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Critical Care Medicine

Ovid Technologies (Wolters Kluwer Health)

All preprints, ranked by how well they match Critical Care Medicine's content profile, based on 12 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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Behavioral Telemetry in the ICU: Missing Orientation Assessment Predicts Mortality in Patients with Low Acute Physiologic Derangement

Born, G.

2026-02-25 health systems and quality improvement 10.64898/2026.02.23.26346916 medRxiv
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BackgroundBehavioral telemetry--the analysis of clinical actions NOT taken--may identify care process failures associated with adverse outcomes. While missed nursing care predicts outcomes in survey-based studies, objective EHR-derived measures are lacking. We hypothesized that missing routine cognitive assessment in ICU patients with low acute physiologic derangement would predict mortality independent of illness severity. MethodsRetrospective cohort study using MIMIC-IV (2008-2022, Beth Israel Deaconess Medical Center) with external assessment of documentation practices in eICU (208 US hospitals). We identified ICU admissions with SOFA 0-2 (low acute physiologic derangement), excluding neurological ICUs. Orientation documentation was classified within 24 hours. Primary outcome was in-hospital mortality. Multivariable logistic regression adjusted for age, sex, SOFA, and Charlson Index. ResultsAmong 46,004 ICU patients with SOFA 0-2, 4,737 (10.3%) had no orientation documentation within 24 hours. These patients had 24.68% mortality versus 7.57% early-assessed and 4.56% late-assessed. After adjustment, missing orientation was associated with 4.29-fold higher odds of death (95% CI 3.95-4.65; E-value 8.0). In SOFA=0 patients (N=23,670), the signal strengthened (OR 5.65, 95% CI 5.03-6.35; E-value 10.8). Late-assessed patients had the LOWEST mortality (OR 0.65), arguing against reverse causation. Patients without orientation had 22% MORE chart events (1,600 vs 1,309), arguing against neglect. External assessment revealed that among 166 eICU hospitals with [≥]100 eligible patients, only 5% documented orientation routinely--92% lack the infrastructure to detect this signal. ConclusionsIn ICU patients with low acute physiologic derangement, absence of orientation assessment is associated with 4-6 fold increased mortality. This association may identify care process failures not captured by severity scores, though prospective studies are needed to establish causality. What is Already Known on This TopicMissed nursing care--care omissions--predicts patient mortality in survey-based studies. Nurse staffing ratios are associated with mortality, but the mechanism is poorly understood. No objective, EHR-derived measure exists to detect care process omissions in real time. What This Study AddsFirst EHR-based operationalization of the missed nursing care construct, enabling objective, real-time detection. Missing orientation assessment associated with 4-6 fold increased mortality (OR 4.29 in SOFA 0-2; OR 5.65 in SOFA=0). Signal strengthens in SOFA=0 patients (E-value 10.8), suggesting finding is not driven by acute illness severity. Argues against reverse causation: late assessment has BETTER outcomes than early or no assessment. Argues against neglect: patients without assessment had MORE documentation, not less. Argues against immortal time bias: Never Documented patients had LONGER ICU stays (7.58 vs 3.09 days). Quantifies association: 10.3% of patients account for 27.2% of deaths. Reveals systemic gap: 92% of US ICUs lack the documentation infrastructure to detect this signal. Key PointsO_ST_ABSQuestionC_ST_ABSDoes absence of routine orientation assessment predict mortality in ICU patients with low acute physiologic derangement (SOFA 0-2), independent of illness severity? FindingsIn this cohort study of 46,004 ICU patients with SOFA 0-2, those without orientation documentation within 24 hours had 4.29-fold higher adjusted odds of death (95% CI 3.95-4.65). In SOFA=0 patients, the signal strengthened to OR 5.65 (E-value 10.8). Patients assessed late (6-24h) had the LOWEST mortality (OR 0.65), arguing against reverse causation. Among 166 eICU hospitals, only 5% document orientation routinely-- 92% lack the infrastructure to detect this signal. MeaningMissing routine cognitive assessment may identify care process failures associated with increased mortality. The finding that 92% of US ICUs lack the documentation infrastructure to detect this signal reveals a systemic gap in care process monitoring.

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Accuracy of Artificial Intelligence-Based Models versus Traditional Scoring Systems (APACHE, SOFA, SAPS) for Predicting Mortality in ICU Patients: A Systematic Review and Meta-Analysis

Pradhan, V.; SHEKHAR, H.; Munda, P. K.; Tiwari, A. K.; Jha, S.; Rai, P.

2026-01-19 intensive care and critical care medicine 10.64898/2026.01.14.26344000 medRxiv
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IntroductionReliable estimation of mortality among critically ill patients is crucial for guiding clinical decisions and optimizing ICU performance. Traditional scoring systems such as APACHE, SOFA, and SAPS are commonly applied, though their predictive capacity is constrained by their reliance on static structures and linear modeling assumptions. Artificial intelligence-based models provide flexible, data-oriented prediction strategies, yet their comparative accuracy remains unclear. This study systematically reviewed and meta-analyzed the performance of Artificial intelligence-based models versus conventional ICU scores for predicting in-hospital mortality in adults admitted to ICU. Materials and MethodsLiterature searches were performed in PubMed, Embase, Web of Science, Scopus and the Cochrane Library from January 2015 to August 2025 for studies comparing AI models with traditional scoring systems. Studies were included if they provided diagnostic performance indicators including AUC, sensitivity, or specificity. Risk of bias was assessed using PROBAST, and pooled statistical estimates were derived through bivariate random-effects modeling with Fisher s Z- transformation. Subgroup analyses examined AI modality, ICU type, and geographic region. ResultsEleven studies involving over one million ICU admissions met inclusion criteria. Two studies (Huang 2023; Lim 2024) provided complete 2 by 2 data for meta-analysis. Pooled sensitivity and specificity for AI models were 0.875 (95% CI: 0.840 - 0.904) and 0.857 (95% CI: 0.845 - 0.868), respectively. AI models achieved higher AUCs (0.82 - 0.90) than APACHE II (0.70 - 0.78), SOFA (0.68 - 0.75), and SAPS II (0.70 - 0.79). Deep learning and ensemble methods performed best across ICU settings and regions. ConclusionAI-based models outperform conventional scoring systems in predicting ICU mortality. Their integration into critical care could enhance early risk stratification and precision prognostication. HighlightsThis meta-analysis highlights that artificial intelligence-based predictive models demonstrated superior predictive performance than conventional ICU scoring systems (APACHE, SOFA, and SAPS) in predicting in-hospital mortality, with higher pooled sensitivity, specificity, and overall discriminative accuracy, particularly for deep learning and ensemble approaches across diverse ICU settings.

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Discordant Care as a Computable Phenotype: Real-Time Detection of Routine Protocol Completion Without Cognitive Patient Engagement Predicts Hospital Mortality in the ICU"

Born, G.

2026-02-26 intensive care and critical care medicine 10.64898/2026.02.24.26347021 medRxiv
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BackgroundQuality measurement in intensive care emphasizes task completion--whether assessments were documented and protocols followed. Electronic health record (EHR) systems capture these signals in real time, yet current metrics cannot distinguish task completion from cognitive clinical engagement. A prior analysis demonstrated that omission of orientation assessment predicted a 4.29-fold increase in hospital mortality among low-acuity ICU patients [1]. Whether combining this marker with routine task-completion data yields a computable phenotype with independent prognostic value has not been studied. ObjectiveTo define, validate, and characterize "discordant care"--a computable EHR phenotype defined as completion of [≥]6 of 8 routine nursing assessments without orientation assessment documentation--as a predictor of hospital mortality, distinguishing patient-level confounding from care process signal. MethodsRetrospective cohort study using MIMIC-IV v3.1 (2008-2022), including 46,004 adult ICU stays with SOFA scores 0-2 and length of stay [≥]24 hours in non-neurological ICUs. Primary exposure: discordant care, computed from structured nursing flowsheet data within 24 hours of admission. Primary outcome: hospital mortality. Progressive covariate adjustment included mechanical ventilation, sedation, and diagnosis. ResultsDiscordant care was present in 8891 patients (19.3%), with 69.7% mechanically ventilated versus 25.3% of concordant patients. Two overlapping signals were identified: a patient-level signal driven by ventilation/sedation (full adjustment OR 1.19, 95% CI 1.09-1.30) and a care process signal in non-ventilated patients (OR 2.14, 1.87-2.44; N=30,314). Among non-ventilated SOFA 0 patients, OR was 2.60 (2.13-3.18; N=16,295). The signal was present across all 7 major diagnosis categories. Quantitative bias analysis indicated unmeasured delirium could attenuate but likely not fully explain the non-ventilated signal. ConclusionsDiscordant care identifies two phenomena: a patient-level signal from ventilation/sedation and a care process signal where assessable patients receive routine care without cognitive engagement (OR 2.14-2.60). This care process signal is invisible to existing quality metrics and detectable in real time. Prospective validation with systematic delirium screening is needed.

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Outcomes in Patients with Acute Hypoxemic Respiratory Failure Secondary to COVID-19 Treated with Noninvasive Respiratory Support versus Invasive Mechanical Ventilation

Fisher, J.; Subbian, V.; Essay, P.; Pungitore, S.; Bedrick, E.; Mosier, J.

2022-12-20 intensive care and critical care medicine 10.1101/2022.12.19.22283704 medRxiv
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PurposeThe goal of this study was to compare noninvasive respiratory support to invasive mechanical ventilation as the initial respiratory support in COVID-19 patients with acute hypoxemic respiratory failure. MethodsAll patients admitted to a large healthcare network with acute hypoxemic respiratory failure associated with COVID-19 and requiring respiratory support were eligible for inclusion. We compared patients treated initially with noninvasive respiratory support (noninvasive positive pressure ventilation by facemask or high flow nasal oxygen) with patients treated initially with invasive mechanical ventilation. The primary outcome was time-to-in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included unweighted and weighted assessments of mortality, lengths-of-stay (intensive care unit and hospital) and time-to-intubation. ResultsOver the study period, 2354 patients met inclusion criteria. Nearly half (47%) received invasive mechanical ventilation first and 53% received initial noninvasive respiratory support. There was an overall 38% in-hospital mortality (37% for invasive mechanical ventilation and 39% for noninvasive respiratory support). Initial noninvasive respiratory support was associated with an increased hazard of death compared to initial invasive mechanical ventilation (HR: 1.61, p < 0.0001, 95% CI: 1.33 - 1.94). However, patients on initial noninvasive respiratory support also experienced an increased hazard of leaving the hospital sooner, but the hazard ratio waned with time (HR: 0.97, p < 0.0001, 95% CI: 0.96 - 0.98). ConclusionThese data show that the COVID-19 patients with acute hypoxemic respiratory failure initially treated with noninvasive respiratory support had an increased hazard of in-hospital death.

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SOFA-2 reclassifies multiorgan dysfunction syndrome in major trauma patients

Krishna, A.; Rosetto, A.; Brohi, K.; Vulliamy, P.; Cole, E.

2026-08-07 intensive care and critical care medicine 10.64898/2026.08.05.26359771 medRxiv
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Objective We aimed to evaluate the performance of the recently updated Sequential Organ Failure Assessment Score-2 (SOFA-2) on organ dysfunction classification and prognostication compared to SOFA-1 in critically injured trauma patients. Methods Adult trauma patients admitted to critical care at four urban Major Trauma Centres between 2011 and 2024 were included. Daily organ dysfunction scoring was performed using SOFA-1 and SOFA-2 until death or discharge. The primary outcome was MODS, defined as SOFA score [&ge;]6. Results In 2162 severely injured patients (median Injury Severity Score 25 [IQR, 17-34]), SOFA-2 reduced the proportion of patients classified as having MODS compared with SOFA-1 (61.6% vs 68.5%, p<0.001). SOFA-2 scores on the first day after admission were lower than SOFA-1 (median 6 [IQR, 3-8] vs 7 [IQR, 4-10], p<0.001), driven predominantly by lower respiratory and cardiovascular scoring. Critical care mortality in trauma patients was increased in respiratory, cardiovascular and renal components of SOFA-2 at the higher ends of the scores, consistent with the aims of the SOFA-2 reclassification. A group of 159 severely injured patients (7.3%) classified as MODS by SOFA-1 were reclassified to no-MODS by SOFA-2. Despite this reclassification, these patients had substantially higher ICU mortality (7.5% vs 0.7%, p<0.01), greater ventilator and vasopressor requirements, and longer hospital stays than patients classified as no-MODS by both systems. Conclusions SOFA-2 reduces MODS prevalence in severely injured patients and changes organ dysfunction classification, with lower rates of severe respiratory and cardiovascular dysfunction. This represents an important update in trauma MODS measurement and has implications for future trauma trial design. However SOFA-2 reclassification generates a small cohort a small but clinically significant group with occult MODS that warrants further evaluation in severely injured trauma patients.

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High-flow nasal cannula vs non-invasive ventilation in acute hypoxia: Propensity score matched study

Munroe, E. S.; Prevalska, I.; Hyer, M.; Meurer, W. J.; Mosier, J. M.; Tidswell, M. A.; Prescott, H. C.; Wei, L.; Wang, H.; Fung, C. M.

2023-09-27 intensive care and critical care medicine 10.1101/2023.09.26.23296167 medRxiv
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RATIONALEThe optimal treatment for early hypoxemic respiratory failure is unclear, and both high-flow nasal cannula and non-invasive ventilation are used. Determining clinically relevant outcomes for evaluating non-invasive respiratory support modalities remains a challenge. OBJECTIVESTo compare the effectiveness of initial treatment with high-flow nasal cannula versus non-invasive ventilation for acute hypoxemic respiratory failure. METHODSWe conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with high-flow nasal cannula or non-invasive ventilation within 24 hours of Emergency Department arrival (1/2018-12/2022). We matched patients 1:1 using a propensity score for odds of receiving non-invasive ventilation. The primary outcome was major adverse pulmonary events (28-day mortality, ventilator-free days, non-invasive respiratory support hours) calculated using a Win Ratio. MEASUREMENTS AND MAIN RESULTS1,265 patients met inclusion criteria. 795 (62.8%) received high-flow oxygen and 470 (37.2%) received non-invasive ventilation. We propensity score matched 736/1,265 (58.2%) patients. There was no difference between non-invasive ventilation vs high-flow nasal cannula in 28-day mortality (17.7% vs 23.1%, p=0.08) or ventilator-free days (median [Interquartile Range]: 28 [25, 28] vs 28 [13, 28], p=0.50), but patients on non-invasive ventilation required treatment for fewer hours (median 7 vs 13, p< 0.001). Win Ratio for composite major adverse pulmonary events favored non-invasive ventilation (1.26, 95%CI 1.06-1.49, p< 0.001). CONCLUSIONSIn this observational study of patients with acute hypoxemic respiratory failure, initial treatment with non-invasive ventilation was superior to high-flow nasal cannula for major pulmonary adverse events. Evaluation of composite outcomes is important in the assessment of respiratory support modalities.

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Clinician contributions to disparities in severity of illness trajectories among mechanically ventilated patients

Chesley, C.; Yakusheva, O.; Lu, Y.; Kohn, R.; Belk, A.; Scott, S.; Halpern, S.; Kerlin, M.

2026-06-25 respiratory medicine 10.64898/2026.06.23.26356358 medRxiv
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Rationale. Racial disparities in outcomes among patients with acute respiratory failure are well-described, but the contributions of clinicians to these disparities have not been evaluated. Objectives. Among mechanically ventilated patients, we evaluated racial disparities in severity of illness trajectories and adapted value-added modeling to quantify nurse and physician relationships with these disparities. Methods. In a retrospective cohort of mechanically ventilated patients across five hospitals between 2018 and 2022, we used generalized estimating equations to model the change in Laboratory-based Acute Physiology Score version 2 (LAPS) from the start to end of intensive care unit admission ({Delta}LAPS). Consistent with value-added modeling, we randomly allocated the cohort into development and testing partitions, and fit separate multiple linear regression models of {Delta}LAPS using concurrent nurse and physician assignments (determined at 4-hour intervals), patient race, and clinician-race interaction terms as fixed effects. Clinician-specific and clinician-race interaction coefficients were extracted to determine race-specific value-add for each clinician. We defined the race-contextual value-add difference (RCVAD) as a clinician-level measurement of the difference in that clinician's value-add between Black and White patients in their care; a positive RCVAD indicates a more favorable severity of illness trajectory for Black relative to White patients and vice versa. Measurement and Main Results. Among 6,555 distinct patients, 7,247 clinical encounters, 405 nurses, and 70 physicians, Black patients accounted for 2,926 (40%) encounters. Overall, Black patients had significantly less improvement in {Delta}LAPS than White patients (difference in LAPS decline = 2.26 [0.23, 4.29], p=0.029). In the development partition, median nurse RCVAD was -0.10 (interquartile range [IQR]: -1.17, 1.14) with 191 (47%) nurses having a positive RCVAD; median physician RCVAD was -0.18 (IQR: -1.34, 0.56) with 29 (41%) having a positive RCVAD. Conclusions. Black mechanically ventilated patients experience less improvement in severity of illness during intensive care unit admission than White patients. While the majority of physicians and nurses were associated with disparities-exacerbating illness trajectories, many other clinicians were associated with disparities-mitigating trajectories. Future work to understand practices associated with disparities-exacerbating and disparities-mitigating care profiles could inform interventions to reduce disparities overall.

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The effect of COVID-19 on critical care research: A prospective longitudinal multinational survey

Duffett, M.; Cook, D. J.; Strong, G.; Lee, J. H.; Kho, M. E.

2020-10-23 intensive care and critical care medicine 10.1101/2020.10.21.20216945 medRxiv
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ImportanceThe COVID-19 pandemic has increased the need for high-quality evidence in critical care, while also increasing the barriers to conducting the research needed to produce such evidence. ObjectiveTo determine the effect of the first wave of the COVID-19 pandemic on critical care clinical research. DesignMonthly electronic survey (March 2020 - February 2021). SettingAdult or pediatric intensive care units (ICUs) from any country participating in at least one research study before the COVID-19 pandemic. ParticipantsWe recruited one researcher or research coordinator per center, identified via established research networks. Intervention(s)None Main Outcome(s) and Measure(s)Primary: Suspending recruitment in clinical research; Secondary: impact of specific factors on research conduct (5-point scales from no effect to very large effect). We assessed the association between research continuity and month, presence of hospitalized patients with COVID-19, and population (pediatric vs. adult ICU) using mixed-effects logistic regression. Results127 centers (57% pediatric) from 23 countries participated. 95 (75%) of centers suspended recruitment in at least some studies and 37 (29%) suspended recruitment in all studies on at least one month. The proportion of centers reporting recruitment in all studies increased over time (OR per month 1.3, 95% CI 1.2 to 1.4, p < 0.001), controlling for hospitalized patients with COVID-19 and type of ICU (pediatric vs. other). The five factors most frequently identified as having a large or very large effect on clinical research were: local prioritization of COVID-19 specific research (68, 54%), infection control policies limiting access to patients with COVID-19 (61, 49%), infection control policies limiting access to the ICU (52, 41.6%), increased workload of clinical staff (38, 30%), and safety concerns of research staff (36, 29%). Conclusions and RelevanceDecisions to pause or pursue clinical research varied across centers. Research activity increased over time, despite the presence of hospitalized patients with COVID-19. Guiding principles with local adaptation to safely sustain research during this and future pandemics are urgently needed. Key PointsO_ST_ABSQuestionC_ST_ABSWhat was the effect of the COVID-19 pandemic on research in 127 adult and pediatric intensive care units (ICUs) between March 2020 and February 2021? Findings95 (75%) centers suspended recruitment into at least some studies. Active recruitment into studies increased over time (OR per month 1.3, 95% CI 1.2 to 1.4, p < 0.001), controlling for ICU type and the presence of patients with COVID-19. MeaningResearch activity varied across centers and increased over time, despite the presence of hospitalized patients with COVID-19. Guiding principles to safely sustain research during this and future pandemics are urgently needed.

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Behavioral Telemetry for ICU Mortality Prediction: Documentation Pattern Analysis in 46,002 Low-Acuity MIMIC-IV Patients

Born, G.

2026-03-02 intensive care and critical care medicine 10.64898/2026.02.25.26347110 medRxiv
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ObjectiveTo develop and validate a predictive model incorporating behavioral telemetry signals--documentation pattern anomalies derived from routine EHR charting--alongside clinical variables for ICU mortality prediction in patients with low acute physiologic derangement. Materials and MethodsRetrospective cohort study of 46,002 adult ICU stays from MIMIC-IV v3.1 (2008-2022) with SOFA scores 0-2, excluding neurological units. We extracted 66 variables spanning demographics, acuity, behavioral telemetry, clinical enrichment, and temporal factors. Progressive logistic regression models (M1-M7) were compared using cross-validation, DeLong tests, net reclassification improvement, and calibration analysis. ResultsOverall mortality was 9.34% (4,295 deaths). The clinical model (M5) achieved cross-validated AUROC 0.691 versus 0.639 for demographics alone (M2; {Delta}AUROC = 0.052, DeLong p = 4.41x10-47). NRI was 24.3%. Discordant care patients received 30.5% more chart events than concordant patients, with the sole deficit in neurological assessments (-15.4%), refuting the neglect hypothesis. Kaplan-Meier analysis confirmed survival separation (log-rank {chi}2 = 138.6, p = 5.32x10-32). In the most conservative subgroup (SOFA 0, no sedation, no ventilation, N = 11,158), orientation omission remained associated with mortality (adjusted OR 1.52, p = 0.027). DiscussionDeep sedation and mechanical ventilation function as mediators on the causal pathway rather than traditional confounders; the discordant care signal retains significance after full sedation adjustment. ConclusionDocumentation pattern analysis adds measurable predictive value for ICU mortality risk stratification and represents a novel signal for real-time EHR-based clinical decision support.

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Long-term survival, psychiatric, physiological, and functional outcomes of critically ill patients requiring prolonged mechanical ventilation: a systematic review.

Ludski, J.; Honeywill, C.

2023-11-27 intensive care and critical care medicine 10.1101/2023.11.27.23299077 medRxiv
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PurposeInvasive mechanical ventilation is utilized in over 50% of Australian Intensive Care Unit patients, with rates increasing world-wide. Prolonged mechanical ventilation is associated with increased length of hospital stay and in-hospital mortality compared with patients ventilated under the time threshold. Previous studies have highlighted mortality rates, but much remains unknown regarding the long-term physiological, functional, and psychiatric effects of prolonged mechanical ventilation. With a greater understanding of these outcomes, models of care can be formulated to reduce long-term morbidity. MethodsMedline, CINAHL and the Cochrane Library were searched between 1998 and March 2019, for PMV, patients in ICU and long-term outcomes. Included studies had patients, that received greater than or equal to 14 days of IMV. Primary outcome was mortality rates with secondary outcomes clustered into physiological, functional, and psychiatric outcomes. Results1057 studies were identified, with 24 included. 73% of PMV patients were discharged from ICU, with mortality rates of 57% and 69% at 12 and 48 months. 30.2% were discharged home, 25% developed new onset ventilator acquired pneumonia and up to 39% experienced psychiatric complications. ConclusionDespite a high proportion of patients surviving to hospital discharge, subsequent outcomes are extremely poor for patients that require PMV.

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Effect of red blood cell transfusion strategies on ICU-acquired infection in patients with sepsis: A target trial emulation using the Medical Information Mart for Intensive Care IV database

YOSHIHIRO, S.; KATAOKA, Y.; NISHIKIMI, M.; SHIME, N.; MATSUO, H.

2026-08-17 intensive care and critical care medicine 10.64898/2026.08.14.26360449 medRxiv
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Purpose To estimate the per-protocol effect of red blood cell (RBC) transfusion strategies on ICU-acquired infection in critically ill adults with sepsis using a target trial emulation framework. We evaluated whether restrictive strategy and liberal strategy, defined by hemoglobin (Hgb) thresholds, differ in their effect on ICU-acquired infection during ICU stay. Methods We conducted a target trial emulation using the MIMIC-IV database and included adults who met Sepsis criteria at ICU admission. Clones were assigned to restrictive or liberal transfusion strategies. Under the restrictive strategy, RBC transfusion was permitted only when Hgb was [&le;]7.0 g/dL, whereas under the liberal strategy, transfusion was permitted when Hgb was >7.0 g/dL. The primary outcome was the first ICU-acquired infection occurring at least 72 hours after ICU admission. Per-protocol effects were estimated using a clone-censor-weight approach with a marginal structural model. A parametric g-formula was used as a complementary analysis that jointly modeled ICU discharge and ICU mortality as competing events to derive strategy-specific 28-day cumulative incidences and risk differences. Results 8 Among 4,013 eligible ICU stays, the liberal-versus-restrictive comparison provided little evidence of a difference in the risk of ICU-acquired infection (adjusted conditional OR, 0.954; 95% CI, 0.797 to 1.142). In the complementary g-formula analysis, the 28-day risk difference for the liberal versus restrictive comparison was -0.02 percentage points (95% CI, -0.15 to 0.11), consistent with the primary analysis. Findings were generally robust across prespecified subgroup and sensitivity analyses. Conclusion In this target trial emulation of adults with sepsis, we observed no clinically meaningful difference in ICU-acquired infection between RBC transfusion strategies defined by hemoglobin thresholds.

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A Modified Delphi Consensus-based Comprehensive Checklist and Angoff Standard for Assessment of Competency in Brain Death/Death by Neurologic Criteria Determination

Harrison, D. S.; Dhruva, N.; Ford, J. L.; Greer, D. M.; Wahlster, S.; Chhabra, N.; Morris, N. A.; The SECOND Investigators,

2025-08-29 medical education 10.1101/2025.08.27.25334589 medRxiv
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ObjectiveTo develop a comprehensive checklist, define critical actions, and establish a minimal passing standard for adult and pediatric critical care clinicians as well as other providers to facilitate formative and summative assessment of brain death/death by neurologic criteria (BD/DNC) determination Design: A pre-specified three round modified Delphi consensus process to define checklist items followed by a modified Angoff standard setting process to determine critical actions and item average ratings. SettingElectronic surveys. SubjectsSelected authors of the 2023 Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Practice Guideline, World Brain Death Project, and experts recommended by these authors (n=16) participated in the Delphi panel. Neurocritical care United Council for Neurologic Subspecialties and Accreditation Council for Graduate Medical Education examination committee members (n= 13) participated in Angoff standard setting. InterventionsNone. Measurements and Main ResultsA total of 98 unique checklist items related to assessment of prerequisites (23 items), performance of the clinical examination (28 items), apnea testing (36 items), and ancillary testing (11 items) were retained by the Delphi panel. Seven items were designated as critical actions based upon Angoff panelist consensus. The remaining 91 items were assigned item average ratings. The minimum passing score for an assessment including all items was set at 89%. ConclusionsThese guideline-concordant consensus checklist items, including critical actions and non-critical actions with their assigned item average ratings, may be applied selectively to simulated cases of BD/DNC determination for adults and children to determine a minimum passing score and readiness for independent practice, mitigating risk of inaccurate BD/DNC determination among critical care clinicians. Our process for systematically defining critical actions on a behavior checklist may be replicated for simulation-based summative assessment of learners in other critical care scenarios. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat behaviors should be included in a checklist for assessment of brain death/death by neurologic criteria (BD/DNC) determination and what level of performance is consistent with readiness for independent practice? FindingsA modified Delphi panel identified 98 checklist items which may be applied selectively to simulated cases of BD/DNC. An Angoff panel identified 7 critical actions and set average ratings for all other items. MeaningThese guideline-concordant consensus checklist items and their average ratings may be applied to assessments of simulated or real cases of BD/DNC, including those intended for summative assessment, to determine learner readiness for independent determination.

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Analytical Performance and Intraoperative Glycemic Efficacy of Continuous Glucose Monitoring Systems in Elective Surgery: A Systematic Review and Meta-Analysis for Perioperative Clinical Guidance

Oliveira Andrade, L. J. d.; Matos de Oliveira, G. C.; Vinhaes Bittencourt, A. M.; Mattos Salles, O. J.; Matos de Oliveira, L.

2026-05-07 endocrinology 10.64898/2026.05.06.26352601 medRxiv
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IntroductionIntraoperative glycemic dysregulation, including unrecognized hypoglycemia and stress-induced hyperglycemia, is common during elective surgery. Conventional point-of-care (POC) monitoring provides only intermittent measurements, limiting the anesthesiologists ability to detect rapid glucose fluctuations. Continuous glucose monitoring (CGM) enables real-time, trend-based assessment, potentially shifting intraoperative glycemic management from reactive to proactive. ObjectiveTo meta-analyze the analytical accuracy, intraoperative glycemic efficacy, and feasibility of subcutaneous CGM in adults undergoing elective surgery, informing anesthesiology practice. MethodsThis systematic review and meta-analysis followed the PRISMA 2020 statement. Searches were conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials from January 2010 to May 2025. Eligible studies included randomized controlled trials and prospective cohorts of adults undergoing elective surgery under general or neuraxial anesthesia using subcutaneous CGM. Primary outcomes were pooled mean absolute relative difference (MARD) and time in range (TIR, 70-180 mg/dL). Random-effects models were applied. ResultsTen studies (3 RCTs, 7 cohorts; N=557) were included. Pooled MARD was 14.1% (95% CI 11.3-16.9%; I{superscript 2}=78%), lower in non-cardiac surgery (12.7%) than cardiac procedures with hypothermia (19.2%; p=0.03). CGM improved TIR by +14.9 percentage points (95% CI 7.2-22.6; p<0.001). Clinically significant hypoglycemia was detected in 43% of patients, all missed by POC. Sensor availability exceeded 96%, with no serious device-related events. ConclusionSubcutaneous CGM provides acceptable intraoperative accuracy and improves glycemic control, supporting its integration into anesthetic management.

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Can Blood Gas Enhance Early Warning Systems by streamlining ICU Transfer Decisions: A Qualitative Systematic Review

Stiller, E.; Meka, P.

2025-10-24 intensive care and critical care medicine 10.1101/2025.10.23.25338637 medRxiv
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ImportanceDelay in transfer to Intensive Care Unit (ICU) is associated with known adverse clinical and economic outcomes. There are several early warning systems (EWS) that help identify patients that could benefit from earlier ICU transfer but are fraught with challenges when used to measure delays. An objective time stamped blood test metric, such as a blood gas analysis (BGA), could be a valuable adjunct in identifying patients and measuring delays in who require intrahospital transfer to the ICU. BackgroundDelays in transferring critically ill patients to the ICU are linked to increased mortality, organ failure, prolonged recovery, and higher hospital costs. While EWS systems like MEWS, NEWS2, and eCART aim to detect deterioration using vital signs and medical data, they often rely on intermittent and/or subjective inputs. Despite advances, including AI-driven models, most systems still lack accuracy to detect and quantify transfer delays, an important operational metric. ObjectiveThis review explores the clinical and operational impact of ICU transfer delays and evaluates the potential role of BGA as an objective, time-stamped adjunct biomarker for early identification of high-risk patients. We also assess whether BGA could be integrated into EWS tools to enhance predictive accuracy. MethodsWe conducted a systematic literature review of studies published between 1994 and 2024 using PubMed, EMBASE, Cochrane, and NIH databases. Inclusion criteria focused on studies that examined ICU transfer delays, BGA parameters (e.g., lactate, pH, base excess), and clinical outcomes in adult or pediatric patients. Studies were excluded if they had small sample sizes (n < 50), lacked outcome data, or were not published in English. ResultsThe review found that delays in ICU transfer are consistently linked to worse clinical outcomes and higher healthcare costs. While EWS tools have improved early recognition of patient deterioration, they still lack objective, time-stamped markers to measure delays. Approximately one-third of the included studies specifically examined BGA parameters in relation to ICU transfer or outcomes. Elevated lactate levels and abnormal pH values correlated with increased ICU admission, adverse prognosis and mortality risk. Despite this, BGA is not currently integrated into most clinical decision-making tools used for ICU triage. ConclusionBGA represents a promising, underutilized tool that could fill a critical gap in current ICU triage systems. As a time-stamped, objective measure of physiological instability, BGA could enhance the accuracy, timeliness and measurability of ICU transfer decisions--especially when combined with electronic medical records and modern EWS platforms. Future research should focus on evaluating BGA as a predictive input within next-generation EWS tools, with the goal of reducing ICU transfer delays, improving patient outcomes, and optimizing hospital resource use.

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Intravenous corticosteroid treatment in adult patients with sepsis defined by the Sepsis-3 criteria: a systematic review and meta-analysis

Wu, Y.-P.; Lin, C.-K.; Hamaya, R.; Huang, F.-Y.; Chien, Y.-S.; Hsu, Y.-T.; Chen, S.-T.; Papatheodorou, S.

2021-10-18 intensive care and critical care medicine 10.1101/2021.10.17.21265100 medRxiv
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ObjectivesTo summarize the effects of intravenous corticosteroid treatment for sepsis defined by the Sepsis-3 criteria in adult patients. DesignSystematic review and meta-analysis. MethodsWe searched RCTs from PubMed, Embase, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Web of Science, and International Clinical Trials Registry Platform from inception to July 12th, 2019 and updated on June 28th, 2020. Conference proceedings from relevant societies and the reference lists of previous reviews were manually screened. Abstract or full-text articles were screened by two independent investigators. We included RCTs where (1) the participants had infections and the baseline Sequential Organ Failure Assessment (SOFA) score [&ge;] 2 (the Sepsis-3 definitions) (2) the intervention involved any intravenous corticosteroids; (3) the control group received placebo or standard of care (4) the outcomes of interest included mortality or clinical recovery. We chose the 28-day mortality as the pre-specified primary outcome and risk ratio (RR) as the effect measure. We followed PRISMA guidelines and chose random-effects models for the pooled analyses. ResultsThis study included 24 RCTs and 19 of them (7,115 participants) reported the 28-day mortality. Pooled analyses showed that intravenous corticosteroid treatment compared to placebo or standard of care was not associated with a lower risk of 28-day mortality (RR, 0.88; 95%CI, 0.73 to 1.05), but with a higher risk of hyperglycemia (RR, 1.16; 95%CI, 1.06 to 1.27). Sensitivity analysis of high-quality studies revealed a similar result for the 28-day mortality (RR, 0.95; 95%CI, 0.86 to 1.05). ConclusionsOur findings suggested that intravenous corticosteroids compared to placebo or standard of care may not reduce the 28-day mortality in adult patients with sepsis defined by the Sepsis-3 criteria. Further studies are warranted to clarify the roles of disease severity and treatment timing in the effects of corticosteroid treatment in this population. PROSPERO registration numberCRD42019143083 Strengths and limitations of this studyO_LIThis is the first systematic review and meta-analysis that summarized the effects of intravenous corticosteroid treatments in patients with sepsis defined by the Sepsis-3 criteria. C_LIO_LIWe provide the quality of evidence to support the development of treatment guidelines specific to the Sepsis-3 cohort. C_LIO_LIWe only include randomized controlled trials in this systematic review and meta-analysis, which exclude less controlled evidences from clinical settings closer to our daily practice. C_LIO_LIThe Sepsis-3 definitions will be retrospectively applied to the included studies, so clinical trials without enough reported baseline data available may be excluded. C_LI

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Association between patient race/ethnicity and invasive ventilation in hypoxemic respiratory failure

Abdelmalek, F. M.; Angriman, F.; Moore, J.; Liu, K.; Burry, L.; Seyyed-Kalantari, L.; Mehta, S.; Gichoya, J. W. J.; Celi, L. A.; Tomlinson, G.; Fralick, M.; Yarnell, C. J.

2022-11-01 intensive care and critical care medicine 10.1101/2022.10.31.22281761 medRxiv
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ImportanceDifferential use of therapies for respiratory failure according to patient race/ethnicity may represent health inequity and could impact patient survival. ObjectiveMeasure the association between patient race/ethnicity and the use of invasive ventilation, and the impact of any association on survival. DesignRetrospective cohort analysis using a Bayesian multistate model that adjusted for baseline covariates and time-varying severity. SettingMulticenter study using the Medical Information Mart for Intensive Care IV (MIMIC-IV) and Phillips eICU (eICU) databases from the USA. ParticipantsNon-intubated adults receiving oxygen within the first 24 hours of ICU admission. ExposurePatient race/ethnicity (Asian, Black, Hispanic, white). Main outcomes and measuresPrimary output was the cause-specific hazard ratio (HR) of invasive ventilation for patient race/ethnicity. Secondary output was change in 28-day survival mediated by differences in invasive ventilation rate. We reported posterior means and 95% credible intervals (CrI). ResultsWe studied 38,263 patients, 52% (20,033) from MIMIC-IV and 48% (18,230) from eICU, 2% Asian (892), 11% Black (4,289), 5% Hispanic (1,964), and 81% white (31,923). Invasive ventilation occurred in 3,511 (9.2%), and 2,869 (7.5%) died. The rate of invasive ventilation was lower in Asian (HR 0.82, CrI 0.70 to 0.95), Black (HR 0.78, CrI 0.71 to 0.86), and Hispanic (HR 0.70, CrI 0.61 to 0.79) patients as compared to white patients. For the average patient, lower rates of invasive ventilation did not mediate differences in survival. For a reference patient with inspired oxygen (FiO2) varied from 0.5 to 1.0, the change in survival mediated by lower rates of invasive ventilation ranged from probable benefit (probability 0.82 for Asian patients, 0.91 for Black patients, and 0.93 for Hispanic patients) at FiO2 0.5 to probable harm (probability 0.87 for Asian patients, 0.92 for Black patients, and 0.97 for Hispanic patients) at FiO2 1.0, although the mean absolute changes in mortality were all less than 1.5%. ConclusionsAsian, Black, and Hispanic patients had a lower rate of invasive ventilation than white patients. The changes in 28-day survival mediated by this difference ranged from slight benefit at lower inspired oxygen fractions to slight harm at inspired oxygen fraction of 1.0, and there was no difference in survival for the average patient. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the association between patient race/ethnicity and the use of invasive ventilation in hypoxemic respiratory failure, and what is the impact of any differences on survival? FindingsWe studied 38,263 patients from two US databases, who were 2% Asian (892), 11% Black (4,289), 5% Hispanic (1,964), and 81% white (31,118). Invasive ventilation occurred in 3,511 (9.2%), and 2,869 (7.5%) died. The hazard ratio (HR) for invasive ventilation was lower in Asian (HR 0.82, CrI 0.70 to 0.95), Black (HR 0.78, CrI 0.71 to 0.86), and Hispanic (HR 0.70, CrI 0.61 to 0.79) patients as compared to white patients. For the average patient, race/ethnicity differences in invasive ventilation rates did not mediate differences in 28-day survival. For the reference patient, at inspired oxygen fractions up to 0.9, lower invasive ventilation rates mediated a modest survival benefit, whereas at inspired oxygen fraction of 1.0, the lower invasive ventilation rates mediated a modest survival decrease, although the absolute changes were all less than 1.5%. MeaningAsian, Black, and Hispanic patients had a lower rate of invasive ventilation than white patients. Although this difference had no impact on 28-day survival for the average patient, the change in survival mediated by lower rates of invasive ventilation could range from slight benefit at lower inspired oxygen fractions to slight harm at inspired oxygen fraction of 1.0.

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Discordant Evidence on Corticosteroids in Sepsis: A Meta-Research Study

Weibel, S.; Duengfelder, H.; Pscheidl, T.; Krone, M.; Meybohm, P.

2026-08-21 intensive care and critical care medicine 10.64898/2026.08.20.26360343 medRxiv
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Background Despite numerous randomized controlled trials (RCTs) and systematic reviews (SRs), current sepsis guidelines continue to issue only weak recommendations for corticosteroids. We examined the clinical scope, underlying study pools, and mortality conclusions of SRs evaluating corticosteroids for sepsis. Methods We conducted a meta-research study of SRs on corticosteroids in sepsis (2015 to 2025), extracting SR characteristics, mortality results, and included RCTs. Study-pool overlap was assessed using an SRxRCT inclusion matrix, Jaccard similarity (J), and hierarchical clustering. SRs and RCTs were classified according to standardized Population, Intervention, Comparison, Outcome (PICO) profiles. We explored discordance in short-term mortality conclusions among clinically comparable SRs and potential associations with study-pool composition, target populations, and methodological characteristics. Results Forty-two SRs including 121 unique RCTs were identified. More than half of pairwise SR comparisons shared no RCTs, and only three pairs showed high overlap (J>0.8). SRs addressing similar intervention and target population profiles frequently relied on different study pools. Among 38 SRs with short-term mortality meta-analyses, 15 (39%) reported benefit and 23 (61%) no evidence of effect. Discordance occurred exclusively among SRs evaluating broad, non-specific corticosteroid strategies; conclusions were consistent for hydrocortisone plus fludrocortisone (benefit) and hydrocortisone, ascorbic acid, and thiamine (no evidence of effect). SRs including sepsis +/- shock populations more frequently reported benefit than those restricted to septic shock (62% vs 22%), although estimates were imprecise. No single methodological or clinical factor consistently explained discordance. Conclusions SRs addressing apparently similar clinical questions frequently synthesized different underlying evidence bases and reported discordant conclusions. Guideline developers should therefore consider not only methodological quality and reported PICO, but also whether the RCTs included in an SR adequately represent the intended clinical question. Clinically coherent evidence syntheses may improve the interpretability of pooled treatment effects and support more targeted corticosteroid therapy in sepsis.

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Social, functional and quality-of-life outcomes among long term acute care hospital survivors with tracheostomy

Naiditch, H.; Moale, A.; Nouraie, S. M.; McVerry, B. J.; Jain, S.; Zemke, A.

2026-01-22 intensive care and critical care medicine 10.64898/2026.01.20.26343699 medRxiv
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RationalePatients receiving prolonged mechanical ventilation are often discharged to long-term acute care hospitals (LTACHs) with hopes of recovery and ultimately return to the community. Among those who survive and undergo tracheostomy, little is known about their quality of life and social outcomes after LTACH discharge. ObjectiveMeasure health related quality of life in a cohort of critical illness survivors who underwent tracheostomy and an LTACH stay MethodsSingle center, prospective observational cohort study conducted at a long-term acute care hospital between 2022-2024. Adults with prolonged mechanical ventilation requiring tracheostomy were eligible. Survivors or surrogates completed a telephone survey 3-6 months after LTACH admission. Surveys included the Katz Index of Independence in Activities of Daily Living (ADL) and Patient-Reported Outcome Measurement Information System (PROMIS) measures of physical, mental, and social health. Descriptive statistics summarized scores; exploratory analyses examined associations between persistent tracheostomy and residence. ResultsSeventy participants were enrolled (median age 64 years; 58.6% male). Median ICU length of stay was 40 days prior to LTACH transfer. By LTACH discharge, 39 people (56%) had been decannulated. At a median follow-up of 5.5 months, 50 participants (71%) were alive, 39 completed the survey. Most respondents reported impairments in feeding, dressing, and bathing. PROMIS t-scores demonstrated severe impairments in physical function (median 26.7), and ability to participate in social roles (37.0), with high symptom burden of depression (61.9) and anxiety (58.3). Greater impairment was observed among participants with ongoing tracheostomy or were not residing at home. Home residence did not differ significantly by decannulation status (61.8% decannulated vs. 46.7% not decannulated; OR 1.85 (95% CI 0.54, 6.30)). ConclusionsSurvivors of PMV and LTACH admission experience marked functional impairments, restricted participation in social roles, and prominent symptoms of depression and anxiety--particularly among patients not living at home or with persistent tracheostomy. These data may help clinicians prepare patients and families for life after tracheostomy and guide tailored support addressing multifaceted needs. Primary Funding SourceNational Institutes of Health

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The Epidemiology of Intensive Care Unit Readmissions Across Ten Health Systems

Amagai, S.; Chaudhari, V.; Chhikara, K.; Ingraham, N. E.; Hochberg, C. H.; Barker, A. K.; Mao, C.; Ortiz, A. C.; Weissman, G. E.; Schmid, B. E.; Schwinne, M.; Bhavani, S. V.; Guleria, S.; Liao, Z.; Markov, N.; Lyons, P. G.; Park-Egan, B.; The CLIF Consortium, ; Parker, W. F.; Luo, Y.; Rojas, J. C.; Gao, C. A.

2025-03-13 intensive care and critical care medicine 10.1101/2025.03.10.25323672 medRxiv
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BackgroundICU readmissions are associated with increased morbidity, mortality, and healthcare costs. As ICU patient complexity increases and care practices evolve, the contemporary epidemiology of ICU readmissions remains unclear. We aimed to examine ICU readmission rates and timing across multiple health systems, focusing on unplanned readmissions occurring within 24, 48, and 72 hours after ICU discharge. MethodsWe performed a retrospective cohort study using federated data from the Common Longitudinal ICU data Format (CLIF) Consortium, comprising nine healthcare systems between January 2020 and December 2021 and the MIMIC-IV database. The cohort included adult patients ([&ge;]18 years) discharged alive from the ICU. Readmissions following planned surgeries or interventional procedures were excluded. Data were analyzed locally at each site without centralizing patient-level data, and analyses focused on patient demographics, discharge disposition, readmission timing, and clinical interventions during ICU stays and readmissions. Statistical comparisons were performed using two-proportion z-tests and chi-squared tests. ResultsAmong 185,241 hospital admissions across 19 hospitals, 8.6% of ICU discharges were readmitted during the same hospitalization. Unplanned readmissions occurred within 24 hours in 1.9% of cases, 3.4% within 48 hours, and 4.5% within 72 hours. Readmitted patients experienced higher in-hospital mortality (20.6% vs. 2.1%, p<0.001). Compared to the initial ICU stay, ICU readmissions were associated with significantly increased respiratory (42.3% vs. 35.3%, p<0.001) and vasopressor support (26.1% vs. 23.1%, p<0.001). ConclusionsICU readmissions remain common and are linked to worse outcomes. Readmissions require more respiratory and vasopressor support. Future work should focus on characterizing these subphenotypes and improving ICU discharge processes to reduce preventable readmissions.

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The impact of Intensive Care Strain on Patients Outcomes during COVID-19 - a UNITE COVID study

Kohler, K.; De Corte, T.; Greco, M.; Povoa, P.; Cecconi, M.; Ostermann, M.; De Waele, J.; Conway Morris, A.; UNITE-COVID investigators,

2025-02-27 intensive care and critical care medicine 10.1101/2025.02.27.25322947 medRxiv
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PurposeIntensive care unit (ICU) strain is associated with increased mortality. Most strain metrics focus on simple measures such as bed occupancy or admission rates. There is limited data on mitigation strategies, such as procedure teams or staff well-being services on strain, or the impact of increased patient-to-nurse ratios and non-ICU trained nurses working in ICU. MethodsUsing the multi-national UNITE-COVID study, collecting data from ICUs on their busiest day in two periods (2020 and 2021) of the COVID-19 pandemic, we evaluated metrics of strain (Bed occupancy, patient: nurse ratio, use of non-ICU staff and shortages of consumables) and potential mitigators (procedural support teams and staff well-being interventions). We examined how these related to outcomes (mortality, complications and length of stay). ResultsIn both epochs, ICUs experienced significant strain, with ICU bed expansion to 133% and 163% respectively, whilst patient-to-nurse ratios increased by 0.4 and 0.3. Consumable shortages were widespread in 2020. Mortality was inversely correlated with staff well-being interventions in both epochs. Complications were inversely correlated with procedure support teams, and positively correlated with staffing ratios. In regression models, pressure sores were reduced in presence of support teams (p=0.004) and increased with the increase in patients per nurse (p=0.05) whilst unplanned extubations were related to non-ICU trained staff working in ICU(p = 0.02). ConclusionsCOVID-19 induced ICU strain had effects beyond mortality, including increases in complications. Staff pressure and lack of ICU training were related to specific complications, whilst support teams and well-being interventions were associated with improved outcomes. Take home messageWe examined the effects of various aspects of ICU strain on patient outcomes during the periods of maximal unit occupancy during the COVID-19 pandemic. We identified adverse relationships between preventable complications and increases in patient:nursing ratios and use of non-ICU trained staff, whilst procedural support teams and staff well-being interventions were associated with better patient outcomes. summaryCOVID strained ICUs. Increased patient:staff ratios & non-ICU staff increased complications, staff well-being initiatives improved outcomes.