EXTENSIVE BURN PATIENTS: IMMUNOLOGICAL PROBLEMS

Visentini P.

Divisione di Chirurgia Plastica e Centro Ustioni dell'ospedale Civile di Udine, Italia

SUMMARY. The bum lesion provokes immune depression, which favours bacterial aggression. This was documented in our laboratory by examining the values of gammoglobulin and T lymphocytes in the blood. General and local treatment for the reduction of the depression of the immunocompetent cells is described, together with results of the monitoring of T3, T4 and T8 lymphocytes. It was observed that the reduction of these immunocompetent cells was evident in extensive bum patients, elderly patients, and those with full-thickness bums. An attempt was made in 72 patients to counteract the reduction of T lymphocytes using thymostimulin (TPI), regulating dosage on the basis of the monitoring of the absolute value of the lymphocytes. With this treatment there was a reduction in infections and improvement in survival, especially in elderly patients and those with full-thickness bums.

The bum patient frequently presents immune system depression which is indicated by:

1. the observation that homologous cutis grafts are eliminated after a longer time period than in other patients;
2. the reduction of gammoglobulins;
3. the often considerable reduction of T lymphocytes, particularly of T4 lymphocytes.

These modifications could be correlated to the difficulties the bum patient has in defending himself from bacterial aggression.
We therefore decided to document this difficulty by monitoring some parameters such as the gammoglobulin rate and the absolute number of T3, T4 and T8 lymphocytes. Our experience, as shown in Fig. 1, indicates that the burn patient presents a reduction of total proteins, which we determined in 160 patients with 2nd or 3rd degree burns in 10-95% BSA, average 29%. The drop in total proteins, as can be seen in Fig. 2, is proportional to the burn surface area.

Fig. 1 - Total proteinaemia, mean values observed in 160 burn patients with burns from 10 to 95% (average 29%). Comparison with mean control values +/- Standard Deviation. Fig. 2 - Values of total proteinaemia in relation to burn surface. Comparison with mean control values +/- Standard Deviation. Fig. 3 - shows that the reduction is due to a temporary reduction in albumin and gammaglobulin.

The determination of T lymphocytes demonstrated that the reduction was more marked in elderly patients, in extensive bum patients and in those with full-thickness bums. In some cases the values measured were similar to those seen in AIDS cases. The condition persisted during the acute phase of the disease and regressed as the patient's health gradually improved.
According to data in the literature, depression of the immunocompetent cells is increased by associated trauma, catheters, insufficient introduction of alimentation, viral and bacterial infections, diabetes mellitus, hepatic cirrhosis, blood transfusions and a number of drugs, such as analgesic-antipyretics derived from pyramidone, corticosteroids, etc. Immune depresion can be controlled in many ways -by an infusive treatment that maintains the protein composition of the blood at about normal values, especially albumin and gammaglobulin, by adequate introduction of alimentation, either orally, parenterally or by naso-gastric tube, by a local and general treatment that reduces infective processes as far as possible, and if necessary by the administration of drugs that stimulate the production of immunocompetent cells. For many years we have treated extensive burn patients from the beginning with human plasma (isogroup, if possible) using the formula we have elaborated (Formula N' 1) for the first 2 days, in order to maintain normal haematocrit values. Fig. 3 - Mean values of protein fractions separable by electro-phoresis, determined in burn patients with lesions of 10-95%. Comparison with mean control values +/Standard Deviation.
We also correct gammoglobulin values. The necessary electrolyte solutions are administered from the beginning. We also administer cimetidine, to prevent gastric stress ulcer, and calciparin in elderly-, and very extensive bum patients, to reduce the risk of pulmonary embolisms. Antibacterial drugs are administered in the presence of signs of infection like fever or a considerable increase in leucocytes, the choice being based on the antibiograms. Alimentatioft is systematically controlled so that the necessary calories are introduced.
Last of all, let us consider the surgical operation, which as early as possible must remove necrotic tissue and replace it with autologous grafts. This is unfortunately possible only in patients with burns of modest extent - in extensive burned patients early treatment is possible only in the face and hands. However all the above procedures are sometimes unable to prevent the reduction in particular cases of the immunocompetent cells, which we a4so have observed, determining systematically the absolute number of T3, T4 and T8 lymphocytes (CD3, CD4, C138).
72 patients of varying age and with different extent and depth of lesion, presenting a marked reduction of immunocompetent cells, were treated with thymostimulin (TPI)*, regulating the dosage on the basis of the monitoring of T lymphocytes. In particular, when the number of immunocompetent cells presented a reduction of at least 20%, we administered I mg/kg of TPI for 7 days. When the reduction of immunocompetent cells was higher, in some cases even 60%, we administered 1.5 mg/kg, also for 7 days.
When the immunocompetent cells returned to near normal values we administered TPI at the rat~ of I mg/kg once or twice a week. We were ready to resume daily administration in the event of reduction of the immunocompetent cells, which generally occurs following surgical operation.
For over a year, before serious operations, we have initiated daily treatment, which we suspend when the immunocompetent cells reach normal values.
As said, the 72 patients treated presented burns of various extent and depth and were of varying age (see Tables). Some with bums in the upper airways had to be tracheotomized; others also had traumas and fractures. The elderly patients often suffered from cardiopathies, diabetes and arteriosclerosis; one patients had AIDS and some were alcoholics or drug addicts with hepatic damage.
In all patients treated with TPI we observed a reduction of bacterial aggression, a lower drop in gammaglobulins, less need to administer antibiotics, favourable progress and the possibility of early operation even in extensive burn patients.
As these data are not easy to document objectively, we have calculated the mortality rate comparing it with that reported in Feller and Crane's Table (Table 1) and with bum patients we treated in previous years (Table 2).
Table 3 refers to 72 patients of varying age and with different extent and depth of lesions treated with TPI in the way described. They present a survival rate of 93.05%, compared to a rate of 82.27% according to Feller and Crane and 90.47% according to Visentim et al.
Table 4 refers to 49 patients with bums of varying extent and depth, aged up to 59 years, treated with TPI. They present a survival rate of 93.87% compared to 87.22% according to Feller and Crane and 94.12% according to Visentini et al. One of the deceased was HIV positive.

Feller and Crane's table

Table 5 refers to 23 patients with full-thickness skin bums aged over 60 years treated with TPI. The survival rate was 91.30% against 71.82% according to Feller and Crane and 82.69% according to Visentini et al.
Table 6 (Feller and Crane) analyses survival rate on the basis of extent and age, considering only full-thickness bums.
Table 7 shows the reduction of mortality, which is very evident, calculating only full-thickness bums in 60 patients treated with TPI. We obtained a survival rate of 93.33% compared to an estimated rate (Feller and Crane) of 71.28%.
The summary table (Table 8) shows that the survival of bum patients treated with TPI administered regulating the amount on the basis of the monitoring of the T cells is very low in young patients, good in elderly patients and very high in bum patients with deep bums.
The techniques currently employed make it possible to cure a high number of patients with extensive and complicated bums, even in elderly patients.
In many cases however the quality of the cure IS not perfect, and 1 think that this is a very important field of research for our younger colleagues.
(*) Thymostimulin - TP1 - produced by Seronno was used

RÉSUMÉ. La réintégration calorique-protéique du brûlé représente un moment thérapeutique très important parce que la prévention ou la réduction du catabolisme peuvent protéger les fonctions organiques et réduire la morbidité et la mortalité. Le but principal est la satisfaction des besoins calorique-protéiques en tentant d'en administrer la quantité maximum entre 3-4 jours après la brûlure, ce qui déchaîne un mécanisme de freinage catabolique. Il faut absolument faire une évaluation précise de l'état nutritionnel du patient au moment de l'hospitalisation et pendant tout le séjour à l'hôpital. A cette fin on emploie divers paramètres de référence chimiques, biohumoraux, anthropométriques et immunologiques. Les Auteurs décrivent les divers types de soutien nutritionnel (Entéral Total, Entéral avec Soutien Parentéral Total) et les tests relatifs, les indications et les contre-indications.

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