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Purpose of Review: To highlight the emerging crisis of critically ill elderly patients and review the unique burden of multidimensional morbidity faced by these patients and caregivers and potential interventions., Recent Findings: Physical, psychological, and cognitive sequelae after critical illness are frequent, durable, and robust across the international ICU outcome literature. Elderly patients are more vulnerable to the multisystem sequelae of critical illness and its treatment and the resultant multidimensional morbidity may be profound, chronic, and significantly affect functional independence, transition to the community, and quality of life for patients and families. Recent data reinforce the importance of baseline functional status, health trajectory, and chronic illness as key determinants of long-term functional disability after ICU. These risks are even more pronounced in older patients., Summary: The current article is an overview of the outcomes of older survivors of critical illness, putative interventions to mitigate the long-term morbidity of patients, and the consequences for families and caregivers. A multimodal longitudinal approach designed to follow patients for one or more years may foster a better understanding of multidimensional morbidity faced by vulnerable older patients and families and provides a detailed understanding of recovery trajectories in this unique population to optimize outcome, goals of care directives, and ongoing informed consent to ICU treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Survivors of pediatric critical illnesses are at risk of significant long-term organ sequelae. Chronic kidney disease (CKD) is a complication of critical illness (and ICU interventions) associated with growth impairment, cardiovascular disease, and early death. Our objective was to synthesize the evidence on the incidence of CKD among survivors of pediatric critical illness., Data Sources: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Register of Controlled Trials from inception to February 2024., Study Selection: Observational studies reporting the incidence of de novo CKD among survivors of pediatric critical illness., Data Extraction: Two reviewers independently extracted data on study design, setting, population, demographics, diagnostic criteria, and outcome., Data Synthesis: Meta-analysis was used to describe the incidence of CKD among survivors, risk of bias (RoB) assessed using the Joanna Briggs Institute Tool, and strength and reliability of evidence assessed with GRADE (Grading of Recommendations, Assessment, Development, and Evaluations). CKD was quantified as an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2 (outcome 1), eGFR less than 60 mL/min/1.73 m2 (outcome 2), and end-stage renal disease (ESRD) as eGFR less than 15 mL/min per 1.73 m2 (outcome 3). Twelve studies (3642 patients) met selection criteria and reported at least one measure of CKD. The median duration of follow-up was 2, 3.6, and 5 years, respectively, for outcomes 1, 2, and 3. For each threshold, the pooled estimate of CKD incidence was 24% (95% CI, 16-32%) for eGFR less than 90, 14% (95% CI, 6-23%) less than 60, and 4% (95% CI, 0-7%) for ESRD. The overall quality assessment indicated a moderate RoB., Conclusions: Among a heterogenous population of pediatric critical illness survivors, an important minority of survivors developed CKD or ESRD. This study highlights the importance of diagnostic criteria for reporting, a greater focus on postcritical care surveillance and follow-up to identify those with CKD. Further study would facilitate the delineation of high-risk groups and strategies for improved outcomes., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: Sociodemographic variables influence health outcomes, either directly (ie, gender identity) or indirectly (eg, structural/systemic racism based on ethnoracial group). Identification of how sociodemographic variables can impact the health of critically ill adults is important to guide care and research design for this population. However, despite the growing recognition of the importance of collecting sociodemographic measures that influence health outcomes, insufficient and inconsistent data collection of sociodemographic variables persists in critical care studies. We aim to develop a set of core data variables (CoDaV) for social determinants of health specific to studies involving critically ill adults., Methods and Analysis: We will conduct a scoping review to generate a list of possible sociodemographic measures to be used for round 1 of the modified Delphi processes. We will engage relevant knowledge users (previous intensive care unit patients and family members, critical care researchers, critical care clinicians and research co-ordinators) to participate in the modified Delphi consensus survey to identify the CoDaV. A final consensus meeting will be held with knowledge user representatives to discuss the final CoDaV, how each sociodemographic variable will be collected (eg, level of granularity) and how to disseminate the CoDaV for use in critical care studies., Ethics and Dissemination: The University of Calgary conjoint health research ethics board has approved this study protocol (REB22-1648)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear., Methods: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding., Results: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups., Conclusions: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Critical illness requiring invasive mechanical ventilation can precipitate important functional disability, contributing to multidimensional morbidity following admission to an intensive care unit (ICU). Early in-bed cycle ergometry added to usual physiotherapy may mitigate ICU-acquired physical function impairment., Methods: We randomly assigned 360 adult ICU patients undergoing invasive mechanical ventilation to receive 30 minutes of early in-bed Cycling + Usual physiotherapy (n=178) or Usual physiotherapy alone (n=182). The primary outcome was the Physical Function ICU Test-scored (PFIT-s) at 3 days after discharge from the ICU (the score ranges from 0 to 10, with higher scores indicating better function)., Results: Cycling began within a median (interquartile range) of 2 (1 to 3) days of starting mechanical ventilation; patients received 3 (2 to 5) cycling sessions for a mean (±standard deviation) of 27.2 ± 6.6 minutes. In both groups, patients started Usual physiotherapy within 2 (2 to 4) days of mechanical ventilation and received 4 (2 to 7) Usual physiotherapy sessions. The duration of Usual physiotherapy was 23.7 ± 15.1 minutes in the Cycling + Usual physiotherapy group and 29.1 ± 13.2 minutes in the Usual physiotherapy group. No serious adverse events occurred in either group. Among survivors, the PFIT-s at 3 days after discharge from the ICU was 7.7 ± 1.7 in the Cycling + Usual physiotherapy group and 7.5 ± 1.7 in the Usual physiotherapy group (absolute difference, 0.23 points; 95% confidence interval, -0.19 to 0.65; P=0.29)., Conclusions: Among adults receiving mechanical ventilation in the ICU, adding early in-bed Cycling to usual physiotherapy did not improve physical function at 3 days after discharge from the ICU compared with Usual physiotherapy alone. Cycling did not cause any serious adverse events. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov numbers, NCT03471247 [full randomized clinical trial] and NCT02377830 [CYCLE Vanguard 46-patient internal pilot].).

Purpose: Frailty is common in critically ill patients but the timing and optimal method of frailty ascertainment, trajectory and relationship with care processes remain uncertain. We sought to elucidate the trajectory and care processes of frailty in critically ill patients as measured by the Clinical Frailty Scale (CFS) and Frailty Index (FI)., Methods: This is a multi-centre prospective cohort study enrolling patients ≥ 50 years old receiving life support > 24 h. Frailty severity was assessed with a CFS, and a FI based on the elements of a comprehensive geriatric assessment (CGA) at intensive care unit (ICU) admission, hospital discharge and 6 months. For the primary outcome of frailty prevalence, it was a priori dichotomously defined as a CFS ≥ 5 or FI ≥ 0.2. Processes of care, adverse events were collected during ICU and ward stays while outcomes were determined for ICU, hospital, and 6 months., Results: In 687 patients, whose age (mean ± standard deviation) was 68.8 ± 9.2 years, frailty prevalence was higher when measured with the FI (CFS, FI %): ICU admission (29.8, 44.8), hospital discharge (54.6, 67.9), 6 months (34.1, 42.6). Compared to ICU admission, aggregate frailty severity increased to hospital discharge but improved by 6 months; individually, CFS and FI were higher in 45.3% and 50.6% patients, respectively at 6 months. Compared to hospital discharge, 18.7% (CFS) and 20% (FI) were higher at 6 months. Mortality was higher in frail patients. Processes of care and adverse events were similar except for worse ICU/ward mobility and more frequent delirium in frail patients., Conclusions: Frailty severity was dynamic, can be measured during recovery from critical illness using the CFS and FI which were both associated with worse outcomes. Although the CFS is a global measure, a CGA FI based may have advantages of being able to measure frailty levels, identify deficits, and potential targets for intervention., (© 2024. The Author(s).)

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 (PaO 2 ) 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 PaO 2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO 2  > 100 mmHg) on day-28 mortality., Results: 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO 2  ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO 2  < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO 2  > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO 2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO 2 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., (© 2024. Crown.)

Importance: Considerable controversy exists regarding the best spontaneous breathing trial (SBT) technique to use., Objective: To summarize trials comparing alternative SBTs., Data Sources: Several databases (MEDLINE [from inception to February 2023], the Cochrane Central Register of Controlled Trials [in February 2023], and Embase [from inception to February 2023] and 5 conference proceedings (from January 1990 to April 2023) were searched in this systematic review and meta-analysis., Study Selection: Randomized trials directly comparing SBT techniques in critically ill adults or children and reporting at least 1 clinical outcome were selected., Data Extraction and Synthesis: Paired reviewers independently screened citations, abstracted data, and assessed quality for the systematic review and meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA guidelines). Data were pooled using random-effects models., Main Outcomes and Measures: Primary outcomes included SBT success, extubation success, and reintubation., Results: The systematic review and meta-analysis identified 40 trials that included 6716 patients. Low-quality evidence (14 trials [n = 4459]) suggested that patients were not more likely to pass a pressure support (PS) compared with a T-piece SBT (risk ratio [RR], 1.04; 95% CI, 0.97-1.11; P = .31; I2 = 73%), unless 1 outlier trial accounting for all heterogeneity was excluded (RR, 1.09; 95% CI, 1.06-1.12; P < .001; I2 = 0% [13 trials; n = 3939]; moderate-quality evidence), but were significantly more likely to be successfully extubated (RR, 1.07; 95% CI, 1.04-1.10; P < .001; I2 = 0%; 16 trials [n = 4462]; moderate-quality evidence). Limited data (5 trials [n = 502]) revealed that patients who underwent automatic tube compensation/continuous positive airway pressure compared with PS SBTs had a significantly higher successful extubation rate (RR, 1.10; 95% CI, 1.00-1.21; P = .04; I2 = 0% [low-quality evidence]). Compared with T-piece SBTs, high-flow oxygen SBTs (3 trials [n = 386]) had significantly higher successful extubation (RR, 1.06; 95% CI, 1.00-1.11; P = .04; I2 = 0%) and lower reintubation (RR, 0.37; 95% CI, 0.21-0.65; P = <.001; I2 = 0% [both low-quality evidence]) rates. Credible subgroup effects were not found., Conclusions and Relevance: In this systematic review and meta-analysis, the findings suggest that patients undergoing PS compared with T-piece SBTs were more likely to be extubated successfully and more likely to pass an SBT, after exclusion of an outlier trial. Pressure support SBTs were not associated with increased risk of reintubation. Future trials should compare SBT techniques that maximize differences in inspiratory support.

The demographic shift, together with financial constraint, justify a re-evaluation of the trajectory of care of very old critically ill patients (VIP), defined as older than 80 years. We must avoid over- as well as under-utilisation of critical care interventions in this patient group and ensure the inclusion of health care professionals, the patient and their caregivers in the decision process. This new integrative approach mobilises expertise at each step of the process beginning prior to intensive care unit (ICU) admission and extending to long-term follow-up. In this review, several international experts have contributed to provide recommendations that can be universally applied. Our aim is to define a minimum core dataset of information to be shared and discussed prior to ICU admission and to facilitate the shared-decision-making process with the patient and their caregivers, throughout the patient journey. Documentation of uncertainty may contribute to a tailored level of care and ultimately to discussions around possible limitations of life sustaining treatments. The goal of ICU care is not only to avoid death, but more importantly to maintain an acceptable quality of life and functional autonomy after hospital discharge. Societal consideration is important to highlight, together with alternatives to ICU admission. We discuss challenges for the future and potential areas of research. In summary, this review provides a state-of-the-art current overview and aims to outline future directions to address the challenges in the treatment of VIP., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear., Methods: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2)., Results: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control., Conclusions: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)., (Copyright © 2023 Massachusetts Medical Society.)

The clinical trajectory of survivors of critical illness after hospital discharge can be complex and highly unpredictable. Assessing long-term outcomes after critical illness can be challenging because of possible competing events, such as all-cause death during follow-up (which precludes the occurrence of an event of particular interest). In this perspective, we explore challenges and methodological implications of competing events during the assessment of long-term outcomes in survivors of critical illness. In the absence of competing events, researchers evaluating long-term outcomes commonly use the Kaplan-Meier method and the Cox proportional hazards model to analyze time-to-event (survival) data. However, traditional analytical and modeling techniques can yield biased estimates in the presence of competing events. We present different estimands of interest and the use of different analytical approaches, including changes to the outcome of interest, Fine and Gray regression models, cause-specific Cox proportional hazards models, and generalized methods (such as inverse probability weighting). Finally, we provide code and a simulated dataset to exemplify the application of the different analytical strategies in addition to overall reporting recommendations.

Background: Tracheal intubation is a high-risk procedure in the critically ill, with increased intubation failure rates and a high risk of other adverse events. Videolaryngoscopy might improve intubation outcomes in this population, but evidence remains conflicting, and its impact on adverse event rates is debated., Methods: This is a subanalysis of a large international prospective cohort of critically ill patients (INTUBE Study) performed from 1 October 2018 to 31 July 2019 and involving 197 sites from 29 countries across five continents. Our primary aim was to determine the first-pass intubation success rates of videolaryngoscopy. Secondary aims were characterising (a) videolaryngoscopy use in the critically ill patient population and (b) the incidence of severe adverse effects compared with direct laryngoscopy., Results: Of 2916 patients, videolaryngoscopy was used in 500 patients (17.2%) and direct laryngoscopy in 2416 (82.8%). First-pass intubation success was higher with videolaryngoscopy compared with direct laryngoscopy (84% vs 79%, P=0.02). Patients undergoing videolaryngoscopy had a higher frequency of difficult airway predictors (60% vs 40%, P<0.001). In adjusted analyses, videolaryngoscopy increased the probability of first-pass intubation success, with an OR of 1.40 (95% confidence interval [CI] 1.05-1.87). Videolaryngoscopy was not significantly associated with risk of major adverse events (odds ratio 1.24, 95% CI 0.95-1.62) or cardiovascular events (odds ratio 0.78, 95% CI 0.60-1.02)., Conclusions: In critically ill patients, videolaryngoscopy was associated with higher first-pass intubation success rates, despite being used in a population at higher risk of difficult airway management. Videolaryngoscopy was not associated with overall risk of major adverse events., Clinical Trial Registration: NCT03616054., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: Readiness to be freed from ventilatory support can be evaluated by spontaneous breathing trial (SBT) assessing the patient's ability to sustain respiratory effort after extubation. Current SBT practices are heterogenous and there are few physiological studies on the topic. The objective of this study is to assess which SBT best reproduces inspiratory effort to breathe after extubation depending on the patient's illness., Methods and Analysis: This will be a multicentre randomised cross-over physiological study, in a large population, in the era of modern intensive care units using last generation modern ventilators. Each included patient will perform three 15-minute SBTs in a random order: pressure support ventilation (PSV) level of 7 cmH 2 O with positive end expiratory pressure (PEEP) level of 0 cmH 2 O, PSV 0 cmH 2 O with PEEP 0 cmH 2 O and T-piece trial. A rest period of baseline state ventilation will be observed between the SBTs (10 min) and before extubation (30 min). Primary outcome will be the inspiratory muscle effort, reflected by pressure time product per minute (PTPmin). This will be calculated from oesophageal pressure measurements at baseline state, before and after each SBT and 20 min after extubation. Secondary outcomes will be PTPmin at 24 hours and 48 hours after extubation, changes in physiological variables and respiratory parameters at each step, postextubation respiratory management and the rate of successful extubation. One hundred patients with at least 24 hours of invasive mechanical ventilation will be analysed, divided into five categories of critical illness: abdominal surgery, brain injury, chest trauma, chronic obstructive pulmonary disease and miscellaneous (pneumonia, sepsis, heart disease)., Ethics and Dissemination: The study project was approved by the appropriate ethics committee (2019-A01063-54, Comité de Protection des Personnes TOURS - Région Centre - Ouest 1, France). Informed consent is required, for all patients or surrogate in case of inability to give consent., Trial Registration Number: NCT04222569., Competing Interests: Competing interests: SJ reports receiving consulting fees from Drager, Mindray, Medtronic, Baxter, Fresenius-Xenios and Fisher & Paykel. ADJ reports receiving consulting fees from Drager, Medtronic and Fisher & Paykel. LB’s lab has received research grants from Medtronic, Drager and Stimit and equipment from Sentec, Fisher & Paykel and Philips and lecture fees from Fisher & Paykel. No potential conflict of interest relevant to this article was reported for other authors., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In critically ill patients receiving KRT, high ultrafiltration rates and persistent fluid accumulation are associated with adverse outcomes. The purpose of this international survey was to evaluate current practices and evidence gaps related to fluid removal with KRT in critically ill patients., Methods: This was a multinational, web-based survey distributed by seven networks comprising nephrologists and intensivists. Physicians involved in the care of critically ill patients were invited to complete a 39-question survey about fluid management practices on KRT. The survey was distributed from September 2021 to December 2021., Results: There were 757 respondents from 96 countries (response rate of 65%). Most respondents practiced adult medicine (89%) and worked in an academic center (69%). The majority (91%) reported aiming for a 0.5- to 2-L negative fluid balance per day when fluid removal is indicated, although there was important variability in what respondents considered a safe maximal target. Intensivists were more likely than nephrologists to use adjunct volume status assessment methods ( i.e. , ultrasound, hemodynamic markers, and intra-abdominal pressure), while nephrologists were more likely to deploy cointerventions aimed at improving tolerance to fluid removal ( i.e. , osmotic agents and low-temperature dialysate). There was a broad consensus that rapid decongestion should be prioritized when fluid accumulation is present, but the prevention of hypotension was also reported as a competing priority. A majority (77%) agreed that performing trials that compare fluid management strategies would be ethical and clinically relevant., Conclusions: We have identified multiple areas of variability in current practice of fluid management for patients receiving KRT. Most nephrologists and intensivists agreed that several knowledge gaps related to fluid removal strategies should be investigated in future randomized controlled trials., (Copyright © 2023 by the American Society of Nephrology.)

Haemodynamic, metabolic, and biochemical derangements in critically ill patients affect drug pharmacokinetics and pharmacodynamics making dose optimisation particularly challenging. Appropriate therapeutic dosing depends on the knowledge of the physiologic changes caused by the patient's comorbidities, underlying disease, resuscitation strategies, and polypharmacy. Critical illness will result in altered drug protein binding, ionisation, and volume of distribution; it will also decrease oral drug absorption, intestinal and hepatic metabolism, and renal clearance. In contrast, the resuscitation strategies and the use of vasoactive drugs may oppose these effects by leading to a hyperdynamic state that will increase blood flow towards the major organs including the brain, heart, kidneys, and liver, with the subsequent increase of drug hepatic metabolism and renal excretion. Metabolism is the main mechanism for drug clearance and is one of the main pharmacokinetic processes affected; it is influenced by patient-specific factors, such as comorbidities and genetics; therapeutic-specific factors, including drug characteristics and interactions; and disease-specific factors, like organ dysfunction. Moreover, organ support such as mechanical ventilation, renal replacement therapy, and extracorporeal membrane oxygenation may contribute to both inter- and intra-patient variability of drug pharmacokinetics. The combination of these competing factors makes it difficult to predict drug response in critically ill patients. Pharmacotherapy targeted to therapeutic goals and therapeutic drug monitoring is currently the best option for the safe care of the critically ill. The aim of this paper is to review the alterations in drug pharmacokinetics associated with critical illness and to summarise the available evidence., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: While early mobilization is commonly implemented in intensive care unit treatment guidelines to improve functional outcome, the characterization of the optimal individual dosage (frequency, level or duration) remains unclear. The aim of this study was to demonstrate that artificial intelligence-based clustering of a large ICU cohort can provide individualized mobilization recommendations that have a positive impact on the likelihood of being discharged home., Methods: This study is an analysis of a prospective observational database of two interdisciplinary intensive care units in Munich, Germany. Dosage of mobilization is determined by sessions per day, mean duration, early mobilization as well as average and maximum level achieved. A k-means cluster analysis was conducted including collected parameters at ICU admission to generate clinically definable clusters., Results: Between April 2017 and May 2019, 948 patients were included. Four different clusters were identified, comprising "Young Trauma," "Severely ill & Frail," "Old non-frail" and "Middle-aged" patients. Early mobilization (< 72 h) was the most important factor to be discharged home in "Young Trauma" patients (OR adj 10.0 [2.8 to 44.0], p < 0.001). In the cluster of "Middle-aged" patients, the likelihood to be discharged home increased with each mobilization level, to a maximum 24-fold increased likelihood for ambulating (OR adj 24.0 [7.4 to 86.1], p < 0.001). The likelihood increased significantly when standing or ambulating was achieved in the older, non-frail cluster (OR adj 4.7 [1.2 to 23.2], p = 0.035 and OR adj 8.1 [1.8 to 45.8], p = 0.010)., Conclusions: An artificial intelligence-based learning approach was able to divide a heterogeneous critical care cohort into four clusters, which differed significantly in their clinical characteristics and in their mobilization parameters. Depending on the cluster, different mobilization strategies supported the likelihood of being discharged home enabling an individualized and resource-optimized mobilization approach., Trial Registration: Clinical Trials NCT03666286, retrospectively registered 04 September 2018., (© 2023. The Author(s).)

Objectives: To determine common "bed-to-physician" ratios during weekday hours across ICUs and assess factors associated with variability in this ratio., Design: Retrospective cohort study., Setting: All ICUs in Australia/New Zealand that participated in a staffing survey administered in 2017-2018., Patients: ICU admissions from 2016 to 2018., Methods: We linked survey data with patient-level data. We defined: 1) bed-to-intensivist ratio as the number of usually available ICU beds divided by the number of onsite weekday daytime intensivists; and 2) bed-to-physician ratio as the number of available ICU beds divided by the total number of physicians (intensivists + nonintensivists, including trainees). We calculated the median and interquartile range (IQR) of bed-to-intensivist ratio and bed-to-physician ratios during weekday hours. We assessed variability in each by type of hospital and ICU and by severity of illness of patients, defined by the predicted hospital mortality., Interventions: None., Measurements and Main Results: Of the 123 (87.2%) of Australia/New Zealand ICUs that returned staffing surveys, 114 (92.7%) had an intensivist present during weekday daytime hours, and 116 (94.3%) reported at least one nonintensivist physician. The median bed-to-intensivist ratio was 8.0 (IQR, 6.0-11.4), which decreased to a bed-to-physician ratio of 3.0 (IQR, 2.2-4.9). These ratios varied with mean severity of illness of the patients in the unit. The median bed-to-intensivist ratio was highest (13.5) for ICUs with a mean predicted mortality > 2-4%, and the median bed-to-physician ratio was highest (5.7) for ICUs with a mean predicted mortality of > 4-6%. Both ratios decreased and plateaued in ICUs with a mean predicted mortality for patients greater than 8% (median bed-to-intensivist ratio range, 6.8-8.0, and bed-to-physician ratio range of 2.4-2.7)., Conclusions: Weekday bed-to-physician ratios in Australia/New Zealand ICUs are lower than the bed-to-intensivist ratios and have a relatively fixed ratio of less than 3 for units taking care of patients with a higher average severity of illness. These relationships may be different in other countries or healthcare systems., Competing Interests: Dr. Wunsch received funding from the Canada Research Chair (Tier 2) in Critical Care Organization and Outcomes. Dr. Gershengorn’s institution received funding from the National Heart, Lung, and Blood Institute; she received funding from the University of Miami Hospital and Clinics through the Data Analytics Research Team, Gilead Sciences, the American Thoracic Society, and Southeastern Critical Care Summit. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: Few quality improvement tools specific to patients with persistent or chronic critical illness exist to aid delivery of high-quality care. Using experience-based co-design methods, we sought consensus from key stakeholders on the most important actionable processes of care for inclusion in a quality improvement checklist., Methods: Item generation methods: systematic review, semi-structured interviews (ICU survivors and family) members, touchpoint video creation, and semi-structured interviews (ICU clinicians). Consensus methods: modified online Delphi and a virtual meeting using nominal group technique methods., Results: We enrolled 138 ICU interprofessional team, patients, and family members. We obtained consensus on a quality improvement checklist comprising 11 core domains: patient and family involvement in decision-making; patient communication; physical comfort and complication prevention; promoting self-care and normalcy; ventilator weaning; physical therapy; swallowing; pharmacotherapy; psychological issues; delirium; and appropriate referrals. An additional 27 actionable processes are contained within 6 core domains that provide more specific direction on the actionable process to be targeted., Conclusions: Using a highly collaborative and methodologically rigorous process, we generated a quality improvement checklist of actionable processes to improve patient and family-centred care considered important by key stakeholders. Future research is needed to understand optimal implementation strategies and impact on outcomes and experience., Competing Interests: Declaration of Competing Interest The authors have no declarations of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Unplanned rehospitalization at a hospital other than the initial hospital may contribute to poor outcomes. We examined the location of rehospitalizations and assessed outcomes following critical illness in a single-payer healthcare system., Materials and Methods: Population-based retrospective cohort study using linked datasets (2012-2017) from Ontario, Canada including adults (≥18 years) with an unplanned rehospitalization within 30-days after an index hospitalization that included an ICU stay with mechanical ventilation. Outcomes were the percentage of 30-day rehospitalizations at non-index hospitals, mortality and costs. We employed logistic regression and generalized linear models to assess associations., Results: There were 14,997 (16.4%) 30-day rehospitalizations. Of these 2765 (18.4%) occurred in a non-index hospital. Distance of home residence from the index hospital was the strongest predictor of a non-index rehospitalization (adjusted odds ratio (aOR) 8.40, 95%CI 7.05-10.01, highest vs. lowest distance quintile). Within 30-days of rehospitalization, deaths (aOR 0.91, 95%CI (0.80-1.04)) and total healthcare costs (adjusted relative risk 1.03 (1.00-1.06)), were similar for patients readmitted to the index or a non-index hospital., Conclusion: Non-index rehospitalization within 30-days of initial discharge is common following critical illness. These rehospitalizations were not significantly associated with an increased risk of harm or higher costs in a single-payer healthcare system., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: During the first wave of the COVID-19 pandemic, restricted visitation policies were enacted at acute care facilities to reduce the spread of COVID-19 and conserve personal protective equipment. In this study, we aimed to describe the impact of restricted visitation policies on critically ill patients, families, critical care clinicians, and decision-makers; highlight the challenges faced in translating these policies into practice; and delineate strategies to mitigate their effects., Method: A qualitative description design was used. We conducted semistructured interviews with critically ill adult patients and their family members, critical care clinicians, and decision-makers (i.e., policy makers or enforcers) affected by restricted visitation policies. We transcribed semistructured interviews verbatim and analyzed the transcripts using inductive thematic analysis., Results: Three patients, eight family members, 30 clinicians (13 physicians, 17 nurses from 23 Canadian intensive care units [ICUs]), and three decision-makers participated in interviews. Thematic analysis was used to identify five themes: 1) acceptance of restricted visitation (e.g., accepting with concerns); 2) impact of restricted visitation (e.g., ethical challenges, moral distress, patients dying alone, intensified workload); 3) trust in the healthcare system during the pandemic (e.g., mistrust of clinical team); 4) modes of communication (e.g., communication using virtual platforms); and 5) impact of policy implementation on clinical practice (e.g., frequent changes and inconsistent implementation)., Conclusions: Restricted visitation policies across ICUs during the COVID-19 pandemic negatively affected critically ill patients and their families, critical care clinicians, and decision-makers., (© 2022. The Author(s).)

Objective: The aim of this study was to synthesize evidence available on continuous infusion ketamine versus nonketamine regimens for analgosedation in critically ill patients., Data Sources: A search of MEDLINE, EMBASE, CINAHL, CDSR, and ClinicalTrials.gov was performed from database establishment to November 2021 using the following search terms: critical care, ICU, ketamine, sedation , and anesthesia . All studies included the primary outcome of interest: daily opioid and/or sedative consumption., Study Selection and Data Extraction: Relevant human studies were considered. Randomized controlled trials (RCT), quasi-experimental studies, and observational cohort studies were eligible. Two reviewers independently screened articles, extracted data, and appraised studies using the Cochrane RoB and ROBINS-I tools., Data Synthesis: A total of 13 RCTs, 5 retrospective, and 1 prospective cohort study were included (2255 participants). The primary analysis of six RCTs demonstrated reduced opioid consumption with ketamine regimens (n = 494 participants, -13.19 µg kg -1 h -1 morphine equivalents, 95% CI -22.10 to -4.28, P = 0.004). No significant difference was observed in sedative consumption, duration of mechanical ventilation (MV), ICU or hospital length of stay (LOS), intracranial pressure, and mortality. Small sample size of studies may have limited ability to detect true differences between groups., Relevance to Patient Care and Clinical Practice: This meta-analysis examining ketamine use in critically ill patients is the first restricting analysis to RCTs and includes up-to-date publication of trials. Findings may guide clinicians in consideration and dosing of ketamine for multimodal analgosedation., Conclusion: Results suggest ketamine as an adjunct analgosedative has the potential to reduce opioid exposure in postoperative and MV patients in the ICU. More RCTs are required before recommending routine use of ketamine in select populations.

Purpose: With an aging global population, the increased proportion of elderly patients in the intensive care unit (ICU) raises important questions regarding optimal management. Currently, data on tracheostomy and its outcomes in the elderly are limited. We aimed to determine the in-hospital survival of elderly ICU patients following tracheostomy, and describe impacts on discharge disposition and functional outcomes., Methods: We conducted a historical cohort study at two academic hospitals in Toronto. All patients aged ≥ 70 yr who received a tracheostomy during their ICU stay between January 2010 and June 2016 were included in a retrospective chart review. Data on patient demographics, frailty, tracheostomy indication, and outcomes were collected., Results: The study included 270 patients with a mean (standard deviation) age of 81 (6) yr. The majority were admitted to ICU for respiratory failure (147/270, 54%) and received a tracheostomy for prolonged mechanical ventilation (202/270, 75%). Intensive care unit and hospital mortality were 26% (68/270) and 46% (125/270), respectively. Twenty-five percent (67/270) of patients were decannulated during hospital admission, a median [interquartile range (IQR)] of 41 [25-68] days after tracheostomy. Intensive care unit and hospital length of stay were 31 [17-53] and 81 [46-121] days, respectively. At hospital discharge, 6% (17/270) of patients were discharged home, all were frail (median Clinical Frailty Score of 7) and most were tube-fed (101/270, 70%), unable to speak (81/270, 56%), and nonambulatory (98/270, 68%)., Conclusions: In patients aged ≥ 70 yr, tracheostomy during ICU stay marked a transition toward prolonged chronic critical illness. Nearly half of the patients died during the admission, and although a quarter were successfully decannulated, the majority of survivors were left with severe frailty and functional impairment., (© 2022. Canadian Anesthesiologists' Society.)

Objectives: We used modified contingent valuation methodology to determine how noninferiority margin sizes influence clinicians' willingness to accept clinical trial results that compare mortality in critically ill children., Methods: We surveyed pediatric infectious diseases and critical care clinicians in Canada, Australia, and New Zealand and randomized respondents to review 1 of 9 mock abstracts describing a noninferiority trial of bacteremic critically ill children assigned to 7 or 14 d of antibiotics. Each scenario showed higher mortality in the 7-d group but met noninferiority criterion. We explored how noninferiority margins and baseline mortality rates influenced respondent acceptance of results., Results: There were 106 survey respondents: 65 (61%) critical care clinicians, 28 (26%) infectious diseases physicians, and 13 (12%) pharmacists. When noninferiority margins were 5% and 10%, 73% (24/33) and 79% (27/33) respondents would accept shorter treatment, compared with 44% (17/39) when the margin was 20% ( P = 0.003). Logistic regression adjusted for baseline mortality showed 5% and 10% noninferiority margins were more likely to be associated with acceptance of shorter treatment compared with 20% margins (odds ratio [OR] 3.5, 95% confidence interval [CI]: 1.3-9.6, P = 0.013; OR 5.1, 95% CI: 1.8-14.6, P = 0.002). Baseline mortality was not a significant predictor of acceptance of shorter treatment., Conclusions: Clinicians are more likely to accept shorter treatment when noninferiority margins are ≤10%. However, nearly half of respondents who reviewed abstracts with 20% margins were still willing to accept shorter treatment. This is a novel application of contingent valuation methodology to elicit acceptance of research results among end users of the medical literature., Highlights: Clinicians are more likely to accept shorter treatment durations based on noninferior mortality results when the noninferiority margin is 5% or 10% than if the margin is 20%.However, nearly half of clinicians would still accept shorter-duration treatment as noninferior with margins of 20%.Baseline mortality does not independently predict acceptance of shorter-duration treatment.Contingent valuation is a novel approach to elicit the acceptance of research design parameters from the perspective of endusers of the medical literature.

Context: Critically-ill patients with hematologic malignancies are increasingly admitted to intensive care units globally. Unrelieved symptoms during intensive care treatment may contribute to poor outcomes., Objective: To better understand the symptom experience(s) for critically-ill patients with hematologic malignancies., Methods: A scoping review was conducted searching Medline, CINAHL, PychInfo, Embase, and ProQuest databases, the Cochrane Library, and the grey literature between January 1st, 1990 and July 15th, 2020. Two authors independently reviewed articles for inclusion and verified abstracted data., Results: Seventeen articles met inclusion criteria, including 11 cohort studies, 1 case-control study, and five review articles. No qualitative or mixed-method studies were retrieved. Symptoms were reported as the primary outcome across two studies (17%). Reported hematologic malignancy subtypes included leukemia and/or myelodysplastic syndrome (9, 53%), lymphoma (8, 47%), multiple myeloma (7, 41%), and aplastic anemia (2, 12%). The principal indication for ICU admission was respiratory failure, followed by cardiogenic shock/cardiac failure, endocrine disturbances, sepsis, and neurological failure. Only one study used validated tools for evaluating symptoms. Thirty-four symptoms were reported: altered level of consciousness/coma (35%); diarrhea (35%); nausea (35%); dyspnea (35%); vomiting (29%); and pain (29%). Two articles (13%) identified symptom clusters., Conclusion: There is minimal research that measures and explores the symptom experiences of critically-ill patients with hematologic malignancies. New research in this domain is needed to inform targeted symptom care for this vulnerable patient population., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Diaphragm ultrasonography is rapidly evolving in both critical care and research. Nevertheless, methodologically robust guidelines on its methodology and acquiring expertise do not, or only partially, exist. Therefore, we set out to provide consensus-based statements towards a universal measurement protocol for diaphragm ultrasonography and establish key areas for research., Methods: To formulate a robust expert consensus statement, between November 2020 and May 2021, a two-round, anonymous and online survey-based Delphi study among experts in the field was performed. Based on the literature review, the following domains were chosen: "Anatomy and physiology", "Transducer Settings", "Ventilator Impact", "Learning and expertise", "Daily practice" and "Future directions". Agreement of ≥ 68% (≥ 10 panelists) was needed to reach consensus on a question., Results: Of 18 panelists invited, 14 agreed to participate in the survey. After two rounds, the survey included 117 questions of which 42 questions were designed to collect arguments and opinions and 75 questions aimed at reaching consensus. Of these, 46 (61%) consensus was reached. In both rounds, the response rate was 100%. Among others, there was agreement on measuring thickness between the pleura and peritoneum, using > 10% decrease in thickness as cut-off for atrophy and using 40 examinations as minimum training to use diaphragm ultrasonography in clinical practice. In addition, key areas for research were established., Conclusion: This expert consensus statement presents the first set of consensus-based statements on diaphragm ultrasonography methodology. They serve to ensure high-quality and homogenous measurements in daily clinical practice and in research. In addition, important gaps in current knowledge and thereby key areas for research are established. Trial registration The study was pre-registered on the Open Science Framework with registration digital object identifier https://doi.org/10.17605/OSF.IO/HM8UG ., (© 2022. The Author(s).)

Purpose: The impact of intensivist workload on intensive care unit (ICU) outcomes is incompletely described and assessed across healthcare systems and countries. We sought to examine the association of patient-to-intensivist ratio (PIR) with hospital mortality in Australia/New Zealand (ANZ) ICUs., Methods: We conducted a retrospective study of adult admissions to ANZ ICUs (August 2016-June 2018) using two cohorts: "narrow", based on previously used criteria including restriction to ICUs with a single daytime intensivist; and "broad", refined by individual ICU daytime staffing information. The exposure was average daily PIR and the outcome was hospital mortality. We used summary statistics to describe both cohorts and multilevel multivariable logistic regression models to assess the association of PIR with mortality. In each, PIR was modeled using restricted cubic splines to allow for non-linear associations. The broad cohort model included non-PIR physician and non-physician staffing covariables., Results: The narrow cohort of 27,380 patients across 67 ICUs (predicted mortality: median 1.2% [IQR 0.4-1.4%]; mean 5.9% [sd 13.2%]) had a median PIR of 10.1 (IQR 7-14). The broad cohort of 91,206 patients across 73 ICUs (predicted mortality: 1.9% [0.6-6.5%]; 7.6% [14.9%]) had a median PIR of 7.8 (IQR 5.8-10.2). We found no association of PIR with mortality in either the narrow (PIR 1st spline term odds ratio [95% CI]: 1 [0.94, 1.06], Wald testing of spline terms p = 0.61) or the broad (1.02 [0.97, 1.07], p = 0.4) cohort., Conclusion: We found no association of PIR with hospital mortality across ANZ ICUs. The low cohort predicted mortality may limit external validity., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Critically ill adults are at increased risk of VTE, including DVT, and pulmonary embolism. Various agents exist for venous thromboprophylaxis in this population., Research Question: What is the comparative efficacy and safety of prophylaxis agents for prevention of VTE in critically ill adults?, Study Design and Methods: Systematic review and network meta-analysis of randomized clinical trials (RCTs) evaluating efficacy of thromboprophylaxis agents among critically ill patients. We searched six databases (including PubMed, EMBASE, and Medline) from inception through January 2021 for RCTs of patients in the ICU receiving pharmacologic, mechanical, or combination therapy (pharmacologic agents and mechanical devices) for thromboprophylaxis. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates., Results: We included 13 RCTs (9,619 patients). Compared with control treatment (a composite of no prophylaxis, placebo, or compression stockings only), low-molecular-weight heparin (LMWH) reduced the incidence of DVT (OR, 0.59 [95% credible interval [CrI], 0.33-0.90]; high certainty) and unfractionated heparin (UFH) may reduce the incidence of DVT (OR, 0.82 [95% CrI, 0.47-1.37]; low certainty). LMWH probably reduces DVT compared with UFH (OR, 0.72 [95% CrI, 0.46-0.98]; moderate certainty). Compressive devices may reduce risk of DVT compared with control treatments; however, this is based on low-certainty evidence (OR, 0.85 [95% CrI, 0.50-1.50]). Combination therapy showed unclear effect on DVT compared with either therapy alone (very low certainty)., Interpretation: Among critically ill adults, compared with control treatment, LMWH reduces incidence of DVT, whereas UFH and mechanical compressive devices may reduce the risk of DVT. LMWH is probably more effective than UFH in reducing incidence of DVT and should be considered the primary pharmacologic agent for thromboprophylaxis. The efficacy and safety of combination pharmacologic therapy and mechanical compressive devices were unclear., Trial Registry: Open Science Framework; URL: https://osf.io/694aj., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: Reliable prediction of early mortality after initiation of renal replacement therapy (RRT) in critically ill patients may inform decision-making regarding this treatment. Our primary objective was to identify predictors of mortality within 2 days of starting RRT., Materials and Methods: Patients with acute kidney injury (AKI), receiving RRT, and admitted to intensive care units of one hospital were included. Associations between baseline risk factors and mortality at 2 days and at hospital discharge were analyzed using logistic regression. Discrimination of both models was assessed., Results: We included 626 patients, treated initially with intermittent RRT (n = 300, 47.9%), continuous RRT (n = 211, 33.7%), or sustained low-efficiency dialysis (n = 115, 18.4%). Two-day mortality after starting RRT was 12.9% (n = 81), and hospital mortality was 50.5% (n = 316). Independent predictors of 2-day mortality included primary diagnostic category (p = 0.004) and sepsis-related organ failure assessment (SOFA) score (odds ratio [OR] 1.36 per point, 95% confidence interval [CI] 1.24-1.50). Independent predictors of hospital mortality included SOFA (1.29, 95%CI 1.21-1.37), Charlson score (1.20, 95%CI 1.18-1.43), and interhospital transfer (OR 0.55, 0.38-0.81). C-statistics were 0.81 (2-day mortality) and 0.80 (hospital mortality)., Conclusions: Higher SOFA was associated with 2-day mortality after RRT initiation and with hospital mortality. Discrimination in both models was modest., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest or applicable financial disclosures. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To describe the modern incidence and predictors of ICU admission for adult patients newly diagnosed with a hematologic malignancy., Methods: We conducted a population-based cohort study of adults with a new diagnosis of hematologic malignancy (April 1, 2006-March 31, 2017) in Ontario, Canada. We described the baseline demographic, clinical and laboratory predictors of ICU admission and subsequent mortality. The primary outcome was the incidence of ICU admission within 1 year of hematologic malignancy diagnosis. We assessed the predictors of ICU admission using Cox-proportional models that accounted for the competing risk of death and reported as subdistribution hazard ratios (sHR) with 95% confidence intervals (CI)., Results: A total of 87,965 patients (mean [SD] age, 67.8 (15.7) years) were included. The 1-year incidence of ICU admission was 13.9% (median time 35 days), ranging from 7.3% (indolent lymphoma) to 22.5% (acute myeloid leukemia). After multivariable adjustment, compared to indolent lymphoma, acute myeloid leukemia (sHR, 3.09; 95% CI 2.84-3.35), aggressive non-Hodgkin lymphoma (sHR, 2.47; 95% CI 2.31-2.65) and acute lymphoblastic leukemia (sHR, 2.46; 95% CI 2.15-2.80) had the highest risk of ICU admission. Comorbidities such as cardiovascular disease (sHR, 2.09; 95% CI 2.01-2.19), chronic obstructive pulmonary disease (sHR, 1.33; 95% CI 1.26-1.39) and baseline laboratory abnormalities (anemia, thrombocytopenia and high creatinine) were also associated with ICU admission. Among ICU patients, 36.7% required invasive mechanical ventilation and in-hospital mortality was 31%., Conclusion: Critical illness in patients with a newly diagnosed hematologic malignancy is frequent, occurring early after diagnosis. Certain baseline characteristics can help identify those patients at the highest risk., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: We declare no competing interests.

Background: There are several reports of extracorporeal membrane oxygenation (ECMO) use in patients with coronavirus disease 2019 (COVID-19) who develop severe acute respiratory distress syndrome (ARDS). We conducted a systematic review and meta-analysis to guide clinical decision-making and future research., Methods: We searched MEDLINE, Embase, Cochrane and Scopus databases from 1 December 2019 to 10 January 2021 for observational studies or randomised clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and meta-regression, assessed risk of bias using the Joanna Briggs Institute checklist and rated the certainty of evidence using the GRADE approach. Survival outcomes were presented as pooled proportions while continuous outcomes were presented as pooled means, both with corresponding 95% confidence intervals [CIs]. The primary outcome was in-hospital mortality. Secondary outcomes were duration of ECMO therapy and mechanical ventilation, weaning rate from ECMO and complications during ECMO., Results: We included twenty-two observational studies with 1896 patients in the meta-analysis. Venovenous ECMO was the predominant mode used (98.6%). The pooled in-hospital mortality in COVID-19 patients (22 studies, 1896 patients) supported with ECMO was 37.1% (95% CI 32.3-42.0%, high certainty). Pooled mortality in the venovenous ECMO group was 35.7% (95% CI 30.7-40.7%, high certainty). Meta-regression found that age and ECMO duration were associated with increased mortality. Duration of ECMO support (18 studies, 1844 patients) was 15.1 days (95% CI 13.4-18.7). Weaning from ECMO (17 studies, 1412 patients) was accomplished in 67.6% (95% CI 50.5-82.7%) of patients. There were a total of 1583 ECMO complications reported (18 studies, 1721 patients) and renal complications were the most common., Conclusion: The majority of patients received venovenous ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1% during the first year of the pandemic, similar to those with non-COVID-19-related ARDS. Increasing age was a risk factor for death. Venovenous ECMO appears to be an effective intervention in selected patients with COVID-19-related ARDS. PROSPERO CRD42020192627.

Delirium, a form of acute brain dysfunction, is very common in the critically ill adult patient population. Although its pathophysiology is poorly understood, multiple factors associated with delirium have been identified, many of which are coincident with critical illness. To date, no drug or non-drug treatments have been shown to improve outcomes in patients with delirium. Clinical trials have provided a limited understanding of the contributions of multiple triggers and processes of intensive care unit (ICU) acquired delirium, making identification of therapies difficult. Delirium is independently associated with poor long term outcomes, including persistent cognitive impairment. A longer duration of delirium is associated with worse long term cognition after adjustment for age, education, pre-existing cognitive function, severity of illness, and exposure to sedatives. Interestingly, differences in prevalence are seen between ICU survivor populations, with survivors of acute respiratory distress syndrome experiencing higher rates of cognitive impairment at early follow-up compared with mixed ICU survivor populations. Although cognitive performance improves over time for some ICU survivors, impairment is persistent in others. Studies have so far been unable to identify patients at higher risk of long term cognitive impairment; this is an active area of scientific investigation., Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following: none., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Mechanical Ventilation (MV) is a complex and central treatment process in the care of critically ill patients. It influences acid-base balance and can also cause prognostically relevant biotrauma by generating forces and liberating reactive oxygen species, negatively affecting outcomes. In this work we evaluate the use of a Recurrent Neural Network (RNN) modelling to predict outcomes of mechanically ventilated patients, using standard mechanical ventilation parameters., Methods: We performed our analysis on VENTILA dataset, an observational, prospective, international, multi-centre study, performed to investigate the effect of baseline characteristics and management changes over time on the all-cause mortality rate in mechanically ventilated patients in ICU. Our cohort includes 12,596 adult patients older than 18, associated with 12,755 distinct admissions in ICUs across 37 countries and receiving invasive and non-invasive mechanical ventilation. We carry out four different analysis. Initially we select typical mechanical ventilation parameters and evaluate the machine learning model on both, the overall cohort and a subgroup of patients admitted with respiratory disorders. Furthermore, we carry out sensitivity analysis to evaluate whether inclusion of variables related to the function of other organs, improve the predictive performance of the model for both the overall cohort as well as the subgroup of patients with respiratory disorders., Results: Predictive performance of RNN-based model was higher with Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.72 (± 0.01) and Average Precision (AP) of 0.57 (± 0.01) in comparison to RF and LR for the overall patient dataset. Higher predictive performance was recorded in the subgroup of patients admitted with respiratory disorders with AUC of 0.75 (± 0.02) and AP of 0.65 (± 0.03). Inclusion of function of other organs further improved the performance to AUC of 0.79 (± 0.01) and AP 0.68 (± 0.02) for the overall patient dataset and AUC of 0.79 (± 0.01) and AP 0.72 (± 0.02) for the subgroup with respiratory disorders., Conclusion: The RNN-based model demonstrated better performance than RF and LR in patients in mechanical ventilation and its subgroup admitted with respiratory disorders. Clinical studies are needed to evaluate whether it impacts decision-making and patient outcomes., Trial Registration: NCT02731898 ( https://clinicaltrials.gov/ct2/show/NCT02731898 ), prospectively registered on April 8, 2016.

Background: The benefit of red blood cell (RBC) transfusion in anemic critically-ill patients with cardiovascular disease is uncertain, as is the optimal threshold at which RBC transfusion should be considered. We sought to examine the association between RBC transfusion and mortality stratified by nadir Hgb level and admission diagnosis among cardiac intensive care unit (CICU) patients., Methods: Retrospective single-center cohort of 11,754 CICU patients admitted between 2007 and 2018. The association between RBC transfusion and hospital mortality at each nadir Hgb (<8 g/dL, 8-9.9 g/dL, ≥10 g/dL) was assessed using multivariable logistic regression adjusted for the propensity to receive RBC transfusion., Results: The study population had a mean age of 68±15 years, including 38% females; 1,134 (11.4%) received RBC transfusion. Admission diagnoses included: acute coronary syndrome , 42%; heart failure, 50%; cardiac arrest , 12%; and cardiogenic shock , 12%. Patients who received RBC transfusion had higher crude hospital mortality (19% vs. 8%, P<.001). RBC transfusion was associated with lower adjusted hospital mortality in patients with nadir Hgb <8 g/dL after propensity adjustment, including subgroups with acute coronary syndrome, cardiac arrest, or cardiogenic shock (all P <.01). RBC transfusion was not associated with lower adjusted hospital mortality in any subgroup of patients with nadir Hgb ≥8 g/dL., Conclusions: These observational data suggest the use of a Hgb threshold <8 g/dL for RBC transfusion in most CICU patients, although we could not exclude a potential benefit of RBC transfusion at a nadir Hgb of 8 to 9.9 g/dL; we did not observe any benefit from RBC transfusion at a nadir Hgb ≥10 g/dL., Competing Interests: Disclosure The authors have no relevant financial disclosures or conflicts of interest related to this work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The growing proportion of elderly intensive care patients constitutes a public health challenge. The benefit of critical care in these patients remains unclear. We compared outcomes in elderly versus very elderly subjects receiving mechanical ventilation., Methods: In total, 5,557 mechanically ventilated subjects were included in our post hoc retrospective analysis, a subgroup of the VENTILA study. We divided the cohort into 2 subgroups on the basis of age: very elderly subjects (age ≥ 80 y; n = 1,430), and elderly subjects (age 65-79 y; n = 4,127). A propensity score on being very elderly was calculated. Evaluation of associations with 28-d mortality was done with logistic regression analysis., Results: Very elderly subjects were clinically sicker as expressed by higher SAPS II scores (53 ± 18 vs 50 ± 18, P < .001), and their rates of plateau pressure < 30 cm H 2 O were higher, whereas other parameters did not differ. The 28-d mortality was higher in very elderly subjects (42% vs 34%, P < .001) and remained unchanged after propensity score adjustment (adjusted odds ratio 1.31 [95% CI 1.16-1.49], P < .001)., Conclusions: Age was an independent and unchangeable risk factor for death in mechanically ventilated subjects. However, survival rates of very elderly subjects were > 50%. Denial of critical care based solely on age is not justified. (ClinicalTrials.gov registration NCT02731898.)., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Objectives: To evaluate the accuracy of a new COVID-19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness., Methods: We conducted a single-center retrospective cohort development and internal validation study of the COVID-19 Worsening Score (COWS), based on a combination of the previously validated COVID-GRAM score (GRAM) variables and LUS. Adult COVID-19 patients admitted to the emergency department (ED) were enrolled. Ten variables previously identified by GRAM, days from symptom onset, LUS findings, and peripheral oxygen saturation/fraction of inspired oxygen (P/F) ratio were analyzed. LUS score as a single predictor was assessed. We evaluated GRAM model's performance, the impact of adding LUS, and then developed a new model based on the most predictive variables., Results: Among 274 COVID-19 patients enrolled, 174 developed critical illness. The GRAM score identified 51 patients at high risk of developing critical illness and 132 at low risk. LUS score over 15 (range 0 to 36) was associated with a higher risk ratio of critical illness (RR, 2.05; 95% confidence interval [CI], 1.52-2.77; area under the curve [AUC], 0.63; 95% CI 0.676-0.634). The newly developed COVID-19 Worsening Score relies on five variables to classify high- and low-risk patients with an overall accuracy of 80% and negative predictive value of 93% (95% CI, 87%-98%). Patients scoring more than 0.183 on COWS showed a RR of developing critical illness of 8.07 (95% CI, 4.97-11.1)., Conclusions: COWS accurately identify patients who are unlikely to need intensive care unit (ICU) admission, preserving resources for the remaining high-risk patients., (© 2021 Wiley Periodicals LLC.)

Introduction: Invasive mechanical ventilation (IMV) is associated with several complications. Placement of a long-term airway (tracheostomy) is also associated with short and long-term risks for patients. Nevertheless, tracheostomies are placed to help reduce the duration of IMV, facilitate weaning and eventually undergo successful decannulation., Methods: We performed a narrative review by searching PubMed, Embase and Medline databases to identify relevant citations using the search terms (with synonyms and closely related words) "non-invasive ventilation", "tracheostomy" and "weaning". We identified 13 publications comprising retrospective or prospective studies in which non-invasive ventilation (NIV) was one of the strategies used during weaning from IMV and/or tracheostomy decannulation., Results: In some studies, patients with tracheostomies represented a subgroup of patients on IMV. Most of the studies involved patients with underlying cardiopulmonary comorbidities and conditions, and primarily involved specialized weaning centres. Not all studies provided data on decannulation, although those which did, report high success rates for weaning and decannulation when using NIV as an adjunct to weaning patient off ventilatory support. However, a significant percentage of patients still needed home NIV after discharge., Conclusions: The review supports a potential role for NIV in weaning patients with a tracheostomy either off the ventilator and/or with its decannulation. Additional research is needed to develop weaning protocols and better characterize the role of NIV during weaning., (Copyright © 2020 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Critically ill patients are at high risk of iatrogenic withdrawal syndrome (IWS), due to exposure to high doses or prolonged periods of opioids and benzodiazepines., Purpose: To examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adults., Methods: We included non-randomised studies of interventions (NRSI) and randomised controlled trials (RCTs), reporting on interventions to prevent or manage IWS in critically ill neonatal, paediatric and adult patients. Database searching included: PubMed, CINAHL, Embase, Cochrane databases, TRIP, CMA Infobase and NICE evidence. Additional grey literature was examined. Study selection and data extraction were performed in duplicate. Data collected included: population, definition of opioid, benzodiazepine or mixed IWS, its assessment and management (drug or strategy, route of administration, dosage and titration), previous drug exposures and outcomes measures. Methodological quality assessment was performed by two independent reviewers using the Cochrane risk of bias tool for RCTs and the ROBINS-I tool for NRSI. A qualitative synthesis of the results is provided. For the subset of studies evaluating multifaceted protocolised care, we meta-analysed results for 4 outcomes and examined the quality of evidence using GRADE post hoc., Results: Thirteen studies were eligible, including 10 NRSI and 3 RCTs; 11 of these included neonatal and paediatric patients exclusively. Eight studies evaluated multifaceted protocolised interventions, while 5 evaluated individual components of IWS management (e.g. clonidine or methadone at varying dosages, routes of administration and duration of tapering). IWS was measured using an appropriate tool in 6 studies. Ten studies reported upon occurrence of IWS, showing significant reductions (n = 4) or no differences (n = 6). Interventions failed to impact duration of mechanical ventilation, ICU length of stay, and adverse effects. Impact on opioid and/or benzodiazepine total doses and duration showed no differences in 4 studies, while 3 showed opioid and benzodiazepine cumulative doses were significantly reduced by 20-35% and 32-66%, and treatment durations by 1.5-11 and 19 days, respectively. Variable effects on intervention drug exposures were found. Weaning durations were reduced by 6-12 days (n = 4) for opioids and/or methadone and by 13 days (n = 1) for benzodiazepines. In contrast, two studies using interventions centred on transition to enteral routes or longer tapering durations found significant increases in intervention drug exposures. Interventions had overall non-significant effects on additional drug requirements (except for one study). Included studies were at high risk of bias, relating to selection, detection and reporting bias., Conclusion: Interventions for IWS management fail to impact duration of mechanical ventilation or ICU length of stay, while effect on occurrence of IWS and drug exposures is inconsistent. Heterogeneity in the interventions used and methodological issues, including inappropriate and/or subjective identification of IWS and bias due to study design, limited the conclusions.

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.