Research from JAMA — Should Immunonutrition Become Routine in Critically Ill Patients? — A Systematic Review of the Evidence — ContextSeveral nutrients have been shown to influence immunologic and inflammatory responses in humans. Whether these effects translate into an improvement in clinical outcomes in critically ill patients remains unclear.ObjectiveTo examine the relationship between enteral nutrition supplemented with immune-enhancing nutrients and infectious complications and mortality rates in critically ill patients.Data SourcesThe databases of MEDLINE, EMBASE, Biosis, and CINAHL were searched for articles published from 1990 to 2000. Additional data sources included the Cochrane Controlled Trials Register from 1990 to 2000, personal files, abstract proceedings, and relevant reference lists of articles identified by database review.Study SelectionA total of 326 titles, abstracts, and articles were reviewed. Primary studies were included if they were randomized trials of critically ill or surgical patients that evaluated the effect of enteral nutrition supplemented with some combination of arginine, glutamine, nucleotides, and omega-3 fatty acids on infectious complication and mortality rates compared with standard enteral nutrition, and included clinically important outcomes, such as mortality.Data ExtractionMethodological quality of individual studies was scored and necessary data were abstracted in duplicate and independently.Data SynthesisTwenty-two randomized trials with a total of 2419 patients compared the use of immunonutrition with standard enteral nutrition in surgical and critically ill patients. With respect to mortality, immunonutrition was associated with a pooled risk ratio (RR) of 1.10 (95% confidence interval [CI], 0.93-1.31). Immunonutrition was associated with lower infectious complications (RR, 0.66; 95% CI, 0.54-0.80). Since there was significant heterogeneity across studies, we examined several a priori subgroup analyses. We found that studies using commercial formulas with high arginine content were associated with a significant reduction in infectious complications and a trend toward a lower mortality rate compared with other immune-enhancing diets. Studies of surgical patients were associated with a significant reduction in infectious complication rates compared with studies of critically ill patients. In studies of critically ill patients, studies with a high-quality score were associated with increased mortality and a significant reduction in infectious complication rates compared with studies with a low-quality score.ConclusionImmunonutrition may decrease infectious complication rates but it is not associated with an overall mortality advantage. However, the treatment effect varies depending on the intervention, the patient population, and the methodological quality of the study.

To examine the relationship between glutamine supplementation and hospital length of stay, complication rates, and mortality in patients undergoing surgery and experiencing critical illness. Computerized search of electronic databases and search of personal files, abstract proceedings, relevant journals, and review of reference lists. We reviewed 550 titles, abstracts, and articles. Primary studies were included if they were randomized trials of critically ill or surgical patients that evaluated the effect of glutamine vs. standard care on clinical outcomes. DATA EXTRACTION We abstracted relevant data on the methodology and outcomes of primary studies in duplicate, independently. DATA SYNTHESIS There were 14 randomized trials comparing the use of glutamine supplementation in surgical and critically ill patients. When the results of these trials were aggregated, with respect to mortality, glutamine supplementation was associated with a risk ratio (RR) of 0.78 (95% confidence interval [CI], 0.58-1.04). Glutamine supplementation was also associated with a lower rate of infectious complications (RR, 0.81; 95% CI, 0.64-1.00) and a shorter hospital stay (-2.6 days; 95% CI, -4.5 to -0.7). We examined several -specified subgroups. Although there were no statistically significant subgroup differences detected, there were some important trends. With respect to mortality, the treatment benefit was observed in studies of parenteral glutamine (RR, 0.71; 95% CI, 0.51-0.99) and high-dose glutamine (RR, 0.73; 95% CI, 0.53-1.00) compared with studies of enteral glutamine (RR, 1.08; 95% CI, 0.57-2.01) and low-dose glutamine (RR, 1.02; 95% CI, 0.52-2.00). With respect to hospital length of stay, all of the treatment benefit was observed in surgical patients (-3.5 days; 95% CI, -5.3 to -1.7) compared with critically ill patients (0.9 days; 95% CI, -4.9 to 6.8). In surgical patients, glutamine supplementation may be associated with a reduction in infectious complication rates and shorter hospital stay without any adverse effect on mortality. In critically ill patients, glutamine supplementation may be associated with a reduction in complication and mortality rates. The greatest benefit was observed in patients receiving high-dose, parenteral glutamine.

To determine the extent to which postpyloric feeding reduces gastroesophageal regurgitation and pulmonary microaspiration in critically ill patients. Randomized trial. A medical/surgical intensive care unit at a tertiary care hospital. Intensive care unit patients were expected to remain ventilated >72 hrs. We excluded patients with esophageal, gastric, or small bowel surgery in the last week and patients with overt or clinically significant gastrointestinal bleeding. We studied 33 patients; 42.4% were female, mean age (sd) was 59.2 (± 16.8) yrs, and mean Acute Physiology and Chronic Health Evaluation II score was 22.5 (7.8). Patients were randomized to gastric or postpyloric enteral feeds. Technetium 99-sulphur colloid was added to the feeds for 6 hrs of each of the first 3 days on study. We sampled the oropharynx and trachea hourly for the 6 hrs per day that patients received radioisotope-labeled enteral feeds, and the level of radioactivity in these specimens was measured. We defined an episode of gastroesophageal regurgitation and microaspiration as an increase in radioactivity >100 counts per minute/g. Patients fed into the stomach had more episodes of gastroesophageal regurgitation (39.8% vs. 24.9%, p = .04) and trended toward more microaspiration (7.5% vs. 3.9%, p = .22) compared with patients fed beyond the pylorus. When the logarithmic mean of the radioactivity count was compared across groups, there was a trend toward an increase in gastroesophageal regurgitation (3.7 vs. 2.9 counts/g, p = .22) and a trend toward increased microaspiration (1.9 vs. 1.4 counts/g, p = .09) in patients fed into the stomach. Patients who had gastroesophageal regurgitation were much more likely to aspirate than patients who did not have gastroesophageal regurgitation (odds ratio: 3.2; 95% confidence interval: 1.36, 7.77). Feeding beyond the pylorus is associated with a significant reduction in gastroesophageal regurgitation and a trend toward less microaspiration.

Anorexia nervosa is a model of simple starvation accompanied by secondary hyperlipoproteinemia. The pattern of plasma fatty acids influences the levels of plasma lipids and lipoproteins. The concentration of plasma lathosterol is a surrogate marker of cholesterol synthesis de novo, concentrations of campesterol and beta-sitosterol reflect resorption of exogenous cholesterol. The aim of the study was to evaluate fatty acids in plasma lipid classes and their relationship to plasma lipids, lipoproteins, cholesterol precursors and plant sterols. We examined 16 women with anorexia nervosa and 25 healthy ones. Patients with anorexia nervosa revealed increased concentrations of total cholesterol, triglycerides, HDL-cholesterol, campesterol and beta-sitosterol. Moreover, a decreased content of n-6 polyunsaturated fatty acids was found in all lipid classes. These changes were compensated by an increased content of monounsaturated fatty acids in cholesteryl esters, saturated fatty acids in triglycerides and both monounsaturated and saturated fatty acids in phosphatidylcholine. The most consistent finding in the fatty acid pattern concerned a decreased content of linoleic acid and a raised content of palmitoleic acid in all lipid classes. The changes of plasma lipids and lipoproteins in anorexia nervosa are the result of complex mechanisms including decreased catabolism of triglyceride-rich lipoproteins, normal rate of cholesterol synthesis and increased resorption of exogenous cholesterol.