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.

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

Do Thresholds for Invasive Ventilation in Hypoxemic Respiratory Failure Exist? A Cohort Study.

Rationale: Invasive ventilation is a significant event for patients with respiratory failure. Physiologic thresholds standardize the use of invasive ventilation in clinical trials, but it is unknown whether thresholds prompt invasive ventilation in clinical practice. Objectives: To measure, in patients with hypoxemic respiratory failure, the probability of invasive ventilation within 3 hours after meeting physiologic thresholds. Methods: We studied patients admitted to intensive care receiving FiO2 of 0.4 or more via nonrebreather mask, noninvasive positive pressure ventilation, or high-flow nasal cannula, using data from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019) and the Amsterdam University Medical Centers Database (AmsterdamUMCdb) (2003-2016). We evaluated 17 thresholds, including the ratio of arterial to inspired oxygen, the ratio of saturation to inspired oxygen ratio, composite scores, and criteria from randomized trials. We report the probability of invasive ventilation within 3 hours of meeting each threshold and its association with covariates using odds ratios (ORs) and 95% credible intervals (CrIs). Measurements and Main Results: We studied 4,726 patients (3,365 from MIMIC, 1,361 from AmsterdamUMCdb). Invasive ventilation occurred in 28% (1,320). In MIMIC, the highest probability of invasive ventilation within 3 hours of meeting a threshold was 20%, after meeting prespecified neurologic or respiratory criteria while on vasopressors, and 19%, after a ratio of arterial to inspired oxygen of <80 mm Hg. In AmsterdamUMCdb, the highest probability was 34%, after vasopressor initiation, and 25%, after a ratio of saturation to inspired oxygen of <90. The probability after meeting the threshold from randomized trials was 9% (MIMIC) and 13% (AmsterdamUMCdb). In MIMIC, a race/ethnicity of Black (OR, 0.75; 95% CrI, 0.57-0.96) or Asian (OR, 0.6; 95% CrI, 0.35-0.95) compared with White was associated with decreased probability of invasive ventilation after meeting a threshold. Conclusions: The probability of invasive ventilation within 3 hours of meeting physiologic thresholds was low and associated with patient race/ethnicity.

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.

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.

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.

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.

Helmet noninvasive ventilation compared to facemask noninvasive ventilation and high-flow nasal cannula in acute respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Although small randomised controlled trials (RCTs) and observational studies have examined helmet noninvasive ventilation (NIV), uncertainty remains regarding its role. We conducted a systematic review and meta-analysis to examine the effect of helmet NIV compared to facemask NIV or high-flow nasal cannula (HFNC) in acute respiratory failure. METHODS: We searched multiple databases to identify RCTs and observational studies reporting on at least one of mortality, intubation, intensive care unit (ICU) length of stay, NIV duration, complications or comfort with NIV therapy. We assessed study risk of bias using the Cochrane Risk of Bias 2 tool for RCTs and the Ottawa-Newcastle Scale for observational studies, and rated certainty of pooled evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) framework. RESULTS: We separately pooled data from 16 RCTs (n=949) and eight observational studies (n=396). Compared to facemask NIV, based on low certainty of evidence, helmet NIV may reduce mortality (relative risk 0.56, 95% CI 0.33-0.95) and intubation (relative risk 0.35, 95% CI 0.22-0.56) in both hypoxic and hypercapnic respiratory failure, but may have no effect on duration of NIV. There was an uncertain effect of helmet NIV on ICU length of stay and development of pressure sores. Data from observational studies were consistent with the foregoing findings but of lower certainty. Based on low and very low certainty data, helmet NIV may reduce intubation compared to HFNC, but its effect on mortality is uncertain. CONCLUSIONS: Compared to facemask NIV, helmet NIV may reduce mortality and intubation; however, the effect of helmet NIV compared to HFNC remains uncertain.

Catheter management across patients with hematologic malignancies and catheter-related blood stream infections: a systematic review.

Catheter-related bloodstream infection (CRBSI) can lead to ICU admission in patients with hematologic malignancy (HM). Variability exists in the management of catheters given the need for long-term access and co-existing thrombocytopenia or coagulopathy. We conducted a systematic review to evaluate catheter management in patients with CRBSI. Literature searches were conducted up to December 20, 2021 across MEDLINE, EMBASE, CENTRAL, CINAHL, and PubMed. Observational studies and RCTs of adults (> 16) with HM were included. Our primary outcome was mortality and secondary outcomes included infection recurrence and ICU admission. We identified 23 studies (N = 2026 patients), of which 22 were observational. Across the 12 studies (N = 801) that reported on bacterial organisms, 528 (65.9%) were gram positive, and 273 (34.1%) were gram negative. Catheters were removed in 1266 (62%) and retained in 760 (38%) patients. Removal was associated with a mean 30-day mortality of 13.14% (SD 9.12; 90/685) and reinfection rate of 5.49% (SD 2.88; 22/401) compared to 39.23% (SD 14.58; 122/311) and 10.75% (SD 21.07; 10/93), respectively, if retained. Catheter retention may be associated with a higher risk of mortality and infection recurrence. Further prospective research should assess catheter management in this population, including potential harms associated with retention.

Predictors and Hospital Outcomes in Pregnant Patients Undergoing Extracorporeal Membrane Oxygenation: A Nationwide Study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe cardiorespiratory collapse. Although prior large database reviews of ECMO use in the peripartum population exist, they do not stratify by ECMO indication nor do they include obstetric conditions such as preeclampsia. Our objective was to characterize the incidence, indication-associated mortality, and factors associated with mortality in pregnant patients who underwent ECMO. METHODS: We examined the United States National Inpatient Sample database to identify hospitalizations for pregnancy from January 1, 2010 to December 31, 2016. We identified pregnant patients who underwent ECMO using International Classification of Diseases ninth and tenth revisions codes. The primary outcome was in-hospital all-cause mortality across pregnant patients who underwent ECMO for any indication. We evaluated the indication for ECMO, incidence, prevalence of risk factors, comorbidities and conditions, and their association with in-hospital mortality. RESULTS: Fifty-nine of 5'346,517 pregnant patients underwent ECMO during our study period (incidence, 1.1; 95% confidence interval [CI], 0.84-1.4 per 100,000 hospitalizations). Indications for ECMO support included respiratory failure (79.7%), cardiogenic shock (64.4%), or circulatory arrest (25.4%). Most patients (57.6%) had more than 1 indication. The overall in-hospital mortality rate was 30.5%. Mortality was 29.8% in patients with respiratory failure, 39.5% with cardiogenic shock, 46.7% with cardiac arrest, and 42.4% in those with combined diagnoses. Cardiogenic shock was associated with a significantly higher mortality rate and adjusted odds ratio 5.0 (95% CI, 1.25-27.0). Most patients (62.7%) had one or more comorbidities. CONCLUSIONS: The frequency of ECMO use across the pregnant population was low over this time period, with a mortality rate of 1 in 3 patients. Mortality was greatest in patients with cardiogenic shock. Further work is needed to understand how best to improve ECMO outcomes in pregnant patients.

Platelet transfusions and thrombocytopenia in intensive care units: Protocol for an international inception cohort study (PLOT-ICU).

INTRODUCTION: Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. METHODS: We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 × 109 /L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. CONCLUSION: The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.

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.

Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. Design, Setting, and Participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. Intervention: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). Main Outcomes and Measures: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. Results: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. Conclusions and Relevance: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT04350723.

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.

The Early Change in PaCO2 after Extracorporeal Membrane Oxygenation Initiation Is Associated with Neurological Complications.

Rationale: Large decreases in PaCO2 that occur when initiating extracorporeal membrane oxygenation (ECMO) in patients with respiratory failure may cause cerebral vasoconstriction and compromise brain tissue perfusion.Objectives: To determine if the magnitude of PaCO2 correction upon ECMO initiation is associated with an increased incidence of neurological complications in patients with respiratory failure.Methods: We conducted a multicenter, international, retrospective cohort study using the Extracorporeal Life Support Organization Registry, including adults with respiratory failure receiving ECMO via any mode between 2012 and 2017. The relative change in PaCO2 in the first 24 hours was calculated as (24-h post-ECMO PaCO2 - pre-ECMO PaCO2)/pre-ECMO PaCO2. The primary outcome was the occurrence of neurological complications, defined as seizures, ischemic stroke, intracranial hemorrhage, or brain death.Measurements and Main Results: We included 11,972 patients, 88% of whom were supported with venovenous ECMO. The median relative change in PaCO2 was -31% (interquartile range, -46% to -12%). Neurological complications were uncommon overall (6.9%), with a low incidence of seizures (1.1%), ischemic stroke (1.9%), intracranial hemorrhage (3.5%), and brain death (1.6%). Patients with a large relative decrease in PaCO2 (>50%) had an increased incidence of neurological complications compared with those with a smaller decrease (9.8% vs. 6.4%; P < 0.001). A large relative decrease in PaCO2 was independently associated with neurological complications after controlling for previously described risk factors (odds ratio, 1.7; 95% confidence interval, 1.3 to 2.3; P < 0.001).Conclusions: In patients receiving ECMO for respiratory failure, a large relative decrease in PaCO2 in the first 24 hours after ECMO initiation is independently associated with an increased incidence of neurological complications.

Intracranial hemorrhage on extracorporeal membrane oxygenation: an international survey.

INTRODUCTION: Intracranial hemorrhage is one of the most dreaded complications associated with extracorporeal membrane oxygenation. However, robust data to guide clinical practice are lacking. We aimed to describe the current perceptions and practices surrounding the risk, prevention, diagnosis, management, and prognosis of intracranial hemorrhage in patients on extracorporeal membrane oxygenation. METHODS: We conducted an international, cross-sectional survey of adult extracorporeal membrane oxygenation centers using a self-administered electronic questionnaire sent to medical directors and program coordinators of all 290 adult centers member of the Extracorporeal Life Support Organization. RESULTS: There were 143 respondents (49%). The median proportion of patients having neuroimaging performed was only 1-25% in venovenous-extracorporeal membrane oxygenation patients and 26-50% in venoarterial-extracorporeal membrane oxygenation and extracorporeal cardiopulmonary resuscitation. The majority of participants (58%) tolerated a PaO2 < 60 mm Hg on venovenous-extracorporeal membrane oxygenation. Lower PaO2 targets were inversely correlated with the reported incidence of intracranial hemorrhage (r =-0.247; p = 0.024). In patients with intracranial hemorrhage, most participants reported stopping anticoagulation, and median targets for blood product administration were 70,000-99,000 platelets/µL, 1.5-1.9 of international normalized ratio, and 1.6-2.0 g/L of fibrinogen. CONCLUSION: We found significant heterogeneity in the perceptions and practices. This underlines the need for more research to appropriately guide patient management. Importantly, neuroimaging was performed only in a minority of patients. Considering the important management implications reported by most centers when intracranial hemorrhage is diagnosed, perhaps clinicians should consider widening their indications for early neuroimaging.

Critical Care Management of Toxicities Associated With Targeted Agents and Immunotherapies for Cancer.

OBJECTIVES: To describe the most common serious adverse effects and organ toxicities associated with emerging therapies for cancer that may necessitate admission to the ICU. DATA SOURCES AND STUDY SELECTION: PubMed and Medline search of relevant articles in English on the management of adverse effects of immunotherapy for cancer. DATA EXTRACTION AND DATA SYNTHESIS: Targeted therapies including tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors, and immune effector cell therapy have improved the outcome and quality of life of patients with cancer. However, severe and life-threatening side effects can occur. These toxicities include infusion or hypersensitivity reactions, cytokine release syndrome, pulmonary, cardiac, renal, hepatic, and neurologic toxicities, hemophagocytic lymphohistiocytosis, opportunistic infections, and endocrinopathies. Cytokine release syndrome is the most common serious toxicity after administration of monoclonal antibodies and immune effector cell therapies. Most of the adverse events from immunotherapy results from an exaggerated T-cell response directed against normal tissue, resulting in the generation of high levels of proinflammatory cytokines. Toxicities from targeted therapies are usually secondary to "on target toxicities." Management is largely supportive and may include discontinuation of the specific agent, corticosteroids, and other immune suppressing agents for severe (grade 3 or 4) immune-related adverse events like neurotoxicity and pneumonitis. CONCLUSIONS: The complexity of toxicities associated with modern targeted and immunotherapeutic agents for cancer require a multidisciplinary approach among ICU staff, oncologists, and organ specialists and adoption of standardized treatment protocols to ensure the best possible patient outcomes.

New-onset atrial fibrillation and associated outcomes and resource use among critically ill adults-a multicenter retrospective cohort study.

BACKGROUND: New-onset atrial fibrillation (NOAF) is commonly encountered in critically ill adults. Evidence evaluating the association between NOAF and patient-important outcomes in this population is conflicting. Furthermore, little is known regarding the association between NOAF and resource use or hospital costs. METHODS: Retrospective analysis (2011-2016) of a prospectively collected registry from two Canadian hospitals of consecutive ICU patients aged ≥ 18 years. We excluded patients with a known history of AF prior to hospital admission. Any occurrence of atrial fibrillation (AF) was prospectively recorded by bedside nurses. The primary outcome was hospital mortality, and we used multivariable logistic regression to adjust for confounders. We used a generalized linear model to evaluate contributors to total cost. RESULTS: We included 15,014 patients, and 1541 (10.3%) had NOAF during their ICU admission. While NOAF was not associated with increased odds of hospital death among the entire cohort (adjusted odds ratio [aOR] 1.02 [95% confidence interval [CI] 0.97-1.08]), an interaction was noted between NOAF and sepsis, and the presence of both was associated with higher odds of hospital mortality (aOR 1.28 [95% CI 1.09-1.36]) than either alone. Patients with NOAF had higher total costs (cost ratio [CR] 1.09 [95% CI 1.02-1.20]). Among patients with NOAF, treatment with a rhythm-control strategy was associated with higher costs (CR 1.24 [95% CI 1.07-1.40]). CONCLUSIONS: While NOAF was not associated with death or requiring discharge to long-term care among critically ill patients, it was associated with increased length of stay in ICU and increased total costs.

Long-term survival and costs following extracorporeal membrane oxygenation in critically ill children-a population-based cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used to provide temporary cardiorespiratory support to critically ill children. While short-term outcomes and costs have been evaluated in this population, less is known regarding long-term survival and costs. METHODS: Population-based cohort study from Ontario, Canada (October 1, 2009 to March 31, 2017), of pediatric patients (< 18 years of age) receiving ECMO, identified through the use of an ECMO procedural code. Outcomes were identified through linkage to provincial health databases. Primary outcome was survival, measured to hospital discharge, as well as at 1 year, 2 years, and 5 years following ECMO initiation. We evaluated total patient costs in the first year following ECMO. RESULTS: We analyzed 342 pediatric patients. Mean age at ECMO initiation was 2.9 years (standard deviation [SD] = 5.0). Median time from hospital admission to ECMO initiation was 5 days (interquartile range [IQR] = 1-13 days). Overall survival to hospital discharge was 56.4%. Survival at 1 year, 2 years, and 5 years was 51.5%, 50.0%, and 42.1%, respectively. Among survivors, 99.5% were discharged home. Median total costs among all patients in the year following hospital admission were $147,957 (IQR $70,571-$300,295). Of these costs, the large proportion were attributable to the inpatient cost from the index admission (median $119,197, IQR $57,839-$250,675). CONCLUSIONS: Children requiring ECMO continue to have a significant in-hospital mortality, but reassuringly, there is little decrease in long-term survival at 1 year. Median costs among all patients were substantial, but largely reflect inpatient hospital costs, rather than post-discharge outpatient costs. This information provides value to providers and health systems, allowing for prognostication of short- and long-term outcomes, as well as long-term healthcare-related expenses for pediatric ECMO survivors.