Temperature, Heart Rate and Respiratory Rate Investigation along with Variability Evaluation (THRRIVE) to Provide Early Diagnosis and Prognosis of Infection. Research has demonstrated that altered variation (i.e. heart rate variability (HRV) and respiratory rate variability (RRV)) is present in association with age and illness, and the degree of alteration correlates with severity of illness. The overall aim of this study is to apply continuous HRV and RRV analysis to track patients as they develop infection, and thus develop novel and earlier means of identifying infection. In this study continuous monitoring of HRV and RRV along with intermittent temperature measurement are performed in patients who have undergone chemotherapy followed by a bone marrow transplant and are at marked risk for infection, in order to directly observe if a change in HRV and or RRV occurs earlier than a change in absolute value of heart rate, respiratory rate or temperature. Our preliminary data demonstrates feasibility of continuous HRV monitoring, and evidence of clear and reproducible changes in HRV many hours prior to clinical diagnosis of infection Given the clinical prevalence of infection and the need for early diagnosis, the results of this bedside application of complex systems science and variability analysis will have widespread clinical application to all patients at risk for infection.


Sedation and Variability (SEVA) - Improving Safety of Sedation Practice and Critical Illness Prognostication through heart rate and respiratory rate variability analysis. We and others have shown that both heart and respiratory rate variability (HRV &RRV) are reduced (i.e. more regular, less adaptable rhythms) in states of critical illness, and variability is also reduced by sedation. In our pilot study it was shown that monitoring variability during the time when sedation is interrupted uncovers the "true" variability relating to the underlying level of illness. The aims of this study are to use this information to improve the safety of sedation practice in critically ill, by determining when it is safe to significantly reduce sedation. Further, our study aims to help clinicians track the underlying severity of organ failure, determine how different types of sedatives alter variability, and identify patterns of altered variation that may help identify pain/agitation/delirium and patients who are over-sedated.


Weaning and Variability Evaluation (WAVE) - an evaluation of altered heart rate and respiratory rate variability to predict extubation failure. To assess a patient's ability to be extubated, a spontaneous breathing trial (SBT) is performed, where the level of ventilator support is reduced, and their response is observed to predict if they will tolerate extubation. We have just completed a CIHR-funded study called the Weaning and Variability Evaluation (WAVE) derivation study where we demonstrated that maintaining a high level of heart rate and respiratory rate variability (HRV and RRV) prior to and throughout the SBT will predict successful extubation, and a reduction in HRV or RRV predicts extubation failure. Furthermore, we demonstrated that variability offers added value to predict outcomes over current standards, and we derived a predictive model based on HRV and RRV, which can identify if a patient is at high risk or low risk for extubation failure. In this validation study, our principal aim is to test our prediction model for extubation failure in an independent patient population. Determination of who and when to extubate critically ill patients remains a daily critical challenge; and improved prediction of extubation failure has potential to save lives and reduce costs in critically ill patients.


Intensive Care Unit - Continuous Individualized Multiorgan Variability Analysis (ICU CIMVA) - an evaluation of ICU-CIMVA as a measure of real-time prognostication in critically ill patients. In order to evaluate the clinical value of multi-dimensional analysis in critically ill patients, we introduce continuous individualized multiorgan variability analysis (CIMVA). CIMVA involves the simultaneous continuous measurement of parameters from multiple organs, along with an evaluation and display of their trends, variability and change in variability over time. To date, our pilot studies have demonstrated feasibility of continuous multiorgan variability analysis in the intensive care. The overall aims of this study include: 1) To pioneer the technological steps to develop a novel monitoring tool to perform continuous individualized multiorgan variability analysis (CIMVA) in critically ill patients; 2) To develop our understanding of the association between altered multiorgan variability in critically ill patients and multiple organ dysfunction syndrome (MODS) through longitudinal and inter-patient evaluation; 3) To explore the utility of CIMVA to identify trajectory of critical illness, such as early detection of clinical deterioration or reliable demonstration of clinical improvement. Potential clinical applications include earlier diagnosis and intervention (i.e. earlier detection and prediction of clinical deterioration), improved tailoring site of care (i.e. outpatient vs. ward vs. ICU bed) to severity of illness, and the potential for directing care based on real-time evaluation of prognosis.


Heart and Respiratory Rate Variability Fitness (HRRV Fit) - an evaluation of heart rate variability as a measure of cardiovascular fitness. Cardiopulmonary fitness is widely accepted as a critical determinant of overall health, and accurate measure of cardiopulmonary fitness has widespread application within healthcare. The current gold standard measure of cardiopulmonary fitness is based on established endpoints in incremental staged exercise testing (e.g. VO2 max, max heart rate); however, some patients may not be able to adequately perform exercise testing due to musculoskeletal disease or lack of motivation. Recent evidence has demonstrated that altered patterns of heart rate variability (HRV) and respiratory rate variability (RRV) are associated with age and illness health and that and exercise training is capable of improving HRV. The fundamental aim of our project is to evaluate a novel multiorgan measure of variability, namely cardiopulmonary variability (CPV), based on simultaneous analysis of heart rate variability (HRV) and respiratory rate variability (RRV), as a novel measure of cardiopulmonary fitness that is reproducible non-invasive and can be performed at rest. In this study, we will perform continuous CPV monitoring at rest and during light exercise in both healthy volunteers and patients with cardiopulmonary illness and compare these measurements to the gold standard measures of cardiopulmonary fitness based upon incremental staged exercise testing. Preliminary data demonstrates feasibility and early evidence of a relationship between CPV and cardiopulmonary fitness. Through this study we will pioneer a novel area of investigation of cardiopulmonary fitness with applications in the risk stratification of surgical patients, frequent evaluation of response to therapy, and other widespread applications in the medical sciences.