Immune-Enhancing Enteral Diet and Mortality in Sepsis
Immune-Enhancing Enteral Diet and Mortality in Sepsis
Abstract & Commentary
Synopsis: An immune-enhancing enteral diet reduced mortality rate and episodes of bacteremia in septic intensive care unit patients.
Source: Galbán C, et al. Crit Care Med 2000;28: 643-648.
Galbán and associates were trying to assess the effects of a dietary formula supplemented with arginine, mRNA, and omega-3 fatty acids from fish oil on clinical outcomes in septic ICU patients. They designed a prospective, randomized, unblinded study to evaluate the outcome differences between a standard enteral feeding formula and an immune-enhancing formulation (Impact, Novartis). Inclusion criteria for the study included sepsis as defined by a) positive culture or b) clinically diagnosed infection, and two or more of the following: body temperature higher than 38ºC or lower than 36ºC, heart rate more than 90 beats/min, respiratory rate more than 20 breaths/min, or arterial PCO2 less than 32 mmHg, and a white blood cell count more than 12,000/mL or less than 4000/mL. Patients also had to have an APACHE II score of 10 or more at the time of admission to the ICU. Patients were excluded if they were pregnant, were younger than 14 years of age, or had the acquired immunodeficiency syndrome, neoplasia, chemotherapy or radiation therapy in the past, or had recently received an immune-enhancing diet or parenteral nutrition. The primary end point was to evaluate mortality differences with the intention to treat analysis, and secondary end points were rate of nosocomial infections with or without bacteremia and length of stay in ICU.
Patients treated with the immune-enhancing diet had a significantly lower mortality rate when compared to the control group (17/89 vs 28/87; P < 0.05). Further analysis showed a nonsignificant trend toward reduced infection-related mortality in the treatment group as compared to the control group. The number of nosocomial bacteremias in the treatment group was also significantly reduced (8% compared to 22%; P = 0.01). No difference was observed in the overall rate of nosocomial infections (with or without bacteremia). The survivors had similar lengths of stay and there was a slightly lower (not statistically significant) number of days on the ventilator in patients in the control group. Patients with APACHE II scores of 10-15 had the most benefit. Galbán et al conclude that the immune-enhancing diet resulted in a lower mortality rate in septic patients admitted to the ICU and resulted in a reduced number of bacteremic nosocomial infections.
COMMENT BY UDAY B. NANAVATY, MD
For more than a decade, attempts have been made to show that immune-enhancing diets improve the outcome in some subgroups of patients. From several randomized clinical trials in a variety of settings it was found that these diets resulted in reduced rates of nosocomial infections. However, it remains unclear as to what the effects of this immune-enhancing diet are that result in reduced rate of infection and for how long the patient should be on it to see potential beneficial effects.
This is the first study to suggest that this immune-enhancing diet can result in reductions in mortality in septic patients admitted to the ICU. While bacteremic nosocomial infections were reduced, the overall nosocomial infection rate in this study was no different between the two groups and infection-related mortality showed only a trend toward reduction. Unfortunately, the study fails to provide a clear mechanism by which the diet worked.
Immune-enhancing diets have received increasing attention in recent years. A recent publication by Gadek et al (Crit Care Med 1999;27:1409-1420) shows that an omega-3 fatty acid and antioxidant-supplemented diet resulted in improvement in oxygenation and a reduction in lung neutrophils on bronchoalveolar lavage when compared to a standard enteric formula in patients with acute respiratory distress syndrome (ARDS). Gadek et al also provided some insight as to how inflammation may be reduced by these fatty acids. The data in Gadek et al’s study were supported by animal and laboratory studies suggesting that proinflammatory mediators are reduced in the treatment group. Unfortunately, such clear data are not available for all the "immune-enhancing" constituents of the diet included in the study under discussion.
Arginine deficiency is harmful in animal models but supplementation of arginine does not result in improved outcome. Similarly, nucleotide or nucleoside supplementation during sepsis in animal models does not result in improved outcome. Due to the complexity of the inflammatory response, it is difficult to analyze inflammatory responses with a single test. However, if a diet is supposed to work like a drug and improve outcome, one would expect to see some mechanistic explanation concurrent with improved outcome rather than using information from historic controls. This immune-enhancing diet seems harmless to try but more data regarding its efficacy and mechanism of action are needed before it can become a recommended standard enteric formula.
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