Mitochondrial Dysfunction in Critical Illness: Implications for Nutritional Therapy
Purpose of the Review
This paper will review the evidence for mitochondrial dysfunction in critical illness, describe the mechanisms which lead to multiple organ failure, and detail the implications of this pathophysiologic process on nutritional therapy.
Mitochondria are particularly sensitive to increased oxidative stress in critical illness. The functional and structural abnormalities which occur in this organelle contribute further to the excessive production of reactive oxygen species and the reduction in generation of adenosine triphosphate (ATP). To reduce metabolic demand, mitochondrial dysfunction develops (a process likened to hibernation), which helps sustain the life of the cell at a cost of organ system failure. Aggressive feeding in the early phases of critical illness might inappropriately increase demand at a time when ATP production is limited, further jeopardizing cell survival and potentiating the processes leading to multiple organ failure.
Several potential therapies exist which would promote mitochondrial function in the intensive care setting through support of autophagy, antioxidant defense systems, and the biogenesis and recovery of the organelle itself. Nutritional therapy should supplement micronutrients required in the mitochondrial metabolic pathways and provide reduced delivery of macronutrients through slower advancement of feeding in the early phases of critical illness. A better understanding of mitochondrial dysfunction in the critically ill patient should lead to more innovative therapies in the future.
KeywordsMitochondrial failure Critical illness Nutritional therapy Multiple organ failure
Compliance with Ethical Standards
Conflict of Interest
Stephen A. McClave declares that he has no conflict of interest.
Paul E. Wischmeyer has received research funding from Baxter, Abbott Laboratories, Fresenius Kabi, the National Institutes of Health (NIH), and Nutricia; has received compensation from Baxter, Abbott Laboratories, and Nutricia for service as a consultant; and has received compensation from Abbott Laboratories and Nutricia for participating in Continuing Medical Education (CME) Speaking programs.
Keith R. Miller has received salary support from Nestlé Nutrition through its Nutritional Educational Fellowship.
Arthur R.H. van Zanten has received research funding from Nutricia, Cardinal Health, and Mermaid Pharmaceuticals GmbH; has received compensation from Baxter, Fresenius Kabi, and Nutricia for service as a consultant; and has received compensation from Baxter, Nestlé, Fresenius Kabi, B. Braun Medical, Inc., and Nutricia for participating in CME Speaking programs.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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