Critical Care Explorations

BackgroundMixed trial results suggest that some ventilated patients with acute respiratory distress syndrome (ARDS) benefit from high PEEP while others may be harmed, indicating heterogeneity of treatment effect (HTE). This study applies data-driven predictive approaches to uncover HTE and re-examines previously hypothesized HTE. This manuscript serves as a pre-registration of planned external validation of our trained models. MethodsWe identified eight randomized trials, and obtained individua...

BackgroundPulse oximeters are typically validated on cohorts of 200-500 subjects under controlled conditions. Whether these cohorts capture the demographic heterogeneity of national clinical practice -- and whether measurement error is associated with patient outcomes -- has not been established at scale. MethodsWe analyzed paired SpO2/SaO2 readings from three independent sources spanning 209 U.S. hospitals: MIMIC-IV (1 hospital; 12,934 ICU stays), eICU-CRD (208 hospitals; 55,178 stays), and th...

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 t...

RationaleAutonomic dysfunction is a hallmark of sepsis pathophysiology, yet its quantification remains challenging. Multiscale entropy (MSE) derived from heart rate variability (HRV) offers a dynamic measure of physiological complexity and may serve as a biomarker of early deterioration associated with subsequent organ failure, vasopressor escalation, or mortality. ObjectiveTo determine whether MSE computed across multiple temporal scales during the first 24 hours of Intensive Care Unit (ICU) a...

RationalePulse oximeter performance may vary by skin pigmentation, but most data are retrospective with key limitations. ObjectiveTo quantify pulse oximeter bias [mean difference between pulse oximeter oxygen saturation (SpO2) and arterial blood functional oxygen saturation (SaO2)], and average root mean square error (ARMS) and estimate adjusted effects of skin pigment on bias or ARMS in critically-ill adults MethodsProspective single-center study of 631 ICU patients (2022-2024) directly obser...

ObjectivesPatients with COVID-19 Acute Respiratory Distress Syndrome (CARDS) appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (Type 1) and a more conventional ARDS phenotype displaying the typical characteristics of the baby lung (Type 2). We aimed to test plausible hypotheses regarding the pathophysiological mechanisms underlying CARDS, and to evaluate the resulting implications for ventilatory managem...

OBJECTIVETimely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. Therefore, we aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review....

BackgroundSepsis-related organ dysfunction results from complex interactions between systemic hemodynamics, microcirculatory alterations, and cellular metabolic failure. Conventional resuscitation strategies guided by global parameters may miss persistent tissue hypoperfusion, a phenomenon termed "hemodynamic incoherence." The PRISM trial was designed to determine whether individualized management guided by advanced multimodal circulatory and perfusion monitoring improves outcomes in septic shoc...

BackgroundProgressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously, but occult hypoxemia can occur in Black patients because the technique is affected by skin color. Oxygen dissociation curves allow non-invasi...

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 routi...

Background: Severity scoring systems such as SOFA, NEWS2, and qSOFA effectively identify deteriorating ICU patients by aggregating physiological parameters into composite indices that trigger clinical alerts. However, these systems evaluate patient state at discrete time points and do not model the temporal dynamics of organ deterioration or the pharmacokinetic constraints that govern whether a given intervention can achieve therapeutic effect before an organ trajectory crosses an irreversible t...

RationaleHeterogeneity of sepsis limits discovery and targeting of treatments. Clustering approaches in critical illness have identified patient groups who may respond differently to therapies. These include in acute respiratory distress syndrome (ARDS) two inflammatory sub-phenotypes, using latent class analysis (LCA), and in sepsis two Sepsis Response Signatures (SRS), based on transcriptome profiling. It is unknown if inflammatory sub-phenotypes such as those identified in ARDS are present in...

BackgroundDelirium during acute respiratory failure is common and morbid. Pharmacologic sedation is a major risk factor for delirium, but some sedation is often necessary for the provision of safe care of mechanically ventilated patients. A simple, transparent model that predicts sedative-associated delirium in mechanically ventilated ICU patients could be used to guide decisions about personalized sedation. Research QuestionCan the risk of sedative-associated delirium be estimated in mechanica...

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...

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 Lon...

Corticosteroids decrease the duration of organ dysfunction in a range of infectious critical illnesses, but their risk and benefit are not fully defined using this construct. This retrospective multicenter study aimed to evaluate the association between usage of corticosteroids and mortality of patients with infectious critical illness by emulating a target trial framework. The study employed a novel stratification method with predictive machine learning (ML) subphenotyping based on organ dysfun...

BackgroundThe role of arterial blood gas (ABG) testing in the intensive care unit (ICU) remains debated within the "less is more" paradigm. While unnecessary testing may pose risks without benefit, timely ABGs provide critical information in unstable patients. Institutional variation in early ABG utilization and its association with outcomes remains unclear. MethodsWe conducted a multicenter retrospective cohort study using the Japanese Intensive Care PAtient Database (JIPAD) between April 2015...

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 20...

IntroWe develop a straightforward ICU acuity score (Q3) that is calculated every 3 hours throughout the first 10 days of the ICU stay. Q3 uses components of the Oxford Acute Severity of Illness Score (OASIS) and incorporates a new component score for vasopressor use. In well-behaved models of ICU mortality, the marginal effects of Q3 are significant across the first 10 days of the ICU stay. In separate models, Q3 has significant effects on ICU remaining length of stay. The score has implications...

IntroductionSepsis diagnosis remains clinical and heterogeneous. We hypothesized that a proteomics-informed machine-learning approach could identify a small, easy-to-use, and optimized set of clinical variables to complement or potentially outperform SOFA. MethodsWe conducted a prospective, single-center, observational study in an academic intensive care unit. Plasma from critically ill patients with and without sepsis was analyzed using liquid chromatography coupled with tandem mass spectromet...