Convergent Evidence and Opinion on Intensive Metabolic Support

The translation of clinical research findings in nutrition and metabolism to clinical practice of intensive metabolic support (IMS) in the ICU has followed an alternating pattern of brief spurts following landmark studies and organized corrections as information is vetted. This past year is no exception as the story of intensive insulin therapy (IIT) and companion role of parenteral nutrition in the ICU was scientifically studied in a highly controlled experimental design. Indeed, 2011 will remain as one of the most productive years in ICU nutrition and metabolism. In response to this event, we invited experts to provide their opinions regarding different aspects of IMS, from nutritional assessment to glycemic control to enteral nutrition to parenteral nutrition and finally, to nutritional pharmacology, all in an effort to garner perspective when interpreting new data. Hiesmayr (pp. 000–000) shows how difficult it still is to assess a patient's nutritional status. The presence of an intense inflammatory response confounds nutrition scores, and the absence of information about preadmission nutritional data even compromises the Nutrition Risk Score (NRS) [1]. The NRS has not been validated in the ICU wherein a value greater than ‘2’ is trivial: it mandates nutrition support but just being in the ICU automatically confers three points. In addition, underfeeding, overfeeding, refeeding, and feeding tolerance surface as highly relevant issues in clinical decision-making. The principle of risk stratification in the ICU takes a small twist in the study by Krinsley et al. (pp. 000–000). Here, prominent experts in the field of glycemic control in the ICU provide an analysis of the literature on how premorbid dysglycemic status modulates the independent effects of hyperglycemia, hypoglycemia, and glycemic variability on mortality. Each of the three glycemic parameters were predictive in patients without diabetes but only hypoglycemia was found to be predictive in patients with diabetes. These results are important because they support the hypothesis that the diabetic state somehow affects the salutary mechanism of IIT. Is this a threshold effect on inflammatory or neuroendocrine function? Is this a metabolic effect that increases the risk of iatrogenic hypoglycemia? The authors correctly assert that premorbid dysglycemia is an important risk stratification tool, but does this also include prediabetes? The authors did not discuss the association of nutrition support modality (enteral nutrition or parenteral nutrition) and sufficiency on glycemic markers – a topic that has received great interest of late [2]. For instance, to what extent can uninterrupted provision of small amounts of dextrose, or alternate fuel sources such as structured lipids or amino acids, have on hyperglycemia, hypoglycemia, and glycemic variability? Once a formal nutritional risk assessment is performed, the status of the gastrointestinal tract must be evaluated. Gastrointestinal motility disorders are common in the ICU and Pfab et al. (pp. 000–000) emphasize that prokinetics should not be considered first-line therapy. Rather, focusing on fluid and electrolyte repletion, using laxatives and peripherally acting μ-opioid receptor antagonists, and considering acupuncture, heat, and massage should be prioritized. Much of the controversy surrounding conventional use of parenteral nutrition in the ICU may be rendered moot if greater enteral nutrition diligence, as advised by guidelines, is practiced. Unfortunately, not every novel intervention to optimize gastrointestinal function has demonstrated unequivocal success. Morrow et al. (pp. 000–000) discuss the probiotic prophylaxis in patients with predicted severe acute pancreatitis – a randomized, double-blind, placebo controlled trial [3], which though open to criticism, found an unexpected increase in mortality associated with probiotics in patients with severe pancreatitis. Although these results should indeed lead to caution in the combination and doses of probiotics used in interventions, the potential for benefit from this approach should not be discarded just because of one failed intervention. Awad and Lobo (pp. 000–000) navigate us through the response to fasting and the prevention of its deleterious effects in scheduled surgery. Carbohydrate loading is a novel way to address the metabolic response to major surgery. Fasting is deleterious as it causes insulin resistance and is associated with poor outcomes. This response can be attenuated in a highly significant manner by simply reducing fasting to 3 h through the delivery of an oral carbohydrate solution. This may apply to the critically ill patient, but certainly not in the form of intravenous glucose loading as employed in the recent early parenteral nutrition completing enteral nutrition in adult critically ill patients (EPaNIC) trial [4]. Rather, carbohydrate loading may exert its benefits through the early delivery of nonparticulate enteral solutions as trickle/trophic feeding. Even in the sickest patients, this technique might prevent gastrointestinal paresis. Wernerman (pp. 000–000) challenges us with a new problem. Although underfeeding related to under-prescription and gastrointestinal dysfunction remains a major problem in most ICU patients, overfeeding has emerged as a comparable problem. The EPaNIC trial [4] investigates very early parenteral nutrition, which is not recommended by The European Society for Clinical Nutrition and Metabolism. The practice of prescribing concentrated glucose or ternary solutions at relatively high rates from ICU day 1 seems to be more widespread in several European hospitals than previously recognized. Despite agreement on most issues, European and North American medical societies disagree on the timing of combined enteral nutrition and parenteral nutrition. The EPaNIC trial demonstrates 20 years after the Veterans Affairs Total Parenteral Nutrition Cooperative Study [5] that even though starting parenteral nutrition by day 1 is not deadly, it still worsens various outcome parameters, thereby confirming the results of the tight calorie control study Trial [6]. American [7], European [8], and Canadian [9] clinical practice guidelines explicitly advocate diligent attempts at enteral nutrition during at least the first 2 ICU days. In those patients receiving insufficient enteral nutrition, the use of parenteral nutrition has been recommended, though again, the timing and formulation remains debated. A Swiss trial [10] selecting those ICU patients failing enteral nutrition by ICU day 3, and randomizing half the patients to supplemental parenteral nutrition from day 4 with energy targets controlled by calorimetry, shows that the cutoff for beneficial parenteral nutrition introduction is between days 3 and 5. This intervention resulted in a significant reduction of infectious complications, with more antibiotic and ventilator-free days by day 28. Finally, adding to the complexity, the recommended energy targets of 25–30 kcal/kg/d seem to be too high; adequate feeding should be individualized and guided by indirect calorimetry. Redell and Cotton (pp. 000–000) remind us of the importance of oxidative stress in critically ill trauma patients, which leads to mitochondrial dysfunction, secondary tissue injury, immune dysfunction, organ failure, and death. Endogenous antioxidants are rapidly depleted with oxidative stress. Intravenous replacement of a combination of trace elements (Se, Zn) and vitamins (B1, C, E) in doses about 10 times the recommended dietary allowance results in significant clinical improvement. Major trauma patients requiring ICU treatment are clearly candidates for a systematic supplementation lasting 5–20 days. The study by Amrein and Venkatesh (pp. 000–000) discusses the pleiotropic roles of vitamin D in critical illness and succeed in setting the stage for future studies. They point out the following issues pertaining to critical care: that more information is required to understand the pathophysiology of vitamin D nutriture and metabolic effects of treatment, whether vitamin D undernutrition is a marker of disease or a causative factor for clinical outcomes, the special case of chronic kidney disease and acute kidney injury, and if treatment is advised, what are the optimal parameters (route, dose, and structure). In consideration of the above evidence and opinion, the integrative roles of nutritional and metabolic assessment to risk stratify ICU patients, optimization of enteral nutrition and micronutrition therapy in all patients, and early/concurrent use of parenteral nutrition to improve clinical outcomes in higher risk patients should be subsumed in a standardized IMS algorithm. Once these individual elements are validated in experimental (controlled) settings, appropriate studies should be designed to test real-life management strategies, generalizable to a broad array of ICU settings. These investigations may require Bayesian design methods to optimize study constraints (patient subsets, decision-trees, limited resources, and belief structures) and systems approaches, including network analyses. In this fashion, the convergence of evidence and opinion can truly lead to optimization of ICU metabolic care. Acknowledgements None. Conflicts of interest J.M. – Abbott Nutrition: speaker honoraria and program development; Select Medical Corporation: research grant support. MB – Baxter, BBrauna, Fresenius Kabi, Nestlé: speaker honoraria and program development; Fresenius Kabi, Aguettant, BBraun, Baxter: research grant support.

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