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General information:
Over the past decade, there have been significant advances in our understanding of the role of nutrition in general, and key nutrients specifically, in the treatment of critically ill patients. Over 40 years ago, when artificial nutrition was developed, it was conceived of as supportive care, as administering metabolic support while the patient recovers from their underlying illness.  Nutrition support teams were developed, malnourished and catabolic patients were identified, measurements and calculations were done, and artificial nutrition was provided to minimize the loss of protein, calories, and micronutrients associated with inflammatory conditions. During this era, very few large-scale trials informed practice patterns. It seemed that as long as the nutrition interventions ‘restored' deficient substrates or reduced the loss of expended substrates, it was provided to broad, heterogeneous groups of patients, with little regard for its effect on clinically important outcomes.  Debates over energy requirements or protein loss dominated the discussion.  Over the last decade, with the application of meta-analytic techniques, and larger randomized clinical trials, stronger signals of therapeutic effect have appeared. Our nutritional strategies appeared to be making an impact on patient outcomes as recently summarized in the form of clinical practice guidelines (i). What was most illuminating from this review process was that the largest treatment effects on clinically important outcomes were from studies of specific nutrients, such as glutamine, antioxidants, fish oils, and arginine.  Thus, the concept of pharmaconutrition emerged.  Distinct from the historical concepts, this new treatment paradigm embraced the fact that nutrients (and some nutritional strategies) have profound effects on underlying inflammatory, immunological, metabolic, and other pathophysiological processes of critically ill patients. The focus was on understanding the influence of these nutrients on the underlying disease process and subsequent clinical outcomes, and less about nitrogen balance or energy requirements.  We have moved from supporting patients while they recover from their underlying illness to modulating that disease response and improving the chances of survival.

Listen to the Podcast of Dr. Daren Heyland on Pharmaconutrition here, presented by the Society of Critical Care Medicine (SSCM)

Recently published reviews:

  • Jones, N. E. Heyland, D. K. Pharmaconutrition: a new emerging paradigm. Current Opinion in Gastroenterology. 2008: 24: 215-222. Pubmed Abstract
  • Wischmeyer, P. E. Glutamine: role in critical illness and ongoing clinical trials. Current Opinion in Gastroenterology. 2008: 24: 190-197. Pubmed Abstract
  • Heyland DK, Jones N, Cvijanovich NZ, Wong H. Zinc supplementation in critically ill patients: a key pharmaconutrient?  JPEN 2008 32(5):509 19. Pubmed Abstract

See the Presentations section for information on Pharmaconutrition.

See the CPGs for randomized controlled trials in pharmaconutrition.




The results of the REDOXS trial have been published in the New England Journal of Medicine. You may view the article here as well as an accompanying NIBBLE (Nutrition Information Byte), a 2-page concise summary of the impact of REDOXS on the future use of glutamine in critically ill patients. Following the publication of the MetaPlus trial, a second NIBBLE was written regarding glutamine supplementation.

A post-hoc analysis by Heyland et al was published in JPEN re-evaluating the effect of glutamine and antioxidant supplementation after controlling for baseline covariates. Results showed that early high doses of glutamine were not beneficial and may have been associated with increased mortality in the critically ill with multi-organ failure. The most harm was seen with both glutamine and antioxidant supplementation in the critically ill with a diagnosis of multi-organ failure including renal failure at time of study enrollment. 

On behalf of Dr. Heyland, Rupinder Dhaliwal, Janet Overvelde and the Critical Care Nutrition and Clinical Evaluation Research Unit teams, we would like to thank all our participating sites and collaborators for their support over the years! Here are some important highlights of the research related to the REDOXS Study:

2004-2005 REDOXS Dose Escalating Study

2005-2006 REDOXS Pilot Study

2007-2012 REDOXS Multicentre Definitive Study: 5 countries participated and 45 sites screened 5639 patients to recruit 1223 patients and collect 355,893 pieces of data!

Thanks for helping us complete this important study which has led to important findings in critical care nutrition.

The REDOXS© Circular provides invaluable updates on enrollment, data entry, regulatory and pharmacy issues, reminders and Frequently Asked Questions. The REDOXS© Bulletin provides in-depth coverage of current issues of interest.

Frequently Asked Questions featured in REDOXS© circula

Frequently Asked Questions

REDOXS© Circular

REDOXS© Bulletin

The resources below have been provided for the sites actively participating in the REDOXS© Study. The information will be useful for Site Investigators, Research Coordinators, Dietitians, Pharmacists and Pharmacy Technicians.
[Right Click on the links: pdf or doc to Save the Target Document.]

Study Procedures Manual

Administration of Study Supplements   pdf
Administration of Study Supplemens - EU version   pdf
Implementation Manual   pdf
Protocol Violations   pdf
Serious Adverse Events*Sept 2008*   pdf
SAE Initial Report Form   pdf
SAE Follow-up Report Form   pdf
Pharmacy Manual   pdf
Pharmacy Manual - EU version   pdf
Pharmacy Worksheets doc pdf
Pharmacy Worksheets - EU version doc pdf
Dietitian Manual   pdf
Research Coordinator Worksheets   pdf
Daily Monitoring Log doc pdf
English (Canadian)   pdf
French (Canadian)   pdf
Child's class C liver disease   pdf
PF ratio table   pdf
Unit conversion calculator   xls
Algorithm for elevated urea   pdf
Lab Study Manual   pdf
Conversion Table for FiO2 when on Mask or Nasal Cannula   pdf
Annotated CRF   pdf
  • Early Enteral Nutrition in the ICU: The Clock is Ticking!
  • NIBBLE: The Importance of Nutritional Adequacy (Or Avoiding Caloric Debt)
  • NIBBLE: Strategies to Deal with GI Intolerance
  • Poster Template for Nutrition Improvement Targets:
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