Septic shock prediction for ICU patients via coupled HMM walking on sequential contrast patterns

© 2016 Background and objective Critical care patient events like sepsis or septic shock in intensive care units (ICUs) are dangerous complications which can cause multiple organ failures and eventual death. Preventive prediction of such events will allow clinicians to stage effective interventions for averting these critical complications. Methods It is widely understood that physiological conditions of patients on variables such as blood pressure and heart rate are suggestive to gradual changes over a certain period of time, prior to the occurrence of a septic shock. This work investigates the performance of a novel machine learning approach for the early prediction of septic shock. The approach combines highly informative sequential patterns extracted from multiple physiological variables and captures the interactions among these patterns via coupled hidden Markov models (CHMM). In particular, the patterns are extracted from three non-invasive waveform measurements: the mean arterial pressure levels, the heart rates and respiratory rates of septic shock patients from a large clinical ICU dataset called MIMIC-II. Evaluation and results For baseline estimations, SVM and HMM models on the continuous time series data for the given patients, using MAP (mean arterial pressure), HR (heart rate), and RR (respiratory rate) are employed. Single channel patterns based HMM (SCP-HMM) and multi-channel patterns based coupled HMM (MCP-HMM) are compared against baseline models using 5-fold cross validation accuracies over multiple rounds. Particularly, the results of MCP-HMM are statistically significant having a p-value of 0.0014, in comparison to baseline models. Our experiments demonstrate a strong competitive accuracy in the prediction of septic shock, especially when the interactions between the multiple variables are coupled by the learning model. Conclusions It can be concluded that the novelty of the approach, stems from the integration of sequence-based physiological pattern markers with the sequential CHMM model to learn dynamic physiological behavior, as well as from the coupling of such patterns to build powerful risk stratification models for septic shock patients

Improved diagnosis and management of sepsis and bloodstream infection

Sepsis is a severe organ dysfunction triggered by infections, and a leading cause of hospitalization and death. Concurrent bloodstream infection (BSI) is common and around one third of sepsis patients have positive blood cultures. Prompt diagnosis and treatment is crucial, but there is a trade-off between the negative effects of over diagnosis and failure to recognize sepsis in time. The emerging crisis of antimicrobial resistance has made bacterial infections more difficult to treat, especially gram-negative pathogens such as Pseudomonas aeruginosa. The overall aim with this thesis was to improve diagnosis, assess the influence of time to antimicrobial treatment and explore prognostic bacterial virulence markers in sepsis and BSI. The papers are based on observational data from 7 cohorts of more than 100 000 hospital episodes. In addition, whole genome sequencing has been performed on approximately 800 invasive P. aeruginosa isolates collected from centers in Europe and Australia. Paper I showed that automated surveillance of sepsis incidence using the Sepsis-3 criteria is feasible in the non-ICU setting, with examples of how implementing this model generates continuous epidemiological data down to the ward level. This information can be used for directing resources and evaluating quality-of-care interventions. In Paper II, evidence is provided for using peripheral oxygen saturation (SpO2) to diagnose respiratory dysfunction in sepsis, proposing the novel thresholds 94% and 90% to get 1 and 2 SOFA points, respectively. This has important implications for improving sepsis diagnosis, especially when conventional arterial blood gas measurements are unavailable. Paper III verified that sepsis surveillance data can be utilized to develop machine learning screening tools to improve early identification of sepsis. A Bayesian network algorithm trained on routine electronic health record data predicted sepsis onset within 48 hours with better discrimination and earlier than conventional NEWS2 outside the ICU. The results suggested that screening may primarily be suited for the early admission period, which have broader implications also for other sepsis screening tools. Paper IV demonstrated that delays in antimicrobial treatment with in vitro pathogen coverage in BSI were associated with increased mortality after 12 hours from blood culture collection, but not at 1, 3, and 6 hours. This indicates a time window where clinicians should focus on the diagnostic workup, and proposes a target for rapid diagnostics of blood cultures. Finally, Paper V showed that the virulence genotype had some influence on mortality and septic shock in P. aeruginosa BSI, however, it was not a major prognostic determinant. Together these studies contribute to better understanding of the sepsis and BSI populations, and provide several suggestions to improve diagnosis and timing of treatment, with implications for clinical practice. Future works should focus on the implementation of sepsis surveillance, clinical trials of time to antimicrobial treatment and evaluating the prognostic importance of bacterial genotype data in larger populations from diverse infection sources and pathogens

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

Machine Learning Methods for Septic Shock Prediction

Sepsis is an organ dysfunction life-threatening disease that is caused by a dysregulated body response to infection. Sepsis is difficult to detect at an early stage, and when not detected early, is difficult to treat and results in high mortality rates. Developing improved methods for identifying patients in high risk of suffering septic shock has been the focus of much research in recent years. Building on this body of literature, this dissertation develops an improved method for septic shock prediction. Using the data from the MMIC-III database, an ensemble classifier is trained to identify high-risk patients. A robust prediction model is built by obtaining a risk score from fitting the Cox Hazard model on multiple input features. The score is added to the list of features and the Random Forest ensemble classifier is trained to produce the model. The Cox Enhanced Random Forest (CERF) proposed method is evaluated by comparing its predictive accuracy to those of extant methods

Infection and sepsis in the Dutch acute care chain:opportunities for optimisation of care

Luckily, most infections resolve spontaneously. Sometimes, however, they become more severe. If, as a result of the infection, organs dysfunction, this is called sepsis. In this thesis, the trajectory of patients with a severe infection through the Dutch acute care chain was studied, with specific attention to possible targets for optimisation of care. The included studies showed that patients with a severe infection are present throughout the entire acute care chain and that general practitioners fulfil an important role. Different parameters are used in the decision whether or not to refer a patient to the hospital, among which a patient’s medical history, vital signs and the healthcare provider’s gut feeling. Unfortunately, vital signs were not measured consistently and there appeared to be opportunities for improvement in the documentation of sepsis and of a sense of urgency. In order to keep improving care, these items deserve the attention of all involved healthcare providers. <br/