The Author
TRAUMATIC shock, whatever the causes, is accompanied by a decrease in blood volume and pressure. Increased capillary permeability, accepted by many as a most important feature of shock, results in loss of blood plasma into surrounding tissues. Increased concentration of the red blood cells following loss of plasma is readily measured by hematocrit readings.
Transfusions of whole blood or plasma, or even of solutions of pectin, gelatin, or glucose and saline restore the pressure and volume of blood.
As a supplement to such well-known therapy, in fact as an occasional emergency substitute, this paper offers clinical evidence of the value of vitamin C given orally or intravenously.
As reported in Science, 1 a group of surgeons in a Western city were highly successful in treating patients collapsing after operations, by intravenous injections of 500 mg. or even 1000 mg. of vitamin C (in sterile, partly buffered solutions). It is generally accepted that a very low level of ascorbic acid is one of the causes of increased permeability of the capillary wall with consequent loss of plasma. Excess of this vitamin makes for a healthy, normal condition of the capillaries, possibly by acting as a detoxifying agent, or possibly by combating tissue anoxia. In a recent war year, 1943, an amazing number of ampoules of vitamin C solution were prepared for some countries, as yet not disclosed. Presumably valuable clinical information was obtained.
At my suggestion, Dr. Harold G. Kuebner of Mercy Hospital, Pittsburgh, kindly consented to extend these earlier experiments. His report in April, 1945, follows, with the caution that comparisons are difficult. “However, I can tell you that during the past six months I have given massive doses up to 2000 mg. of vitamin C intravenously, both pre-and postoperatively to 50 seriously ill patients who underwent major abdominal operations. These were gastric resections, seriously complicated gallbladder and liver operations, rectal resections, and bowel resections, not simply run-of-mine laparotomies.
“I am definitely convinced that these cases have made a more prompt and more vital convalescence with less serious complications or sequellae than 50 such cases which were operated on without the aid of vitamin C.”
In battle, auto accidents, or accidents in home or factory, there may be a dangerous delay in receiving adequate medical aid. Consequently it was evident that oral administration of vitamin C tablets — requiring no technical skill — should be tested for influence in lessening secondary shock in spite of a belief that some vitamins are more effective when given by injection. The minor surgery of tooth extraction afforded convenient opportunities for the test.
Dr. Charles Wilbur Carrick of Oberlin, Ohio, was the first dentist to cooperate (in 1942) and he has continued ever since with great enthusiasm. He was advised to give the adult patient 500 mg. of vitamin C, by mouth, from 30 to 45 minutes before tooth extraction. Admittedly, only a lesser fraction of such patients without aid of ascorbic acid would complain of shock or postoperative weakness, yet, in many cases, shock is quite severe. Over 30 years ago, Dr. Martin H. Fischer insisted that tooth extraction was not a trifling affair, but required more or less postoperative rest.
Several other dentists cooperated with generally excellent results. Since little or no postoperative weakness was reported, out of perhaps 2,000 cases, it seemed fair to credit some value to the oral use of vitamin C. A few brief statements from cooperative dentists follow:
Dr. George M. Quinn of Chicago reporting for the five dentists of his group wrote: “We used 900 mg. of vitamin C giving it by mouth in doses of 100 mg. each, three times daily for three days before the extractions. With this, we used 7.5 grains of sulfadiazene every four hours for three days. After the extraction we used the same dosages as before. Sulfadiazene was increased to 15 grains every four hours and then reduced to 7.5 grains every four hours for the next two days.
“Shock was almost completely eliminated, as well as severe postoperative pain. In none of the cases did we have muscle trismas.”
Dr. Quinn added the sulfa treatment on his own initiative. It should be stated that he receives a large number of very difficult extraction cases sent by other dentists.
Dr. Harold L. Aylesworth, Cleveland Heights, Ohio, reported: “We have had a chance to administer vitamin C, as recommended by you, in severe surgical cases to the same patients in whom we had previously observed shock. The lack of shock in case after case was so evident that I can enthusiastically say that large doses of vitamin C certainly do seem beneficial in the alleviation of shock.”
Dr. B. E. Saunders, Elyria, Ohio, wrote, “There was very marked freedom from shock in most of the cases (about 200) given 250 or 500 mg. of vitamin C. There were no dry sockets and these patients were more relaxed in the chair.”
Dr. Paul J. Aufderheide, Cleveland, reported: “Twenty-seven patients that I had operated on before and proved neurotic, were given 250 mg. of vitamin C. These patients experienced less reaction in comparison to their previous experience.”
As an illustration of an extreme case it may be added that a patient having a dead brittle molar extracted was in the chair two hours. The dentist urged him to go home to bed and to take codeine. However, the patient went at once to a gay social gathering and returned home after six hours “feeling fine.”
These results in dentistry seemed to justify further tests in major surgery.
With a view to emergency use of vitamin C tablets by wounded soldiers, I asked Dr. Harold G. Kuehner, who has great numbers of coal mine accident cases to care for, to have his first-aid staff administer 500 mg. of vitamin C orally to the injured men at the mine in order to help them during the delay in transportation to Mercy Hospital, Pittsburgh. In July, 1945, he wrote as follows:
“We have used vitamin C tablets in approximately 35 assorted cases of miner’s injuries to date. We have not used it on the very simple ones nor on those with some degree of early shock. This group includes three badly fractured pelves, a fractured humerus, a fractured femur, and two chest crushes. The remainder were lesser fractures, contusions, etc. Of course, the evaluation of results is extremely difficult because of the fact that the reports are all relative and personal, but I am thoroughly satisfied that there is betterment in these cases as compared with similar ones. When they reached the hospital we seem to be able to go ahead with vital procedures indicated more readily than when we were not using vitamin C.”
Dr. George U. Curtis of Ohio State University Medical School kindly consented to make some preliminary tests of the value of vitamin C in preparing patients for major operations. He reported as follows: “We have made a number of preliminary tests with vitamin C tablets giving them preoperatively to patients who were to undergo severe surgical operations. These observations have been encouraging.” Later, “We have continued to use vitamin C preoperatively. The clinical results are good. However, they should be more carefully controlled before being presented.” On April 8, 1946, he wrote, “There is now little doubt of the value of vitamin C in the prevention of shock.”
Dr. R. H. Aldrich, Boston, wrote in March, 1944, “I have been using vitamin C in the treatment of shock for over a year and am very well pleased with the results. Most of the cases in which it has been used have been severe burns but I have also used it on preoperative cases in an attempt to lessen surgical shock, with good results so far.” Later he wrote, “Since 1944, I have been using vitamin C routinely to lessen traumatic shock and preoperatively to prevent or lessen surgical shock. The end results were uniformly good.”
Dr. R. W. Bradshaw had a patient in the Oberlin College hospital with serious illness complicated by alarming bleeding into the urine. My suggestion that capillary weakness might be corrected by 500 mg. of vitamin C was adopted and the bleeding stopped early the next day.
Two cases of chronic bleeding of the gums and one of repeated nose bleeding (following prolonged sulfa drug treatment) were promptly relieved by large oral doses of vitamin C. Six more operations, most of them abdominal, were accompanied by administration of 500 mg. of vitamin C an hour before. Freedom from shock and speed of recovery were gratifying to the surgeons.
The value of excess vitamin C in wound healing is generally recognized but its relation to shock prevention has not yet found general favor. However, one or two references to the literature may be interesting.
McDevitt, Duryea, and Lowenstein 2 believe:
“Vitamin C plays a definite role in the picture of traumatic shock.”
Wolfer 3 states: “The deficient patient should receive 1,000 mg. of ascorbic acid daily for ten days before any surgical procedure is attempted and this should be continued until wound healing is complete.”
Andrus and Barnes 4 agree and add: “For the poor sick patient not frankly deficient in vitamin C, smaller doses (200 mg.) may suffice.”
Miss Margene Anderson cooperated in an effort to learn the time required for peak concentration in blood plasma after oral administration of vitamin C. Data are taken from her publication 5 and from personal communications. With 20 healthy people, after a few days on a fasting level, the vitamin C content of blood plasma fell to a few tenths of a milligram per 100 cc. All were then given 250 mg. of the vitamin by mouth for the first series. Maximum concentrations were observed in one or two hours. On repeating the experiment with higher intakes, the peak was generally reached in two or three hours. Number of people reaching peak concentration in given time:
|
Dose |
1 hr. |
2 hrs. |
3 hrs. |
4 hrs. |
|
250 mg. |
7 |
10 |
3 |
0 |
|
500 mg. |
1 |
9 |
10 |
0 |
|
750 mg. |
3 |
8 |
8 |
1 |
|
1000 mg |
0 |
8 |
11 |
1 |
Apparently the tissues removed this vitamin from plasma quite rapidly and so only after saturation is a peak concentration attained in the plasma. Helpful effects in the tissues may occur sooner than the plasma reading indicates. After six hours, the blood plasma concentration of most of the people given only 250 mg. returned to the fasting level, but with those given 500 mg. or more, the plasma concentration after six hours ranged from 0.2 mg. to 0.7 mg. per 100 cc. higher than the fasting level. Concurrent twelve-hour urinary excretion showed that the larger the test dose of vitamin C (within the limits stated) the greater the amount retained in the body. There was not much gain on increasing the dose above 500 mg., but it was clear that 500 mg. was distinctly superior to 260 mg.
With intravenous injections a greater percentage of vitamin C administered was lost in the urine (in the first four hours) than when given orally, ranging from 25 to 65 per cent. The peak concentration in plasma after intravenous injections was reached in three to five minutes but the high plateau level was of distinctly shorter duration than in cases of oral administration.
In my own laboratory, one person’s plasma level, after oral Intake of this vitamin, rose in 46 minutes from 0.60 mg. per 100 cc. to a peak of 1.51 mg. An hour later it was 1.48 mg. With another person, plasma level rose in 75 minutes from 0.44 mg. to a peak of 1.10 mg.
If capillary loss of plasma is accepted as the primary feature of traumatic shock, the possibility of increase in capillary permeability by action of toxic products deserves careful consideration. There has been much controversy over this toxic theory yet there is no debate on the value of adequate amounts of vitamin C in helping maintain a healthy condition of the capillary wall.
It is possible that vitamin C acts as a detoxifying agent in shock treatment (whatever the toxins may be) as it has been shown to be in lead poisoning, 6 in the disturbances caused by organic arsenic and bismuth compounds, sulfa drugs, 7 and factory dusts. There may be some significance in my finding that histamine and vitamin C in the presence of oxygen, react with accelerated destruction of both.
Dale 8, 9 and associates blamed histamine in traumatic shock or products of protein cleavage due to bacteria in severe infections for the loss of tone and increased permeability of capillary endothelium.
Harkins and Harmon 10 report loss of plasma-like fluid from the blood stream in burns, freezing, pneumonia, bile peritonitis, acute pancreatitis, and other conditions. Barsum and Gaddum 11 observed a five-fold increase in the concentration of blood histamine during the first week after severe burns. Lewis 12 believed that the fluid lost from circulation on prolonged exposure to cold was caused by histamine-like substances released from injured cells and acting on the walls of blood vessels.
Slotkin and Fletcher 13 found that ascorbic acid, by decreasing capillary permeability, is of great value in the complication of “wet chests” that sometimes follows prostatic surgery in elderly, debilitated patients. It is a valuable adjunct, they stated, in tiding patients over the critical postoperative period irrespective of the blood levels or amounts of deficiency demonstrated to be present before or during the operation.
The effect of anoxia in shock is stressed by several workers. It would seem that the oxidation-reduction cycle of vitamin C may be of value in combating anoxia. Andrus 14 states:
“There would seem to be fairly uniform agreement that oxygen utilization is diminished in shock.” Krogh 15 and others emphasize the fact that anoxia by damaging capillary endothelium and thus increasing capillary permeability, is the second major factor in shock. Blalock 15 asks for additional information on the question: “Are vitamin C and thiamin, in the absence of deficiencies, helpful in the prevention and treatment of shock?”
From The Ohio State Medical Journal, Volume 42, December, 1946, Number 12, pp. 1261-1264
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