Elsevier

Clinical Nutrition

Volume 22, Issue 3, June 2003, Pages 221-233
Clinical Nutrition

Review Article
Immunonutrition in the intensive care unit. A systematic review and consensus statement

https://doi.org/10.1016/S0261-5614(03)00007-4Get rights and content

Abstract

Objective: To systematically review the effects of enteral nutrition with pharmaconutrients-enriched diets in critically ill patients and to establish recommendations for their use.

Data sources: Computerized bibliographic search of published research and citation review of relevant articles.

Study selection: Randomized clinical trials of critically ill patients treated with enteral nutrition comparing diets enriched with pharmaconutrients vs not enriched diets were included. Infectious complications and outcome variables (days on mechanical ventilation, ICU and hospital length of stay and mortality) were evaluated. Studies were classified in four subgroups according to the patient's primary diagnosis: surgical, trauma, burned or medical.

Data extraction: A group of experts in methodology performed data extraction and statistical processes. A global analysis of the studies was done and also a separate study for each subgroup. Results of the meta-analysis were discussed within a ‘clinical group’ of clinicians with experience in the nutritional support of ICU patients, in order to find agreement about recommendations for the use of pharmaconutrients-enriched diets in critically ill patients.

Results: Independent review of 267 articles identified 26 relevant primary studies. Global results indicate that there was a reduction in infection rate in the pharmaconutrition group, considering the appreciated lower incidence in abdominal abscesses (OR: 0.26, CI: 0.12–0.55) (P=0.005), nosocomial pneumonia (OR: 0.54, CI: 0.35–0.84) (P=0.007) and bacteremia (OR: 0.45, CI: 0.35–0.84) (P=0.0002). Also, patients treated with pharmaconutrition diets have a reduction in time on mechanical ventilation (mean 2.25 days, CI: 0.5–3.9) (P=0.009), ICU length of stay (mean reduction of 1.6 days, CI: 1.9–1.2) (P<0.0001) and hospital length of stay (mean reduction of 3.4 days, CI: 4.0–2.7) (P<0.0001). No effects were appreciated on mortality (OR: 1.10, CI: 0.85–1.42) (P=0.5). Nevertheless, the separate analysis for each subgroup showed that the reported beneficial effects were not the same for each patient population. Also, the clinician panel of experts identifies several problems in the published data about enteral pharmaconutrition in critically ill patients. In spite of the subgroup differences and of the problems detected, the clinician group considered that the appreciated results could support a Grade B recommendation for the use of these formulas in ICU patients.

Conclusions: Considering the beneficial effects and the absence of detrimental ones, the use of diets enriched with pharmaconutrients could be recommended in ICU patients requiring enteral feeding. Nevertheless, more investigation is needed in this field in order to find the more appropriate population of patients that can be beneficed with this nutritional therapy.

Introduction

Enteral nutrition is the preferred method for feeding critically ill patients with functioning gastrointestinal tract. Enteral nutrition improves several clinical outcomes like infectious complications and ICU or hospital length of stay. Indeed, enteral nutrition seems to play a role in the modulation of the immune system of critically ill patients. Several specific substrates with immunological effects have been added, alone or in combination, to standard diets trying to modify the immune response of the patients. The number of these key nutrients, also called nutraceuticals or pharmaconutrients, is now increasing but arginine, glutamine, nucleotides and omega-3 polyunsaturated fatty acids seems to play a primordial role in the regulation of immunological and inflammatory responses in critically ill patients (1).

Enteral diets enriched with pharmaconutrients have been also called immune-enhancing diets. These immunonutrition formulas have been used in several studies trying to demonstrate their beneficial effects on laboratory, immunological and clinical parameters in comparison with standard diets in critically ill patients. However, results of these trials are controversial due to methodological limitations and to the heterogeneity of the studied patient populations. In order to advance in the knowledge in this field, the evidence-based medicine methodology has been also applied. Two meta-analysis 2., 3. have been recently published and both concluded that immunonutrition in critically ill patients could improve the incidence of nosocomial infections and shorten the length of stay, but do not improve mortality. This conclusion is also supported in another systematic review (4) but these authors also suggests that the effects of the immune-enhancing diets can be different depending on the subset of patients analyzed or on the methodological quality of the studies included in the meta-analysis.

The purpose of this study was to answer the following question: Compared to enteral nutrition with standard diets, has the use of diets enriched with pharmaconutrients a significant effect on the outcome of critically ill patients? In order to develop a process with clinical-practice implications we decided to use a combined methodology. A methodological group performed a systematic review. After this, a group of clinicians with experience in the field of nutritional support in critically ill patients discussed the appreciated results in order to obtain a consensus about the relevance of the result for the clinical practice and, finally, establish clinical recommendations about the use of pharmaconutrition in critically ill patients.

Section snippets

Working group configuration

Two separated working groups were created. A methodological group was formed with experts from the Ibero-American Cochrane Center. A clinical group was created with members of the Nutritional and Metabolic Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units, clinicians with a large experience in the field of nutritional support of critically ill patients, asked by one of the authors (JCM, study coordinator) to participate in the project.

Parts of the study

The study was designed in a

Study identification and selection

Search strategy retrieved a number of 684 references. Finally, we reviewed 35 randomized studies. Seven of them 10., 11., 12., 13., 14., 15., 16. were papers with secondary data coming from one original study (Table 2). Data from these studies were similar to those provided by the primary published study. Another two studies were excluded 17., 18. because results from the control and the study groups were not clearly identified.

Twenty-six studies met the inclusion and exclusion criteria and

Discussion

Clinical guidelines are systematically developed statements designed to provide the best evidence to support the management strategies for patients with specific conditions. This paper represents the work of an independent group of experts trying to find the best evidence about the use of immune-enhancing diets in critically ill patients using the method of consensus (45). The methodology included a systematic review of the published trials (46) done by a group of epidemiologists and the

Acknowledgements

The authors thank Mireia Morera and Xavi Planet, from Novartis Consumer Health, for their assistance in making this study possible. The study was partially supported by a grant from Novartis Consumer Health (Barcelona, Spain).

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