To examine 11-year trends in adverse events (AEs) in a pediatric critical care unit (PCCU), assess the impact of the COVID-19 pandemic on patient safety, and evaluate associations between patient acuity and AE severity. Retrospective cohort study using interrupted time series analyses and mixed-effects multinomial regression. A single-center PCCU monitored via the Adverse Event Management System from January 2013 to December 2023. A total of 7290 critically ill and injured pediatric patients admitted to the PCCU over the study period. None (observational study). Exposure variables included the COVID-19 pandemic period, invasive mechanical ventilation and noninvasive ventilation. Demographics, length of stay (LoS), disposition, and AE severity were assessed. The baseline AE rate was 11.94 events per 100 cases. At pandemic onset, AE rates rose by 5.20 events per 100 cases (p = 0.004), then declined 0.81 events per 100 cases quarterly (p = 0.010). Post-pandemic, rates increased 1.94 events per 100 cases quarterly (p = 0.009). LoS decreased 0.01 days quarterly pre-pandemic (p = 0.009), was stable during the pandemic, then increased 0.25 days quarterly post-pandemic (p = 0.033). Higher Pediatric Index of Mortality 2 scores were associated with fewer "near miss" events and more "MinModSev" (minimal, moderate, or severe) AEs. Both mechanical ventilation (p = 0.039) and noninvasive ventilation (p = 0.015) increased the odds of "MinModSev" AEs. This PCCU experienced a transient increase in AEs during COVID-19, followed by recovery and a post-pandemic rise in both AE rates and LoS. Higher illness severity and respiratory support were associated with more severe AEs. These findings underscore the importance of data-driven monitoring systems to sustain patient safety during and after healthcare crises.

We conducted a systematic review and meta-analysis to compare continuous ketamine infusion to other analgosedatives in critically ill children receiving invasive mechanical ventilation (IMV). We searched four electronic databases and trial registries to September 1, 2025. We searched published conference abstracts from two major critical care conferences (2022 to 2025). We preregistered the protocol on PROSPERO (CRD42025631768). Reviewers screened abstracts and full texts independently and in duplicate. We included randomized controlled trials (RCTs) and nonrandomized studies comparing ketamine to other analgosedatives in critically ill children receiving IMV. Independently and in duplicate, we conducted data extraction. We assessed risk of bias using the Risk Of Bias instrument for Use in SysTematic reviews for RCTs or Risk Of Bias In Nonrandomized Studies of Interventions tool, and certainty of evidence using Grading of Recommendations, Assessment, Development, and Evaluation. We pooled data using random-effects models. We included three RCTs and five nonrandomized studies (n = 1436 participants). Pooled analysis demonstrated that ketamine may have no effect on IMV duration (mean difference, 0.00 d; 95% CI, 0.03 d fewer to 0.03 d more; low certainty) and may reduce opioid exposure (mean difference, -8.88 µg/kg cumulative fentanyl equivalents; 95% CI, -6.99 to -10.77; low certainty). We found an uncertain effect of ketamine on delirium, withdrawal, length of stay, clinically important hypotension, and mortality compared with other analgosedatives. Long-term outcomes were not measured in included studies. There is a paucity of studies examining ketamine analgosedation in children receiving IMV, yielding mostly very low certainty evidence for patient-important outcomes due to imprecision and issues related to serious risk of bias of included studies. Methodologically rigorous RCTs are needed to better understand the potential role of ketamine analgosedation in the PICU.

Substance use complicates many hospitalizations by increasing delirium rates, acuity, and costs. Its prevalence rose during the COVID-19 pandemic, potentially contributing to increased delirium in hospitalized patients. To describe trends in substance use and delirium complicating ICU and floor admission around the COVID-19 pandemic and determine whether increased societal substance use was associated with increased prevalence of delirium and substance use in the critically ill. Retrospective cohort study using a large deidentified database of patients admitted to the medical ICU and medicine wards at a single U.S. academic center. We used International Classification of Diseases, Tenth Revision (ICD-10) codes for substance use and a validated ICD-based delirium phenotype to identify exposures. Monthly prevalence of delirium and substance use was calculated in the ICU and on the floor. We performed interrupted time series analysis to determine the effect of the COVID-19 pandemic on these trends. Pre-pandemic, ICU admissions complicated by substance use were declining. The onset of COVID-19 marked a significant reversal, with stepwise continued increase upon entering the recovery phase of the pandemic. Floor admissions complicated by substance use were gradually decreasing pre-pandemic, remained steady during lockdowns, and rose in the recovery phase. ICU delirium prevalence was decreasing pre-pandemic but rose abruptly with the onset of lockdowns, then declined during the pandemic. Delirium prevalence on the floor was increasing before the pandemic and remained stable during the peak and has continued to rise into the recovery phase. Post-COVID, substance use increased in both ICU and floor admissions. Delirium increased during COVID but has since decreased in the ICU. Prevalence has continued to rise on the floor. Substance use and delirium trends during the COVID-19 pandemic reflect strain on the healthcare system during this time.

Test the hypothesis that conservative fluid management with active deresuscitation would not adversely affect tissue perfusion or kidney injury and would be associated with reduced vascular injury compared with usual care. Secondary analysis of the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) trial. ICUs. Critically ill patients enrolled in the RADAR-2 trial. Conservative fluid management with active deresuscitation vs. usual care. Measures of tissue hypoperfusion (whole blood lactate), acute kidney injury (AKIRisk score and urinary cystatin-C), and vascular injury (plasma hyaluronan, syndecan-1, and angiopoietin-2) were compared between groups. For each analyte, change from baseline was compared between groups and the median inter-group difference at each timepoint was estimated with bootstrapped CIs. Exploratory logistic regression examined associations between plasma biomarker levels (including N-terminal pro-B-type natriuretic peptide [NT-proBNP]), 28-day mortality, and treatment allocation. Whole blood lactate levels were similar between groups at all timepoints. Using change from baseline comparisons, no statistically detectable between-group differences were observed in AKIRisk scores or urinary cystatin-C levels. Plasma vascular injury biomarkers showed no statistically detectable between-group differences at any timepoint. High baseline hyaluronan (adjusted odds ratio [aOR], 5.75; 95% CI, 1.94-17.02; p = 0.002), syndecan-1 (aOR, 8.82; 95% CI, 2.67-29.15; p < 0.001), and NT-proBNP greater than 2500 pg/mL (aOR, 21.48; 95% CI, 3.57-129.41; p < 0.001) were independently associated with increased 28-day mortality. There was no evidence of differential treatment response based on these biomarker levels. Conservative fluid management and active deresuscitation were not associated with worsening tissue perfusion or acute kidney injury. A reduction in vascular injury markers was not observed. Given the modest sample size and resultant imprecision, clinically important effects cannot be excluded.

IMPORTANCE:Inflammation, endothelial dysfunction, and complement activation are associated with COVID-19 acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).OBJECTIVES:We hypothesized that higher levels of inflammation, endothelial dysfunction, and complement activation implicated in more severe COVID-19 ALI/ARDS are associated with post-acute sequelae of COVID-19 (PASC) phenotypes in the 3 years after hospitalization.DESIGN, SETTING, AND PARTICIPANTS:A single-center prospective cohort of 150 adult survivors of severe and critical COVID-19 from the first wave of the pandemic with sampling weighted to include 50% survivors of mechanical ventilation.MAIN OUTCOMES AND MEASURES:Eleven serum biomarkers at hospital discharge, 4 months, 15 months, and 3 years, and symptoms and physical function at 15 months and 3 years. PASC presence was defined using the 12 symptoms and scoring from the Researching COVID to Enhance Recovery (RECOVER) definition. We tested associations of biomarkers with PASC and symptom phenotypes of post-exertional malaise, fatigue, and brain fog while adjusting for age, sex, body mass index, comorbidities, and days since COVID-19 diagnosis.RESULTS:The mean (sd) age of the cohort was 56 years (13); 67% were Hispanic and 25% were Black. PASC was present in 26% of participants at both 15 months and 3 years. PASC and symptom phenotypes at 15 months and 3 years were consistently associated with higher frailty phenotype category, worse short physical performance battery scores, and shorter 6-minute walk distance. Biomarkers of inflammation, including interleukin-6 and soluble tumor necrosis factor receptor-1, endothelial function, including angiopoietin, and complement, including C2, C4b, and C5, were not associated with PASC or symptom phenotypes in cross-sectional or longitudinal analyses.CONCLUSIONS AND RELEVANCE:PASC persists for 3 years after acute COVID-19 ALI/ARDS, is associated with frailty, but not associated with persistently higher levels of inflammatory, endothelial, and complement biomarkers implicated in worse short-term outcomes in acute COVID-19, non-COVID-19 ARDS, and sepsis. Future studies should employ multiomics to elucidate potential mechanisms of PASC.

To summarize the effectiveness of critical care ultrasonography (CCUS) in adult patients with cardiogenic shock vs. standard of care without CCUS on patient-relevant outcomes. We performed a scoping review across MEDLINE, Embase, CENTRAL, World Health Organization, International Clinical Trials Registry, ClinicalTrials.gov, and published and unpublished sources from inception until February 2024. The emergency department, ward, or ICU. We included randomized clinical trials (RCTs) and observational studies comparing CCUS to non-CCUS care in adult patients with cardiogenic shock. We included any type of ultrasound measure for the intervention in adult patients (≥ 18 yr old). CCUS. We included two RCTs (n = 573 patients) and one observational study (n = 30 patients). RCT data suggested that CCUS, with transesophageal echocardiography in particular, in adult patients with cardiogenic shock may shorten time to resolution of hemodynamic instability at 72 hours (subhazard ratio [SHR], 1.26; 95% CI, 1.02-1.55) but failed to influence mortality (risk difference, -0.03; 95% CI, -0.1 to 0.05), time to resolution of hemodynamic instability within 6 days (SHR, 1.20; 95% CI, 0.98-1.46), ICU length of stay (LOS; p = 0.87), hospital LOS (p = 0.91), duration of mechanical ventilation (p = 0.73), or duration of renal replacement therapy (RRT; p = 0.68). In adult patients with cardiogenic shock, CCUS does not impact mortality, time to resolution of hemodynamic instability within 6 days, ICU and hospital LOS, nor mechanical ventilation or RRT duration. Notably, CCUS may hasten resolution of hemodynamic instability at 72 hours, but such evidence is limited by imprecision and indirectness.

Cefepime, a cornerstone antibiotic in critical care, is associated with underrecognized cefepime-induced neurotoxicity (CIN), particularly in patients 65 years old and older. The true incidence is unknown due to inconsistent monitoring and a lack of diagnostic criteria. The recent Antibiotic Choice on Renal Outcomes (ACORN) trial underscored CIN’s clinical significance, finding that cefepime recipients experienced 21% fewer delirium- and coma-free days than those on piperacillin-tazobactam. Current guidelines lack active surveillance recommendations, leading to delayed diagnosis and intervention. We propose three informatics-based strategies to address these challenges: 1) electronic health record (EHR)-integrated datasets utilizing machine learning and natural language processing to identify CIN at scale, 2) automated electroencephalogram tools to provide real-time alerts to clinicians, and 3) dynamic risk scores that continuously update from EHR data to guide prescribing. Implementing these safeguards to optimize CIN prevention, which may be relevant for other antibiotics with neurotoxicity risk, can improve neurologic outcomes and patient safety in critically ill populations.

Delirium is a neuropsychiatric syndrome characterized by fluctuating disturbances in attention and awareness, associated with worse clinical outcomes and higher mortality. Previous research studies have noted an association between geographic disadvantage and delirium, but it is unknown if this association extends to critically ill adults. This study aimed to explore the relationship between geographic disadvantage and ICU delirium characteristics. We performed a secondary analysis of data collected from an National Institutes of Health-funded clinical trial, the Pharmacologic Management of Delirium study. Adults 18 years old or older admitted to the ICU who experienced delirium based on the Confusion Assessment Method for the ICU (CAM-ICU) were included. None. The study population included 326 participants: 54.5% were female and 48% Black, with a mean age of 60.3 years, mean Acute Physiology and Chronic Health Evaluation II score of 20, and in-hospital mortality rate of 12.3%. The area deprivation index (ADI), a composite measure of geographic disadvantage derived from census data that yields a national percentile score ranging from 1 to 100 (with higher scores representing greater disadvantage), was obtained for each participant's address. Main outcome variables included delirium duration, which was assessed by the number of delirium- and coma-free days (DCFDs), and delirium severity, which was assessed by mean CAM-ICU-7 scores. Analysis of covariance models were used to examine differences in DCFDs and mean CAM-ICU-7 scores between ADI quintiles while controlling for demographic and clinical variables. Other clinical outcomes of interest included discharge home rates and in-hospital mortality. The sample was heavily skewed toward higher national ADI percentile scores (indicating greater disadvantage); only 11.7% of patients had an ADI score lower than 50. Our regression analyses did not reveal any associations between ADI quintile and DCFDs or mean CAM-ICU-7 scores, or between ADI quintile and discharge home rates or in-hospital mortality. However, the Black race was associated with longer delirium duration and greater delirium severity in the first week of ICU hospitalization. Our study did not find an association between geographic disadvantage and delirium duration or severity in the ICU. However, an association with race was observed, highlighting the need for further research into how socioeconomic determinants of health relate to delirium.

BACKGROUND:Immune-related adverse events (irAEs) induced by immune checkpoint inhibitors vary widely, raising diagnostic challenges. The management of suspected irAEs requires close collaboration between oncologists and organ specialists. Rarely, irAEs can occur as overlap syndromes and may require intensive care.CASE SUMMARY:A 69-year-old man required intensive care for severe overlap syndrome induced by a programmed death-ligand 1 inhibitor. The presentation as recurrent hypercapnic coma complicated the diagnosis of polyradiculoneuritis combined with myocarditis. The finding of anti-titin autoantibodies assisted in the diagnosis. The patient was successfully treated with corticosteroids, polyvalent immunoglobulins, abatacept, and ruxolitinib. The irAEs abated but the polypharmacy contributed to the development of fatal hemorrhagic shock.CONCLUSIONS:This is the first reported case of seropositive, overlap irAEs consisting of myocarditis and polyradiculoneuritis. Early immunosuppressive therapy can alleviate irAEs but can also lead to serious complications in frail patients. This underscores the importance of carefully balancing expected therapeutic benefits against potential risks.

IMPORTANCE:This study provides nationally representative data on critical care advanced practice provider (APP) workforce structure and practice, addressing gaps in onboarding, productivity assessment, and administrative roles that influence workforce sustainability.OBJECTIVES:To analyze the composition of the clinical practice and workforce demographics of critical care medicine APPs.DESIGN, SETTING, AND PARTICIPANTS:We utilized a cross-sectional survey, which was distributed via email through the Society of Critical Care Medicine email list, targeting critical care APPs.MAIN OUTCOMES AND MEASURES:A total of 518 critical care APPs participated in the survey, comprising 63.2% advanced practice registered nurses, 28.8% physician assistants, and 8% clinical nurse specialists. The majority of the sample APPs worked 12-hour shifts covering days, nights, and weekends, with over 50% managing 6–10 patients per day shift. Common billing practices included critical care time (60.6%) and bedside invasive procedures (64.3%). Formal onboarding was reported by 68.6% of respondents, with academic hospitals more likely to offer such programs than community hospitals (72.3% vs. 27.7%; p < 0.001). Administrative APP roles were more prevalent in academic centers (p < 0.001) and were associated with greater access to professional development opportunities (p < 0.001). A significant proportion of respondents (41.5%) reported that their productivity was not formally measured. Notably, 22% of respondents reported an intent to leave the profession, particularly those lacking leadership or professional growth opportunities (p < 0.01).CONCLUSIONS AND RELEVANCE:This study captures practice trends and demographics of the critical care APP workforce. Day-to-day tasks among all respondents were globally clinically focused, but there were disparities in workload distribution, onboarding, productivity measurement, and administrative roles across types of centers. Additionally, there was significant association between limited professional growth opportunities and intent to leave critical care. These findings underscore the need for healthcare systems to invest in structured support, leadership development, and professional growth to enhance APP retention, engagement, and productivity. Further research is needed to identify efficient workload and staffing models.