A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

Core outcome measures for clinical effectiveness trials of nutritional and metabolic interventions in critical illness: an international modified Delphi consensus study evaluation (CONCISE).

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.

[Advocacy for an improved training in clinical nutrition during the medical cursus]. / Plaidoyer pour l'enseignement de la nutrition clinique aux futurs médecins.

The knowledge of physicians regarding nutrition is often far below the expectations of patients, and does not comply with official recommendations. However, poor-quality nutrition and diet represent the first cause of mortality worldwide. As a result of an insufficient training and awareness, many physicians cannot meet patients' expectations. Moreover, nutrition is sometimes felt as a field of low scientific level, thereby opening the area to pseudo-scientific drifts. We advocate an improvement in the training in nutrition during the medical cursus, namely by the transversal integration of nutritional insights into medical courses, and the recognition of post-university training validated by the academic authorities. A clarification of the roles and the recognition of the competency are urgently required to promote the professionalism of nutritional counselling.

Les connaissances des médecins en matière d'alimentation et de nutrition sont souvent en-deçà des attentes des patients et en décalage par rapport aux recommandations officielles. Pourtant, la mauvaise alimentation constitue la première cause de mortalité à l'échelle planétaire. Les attentes des patients sont importantes en matière de nutrition et le médecin y est mal préparé en raison d'une formation insuffisante. De plus, la nutrition est parfois perçue comme une matière peu scientifique, et la reconnaissance des compétences en nutrition est insuffisante, ouvrant le champ à des dérives pseudo-scientifiques. Nous plaidons pour une meilleure formation en nutrition dans le cursus des études médicales, notamment en intégrant les aspects nutritionnels de manière transversale au cours de la formation des futurs médecins, et pour la reconnaissance des cursus de formation post-universitaires validés par les autorités académiques. Une clarification des rôles et une reconnaissance des compétences sont urgentes afin de professionnaliser les conseils nutritionnels.

[Religious and cultural aspects of organ transplantation]. / Aspects religieux et culturels liés à la transplantation d'organes.

The number of transplantations is mainly limited by the shortage of organs, thereby leading to potentially lethal delays for patients registered on waiting lists. Among the causes of refusals of organ donation, religious reasons are often advocated. In order to make the point, we organized a debate between representatives of secularism ( " laïcité ") and of the most represented religions in Belgium, i.e. catholic, Islamic and Judaic. Even though the representation of death was variable, organ donation is authorized and even encouraged by the fundamental texts. Refusals of organ donation result more often from personal interpretations by local preachers. Therefore, the gathering of political and religious authorities in order to promote organ donation is desirable instead of sowing doubt for pseudo-religious reasons.

En médecine de transplantation, la pénurie d'organes représente le principal obstacle et cause de retard aux greffes vitales pour les receveurs inscrits sur liste d'attente. Parmi les causes de refus de don d'organes, des raisons d'ordre religieux sont souvent invoquées. Afin de faire le point sur cette problématique, nous avons organisé un débat rassemblant des représentants de la laïcité et des religions monothéistes les plus représentées en Belgique : catholicisme, islam, judaïsme. Il est apparu que, si la représentation de la mort varie selon les courants, le don d'organes est en fait autorisé, voire encouragé par les textes fondateurs des trois religions. Les refus sont plutôt le fait d'une interprétation personnelle par des prédicateurs. Dès lors, il serait judicieux de rassembler les forces politiques et spirituelles afin de promouvoir le don d'organes plutôt que de semer le doute à son sujet sous des prétextes pseudo-religieux.

Metabolic response to the stress of critical illness.

The metabolic response to stress is part of the adaptive response to survive critical illness. Several mechanisms are well preserved during evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors, triggered to increase the provision of energy substrates to the vital tissues. The pathways of energy production are altered and alternative substrates are used as a result of the loss of control of energy substrate utilization by their availability. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycaemia, changes in body composition, and psychological and behavioural problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake, and early mobilization, are investigated. This review aims to summarize the pathophysiological mechanisms, the clinical consequences, and therapeutic implications of the metabolic response to stress.

Intensive care units follow-up: a scoping review protocol.

INTRODUCTION: Increasing numbers of patients are surviving critical illness, leading to growing concern about the potential impact of the long-term consequences of intensive care on patients, families and society as a whole. These long-term effects are together known as postintensive care syndrome and their presence can be evaluated at intensive care unit (ICU) follow-up consultations. However, the services provided by these consultations vary across hospitals and units, in part because there is no validated standard model to evaluate patients and their quality of life after ICU discharge. We describe a protocol for a scoping review focusing on models of ICU follow-up and the impact of such strategies on improving patient quality of life. METHODS AND ANALYSIS: In this scoping review, we will search the literature systematically using electronic databases (MEDLINE - from database inception to June 15th 2020) and a grey literature search. We will involve stakeholders as recommended by the Joanna Briggs Institute approach developed by Peters et al. The research will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. ETHICS AND DISSEMINATION: This study does not require ethics approval, because data will be obtained through a review of published primary studies. The results of our evaluation will be published in a peer-reviewed journal and will also be disseminated through presentations at national and international conferences.

Association of transcription factor 7-like 2 gene (TCF7L2) polymorphisms with stress-related hyperglycaemia (SRH) in intensive care and resulting outcomes: The READIAB study.

OBJECTIVE: The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose≥11mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU. METHODS: This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for<48h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded. MAIN RESULTS: The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB-G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P=0.078): OR(peroneTcopy): 1.24, 95% CI: 0.98-1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P=0.026), but was no longer significant at 1 year (P=0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43-3.06; P<0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32-2.28; P<0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07-4.20; P=0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71-2.96; P=0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P=0.72) or 1 year (P=0.64). CONCLUSION: This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development.

Pulmonary veno-occlusive disease in myeloproliferative disorder.

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The pulmonary disease evolved favourably under treatment with defibrotide, a pro-fibrinolytic medication used in hepatic veno-occlusive disease.

[Management of blood glucose level in intensive care]. / Gestion de la glycémie aux soins intensifs.

The aim of this article is to describe the current status and understanding and the clinical data related to the effects of Tight Glucose Control by Intensive Insulin therapy, TGCIIT, in critically ill patients. Recent prospectively collected data, from one centre, demonstrated decreases of mortality and of various other outcomes in critically ill patients treated with TGCIIT. These results are currently awaiting confirmation, although available data from prospective multi-centre studies do not seem to support the external validity of the beneficial effects of TGCIIT titrated to restore blood glucose between 80 and 110 mg/dl. Also, recent data raised new closely related and relevant issues including the variability of blood glucose, the risks of hypoglycaemia, and the delineation of the categories of patients in whom TGCIIT could bring an actual benefit.

[What's new in intensive care medicine?]. / Actualités thérapeutiques en médecine intensive.

Over the last ten years, much progress has been achieved in intensive care medicine. Large randomized studies, most often their multicentric, were performed and their results were translated into rules to be followed for the most appropriate treatment of life-threatening organ failures. The place of non-invasive ventilation in the management of hypercapnic or hypoxic respiratory insufficiencies was thus defined, and the methods for less traumatic mechanical ventilation were specified. The techniques of renal replacement therapy were compared and the optimal doses of dialysis or hemofiltration were established. The metabolic support of the patients was also altered following landmark studies, such as the management of blood glucose, which deeply influenced the approach to critically ill patients.

Carbohydrates and insulin resistance in clinical nutrition: Recommendations from the ESPEN expert group.

Growing evidence underscores the important role of glycemic control in health and recovery from illness. Carbohydrate ingestion in the diet or administration in nutritional support is mandatory, but carbohydrate intake can adversely affect major body organs and tissues if resulting plasma glucose becomes too high, too low, or highly variable. Plasma glucose control is especially important for patients with conditions such as diabetes or metabolic stress resulting from critical illness or surgery. These patients are particularly in need of glycemic management to help lessen glycemic variability and its negative health consequences when nutritional support is administered. Here we report on recent findings and emerging trends in the field based on an ESPEN workshop held in Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology, clinical impact, and nutritional recommendations for carbohydrate utilization and management in nutritional support. The main conclusions were: a) excess glucose and fructose availability may exacerbate metabolic complications in skeletal muscle, adipose tissue, and liver and can result in negative clinical impact; b) low-glycemic index and high-fiber diets, including specialty products for nutritional support, may provide metabolic and clinical benefits in individuals with obesity, insulin resistance, and diabetes; c) in acute conditions such as surgery and critical illness, insulin resistance and elevated circulating glucose levels have a negative impact on patient outcomes and should be prevented through nutritional and/or pharmacological intervention. In such acute settings, efforts should be implemented towards defining optimal plasma glucose targets, avoiding excessive plasma glucose variability, and optimizing glucose control relative to nutritional support.

Nitric oxide-related products and myeloperoxidase in bronchoalveolar lavage fluids from patients with ALI activate NF-kappa B in alveolar cells and monocytes.

An increased production of NO* and peroxynitrite in lungs has been suspected during acute lung injury (ALI) in humans, and recent studies provided evidence for an alveolar production of nitrated compounds. We observed increased concentrations of nitrites/nitrates, nitrated proteins and markers of neutrophil degranulation (myeloperoxidase, elastase and lactoferrine) in the fluids recovered from bronchoalveolar lavage fluids (BALF) of patients with ALI and correlated these changes to the number of neutrophils and the severity of the ALI. We also observed that BALFs stimulated the DNA-binding activity of the nuclear transcription factor kappa B (NF-kappaB) as detected by electrophoretic mobility shift assay in human alveolar cells (A549) and monocytes (THP1). The level of activation of the NF-kappaB-binding activity was correlated to the concentration of nitrated proteins and myeloperoxidase. Furthermore, in vitro studies confirmed that NO*-derived species (peroxynitrite and nitrites) and the neutrophil enzyme myeloperoxidase by themselves increased the activation of NF-kappaB, thereby arguing for an in vivo pathogenetic role of NO*-related products and neutrophil enzymes to human ALI.

Hemodynamic responses to successful weaning from mechanical ventilation after cardiovascular surgery.

Weaning from mechanical ventilation is usually associated with an increase in oxygen consumption (VO2), which may stress the cardiovascular system. We studied relative changes in the cardiac index and oxygen extraction ratio (EO2) during successful weaning in patients after cardiac surgery (n = 52), cardiac transplantation (n = 17), or abdominal aortic surgery (n = 11). Cardiac index was determined by the thermodilution technique and arterial and mixed venous blood gases were obtained before and 30 min after the start of weaning through a T-piece. The cardiovascular changes were evaluated in 42 patients in whom VO2 (calculated by Fick's equation) increased by more than 10%. Cardiac index increased more after abdominal aortic surgery (from 3.27 +/- 0.77 to 4.44 +/- 0.581 min(-1) m(-2), p < 0.01) than after cardiac surgery (from 2.53 +/- 0.59 to 2.87 +/- 0.46 1 min(-1) m(-2), p < 0.01) or cardiac transplantation (from 2.99 +/- 0.64 to 3.33 +/- 0.741 min(-1) m(-2), p < 0.05). EO2 remained stable in patients after aortic surgery (from 25.9 +/- 7.1 to 25.2 +/- 5.6 %, NS) but increased slightly after cardiac surgery (from 33.3 +/- 6.1 to 37.3 +/- 6.4%, NS) and significantly after cardiac transplantation (from 25.8 +/- 4.1 to 28.2 +/- 4.0%, p < 0.05). Hence the cardiovascular response to weaning from mechanical ventilation may vary according to the type of surgery.

Transthoracic electrical bioimpedance versus thermodilution technique for cardiac output measurement during mechanical ventilation.

To study the possible influence of mechanical ventilation on the accuracy of thoracic electrical bioimpedance (TEI) in the measurement of cardiac output, we determined cardiac output concurrently by TEI using Kubicek's equation and by thermodilution in 8 acutely ill patients who were mechanically ventilated (assist/control mode) but who had no underlying respiratory failure. Cardiac outputs were lower with TEI than with thermodilution (3.97 +/- 0.80 vs 4.83 +/- 1.16 l/min p = 0.004) and there was poor correlation between the values (r = 0.41). Although there is a need to develop non-invasive techniques to measure cardiac output, the present study indicates that TEI is not reliable in mechanically ventilated patients.

Management of nutrition in European intensive care units: results of a questionnaire. Working Group on Metabolism and Nutrition of the European Society of Intensive Care Medicine.

OBJECTIVE: To describe the practical aspects of nutritional management in intensive care units (ICUs). DESIGN: A 49-item questionnaire was sent to the physician members of the European Society for Intensive Care Medicine. The issues addressed included: medical environment, assessment of nutritional status and current practice for enteral and parenteral nutrition. SETTING: 1608 questionnaires were sent in 35 European countries. ANALYSIS: The answers were pooled and stratified by country. RESULTS: 271 questionnaires were answered (response rate 17%). Assessment of nutritional status was generally based on clinical (99%) and biochemical (82%) parameters rather than on functional (24%), anthropometric (23%), immunological (18%) or questionnaire-based (11%) data. Two thirds of 2774 patients hospitalised in the corresponding ICUs at the time the questionnaire was answered were receiving nutritional support; 58% of those were fed by the enteral route, 23% by the parenteral route and 19% by combined enteral and parenteral. The preferred modality was enteral nutrition, instituted before the 48th h after admission, at a rate based on estimated caloric requirements. Specific and modified solutions were rarely used. Parenteral nutrition was less commonly used than enteral, although the practices differed between countries. It was mainly administered as hospital-made all-in-one solutions, at a rate based on calculated caloric requirements. CONCLUSIONS: European intensivists are concerned by the nutritional management of their patients. The use of nutritional support is common, essentially as early enteral feeding.

Enteral nutrition in intensive care patients: a practical approach. Working Group on Nutrition and Metabolism, ESICM. European Society of Intensive Care Medicine.

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients, due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of the management of these patients. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decisions when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements, and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.

Effects of nitric oxide on blood flow distribution and O2 extraction capabilities during endotoxic shock.

The effects of the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) and the NO donor 3-morpholinosydnonimine (SIN-1) were tested in 18 endotoxic dogs. L-NMMA infusion (10 mg . kg-1 . h-1) increased arterial and pulmonary artery pressures and systemic and pulmonary vascular resistances but decreased cardiac index, left ventricular stroke work index, and blood flow to the hepatic, portal, mesenteric, and renal beds. SIN-1 infusion (2 microg . kg-1 . min-1) increased cardiac index; left ventricular stroke work index; and hepatic, portal, and mesenteric blood flow. It did not significantly influence arterial and pulmonary artery pressures but decreased renal blood flow. The critical O2 delivery was similar in the L-NMMA group and in the control group (13.3 +/- 1.6 vs. 12.8 +/- 3.3 ml . kg-1 . min-1) but lower in the SIN-1 group (9.1 +/- 1.8 ml . kg-1 . min-1, both P < 0.05). The critical O2 extraction ratio was also higher in the SIN-1 group than in the other groups (58.7 +/- 10.6 vs. 42.2 +/- 7.6% in controls, P < 0.05; 43.0 +/- 15.5% in L-NMMA group, P = not significant). We conclude that NO is not implicated in the alterations in O2 extraction capabilities observed early after endotoxin administration.

Effects of nitric oxide donor SIN-1 on oxygen availability and regional blood flow during endotoxic shock.

BACKGROUND: An excessive release of nitric oxide (NO) has been incriminated in the circulatory disturbances of septic shock. OBJECTIVE: To study the effects of an NO donor, 3-morpholinosydnonimine (SIN-1), an oxygen availability and regional blood flow during endotoxic shock to see if a beneficial effect of NO synthase inhibitors in septic shock could be conclusively demonstrated. MATERIALS AND METHODS: In 14 anesthetized and mechanically ventilated dogs, global invasive hemodynamic monitoring was completed and ultrasonic flow probes were placed around the superior mesenteric, left renal, and left femoral arteries for simultaneous measurements of regional blood flow. All dogs received Escherichia coli endotoxin, 2 mg/kg. A control group (n = 7) was administered saline at 20 mL/kg per hour, and a SIN-1 group (n = 7) was given a combination of saline with SIN-1 at successive doses of 1, 2, and 4 micrograms/kg per minute. RESULTS: Neither systemic nor pulmonary arterial pressures were influenced by SIN-1. Cardiac index, stroke index, and left ventricular stroke work index did increase at low to moderate doses of SIN-1 but tended to decrease at the highest dose. Systemic and pulmonary vascular resistances decreased. Fractional blood flow increased in the mesenteric bed at all doses used, was not influenced in the renal bed, but decreased in the femoral bed at the highest dose. Oxygen-derived variables were similar in the 2 groups. Blood lactate and plasma concentrations of tumor necrosis factor were not significantly influenced. At the end of the SIN-1 infusion, the administration of 5 mg/kg of methylene blue increased arterial pressure, pulmonary arterial pressure, and systemic and pulmonary vascular resistances but decreased cardiac index and regional blood flow. CONCLUSIONS: The administration of low to moderate doses of the NO donor SIN-1 can significantly increase cardiac index and superior mesenteric blood flow without deleterious effects on arterial pressure in this model of endotoxic shock. These findings support the hypothesis that NO is essential to maintain organ blood flow even during endotoxic shock.

Enteral nutrition in intensive care patients: a practical approach.

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients, due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of these patient's management. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decision-making when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.

Metabolic effects of arginine addition to the enteral feeding of critically ill patients.

BACKGROUND: Some studies have suggested that the addition of arginine to enteral feeding solutions may improve outcome in critically ill patients, but the mechanism is incompletely explained. In particular, the availability and utilization of arginine administered enterally is not well defined. METHODS: This prospective, randomized, double-blind, placebo-controlled study performed in a Department of Medicosurgical Intensive Care included 51 patients likely requiring long-term enteral feeding. Thirty-seven patients (57 +/- 7 years, SAPS II 33 +/- 6) completed the 7-day study, of whom 20 received the formula enriched with free arginine (6.3 g/L) and 17 received an isocaloric and isonitrogenous control solution. Arginine absorption was assessed from plasma arginine concentrations in serial samples. Three pathways of arginine utilization were explored: (1) the production of nitric oxide, assessed by the plasma concentration of nitrite/nitrate (NOx) and citrulline, and 24-hour urinary excretion of NOx; (2) the protein turnover, estimated by the phenylalanine concentrations; and (3) the activity of arginase, reflected by the ornithine concentration. RESULTS: The plasma concentrations of arginine and ornithine increased in the group fed with the enriched formula (from 55 +/- 9 micromol/L to 102 +/- 9 micromol/L and from 57 +/- 7 to 135 +/- 11 micromol/L, respectively, p < .05), but not with the control formula. There was no difference between groups in either NO production or phenylalanine concentration. CONCLUSIONS: Supplemental arginine in enteral feeding is readily absorbed, and mainly metabolized into ornithine, presumably by the arginase enzyme.