Annals of Burns and Fire Disasters - vol. X1 - n. 3 - September 1998

DIABETES AND BURNS - PROBLEMS OF DIAGNOSES AND THERAPY

Napoli B., D'Arpa N., Masellis M.

Divisione di Chirurgia Plastica e Terapia delle Ustioni, Ospedale Civico, Palermo, ltaly

SUMMARY. The gradual average aging of the population has led to an increasing number of middle-aged and elderly persons suffering burns as a result of the alterations in glucose metabolism typical at this age which the burn highlights or aggravates. There is bound to be an increasing need to deal with cases of hyperglycaemia that were undetected or kept under control prior to the burn trauma. In view of the scarce amount of literature available, this article considers differential diagnoses between the various conditions of hyperglycaemia and the reasons for administering insulin therapy, with its immediate and long-term risks. Certain parameters are also considered (diuresis, natraemia, urea creatininaemia, plasma osmolarity, glycosuria and glycaemia). The accurate monitoring and interpretation of these parameters is basic to the management of the burned diabetic patient.

Introduction

The literature dealing with the problems of diagnosis and therapy in relation to diabetes in burn patients is extremely limited. The problem is however ever-present and will be increasingly common in future years for the following two reasons:

1. increasing age leads to an increase in the likelihood of being involved in burns accidents
2. the process of aging produces a reduced tolerance of glucose which may become evident as soon as there are conditions of stress.

In our approach to the problem we aim to provide guidelines to be followed in middle-aged and elderly patients suffering from hyperglycaemia.

Importance of differential diagnoses in various conditions of hyperglycaemia

In many cases the hyperglycaernic condition was unknown to the patient prior to the burn. In the absence of anammestic evidence, it is important to establish the nature of the hyperglycaemia. The examination of the various pathological conditions in which hyperglycaemia may be present (Cushing syndrome, acromegaly, lipodystrophic diabetes, haernochromatosis, Werner syndrome, Acantosis nigricans, idiopathic or immunemediated insulin resistance, and serious infection) is theoretic rather than real, as they are clinically well characterized. The problem of differential diagnosis therefore more closely concerns what is known as "stress diabetes", as distinct from diabetes mellitus proper, considering that the clinical manifestations of stress diabetes, as also those of diabetes mellitus, are glycosuria, hyperglycaemia, and absence of ketonuria. However, as stress diabetes (which is the result of a systemic response to the heat trauma) ceases when the burns heal, and as the treatment of hyperglycaernia (whether due to stress or diabetes mellitus) remains the same, being based on the administration of insulin, and as diagnostic tests like the measurement of insulin and C-peptide, as well as glucose tolerance tests, are performed following suspension of insulin, a differential diagnosis between stress diabetes and diabetes mellitus of the second type is of little practical significance. As these investigations are performed after the patient's clinical recovery, immediately before or soon after discharge, they are useful only for future reference and subsequent management of the burn disease.

When insulin treatment becomes necessary and the amount to be administered

Two forms of diabetes mellitus are known to exist:

• insulin-dependent (IDDM), or type one
• non-insulin-dependent (NIDDM), or type two

The treatment of type-two diabetes mellitus is based on diet and physical exercise. If that is not sufficient to keep glycaernia under control, oral hypoglycaernic drugs are generally used. These drugs may however cause hypoglycaemic attacks with few or no symptoms, sometimes leading to mental deterioration, and their use should be avoided in elderly or obese patients and in those suffering from hepatic or renal diseases.' These different treatments, from the asymptomatic untreated phase to when insulin treatment is necessary, from phases when only diet is controlled to when oral agents are used, may correspond to different stages in the disease's natural development. There are however conditions in which - even in patients with well-controlled non-insulin-dependent diabetes - it is necessary to have temporary recourse to the use of insulin treatment.` These conditions are the following:

• psychological stress
• hyperthermia
• sepsis
• surgical operations

Each of these conditions, as a result of the mediation of hormonal and nervous stimuli, induces a state of hypermetabolism and represents an opportunity for the manifestation of hyperglycaemia ("stress diabetes"), latent diabetes, or aggravation of pre-existing hyperglycaemia. All of these conditions can be present in the burn trauma, with the result that insulin treatment becomes imperative in order to prevent the development of severe metabolic decompensation, which in type-two diabetes is manifested in hyperosmolar coma. This type of coma, representing about 10% of hyperglycaemic emergencies (mortality up to 50%), can be precipitated by treatment with thiazides, beta-blockers and steroids. The condition is encountered in some middle-aged and elderly patients, who often present only moderate hyperglycaemia and do not usually require insulin therapy. In about two-thirds of the cases diabetes was not previously diagnosed.
The insulin requirements of patients who really need it may vary rapidly. In a recently reported case, the patient (seriously burned and not previously diagnosed as being diabetic) needed progressively increasing doses of insulin until he required a total of 2104 units per day by continuous i.v. infusion. Insulin dosages can however subsequently be reduced and eventually suspended.' Inglis et al.' described a case of hyperosmolar coma in which initially 16 U/h of insulin were administered, then reduced, and finally suspended after 8 days of treatment. These sudden changes in insulin requirements, if not quickly recognized, can cause an alarmingly rapid hypoglycaemic coma. In the burn patient it is therefore preferable to accept somewhat higher than normal glycaemia levels rather than risk the possible consequences of an insulin overdose.

Why insulin treatment has to be suspended when the patient recovers from the burn wound

Insulin resistance and the sudden reduction in insulin requirements make frequent glycaemia tests necessary. After discharge patients must be followed up by a diabetologist with a view to gradual suspension of insulin - continued use is not advisable. The main reasons for suspending insulin, in the event of temporary use, are the following:

1. the habitual insulin-resistance of these patients can increase their need of the hormone. However the drug's pharmacological action aggravates the state of obesity that is generally present, so that insulin-resistance is accentuated
2. the condition of hyperinsulinaernia produced by this therapeutic approach presents another atherogenic risk in patients in whom one of the most feared chronic complications (and a common cause of death in type-two diabetes) is atherosclerotic angiopathy. For the same reasons, insulin is not used in the treatment of type diabetes until it is really necessary.

Importance of certain laboratory findings

A number of other important factors have to be taken into consideration in the treatment of diabetic burn patients.

1. The finding of glycosuria is not sufficient to establish possible therapeutic measures - for this purpose it is also necessary to perform tests on glucose concentration in the urine and on glycaemia levels. It is in fact possible to find very high glycosuria levels with a glycaemia rate only a little over the threshold level and, on the contrary, absence of glucose in urine showing very high glycaemia.
2. The plasma osmolarity rate, considered alone and not in relation to the degree of concentration of all the solutes that determine it (i.e., electrolytes, urea, glucose), is no indication of the patient's hydration state. Osmolaritycan be increased, when other solutes are normal, merely due to an increase in glycaemia, without the patient requiring liquids.'
3. Natraemia, besides increasing and contributing to the aggravation of hypertonicity due to sugar overload in cases of hyperosmolar coma, may be reduced in diabetic patients. The plasma hypertonicity due to glucose overload, when glycaemia increases slowly, causes a gradual absorption of liquids, as tonicity increases, from the extravascular compartment, with consequent hyponatraemia due to haemodilution. These sodium variations can be explained by the relationship between this electrolyte and concentration of glucose, which is mainly limited to extracellular liquid. A condition of hyponatraemia due to dilution can therefore be dangerous if the glycaemia is corrected rapidly; it is thus necessary to be ready for the sodium increase that follows hyperglycaemia, as there is a risk of hypernatraemia. A number of special formulae permit the calculation of the correct amount of sodium on the basis of the amount of sodium measured. The most commonly used formula is the following:

The treatment of extracellular hypertonicity must also take into account one of its possible complications, i.e. cerebral oedema. It has been seen that extracellular hypertonicity due to an increase in serum glucose levels leads to the passage of intracellular water (cell dehydration) into the extracellular snace. However the brain Possesses a defence mechanism (intracellular development of idiogenic osmols) that enables it to resist dehydration. If the lowering of extracellular tonicity is too rapid, there will be a transfer of water to the brain and, as a consequence, cerebral oedema. It is therefore advisable to administer not only insulin but also hypotonic (0.45%) saline solution, 2.5-5% glucose solution, and potassium salts.

4. The destruction of large quantities of fat and glycogen, which contain and liberate potassium, leads to increased losses in the urine. In severely burned patients with diabetic complications this loss can exceed sodium losses. Thus, in conditions of hypernatraemia, there can be a normal level of serum potassium, or a low level. This condition is inverted with regard to urinary elimination of electrolytes. Also, the ratio of urine potassium to urine nitrogen (normally 2.7/1 mEq/g) - the latter originating mainly from protein degradation - can increase.

Susceptibility to infection and local treatment in the burned diabetic patient

Diabetic patients are notably susceptible to infections of both bacterial origin (especially those caused by Staphylococcus aureus and epidermidis) and mycotic origin (Candida, Mucor), due to an inadequate inflammatory response and reduced white globule activity (chemotaxis, phagoeytosis, and intracellular lysis of ingested bacteria). This susceptibility means that particular attention has to be paid to the local treatment of the burned body areas, the sites of venous and arterial access, bladder catheterization, etc. As cause and effect interact reciprocally, diabetes and infection can set up a vicious circle that may lead to septicaemia and death. 
The use of salicylate vaseline in the local treatment of burns in the diabetic patient reduces their spread and rapidly leads to healing in deep second~degree burn areas, promoting rapid chemical escharectomy in full-thickness burn areas. This may be due to the hypoglycaemic activity of salicylates which are known to reduce insulin hormone requirements. For this reason salicylate vaseline must be used with caution.

Nutritional aspects

Diet restrictions, which are central to treatment in the diabetic patient, do not present any particular indications with regard to the protein and calorie requirements of the burn patient. The nutritional needs of the burn patient who is also diabetic are identical to those of any other burn patient.

Conclusions

We have reached a number of conclusions.

1. The monitoring of glycaemia is of fundamental importance. This is due to the fact that the typical symptoms of hyperglycaemia can be misleading in a burn patient. It has to be considered that while polyphagia rarely occurs in burn patients, polydypsia is generally present and is indeed typical. Polyuria can be caused by hypereatabolism and by renal tubular damage that may derive from the use of antibiotics. We have already said that glycaemia and glycosuria may not be correlated and we would add that glycosuria may also be due to the rapid infusion of hypertonic glucose solution. The monitoring of glycaemia (and the performance of glucose tolerance tests, when possible) is therefore necessary - but also sufficient - for diagnosis.

2. If the onset of polyuria is slow and gradual over a period of several days, in a patient with high glycaemia, there are sufficient grounds for suspecting that the condition of plasma hypertonicity responsible for the increased sugar load in the urine is about to be further complicated. If the hyperglycaemia is not kept under control, the increase in (osmotic) diuresis will lead to dehydration, a reduction in renal blood supply with a consequent loss of urinary elimination of glucose, and a further increase of glycaemia to values that may exceed 900 mg/dl. The hyperosmolar coma that thus develops (the pathogenesis of which explains the fact that this definition is reserved to cases in which it is an overload of solutes, rather than a loss of liquids, that leads to hypertonicity and dehydration) is therefore characterized by all the signs of dehydration and prerenal renal failure: hypernatraemia and a marked increase in plasma osmolarity, urea and creatininaemia.' The monitoring of diuresis, which is relatively important from the purely diagnostic viewpoint, if associated with that of the other laboratory parameters that are altered by non-ketotic hyperosmolar syndrome in non-insulindependent diabetic patients (glycaemia, glycosuria, natraemia, urea, creatininaemia and plasma osmolarity), becomes of fundamental importance in the management of the burned diabetic patient.

3. The use of the insulin hormone is not without its risks, which may be either immediate (convulsions and hypoglycaemic coma related to the rapid change in insulin requirements) or delayed (elevated atherogenic risk). We would also add that as insulin therapy in these patients is restricted to limited periods of time, it is essential to use highly purified insulin in order to avoid creating insulinresistance with an antibody basis.

RESUME. Le vieillissement moyen de la population, avec l'incrément conséquent du numéro des personnes d'un certain âge et des vieux atteints de brûlures, à cause des altérations du métabolisme du glucose typiques de cet âge et que la brûlure met en évidence ou aggrave, dans un proche avenir créera plus fréquemmement la nécessité d'affronter des cas d'hyperglycémie non identifiée ou de toute façon bien contrôlée avant l'épisode traumatique. Les Auteurs soulignent le manque de données dans la littérature scientifique, et considèrent la diagnostic différentiel entre les diverses conditions d'hyperglycémie et les motifs pour la nécessité du traitement insulinique, avec tous les risques immédiats et à long terme que ce traitement peut présenter. Ils examinent en outre le comportement de certains paramètres (diurèse, natrémie, urée, créatininémie, osmolarité plasmatique, glycosurie et, naturellement, glycémie), dont le monitorage et l'interprétation correcte sont d'une importance fondamentale dans la gestion des patients diabétiques.

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