Journal of Intensive Care Medicine最新文献

{"title":"Association Between Blood Pressure Response Index and Prognosis in Patients with Septic Shock Caused by Pneumonia.","authors":"Yi Zhang, Xuanmin Lin, Fang Jin, Lingling Zhang, Tongbao Feng, Yiming Jiang","doi":"10.1177/08850666261441512","DOIUrl":"https://doi.org/10.1177/08850666261441512","url":null,"abstract":"<p><p>BackgroundNo noninvasive index exists to assess vasopressor responsiveness for maintaining blood pressure in severe pneumonia-induced shock. This study evaluated the association between the blood pressure response index (BPRI) and prognosis in such patients.MethodsA mixed retrospective and prospective cohort study analyzed clinical data from patients admitted to tertiary hospitals between January 2018 and January 2025. BPRI is the ratio between the mean arterial pressure and the vasoactive inotropic score. Cox regression analysis assessed the impact of BPRI on mortality risk, while Kaplan-Meier curves compared 30-day cumulative survival rates across BPRI tertiles. The receiver operating characteristic (ROC) curves evaluated BPRI's predictive accuracy for mortality. Restricted cubic spline (RCS) analysis explored potential nonlinear relationships between BPRI and mortality risk.ResultsThe retrospective cohort included 618 patients, with 332 (52.7%) fatalities. In the prospective cohort, 65 patients were enrolled, with 30 (46.2%) death. Cox regression analysis of the retrospective dataset indicated that higher BPRI values correlated with lower mortality risk (adjusted hazard ratio [HR]= 0.843, 95% confidence interval [CI] [0.811, 0.877]). The ROC analysis demonstrated that BPRI predicted 30-day mortality (area under the curve [AUC] = 0.7404, 95%=[0.7018,0.7790]) more accurately than the vasoactive inotropic score (AUC=0.7034, 95%CI = [0.6627,0.7440]) and mean arterial pressure (AUC=0.6638, 95%CI = [0.6201,0.7075]), consistent with prospective findings. The RCS analysis revealed a nonlinear relationship between BPRI and mortality risk, with a cutoff value of 9.05.ConclusionA lower BPRI was significantly associated with increased mortality risk, following a nonlinear pattern. BPRI demonstrated substantial predictive value for severe pneumonia-induced shock.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261441512"},"PeriodicalIF":2.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vasopressors Combination Therapy (Norepinephrine Plus Vasopressin Receptor Agonists) Improve Septic Shock Outcome: A Systematic Review and Meta-Analysis.","authors":"Weijie Yu, Yanjie Zhang, Zhu Luo, Xiner Cai, Jiyue Shao, Wanting Lin, Jingyuan Xu","doi":"10.1177/08850666261500019","DOIUrl":"https://doi.org/10.1177/08850666261500019","url":null,"abstract":"<p><p>BackgroundStudies showed different results of vasopressors combination therapy in septic shock patients. This meta-analysis aimed to evaluate the outcomes of combination of norepinephrine plus vasopressin receptor agonists in adult septic shock.MethodsCochrane Library, Embase, Web of Science, and PubMed databases were searched up to September 27, 2026, to identify randomized controlled trials (RCTs) comparing the combination of norepinephrine plus vasopressin receptor agonists versus norepinephrine alone in septic shock patients. Two reviewers independently extracted data on mortality, ICU length of stay, renal replacement therapy (RRT) and adverse events. Trial sequential analysis (TSA) was applied to assess random error.ResultsTwenty-one RCTs involving 3873 septic shock patients were included. The results showed that the combination of norepinephrine plus vasopressin receptor agonists was associated with lower mortality at the longest complete follow-up compared with norepinephrine alone (RR = 0.90, 95% CI 0.83 to 0.99, <i>P</i> = .02), but with an increased risk of digital ischemia (RR = 2.21, 95% CI 1.15 to 4.27, <i>P</i> = .02). Subgroup analysis indicated that the combination of norepinephrine plus vasopressin receptor agonists may provide survival benefits for more severe septic shock patients (RR = 0.90, 95% CI 0.81 to 1.00, <i>P</i> = .04). Moreover, compared with norepinephrine alone, the combination of norepinephrine plus vasopressin showed a trend towards reducing the longest follow-up mortality (RR = 0.89, 95% CI 0.80 to 1.00, <i>P</i> = .05). TSA indicated lack of firm evidence for a beneficial effect.ConclusionsIn adults with septic shock, the combination of norepinephrine plus vasopressin receptor agonists may reduce mortality at the longest complete follow-up compared with norepinephrine alone (low quality of evidence), but may increase risk of digital ischemia (low quality of evidence). This benefit mainly appeared in more severe septic shock patients. Moreover, norepinephrine plus vasopressin may confer a survival advantage.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261500019"},"PeriodicalIF":2.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balanced Solutions Versus Normal Saline in Pediatric Septic Shock: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Mohammed A Elbahloul, Aliaa Gamal, Bandar Alawlaqi, Ahmed F Abumezed, Mohamed Farahat, Logina Salam, Al-Walid A Abumezied, Ismail M Aburekab, Abdelrhman W Mohamed","doi":"10.1177/08850666261498038","DOIUrl":"https://doi.org/10.1177/08850666261498038","url":null,"abstract":"<p><p>BackgroundIn pediatric septic shock, early fluid resuscitation is a vital approach to treat this condition. The appropriate isotonic crystalloid to use (balanced salt solution [BSS] vs normal saline [NS]) remains debated. We performed an updated systematic review and meta-analysis to evaluate the safety and efficacy of both isotonic crystalloid solutions in this patient population.MethodsWe systematically searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception until May 1, 2026, for randomized controlled trials (RCTs) comparing BSS with NS for fluid resuscitation in children (<18 years) with septic shock or sepsis. The primary outcome was hospital or 30-day mortality. We synthesized data using frequentist inverse-variance random-effects models. The protocol was registered in PROSPERO (CRD420261391864), and the certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for all outcomes.ResultsSix RCTs involving 9743 participants were included. For the primary outcome, BSS and NS demonstrated no significant differences in hospital or 30-day mortality rates (3.5% vs 3.7%; RR: 0.97, 95% CI: 0.81-1.16, <i>P</i> = .72). Secondary analyses revealed that BSS significantly reduced the requirement for renal replacement therapy (RRT) (RR: 0.68, 95% CI: 0.47-0.97) and hyperchloremia (RR: 0.65, 95% CI: 0.57-0.75).ConclusionThe use of BSS versus NS showed no significant difference in short-term mortality among children with septic shock; however, BSS provided significant clinical and physiological advantages, including reduced incidences of hyperchloremia and the need for RRT.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261498038"},"PeriodicalIF":2.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Alcohol-Associated Hepatitis: The Role of Liver Transplantation.","authors":"Amish M Khan, Shahid M Malik","doi":"10.1177/08850666261498029","DOIUrl":"https://doi.org/10.1177/08850666261498029","url":null,"abstract":"<p><p>Severe alcohol-associated hepatitis (AH) remains one of the most challenging syndromes in hepatology and critical care, with high short-term mortality despite advances in supportive management. Although corticosteroids remain the only guideline-endorsed pharmacologic therapy shown to improve early survival, their benefit is modest, limited to selected patients, and frequently complicated by infection. Consequently, contemporary management extends well beyond corticosteroid therapy and requires meticulous supportive care, nutritional optimization, infection surveillance, management of portal hypertensive complications and acute-on-chronic liver failure (ACLF), and early multidisciplinary involvement. This review summarizes the current evidence regarding the diagnosis, prognostic assessment, and medical management of severe AH. Key prognostic models, including MELD, Maddrey Discriminant Function, and the Lille score, are discussed together with evolving evidence supporting individualized corticosteroid use and emerging investigational therapies. Particular emphasis is placed on critically ill patients with ACLF, in whom extrahepatic organ failure often supersedes liver dysfunction as the principal determinant of outcome. The review also examines the evolving role of early liver transplantation (LT), one of the most important paradigm shifts in modern transplant hepatology. Contemporary approaches to patient selection, psychosocial assessment, relapse-risk evaluation, living donor transplantation, and the management of patients with catastrophic AH are discussed, along with ethical considerations surrounding organ allocation, medical urgency, and stewardship of scarce donor organs. Despite important advances in supportive care and transplantation, severe AH continues to carry substantial mortality. Optimizing outcomes requires timely diagnosis, multidisciplinary management, careful selection for medical therapy, and early recognition of patients unlikely to recover without liver transplantation.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261498029"},"PeriodicalIF":2.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escalating Vasopressor Intensity and the Goals-of-Care Documentation Gap in Septic Shock: Relevance to the Proposed Refractory Shock Threshold.","authors":"Imran Khalid, Javier Diaz-Mendoza, Manahil Imran, Raafey Imran, Muhammad Ali Akhtar, Basel Ghurm Alshehri, Amir Iqbal, Ibrahim Muhammad Imran, Ibrahim T Malik, Tabindeh Jabeen Khalid, Mohsin Iqbal, Maryam Imran","doi":"10.1177/08850666261490895","DOIUrl":"https://doi.org/10.1177/08850666261490895","url":null,"abstract":"<p><p>BackgroundThe 2026 joint SCCM/ESICM Delphi consensus identified vasopressor intensity as a defining feature of refractory septic shock, yet its relationship to real-world goals-of-care documentation remains unclear.ObjectivesWe assessed the association between escalating vasopressor intensity and documented surrogate goals-of-care markers among septic shock decedents.MethodsRetrospective cohort study of adult septic shock decedents in MIMIC-IV (2008-2022) requiring vasopressors ≥6 h and surviving ≥24 h after initiation. Vasopressor intensity was quantified by peak norepinephrine equivalent (NEE) dose during ICU stay and stratified as: 0.01-0.50 (stratum 1), >0.50-0.99 (stratum 2), and ≥1.00 µg/kg/min (stratum 3). The primary outcome was death without documented surrogate goals-of-care markers, defined as having neither a documented do-not-resuscitate (DNR) order nor documented palliative care involvement.ResultsThe final cohort included 2458 patients: stratum 1 (n = 1033), stratum 2 (n = 909), and stratum 3 (n = 516). Death without documented goals-of-care markers increased across strata (23.8%, 28.3%, 31.2%; p-for-trend=0.001). After multivariable adjustment, stratum 3 patients remained more likely than stratum 1 to die without documented goals-of-care markers (aOR 1.32; 95% CI 1.02-1.69; p = 0.03). Palliative care documentation declined progressively with increasing vasopressor intensity (59.2%, 52.0%, 46.9%; p-for-trend<0.001), accompanied by lower rates of integrated DNR/palliative care documentation (47.0%, 40.0%, 36.4%; p-for-trend<0.001). Patients exceeding the Delphi-proposed refractory shock threshold (NEE >0.50 µg/kg/min) were more likely to die without documented goals-of-care markers than those below the threshold (29.3% vs 23.8%; p = 0.002).ConclusionHigher vasopressor intensity was paradoxically associated with a greater likelihood of death without documented goals-of-care markers and with lower palliative care documentation. These findings suggest a disconnect between escalating physiologic severity and documentation of surrogate goals-of-care markers in refractory septic shock and warrant further evaluation.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261490895"},"PeriodicalIF":2.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Decompressive Craniectomy for Severe Refractory Head Injury.","authors":"Frederick B Rogers, Nicholas Larson, Benoit Blondeau, Kwok M Ho","doi":"10.1177/08850666261473869","DOIUrl":"https://doi.org/10.1177/08850666261473869","url":null,"abstract":"<p><p>Decompressive craniectomy is a potential therapeutic option for patients with severe traumatic brain injury and refractory intracranial hypertension, although its indications and clinical benefits remain controversial. A total of 4060 articles were identified, with 94.6% published after 2010. Several major randomized clinical trials have shaped current understanding of decompressive craniectomy, including the RESCUE-ASDH for primary intracranial hypertension, and the DECRA and RESCUEicp for secondary intracranial hypertension. RESCUE-ASDH and DECRA showed no overall benefit and suggested potential harm associated with decompressive craniectomy. RESCUEicp trial showed reduced mortality and sustained long-term improvement in a subset of patients, although many survivors remained in a dependent state. Critical appraisal of the inclusion and exclusion criteria of these trials, together with supporting evidence from animal studies, suggest that decompressive craniectomy should not be treated as primary intervention for traumatic brain injury. Instead, it may be more appropriately used as an adjunct procedure to prevent worsening cerebral edema <i>following</i> other neurosurgical interventions - such as evaluation of contusions or hematomas - when the operative hemisphere is tight and swollen. Decompressive craniectomy performed solely to control refractory intracranial hypertension in traumatic brain injury is unlikely to provide meaningful patient-centered benefit. Its role as an adjunct procedure after evacuation of contusions or hematomas remains uncertain, particularly in patients with a low predicted risk of unfavorable outcome. Decision regarding decompressive craniectomy should incorporate shared decision making and reflect careful consideration of the functional outcomes acceptable to patients and their families.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261473869"},"PeriodicalIF":2.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nailfold Capillaroscopy Reveals Peripheral Microcirculatory Trajectories in Septic Shock.","authors":"Koichi Inukai, Shiho Tane, Hirotada Kittaka, Hirotaka Sawano, Yusuke Ito, Masanori Morita","doi":"10.1177/08850666261496220","DOIUrl":"https://doi.org/10.1177/08850666261496220","url":null,"abstract":"<p><p>BackgroundSepsis-induced microcirculatory dysfunction may persist despite systemic hemodynamic stabilization, yet longitudinal changes in peripheral microvascular structure and flow during recovery remain insufficiently characterized. We used nailfold capillaroscopy (NFC) to characterize these changes during recovery from septic shock.MethodsIn this prospective two-center study, patients with Sepsis-3 septic shock underwent NFC during shock and after clinician-confirmed hemodynamic stabilization. Baseline NFC analyses required analyzable initial recordings; longitudinal analyses required paired assessments and survival to reassessment. Mortality was prespecified as the primary outcome. Longitudinal NFC changes and the association between change in red blood cell (RBC) velocity and lactate clearance were prespecified; outcome-stratified analyses were post hoc and exploratory.ResultsOf 25 patients meeting clinical eligibility criteria, 21 were enrolled, 19 had analyzable baseline NFC recordings, and 15 had paired assessments; four died before reassessment. Baseline RBC velocity was 0.268 mm/s in survivors and 0.290 mm/s in non-survivors (P = 0.653). In the paired cohort, RBC velocity increased from 0.295 to 0.550 mm/s; median within-patient change was 0.167 mm/s (95% CI, 0.067 to 0.609; P = 0.1531). The median within-patient change in capillary length was 42.1 μm (95% CI, -7.3 to 65.3; P = 0.0125). Median ΔRBC velocity was 0.393 mm/s in survivors and -0.127 mm/s in non-survivors; the between-group median difference was 0.520 mm/s (95% CI, -0.042 to 1.368; P = 0.0256). The prespecified association between ΔRBC velocity and lactate clearance was positive but imprecise (Spearman's rho = 0.41; 95% CI, -0.15 to 0.77; P = 0.133).ConclusionsNFC captured dynamic and heterogeneous peripheral microcirculatory changes despite systemic hemodynamic stabilization. Increased RBC velocity among survivors suggests that serial NFC may complement conventional macrocirculatory assessment by providing information on microcirculatory recovery. These findings support further prospective evaluation of NFC as a feasible bedside tool for longitudinal microcirculatory monitoring.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261496220"},"PeriodicalIF":2.3,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Machine Learning Model for Predicting 28-Day Mortality in Patients with Sepsis-Associated Encephalopathy and Heart Failure.","authors":"Hai-Peng Wu, Kai Liu, Xiao-Yi Hu","doi":"10.1177/08850666261495897","DOIUrl":"https://doi.org/10.1177/08850666261495897","url":null,"abstract":"<p><p>IntroductionPatients with sepsis-associated encephalopathy (SAE) and heart failure (HF) represent a clinically relevant but understudied subgroup in the intensive care unit, and early risk stratification may be important for guiding management. This study aimed to develop and temporally validate machine-learning models for predicting 28-day mortality in patients with SAE and HF.MethodsIn this retrospective cohort study, patients with SAE and HF were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and III (MIMIC-III) databases. The MIMIC-IV cohort was randomly divided into a training set and an internal testing set, whereas the MIMIC-III cohort served as a temporally distinct testing set. Variables with more than 30% missing data were excluded, and the remaining missing values were handled using multiple imputation. Candidate predictors were first screened by univariable analysis and then entered into multivariable logistic regression to identify independent predictors of 28-day mortality. Six variables (age, weight, respiratory rate, Logistic Organ Dysfunction System score, first 24-h urine output, and Charlson Comorbidity Index) were used to construct five models: logistic regression, XGBoost, LightGBM, support vector machine, and AdaBoost. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), classification metrics, calibration, and decision-curve analysis.ResultsA total of 1249 patients with SAE and HF were included, comprising 833 in the training set, 205 in the internal testing set, and 211 in the temporal testing set. Machine-learning models and logistic regression outperformed conventional severity scores (SOFA, SAPS II, and LODS). In the temporal testing set, XGBoost achieved the highest AUROC (0.824), whereas logistic regression showed similar discrimination (AUROC 0.816) but more stable calibration and better overall balance across performance domains.ConclusionWe developed and temporally validated models for predicting 28-day mortality in patients with SAE and HF. Among the evaluated models, logistic regression showed the most balanced overall performance and may be the most clinically applicable model for individualized risk stratification.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261495897"},"PeriodicalIF":2.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapidly Improving Acute Hypoxemic Respiratory Failure: A Biological Phenotype or a Care-Dependent Clinical Trajectory?","authors":"Chenxiao Ding, Liang Wu","doi":"10.1177/08850666261493109","DOIUrl":"https://doi.org/10.1177/08850666261493109","url":null,"abstract":"","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261493109"},"PeriodicalIF":2.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing of Vasopressin Initiation in Sepsis Patients on Norepinephrine: A Target Trial Emulation.","authors":"Xiao Zhang, Xinghe Shangguan, Xiayoumei Wu, Puxiu Liu, Xiaofan Zou, Qianyu Yuan, Yang Zhou, Yuanqi Gong","doi":"10.1177/08850666261479700","DOIUrl":"https://doi.org/10.1177/08850666261479700","url":null,"abstract":"<p><p>BackgroundThe optimal timing for initiating vasopressin in septic shock remains uncertain, with conflicting evidence potentially arising from variations in patient severity and methodological limitations such as immortal time bias. This study aimed to evaluate the time-varying effect of early vasopressin initiation across a spectrum of baseline norepinephrine dose requirements.MethodsWe included 5461 patients with septic shock from the MIMIC-IV 2.2 database. A target trial emulation framework was applied, using a clone-censor-weight approach with inverse probability of censoring weighting to address immortal time bias. The primary and secondary outcomes were 14-day and 28-day all-cause mortality. Time-varying treatment effects of early vasopressin initiation (defined by a 1-h primary grace period) were assessed via piecewise landmark Cox models, with analyses stratified by baseline norepinephrine equivalent dose thresholds (>0.1, >0.25, >0.5, and >0.75 μg/kg/min).ResultsThe association between early vasopressin initiation and 28-day mortality varied by both baseline norepinephrine dose and time since initiation. Among patients with low-to-moderate shock severity (NE 0.1-0.5 μg/kg/min), a pattern of delayed benefit was observed. The absolute risk reduction in the broad >0.1 μg/kg/min cohort was not statistically significant, but a survival benefit emerged in the late phase for the >0.25 μg/kg/min subgroup (late-phase HR 0.82, 95% CI 0.69-0.97, P=.018). In contrast, for patients with more severe shock (NE >0.5 μg/kg/min), early initiation was associated with increased risk in the first 48 h. This early hazard was most pronounced in the >0.75 μg/kg/min subgroup, where the point estimate for short-term mortality was markedly elevated (HR 2.87, 95% CI 1.68-4.90, P<.001). Although long-term point estimates at higher thresholds favored vasopressin, the confidence intervals were extremely wide and crossed the null, precluding firm conclusions. Subgroup analyses suggested that older age and concomitant renal dysfunction might amplify susceptibility to higher early mortality.ConclusionIn this target trial emulation, the benefit of early vasopressin initiation appeared dependent on baseline shock severity. The findings suggest a potential therapeutic window at norepinephrine equivalent doses between 0.1 and 0.5 μg/kg/min, with the most consistent benefit around 0.25 μg/kg/min. For patients requiring >0.5 μg/kg/min, early initiation was associated with higher early mortality, which may reflect residual confounding by shock severity rather than a direct causal harm, and the current analysis did not support a definitive compensatory long-term survival benefit.</p>","PeriodicalId":16307,"journal":{"name":"Journal of Intensive Care Medicine","volume":" ","pages":"8850666261479700"},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}