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Revista do Hospital das Clínicas

On-line version ISSN 1678-9903

Rev. Hosp. Clin. vol.54 n.1 São Paulo Jan./Feb. 1999 




Eliana Barbosa, Emília A.M. Moreira, José Eduardo Goes and Joel Faintuch



BARBOSA, E et al. - Pilot study with a glutamine-supplemented enteral formula in critically ill infants. Rev. Hosp. Clin. Fac. Med. S. Paulo 54 (1): 21 - 24, 1999.


SUMMARY: Seriously ill infants often display protein-calorie malnutrition due to the metabolic demands of sepsis and respiratory failure. Glutamine has been classified as a conditionally essential amino acid, with special usefulness in critical patients. Immunomodulation, gut protection, and prevention of protein depletion are mentioned among its positive effects in such circumstances. With the intent of evaluating the tolerance and clinical impact of a glutamine supplement in seriously ill infants, a prospective randomized study was done with nine patients. Anthropometric and biochemical determinations were made, and length of stay in the intensive care unit (ICU), in the hospital, and under artificial ventilation, and septic morbidity and mortality were tabulated. Infants in the treatment group (n=5) were enterally administered 0.3 g/kg of glutamine, whereas controls received 0.3 g/kg of casein during a standard period of five days. Septic complications occurred in 75% of the controls (3/4) versus 20% of the glutamine-treated group (1/5, p£0.10), and two patients in the control group died of bacterial infections (50% vs. 0%, p£0.10). Days in the ICU, in the hospital, and with ventilation numerically favored glutamine therapy, although without statistical significance. The supplements were usually well tolerated, and no patient required discontinuation of the program. The conclusion was that glutamine supplementation was safe and tended to be associated with less infectious morbidity and mortality in this high-risk population.


DESCRIPTORS: Pediatric critical care. Pediatric nutrition. Glutamine. Enteral nutrition. Sepsis.



The role of enteral alimentation as a key element in the global assistance of seriously ill patients has been repeatedly emphasized in the last decade. In comparison with parenteral nutrition, enteral feeding protects surgical subjects from postoperative septic complications3. The advent of glutamine and other immune-enhancing nutrients has further highlighted the importance of maintaining the integrity of the gut mucosal barrier during acute aggressions and organ failures in order to improve the outcome of such individuals1,2.

Clinical experience with glutamine supplementation in infants is scarce. Therefore, a prospective randomized pilot study was devised to examine the tolerance and efficiency of glutamine in an intensive care unit (ICU) setting.



During a three-month period, all infants admitted at the ICU of Hospital Infantil Joana de Gusmão (Florianópolis, SC) were considered for this protocol.

Criteria for inclusion:

Age one month - two years

Tolerating enteral nutrition

Serum albumin 3.5 g/dL or diagnosis of sepsis/respiratory failure

Written consent

Criteria for exclusion:

Shock, multiple organ failure, AIDS or HIV+

Immune suppressive drugs, cancer, chemotherapy, or recent surgery

Diabetes mellitus, hepatic or renal failure

Less than 5 days of enteral supplementation

Randomization: Patients were randomized to receive a daily enteral supplement of commercial glutamine (Support), 0.3 g/kg of body weight (treatment group, n=5) or the same amount of casein (control group, n=4).

Nutritional routine: A semi-elemental formula was simultaneously given by naso-enteral tube in the approximate proportion of 100 kcal and 3.0 g protein/kg/day.

Methods: The following variables were documented:

Demographic and clinical information: Age, sex, birth weight, duration of breast feeding, presence of sepsis at admission, duration of ventilator assistance, length of stay (LOS) in the ICU and in the hospital, septic morbidity, and mortality.

Anthropometric and dietetic monitoring: Weight, length, calorie and protein intake, gastrointestinal abnormalities (vomiting, diarrhea, colic, abdominal distension).

Biochemical and hematologic measurements: Serum albumin, pre-albumin, total lymphocytes, glycemia, blood urea nitrogen (BUN), creatinine, total bilirubin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP).

Statistical methods: Parametric and non-parametric tests were applied as appropriate, and a signifícance level of 5% was adopted.

Preliminary findings:

As shown in table 1, control infants were somewhat younger and had slightly smaller body weight and length, but these differences were not significant. On the other hand, these same patients had a numerically longer period of nutritional support with a greater input of calories and protein, again without statistical significance (Table 2).






Biochemical and hematologic determinations in both groups underwent changes between the first and last (5th) day of the protocol, but no statistical significance was demonstrated within each group or between the groups (Table 3).



Duration of mechanical ventilation (11.4 + 20.1 vs. 14.8 ± 12.4 days, NS), LOS in the ICU (14.5 + 23.8 vs. 17.5 + 11.3 days, NS) , and LOS in the hospital (30.0 + 31.0 vs. 34.0 ± 9.8 days, NS), were similar in the two populations, but all higher means corresponded to the control group.

Tolerance to the diet and supplements was good, with only two episodes of diarrhea (one in each group), and all patients completed their therapeutic program.

Bacterial infections occurred in 75% of the placebo population (3/4) and 20% of the treated subjects (1/5, p£0.10), suggesting a beneficial effect of glutamine. A similar trend was seen with mortality: there were two deaths in this series, both caused by microbial complications, and both in the control group (2/4 or 50%), whereas no deaths, septic or otherwise, occurred in the glutamine-treated group (0/5 or 0%, p £ 0.010).



Since 1991 it has been believed, on the basis of glutamine concentrations in amniotic fluid and breast milk, that glutamine is important for newborn or premature children8. Yet it has also been known for some time that conventional proteins, as well as polymeric and hydrolysed enteral formulas, contain variable amounts of glutamine-up to 0.20 - 0.25 g/100 kcal-perhaps rendering exogenous supplementation unnecessary7.

In the past few years, an encouraging experience with glutamine in adults has been reported 1,2, making it desirable that clinical trials in pediatrics be performed as well5. Indeed, the first investigations in this area confirm the expectations regarding diminished nosocomial infections and global morbidity4,6. Still, many questions remain unanswered concerning precise indications and contraindications, duration of treatment, and dosage schedules. In the studies mentioned, administration of the supplement ranged from 0.08 to 0.31 g/kg/day for periods up to 30 days.

In the present study, a prescription of 0.30 g/kg/day was adopted for five days with good tolerance. However, our population differs from those of previous studies, in that we were dealing with critical infants, not premature infants. Nevertheless, a similar trend toward reduced septic morbidity and mortality was revealed.

One limitation of our investigation was the strict criteria for inclusion and exclusion, which severely limited the number of eligible patients. Therefore, these results must be considered as preliminary, and further studies are mandatory to extend the conclusions from our findings to a larger population.



Based on this study, we concluded that enteral glutamine supplementation in the amount of 0.3 g/ kg/ day, for critically ill infants with malnutrition, sepsis, and respiratory failure, (1) was well tolerated, and (2) resulted in a tendency for reduced septic morbidity and mortality.




BARBOSA, E. et al. - Estudo piloto com suplementação de glutamina na nutrição enteral de pacientes pediátricos críticos. Rev. Hosp. Clín. Fac. Med. S. Paulo 54(1): 21 - 24, 1999.


Lactentes criticamente enfermos freqüentemente apresentam desnutrição calórico-protéica em decorrência de demandas aumentadas por sepse e falência respiratória. A glutamina é atualmente classificada como um aminoácido condicionalmente essencial, de interesse especial para pacientes graves. A imunomodulação, a proteção intestinal, e a prevenção da depleção protéica estão entre os argumentos citados a favor de sua utílização. Tendo como propósito averiguar a tolerância e o impacto clínico da glutamina em lactentes graves, efetuou-se um estudo piloto prospectivo e randomizado com nove casos. Os métodos incluiram determinações antropométricas e bioquímicas, duração da hospitalização geral na UTI e sob ventilação mecânica, assim como a morbidade e mortalidade infecciosa. O grupo glutamina (n=5) foi suplementado com 0,3 g/kg/dia daquele aminoácido, sendo que os controles (n=4) receberam igual dose de caseina. Ocorreram complicações sépticas em 75% dos controles(3/4) versus 20% do grupo glutamina (1/5,p£0,10). Ocorreram dois óbitos, ambos de etiología infecciosa, e situados no grupo placebo (50% vs 0%,p£0,10). A permanência na UTI, no hospital e sob ventilação artificial embora estatisticamente sem diferenças, foi numericamente mais favorável para o grupo da glutamina. Conclui-se que a suplementação de glutamina foi bem tolerada e tendeu a se associar a menos complicações infecciosas e menor mortalidade nesta população de alto risco.


DESCRITORES: Terapia intensiva pediátrica. Nutrição pediátrica. Glutamina. Nutrição enteral. Sepse.



1. CALDER PC. - Glutamine and the immune system. Clin Nutrition 1994;13:2-8.         [ Links ]

2. FAINTUCH J. - Dipeptídeos da glutamina em nutrição enteral. Nutrição Enteral 1997;13:9-11.         [ Links ]

3. MOORE FA, FELICIANO DV, ANDRASSY RJ et al. - Early enteral feeding, compared with parenteral, reduces postoperative septic complications. Ann Surg.1992;216:172-183.         [ Links ]

4. NEU J, ROIG JC, MEETZE WH et al. - Enteral glutamine supplementation for very low birth weight infants decreases morbidity. J Pediatr 1997;131:691-699.         [ Links ]

5. NEU J, SHENOY V, CHAKRABARTI R. - Glutamine nutrition and metabolism: Where do we go from here? Faseb J 1996;10:829-837.         [ Links ]

6. ROIG JC, BOWLING D, DALLAS M et al. - Enteral glutamine supplementation decreases nosocomial infection and alters T cell subset in the very low birth weight infant. (Abstract) Pediatr Res 1995;37:285A.         [ Links ]

7. SWAILS WS, BELL SJ, BORLASE BC et al. - Glutamine content of whole proteins: implications for enteral formulas. Nutr Clin Pract 1992;7:77-80.         [ Links ]

8. WOOD BR, HUDDLESTON KC, & FRAZIER,T. - Glutamine levels in amniotic fluid, breast milk, and premature infant formula: non-essentíal amino acid or essential nutrient (Abstract). Pediatr Res 1991;29:306A.         [ Links ]



Received for publication on the 12/11/98.


Hospital Infantil Joana de Gusmão, Department of Nutrition of the Federal University of Santa Catarina, and Hospital das Clínicas, São Paulo University Medical School.

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