Prevention Of and Defense Against Operative Shock by Vitamin C

by Dr. Zs. Pataky, Dr. L Molnár and Dr. I. Pálla

From the I. Surg. University clinic Budapest
(director: Professor Dr. E. Hedri)

The investigations of Popov and Cagerejvili first reported the connection between shock and vitamin C. Experiments with guinea pigs showed that animals fed 10 to 20 days with ascorbic acid-free feed are particularly sensitive to pain stimulus and are immediately sent into shock by primary stimulus of the Nervus ischiadicus. Gyernovski and Lebedinskaja determined that traumatized organs lose their vitamin C content very quickly. Diel and Neumann observed the difference in vitamin C content of the human nervous system under normal and pathological conditions. Zilva observed in guinea pigs the extreme depletion of vitamin C under anesthesia and under the local effect of Novocain. Svirbeli determined the reduction of ascorbic acid content after anesthesia in rat liver, Kochel and Michel against it in the rat adrenal gland. Belsin, Laubel, Nafziegel, in their work entitled “Effect of Narcosis and Operations on the Vitamin C Budget” dealing with their animal experiments, draw the clinical conclusion that a vitamin C-poor organism loses its ascorbic acid reserve under narcosis, and that operations - even simple test laparotomies - act detrimentally on the regeneration of the organism and reduce the prospects of the fight against infections. All the authors as well as Silocev and Mergold maintain that preoperatively-administered vitamin C, in the form of commercial preparations and raw fruit [??-Brom und Rohobst], plays an important role in the prevention of shock. Hochwald, Recht, Gerloczy and others prevented anaphylactic shock in guinea pigs by preoperative vitamin C doses. According to Solomonica success is had even if vitamin C and allergens are given together during new inoculations. Hochwald poses the hypothesis that under anaphylactic shock vitamin C prevents histamine formation, and that in shock the components belonging to the redox system like glutathione, cystein and ascorbic acid are used in increased measure. Well known is the favorable effect of ascorbic acid on the acceleration of blood clotting, bone and callus development and diuresis (Abbasy); it reduces fever and the permeability of cell membranes, and promotes phagocytosis. The investigations of Jeney and Korpássy, whose animal experiments clarified the significance of vitamin C in wound healing, deserve attention.

Older sources treat the functional mechanism of ascorbic acid of only minor importance. Also unspecified is the most important characteristic vitamin of C, i.e. that of its anti-schock mechanism. Therefore we just directed our attention in the course of our experiments toward this anti-schock mechanism. At first we observed, in what respect the organism’s lack of vitamin C during the winter months affects wound healing and post-operative complications. With patients admitted operations, the vitamin C content of the blood and the urine was determined; it was established that in 23 of 35 cases in which the vitamin C level of the blood remained under 0.4 mg%, the urine was quite devoid of the vitamin. 3[00] to 500 mg vitamin C was given daily to these patients (over 3 to 5 days, approximately 1500 to 2000 mg total dosage), whereby the vitamin C content of the blood could be increased to a level of 1 to 2.5 mg%. The general feeling and condition of the patients improved substantially, and in this way the prepared patients remained immune from operative and post-operative shock. These observations formed the results for further investigations intended to clarify the preventative or eliminatory action mechanism of vitamin C.


(Clinical Case Studies)

In 40 cases the vitamin C level of the blood and urine was confirmed preoperatively, during the operation and post-operatively. Results:

I. 1. With 30 patients under ether narcosis whose vitamin C level exceeded 0.4 mg%, the level decreased according to the quantity of ether administered. After inhalation of 200 g ether, vitamin C could no longer be detected in the blood.

2. In the same 30 cases the post-operative quantity of ascorbic acid in the urine (obtained by catheter) increased substantially.

3. In this group a steady depression of blood pressure was observed during the operation.

II. With 10 operations under Novocain anesthesia, the reduction of the vitamin C level in the blood and the increase of the same in the urine corresponded to the operation’s duration and difficulty (with appendectomies less, with intestinal resections more).

These investigations led to the hypothesis that the lowering of blood pressure during operations has a certain relationship with the depletion of vitamin C; therefore we gave large vitamin C doses to 80 patients admitted for operations. On the basis of uniform criteria we examined the same patients for changes in blood pressure, pulse, respiration, blood sugar, potassium and calcium coefficients, qualitative and quantitative blood picture, as well as the absolute eosinophil count, preoperatively, during the operation and 24 hours after the operation. In all cases the vitamin C content of the blood and urine was determined.

These 80 patients were divided into 2 groups. The 50 patients of the first group had a vitamin C level over 0.4 mg%. The details of the above-mentioned investigations showed with these patients almost normal values, normo- to hypertonic. From these patients the first 25 received vitamin C only during the operation, in the period of blood pressure depression.

With a single dosage we observed the best results over 500 mg, observing an effect thereby of a two-phase curve in the alteration of tension. The effect of the injection given after the blood pressure depression was that the tension increased within 1 to 2 minutes by 20 to 40 mm Hg; within 2 to 3 minutes it dropped to the original value.

Thereafter a constant blood pressure rise was observed, which resulted in 10 to 15 minutes after the injection - depending on the size of the blood pressure depression - an increase of 50 to 100 mm Hg. The blood pressure thus reached the original level, even exceeded the same in some cases around 10 to 20 mm Hg. The singly-administered 500 mg vitamin C quantity was not adequate in preventing those blood pressure depressions which occurred during the operation as consequence of pain or the conversion of local anesthesia to narcosis. In these cases a quantity of 500 mg vitamin C had to be given anew in order to bring the blood pressure to the original level.

The other 25 patients received a 500 mg vitamin C dose 10 to 15 minutes preoperative, intravenously. Consequently both the psychological blood pressure increase following the blood pressure lowering were absent, as well as the evoked blood pressure decrease from lumbal [lumbar?] anesthesia or from narcosis drugs. During the operation however a new vitamin C administration - because of the above-mentioned reasons - could not be avoided. The total quantity of vitamin C given did not exceed 2000 mg in any of the group. The effect of vitamin C is independent of whether it proves necessary to give a blood plasma transfusion or different infusion solutions during the operation. This statement is confirmed by our own observations, where vitamin C without infusion or transfusion was successfully applied.

In the second group belonged 30 hypotonic patients, whose blood pressure measured 100 mm Hg lower. Here the vitamin C level of the blood reached only 0.4 mg% or 0. (on the possible connections of hypertonia and C-avitaminosis we will report later). The dosage of vitamin C was done in this group partly for lowering the tension, partly preventively, with similar success, as in the other group.

A large single dose of vitamin C could thus in no case ensure a long-lasting blood pressure increase, and the blood pressure depression during the operation could become balanced only by additional vitamin C doses. Therefore an infusion procedure had to be applied, which holds the vitamin C level of the blood at a constant capacity, and which is capable of keeping up with the increased depletion of vitamin C during the operation (on the relevant therapeutic experiences we report following).

The laboratory results in patients treated with large vitamin C doses were: vitamin C levels blood could generally be raised to 2 to 3 mg%; while the same in urine was variable, depending on whether patients with normal vitamin C blood mirror [Blutspiegel] or with pronounced hypovitaminosis were considered. The blood sugar curve, otherwise determined during the operation, is characteristic of hypoglycemia. In the blood picture we observed a marked left shift [Linksverschiebung: a high occurrence or an increase of metamyelocytes (granulocytes) in the white blood count]. 24 hours after the operation the above values approached preoperative levels. The values of potassium content and Ca-K-coefficient, which according to the literature specification tended to increase in shock, showed in our cases no increase. The absolute eosinophil count decreased.


To Summarize:

1. Patients admitted for operations during the winter months suffer to a large percentage with hypo- or avitaminosis. These patients can be reckoned to develop large blood pressure fluctuations and shock during operations.

2. In ether narcosis and in novocain anesthesia the vitamin C level of the blood decreased according to the ether quantity administered and to the operation’s duration and severity; it can even disappear, with increased spillage to the urine. The reduction of the vitamin C level in the blood is connected with the intense fluctuation of blood pressure occurring with pre-shock or shock.

In both groups the requirement is, on the one hand, to correct the vitamin C deficiency; and on the other to replace the vitamin C lost during the operation in order restore the original vitamin C level. An appropriate dose would be 500 mg preoperatively, and in the individual phases of the operation two to three additional 500 mg doses (a total quantity of 1500 to 2000 mg). A relatively large quantity of vitamin C - otherwise completely innocuous - is necessary, because it is almost completely depleted or dissociated during the operation.

It is well known that during shock a disturbance and crisis of the sympathetic adrenalin system occurs following deep metabolic disturbance, acid-base equilibrium disruption, increase of the permeability of the capillary cells, blood pressure depression, etc. According to Burdenko both endogenous and introduced adrenalin loses its physiological activity due to adrenalin decomposition, and in the organism a chemical disaccommodation develops. Friedmann, Cannon and Popov ascribe great importance likewise to functional changes of the adrenal gland in the pathogenesis of shock. Due to a trauma, as in the partial appearance of Cannon’s Syndrome, the adrenal glands secrete increased amounts of adrenalin; later however hyperfunction is replaced by hypofunction and the blood pressure drops.

In our operation cases a reduction of the vitamin C level in the blood preceded the blood pressure drop. The investigations of Svirbeli, Kocher and Michel corroborate our own experiences, namely observing the reduction of ascorbic acid content in rat livers and the adrenal gland during ether narcosis. There are also different authors well-known by us, who refer to the connection between ascorbic acid the adrenal gland and neuroendocrine system. As first established by Szent-Györgyi, and later Mosonyi and Ungar, ascorbic acid prevents the oxidation of adrenalin. In an organism beset with trauma, however, ascorbic acid is absent; therefore, adrenalin is decomposed in increased measure, as was observed in our operation cases. Our comprehension is that adrenalin decomposition, vitamin C elimination, blood pressure depression and formation of the chemical disaccommodation are parallel. In the [operation] cases these heavy disturbances, which we encounter in shock, occur in the organism.


Summary

In the course of our investigations with 80 patients admitted for operations we stated that we can, by administration of large doses of ascorbic acid, eliminate or prevent the disturbance of the sympathetic adrenalin system in the pathogenesis of shock. Thereby one prevents the emergence of serum- or plasmadiapedesis with an appropriately large dose of vitamin C. In our cases we succeeded in suppressing and preventing operative shock with large doses of vitamin C.


Bibliography

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The experiments were carried out with Redox Forte injections, and for the generous supplying of same we would like herein to deeply thank the La Roche Company.


[Translator’s Notes: As with all inter-language conversions, some liberty was necessarily taken with cases, tenses, plurals and sentence construction.  Difficult translations or uncertainties are noted with [??] fields and the original text for the reader’s convenience.

A sincerest tip of the hat to Hildegard Sutter for help with the more obscure medical jargon. - AscorbateWeb Editor]

From Zentralblatt für Chirurgie, Volume 21, 25 May 1957, pp. 883-887

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