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. RECENT FINDINGS: 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.

Energy Expenditure and Protein Requirements Following Burn Injury.

Severe burn injuries have long been known to have a profound effect on metabolic equilibrium that can persist after resolution of the cutaneous injuries. Following burn injury, metabolism is a dynamic state resulting in the need for frequent interval reassessment over the course of the care continuum. The acute phase of injury transitions to chronic alterations in macronutrient utilization characterized by futile energy cycling and disproportionate catabolism of skeletal muscle. Protein supplementation appears to be preferentially distributed to the burn wound rather than the skeletal muscle pool. Accurate assessment of caloric and protein requirements is extremely difficult in these patients but is an essential step in efforts to attenuate functional impairment. Indirect calorimetry should be utilized to determine caloric requirements, but trophic feeding strategies are preferred in the initial resuscitative phase to prevent overfeeding while maintaining enteric and immune function. Controversy persists regarding optimal protein targets, and weight-based estimates remain the norm. Exogenous protein and caloric provision performed in isolation is insufficient to optimize outcomes and should be incorporated within a multidisciplinary approach to include muscle loading and pharmaceutical adjuncts.

The use of ABC score in activation of massive transfusion: The yin and the yang.

BACKGROUND: Hemorrhage is the most common cause of early death in trauma patients. Massive transfusion protocols (MTPs) have been designed to accelerate the release of blood products but can result in waste if activated inappropriately. The Assessment of Blood Consumption (ABC) score has become a widely accepted score for MTP activation. In this study, we compared the use of ABC criteria to physician judgment in MTP activation. METHODS: Adult trauma patients treated at University of Louisville Trauma Center from January 2016 to December 2016 were studied. Activation via ABC score was assessed retrospectively from emergency department (ED) data. Location, timing of activation, percent of patients using more than 5 units of packed red blood cells, amount of product waste, factors associated with early activation by physicians, and mortality were analyzed. RESULTS: Three thousand four hundred twenty-one patients were included in this study. Only 33% of the patients who would have had MTP activation based on the ABC criteria used more than 5 units of blood products within 24 hours of admission compared with 65% of the patients in whom clinical judgment was used. Seventy-six percent of all MTP activations from clinical judgment would have been activated by the ABC criteria in the ED. Fifty-five percent of all MTP activations via clinical judgment were activated in the operating room and 41% in the ED. Eighty-one percent of activations that occurred in the operating room by physician judgment could have been activated earlier in the ED if the ABC criteria had been used. However, ABC score can lead to higher potential fresh frozen plasma waste (588 vs. 84 units) compared with physician judgment. CONCLUSIONS: The ABC criteria overestimate need for massive transfusion and can lead to increased product waste compared with physician judgment, but its use leads to earlier MTP activation. Criteria to trigger MT activation should rely on both clinical acumen and validated prediction tools. LEVEL OF EVIDENCE: Prognostic, level III.

When Is It Appropriate to Use Arginine in Critical Illness?

In health, arginine is considered a nonessential amino acid but can become an essential amino acid (ie, conditionally essential amino acid) during periods of metabolic or traumatic stress as endogenous arginine supply is inadequate to meet physiologic demands. Arginine depletion in critical illness is associated with impairments in microcirculatory blood flow, impaired wound healing, and T-cell dysfunction. The purpose of this review is to (1) describe arginine metabolism and role in health and critical illness, (2) describe the relationship between arginine and asymmetric dimethylarginine, and (3) review studies of supplemental arginine in critically ill patients.

Vitamin D Status and Supplementation in the Critically Ill.

Vitamin D deficiency has recently been recognized as a widespread global disorder. Generally considered a direct extension of malnutrition, even subclinical hypovitaminosis D is now recognized in adequately nourished populations. Compared to the general population, the prevalence of hypovitaminosis D is greater in the critically ill population. In fact, several studies have shown poorer outcomes in critically ill patients discovered to be vitamin D deficient or insufficient. Controversy persists regarding vitamin D measurements, quantity of supplementation, and appropriate target level in various populations. Vitamin D has a vital role in calcium homeostasis and extra-skeletal health, such as immune function. Therefore, vitamin D supplementation may have a role for improving outcomes in critically ill patients. In this review, we will first discuss the metabolism and function of vitamin D under normal physiologic conditions. We will then explore the prevalence and prognostic value of vitamin D deficiency in critical illness. Finally, we will examine recent trials focusing on appropriate dosing, route of administration, and outcomes associated with vitamin D supplementation in the ICU.

Targeted Physician Education Positively Affects Delivery of Nutrition Therapy and Patient Outcomes: Results of a Prospective Clinical Trial.

BACKGROUND: Malnutrition is a continuing epidemic among hospitalized patients. We hypothesize that targeted physician education should help reduce caloric deficits and improve patient outcomes. MATERIALS AND METHODS: We performed a prospective trial of patients (n = 121) assigned to 1 of 2 trauma groups. The experimental group (EG) received targeted education consisting of strategies to increase delivery of early enteral nutrition. Strategies included early enteral access, avoidance of nil per os (NPO) and clear liquid diets (CLD), volume-based feeding, early resumption of feeds postprocedure, and charting caloric deficits. The control group (CG) did not receive targeted education but was allowed to practice in a standard ad hoc fashion. Both groups were provided with dietitian recommendations on a multidisciplinary nutrition team per standard practice. RESULTS: The EG received a higher percentage of measured goal calories (30.1 ± 18.5%, 22.1 ± 23.7%, P = .024) compared with the CG. Mean caloric deficit was not significantly different between groups (-6796 ± 4164 kcal vs -8817 ± 7087 kcal, P = .305). CLD days per patient (0.1 ± 0.5 vs 0.6 ± 0.9), length of stay in the intensive care unit (3.5 ± 5.5 vs 5.2 ± 6.8 days), and duration of mechanical ventilation (1.6 ± 3.7 vs 2.8 ± 5.0 days) were all reduced in the EG compared with the CG (P < .05). EG patients had fewer nosocomial infections (10.6% vs 23.6%) and less organ failure (10.6% vs 18.2%) than did the CG, but these differences did not reach statistical significance. CONCLUSION: Implementation of specific educational strategies succeeded in greater delivery of nutrition therapy, which favorably affected patient care and outcomes.

When can nutritional therapy impact liver disease?

This article reviews the current literature regarding nutritional therapy in liver disease, with an emphasis on patients progressing to liver failure as well as surgical patients. Mechanisms of malnutrition and sarcopenia in liver failure patients as well as nutritional assessment, nutritional requirements of this patient population, and goals and methods of therapy are discussed. Additionally, recommendations for feeding, micronutrient, branched chain amino acid supplementation, and the use of pre- and probiotics are included. The impact of these methods can have on patients with advanced disease and those undergoing surgical procedures will be emphasized.

Nutrition therapy issues in esophageal cancer.

Esophageal cancer has traditionally been a disease with poor long term outcomes in terms of both survival and quality of life. In combination with surgical and pharmacologic therapy, nutrition support has been demonstrated to improve patient tolerance of treatment, quality of life, and longterm outcomes. An aggressive multi-disciplinary approach is warranted with nutrition support remaining a cornerstone in management. Historically, nutrition support has focused on adequate caloric provision to prevent weight loss and allow for tolerance of treatment regimens. Alterations in metabolism occur in these patients making their use of available calories inefficient and the future of nutritional support may lie in the ability to alter this deranged metabolism. The purpose of this article is to review the current literature surrounding the etiology, treatment, and role of nutrition support in improving outcomes in esophageal cancer.

"CAN WE FEED?" A mnemonic to merge nutrition and intensive care assessment of the critically ill patient.

As care of the critically ill patient grows more complex, so does the breadth of knowledge required of the intensivist to deliver quality service. Nutrition is one area of many where the complexity of care has grown and the opportunity for improving patient outcomes has become evident. The use of mnemonics has proven successful in compartmentalizing information that must be considered in complex decision-making processes. The authors propose one such mnemonic, "CAN WE FEED?" to assist in the development and initiation of early enteral nutrition therapy in the intensive care unit (ICU). Critical illness severity (C), age (A), and nutrition risk screening (N) are considered when performing a baseline evaluation of the critically ill patient upon presentation to the ICU. Wait for resuscitation (W) is a key component in the care of most critically ill patients and is an important consideration prior to the initiation of feeding. Energy requirements (E) are determined using conventional weight-based equations, indirect calorimetry, or combinations of both techniques. The more practical aspects of support that follow include formula selection (F), enteral access (E), efficacy (E), and the determination of tolerance (D). With careful consideration of these components through the use of the mnemonic "CAN WE FEED?" the intensivist can successfully implement a nutrition plan, and the clinical nutritionist can appreciate where nutrition therapy appropriately intervenes in the initial resuscitation and management of the critically ill patient.