THE EFFECT OF VERY EARLY ENTERAL TUBE FEEDING ON THE HUMORAL IMMUNITY OF BURNED CHILDREN

Germenis A.E., Achilleos O.A., Stavropoulos-Giokas C., loannovich J., Vaos G., Rondras K.

2nd Department of Paediatric Surgery, Children's Hospital P. & A. Kyriakou & Department of Immunology, General Hospital of Athens, Athens, Greece

SUMMARY. A comparative study was made of the effects in severely burned children of very early enteral tube feeding (VEETF) and of per os feeding. It was found that a) VEETI` produced a significantly higher elevation of IgG, IgM and C4 serum levels, b) both feeding schemes caused a significant elevation of C3 scrum levels, that of VEETI` being higher; and c) neither feeding scheme had a significant effect on lgA scrum levels. It is concluded that VEETF in severely burned children has a more favourable effect on their humoral immunity than per os feeding.

Introduction
The term Enteral Tube Feeding (ETF) is used to mean the supply, in liquid form, of all the necessary nutrient to a certain section of the gastrointestinal tube, through a nasogastric or a nasointestinal tube, through a gastrostomy or through a jejunostomy. The term Very Early Enteral Tube Feeding (VEETF), in the case of a burn patient, is used to mean its performance within the first 6 hours after the accident. Delay in performing ETF until the motility of the gastrointestinal tube is fully restored may cause a serious delay in per os feeding. This would increase the frequency of complications, as well as mortality. VEETF in burn patients contributes to the preservation of the integrity of the intestinal mucosa and inhibits the translocation of the microbic stems through the intestinal epithelium to the portal circulation and, consequently, septic complications. This is the main reason for using it in burn patients.
In 1971, Adibi showed that a short period of deprivation of per os feeding, without any other nutritive support, causes a quick and extensive decrease of the epithelial cells of the intestine and a decreased absorption of peptids and aminoacids. In 1974, Levin proved that ETF is superior to total parenteral feeding, as regards the function and integrity of the gastrointestinal tube. In experimental models (mice) it has been observed that under complete feeding suspension the intestinal mucosa becomes atropic within I to 2 days and the weight decreases to half within 6 days. Furthermore, ETF has fewer metabolic and technical complications.

Material and methods
The patients (Table 1) in our study consisted of a group of 15 children (mean age 5.4 years) with an average body surface area burned (BSAB) of 32.6% in whom we performed VEETF, and a group of 6 children (mean age 5.2 years) with an average BSAB of 19.5% in whom we performed per os feeding immediately after admission to our Hospital.
As a solution we used the product Reabilan, which contains per litre:

31.5 gr protein (natural oligopeptids) 12.5% energy 39.0 gr lipids (NICT linoleic acid 35.0% energy a-linolenic acid, y-linolenic acid)
31.5 gr carbohydrate
Osmolality 300 mosmol/It
52.5% energy

There was a continuous performance with an enteral tube feeding-pump that assured accurate regulation of the application speed. The parameters valued were the immunoglobulins IgG, IgM, lgA, C3, C4 and PINI. The counting method was nephelometry. To estimate the changes in concentration of the parameters that we evaluated, according to the feeding method, in an attempt to avoid the confusing effect of the nutritional condition and the acute phase reaction - as this is estimated by PINI values - a multifactor analysis of variance was performed.
This is an inflammation/feeding indicator. Its value depends on the elevation of the acute phase proteins as well as on the decrease of all the other proteins and especially of prealburnin, albumin, C3, etc. (Table 2). The acute phase proteins indicate inflammation and albumin-prealbumin indicates the feeding condition.

Results

1. VEETF, in contrast to per os feeding, causes significantly high elevation of the lgC, IgM and C4 serum levels (P= 0.002, 0.015 and 0.03 compared to 0.07, 0.1 and 0.4, respectively).
2. The two feeding methods both provide an important increase of the C3 serum levels (P= 0.000 1 compared to P= 0.0 1).
3. The lgA levels do not alter significantly in either of the two methods.

A small decrease of the IgG value is noted in the first 48 hours which may be caused by the rapid hydration during these 48 hours. Between the 3rd and the 10th day, an elevation of the IgG values is noted in both groups and between the 10th and the 15th day the IgG values increase rapidly in the VEETF group over the normal limit, in contrast to the per os feeding group, in which the IgG values remain at the normal lower limit. There is a significantly high elevation in the VEETF group (Fig. 1). Until the 3rd week, there is a tendency to return to the initial values and it is supposed that the burned child's organism overcomes the necessity of a massive immune response in the middle of the 3rd week.

Fig. I Alteration of IgG.

Regarding IgM there is a proportional alteration (compared to the IgG levels), and a quicker increase of the IgM values is noted which remain at high levels for a longer time. A significantly high elevation is noted in the VEETF group (Fig. 2).
A delayed response is noted and the alteration is not of statistical significance. In the VEETF group the IgA values are however closer to the limits of statistical significance (Fig. 2).
There is an increase of the C3 values between the I Oth and 20th day, which is of statistical importance. C4 has a higher increase in the VEETF group after the first 4 8 hours, which is also of statistical significance (Fig. 3).

Fig. 2 Alteration of 19M and IgA. Fig. 3 Alteration of C3c and C4.

Discussion
Per os feeding is sometimes inadequate for the needs of a burn patient, and a face trauma makes it impossible for technical reasons. Furthermore, the patient's negation leads to a decreased per os supply. VEETF within the first hours after the accident, using a nasogastric or nasojejunal tube, is in general the best feeding method when it can be applied. Modem experimental and clinical studies show that the immediate application of enteral tube feeding decreases the high metabolic function rate by decreasing the production of the catabolic hormones (cortisol, catecholamines, glucagon). It reverses the negative nitrogen balance, more rapidly inhibits intestinal mucosa atrophy and preserves the intestinal bar.
There is a close relationship between the nutritive condition of a patient and the function of his immune system. Feeding disorders are considered to be one of the main factors influencing the process of inflammation. It has been proved that inadequate feeding alters the immune response. By correcting feeding disorders we restore normal functioning of the immune system. Inadequate feeding decreases the levels of the immunoglobulins, the opsonins and the complement.
The complement system, which participates in bacteriolysis, chemotaxis, opsonization and fixation, is decreased because of inadequate feeding, but immediately increases to normal limits after restoration of feeding. It has been observed that in patients with feeding disorders there is an activation of factors that act against the complement system; this is caused by inadequate feeding of proteins rather than calories. In patients with feeding disorders complement activity is decreased because of the decrease in cytogenes and because of the activation of certain factors which induce consumption of complement system proteins. The IgG, IgM and lgA immunoglobulins are decreased, the rate depending on the patient's condition. In burn patients serum immunoglobulins are decreased (but this is not related to the infection or recovery rate). Generally the bibliography is poor regarding elements that concern the complement, the immunoglobulins and their correlation to enteral tube feeding, especially VEETF, although it has been performed in burn patients for the last 4 years. In burned children high and direct caloric support improves survival and the immune defence and is more successful if associated with VEETF application.
In conclusion, VEETF in children with extensive burn injuries seems to have a more favourable effect on the main parameters of humoral immunity than per os feeding. VEETF can supply the calorie requirements of an organism - like that of a burned child - which needs an alerted immune system capable of becoming fully activated. Our results show that we succeeded in avoiding disorders of the immune system, which are the main cause of increased mortality, septicaemia and, in general, non-favourable prognosis.

RÉSUMÉ. Les effets chez les grands brúlés d'áge pédiatrique de l'alimentation entérale trés précoce par tube (VEETF) et de l'alimentation per os ont été confrontés. On a trouvé que a) la VEETF produit une élévation significativement plus haute des niveaux sériques de IgG, IgM et C4; b) toutes les deux méthodes Walimentation causent une élévation significative des niveaux sériques de C3 (celle de la VEETF est la plus haute); et c) aucune des deux méthodes Walimentation ne provoque un effect significatif sur les niveaux sériques de IgA. On conclut que la VEETF chez les enfanis sévérement brúlés a un effet plus favorable sur leur immunité humorale que l'alimentation per os.

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