30 Dec 07
By PE Wischmeyer
Critical Care Medicine 2007;35:S541-S544
A recent editorial in Critical Care Medicine was titled Glutamine, a life-saving nutrient, but why? (2003; 31:2555-2556). This review will attempt to utilize new understanding of gene-nutrient interactions and molecular medicine to address potential mechanisms by which glutamine may be lifesaving after critical illness and injury. Recent meta-analysis data reveal that glutamine seems to exert a beneficial effect on mortality in critically ill patients. However, this effect seems to be dose and route dependent. The questions that remain to be answered are in what settings and via what method of administration does this phamaconutrient show optimal benefit? It is likely that examination of the molecular mechanisms by which glutamine exerts its effects will lead to an understanding of how best to utilize glutamine as both a pharmacologic and a nutritional agent. Clearly, clinical critical illness leads to a marked deficiency in glutamine that is correlated with mortality in the intensive care unit setting. It makes obvious sense that the deficiency of this vital stress nutrient should be replaced. In addition, recent laboratory data reveal glutamine may act via mechanisms independent of its role as a metabolic fuel. These include enhanced stress protein response, attenuation of the inflammatory response, improved tissue metabolic function, and attenuation of oxidant stress. Present data indicate that glutamine functions as a metabolic fuel and stress-signaling molecule after illness and injury. Thus, deficiencies observed in critical illness demand replacement for both pharmacologic and metabolic optimization. Presently, randomized, multicenter, clinical trials utilizing glutamine as a pharmacologic and a nutritional agent are ongoing.
By RD Stapleton, N Jones, DK Heyland
Critical Care Medicine 2007;35:S535-S540
Hypermetabolism and malnourishment are common in the intensive care unit. Malnutrition is associated with increased morbidity and mortality, and most intensive care unit patients receive specialized nutrition therapy to attenuate the effects of malnourishment. However, the optimal amount of energy to deliver is unknown, with some studies suggesting that full calorie feeding improves clinical outcomes but other studies concluding that caloric intake may not be important in determining outcome. In this narrative review, we discuss the studies of critically ill patients that examine the relationship between dose of nutrition and clinically important outcomes. Observational studies suggest that achieving targeted caloric intake might not be necessary since provision of approximately 25% to 66% of goal calories may be sufficient. Randomized controlled trials comparing early aggressive use of enteral nutrition compared with delayed, less aggressive use of enteral nutrition suggest that providing increased calories with early, aggressive enteral nutrition is associated with improved clinical outcomes. However, energy provision with parenteral nutrition, either instead of or supplemental to enteral nutrition, does not offer additional benefits. In summary, the optimal amount of calories to provide critically ill patients is unclear given the limitations of the existing data. However, evidence suggests that improving adequacy of enteral nutrition by moving intake closer to goal calories might be associated with a clinical benefit. There is no role for supplemental parenteral nutrition to increase caloric delivery in the early phase of critical illness. Further high-quality evidence from randomized trials investigating the optimal amount of energy intake in intensive care unit patients is needed.
By J-C Preiser, PM Devos
Critical Care Medicine 2007;35:S503-S507
To describe the current status and the clinical data related to the effects of tight glucose control by intensive insulin therapy in critically ill patients.
Medical and surgical critically ill patients in whom a correlation between blood glucose and outcome variables were searched.
Tight glucose control by intensive insulin therapy.
Measurements and Main Results
In contrast to the decreases in mortality and to low severity of adverse effects reported when insulin rate was titrated to keep blood glucose between 80 and 110 mg/dL, the benefits were not confirmed in multicenter prospective studies. Retrospective data found an association between a mean blood glucose level of <140-150 mg/dL and improved outcome. Currently unanswered issues include the optimal target for blood glucose, the effects of high blood glucose variability, the risks and hazards of hypoglycemia, and the potential influence of the underlying disorder on the effects of tight glucose control.
Recommendations regarding the practical aspects of tight glucose control by intensive insulin therapy cannot be presently issued. An intermediate target level for blood glucose of 140-180 mg/dL seems to be associated with the lowest risk-to-benefit ratio.
By I Vanhorebeek, L Langouche, G Van den Berghe
Critical Care Medicine 2007;35:S496-S502
In two large, randomized studies, maintenance of normoglycemia with intensive insulin therapy largely prevented morbidity and reduced mortality of critically ill patients. Recently, questions have been raised about the efficacy and safety of this therapy. These issues are systematically addressed and discussed with the evidence available from these and other studies. The available studies show that an absolute reduction in risk of hospital death of 3% to 4% is to be expected from intensive insulin therapy in an intention-to-treat analysis. Future studies designed to confirm a statistically significant survival benefit should be adequately powered, with inclusion of ≥5,000 patients. When patients are treated with intensive insulin therapy for >3 days, the absolute reduction in the risk of death increases to approximately 8%. Insulin therapy also improves morbidity, more so when continued for >3 days. Strict blood glucose control to normoglycemia (<110 mg/dL) is required to obtain the most clinical benefit, but this inherently increases the risk of hypoglycemia. It remains unclear whether short hypoglycemic episodes are truly harmful for these patients. In conclusion, demonstration of the clinical benefits of intensive insulin therapy depends on the quality of blood glucose control and the statistical power of the studies.