The Global Open Source Severity of Illness Score (GOSSIS).

OBJECTIVES: To develop and demonstrate the feasibility of a Global Open Source Severity of Illness Score (GOSSIS)-1 for critical care patients, which generalizes across healthcare systems and countries. DESIGN: A merger of several critical care multicenter cohorts derived from registry and electronic health record data. Data were split into training (70%) and test (30%) sets, using each set exclusively for development and evaluation, respectively. Missing data were imputed when not available. SETTING/PATIENTS: Two large multicenter datasets from Australia and New Zealand (Australian and New Zealand Intensive Care Society Adult Patient Database [ANZICS-APD]) and the United States (eICU Collaborative Research Database [eICU-CRD]) representing 249,229 and 131,051 patients, respectively. ANZICS-APD and eICU-CRD contributed data from 162 and 204 hospitals, respectively. The cohort included all ICU admissions discharged in 2014-2015, excluding patients less than 16 years old, admissions less than 6 hours, and those with a previous ICU stay. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: GOSSIS-1 uses data collected during the ICU stay's first 24 hours, including extrema values for vital signs and laboratory results, admission diagnosis, the Glasgow Coma Scale, chronic comorbidities, and admission/demographic variables. The datasets showed significant variation in admission-related variables, case-mix, and average physiologic state. Despite this heterogeneity, test set discrimination of GOSSIS-1 was high (area under the receiver operator characteristic curve [AUROC], 0.918; 95% CI, 0.915-0.921) and calibration was excellent (standardized mortality ratio [SMR], 0.986; 95% CI, 0.966-1.005; Brier score, 0.050). Performance was held within ANZICS-APD (AUROC, 0.925; SMR, 0.982; Brier score, 0.047) and eICU-CRD (AUROC, 0.904; SMR, 0.992; Brier score, 0.055). Compared with GOSSIS-1, Acute Physiology and Chronic Health Evaluation (APACHE)-IIIj (ANZICS-APD) and APACHE-IVa (eICU-CRD), had worse discrimination with AUROCs of 0.904 and 0.869, and poorer calibration with SMRs of 0.594 and 0.770, and Brier scores of 0.059 and 0.063, respectively. CONCLUSIONS: GOSSIS-1 is a modern, free, open-source inhospital mortality prediction algorithm for critical care patients, achieving excellent discrimination and calibration across three countries.

A novel artificial intelligence based intensive care unit monitoring system: using physiological waveforms to identify sepsis.

A massive amount of multimodal data are continuously collected in the intensive care unit (ICU) along each patient stay, offering a great opportunity for the development of smart monitoring devices based on artificial intelligence (AI). The two main sources of relevant information collected in the ICU are the electronic health records (EHRs) and vital sign waveforms continuously recorded at the bedside. While EHRs are already widely processed by AI algorithms for prompt diagnosis and prognosis, AI-based assessments of the patients' pathophysiological state using waveforms are less developed, and their use is still limited to real-time monitoring for basic visual vital sign feedback at the bedside. This study uses data from the MIMIC-III database (PhysioNet) to propose a novel AI approach in ICU patient monitoring that incorporates features estimated by a closed-loop cardiovascular model, with the specific goal of identifying sepsis within the first hour of admission. Our top benchmark results (AUROC = 0.92, AUPRC = 0.90) suggest that features derived by cardiovascular control models may play a key role in identifying sepsis, by continuous monitoring performed through advanced multivariate modelling of vital sign waveforms. This work lays foundations for a deeper data integration paradigm which will help clinicians in their decision-making processes. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Delaying initiation of diuretics in critically ill patients with recent vasopressor use and high positive fluid balance.

BACKGROUND: Fluid overload is associated with poor outcomes. Clinicians might be reluctant to initiate diuretic therapy for patients with recent vasopressor use. We estimated the effect on 30-day mortality of withholding or delaying diuretics after vasopressor use in patients with probable fluid overload. METHODS: This was a retrospective cohort study of adults admitted to ICUs of an academic medical centre between 2008 and 2012. Using a database of time-stamped patient records, we followed individuals from the time they first required vasopressor support and had >5 L cumulative positive fluid balance (plus additional inclusion/exclusion criteria). We compared mortality under usual care (the mix of care actually delivered in the cohort) and treatment strategies restricting diuretic initiation during and for various durations after vasopressor use. We adjusted for baseline and time-varying confounding via inverse probability weighting. RESULTS: The study included 1501 patients, and the observed 30-day mortality rate was 11%. After adjusting for observed confounders, withholding diuretics for at least 24 h after stopping most recent vasopressor use was estimated to increase 30-day mortality rate by 2.2% (95% confidence interval [CI], 0.9-3.6%) compared with usual care. Data were consistent with moderate harm or slight benefit from withholding diuretic initiation only during concomitant vasopressor use; the estimated mortality rate increased by 0.5% (95% CI, -0.2% to 1.1%). CONCLUSIONS: Withholding diuretic initiation after vasopressor use in patients with high cumulative positive balance (>5 L) was estimated to increase 30-day mortality. These findings are hypothesis generating and should be tested in a clinical trial.

Quantitative Electroencephalogram Trends Predict Recovery in Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: Electroencephalogram features predict neurologic recovery following cardiac arrest. Recent work has shown that prognostic implications of some key electroencephalogram features change over time. We explore whether time dependence exists for an expanded selection of quantitative electroencephalogram features and whether accounting for this time dependence enables better prognostic predictions. DESIGN: Retrospective. SETTING: ICUs at four academic medical centers in the United States. PATIENTS: Comatose patients with acute hypoxic-ischemic encephalopathy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 12,397 hours of electroencephalogram from 438 subjects. From the electroencephalogram, we extracted 52 features that quantify signal complexity, category, and connectivity. We modeled associations between dichotomized neurologic outcome (good vs poor) and quantitative electroencephalogram features in 12-hour intervals using sequential logistic regression with Elastic Net regularization. We compared a predictive model using time-varying features to a model using time-invariant features and to models based on two prior published approaches. Models were evaluated for their ability to predict binary outcomes using area under the receiver operator curve, model calibration (how closely the predicted probability of good outcomes matches the observed proportion of good outcomes), and sensitivity at several common specificity thresholds of interest. A model using time-dependent features outperformed (area under the receiver operator curve, 0.83 ± 0.08) one trained with time-invariant features (0.79 ± 0.07; p < 0.05) and a random forest approach (0.74 ± 0.13; p < 0.05). The time-sensitive model was also the best-calibrated. CONCLUSIONS: The statistical association between quantitative electroencephalogram features and neurologic outcome changed over time, and accounting for these changes improved prognostication performance.

The association between autoimmune disease and 30-day mortality among sepsis ICU patients: a cohort study.

INTRODUCTION: Sepsis results from a dysregulated host response to an infection that is associated with an imbalance between pro- and anti-inflammatory cytokines. This imbalance is hypothesized to be a driver of patient mortality. Certain autoimmune diseases modulate the expression of cytokines involved in the pathophysiology of sepsis. However, the outcomes of patients with autoimmune disease who develop sepsis have not been studied in detail. The objective of this study is to determine whether patients with autoimmune diseases have different sepsis outcomes than patients without these comorbidities. METHODS: Using the Multiparameter Intelligent Monitoring in Intensive Care III database (v. 1.4) which contains retrospective clinical data for over 50,000 adult ICU stays, we compared 30-day mortality risk for sepsis patients with and without autoimmune disease. We used logistic regression models to control for known confounders, including demographics, disease severity, and immunomodulation medications. We used mediation analysis to evaluate how the chronic use of immunomodulation medications affects the relationship between autoimmune disease and 30-day mortality. RESULTS: Our study found a statistically significant 27.00% reduction in the 30-day mortality risk associated with autoimmune disease presence. This association was found to be the strongest (OR 0.71, 95% CI 0.54-0.93, P = 0.014) among patients with septic shock. The autoimmune disease-30-day mortality association was not mediated through the chronic use of immunomodulation medications (indirect effect OR 1.07, 95% CI 1.01-1.13, P = 0.020). CONCLUSIONS: We demonstrated that autoimmune diseases are associated with a lower 30-day mortality risk in sepsis. Our findings suggest that autoimmune diseases affect 30-day mortality through a mechanism unrelated to the chronic use of immunomodulation medications. Since this study was conducted within a single study center, research using data from other medical centers will provide further validation.

Obesity, Acute Kidney Injury, and Mortality in Critical Illness.

OBJECTIVES: Although obesity is associated with risk for chronic kidney disease and improved survival, less is known about the associations of obesity with risk of acute kidney injury and post acute kidney injury mortality. DESIGN: In a single-center inception cohort of almost 15,000 critically ill patients, we evaluated the association of obesity with acute kidney injury and acute kidney injury severity, as well as in-hospital and 1-year survival. Acute kidney injury was defined using the Kidney Disease Outcome Quality Initiative criteria. MEASUREMENTS AND MAIN RESULTS: The acute kidney injury prevalence rates for normal, overweight, class I, II, and III obesity were 18.6%, 20.6%, 22.5%, 24.3%, and 24.0%, respectively, and the adjusted odds ratios of acute kidney injury were 1.18 (95% CI, 1.06-1.31), 1.35 (1.19-1.53), 1.47 (1.25-1.73), and 1.59 (1.31-1.87) when compared with normal weight, respectively. Each 5-kg/m² increase in body mass index was associated with a 10% risk (95% CI, 1.06-1.24; p < 0.001) of more severe acute kidney injury. Within-hospital and 1-year survival rates associated with the acute kidney injury episodes were similar across body mass index categories. CONCLUSION: Obesity is a risk factor for acute kidney injury, which is associated with increased short- and long-term mortality.

Evaluating Prognostic Bias of Critical Illness Severity Scores Based on Age, Sex, and Primary Language in the United States: A Retrospective Multicenter Study.

OBJECTIVES: Although illness severity scoring systems are widely used to support clinical decision-making and assess ICU performance, their potential bias across different age, sex, and primary language groups has not been well-studied. DESIGN SETTING AND PATIENTS: We aimed to identify potential bias of Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) IVa scores via large ICU databases. SETTING/PATIENTS: This multicenter, retrospective study was conducted using data from the Medical Information Mart for Intensive Care (MIMIC) and eICU Collaborative Research Database. SOFA and APACHE IVa scores were obtained from ICU admission. Hospital mortality was the primary outcome. Discrimination (area under receiver operating characteristic [AUROC] curve) and calibration (standardized mortality ratio [SMR]) were assessed for all subgroups. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 196,310 patient encounters were studied. Discrimination for both scores was worse in older patients compared with younger patients and female patients rather than male patients. In MIMIC, discrimination of SOFA in non-English primary language speakers patients was worse than that of English speakers (AUROC 0.726 vs. 0.783, p < 0.0001). Evaluating calibration via SMR showed statistically significant underestimations of mortality when compared with overall cohort in the oldest patients for both SOFA and APACHE IVa, female patients (1.09) for SOFA, and non-English primary language patients (1.38) for SOFA in MIMIC. CONCLUSIONS: Differences in discrimination and calibration of two scores across varying age, sex, and primary language groups suggest illness severity scores are prone to bias in mortality predictions. Caution must be taken when using them for quality benchmarking and decision-making among diverse real-world populations.

Deep neural networks detect regional wall motion abnormalities and preclinical cardiovascular disease from 12-lead ECGs.

Background: Identifying regional wall motion abnormalities (RWMAs) is critical for diagnosing and risk stratifying patients with cardiovascular disease, particularly ischemic heart disease. We hypothesized that a deep neural network could accurately identify patients with regional wall motion abnormalities from a readily available standard 12-lead electrocardiogram (ECG). Methods: This observational, retrospective study included patients who were treated at Beth Israel Deaconess Medical Center and had an ECG and echocardiogram performed within 14 days of each other between 2008 and 2019. We trained a convolutional neural network to detect the presence of RWMAs, qualitative global right ventricular (RV) hypokinesis, and varying degrees of left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤50%, LVEF ≤40%, and LVEF ≤35%) identified by echocardiography, using ECG data alone. Patients were randomly split into development (80%) and test sets (20%). Model performance was assessed using area under the receiver operating characteristic curve (AUC). Cox proportional hazard models adjusted for age and sex were performed to estimate the risk of future acute coronary events. Results: The development set consisted of 19,837 patients (mean age 66.7±16.4; 46.7% female) and the test set comprised of 4,953 patients (mean age 67.5±15.8 years; 46.5% female). On the test dataset, the model accurately identified the presence of RWMA, RV hypokinesis, LVEF ≤50%, LVEF ≤40%, and LVEF ≤35% with AUCs of 0.87 (95% CI 0.858-0.882), 0.888 (95% CI 0.878-0.899), 0.923 (95% CI 0.914-0.933), 0.93 (95% CI 0.921-0.939), and 0.876 (95% CI 0.858-0.896), respectively. Among patients with normal biventricular function at the time of the index ECG, those classified as having RMWA by the model were 3 times the risk (age- and sex-adjusted hazard ratio, 2.8; 95% CI 1.9-3.9) for future acute coronary events compared to those classified as negative. Conclusions: We demonstrate that a deep neural network can help identify regional wall motion abnormalities and reduced LV function from a 12-lead ECG and could potentially be used as a screening tool for triaging patients who need either initial or repeat echocardiographic imaging.

INSPIRE, a publicly available research dataset for perioperative medicine.

We present the INSPIRE dataset, a publicly available research dataset in perioperative medicine, which includes approximately 130,000 surgical operations at an academic institution in South Korea over a ten-year period between 2011 and 2020. This comprehensive dataset includes patient characteristics such as age, sex, American Society of Anesthesiologists physical status classification, diagnosis, surgical procedure code, department, and type of anaesthesia. The dataset also includes vital signs in the operating theatre, general wards, and intensive care units (ICUs), laboratory results from six months before admission to six months after discharge, and medication during hospitalisation. Complications include total hospital and ICU length of stay and in-hospital death. We hope this dataset will inspire collaborative research and development in perioperative medicine and serve as a reproducible external validation dataset to improve surgical outcomes.

Proton-pump inhibitor use is associated with low serum magnesium concentrations.

Although case reports link proton-pump inhibitor (PPI) use and hypomagnesemia, no large-scale studies have been conducted. Here we examined the serum magnesium concentration and the likelihood of hypomagnesemia (<1.6 mg/dl) with a history of PPI or histamine-2 receptor antagonist used to reduce gastric acid, or use of neither among 11,490 consecutive adult admissions to an intensive care unit of a tertiary medical center. Of these, 2632 patients reported PPI use prior to admission, while 657 patients were using a histamine-2 receptor antagonist. PPI use was associated with 0.012 mg/dl lower adjusted serum magnesium concentration compared to users of no acid-suppressive medications, but this effect was restricted to those patients taking diuretics. Among the 3286 patients concurrently on diuretics, PPI use was associated with a significant increase of hypomagnesemia (odds ratio 1.54) and 0.028 mg/dl lower serum magnesium concentration. Among those not using diuretics, PPI use was not associated with serum magnesium levels. Histamine-2 receptor antagonist use was not significantly associated with magnesium concentration without or with diuretic use. The use of PPI was not associated with serum phosphate concentration regardless of diuretic use. Thus, we verify case reports of the association between PPI use and hypomagnesemia in those concurrently taking diuretics. Hence, serum magnesium concentrations should be followed in susceptible individuals on chronic PPI therapy.

Accessing the public MIMIC-II intensive care relational database for clinical research.

BACKGROUND: The Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database is a free, public resource for intensive care research. The database was officially released in 2006, and has attracted a growing number of researchers in academia and industry. We present the two major software tools that facilitate accessing the relational database: the web-based QueryBuilder and a downloadable virtual machine (VM) image. RESULTS: QueryBuilder and the MIMIC-II VM have been developed successfully and are freely available to MIMIC-II users. Simple example SQL queries and the resulting data are presented. Clinical studies pertaining to acute kidney injury and prediction of fluid requirements in the intensive care unit are shown as typical examples of research performed with MIMIC-II. In addition, MIMIC-II has also provided data for annual PhysioNet/Computing in Cardiology Challenges, including the 2012 Challenge "Predicting mortality of ICU Patients". CONCLUSIONS: QueryBuilder is a web-based tool that provides easy access to MIMIC-II. For more computationally intensive queries, one can locally install a complete copy of MIMIC-II in a VM. Both publicly available tools provide the MIMIC-II research community with convenient querying interfaces and complement the value of the MIMIC-II relational database.

Clinically Interpretable Machine Learning Models for Early Prediction of Mortality in Older Patients with Multiple Organ Dysfunction Syndrome: An International Multicenter Retrospective Study.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is associated with a high risk of mortality among older patients. Current severity scores are limited in their ability to assist clinicians with triage and management decisions. We aim to develop mortality prediction models for older patients with MODS admitted to the ICU. METHODS: The study analyzed older patients from 197 hospitals in the United States and 1 hospital in the Netherlands. The cohort was divided into the young-old (65-80 years) and old-old (≥80 years), which were separately used to develop and evaluate models including internal, external, and temporal validation. Demographic characteristics, comorbidities, vital signs, laboratory measurements, and treatments were used as predictors. We used the XGBoost algorithm to train models, and the SHapley Additive exPlanations (SHAP) method to interpret predictions. RESULTS: Thirty-four thousand four hundred and ninety-seven young-old (11.3% mortality) and 21 330 old-old (15.7% mortality) patients were analyzed. Discrimination AUROC of internal validation models in 9 046 U.S. patients was as follows: 0.87 and 0.82, respectively; discrimination of external validation models in 1 905 EUR patients was as follows: 0.86 and 0.85, respectively; and discrimination of temporal validation models in 8 690 U.S. patients: 0.85 and 0.78, respectively. These models outperformed standard clinical scores like Sequential Organ Failure Assessment and Acute Physiology Score III. The Glasgow Coma Scale, Charlson Comorbidity Index, and Code Status emerged as top predictors of mortality. CONCLUSIONS: Our models integrate data spanning physiologic and geriatric-relevant variables that outperform existing scores used in older adults with MODS, which represents a proof of concept of how machine learning can streamline data analysis for busy ICU clinicians to potentially optimize prognostication and decision making.

Illness severity assessment of older adults in critical illness using machine learning (ELDER-ICU): an international multicentre study with subgroup bias evaluation.

BACKGROUND: Comorbidity, frailty, and decreased cognitive function lead to a higher risk of death in elderly patients (more than 65 years of age) during acute medical events. Early and accurate illness severity assessment can support appropriate decision making for clinicians caring for these patients. We aimed to develop ELDER-ICU, a machine learning model to assess the illness severity of older adults admitted to the intensive care unit (ICU) with cohort-specific calibration and evaluation for potential model bias. METHODS: In this retrospective, international multicentre study, the ELDER-ICU model was developed using data from 14 US hospitals, and validated in 171 hospitals from the USA and Netherlands. Data were extracted from the Medical Information Mart for Intensive Care database, electronic ICU Collaborative Research Database, and Amsterdam University Medical Centers Database. We used six categories of data as predictors, including demographics and comorbidities, physical frailty, laboratory tests, vital signs, treatments, and urine output. Patient data from the first day of ICU stay were used to predict in-hospital mortality. We used the eXtreme Gradient Boosting algorithm (XGBoost) to develop models and the SHapley Additive exPlanations method to explain model prediction. The trained model was calibrated before internal, external, and temporal validation. The final XGBoost model was compared against three other machine learning algorithms and five clinical scores. We performed subgroup analysis based on age, sex, and race. We assessed the discrimination and calibration of models using the area under receiver operating characteristic (AUROC) and standardised mortality ratio (SMR) with 95% CIs. FINDINGS: Using the development dataset (n=50 366) and predictive model building process, the XGBoost algorithm performed the best in all types of validations compared with other machine learning algorithms and clinical scores (internal validation with 5037 patients from 14 US hospitals, AUROC=0·866 [95% CI 0·851-0·880]; external validation in the US population with 20 541 patients from 169 hospitals, AUROC=0·838 [0·829-0·847]; external validation in European population with 2411 patients from one hospital, AUROC=0·833 [0·812-0·853]; temporal validation with 4311 patients from one hospital, AUROC=0·884 [0·869-0·897]). In the external validation set (US population), the median AUROCs of bias evaluations covering eight subgroups were above 0·81, and the overall SMR was 0·99 (0·96-1·03). The top ten risk predictors were the minimum Glasgow Coma Scale score, total urine output, average respiratory rate, mechanical ventilation use, best state of activity, Charlson Comorbidity Index score, geriatric nutritional risk index, code status, age, and maximum blood urea nitrogen. A simplified model containing only the top 20 features (ELDER-ICU-20) had similar predictive performance to the full model. INTERPRETATION: The ELDER-ICU model reliably predicts the risk of in-hospital mortality using routinely collected clinical features. The predictions could inform clinicians about patients who are at elevated risk of deterioration. Prospective validation of this model in clinical practice and a process for continuous performance monitoring and model recalibration are needed. FUNDING: National Institutes of Health, National Natural Science Foundation of China, National Special Health Science Program, Health Science and Technology Plan of Zhejiang Province, Fundamental Research Funds for the Central Universities, Drug Clinical Evaluate Research of Chinese Pharmaceutical Association, and National Key R&D Program of China.

MIMIC-IV, a freely accessible electronic health record dataset.

Digital data collection during routine clinical practice is now ubiquitous within hospitals. The data contains valuable information on the care of patients and their response to treatments, offering exciting opportunities for research. Typically, data are stored within archival systems that are not intended to support research. These systems are often inaccessible to researchers and structured for optimal storage, rather than interpretability and analysis. Here we present MIMIC-IV, a publicly available database sourced from the electronic health record of the Beth Israel Deaconess Medical Center. Information available includes patient measurements, orders, diagnoses, procedures, treatments, and deidentified free-text clinical notes. MIMIC-IV is intended to support a wide array of research studies and educational material, helping to reduce barriers to conducting clinical research.

A contrastive learning approach for ICU false arrhythmia alarm reduction.

The high rate of false arrhythmia alarms in Intensive Care Units (ICUs) can lead to disruption of care, negatively impacting patients' health through noise disturbances, and slow staff response time due to alarm fatigue. Prior false-alarm reduction approaches are often rule-based and require hand-crafted features from physiological waveforms as inputs to machine learning classifiers. Despite considerable prior efforts to address the problem, false alarms are a continuing problem in the ICUs. In this work, we present a deep learning framework to automatically learn feature representations of physiological waveforms using convolutional neural networks (CNNs) to discriminate between true vs. false arrhythmia alarms. We use Contrastive Learning to simultaneously minimize a binary cross entropy classification loss and a proposed similarity loss from pair-wise comparisons of waveform segments over time as a discriminative constraint. Furthermore, we augment our deep models with learned embeddings from a rule-based method to leverage prior domain knowledge for each alarm type. We evaluate our method using the dataset from the 2015 PhysioNet Computing in Cardiology Challenge. Ablation analysis demonstrates that Contrastive Learning significantly improves the performance of a combined deep learning and rule-based-embedding approach. Our results indicate that the final proposed deep learning framework achieves superior performance in comparison to the winning entries of the Challenge.

Outcome of critically ill patients with acute kidney injury using the Acute Kidney Injury Network criteria.

OBJECTIVE: Acute kidney injury affects 5% to 7% of all hospitalized patients with a much higher incidence in the critically ill. The Acute Kidney Injury Network proposed a definition in which serum creatinine rises (>0.3 mg/dL) and/or oliguria (<0.5 mL/kg/hr) for a period of 6 hrs are used to detect acute kidney injury. Accurate urine output measurements as well as serum creatinine values from our database were used to detect patients with acute kidney injury and calculate their corresponding mortality risk and length of stay. DESIGN: Retrospective cohort study. SETTING: Seven intensive care units at a large, academic, tertiary medical center. PATIENTS: Adult patients without evidence of end-stage renal disease with more than two creatinine measurements and at least a 6-hr urine output recording who were admitted to the intensive care unit between 2001 and 2007. INTERVENTIONS: Medical records of all the patients were reviewed. Demographic information, laboratory results, charted data, discharge diagnoses, physiological data, and patient outcomes were extracted from the Multiparameter Intelligent Monitoring in Intensive Care II database using a SQL query. MEASUREMENTS AND MAIN RESULTS: From 19,677 adult patient records, 14,524 patients met the inclusion criteria. Fifty-seven percent developed acute kidney injury during their intensive care unit stay. Inhospital mortality rates were: 13.9%, 16.4%, 33.8% for acute kidney injury 1, 2, and 3, respectively, compared with only 6.2% in patients without acute kidney injury (p < .0001). After adjusting for multiple covariates, acute kidney injury was associated with increased hospital mortality (odds ratio 1.4 and 1.3 for acute kidney injury 1 and acute kidney injury 2 and 2.5 for acute kidney injury 3; p < .0001). Using multivariate logistic regression, we found that in patients who developed acute kidney injury, urine output alone was a better mortality predictor than creatinine alone or the combination of both. CONCLUSIONS: More than 50% of our critically ill patients developed some stage of acute kidney injury resulting in a stagewise increased mortality risk. However, the mortality risk associated with acute kidney injury stages 1 and 2 does not differ significantly. In light of these findings, re-evaluation of the Acute Kidney Injury Network staging criteria should be considered.

Multiparameter Intelligent Monitoring in Intensive Care II: a public-access intensive care unit database.

OBJECTIVE: We sought to develop an intensive care unit research database applying automated techniques to aggregate high-resolution diagnostic and therapeutic data from a large, diverse population of adult intensive care unit patients. This freely available database is intended to support epidemiologic research in critical care medicine and serve as a resource to evaluate new clinical decision support and monitoring algorithms. DESIGN: Data collection and retrospective analysis. SETTING: All adult intensive care units (medical intensive care unit, surgical intensive care unit, cardiac care unit, cardiac surgery recovery unit) at a tertiary care hospital. PATIENTS: Adult patients admitted to intensive care units between 2001 and 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database consists of 25,328 intensive care unit stays. The investigators collected detailed information about intensive care unit patient stays, including laboratory data, therapeutic intervention profiles such as vasoactive medication drip rates and ventilator settings, nursing progress notes, discharge summaries, radiology reports, provider order entry data, International Classification of Diseases, 9th Revision codes, and, for a subset of patients, high-resolution vital sign trends and waveforms. Data were automatically deidentified to comply with Health Insurance Portability and Accountability Act standards and integrated with relational database software to create electronic intensive care unit records for each patient stay. The data were made freely available in February 2010 through the Internet along with a detailed user's guide and an assortment of data processing tools. The overall hospital mortality rate was 11.7%, which varied by critical care unit. The median intensive care unit length of stay was 2.2 days (interquartile range, 1.1-4.4 days). According to the primary International Classification of Diseases, 9th Revision codes, the following disease categories each comprised at least 5% of the case records: diseases of the circulatory system (39.1%); trauma (10.2%); diseases of the digestive system (9.7%); pulmonary diseases (9.0%); infectious diseases (7.0%); and neoplasms (6.8%). CONCLUSIONS: MIMIC-II documents a diverse and very large population of intensive care unit patient stays and contains comprehensive and detailed clinical data, including physiological waveforms and minute-by-minute trends for a subset of records. It establishes a new public-access resource for critical care research, supporting a diverse range of analytic studies spanning epidemiology, clinical decision-rule development, and electronic tool development.

An investigation of patterns in hemodynamic data indicative of impending hypotension in intensive care.

BACKGROUND: In the intensive care unit (ICU), clinical staff must stay vigilant to promptly detect and treat hypotensive episodes (HEs). Given the stressful context of busy ICUs, an automated hypotensive risk stratifier can help ICU clinicians focus care and resources by prospectively identifying patients at increased risk of impending HEs. The objective of this study was to investigate the possible existence of discriminatory patterns in hemodynamic data that can be indicative of future hypotensive risk. METHODS: Given the complexity and heterogeneity of ICU data, a machine learning approach was used in this study. Time series of minute-by-minute measures of mean arterial blood pressure, heart rate, pulse pressure, and relative cardiac output from 1,311 records from the MIMIC II Database were used. An HE was defined as a 30-minute period during which the mean arterial pressure was below 60 mmHg for at least 90% of the time. Features extracted from the hemodynamic data during an observation period of either 30 or 60 minutes were analyzed to predict the occurrence of HEs 1 or 2 hours into the future. Artificial neural networks (ANNs) were trained for binary classification (normotensive vs. hypotensive) and regression (estimation of future mean blood pressure). RESULTS: The ANNs were successfully trained to discriminate patterns in the multidimensional hemodynamic data that were predictive of future HEs. The best overall binary classification performance resulted in a mean area under ROC curve of 0.918, a sensitivity of 0.826, and a specificity of 0.859. Predicting further into the future resulted in poorer performance, whereas observation duration minimally affected performance. The low prevalence of HEs led to poor positive predictive values. In regression, the best mean absolute error was 9.67%. CONCLUSIONS: The promising pattern recognition performance demonstrates the existence of discriminatory patterns in hemodynamic data that can indicate impending hypotension. The poor PPVs discourage a direct HE predictor, but a hypotensive risk stratifier based on the pattern recognition algorithms of this study would be of significant clinical value in busy ICU environments.

Do Hyponatremia or Its Underlying Mechanisms Associate With Mortality Risk in Observational Data?

OBJECTIVES: Whether unaccounted determinants of hyponatremia, rather than water excess per se, primarily associate with mortality in observational studies has not been explicitly examined. DESIGN: Retrospective cohort study of the association between hyponatremia and mortality, stratified by outpatient diuretic use in three strata. SETTING: An inception cohort of 13,661 critically ill patients from a tertiary medical center. MEASUREMENTS AND MAIN RESULTS: Admission serum sodium concentrations, obtained within 12 hours of admission to the ICU, were the primary exposure. Hyponatremia was associated with 1.82 (95% CI, 1.56-2.11; p < 0.001) higher odds of mortality, yet differed according to outpatient diuretic use (multiplicative interaction between thiazide and serum sodium < 133 mEq/L; p = 0.002). Although hyponatremia was associated with a three-fold higher (odds ratio, 3.11; 95% CI, 2.32-4.17; p < 0.001) odds of mortality among those prescribed loop diuretics, no increase of risk was observed among thiazide diuretic users (odds ratio, 0.87; 95% CI, 0.47-1.51; p = 0.63). When examined as a continuous variable, each one mEq/L higher serum sodium was associated with 8% (odds ratio, 0.92; 95% CI, 0.90-0.94; p < 0.001) lower odds of mortality in loop diuretic patients and 5% (odds ratio, 0.95; 95% CI, 0.93-0.96, p < 0.001) lower in diuretic naïve patients, but was not associated with mortality risk among thiazide users (odds ratio, 0.99; 95% CI, 0.95-1.02; p = 0.45). CONCLUSIONS: Hyponatremia is not uniformly associated with increased mortality, but differs according to diuretic exposure. Our results suggest that the underlying pathophysiologic factors that lead to water excess, rather water excess itself, account in part for the association between hyponatremia and poor outcomes. More accurate estimations about the association between hyponatremia and outcomes might influence clinical decision-making.