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      Associations of serum lactate and lactate clearance with delirium in the early stage of ICU: a retrospective cohort study of the MIMIC-IV database

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          Abstract

          Aim

          This study aimed to investigate the associations of serum lactate level [within and after 24 h of the intensive care unit (ICU) admission] and lactate clearance rate with delirium and assess associations of lactate and lactate clearance rate with 30-day mortality in delirium patients.

          Methods

          Data in this retrospective cohort study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database in 2012–2019. The associations of lactate and lactate clearance rate with delirium were explored through univariable and multivariable logistic regression analyses, whereas the associations of lactate and lactate clearance rate with 30-day mortality in delirium patients were investigated using univariable and multivariable Cox regression analyses. Subgroup analysis was performed for age, gender, sepsis, hypertension, sedative drug, ventilation, antibiotic drug, vasopressors, and the Sequential Organ Failure Assessment (SOFA) score. The evaluation indexes were odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs).

          Results

          Among 7,812 (14.58%) eligible participants, 4,338 (8.19%) had delirium and 1,903 (24.36%) died within 30 days. After adjusting for covariates, patients with lactic acidosis (lactate level > 5 mmol/L and PH < 7.35) at T0 (within 24 h of the ICU admission) had higher odds of delirium (OR = 1.235, 95%CI: 1.105–1.382). Hyperlactatemia (lactate level 2–5 mmol/L and PH > 7.35) at T1 (after 24 h of the ICU admission) was also associated with higher odds of delirium (OR = 1.277, 95%CI: 1.126–1.447). Lactate clearance rate > 50% was linked to lower odds of delirium (OR = 0.705, 95%CI: 0.613–0.811), and this relationship was also observed in ≥65 years old, female, male, non-sepsis, sepsis, non-hypertension, non-sedative drug use, sedative drug use, ventilation, antibiotic drug use, use of vasopressors, and different SOFA score subgroups (all p < 0.05). Additionally, hyperlactatemia and lactic acidosis (whether at T0 or T1) may be potential risk factors for 30-day mortality in delirium patients, whereas lactate clearance rate ≥ 0 had a potential protective effect on 30-day mortality (all p < 0.05).

          Conclusion

          Higher serum lactate levels in the early stage of the ICU were associated with a higher risk of delirium and subsequent mortality. Measures taken to increase the lactate clearance rate are necessary to reduce potential delirium or mortality risk in clinical settings. However, more evidence from prospective studies is needed to verify these findings.

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          Most cited references37

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          Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).

          Delirium is a common problem in the intensive care unit (ICU). Accurate diagnosis is limited by the difficulty of communicating with mechanically ventilated patients and by lack of a validated delirium instrument for use in the ICU. To validate a delirium assessment instrument that uses standardized nonverbal assessments for mechanically ventilated patients and to determine the occurrence rate of delirium in such patients. Prospective cohort study testing the Confusion Assessment Method for ICU Patients (CAM-ICU) in the adult medical and coronary ICUs of a US university-based medical center. A total of 111 consecutive patients who were mechanically ventilated were enrolled from February 1, 2000, to July 15, 2000, of whom 96 (86.5%) were evaluable for the development of delirium and 15 (13.5%) were excluded because they remained comatose throughout the investigation. Occurrence rate of delirium and sensitivity, specificity, and interrater reliability of delirium assessments using the CAM-ICU, made daily by 2 critical care study nurses, compared with assessments by delirium experts using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. A total of 471 daily paired evaluations were completed. Compared with the reference standard for diagnosing delirium, 2 study nurses using the CAM-ICU had sensitivities of 100% and 93%, specificities of 98% and 100%, and high interrater reliability (kappa = 0.96; 95% confidence interval, 0.92-0.99). Interrater reliability measures across subgroup comparisons showed kappa values of 0.92 for those aged 65 years or older, 0.99 for those with suspected dementia, or 0.94 for those with Acute Physiology and Chronic Health Evaluation II scores at or above the median value of 23 (all P<.001). Comparing sensitivity and specificity between patient subgroups according to age, suspected dementia, or severity of illness showed no significant differences. The mean (SD) CAM-ICU administration time was 2 (1) minutes. Reference standard diagnoses of delirium, stupor, and coma occurred in 25.2%, 21.3%, and 28.5% of all observations, respectively. Delirium occurred in 80 (83.3%) patients during their ICU stay for a mean (SD) of 2.4 (1.6) days. Delirium was even present in 39.5% of alert or easily aroused patient observations by the reference standard and persisted in 10.4% of patients at hospital discharge. Delirium, a complication not currently monitored in the ICU setting, is extremely common in mechanically ventilated patients. The CAM-ICU appears to be rapid, valid, and reliable for diagnosing delirium in the ICU setting and may be a useful instrument for both clinical and research purposes.
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            Early lactate clearance is associated with improved outcome in severe sepsis and septic shock.

            Serial lactate concentrations can be used to examine disease severity in the intensive care unit. This study examines the clinical utility of the lactate clearance before intensive care unit admission (during the most proximal period of disease presentation) as an indicator of outcome in severe sepsis and septic shock. We hypothesize that a high lactate clearance in 6 hrs is associated with decreased mortality rate. Prospective observational study. An urban emergency department and intensive care unit over a 1-yr period. A convenience cohort of patients with severe sepsis or septic shock. Therapy was initiated in the emergency department and continued in the intensive care unit, including central venous and arterial catheterization, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, and inotropes when appropriate. Vital signs, laboratory values, and Acute Physiology and Chronic Health Evaluation (APACHE) II score were obtained at hour 0 (emergency department presentation), hour 6, and over the first 72 hrs of hospitalization. Therapy given in the emergency department and intensive care unit was recorded. Lactate clearance was defined as the percent decrease in lactate from emergency department presentation to hour 6. Logistic regression analysis was performed to determine independent variables associated with mortality. One hundred and eleven patients were enrolled with mean age 64.9 +/- 16.7 yrs, emergency department length of stay 6.3 +/- 3.2 hrs, and overall in-hospital mortality rate 42.3%. Baseline APACHE II score was 20.2 +/- 6.8 and lactate 6.9 +/- 4.6 mmol/L. Survivors compared with nonsurvivors had a lactate clearance of 38.1 +/- 34.6 vs. 12.0 +/- 51.6%, respectively (p =.005). Multivariate logistic regression analysis of statistically significant univariate variables showed lactate clearance to have a significant inverse relationship with mortality (p =.04). There was an approximately 11% decrease likelihood of mortality for each 10% increase in lactate clearance. Patients with a lactate clearance> or =10%, relative to patients with a lactate clearance <10%, had a greater decrease in APACHE II score over the 72-hr study period and a lower 60-day mortality rate (p =.007). Lactate clearance early in the hospital course may indicate a resolution of global tissue hypoxia and is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hrs of emergency department intervention have improved outcome compared with those with lower lactate clearance.
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              The MIMIC Code Repository: enabling reproducibility in critical care research

              Abstract Objective Lack of reproducibility in medical studies is a barrier to the generation of a robust knowledge base to support clinical decision-making. In this paper we outline the Medical Information Mart for Intensive Care (MIMIC) Code Repository, a centralized code base for generating reproducible studies on an openly available critical care dataset. Materials and Methods Code is provided to load the data into a relational structure, create extractions of the data, and reproduce entire analysis plans including research studies. Results Concepts extracted include severity of illness scores, comorbid status, administrative definitions of sepsis, physiologic criteria for sepsis, organ failure scores, treatment administration, and more. Executable documents are used for tutorials and reproduce published studies end-to-end, providing a template for future researchers to replicate. The repository’s issue tracker enables community discussion about the data and concepts, allowing users to collaboratively improve the resource. Discussion The centralized repository provides a platform for users of the data to interact directly with the data generators, facilitating greater understanding of the data. It also provides a location for the community to collaborate on necessary concepts for research progress and share them with a larger audience. Consistent application of the same code for underlying concepts is a key step in ensuring that research studies on the MIMIC database are comparable and reproducible. Conclusion By providing open source code alongside the freely accessible MIMIC-III database, we enable end-to-end reproducible analysis of electronic health records.
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                Author and article information

                Contributors
                Role: Role:
                Role: Role:
                Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2632485/overviewRole:
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                01 July 2024
                2024
                : 15
                : 1371827
                Affiliations
                [1] 1Department of Emergency Medicine, Linping Campus, The Second Affiliated Hospital of Zhejiang University School of Medicine , Hangzhou, Zhejiang, China
                [2] 2Department of Emergency Medicine, The Second Affiliated Hospital Zhejiang University School of Medicine , Hangzhou, Zhejiang, China
                Author notes

                Edited by: Paolo Mazzola, University of Milano-Bicocca, Italy

                Reviewed by: Maria Cristina Ferrara, University of Milano-Bicocca, Italy

                Sunil Swami, Blue Health Intelligence (BHI), United States

                Jaime Daniel Mondragón, San Diego State University, United States

                *Correspondence: Yong’an Xu, xuyongan_2000@ 123456163.com
                Article
                10.3389/fneur.2024.1371827
                11246852
                39011361
                5bce5cc0-ad22-41ac-88f5-69cfd4b253e8
                Copyright © 2024 Qian, Sheng, Jiang and Xu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 January 2024
                : 12 June 2024
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 37, Pages: 11, Words: 7439
                Funding
                Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;
                Award ID: 81571916
                Award ID: 81201478
                Funded by: Key Research and Development Program of Zhejiang Province
                Award ID: 2024C03186
                Funded by: National-Zhejiang Provincial Administration of Traditional Chinese Medicine
                Award ID: GZY-ZJ-KJ-24030
                Funded by: Hangzhou Health Technology Development
                Award ID: B20220306
                Funded by: Hangzhou Biomedicine and Health Industry
                Award ID: 2021WJCY390
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported in part by the National Natural Science Foundation of China (No. 81571916 and 81201478); the Key Research and Development Program of Zhejiang Province (No. 2024C03186); the Major Project of National-Zhejiang Provincial Administration of Traditional Chinese Medicine (GZY-ZJ-KJ-24030); the Hangzhou Health Technology Development Project (B20220306); and the Hangzhou Biomedicine and Health Industry Development Project (2021WJCY390).
                Categories
                Neurology
                Original Research
                Custom metadata
                Cognitive and Behavioral Neurology

                Neurology
                lactate,lactate clearance rate,delirium,mimic-iv,early stage of icu
                Neurology
                lactate, lactate clearance rate, delirium, mimic-iv, early stage of icu

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