• Canadian Critical Care Trials Group
    The Canadian Critical Care Trials Group (CCCTG) is a highly collegial group that is dedicated to the pursuit of excellence and advancement of critical care research in Canada.
  • Canadian Critical Care Trials Group
    The CCCTG has are more than 30 research programs underway and over 100 peer-reviewed publications to its credit, with direct impact on clinical practice in critical care.
  • Canadian Critical Care Trials Group
    The Canadian Critical Care Trials Group (CCCTG) is a national organization of more than 300 individuals with research interests in the management of the critically ill patient.
  • Canadian Critical Care Trials Group
    Endorsement by the CCCTG communicates our full commitment to ensure that the work is undertaken in a rigorous and ethical manner, and communicated in a timely and effective way.

Principal Investigator(s)


Anna Fazekas



WAVE - A Multicenter Evaluation of Altered Heart Rate and Respiratory Rate Variability to Predict Ex

Knowing when to liberate critically ill patients from mechanical ventilation (i.e. extubation) is of great importance as both prolonged ventilation and failed extubation are both associated with increased risk of death. Our objective is to improve the safety of extubation by harnessing hidden information contained in the patterns of variation of heart and respiratory rate measured over intervals-in-time. Currently, to assess a patient's ability to be extubated, a spontaneous breathing trial (SBT) is routinely performed, where the level of ventilator support is reduced, and we observe their response in order to help predict if they will tolerate extubation (i.e. complete removal of ventilator support). Given that health is associated with a high degree of variation of physiologic parameters (e.g. heart and respiratory rate), and illness and stress are associated with a loss of variability, we hypothesize that maintaining stable heart rate and respiratory rate variability (HRV and RRV) throughout the SBT will predict subsequent successful extubation, and conversely, a reduction in either HRV or RRV manifested during a SBT predicts extubation failure. A pilot study has demonstrated that RRV is decreased in patients who subsequently failed extubation, despite having being deemed ready for extubation through traditional clinical assessment. The lack of correlation with traditional measures and the greater predictive capacity of altered RRV suggest independently useful information contained in variability analysis. Determination of who and when to extubate critically ill patients remains a high-stakes clinical challenge; and improved prediction of extubation failure has potential to save lives and reduce costs in critically ill patients.

Current Status: Near Completion. This represents the first simultaneous measure of HRV and RRV as predictors of failed extubation. The results are widely applicable and are being submitted for publication. The 14-center WAVE study is funded by a CIHR operating grant awarded in June 2010, (projected n=660, current accrual n=650 patients) is nearing completion this fall 2012.

Overall Theme:

Development, Clinical Evaluation & Understanding of Multiorgan Variability Monitoring

Overall Objectives:

• Pioneer the development of software to perform multiorgan variability monitoring
• Definition of physiologic variability at rest and during exercise
• Characterize patterns of pathologic variability at risk for or with existing critically illness
• Define a systematic approach to selecting biologic variables for dynamical analysis
• Understand patterns of alteration of inter-organ variability alteration in critical illness
• Understand temporal evolution of multiorgan variability compared to clinical events
• Define relationship between multiorgan variability and physiologic measures
• Evaluate the role of variability monitoring to improve clinical decision making


Niall Ferguson, Dean A Fergusson, Francois Lellouche, John Marshall, Jonathan Hooper, Donna Maziak, Laura-Lyn McIntyre, Tim Ramsay, Gordon Rubenfeld, Damon Scales, Peter Wilkes, Ryan Zarychanski

Participating Centers

The Ottawa Hospital (General Campus) – Dr. Andrew Seely, The Ottawa Hospital (Civic Campus) – Dr. Jonathan Hooper, Ottawa Heart Institute – Dr. Peter Wilkes, London Health Sciences Centre – Dr. Claudio Martin, Mount Sinai Hospital – Dr. Sangeeta Mehta, University of Michigan – Dr. James Blum, University Hospitals of Cleveland – Dr. Frank Jacono, University of British Columbia – Dr. Peter Dodek, Billings Clinic – Dr. Robert Merchant, Intermountain Medical Center/University of Utah – Dr. Samuel Brown, University of Pennsylvania – Dr. Soojin Park, St. Michael’s Hospital – Dr. John Marshall, Columbia University – Dr. J. Michael Schmidt