IMPORTANCE:Patients with acute respiratory distress syndrome (ARDS) are at risk for higher morbidity and mortality with concurrent acute kidney injury (AKI). AKI diagnosis relies on serum creatinine, which is confounded by fluid overload. Use of fluid overload-adjusted creatinine can diagnose AKI (termed Cryptic AKI) that would otherwise be missed by the traditional Kidney Disease Improving Global Outcomes (KDIGO) definition. It is unknown whether Cryptic AKI is biochemically distinct from patients without AKI. OBJECTIVES:Determine whether pediatric ARDS patients with Cryptic AKI have a biochemical profile that is similar or distinct from patients with KDIGO-defined AKI or no AKI. DESIGN SETTING AND PARTICIPANTS:Observational study of 333 pediatric ARDS patients in a quaternary PICU. MAIN OUTCOMES AND MEASURES:Mortality, length of stay, and ventilator-free days were measured for all patients. Biomarkers indicative of tissue damage and inflammation were measured on days 1, 3, and 7 of ARDS. RESULTS:Cryptic AKI was associated with higher mortality and longer length of stay than no AKI, similar to KDIGO AKI. Biomarkers angiopoietin-2, pro-collagen III N-terminal peptide, heat shock protein 70, tumor necrosis factor receptor 1, and interleukin-8 were significantly higher in Cryptic and KDIGO AKI than in no AKI. CONCLUSIONS AND RELEVANCE:Cryptic AKI is clinically significant and represents true kidney injury, with a biomarker profile similar to KDIGO AKI and distinct from patients without AKI.
OBJECTIVES:To compare transthoracic echocardiography (TTE) and cardiovascular parameters in patients with hyper- and hypoinflammatory acute respiratory distress syndrome (ARDS), derived using a validated, artificial intelligence clinical classifier. To compare overlap between latent class analysis-derived cardiovascular subphenotypes and clinical classifier-derived inflammatory subphenotypes of ARDS. DESIGN:Retrospective single-center cohort study. SETTING:University Hospital ICU, Birmingham, United Kingdom. PATIENTS:Intubated patients who received a transthoracic echocardiogram within 7 days of ARDS onset between April 2016 and December 2021. MEASUREMENTS AND MAIN RESULTS:A total of 691 patients were included, age 61 years (interquartile range, 50-72 yr), 65% male, 41% 90-day mortality rate. A total of 30% (n = 207) were classified as hyperinflammatory and had higher mortality (64% vs. 31%; p < 0.0001) compared with the hypoinflammatory subgroup. Right ventricular (RV) size and function did not differ between hyper- and hypoinflammatory subphenotypes. Instead, the hyperinflammatory subgroup exhibited a hyperdynamic cardiovascular profile with higher left ventricular ejection fraction and cardiac output. Latent class analysis identified four cardiovascular subphenotypes; RV-related profiles were predominantly hypoinflammatory, whereas the hyperdynamic cardiovascular subtype was enriched in hyperinflammatory patients. CONCLUSIONS:Inflammatory and cardiovascular subphenotypes represent complementary but distinct axes of ARDS pathobiology. The hyperinflammatory subphenotype aligns with a hyperdynamic circulation, whereas RV dysfunction may be mechanistically independent.
IMPORTANCE:Cardiac dysfunction following blunt traumatic brain injury (TBI) has been commonly defined as new decreased ejection fraction (EF) or new regional wall motion abnormalities (RWMAs). OBJECTIVES:We assessed cardiac dysfunction after blunt TBI by echocardiographic signatures, association with intracranial abnormalities, and clinical findings. DESIGN, SETTING, AND PARTICIPANTS:Retrospective cohort study of adult blunt TBI patients hospitalized at an American College of Surgeons verified Level 1 Trauma Center during 2022-2023 who underwent echocardiography (echo) within 48 hours of admission. Patients with preexisting cardiac comorbidities were excluded. MAIN OUTCOMES AND MEASURES:The trauma registry at a Level 1 Trauma Center and corresponding electronic medical record were reviewed for TBI patients. Echo reports were evaluated for cardiac dysfunction as measured by EF, RWMAs, and fractional shortening (FS). FS is a simple M-mode measure predictive of systolic function defined as the percentage change in left ventricular diameter between the end of diastole and systole. RESULTS:Of 105 blunt TBI patients meeting inclusion criteria, 81 had normal FS, 23 patients had decreased FS below 30%, and 1 had increased FS on echo. All 81 patients with normal FS had preserved EF, but 19 of 23 (83%) patients with decreased FS also had preserved EF. Patients with decreased FS had increased ICU length of stay, inpatient mortality, and craniotomy/craniectomy rates. Subarachnoid hemorrhage was the most frequent intracranial abnormality in patients with decreased FS. CONCLUSIONS AND RELEVANCE:FS was depressed in a subset of TBI patients with above adverse in-hospital outcomes. Our data suggest FS below 30% may be a useful echocardiographic parameter associated with clinically significant cardiac dysfunction in blunt TBI patients.
OBJECTIVES: Among precision medicine approaches in critical care, protein biomarker quantification offers a timely and reproducible route to patient subtyping, but the landscape of automated platforms suitable for near-patient deployment remains unclear. This review aimed to identify available automated platforms for quantitative measurement of human protein biomarkers in blood, serum, or plasma, in order to support planning for precision medicine trials. DATA SOURCES: PubMed, Embase, and Espacenet were searched for eligible sources. Relevant company correspondence was also included where available. STUDY SELECTION: Publication reports, patent reports, and company correspondence were eligible if they described commercially available platforms meeting a prespecified definition of automation for quantitative measurement of one or more human protein biomarkers in blood, serum, or plasma. DATA EXTRACTION: Data were extracted on device model, manufacturer, and analytes measured. Eligible devices were extracted as separate device records, including multiple devices reported within a single source. DATA SYNTHESIS: Overall, 228 sources were included, comprising 211 publication reports, 14 patent reports, and three company correspondence reports. Publications contributed 256 publication-derived device records representing 74 distinct automated device models from 34 manufacturers. The most frequently represented devices were Ella ( n = 48), LUMIPULSE G1200 ( n = 25), LUMIPULSE G600II ( n = 17), cobas e 411 ( n = 13), and Simoa HD-X ( n = 12). Multiplex capability was identified for eight devices in included publications, with two additional multiplex-capable platforms identified through company correspondence. Across publication-derived device records, inflammatory and neurologic biomarkers predominated. The most frequently reported inflammatory biomarkers were procalcitonin ( n = 36), interleukin (IL)-6 ( n = 35), tumor necrosis factor (TNF)-α ( n = 22), and IL-10 ( n = 14). The most frequently reported neurologic biomarkers were neurofilament light chain ( n = 34), p-tau217 ( n = 31), Aβ42 ( n = 29), Aβ40 ( n = 27), and p-tau181 ( n = 27). CONCLUSIONS: Automated platforms for quantitative protein biomarker measurement span numerous devices and manufacturers, but multiplex capability remains limited. More standardized device-level reporting would strengthen platform selection for biomarker-enabled trials and future clinical implementation.
OBJECTIVE:To describe site-level ICU organizational policies and implementation of pain, agitation, and delirium (PAD) best practices before the COVID-19 pandemic, and perceived changes during the pandemic. DESIGN:International site-level questionnaire study. SETTING:Participating sites completed a standardized electronic Case Report Form between January 5, 2022 and March 31, 2023. PATIENTS/CENTERS:Ninety-three ICUs caring for adult patients from 79 hospitals across 27 countries in North America, South America, and Europe. INTERVENTIONS:Each ICU submitted data on site characteristics, staffing, implementation of PAD protocols and assessment tools prepandemic, and perceived changes during the COVID-19 pandemic. Descriptive statistics and multivariable logistic regressions were performed using R. MEASUREMENTS AND MAIN RESULTS:Of 93 ICUs, 63% were university-affiliated, and 59% reported a closed physician staffing model. Most managed mixed patient populations (78%), with a nurse-to-patient ratio for ventilated patients of 1:2 (45%) or 1:1 (39%). Physiotherapists and pharmacists were available in 83% and 68% of ICUs, respectively. Over 75% reported routine use of validated PAD scales, most commonly Richmond Agitation Sedation Scale (86%), Confusion Assessment Method for ICU (59%), and Numeric Rating Scale (44%). Protocols were most available for spontaneous breathing trials (60%) and sedation (58%), followed by delirium (53%), mobilization (47%), and pain (46%). University affiliation and 1:1 nurse staffing was associated with reported use of delirium or mobilization protocols. The presence of a weaning protocol was associated with higher odds of daily sedation interruption (adjusted odds ratio [aOR] 3.80; 95% CI, 1.43-10.89; p = 0.009), and use of sedation protocols (aOR 5.95; 95% CI, 2.29-16.86; p < 0.001). Nearly one-half of ICUs reported drug shortages during the pandemic, and 62% prohibited any visitation. CONCLUSIONS:ICU organizational structures and reported PAD practices vary widely worldwide. Despite international guidelines, many ICUs lack consistent implementation of evidence-based sedation, analgesia, and delirium management strategies.
IMPORTANCE: Biologically defined sepsis subtypes have been identified in low- and middle-income countries (LMICs), but limited access to molecular diagnostics constrains broader evaluation and implementation in resource-limited settings. OBJECTIVES: To determine whether bedside-accessible variables could approximate molecular sepsis subtype assignments among Ugandan adults with sepsis. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of two prospective observational sepsis cohorts conducted at Tororo General Hospital (Research in the Epidemiology of Severe and Emerging Infections in Uganda-2-Tororo [RESERVE-U-2-TOR]) and Entebbe Regional Referral Hospital (Research in the Epidemiology of Severe and Emerging Infections in Uganda-1-Entebbe [RESERVE-U-1-EBB]), Uganda. Participants were adults 18 years old or older hospitalized with sepsis who underwent transcriptomic ( n = 355) and/or proteomic ( n = 495) profiling. MAIN OUTCOMES AND MEASURES: Prespecified clinical and clinico-microbiologic models were evaluated for discrimination and calibration against Uganda-derived transcriptomic and proteomic sepsis subtypes and, secondarily, high-income country (HIC)-derived sepsis subtypes and immune dysregulation frameworks. RESULTS: In RESERVE-U-2-TOR, clinical models incorporating demographic and physiologic variables showed moderate discrimination for transcriptomic and proteomic subtypes (area under the receiver operating characteristic curve [AUROC], 0.75 [95% CI, 0.69–0.81] and 0.73 [95% CI, 0.66–0.80], respectively), with generally acceptable calibration. Adding rapid HIV, malaria, and tuberculosis test results did not meaningfully improve performance. In RESERVE-U-1-EBB, discrimination was more variable (AUROC range, 0.63–0.75), with generally acceptable calibration. Performance was similarly modest for HIC-derived sepsis subtypes and immune dysregulation axes. CONCLUSIONS AND RELEVANCE: Bedside-accessible clinical variables, with or without rapid microbiologic testing, only partially approximated molecular sepsis frameworks in Uganda. Scalable molecular biomarker platforms are needed to advance precision medicine for sepsis in LMICs.
OBJECTIVES: Public insurance reduces financial barriers to healthcare but may not fully mitigate the influence of neighborhood opportunity on pediatric critical care utilization. We examined the association between neighborhood opportunity and PICU utilization, including costs, and assessed whether public insurance modified these relationships. DESIGN: Population-level retrospective observational study. SETTING: A single, free-standing quaternary children’s hospital in southwestern Ohio. PATIENTS: Children 18 years or younger admitted to the PICU between January 1, 2016, and December 31, 2022, residing within the hospital’s primary service area. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were census tract (CT) level PICU admission rates and median PICU costs. Very low opportunity neighborhoods had the highest PICU admission rates (3.41 vs. 1.76 admissions per 1000 children in very high opportunity neighborhoods; p < 0.001). Overall CT level median PICU costs did not differ by Child Opportunity Index (COI; p = 0.582). Publicly insured children were more likely to reside in very low opportunity neighborhoods (44% vs. 10%; p < 0.001). Within very low opportunity neighborhoods, publicly insured children had lower median PICU costs than children with other insurance ($16,693 vs. $22,585; p = 0.008); costs were similar across insurance groups in other COI quintiles. In multivariable analyses, the interaction between insurance status and neighborhood opportunity was not statistically significant ( p = 0.099). CONCLUSIONS: Children from low opportunity neighborhoods experienced higher PICU admission rates, while neighborhood opportunity and public insurance jointly influenced patterns of PICU resource utilization. Expanding insurance coverage alone is unlikely to eliminate disparities; improving neighborhood conditions and implementing place-based strategies may help mitigate PICU utilization.
IMPORTANCE: Phenobarbital use in ICU alcohol withdrawal syndrome (AWS) may reflect severe or refractory withdrawal and treatment escalation, making multicenter data important to understand its use within ICU practice and its relationship with clinical outcomes. OBJECTIVES: To evaluate phenobarbital use in real-world ICU AWS as a marker of severe or refractory withdrawal and treatment escalation. We also examined its association with time-to-discharge and safety outcomes compared with nonphenobarbital regimens. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study using multiple imputation and propensity score matching. Adults with AWS, defined as Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score greater than or equal to 10, were included if they received a phenobarbital-based or nonphenobarbital-based regimen in ICUs across a large academic health system from June 30, 2017, to July 1, 2024. Postoperative ICU admissions were excluded. MAIN OUTCOMES AND MEASURES: Primary outcomes were time to ICU and hospital discharge alive from treatment initiation. Safety outcomes were hypotension, new intubation, and aspiration within 48 hours. RESULTS: Of 1216 patients, 345 (28.4%) received phenobarbital. Before matching, phenobarbital-treated patients had higher CIWA-Ar, Acute Physiology and Chronic Health Evaluation III, and pre-ICU benzodiazepine exposure, consistent with more severe or refractory withdrawal. In adjusted time-to-discharge models, phenobarbital use was not significantly associated with time to hospital discharge alive (discharge rate ratio [DRR], 0.91; 95% CI, 0.74–1.12; p = 0.370) or ICU discharge alive (DRR, 0.77; 95% CI, 0.59–1.01; p = 0.057). Hypotension and intubation were similar, and aspiration was less frequent with phenobarbital. CONCLUSIONS: In a contemporary ICU cohort, phenobarbital use reflected treatment escalation in patients with more severe or refractory AWS. After adjustment, time to ICU and hospital discharge alive did not differ significantly, hypotension and intubation were similar, and aspiration was less frequent with phenobarbital. Future studies should define optimal timing, dosing, and patient selection.
OBJECTIVES: To summarize the research methods, patient populations, and measures used to examine the associations between community-level social determinants of health (SDoH) and sepsis risk, and to describe the findings of the current evidence. DATA SOURCES: PubMed, Embase, Web of Science, Global Health, Cochrane Library, Scopus, Web of Science-Core Collection, and Latin American and Caribbean Literature on Health Sciences Database from January 1, 1991, to October 31, 2024. STUDY SELECTION: Studies were included if they evaluated the quantitative association between at least one community-level SDoH, measured at a spatial level smaller than a country and larger than a household, and sepsis incidence and/or mortality. DATA EXTRACTION: Titles, abstracts, and full-text articles were independently screened in duplicate. Data extraction was performed in duplicate using a standardized form capturing study design, sepsis definition, patient population, community-level SDoH domains, and outcomes. DATA SYNTHESIS: Of the 10,504 studies retrieved, 63 studies were included in the final analysis. The majority of studies ( n = 39, 62%) were published between 2020 and 2024. Children ( n = 10, 16%) and people in low- or middle-income countries ( n = 9, 14%) were the least represented study populations. The most common domains of evaluated SDoH were demographic ( n = 31, 49%), health access ( n = 17, 27%), and economic ( n = 16, 25%), with the most frequent variables being rurality ( n = 24, 40%) and median household income by ZIP code ( n = 10, 16%). There were 10 (16%) prospective cohort studies, 43 (68%) retrospective cohort, 6 (10%) case-control, and 4 (6%) ecological. Most studies ( n = 54, 86%) reported a significant association between at least one community-level SDoH and sepsis incidence and/or mortality. CONCLUSIONS: There is a growing but heterogeneous body of evidence on the associations between community-level SDoH and sepsis risk. Future research requires better representation from populations with the highest sepsis burden, more consistent definitions, and more rigorous, innovative methods to elucidate the mechanisms driving associations between multiple community-level SDoH and sepsis.
IMPORTANCE:Early mobilization (EM) in the ICU mitigates post-intensive care syndrome (PICS) and improves functional outcomes. However, comprehensive national data on mobilization practices and patient-level barriers in Japan's super-aged society remain limited. OBJECTIVES:To describe current mobilization and rehabilitation practices, the prevalence of EM, and factors associated with remaining in bed among adult ICU patients in Japan. DESIGN, SETTING, AND PARTICIPANTS:This nationwide, multicenter, cross-sectional, 1-day point-prevalence study was conducted on February 20, 2024, across ICUs in Japan. All adult patients (18 yr or older) physically present in the ICU between 00:00 and 14:00 were included. MAIN OUTCOMES AND MEASURES:The highest mobilization level was assessed using the ICU Mobility Scale (IMS). Out-of-bed mobilization was defined as IMS greater than or equal to 3, and EM as IMS greater than or equal to 3 within 48 hours of ICU admission. Patient characteristics, treatments, and perceived barriers were extracted from medical records. Multivariable logistic regression was performed to identify factors independently associated with remaining in bed. RESULTS:Data were collected from 81 ICUs in 72 hospitals, and 693 patients were included in the analysis (median age, 72 yr; 68% 65 yr or older). Of these, 269 patients (38.8%) were receiving mechanical ventilation. Out-of-bed mobilization occurred in 42.6% of patients overall and in 17.8% of mechanically ventilated patients. EM within two days of ICU admission was achieved in 44.7% of patients overall and in 13.6% of mechanically ventilated patients. Multivariable analysis demonstrated that mechanical devices, particularly mechanical ventilation with an endotracheal tube, vasopressor use, sedative and analgesic administration, and coma were independently associated with a higher likelihood of remaining in bed. Conversely, the presence of delirium and higher nutritional intake were associated with a higher likelihood of achieving out-of-bed mobilization. Subjective assessments identified pathologic and psychoneurological factors as the predominant barriers. CONCLUSIONS AND RELEVANCE:Despite advanced patient age, mobilization and EM rates in Japanese ICUs were comparable to those reported internationally. However, patients at the highest risk for PICS, particularly those requiring advanced organ support or intensive sedation, were the least likely to achieve out-of-bed mobilization. These findings highlight a persistent clinical dilemma and suggest the need for tailored strategies to safely expand mobilization among the most vulnerable ICU populations in super-aged societies.
OBJECTIVES:Post-intensive care syndrome (PICS) and PICS-family (PICS-F) lead to lasting physical, cognitive, and psychologic challenges among survivors of critical illness and their caregivers. It is unclear how best to support these individuals. We aimed to evaluate the feasibility of a co-designed, multicomponent post-ICU follow-up intervention and to explore its association with symptoms of PICS and PICS-F. DESIGN:This was a pragmatic, mixed-methods randomized controlled trial. SETTING:This study was conducted at an academic ICU in Canada. PATIENTS:We enrolled 20 patient-caregiver dyads (n = 40 participants). Patients were eligible if they were 18 years old or older, expected to survive greater than or equal to 6 months after discharge from ICU, and were at high-risk for PICS. Caregiver participants were adult caregivers of enrolled patients. INTERVENTIONS:Dyads were randomized 1:1 to receive usual care or an intervention bundle co-designed with patients and caregivers, consisting of an ICU diary, informational materials, and two multidisciplinary follow-up clinic visits at 1 and 3 months after ICU discharge. MEASUREMENTS AND MAIN RESULTS:Trial outcomes included feasibility metrics, qualitative interviews, process evaluation, and clinical measures at 6 months. Qualitative data were analyzed using reflexive thematic analysis. Quantitative outcomes included PICS symptomatology, quality of life, caregiver burden, healthcare utilization, and functional status. The consent rate was 87.5%, with a mean enrollment of 5.25 participants/month. Twenty dyads were randomized; one ICU participant in each group died before their 6-month follow-up. Seven of nine dyads in the intervention and all nine in the control completed 6-month follow-up. Intervention group survivors had lower depressive symptom scores compared with controls. Intervention group caregivers reported higher emotional well-being and social functioning scores and lower anxiety, depression, and caregiver burden. Qualitative findings demonstrated greater emotional support, preparedness, and continuity of care in the intervention group. CONCLUSIONS:Our post-ICU care bundle was feasible and may be associated with improved psychosocial outcomes.
OBJECTIVES:Optimal postextubation respiratory support for critically ill patients at high risk of reintubation remains uncertain. We aimed to compare the efficacy of high-flow nasal cannula (HFNC) vs. noninvasive ventilation (NIV) in preventing reintubation among critically ill adults at high risk of extubation failure. DATA SOURCES:PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov were systematically searched from inception through the latest available date. STUDY SELECTION:HIGH-FLOW OXY is a systematic review and meta-analysis comparing HFNC with NIV in ICU patients at high risk of extubation failure. The primary outcome was short-term reintubation within 3 days postextubation. Secondary outcomes included ICU mortality, ICU length of stay, sepsis, and nosocomial pneumonia. DATA EXTRACTION:Data were extracted using predefined criteria. Risk of bias (RoB) was assessed with the Cochrane tool, and certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used for pooled analyses. Prespecified subgroup analyses included obese patients, very high-risk patients, elderly individuals, and those with acute exacerbations of chronic obstructive pulmonary disease. DATA SYNTHESIS:Fifteen randomized controlled trials (RCTs; n = 2073) were included. HFNC and NIV did not differ significantly in reintubation (odds ratio [OR], 1.19; 95% CI, 0.88-1.59), ICU mortality (OR, 0.74; 95% CI, 0.40-1.38), sepsis (OR, 1.29; 95% CI, 0.71-2.35), nosocomial pneumonia (OR, 1.01; 95% CI, 0.67-1.52), or ICU length of stay (MD -0.37 d; 95% CI, -1.42 to 0.68). Subgroup analyses suggested a higher reintubation risk with HFNC among very high-risk patients (OR, 1.63; 95% CI, 1.05-2.53) and nonoperative obese patients (OR, 2.52; 95% CI, 1.45-4.38). Sensitivity analysis excluding trials at high RoB indicated a potential increase in reintubation with HFNC (OR, 1.32; 95% CI, 1.02-1.71). Overall, certainty of evidence was low across outcomes. CONCLUSIONS:Among ICU patients at high risk of extubation failure, HFNC did not reduce reintubation compared with NIV, and may be associated with increased risk in selected high-risk subgroups. Further adequately powered, risk-stratified RCTs are warranted to define the optimal postextubation respiratory support strategy.
OBJECTIVES:To compare the function of positive end-expiratory pressure (PEEP) titration guided by transpulmonary pressure (Ptp) with traditional lung-protective ventilation to optimize pulmonary arterial compliance (Cpa) in acute respiratory distress syndrome (ARDS) patients. DESIGN:A single center, randomized controlled pilot pathophysiological study. SETTING:A respiratory ICU in China. PATIENTS/SUBJECTS:Adult patients diagnosed with ARDS who had received invasive mechanical ventilation for less than 72 hours. INTERVENTIONS:Patients were randomized to the Ptp group or empirical low tidal volume lung-protective group. MEASUREMENTS AND MAIN RESULTS:The primary endpoint was the difference in the Cpa dynamic changes between the two groups during the first 72 hours of intervention following enrollment. A total of 40 patients were included in the study, with 20 patients in the Ptp group and 20 patients in the control group. The Cpa in the Ptp group was 3.98 ± 0.46 mL/mm Hg at randomization, which was not significantly different from that in the control group (3.89 ± 0.40 mL/mm Hg). The Cpa in the Ptp group was significantly higher than that in the control group (p = 0.039) during the 72 hours of dynamic monitoring performed after enrollment. However, Cpa did not change significantly over time, and there was no significant difference in the trend between the two groups. There was a significant difference in the dynamic change of the right ventricular ejection fraction and oxygen delivery index between the two groups within 72 hours after randomization (p < 0.05). The change in the right ventricular end-diastolic transverse diameter/left ventricular end-diastolic transverse diameter ratio and in the tricuspid annular plane systolic excursion was significantly different between the two groups (p < 0.05). CONCLUSIONS:Ptp-guided PEEP titration was superior to traditional lung-protective ventilation in maintaining a higher Cpa and preserving right ventricular function in patients with moderate-to-severe ARDS caused by pneumonia.
IMPORTANCE:Electrical impedance tomography (EIT) offers a noninvasive, radiation-free imaging alternative, but its perfusion evaluation capability in children is understudied. Hypertonic saline-enhanced EIT may address this gap, enabling real-time guidance for individualized respiratory support. OBJECTIVES:This study aims to systematically assess the safety and efficacy of hypertonic saline-enhanced bedside EIT in evaluating pulmonary perfusion in pediatric patients with acute respiratory distress syndrome (ARDS). DESIGN:Single-center prospective observational study. SETTING AND PARTICIPANTS:Pediatric ARDS patients undergoing invasive mechanical ventilation were enrolled at the PICU of the Capital Center for Children's Health, Capital Medical University, China, from December 29, 2024, to August 7, 2025. MAIN OUTCOMES AND MEASURES:Each participant received a central venous bolus of 0.2 mL/kg (up to a maximum of 10 mL) of a 10% hypertonic saline. EIT data were collected from 2 minutes before the injection to 1-2 minutes following it. Key parameters, including dead space ventilation fraction, intrapulmonary shunt fraction, and ventilation/perfusion (V/Q) matching percentage, were analyzed to evaluate lung pathophysiology and inform therapeutic strategies. The study monitored eight patients (four males, four females; ages ranging from 4 mo to 11 yr). RESULTS:All procedures were well-tolerated, with no adverse events, including hypernatremia. In five patients who also underwent contrast-enhanced CT, EIT findings were consistent with CT results. Seven patients demonstrated matched V/Q ratios (74.97-80.39%), while one patient with pulmonary embolism exhibited increased dead space ventilation (37.03%) and decreased V/Q matching (60.71%). CONCLUSIONS AND RELEVANCE:Hypertonic saline-enhanced EIT is a safe, effective, and feasible bedside method for evaluating pulmonary perfusion in mechanically ventilated children with ARDS. These findings implied potential associations with the CT outcomes, indicating its significant potential for guiding targeted respiratory management. Although promising, these results stem from a small sample size, necessitating further validation in larger studies.
IMPORTANCE:Diabetic ketoacidosis (DKA) is an acute metabolic emergency characterized by hyperglycemia, ketosis, and acidosis due to insulin deficiency. While ICU admission is frequently considered for DKA, admission thresholds and resource utilization vary across countries and institutions. Current data linking admission severity to clinical outcomes among ICU-admitted patients with DKA remain limited. OBJECTIVES:To describe clinical outcomes and ICU length of stay (LOS) stratified by arterial pH recorded during ICU day 1 among ICU-admitted patients with DKA in Japan. DESIGN, SETTING, AND PARTICIPANTS:Retrospective, multicenter observational study of adult patients admitted with a diagnosis of DKA to 95 ICUs across Japan between fiscal years 2015 and 2022. Patients were stratified by arterial pH recorded during ICU day 1 into severe (pH < 7.00), moderate (7.00 ≤ pH < 7.25), and mild (pH ≥ 7.25) groups. MAIN OUTCOMES AND MEASURES:The primary outcome was the in-hospital mortality rate. The secondary outcomes were ICU mortality, hospital LOS, and ICU LOS. RESULTS:Among 866 eligible patients (mild, n = 449; moderate, n = 347; severe, n = 70), in-hospital mortality was low regardless of ICU day 1 pH severity (mild: 4.5%, moderate: 3.2%, and severe: 5.7%). ICU mortality was also low (mild: 1.6% [7/449], moderate: 1.4% [5/347], and severe: 2.9% [2/70]). Hospital LOS was similar across groups (mild: 17.0 d, interquartile range [IQR], 10.0-26.0 d; moderate: 15.0 d, IQR, 9.0-24.0 d; and severe: 15.0 d, IQR, 10.0-22.0 d), whereas ICU LOS tended to increase with severity (mild: 44.3 hr, IQR, 24.6-72.9 hr; moderate: 48.3 hr, IQR, 27.9-76.8 hr; and severe: 57.5 hr, IQR, 31.1-115.0 hr). CONCLUSIONS AND RELEVANCE:In this nationwide ICU registry, in-hospital mortality was low across arterial pH recorded during ICU day 1-defined severity strata, while ICU LOS tended to be longer in strata with more severe DKA. These findings are descriptive; clinically meaningful mortality differences cannot be excluded due to the small number of events, and further studies are needed to evaluate prognostic models and triage strategies.
OBJECTIVES:To determine whether early total bilirubin (T-Bil) trajectories during the first 72 hours after intubation identify trajectory-defined groups with distinct prognostic profiles associated with short-term mortality in mechanically ventilated ICU patients. DESIGN:Multicenter retrospective cohort study with a prespecified day 3 landmark design to mitigate immortal-time bias. SETTING:Mixed medical-surgical ICUs at four tertiary centers. PATIENTS:Adults receiving invasive mechanical ventilation who survived to the day 3 landmark and had serial T-Bil measurements on day 0 and day 3 (± 24 hr). INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Patients were classified according to baseline T-Bil (≤ 1.2 vs. > 1.2 mg/dL) and the direction of change between day 0 and day 3 (change in T-Bil [ΔT-Bil]), yielding four trajectory-defined groups. The primary outcome was 30-day all-cause mortality after the day 3 landmark; 90-day mortality was secondary. Conditional survival was assessed using Kaplan-Meier methods with log-rank tests. Multivariable Cox models adjusted for prespecified covariates available by day 3 (age, sex, body mass index, intubating department, baseline mean arterial pressure, log-transformed aspartate aminotransferase/alanine aminotransferase ratio and platelet count, creatinine, renal replacement therapy, and vasoactive support). Rising T-Bil trajectories were independently associated with higher 30-day mortality, with the strongest association among patients with normal baseline T-Bil who exhibited early increases. In contrast, elevated baseline T-Bil followed by early decline was not associated with excess risk. Findings were consistent in complete-case analyses, in models incorporating day 3 partial Sequential Organ Failure Assessment for severity adjustment, and in analyses of 90-day mortality. Restricted cubic spline analyses demonstrated a nonlinear dose-response relationship between ΔT-Bil and mortality. CONCLUSIONS:Early T-Bil dynamics within 72 hours after intubation were associated with distinct prognostic profiles beyond baseline bilirubin levels and may provide a pragmatic marker for early risk stratification in mechanically ventilated ICU patients.
IMPORTANCE:ICUs contribute substantial environmental impact within the healthcare industry, yet few practical solutions have been published to implement environmentally sustainable practices. OBJECTIVES:To describe the implementation of a systemwide Green ICU initiative using a previously published sustainability pathway and to report early outcomes and lessons learned. DESIGN, SETTING, AND PARTICIPANTS:Observational implementation study within a large, multihospital U.S. healthcare system with adult ICUs. The initiative focused on operational and systems-level ICU processes rather than individual participant outcomes. MAIN OUTCOMES AND MEASURES:A coordinated sustainability infrastructure was established through partnerships among ICU clinicians, the Office of Sustainability, supply chain, and a multidisciplinary "Critical Care Sustainability Work Group." External engagement was expanded through the creation of a national "Green ICU Collaborative." Pilot projects were developed across the "reduce, rethink, recycle" framework. All emissions calculations were done using the Greenhouse Gas Protocol, the U.S. Environmental Protection Agency's U.S. Environmentally-Extended Input-Output modeling framework, and the Intergovernmental Panel on Climate Change accounting principles. The methodology uses large language models for classification to enable scalable, consistent categorization of procurement activities. Key outcomes included medication waste reduction, supply use optimization, and recycling. RESULTS:Medication waste transitioned to on-demand preparation which reduced IV medication waste from 4.8% to 1.4%. Reduction in unnecessary supplies entering ICU rooms diverted an estimated 3401 metric tons of carbon dioxide equivalent annually across 350 ICU beds. A saline flush recycling program collected more than 1600 lbs of recyclable material in its first year. Implementation revealed critical lessons, including the need for early verification of material composition, the incorporation of patients and families into sustainability workflows, and the development of adaptable metrics that align unit-level initiatives with systemwide emissions baselines. CONCLUSIONS AND RELEVANCE:Operationalizing a Green ICU pathway in a large health system is feasible and produces measurable environmental and financial benefits. Establishing strong partnerships, structured processes, and adaptable evaluation strategies is essential for scaling sustainability efforts. This work provides a detailed implementation roadmap to advance Green ICU initiatives and contributes the guidance needed to a growing yet underdeveloped field.
OBJECTIVES: To evaluate randomized adult evidence on adjunctive immunoglobulin M (IgM)-enriched immunoglobulin for sepsis and septic shock, with emphasis on short-term mortality, endpoint heterogeneity, statistical robustness, and harms reporting. DATA SOURCES: MEDLINE, PubMed, Embase, CENTRAL, and Web of Science were searched from inception to September 2025. Reference lists of eligible articles and relevant reviews were screened, forward citation searching was performed, and study registers were checked for additional records. STUDY SELECTION: Randomized controlled trials enrolling adults with sepsis, severe sepsis, or septic shock were eligible when they evaluated an IgM-enriched immunoglobulin preparation in addition to standard care and reported extractable mortality or clinically relevant outcomes. The protocol-concordant core synthesis included English-language adult Pentaglobin trials with extractable short-term mortality data. Two post hoc extensions were labeled explicitly: a language-inclusive Pentaglobin sensitivity analysis and an exploratory formulation-class analysis incorporating the phase II Concentrated IgM for Application (CIGMA) trimodulin trial. DATA EXTRACTION: Two reviewers independently screened records, assessed full texts, extracted study characteristics, endpoint timing, mortality events, and reported adverse events, and resolved disagreements by discussion or third-reviewer adjudication. Risk of bias was assessed with Cochrane Risk of Bias 2 tool for randomized trials, and certainty was judged with the Grading of Recommendations Assessment, Development, and Evaluation principles. DATA SYNTHESIS: Six English-language randomized Pentaglobin trials with extractable short-term mortality data (411 participants) contributed to the protocol-concordant core synthesis. The primary pooled estimate was directionally favorable but statistically inconclusive (odds ratio [OR], 0.65; 95% CI, 0.39–1.07; I 2 = 9%). Restriction to exact 28-day mortality also remained inconclusive (OR, 0.84; 95% CI, 0.50–1.43; I 2 = 0%). An alternative risk-ratio model was similarly nonsignificant (risk ratio, 0.76; 95% CI, 0.55–1.06; I 2 = 0%). Statistically significant estimates arose only in exploratory post hoc analyses: the language-inclusive Pentaglobin sensitivity analysis (OR, 0.57; 95% CI, 0.34–0.95; I 2 = 16%) and the exploratory formulation-class model including CIGMA (OR, 0.64; 95% CI, 0.43–0.94; I 2 = 5%). Safety reporting was incomplete in most Pentaglobin reports. CONCLUSIONS: Current randomized adult evidence does not justify routine use of IgM-enriched immunoglobulin in unselected sepsis or septic shock. Direct Pentaglobin evidence remains statistically inconclusive, whereas statistically significant estimates appear only after exploratory expansion to historical or indirect formulation-level evidence. Efficacy remains unproven, but the recurrent direction of effect supports a modern, adequately powered, phenotype-guided trial with standardized day-28 mortality and rigorous safety assessment.
