ELECTROLYTE CHANGES AFTER BURN INJURY AND EFFECT OF TREATMENT

218

higher influences 3; indeed, the clinical syndrome produced by head injury may closely resemble that produced-, by cardiac arrest when the primary damage is almost all in the cortex and in the basal ganglia." The present study suggests that the pathological features characteristic of primary-impact damage to the brainstem are lesions adjacent to one or both superior cerebellar peduncles, and retraction balls, microglial stars, or long-tract degeneration in the brainstem, but in none of our 7 cases were abnorfrom

malities restricted to the brainstem. We suggest, therefore, that the principal reason for the difficulty in defining primary localised brainstem damage due to a blunt head injury is that it does not exist as a pathological entity. The clinical syndrome is but one manifestation of diffuse brain damage brought about directly by forces engendered at the moment of impact. We thank the staff of the Division of Neurosurgery in the Institute and Prof. G. Forbes and his staff in the University Department of Forensic Medicine for their willing cooperation. Requests for reprints should be addressed to J. H. A. REFERENCES 1. 2.

3. 4. 5. 6. 7.

8. 9. 10. 11. 12. 13.

Johnston, I. H., Johnston, J. A., Jennett, B. Lancet, 1970, ii, 433. Adams, H., Graham, D. I. in Intracranial Pressure (edited by M. Brock and H. Dietz); p. 250. Berlin, 1972. Jennett, B., Plum, F. Lancet, 1972, i, 733. Strich, S. J. J. Neurol. Neurosurg. Psychiat. 1956, 19, 163. Strich, S. J. Lancet, 1961, ii, 443. Oppenheimer, D. R. F. Neurol. Neurosurg. Psychiat. 1968, 31, 299. Adams, H., Graham, D. I. in Scientific Foundations of Neurology (edited by M. Critchley, J. O’Leary, and B. Jennett); sect. x, chap. 6. London, 1972. Tomlinson, B. E. J. clin. Path. 1970, 23, suppl. 4, 154. Nevin, N. C. J. Neuropath. exp. Neurol. 1967, 26, 77. Peerless, S. J., Rewcastle, N. B. Can. med. Ass. J. 1967, 96, 577. Brierley, J. B., Adams, J. H., Graham, D. I., Simpsom, J. A. Lancet, 1971, ii, 560. Graham, D. I., Adams, J. H. ibid. 1971, i, 265. Jennett, B., Graham, D. I., Adams, H., Johnston, I. H. in Cerebral Vascular Diseases, Eighth Conference (edited by F. H. McDowell and R. W. Brennan); p. 163. New York, 1973.

ELECTROLYTE CHANGES AFTER BURN INJURY AND EFFECT OF TREATMENT PAMELA HINTON * S. P. ALLISON † SHEILA LITTLEJOHN J. LLOYD Burns Unit and Department of Biochemistry and

Pathology, Birmingham Accident Hospital, and Department of Medicine, University of Birmingham

Following burn injury, as after other forms of trauma, there is renal sodium and water retention with increased urinary potassium losses. The hyponatræmia in these cases results from sodium deficit but usually from excess rarely water retention and entry of sodium into the cells. These changes may in some patients be reversed by blood-transfusion, by insulin and glucose infusions, or by both together. Improvements in supportive have reduced therapy morbidity and mortality. Summary

Introduction THE

electrolyte changes following injury have been by many workers, including Mooreand

discussed

*

Dr Hinton died on Feb. 13, 1973. &dag er; Present address: Nottingham General Hospital.

Flear.Moore described these changes as occurring in two phases. During the initial phase there is renal retention of sodium and water even when the total body sodium and water are increased by treatment. At the same time plasma sodium and chloride levels fall and renal potassium excretion rises. All these changes are reversed spontaneously during the In severe burns the spontaneous recovery phase. reversal of these changes may be delayed, and they may persist for as long as the burn illness lastssometimes for many weeks or until death. This may occur despite a large positive sodium balance resulting from the administration of large quantities of sodium-

containing crystalloid solutions. We have previously shownthat insulin and glucose therapy results in a large reduction of both nitrogen and potassium losses in burned patients. We show here the effect of insulin on plasma and urine sodium and chloride levels in the same patients. Patients and Methods A total of 64 patients admitted to the

Birmingham

Accident Hospital in 1968 and 1969 were studied. Each patient had burn or scald injuries exceeding 15% of the body-surface. During the first forty-eight hours after injury (the shock phase) all were treated according to the routine regimen of the unit. Plasma was infused intravenously in amounts required to maintain a normal haematocrit and urine output. Oral fluids were also given in a volume equal to the normal requirements for comparable healthy subjects. Local treatment varied according to the dressing trials in progress. Following the shock phase, the treatment of individual patients was varied in certain respects according to their needs. The patients were fed with a high-protein (approximately 100 g. a day), high-calorie (approximately 5000 calories a day) oral diet whenever possible. Vitamin, iron, and calcium supplements were also given. All patients were given cloxacillin (or erythromycin if the patient was known to be penicillin-sensitive) for the first five days. Thereafter, antibiotic therapy was adjusted according to the results of bacteriological in-

vestigations. Initially, blood was transfused whenever the haemoglobin fell below 80% of normal, but in the latter part of the study this criterion for transfusion was abandoned and blood was transfused according to clinical assessment of peripheral perfusion and to changes in urine Na excretion as described previously.4 Initially also, a fall in plasma Na+ to 130 meq. per litre was taken to be an indication for giving sodiumchloride supplements. However, this policy was soon abandoned when it was realised that most of sucb patients had large positive Na+ balances. Approximate sodium balances were assessed by calculation of intake and urine loss, and assuming losses of 150 meq. per day from burn areas and a deliberately high figure of 100 meq. per day for all other possible losses. Whenever a high catabolic rate was found (manifest by a high urea excretion) or urinary sodium excretion of 50 meq. per day persisted in the presence of a positive Na+ balance of more than 500 meq., sodium-chloride supplements were discontinued and the supportive therapy was modified to include a high water intake (at least 3 litres per da) or 1-5 ml. per kg. per l°o area of burn, whichever was greater) and insulin and glucose infusions (as describe previously).3 The infusions consisted of 50% gluCQ5è in water, containing soluble insulin and potassium chloride, giving a daily dose of 600 g. glucose and 200-600 unit; of insulin. The insulin dose was adjusted to maintain

219

0-0.25% glycosuria by the ’Clinitestmethod and bloodglucose levels of 100-200 mg. per 100 ml. Potassium chloride was added in amounts varying from 100 to 300 meq. per day. Urine Na+, K+, and Cl- levels were measured in consecutive twenty-four-hour urine collections and frequent plasma-electrolyte measurements were also made. Results The patients fall into four groups according to their clinical course and the regimen of treatment. Group 1 consisted of 14 patients with mild burn injury involving 15-26 % of the body-surface. In each patient there was a spontaneous reversal of electrolyte abnormalities and recovery was uneventful. The sodium diuresis phase (a rise in urine Na+ excretion and a fall in urine K+ levels such that the urine Na/K ratio rose above 1) was established within five days after injury, and there was no recurrence of sodium retention after this time. All patients received the conventional therapy only, and in no case did the plasma Na+ fall below 130 meq. per litre. The changes in this group are exemplified in fig. 1. Group 2 consisted of 13 patients with more severe burns (up to 65 % of the body-surface) in whom the changes characteristic of the sodium-retention phase persisted or recurred after the fifth day following injury. Conventional therapy was employed in all patients in this group. In 12 patients sodium-chloride supplements were given, since plasma-Na+ levels fell below 130 meq. per litre. This treatment failed to Bloodcause a rise in plasma-Na levels (see fig. 2). transfusion was only given when Hb levels fell below 80% of normal, but in four instances the sodium-

changes

Fi. 1-patient A (aged 26, 20% burns): in plasma and urine electrolytes following mild burn injury with spontaneous recovery and development of the sodium diuresis phase.

Fig. 2-Patient

diuresis changed after blood-transfusion.4 In 5 patients the sodium-retention phase persisted until the burned area had healed. A massive sodium diuresis at that time supported evidence from the approximate Na+ balance calculations that they had been in positive Na balance. In 4 patients the sodium-retention phase persisted in an extreme form. Each died before surgical repair could be completed. The electrolyte changes seen in these patients are exemplified in fig. 2 by patient B, aged 18 years, who had 60% burns. At the time of his death he was in positive Na balance by approximately 2000 meq. per litre, yet hyponatrxmia and renal Na retention had persisted. He was in negative K balance by approximately 1000 meq., yet his plasma-K level, initially low, rose terminally to abnormal levels. Group 3 consisted of 28 patients with major burns (20-65 % of the body-surface) who were at first treated in a similar manner to those in group2, since in each case electrolyte changes of the sodium-retention phase had persisted or recurred five days or more after injury. All were in positive Na balance by at least 500 meq., yet were excreting less than 50 meq. of Na daily. The supportive therapy was modified, usually one to three weeks after injury, at a time when there was clinical deterioration (manifest by lowering of consciousness and hyperventilation) with sodium retention and large negative nitrogen and potassium balances. At this stage sodium-chloride supplements were discontinued, and the water intake, over and above the fluid content of the diet, was increased to 3 litres per day or 1-5 ml. per kg./% area of burn, whichever was greater. Infusions of

B (aged 17, 60% and eventually lethal burn.

burns): electrolyte changes following

Sodium retention and hyponatrxmia persist despite

a

large

a

major

sodium intake.

220 in whom no the and plasma-Na

insulin and glucose were begun. In some instances this treatment was combined with blood-transfusion, if there was clinical evidence of peripheral circulatory failure (superficial venous collapse and delayed

of 50% glucose alone in increase in urine Na was concentration fell.

capillary refilling following pressure on an extremity). 4 patients were given 50% glucose without insulin The effect of insulin and glucose to act as controls. on the electrolyte changes in patient C are shown in fig. 3. A large Na diuresis was obtained and the plasma-Na concentration rose. A fall in plasma and urine K concentration was observed together with a marked rise in the urine Na/K ratio. Clinical also 3 shows the occurred. Fig. effect improvement

treated with insulin and glucose from the shock phase onwards whenever urine Na levels fell despite an adequate Na intake, and whenever urine urea and K excretion In this group the aim was to prevent, if posrose. sible, severe biochemical disturbances and clinical deterioration rather than to treat them when the; had already occurred.

patient D, seen

Group 4 consisted of 9 patients (23-70% of the body-surface) who

with

major burns

were

Urinary Electrolyte Changes with Treatment Changes in urine Na, Na/K ratio, and Cl (meq. per twenty-four hours) with four different treatment regimens are illustrated in fig. 4. The results are shown for the day preceding treatment (day -1), the day when treatment was started (day 0), and the second day of treatment (day + 1). 50% glucose produced no change on its own, thus excluding any osmotic effect as responsible for the marked Na+ and Cl- diuresis when insulin and glucose were infused either on their own or with blood. Bloodtransfusion alone produced a similar effect in some patients,1 although the diminution in K excretion and the increase in Na/K ratio was less than that seen with insulin and glucose, even though a large amount of K (100-300 meq. per day) was given with the

insulin and

glucose.

In order to elucidate the mechanism of the rise in concentration following insulin and glucose, the results are shown in table I of 5 patients who, at the time of their Na+ diuresis, were also put into an increasingly positive water balance by infusion of large volumes of 5 % dextrose. To exclude the error involved in calculating absolute water balance in badly burned patients, the results have been expressed as a change in water balance. For example, in patient E water intake exceeded urine output during the forty-eight hours before treatment by 6’5 litres,

plasma-Na+

Fig. 3-Effects of 50% glucose alone (patient C, aged 24, 65% burns) and insulin+50% glucose (patient D, aged 32, 60% burns) on plasma and urinary electrolytes after major burns. TABLE I-CHANGES IN PLASMA AND URINE

Na

LEVELS DURING TREATMENT ON

6 OCCASIONS

IN

5

PATIENTS

221

Discussion We have previously demonstrated the usefulness of insulin and glucose in helping to reverse the nitrogen and potassium losses which follow injury.a In the present paper insulin has been shown also to reverse the sodium-retention phase of injury in some patients. Probably several factors contribute to sodium retention following injury. That due to circulatory underperfusion can be reversed by blood-transfusion (see fig. 4). In other cases a sodium diuresis could be produced by insulin and glucose either on their own or in combination with blood-transfusion. These were not seen to have any effect in the absence of a positive sodium balance. Table i shows that insulin caused a rise in plasma-sodium concen-

regimens

tration, even though a negative sodium and positive water balance were being achieved simultaneously. The changes in sodium excretion were paralleled by changes in chloride excretion (fig. 4). These data suggest that insulin may have caused sodium and chloride to pass from the intracellular to the extracellular space, and would fit with the observation of Flearthat severe injury may be associated with a failure of cellmembrane function allowing excess sodium and chloride to pass into cells. Zierlerhas reported that insulin not only causes potassium to pass into muscle-cells in vitro but enhances the extrusion of sodium. These studies illustrate to the a therapeutic approach Fig. 4-Changes in urinary electrolyte excretion induced by different treatment regimens (see text). burn illness and emphasise once again the avidity witti wtilcil injured patients the after treatment retain sodium. hours and during forty-eight by They also show that, as in other forms of injury, hyponatrxmia is rarely caused by 8’1 litres, giving an increase of 1-6 litres. sodium deficiency. It is usually due either to excess Effect on Morbidity and Mortality water retention1 or to loss of sodium into the cells,2 or Insulin and glucose produced not only striking both. The mortality figures suggest that improvebiochemical changes in some patients but also an ments in supportive therapy of the burn illness may improvement in their clinical state. It is impossible produce a worth-while dividend in terms of survival. in this study to divorce the respective effects on mortality of insulin and glucose, blood-transfusion, and We thank Mr D. M. Jackson and Mr J. S. Cason for meticulous attention to nutrition and to water and encouragement during this work; the nursing staff of the burns unit of the Birmingham Accident Hospital for help;’ electrolyte balance. The combined effect of the treatthe Medical Research Council for support to one of us ment, described here and in previous studies on burn (S. P. A.); and Dr Glyn Walters, of the department of mortality, is summarised in table 11. Mortality was chemical pathology, Bristol Royal Infirmary, for advice in the appreciably reduced in groups 3 and 4, in which these preparation of the manuscript.

regimens

were

employed.

TABLE II-COMPARISON OF EXPECTED AND ACTUAL MORTALITY IN THE FOUR TREATMENT GROUPS

Requests for reprints should be addressed General Hospital, Nottingham NG 6HA.

to

S. P.

A.,

REFERENCES 1.

Moore, F. D. Metabolic Care of the Surgical Patient. Philadelphia,

2. 3.

Flear, C. T. G. J. clin. Path. 1970, suppl. 4, p. 16. Hinton, P., Allison, S. P., Littlejohn, S., Lloyd, J. Lancet, 1971, i,

1959.

767.

Hinton, P., Allison, S. P., Farrow, S., Littlejohn, S., Lloyd, J. ibid. 1972, i, 913. 5. Cason, J. S., Lowbury, E. J. L. in Recent Advances in Surgery (edited by Selwyn Taylor). London, 1964. 6. Zierler, K. L. Am. J. Med. 1966, 40, 735. 4.

Expected mortality-rates have been calculated from standard charts relating age and area of burn to statistical likelihood of death.’