Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysis

BackgroundTuberculous meningitis (TBM) complicated by intracranial hypertension requires aggressive neurocritical care, yet the mortality impact of sedative and antipsychotic exposure remains controversial. This study investigates the association between sedative exposure and mortality while identif...

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Main Authors: Shijuan Cui, Fazheng Shen, Jianing Liang, Fan Li, Xiangyang Wang, Xin Liu, Haigang Chang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1620858/full
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author Shijuan Cui
Fazheng Shen
Jianing Liang
Fan Li
Xiangyang Wang
Xin Liu
Haigang Chang
author_facet Shijuan Cui
Fazheng Shen
Jianing Liang
Fan Li
Xiangyang Wang
Xin Liu
Haigang Chang
author_sort Shijuan Cui
collection DOAJ
description BackgroundTuberculous meningitis (TBM) complicated by intracranial hypertension requires aggressive neurocritical care, yet the mortality impact of sedative and antipsychotic exposure remains controversial. This study investigates the association between sedative exposure and mortality while identifying modifiable risk factors in this vulnerable population.MethodsIn this retrospective cohort study, we analyzed 1,875 intracranial hypertensive TBM patients from the MIMIC-IV database (v2.0). Exposure was stratified by cumulative sedative days (>3 vs. ≤3). Primary outcomes included 200-day mortality assessed using multivariable logistic regression and Cox proportional hazards models. Propensity score matching (PSM) was performed to adjust for confounding, and machine learning (XGBoost) was used to predict mortality and evaluate feature importance.ResultsUnadjusted analyses identified age (odds ratio [OR] = 1.03 per year; 95% confidence interval [CI]: 1.01–1.05), sedative duration (OR = 1.13 per day; 95%CI: 1.04–1.22), and hospital length of stay (LOS; OR = 1.02 per day; 95%CI: 1.00–1.03) as significant mortality predictors. In the PSM cohort (n = 160 matched pairs), crude mortality rates were 16% in sedated versus 2.6% in non-sedated patients (p < 0.001), though the adjusted hazard ratio was non-significant (hazard ratio [HR] = 1.12; 95%CI: 0.83–1.50). Survival curves showed 200-day survival rates of 82% (95%CI: 79%–85%) for non-sedated and 47% (95%CI: 39%–55%) for sedated patients. The XGBoost model achieved an AUC-ROC of 0.79, identifying gender (SHAP value = 0.41), age (0.38), and LOS (0.29) as top predictors of mortality.ConclusionProlonged sedation (>3 days) is associated with substantially reduced survival in intracranial hypertensive TBM, potentially reflecting both underlying disease severity and iatrogenic effects. Although residual confounding remains, machine learning analysis highlights the critical influence of gender and LOS on outcomes. These findings demonstrate the need for randomized trials evaluating targeted sedation minimization strategies to improve neurotuberculosis care.
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spelling doaj-art-294a1d4366c04f7199164969d0d7fae62025-08-20T03:28:52ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16208581620858Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysisShijuan Cui0Fazheng Shen1Jianing Liang2Fan Li3Xiangyang Wang4Xin Liu5Haigang Chang6Department of Tuberculosis Internal Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, ChinaDepartment of Intensive Care Medicine, The First Affiliated Hospital of Changsha Medical University, Changsha, Hunan, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, ChinaBackgroundTuberculous meningitis (TBM) complicated by intracranial hypertension requires aggressive neurocritical care, yet the mortality impact of sedative and antipsychotic exposure remains controversial. This study investigates the association between sedative exposure and mortality while identifying modifiable risk factors in this vulnerable population.MethodsIn this retrospective cohort study, we analyzed 1,875 intracranial hypertensive TBM patients from the MIMIC-IV database (v2.0). Exposure was stratified by cumulative sedative days (>3 vs. ≤3). Primary outcomes included 200-day mortality assessed using multivariable logistic regression and Cox proportional hazards models. Propensity score matching (PSM) was performed to adjust for confounding, and machine learning (XGBoost) was used to predict mortality and evaluate feature importance.ResultsUnadjusted analyses identified age (odds ratio [OR] = 1.03 per year; 95% confidence interval [CI]: 1.01–1.05), sedative duration (OR = 1.13 per day; 95%CI: 1.04–1.22), and hospital length of stay (LOS; OR = 1.02 per day; 95%CI: 1.00–1.03) as significant mortality predictors. In the PSM cohort (n = 160 matched pairs), crude mortality rates were 16% in sedated versus 2.6% in non-sedated patients (p < 0.001), though the adjusted hazard ratio was non-significant (hazard ratio [HR] = 1.12; 95%CI: 0.83–1.50). Survival curves showed 200-day survival rates of 82% (95%CI: 79%–85%) for non-sedated and 47% (95%CI: 39%–55%) for sedated patients. The XGBoost model achieved an AUC-ROC of 0.79, identifying gender (SHAP value = 0.41), age (0.38), and LOS (0.29) as top predictors of mortality.ConclusionProlonged sedation (>3 days) is associated with substantially reduced survival in intracranial hypertensive TBM, potentially reflecting both underlying disease severity and iatrogenic effects. Although residual confounding remains, machine learning analysis highlights the critical influence of gender and LOS on outcomes. These findings demonstrate the need for randomized trials evaluating targeted sedation minimization strategies to improve neurotuberculosis care.https://www.frontiersin.org/articles/10.3389/fphar.2025.1620858/fullintracranial hypertensionmachine learningmortalitysedative exposuretuberculous meningitis
spellingShingle Shijuan Cui
Fazheng Shen
Jianing Liang
Fan Li
Xiangyang Wang
Xin Liu
Haigang Chang
Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysis
Frontiers in Pharmacology
intracranial hypertension
machine learning
mortality
sedative exposure
tuberculous meningitis
title Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysis
title_full Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysis
title_fullStr Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysis
title_full_unstemmed Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysis
title_short Sedative exposure and mortality in intracranial hypertensive tuberculous meningitis: a cohort study with propensity-score matching and machine learning analysis
title_sort sedative exposure and mortality in intracranial hypertensive tuberculous meningitis a cohort study with propensity score matching and machine learning analysis
topic intracranial hypertension
machine learning
mortality
sedative exposure
tuberculous meningitis
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1620858/full
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