Nazeha N, Okada Y, Shahidah N
… +11 more, Chakaramakkil MJ, Ramanathan K, Kiguchi T, Takegawa R, Nishimura T, Kitamura T, Iwami T, Graves N, Ong MEH, Kularatna S, Singapore Pan-Asian Resuscitation Outcomes Study (PAROS) Investigators
Crit Care Med
· 2026 Jul · PMID 42378681
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OBJECTIVES: To evaluate the cost-effectiveness of implementing an extracorporeal cardiopulmonary resuscitation (ECPR) strategy for refractory out-of-hospital cardiac arrest (OHCA) compared with current practice in Singap...OBJECTIVES: To evaluate the cost-effectiveness of implementing an extracorporeal cardiopulmonary resuscitation (ECPR) strategy for refractory out-of-hospital cardiac arrest (OHCA) compared with current practice in Singapore, where it is not routinely used. DESIGN: We performed a simulation-based cost-effectiveness analysis using a decision tree to model acute phase and a Markov model for long-term outcomes over a lifetime horizon, from a healthcare provider perspective. SETTING: Singapore healthcare system. PATIENTS: Nontraumatic adult OHCA patients from Singapore with initial shockable rhythm and no prehospital return of spontaneous circulation were analyzed. INTERVENTIONS: We modeled the implementation of an ECPR strategy and compared it with current practice using only conventional cardiopulmonary resuscitation. Transition probabilities of existing practice were derived from the nationwide Singapore OHCA registry (Pan-Asian Resuscitation Outcomes Study: PAROS), (2010-2016), while ECPR outcomes were based on the Comprehensive Registry of Intensive Care for OHCA Survival in Osaka (Osaka CRITICAL study) (2012-2019). Costs and quality-adjusted life-years (QALYs) were compared between strategies, with scenario analyses conducted to assess the impact of lower age eligibility thresholds and increased transport time to extracorporeal membrane oxygenation-capable hospitals. Incremental cost-effectiveness ratios (ICERs) were estimated using a willingness-to-pay threshold of S$45,000 per QALY. MEASUREMENTS AND MAIN RESULTS: A total of 1462 OHCA cases from Singapore were analyzed; the mean age of patients was 57 years (sd, 11 yr), and 87% were male. In base-case analysis, ICER was estimated at $34,320/QALY, with a positive net monetary benefit of $8,532. Scenario analyses demonstrated that an age-restricted ECPR strategy (< 65 yr) yielded a similar ICER ($33,469/QALY) to the base case. In contrast, incorporating a 10-minute transport extension slightly exceeded the willingness-to-pay threshold ($47,158/QALY). CONCLUSIONS: In this modeling study, adopting an ECPR strategy for OHCA in Singapore was likely to be cost-effective across different age-based eligibility thresholds; however, it was sensitive to delays in transport time. Further implementation research is important to guide scale-up and policy decisions.
Fontenot T, Grisel B, Freeman J
… +13 more, Cantrell S, Tripoli T, Swain S, Singhania S, Lin S, Leon L, Park E, Kreinbrook J, James A, Pitre L, Yang R, Agarwal S, Haines KL
Crit Care Med
· 2026 Jun · PMID 42339875
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OBJECTIVES: Policies that make cardiopulmonary resuscitation (CPR) the default or require it at patient or family request, combined with physician reluctance to decline nonbeneficial resuscitation, may contribute to the...OBJECTIVES: Policies that make cardiopulmonary resuscitation (CPR) the default or require it at patient or family request, combined with physician reluctance to decline nonbeneficial resuscitation, may contribute to the practice of a "slow code," in which clinicians appear to perform advanced cardiac life support without fully committing to resuscitative efforts. The space between "full code" and "comfort measures" in medically futile situations presents significant ethical challenges. This systematic review examines the ethical implications of slow codes and factors influencing their use. DATA SOURCES: We conducted a qualitative systematic review of slow codes in U.S. hospitals. A librarian searched MEDLINE, Embase, CINAHL, and Web of Science using terms related to CPR, futility, and ethics. The initial search was performed on May 16, 2024, with an updated search on August 7, 2025, including "slow code" and "partial code." STUDY SELECTION: After duplicate removal, 12,863 articles underwent dual, independent screening. Thirty-four studies met inclusion criteria. Included articles were ethics literature (academic articles, commentaries, and opinion pieces) and excluded empirical studies. DATA EXTRACTION AND SYNTHESIS: Of 34 articles analyzed, 61.8% ( n = 21) argued physicians ought to be allowed to refuse CPR in futile cases, whereas 23.5% ( n = 8) supported slow/partial codes when patients or families request full resuscitation. A further 26.5% ( n = 9) described nuanced approaches. Ethical concerns included deception, patient harm, violation of autonomy, paternalism, moral distress, legal considerations, and communication breakdown. CONCLUSIONS: Most ethics literature deems slow codes impermissible. Their use often reflects concerns that surrogate decision-makers may not fully understand the implications or mechanics of CPR. In medically futile situations, choosing between "do nothing" and "do everything" can be distressing for families, whereas performing resuscitation can be distressing for clinicians. Physicians remain divided in practice, highlighting the need for clear communication and ethical guidance to support transparent, patient-centered end-of-life care.
van Herwerden MC, Groenland CNL, Termorshuizen F
… +18 more, Rietdijk WJR, Blokzijl F, Boer DP, Dormans T, Epker JL, Feyz L, Gommers DAMPJ, Gritters van den Oever N, van der Heiden P, de Jonge E, Latten GHP, Pruijsten RV, Sir Ö, Spronk PE, Vermeijden WJ, van Vliet P, de Keizer NF, den Uil CA
Crit Care Med
· 2026 Jun · PMID 42312687
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OBJECTIVES: To assess the association between emergency department (ED)-to-ICU transfer time and hospital mortality across common ICU diagnoses. DESIGN, SETTING, AND PATIENTS: Secondary analysis of a Dutch retrospective...OBJECTIVES: To assess the association between emergency department (ED)-to-ICU transfer time and hospital mortality across common ICU diagnoses. DESIGN, SETTING, AND PATIENTS: Secondary analysis of a Dutch retrospective cohort (2009-2020). Twelve hospitals (four academic and eight nonacademic teaching [NACT]) provided ED arrival and ICU admission times. Adult patients directly admitted from the ED to the ICU were included. Seven diagnostic groups (> 1500 patients each) were analyzed: out-of-hospital cardiac arrest (OHCA), nonoperative trauma, overdose, sepsis, pneumonia, respiratory failure (excluding pneumonia), and intracranial hemorrhage (ICH). Logistic regression assessed associations between ED-to-ICU time quintiles and hospital mortality, adjusting for hospital of admission, and Acute Physiology and Chronic Health Evaluation III score. Analyses were stratified by hospital type. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 18,798 patients, median ED-to-ICU time was 1.9 hours (interquartile range, 1.2-3.1 hr). In OHCA ( n = 3,818), associations differed by hospital type. In academic hospitals, prolonged ED-to-ICU time was associated with higher mortality (odds ratio [OR], 1.48; 95% CI, 1.08-2.02 at 1.1-1.6 hr; OR, 2.94; 95% CI, 1.80-4.78 at > 3.4 hr; Wald χ 2p < 0.001). In NACT hospitals, prolonged ED-to-ICU time was negatively associated with mortality, with ORs less than 1.0 across quintiles (Wald χ 2p < 0.001). In nonoperative trauma, a positive association between ED-to-ICU time and hospital mortality was observed in the overall cohort (OR, 1.90; 95% CI, 1.12-3.21 at > 3.4 hr; Wald χ 2p = 0.05) but was not reproduced after stratification for hospital. No associations were observed in overdose, sepsis, pneumonia, respiratory failure, or ICH. CONCLUSIONS: The association between ED-to-ICU time and hospital mortality varied across diagnostic groups and hospital types. In OHCA, opposing associations were observed in academic and NACT hospitals. In nonoperative trauma, a positive association was observed only in the overall cohort. Prospective studies in homogeneous, risk-defined subgroups with detailed process-of-care data are needed to identify modifiable delays and define transfer-time thresholds.
Sethi I, Khan S, Lyons PG
… +15 more, Gao CA, Luo Y, Miltz D, Tovar S, Lohuis CT, Polly DM, Dave SB, Sterling M, Rojas JC, Han X, Sakhuja A, Celi LA, Martin GS, Coopersmith CM, Bhavani SV
Crit Care Med
· 2026 Jun · PMID 42307255
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OBJECTIVES: To evaluate the performance of Chat Generative Pre-Trained Transformer-4 Omni (ChatGPT-4o) in answering multimodal critical care board review questions, with a focus on accuracy, image interpretation, reasoni...OBJECTIVES: To evaluate the performance of Chat Generative Pre-Trained Transformer-4 Omni (ChatGPT-4o) in answering multimodal critical care board review questions, with a focus on accuracy, image interpretation, reasoning quality, and potential for harm. DESIGN: Observational study using a validated item bank of multiple-choice questions accompanied by clinical images, analyzed through a custom ChatGPT-4o profile built using a validated framework. SETTING: Simulated environment mimicking critical care board examination conditions, with artificial intelligence responses reviewed by a panel of experienced critical care clinicians. SUBJECTS: One hundred eighty-three board-style questions from the Society of Critical Care Medicine item bank, representing a range of critical care domains and imaging modalities. ChatGPT-4o was evaluated on its responses, which were assessed by 14 clinical reviewers (physicians, advanced practice providers, and pharmacists). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ChatGPT-4o answered 74.9% of questions correctly, higher than pooled clinician responses (71.1%; p = 0.03). It showed strengths in question comprehension (87.4% correct) but lower performance in image interpretation (61.7%), reasoning (68.3%), and supporting information (66.1%). ChatGPT-4o excelled in pulmonary disease (91.7%), surgery and trauma (87.5%), and neurologic disorders (81.8%), and underperformed in critical care ultrasound (51.1%). Notably, 33.3% of its responses were associated with potential for clinical harm, often due to incorrect image interpretation and treatment recommendations. CONCLUSIONS: ChatGPT-4o demonstrates performance slightly above pooled clinician benchmarks on critical care board-style questions but has substantial limitations in multimodal question interpretation. Despite its high comprehension, deficiencies in ChatGPT-4o's reasoning and image analysis may lead to harmful clinical conclusions in high-stakes clinical decision-making or clinical education.
Chesnut RM, Temkin N, Barber J
… +3 more, Park C, Bonow RH, Brain Tissue Oxygen Monitoring and Management in Severe Traumatic Brain Injury II (BOOST II) Investigators
Crit Care Med
· 2026 Jun · PMID 42302399
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OBJECTIVE: Traumatic brain injury (TBI) research and intracranial pressure (ICP) management depends on bedside ICP (B-ICP) crisis identification. We analyzed background-collected electronic ICP (E-ICP) data to study the...OBJECTIVE: Traumatic brain injury (TBI) research and intracranial pressure (ICP) management depends on bedside ICP (B-ICP) crisis identification. We analyzed background-collected electronic ICP (E-ICP) data to study the concordance of this identification. DESIGN: Post hoc comparison of background-collected continuous E-ICP data to routine B-ICP information during severe TBI management in the Brain Tissue Oxygen Monitoring and Management in Severe TBI (BOOST II) randomized trial. SETTING: Ten U.S. ICUs. PATIENTS: Seventy of 110 randomized BOOST II severe TBI patients with complete datasets for this study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied "minimalist" B-ICP episodes lasting less than or equal to 60 minutes and requiring only tier 1 treatments (83% of total BOOST II I isolated ICP episodes). Bedside clinicians (BCs) identified and treated 509 minimalist B-ICP episodes, defined by 5 minutes of B-ICP greater than or equal to 20 mm Hg (B-ICP 5 ). Corresponding E-ICP during this defining period (E-ICP 5 ) confirmed only 47% of these. The 241 "concordant" B-ICP episodes (both B-ICP 5 and E-ICP 5 ≥ 20 mm Hg) had average E-ICP values for the entire B-ICP episodes (E-ICP AVG ) less than 20 mm Hg in 38%. The 286 "discordant" B-ICP episodes (B-ICP 5 ≥ 20 mm Hg but E-ICP 5 < 20 mm Hg) had E-ICP AVG values less than 20 mm Hg in 76% and both E-ICP AVG and maximal E-ICP's (E-ICP MAX ) values less than 20 mm Hg in 31%. Testing for confounding (e.g., brief, first, or easily controlled B-ICP episodes) did not provide explanations. Insufficient data were available to evaluate temporal asynchrony between BC and electronic datapoints. Study limitations were lacking a rigid end-of-B-ICP episode definition and inability to fully control for temporal synchrony confounding. CONCLUSIONS: Our findings suggest that current methods of clinical identification of B-ICP episodes may not reliably distinguish true episodes of sustained ICP for the most common B-ICP episode type. We suggest developing open-source, real-time, temporally synchronized electronic B-ICP episode definition methods to direct future treatment and research.
Monet C, Allegre L, Kozoriz A
… +7 more, Herman F, Lakbar I, Prades A, Pensier J, De Jong A, Molinari N, Jaber S
Crit Care Med
· 2026 Jun · PMID 42301229
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OBJECTIVES: To assess the impact of Molecular Adsorbent Recirculating System (MARS) therapy on total plasma piperacillin concentrations in critically ill patients with acute liver failure or acute-on-chronic liver failur...OBJECTIVES: To assess the impact of Molecular Adsorbent Recirculating System (MARS) therapy on total plasma piperacillin concentrations in critically ill patients with acute liver failure or acute-on-chronic liver failure. DESIGN: Retrospective, single-center observational cohort study. SETTING: University ICU. PATIENTS: Consecutive adult patients treated with MARS therapy and piperacillin-tazobactam between March 2023 and June 2025. INTERVENTIONS: MARS therapy was delivered as 8-hour sessions for up to three consecutive days. Piperacillin-tazobactam was administered by continuous infusion following a loading dose. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were collected immediately before and after each MARS session. Total piperacillin concentrations were quantified using ultrahigh-performance liquid chromatography. The primary endpoint was the relative reduction in plasma piperacillin concentration induced by MARS therapy. Thirty patients (121 piperacillin measurements across 77 sessions) were analyzed. Seventy-three percent had cirrhosis (median Model for End-Stage Liver Disease Score 31 [23-38]). The mean relative reduction in piperacillin concentration per session was 34% (± 7.9%; p < 0.05). In univariable mixed-effects analysis, MARS session (β -47.49 mg/L; p < 0.001) and creatinine clearance (β -0.37 mg/L per mL/min; p < 0.001) were associated with lower concentrations. In multivariable modeling, higher creatinine clearance was independently associated with greater intra-session piperacillin loss (p < 0.001), whereas higher bilirubin levels were associated with reduced drug loss (p = 0.01). Overall, 31.6% of post-session concentrations were less than 80 mg/L, and 38% of patients had at least one concentration outside the predefined target range. CONCLUSIONS: MARS therapy was associated with a one-third reduction in total plasma piperacillin concentrations per session. These findings support systematic therapeutic drug monitoring and individualized antibiotic dose adjustment during MARS therapy.
Safavynia SA, Barra ME, Der Nigoghossian C
… +15 more, Shinnick D, Waldrop G, Choi JM, Ganglberger W, Shen Q, Doyle K, Walline MC, Westover MB, Brown EN, Fins JJ, Victor J, Edlow BL, Claassen J, Schiff ND, Thaweethai T
Crit Care Med
· 2026 Jun · PMID 42294965
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OBJECTIVES: Prolonged disorders of consciousness are common in critically ill patients receiving mechanical ventilation and are often attributed to prolonged sedative exposure in the setting of decreased drug clearance a...OBJECTIVES: Prolonged disorders of consciousness are common in critically ill patients receiving mechanical ventilation and are often attributed to prolonged sedative exposure in the setting of decreased drug clearance and/or reduced metabolism. Here, in a large sample of critically ill COVID patients obtained over a short period, we tested the assumption that prolonged unconsciousness following benzodiazepine and/or propofol sedation can be attributed to residual exposure. Further, we examine associations between clinical variables on time to recovery of consciousness (RoC) as a framework for the broader critically ill population. DESIGN: Retrospective cohort study. SETTING: Massachusetts General Hospital, Weill Cornell Medicine, Columbia University Irving Medical Center. PATIENTS: Seven hundred eighty-four patients with COVID-19 critical illness in Spring-Summer 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We estimated the latest expected RoC (LERoC) using models of sedation exposure that account for sedative-specific pharmacokinetics and critical illness. Our primary exposure variable was a time-weighted dose of analgosedative agents at benzodiazepine and/or propofol cessation; our primary outcome was time to RoC. We estimated relative risks for late RoC (i.e., after LERoC) via multinomial logistic regression. Among individuals with late RoC, we fit a multivariate subdistribution hazard model for time to RoC. Seventy-three percent of patients had RoC before hospital discharge, yet 34% of patients achieving RoC did not do so within pharmacologically plausible sedative elimination times. Patients with late RoC were older and exhibited hypoxemia and acute kidney injury. Patients with dexmedetomidine as an adjunct sedative had a disproportionately larger incidence of early recovery. Patients with early vs. late RoC did not have significantly different discharge dispositions. CONCLUSIONS: In our cohort, the time to RoC was commonly prolonged beyond that expected from sedation exposures alone. These data may aid clinicians and families with expectations of RoC and warrant investigation of alternative determinants of delayed RoC in this population.