les interventions potentiellement discordantes par rapport à ces objectifs.

Extracorporeal membrane oxygenation in adults receiving haematopoietic cell transplantation: an international expert statement.

Combined advances in haematopoietic cell transplantation (HCT) and intensive care management have improved the survival of patients with haematological malignancies admitted to the intensive care unit. In cases of refractory respiratory failure or refractory cardiac failure, these advances have led to a renewed interest in advanced life support therapies, such as extracorporeal membrane oxygenation (ECMO), previously considered inappropriate for these patients due to their poor prognosis. Given the scarcity of evidence-based guidelines on the use of ECMO in patients receiving HCT and the need to provide equitable and sustainable access to ECMO, the European Society of Intensive Care Medicine, the Extracorporeal Life Support Organization, and the International ECMO Network aimed to develop an expert consensus statement on the use of ECMO in adult patients receiving HCT. A steering committee with expertise in ECMO and HCT searched the literature for relevant articles on ECMO, HCT, and immune effector cell therapy, and developed opinion statements through discussions following a Quaker-based consensus approach. An international panel of experts was convened to vote on these expert opinion statements following the Research and Development/University of California, Los Angeles Appropriateness Method. The Appraisal of Guidelines for Research and Evaluation statement was followed to prepare this Position Paper. 36 statements were drafted by the steering committee, 33 of which reached strong agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and expert panel, and rephrased before an additional round of voting. At the conclusion of the process, 33 statements received strong agreement and three weak agreement. This Position Paper could help to guide intensivists and haematologists during the difficult decision-making process regarding ECMO candidacy in adult patients receiving HCT. The statements could also serve as a basis for future research focused on ECMO selection criteria and bedside management.

Epinephrine in Out-of-Hospital Cardiac Arrest: A Network Meta-analysis and Subgroup Analyses of Shockable and Nonshockable Rhythms.

BACKGROUND: Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed. RESEARCH QUESTION: What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA? STUDY DESIGN AND METHODS: In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome. RESULTS: We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85). INTERPRETATION: Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm. TRIAL REGISTRY: Center for Open Science: https://osf.io/arxwq.

Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts.

BACKGROUND: The optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower versus higher hypoxemia severity thresholds for initiating invasive ventilation. METHODS: This target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008-2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003-2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF < 110, < 98, and < 88 on 28-day mortality. MIMIC-IV was used for the primary analysis and AmsterdamUMCdb for the secondary analysis. We obtained posterior means and 95% credible intervals (CrI) with nonparametric Bayesian G-computation. RESULTS: We studied 3,357 patients in the primary analysis. For invasive ventilation initiation thresholds SF < 110, SF < 98, and SF < 88, the predicted 28-day probabilities of invasive ventilation were 72%, 47%, and 19%. Predicted 28-day mortality was lowest with threshold SF < 110 (22.2%, CrI 19.2 to 25.0), compared to SF < 98 (absolute risk increase 1.6%, CrI 0.6 to 2.6) or SF < 88 (absolute risk increase 3.5%, CrI 1.4 to 5.4). In the secondary analysis (1,279 patients), the predicted 28-day probability of invasive ventilation was 50% for initiation threshold SF < 110, 28% for SF < 98, and 19% for SF < 88. In contrast with the primary analysis, predicted mortality was highest with threshold SF < 110 (14.6%, CrI 7.7 to 22.3), compared to SF < 98 (absolute risk decrease 0.5%, CrI 0.0 to 0.9) or SF < 88 (absolute risk decrease 1.9%, CrI 0.9 to 2.8). CONCLUSION: Initiating invasive ventilation at lower hypoxemia severity will increase the rate of invasive ventilation, but this can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context.

The association between nutritional risk index and ICU outcomes across hematologic malignancy patients with acute respiratory failure.

Patients with hematological malignancies (HM) are at risk of acute respiratory failure (ARF). Malnutrition, a common association with HM, has the potential to influence ICU outcomes. Geriatric nutritional risk index (G-NRI) is a score derived from albumin and weight, which reflects risk of protein-energy malnutrition. We evaluated the association between G-NRI at ICU admission and ICU mortality in HM patients with ARF. We conducted a single center retrospective study of ventilated HM patients between 2014 and 2018. We calculated G-NRI for all patients using their ICU admission albumin and weight. Our primary outcome was ICU mortality. Secondary outcomes included duration of mechanical ventilation and ICU length of stay. Two hundred eighty patients were admitted to the ICU requiring ventilation. Median age was 62 years (IQR 51-68), 42% (n = 118) were females, and median SOFA score was 11 (IQR 9-14). The most common type of HM was acute leukemia (54%) and 40% underwent hematopoietic cell transplant. Median G-NRI was 87 (IQR 79-99). ICU mortality was 51% (n = 143) with a median duration of ventilation of 4 days (IQR 2-7). Mortality across those at severe malnutrition (NRI < 83.5) was 59% (65/111) compared to 46% (76/164) across those with moderate-no risk (p = 0.047). On multivariable analysis, severe NRI (OR 2.34, 95% CI 1.04-5.27, p = 0.04) was significantly associated with ICU mortality. In this single center, exploratory study, severe G-NRI was prognostic of ICU mortality in HM patients admitted with respiratory failure.