Background: While the provision of adequate nutrition support in critically ill patients has been shown to have an impact on short-term clinical outcomes, relatively little is known about subsequent long-term outcomes. We aimed to examine the association between nutritional adequacy and long-term outcomes including survival and health-related quality of life (HRQoL) in critically ill patients requiring prolonged mechanical ventilation. Methods:The study was conducted as a retrospective cohort study on data collected prospectively in the context of a multicenter randomized controlled trial (RCT) in critically ill patients. Randomized patients who stayed in the intensive care unit (ICU) and were mechanically ventilated for >8 days were eligible for the study, but only six-month survivors were considered for the assessment of HRQoL. Nutritional adequacy was obtained from the average proportion of prescribed calories received during the first eight days of mechanical ventilation in the ICU.Survival status and HRQoL as assessed using Short-Form 36 Health Survey (SF-36) were obtained prospectively as part of the RCT protocol at three-months and six-months post ICU admission.Results: Of the 1223 patients enrolled in the randomized controlled trial, 475 met the inclusion criteria for this study. At six-month follow-up, 302 of the 475 patients were alive. Among critically ill patients with >8 days of mechanical ventilation in the ICU, survival time in those who received low nutritional adequacy was significantly shorter than for those who received high nutritional adequacy after adjusting for important covariates. Among six-month survivors, clinically meaningful and statistical significant associations between increase in scores of Physical Functioning (PF) and Role Physical domains (RP) of the SF-36 and 25% increase in iii nutritional adequacy were observed at three-months follow-up. No significant associations were observed at six-months. Conclusions:Our findings suggest that nutritional adequacy received as early as the first week in the ICU seems beneficial to longer survival time and faster physical recovery post ICU discharge in critically ill patients requiring prolonged mechanical ventilation in the ICU. Well-designed randomized controlled trials are needed to provide stronger assessment of the causal impact of nutrition therapy on long-term outcomes.iv Co-AuthorshipThis thesis was the work of Xuejiao Wei in collaboration with her supervisors Dr. Daren Heyland, Dr. Hélène Ouellette-Kuntz, and Mr. Andrew Day. Data management and statistical analyses for the thesis were performed by Xuejiao Wei, with insight and guidance from Mr.Andrew Day. Interpretation of results and writing of the thesis was performed by Xuejiao Wei,
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