PERSONALIZED THERAPY SCHEDULES IN THE SERIOUSLY BURNED PATIENT

Brienza E, Di Lonardo A., Cannone M., Macripò

Istituto Policattedra di Chirurgia d'Urgenza e Chirurgia Plastica, Cattedra di Chirurgia Plastica, Universita di Bari, Italia

SUMMARY. A prognostic index is presented on the basis of which it is possible to programme a differential therapeutic approach for different risk classes of burned patients. The index takes into account total bum %, deep bums %, age of patient, time period between bum and hospitalization, site of bum, and associated diseases. The various aspects of therapy in the severely burned patient are considered (systemic treatment and fluid therapy, nutritional, immunological and antibiotic therapy, and topical and surgical treatment). Special reference is made to Class IV patients, i.e. those at greatest risk.

There is perhaps no overall ideal therapy for the treatment of the seriously burned patient, as this depends on the contingent conditions of the patient and on the kind of facility in which he is being treated.
This premise presupposes that each individual Centre for the treatment of bum patients has prepared a therapeutic protocol which is based on the clinical experience of that Centre and which is often compared with that of other Centres.
This paper is the result of a rigorous analysis of 12 years of activity at the Bari Bum Centre, Italy, on the basis of which we stress the importance, if we wish to have precise therapeutic organization in a clinical protocol, of the absolute necessity of a prognostic index that permits the subdivision of hospitalized patients into determined risk classes.
A categorization of this nature programme a differential therapeutic approach for each single class of patient and to carry out statistical surveys of the results in homogeneous groups.
Our index (Bridi) does not have an absolute value and it can easily be replaced by others, such as the Rol index, which most Italian Centres will probably soon have to adopt in order to define common working strategies.
We will exclude from our analysis therapeutic protocols for Classes I and II (i.e. non- and mediumserious patients).
Patients belonging to Class III are observed for the first time in a state of hypovolaernic shock, although there may be exceptions, but for the sake of clarity we prefer to define a standard procedure.
As shown by physiopathological events, hypovolaemia is caused by a considerable loss of fluids from the intravascular compartment, due either to lesions or to impaired capillary permeability.
The amount of intercompartmental fluid transfer is directly proportional to the extent of the burns.
The resultant soft tissue oedema is its clinical expression. In cases of 40% BSA bums it is evident also in tissues not directly affected by the trauma.
The literature offers numerous explanations for this altered capillary permeability (1, 2):

1. entry into the circulation of vasoactive substances, such as serotonin, histamine, kinins and prostaglandins, traces of which have been identified in damaged tissue but not so significantly and constantly in the general circulation;

2. increased tissue osmolality, the value of which cannot be confirmed because no really osmotically active substance has ever been identified in the circulation;

3. production of fibrin demolition products, principally of the D fragment.

Whatever the aetiology, the increase in capillary permeability leads to an increased passage of plasma proteins in the interstitial space, with a relative reduction of vasal oncotic pressure.
The fluid forming the oedema gathers progressively during the first 24-36 hours after the trauma, with a maximum loss in the first 6-8 hours (3).
Subsequently the oedema develops less quickly, because of the effect of physiopathological conditions reducing the capillary surface: vasoconstriction, the resulting haemoconcentration and therefore erythrocyte and platelet aggregation.
This sudden transfer of fluids, with an evident reduction of plasma volume in the first post-bum hours, can be reduced to more or less controllable conditions if effective fluid therapy is immediately initiated.
The degree of this reanimatory procedure is proportional above all to the extent of the burn and to the patient's body weight.
Before describing . in terms of therapeutic possibilities the significance and the various indications for fluid therapy in the severely burned patient, we must stress the necessity of applying a high-flow central venous catheter.
This catheter must be applied in all high-risk patients, as also in children with bums in more than 20% BSA; in the great majority of cases the hydroclectrolyte infusion must also be associated with nutritional therapy.
Despite the validity of the techniques of closed cannulation, for reasons of stability and in order to stabilize the fitted catheter it is advisable to leave sonic distance between the cannulated venous vessel and the point of entry through the skin, by creating a long subcutaneous tunnel.
We now tend to use, also on the advice of our paediatric surgeon colleagues, either Broviac di Hichman catheters fitted with a preterminal Dacron cuff or Vygon, Nutricath S catheters which can be replaced every 10-15 days, using Sellinger's method.

Guided by instrumental monitoring (PVC, ECG, thorax radiography) and laboratory tests (HCT, electrolytes, proteins, osmolarity, urine, etc.) performed every 6 h for 24-36 h, plus computerized diuresis control, we infuse In the first 24-48 h isotomc or hypertonic Ringer's lactate or acetate solutions in quantities calculated on the basis of the extent of the burn (Rule of 9) and of the patient's weight, hypovolaemic state and hydroelectrolyte balance conditions. In the first instance we use a pre-established formula which is subsequently modified in the light of the on-going monitoring (3).

Systemic therapy is initiated by cardiovascular administration of Ant, H2 in amounts proportional to the patient's weight.

We routinely administer heparin in quantities proportional to the patient's weight, together with AT III (10) (antithrombin III) after blood tests, in order to facilitate the action of heparin in conditions of systemic cofactor deficiency.

Early total parenteral nutrition (TPN) is initiated after 72 h, and mixed enteroparenteral nutrition after 6-8 days. The nutritional therapy is guided by monitoring of the nitrogen balance as a function of the patient's metabolic reintegration.

The patient is subjected to weekly cycles of immunostimulation (8) with thymopentin and to periodic infusion (every 10 days) of full-quantity plasma cryoprecipitate human immunoglobulin (7).

The immunological state is investigated every other day by examining the following parameters:

• number of total leucocytes and T lymphocytes
• ratio of T lymphocyte subpopulations
• quantity of serum Ig
• calculation of blood complement (fractions C3 and C4).

No antibiotic therapy is performed. This aspect is dealt with by short-term perioperative treatment and exclusively in clear cases of sepsis, following haematic microbiological analysis (haemoculture) or analysis of the wounds (tissue biopsy) (5).

While it is more or less possible to define and standardize therapeutic protocols for the early surgical treatment and the nutritional and immunological support of the bum patient, the strategy for effective antiseptic treatment of the lesions is much more complex and difficult to define, considering the particular needs that have to be met, such as the use of noncytotoxic topical agents. The complexity of this treament depends on a series of a) anatomopathological, b) microbiological and c) clinical problems (11).

1. Burns are notoriously ischaemic lesions (because of more or less intense and extensive thrombotic phenomena affecting the cutaneous vascular network), characterized by the presence of necrotic tissues, an ideal substrate for bacterial proliferation. This anatomopathological condition invalidates any antibacterial treatment by the systemic treatment. approach, as said above, so that only topical antiseptics can have an important role in the control of bacterial contamination.
2. It is more and more frequently observed in hospitals that the ambient bacterial flora is modified, with the appearance of polychemoresistant bacterial strains selected as a result of prolonged and generalized wide use of antibacterial agents in a confined environment.
3. It is not always possible to use an antiseptic having sure and documented action against a given bacteriological type, since one must take into account the cytohistotoxicity of the product which in particular clinical conditions may counterindicate its use (MIC= minimum inhibiting concentration= lowest concentration of the disinfecting substance's active principle at which bacterial reproduction is inhibited. This process is obtained only during the period of application of the disinfectant).

In the light of the above considerations, it is clear how important the topical treatment of the lesions is in the bum patient and how useful it is to have a thorough knowledge of the microbiological and cytohistotoxic characteristics of the antiseptics at our disposal, together with complete documentation of the microbiological characteristics of the bacterial strains involved. Some years ago we accordingly initiated at our Burns Centre a thorough microbiological depistage to be performed routinely on bum patients (qualitative and quantitative evaluation of wound contamination, haemocultures, urinocultures, etc.), on the medical and paramedical staff (oropharyngeal swabs), and on the hospital structures (medication rooms, balneotherapy tubs, surgical instruments, air, floors, walls, etc.).
We thus obtained a map of the most frequently occurring bacterial strains, with their serological differentiation, on which it was possible to test one by one the commonest clinically employed antiseptics, according to established laboratory methods, in order to establish their effectiveness and to evaluate their MIC.
Our practice is to perform daily balneotherapy in special tubs, with cleansing of the wounds using inert soapy solutions and physiological solution.
Medication, after microbiological assessment as described above, is performed with the application of topical antiseptics such as:

• silver sulphadiazine ointment
• polyvinylpyrrolidone solutions
• 0.5% silver nitrate solution
• Mercurochrome.

Apart from areas at high risk of functional deficit, such as head/neck and the hands, which are subjected to early reconstruction 6 or 7 days after hospitalization, surgical procedures in the burn patient, according to our protocol, are performed on about day 10 post-bum.
The surgical treatment is in two phases: first escharectomy and then coverage of the bloody areas by means of dermoepidermic antografts after haemostasis with human fibrin cement, which also acts as a biological cement. We have used this technique for about 4 years in all surgically operated patients without observing any counterindications. There are considerable benefits due to the greater take of the grafts in an absolute sense (effective haemostasis of the fundus and the cementing effect) and to the reduction in operating time (no suturing material is used), with a reduction in overall blood losses.
In conclusion we will consider the surgical approach in patients in the class IV risk category suffering from burns in such an extensive body area as to require coverage with autologous cultures of epidermis cultured in vitro.

This class includes patients in a critical state because of the extent of their lesions and/or their very severe systemic conditions
The topical and systemic treatment does not differ from that described for Class III patients.
What differentiates the treatment of these patients is the surgical approach for the preparation of areas for the grafting of autologous epidermis cell cultures developed in vitro.
The patient selected for treatment is subjected to a lozenge-shaped full-thickness skin biopsy (about 10 CM2), which is used for cell development.
Surgery is performed at 7-day intervals until day 20 (after the biopsy), at which time it is possible to implant flaps of cultured epidermis (9, 12).
As said before, the preparation of the graft area is of great importance, as the cultures are extremely labile. At the moment of reconstruction the areas must be free of any sort of pollution and their surface must be homogeneous, vascularized and not bleeding (i.e. haemostasis must be accurately performed).
In order to achieve these goals it is decided in some cases to perform escharectomy as far as the muscular fascia (upper and lower limbs), together with temporary application of high-porosity biological or synthetic skin substitutes which will contain hydroprotein losses and prevent bacterial pollution during the single phases of surgical preparation.

RÉSUMÉ. Les Auteurs présentent un index pronostique qui permet de programmer une approche thérapeutique differenciée pour les différentes "classes de risque" des patients brûlés. L'index prend en considération le pourcentage total des brûlures, le pourcentage des brûlures profondes, l'âge du patient, le temps passé entre la lésion et l'hospitalisation, le site de la brûlure, et les maladies associées. Les divers aspects de la thérapie du grand brûlé sont considérés (traitement systémique et fluidothérapie, thérapie nutritionnelle, immunologique et antibiotique, traitement topique et chirurgical). Les Auteurs se réfèrent en manière particulière aux patients de la quatrième classe, c'est-à-dire les patients les plus exposés au risque.

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