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THE study of the treatment of burns with ascorbic acid was undertaken while the author was a member of the Armed Forces during World War II and continued at the Greenpoint Hospital, Brooklyn, with the assumption that the manifestations observed in the burned patient were probably due to an overabundance of histamine and histamine-like substances in the body tissues.1,* The hypothesis was carried still further, based on the probability that the sudden destruction of tissues by the burning agent first decomposes the protein molecules in the tissues into alpha-amino acids by a process similar to that of the proteolytic enzymes in digestion. These amino acids may be decomposed further, not according to the normal method of deamination and oxidation but by losing carbon dioxide from the carboxyl group (decarboxylation) with the formation of a corresponding alkylamine, as
R—CH(NH2)COOH—> (-CO2)—>R—CH2NH 2.
Various studies have shown that the monoamines, such as tyramine and histamine, have a powerful physiologic action even in minute quantities. Histamine when injected into the body promptly causes increased arterial tension by its direct action on the arteriolar wall, and later a fall in blood pressure results from increasing capillary permeability. This would probably explain the hyperemia, blister formation, accumulation of interstitial fluid, and shock that is observed in the burned patient.2, 3
An idea was conceived that since one of the physiologic actions of ascorbic acid is to maintain vascular tone, especially of the vascular endothelium, ascorbic acid might counteract the toxic actions of alkylamine-like histamine. Experimental studies carried out by myself on rabbits, employing histamine and ascorbic acid, proved this to be true.
Many researchers have demonstrated considerable alterations in the metabolism of ascorbic acid in burns. Lam has reported a decrease in the plasma ascorbic acid concentration in patients with extreme burns.4 Clark and Rossiter, Harkins, and Uzbekov have reported decreased ascorbic acid content of the adrenal cortex in burned guinea pigs and rabbits.5, 6, 7 Ludening and Chanutin studied the adrenal cholesterol and ascorbic acid content after injury, which they found to be disturbed.8
During the course of the study, 62 cases of burns were treated and observed. These ranged from mild to severe types and were caused various agents such as hot water, hot grease, gasoline explosions, chemical agents, etc. The treatment of burns with ascorbic acid was directed primarily as an adjunct in the relief of pain and shock, immediate care of the local wound, handling of the metabolic problem of burned patient, and toward the reduction of the time interval necessary for the preparation of skin grafting of markedly destroyed areas.
In treatment, the ascorbic acid was used both locally and parenterally, either per os, intramuscularly, or intravenously when vomiting or shock was present. If there was no immediate necessity to institute shock therapy, the burned area was cleansed with sterile water and gauze, or with ether soap if greasy, and a 1 per cent solution of ascorbic acid in normal saline or distilled water was applied. No attempt was made at debridement except to remove any foreign bodies that may have been present. The solutions may be applied to any part of the body without harmful effects. This includes eyes and mucous membranes such as mouth and throat. It is of interest to note that the hoarseness and pain resulting from swallowing smoke may be alleviated in a short period of time either by gargling or spraying the throat with a 1 per cent solution of ascorbic acid in normal saline. When it is felt inadvisable to use the ascorbic acid solution, a 2 per cent ascorbic acid ointment in a water-soluble base may be employed. This ointment was also employed in the continuation of treatment of the burned area. The solution was normally used only during the first forty-eight to seventy-two hours following the burn, and the areas were kept constantly moist during this period. The originally applied soaked dressings were not changed but kept moist. No attempt was made to use compression dressings.
Of noteworthy interest is the fact that when the solution was applied to the burned area, there was an almost immediate alleviation of pain, which in most cases continued, thus bringing down to a minimum the use of morphine. Studies by Elman and Beecher demonstrated the harmful effects of morphine when employed during treatment of burns and injuries.9, 10
As a part of the general supportive treatment in moderate and severe burns, ascorbic acid was given in doses ranging between 300 and 2,000 mg. daily in divided doses, either per os or parenterally. This was in addition to the quantity used in local treatment. Children received 300 to 900 mg. daily and adults 500 to 2,000 mg. This dosage was continued until there was improvement. At no time were deleterious effects from the drug observed. Of interest was the fact that after the first or second day following a severe burn, when there is usually a suppression of urine with hemodilution lasting until about the fourteenth day, treatment with ascorbic acid kept the urinary output at almost normal levels.11 Later there was a definite increase in the urinary output. Apparently the ascorbic acid acts as a physiologic diuretic and possesses the possibilities of preventing renal ischemia that is observed in the severely burned.12
Furthermore, the local application of the 2 per cent ascorbic acid ointment to moderately severe and severely burned areas in the continuation of treatment of the acute phase reduced the time interval necessary for skin grafting. The daily application of the ointment produced a healthy granulation tissue bed with practically no redundancy as observed in the use of such agents as sulfanilamide ointment, Furacin, or sterile vaseline dressings. Local edema, which usually interferes with the proper take of a skin graft, was down to a minimum.
Since ascorbic acid is a mild oxidizing and a strong reducing agent, it astringent properties as a local wound dressing. These properties are similar to those found in hydrogen peroxide. Because of that, very little antibiotic therapy was necessary. Antibiotic treatment was employed only in severe cases and where undue secondary infection had set in. Where marked sloughing of the wound was present, a 0.5 to 1 per cent acetic acid solution or a solution of penicillin in normal saline, containing 1,000 units of penicillin per cubic centimeter, was used daily in conjunction with the ascorbic acid ointment dressings.
In the estimation of the severity of a burn, Berkow’s method of percentage of skin surface and degree of the burn was employed. Comparative studies were not feasible since one rarely observes burns which are alike in all respects. Furthermore, the physical status of the patient at the time he was burned is a factor which interferes with comparative studies. It has been shown that the poorly nourished patient who has suffered a burn does not do as well as the well nourished.13 However, from close clinical observations it is felt that the use of ascorbic acid in the burned patient will alter his course considerably. Remarkable improvement is noted in burns of lesser degrees and a shortening of the healing period of burns of more severe degrees.
Case 8.—J. R., well-nourished white male, age twenty-two, suffered first and second degree flash burns involving approximately 30 per cent of his upper body surface. This included both arms, anterior chest wall, neck, and head, and resulted from a gasoline explosion when his plane collided in mid-air with another (Fig. 1). When first seen, which was one and a half hours following his landing by parachute on the pound, he was in severe pain. An hour before, he had been given a syrette of morphine (solution morphine tartrate, ½, grain in 1.5 cc.). A 1 per cent solution of ascorbic acid in normal saline was applied to his wounds, and there was almost immediate relief of pain. This relief of pain continued, and no further morphine had to he given. One unit of plasma was given prophylactically six hours later. He began taking nourishment by mouth as soon as he was relieved from pain and continued on a regular diet throughout his hospital stay. His temperature, pulse, blood pressure, and respiration remained within normal limits throughout the treatment period. The daily urinary output was normal, and there was no weight loss. He made an uneventful recovery in a little over a month.
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Fig. 1. First and second degree flash burns
involving |
Cases 40 and 41.—C. B., white male, age fifty-five, and T. B., Negro, age twenty-one, as a result of a gasoline explosion, suffered similar flash burns at the same time, involving the neck, face, scalp, both hands, and wrists of each. These were second degree burns involving 8 per cent of the head and neck and 10 per cent of both hands and wrists (Fig. 2).
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Fig. 2. Second degree burns involving 18 per cent |
Both were well nourished and presented a non-contributory past history. The head and neck regions were treated during the first seventy-two hours with a 1 per cent solution of ascorbic acid in normal saline, followed by daily dressings with a 2 per cent ascorbic acid ointment. The hands and wrists were treated, at first, with sterile vaseline gauze and compression dressings, followed by dressings with Furacin ointment. Each received per os 200 mg. of ascorbic acid four times daily throughout the treatment period.
C. B. had a rise in temperature to 103.4 F. on the fifth hospital day. This came down gradually to normal on the eighth hospital day and remained within normal limits until discharge. T. B. had a rise in temperature to 100.6 F. on the sixth hospital day. Thereafter, it remained within normal limits until discharge. The daily urinary output of each was adequate. Their general condition throughout the hospital stay was good, and they lost no weight.
At the end of three weeks, the head and neck of each was healed. The hands and wrists, at the end of this period, were still discharging serosanguinous exudate and required approximately thirty days more for complete healing.
Case 46.—R. C., white male, age two and one-half, suffered second and third degree burns of his anterior chest wall and abdomen, involving approximately 15 per cent of body surface, when his clothing caught fire (Fig. 3). He entered the hospital one week following his burn. The wound was infected, and his nutritional state poor. He was placed on a high caloric diet and was given multiple vitamins which included 900 mg. of ascorbic acid in divided doses per os. The wound infection was cleared up, at first by intramuscular penicillin and later by a daily local application of a solution of penicillin in normal saline (1,000 units per cc.), followed by a dressing of a 2 per cent ascorbic acid ointment. The wound filled in by gradual epithelization and required no skin grafting. Complete epithelization occurred in approximately five months without undue scarring. His general condition throughout his hospital stay was very good, and he gained considerable weight.
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Fig. 3. Second and third degree burns involving |
Case 55.—M. L., a fifty-six-year-old, well-nourished white male, was admitted to the hospital shortly after receiving flash burns from an oil burner, involving the right side of his face, neck and shoulder girdle, and right arm and hand. These were second degree burns of the face, neck, shoulder girdle, arm, and hand, and third degree burns of thumb, index finger, and middle finger. The total area of body surface burned was approximately 25 per cent (Fig. 4). He gave a history of drinking alcohol in moderate amount for many years. Apparently, he had also been eating fairly well for he was well nourished. There were no signs of intoxication on admission.
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Fig. 4. Second and third degree burns involving |
The burned areas were treated during the first forty-eight hours with a 1 per cent solution of ascorbic acid in normal saline, followed by daily dressings with a 2 per cent ascorbic acid ointment. During the first few days, he was given 500 mg. of ascorbic acid intramuscularly three times daily. This was followed by 300 mg. of ascorbic acid four times daily per os. He was placed on a high caloric diet and received penicillin daily during the first week.
His general condition was good throughout his hospital stay. The temperature, pulse, and respiration remained within normal limits. His daily urinary output was normal. On the fifty-second hospital day, his wounds were healed with the exception of the finger tips. These epithelized gradually and were healed, without undue scarring, on the sixty-ninth hospital day.
Case 56.—J. G., a thirty-nine-year-old white L well-nourished, with a noncontributory past was admitted to the hospital shortly after suffering flash burns from an oil burner, involving his face, both hands, and wrists. These were second degree burns. The total area of body surface involved was approximately 12 per cent (Fig. 5). The burned areas were treated during the first forty-eight hours with a 1 per cent solution of ascorbic acid in normal saline, followed by daily dressings with a 2 per cent ascorbic acid ointment. He received 300 mg. of ascorbic acid four times daily per os throughout his treatment period and was on a regular diet.
On the third hospital day, his temperature rose to 101.2 F. Penicillin brought the temperature down to normal on the seventh day, and it remained within normal limits until discharge. His daily urinary output was normal. He was discharged on the fifteenth hospital day as healed.
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Fig. 5. Second degree burns involving |
From observation of the cases studied, it is felt that ascorbic acid can play a powerful role in the treatment of burns. In minor burns it is adequate in alleviating pain and hastens the healing period. In the severely burned it aids in combating the accumulation of the toxic protein metabolites. It lessens the need for extensive supportive therapy; however, it does not eliminate such immediate supportive therapy as adequate fluid needs of the body, replacement of losses of sodium and potassium ions, electrolytes, and acid-base balances which are so vitally important in the treatment during the acute phase of a burn. This is best accomplished by the judicious use of whole blood transfusions. Plasma is felt to be not as efficacious as whole blood. In a series of patients treated with large amounts of plasma, the edema in the burned areas remained for longer periods of time than it did in those patients treated with whole blood and an electrolyte solution.11, 14 This was probably due to an escape of relatively large amounts of protein into the extravascular spaces of the burned areas.
Whole blood transfusions should be given to all severely burned cases, especially when there is low blood pressure or hemoconcentration. Hemoconcentration is not necessarily a contraindication to blood transfusion. 14 If found necessary, as much as 1,000 to 2,000 cc. of whole blood may be given during the first twenty-four hours. The balance of the fluid needs of the body may be supplied by the use of a sodium and potassium containing electrolyte solution.15 This solution should include 1,000 mg. of ascorbic acid plus the other water soluble vitamins. The judicious use of both will have an osmotic effect on the protein molecules and will reduce the existing hemoconcentration as well as keep the urinary output above 1,500 cc. per day.
Because ascorbic acid therapy, both locally and parenterally or per os, hastens the healing of wounds by producing healthy granulation tissues and reducing local edema, skin grafting may be accomplished at the earliest possible date. It thus reduces the chances of wound infection and prolonged convalescence from open wounds. As a result, the morbidity and mortality rates of burns may be kept down to a minimum.
Ascorbic acid was used, both topically and per os or parenterally, in the treatment of burns. Clinical observation of the cases studied showed that ascorbic acid is capable of alleviating pain in minor burns, hastens the healing period, aids in combating the accumulation of toxic protein metabolites in the severely burned, and reduces the time interval necessary for skin grafting.
129 Clarkson Avenue
Sincere appreciation is extended to Dr. Harry Feldman and his surgical staff and to the resident and nursing staffs of the Greenpoint Hospital, Brooklyn, for their assistance and cooperation in this study.
* A generous supply of ascorbic acid was supplied by Hoffmann-La Roche. Inc., Nutley, New Jersey, for a portion of this study.
From The New York State Journal of Medicine, Volume 51, October 15, 1951, Number 20, pp. 2388-2392
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