HYPERVITAMIN THERAPY IN SURGICAL PRACTICE

MARTIN G. VORHAUS, M.D.

NEW YORK, CITY

T HE internist of today is awake to the probIem of deficiency states. His interest has been aroused by the

biochemist. Purification, isoIation and syn- thesis of one vitamin after another have pIaced in his hands potent therapeutic agents. The frequent case reports of scurvy, beriberi, peIIagra, and other single vitamin deficiency diseases are indicative of the increasing clinica awareness of the modern cIinician. In medica circIes attention is now being directed toward the recognition and treatment of the subcIinica1 states arising from partia1 deficiency of many vitamins.

Surgery has offered a fertiIe soi for vitamin investigation. UIcer, carcinoma, biIiary caIcuIi, chronic sepsis and hyper- thyroidism are some of the surgica1 dis- eases aIready stressed in the growing vitamin Iiterature. Avitaminosis or a sub- clinica state of deficiency coexists with so many surgical states that vitamin therapy has become increasingly important in surgica1 practice. A summary of recent contributions in the vitamin fieId that bear upon surgery is presented here. Based upon investigations in vitamin research, a therapeutic anaIysis of the significance of vitamins in surgica1 practice is outIined beIow.

GENERAL CONSIDERATIONS

AIthough specific effects of each vitamin have been recognized for a Iong time, there exists a definite interreIationship between the vitamins, which is of impor- tance to the surgeon. Thus, the fat soIubIe vitamins A, D, E, and K require the presence of biIe in the intestine for their absorp- tion.ll In a11 cases of obstructive jaundice there is a great IikeIihood that these vitamins are deficient in the body, even though the patient has been on a we11

pIanned diet. 26 This group-the fat soIubIe vitamins-is stored in the body in fairIy good amounts. In addition, vitamins A

and D bear a definite synergism to each other in their physioIogic activities.

The water soIubIe vitamins ~~ (thiamin), and c (ascorbic acid), as we11 as the components of the vitamin G compIex (nicotinic acid and riboflavin) are readily absorbed from the gastrointestina1 tract under norma conditions. In the presence of achyIia gastrica the destruction of some of these vitamins takes pIace readiIy in the stomach.20*18 In that event a Iarger intake than seems necessary must be given in order to make up an existing deficiency. Vitamins ~1’~ and c,” and probabIy nico- tinic acid as weI1, pIay an important rBIe in the utiIization of carbohydrates, not onIy in the Iiver, but in the tissues throughout the body. There is a synergistic action between riboffavin and vitamin B

and simiIar synergisms may be present between a11 of the water soIubIe vitamins.7

These vitamins are cataIysts in the basic oxidation-reduction systems of ceIIuIar activity and the partiaI deficiency of one or severa of them resuIts in a disturbance of the sugar metabolism. When we consider the importance of gIucose administration in surgica1 procedures it becomes apparent that deficiencies of these vitamins may be extremeIy important. The water soIubIe vitamins are not we11 stored in the body3p21 and a deficiency state may occur earIy in any given disease. It has been estabIished that vitamins ~~~ and c30 are required in Iarger amounts whenever the metaboIism of the body is eIevated. This occurs in the presence of febriIe diseases, some cases of sepsis and in hyperthyroidism, and under these conditions the requirement of the body for the water soIubIe vitamins is materiaIIy increased.

350

NEW SERIES VOL. XLII, No. 2 Vorhaus-Hypervitamin Therapy American ~~~~~~~ ()I surgery 33 I

The Iiver has an important and com- pIicated rBIe in the storage and utiIization of apparentIy a11 the known vitamins. In the event of a partia1 deficiency of one or more of the vitamins, Iiver function is often disturbed and at times severeIy deranged. Thus diminished or increased fat content of the Iiver, changes in the storage and breakdown of gIycogen and in the power of detoxication in the Iiver have a11 been observed experimentaIIy with one or more vitamin deficiency states.

Since norma Iiver function is of great significance in the response of the body to anesthesia, it is apparent that the vitamin state of a given patient becomes the con- cern of the surgeon. It has been estabIished that there is no one test that can give an adequate picture of the Iiver prior to anesthesia or operation. Under some circumstances it is possibIe to estimate roughIy the degree of deficiency of a given vitamin-as for exampIe, the use of the biophotometer in the case of vitamin A deficiency12 and the intravenous test to determine vitamin c saturation.22 These tests require specia1 apparatus and training and are often not avaiIabIe in routine surgica1 practice. Furthermore, in the case of the other vitamins there is as yet no satisfactory method for determining the amount present in the body other than the recognition of the cIinica1 state of a singIe deficiency or an awareness of the possibiIity of muItipIe deficiencies. This brings up the question of the vaIue of vitamin administration in preoperative preparation of the surgica1 patient and wiII be discussed as part of the therapeutic 0utIine.

This short review of the genera1 con- siderations in the vitamin probIem indi- cates the interrerationship between the vitamins themseIves as we11 as their significance in the carbohydrate metabo- Iism and in Iiver function. The severa vitamins have specific effects which per- tain to surgica1 states and these are brieff y outIined under separate headings.

Vitamin A2 is reIated to the nutrition of the mucous membranes of the body. This is particuIarIy true, of course, in reIation to the epiderma1 tissues of the eye, but there is suggestive evidence that it bears a reIationship to the heaIing and repair mechanisms of other mucous mem- branes. Vitamin A deficiency is a primary essentia1 condition for metapIasia and there is a question as to the reIationship between vitamin A deficiency and meta- plasia as seen in the thyroid gIand. Vitamin A is stored in the Iiver and is of importance in maintaining norma Iiver function. There is aIso experimental evi- dence to suggest that it bears a reIation- ship to the reticuIo-endotheIia1 system; If this is true, it is of importance in those septic states in which the reticuIoendo- theIia1 system pIays an important part.

Vitamin B1,31 because of its essentia1 r6Ie in carbohydrate metaboIism, has a very widespread appIication. It has a great dea1 to do with the gIycogen metabo- Iism in the Iiver and has been shown to offset the effect of choIine in depriving the Iiver of fat. In the presence of vitamin ~~ deficiency, Iactic acid formation in the tissues occurs very readily and may be of significance in the production of surgica1 acidosis. This vitamin bears a cIose rela- tion to the extrinsic factor in anemia and has some vaIue in bIood regeneration. As has been stated above, there is a greater need on the part of the body for this vitamin in the presence of infections, fevers and other states of increased metabo- Iism. Furthermore, the greater the carbo- hydrate intake the greater is the need for vitamin B1. In those postoperative condi- tions in which the nutrition of the body depends entireIy upon the intravenous administration of gIucose, the degree of saturation of the body with ~~ at such a time is of the greatest importance. The specific effect of this vitamin in the nutri- tion of nerve tissue is we11 known and cIinicaIIy it is a potent therapeutic agent in the treatment of postoperative neuritis. Another specific effect is its vaIue in x-ray

352 American Journal of Surgery Vorhaus-Hypervitamin Therapy NOVEMBER, 1938

sickness. Increasing numbers of reports of rapid improvement foIlowing the adminis- tration of vitamin ~~ in this condition are appearing in the Iiterature.14

Vitamin C.l’ This vitamin aIs0 is of great importance in the carbohydrate metabolism not onIy in the Iiver but eIsewhere in the body and bears a simiIar reIationship to vitamin ~~ in regard to infections, anemia and states of increased metaboIism (hyperthyroidism).28 In addi- tion, it has a specific effect upon the tendency towards hemorrhage. Deficiencies of this vitamin resuIt in abnormaIities of al1 interceIIuIar substances having coIIagen as their basis, and its absence prevents the formation of the matrices of white fibrous tissue, bone, cartilage and dentine. This expIains the frequent tendency to- wards hemorrhage in partia1 vitamin c deficiency.

A curious reIationship between vitamin c and the adrenaIs has been known to exist for a Iong time.8 Since the adrenaIs have often been incuIpated in the minds of the surgeons with the condition of “shock” the possibIe relationship to vita- min c deficiency requires carefu1 considera- tion. There is good experimenta evidence that this vitamin aids in the body’s defense against infectious diseases and Iarge doses seem to increase antibody production.l3

Vitamin D25 is of somewhat Iess impor- tance to the surgeon than the other vita- mins. It is, however, apparentIy invoIved in hemostasis, and may be of significance in the question of postoperative bIeeding where a relative deficiency exists. There is additiona evidence that it bears reIation- ship to cicatrization of tissue1 and in this connection may be of greater significance in surgica1 practice than is apparent from experimenta work that has been reported. Vitamin D has a very definite and impor- tant reIation to caIcium and water metabo- lism.4 It may at times be a factor in disturbances of water mobiIization and because of this concept its deficiency must be borne in mind by the surgeon. It is,

Iike the other fat soIubIe vitamins, stored in the Iiver in Iarge amounts and bears a definite reIation to Iiver function. It is we11 to emphasize again the synergism that exists between vitamins A and D and the growing cIinica1 concept that these vita- mins shouId aIways be administered to- gether rather than separately.

Vitamin G Complex.24’10 There is IittIe doubt in the minds of investigators in the vitamin field that what was previousIy known as vitamin G is reaIIy a complex group containing many factors. Of these the best known are riboflavin and nicotinic acid. Other components of this group are less we11 known, but one of the most favorabIe sources for the administration of this entire group is Iiver extract. The specific effect of nicotinic acid is, of course, upon the mucous membrane Iesions of peIIagra, of which the most we11 known are the tongue changes. These are of significance in the surgery of the tongue, but it is extremeIy likely that the nicotinic acid administration aIso has an effect upon the gastrointestina1 mucous membrane and therefore has a direct appIication in gastrointestina1 surgery as weI1. Many of the components of the vitamin G group are Iost in infections, whiIe the need of the body is much greater in the presence of sepsis. Vitamin G also bears a definite relation to Iiver function and is a part of the compIex interreIationship between the vitamins and the Iiver. The component eIements of G have an as yet unexpIained reIationship to the cortica1 suprarenal hormone.23 This brings up the question of surgical shock, as it has been a growing concept for many years that shock and a decreased output of cortica1 adrena hor- mone are cIoseIy reIated. There is very Iittle pubhshed work aIong these Iines, but there is suggestive evidence that a Iarge intake of the components of vitamin G

may effect the state of adrenal cortica1 hormone equilibrium.

Vitamin E investigations have not dis- cIosed any properties which might have a bearing upon surgica1 diseases.

NEW SERIES VOL. XLII, No. 2 Vorhaus-Hypervitamin Therapy American ~~~~~~~ of surgery 353

Vitamin K. 15v5 Comparatively IittIe is as yet known of this vitamin. It beIongs to the fat-soIubIe group and requires biIe for its absorption from the gastro- intestina1 tract. It appears to have a very important reIationship to bIeeding other than that which is reIated to a vitamin c deficiency, and its vaIue in the contro1 of bIeeding in jaundice has been recorded in a preliminary note. The work on this vitamin is so recent that it is not possibIe to give a satisfactory summary of its value at the present time.

This short summary indicates the impor- tance of vitamin deprivation in reIation to surgical diseases. Emphasis shouId be given to many other conditions which influence the vitamin intake in diseased states where uItimate surgica1 intervention is necessary. Mention2g is made first of the errors in eating due to either economic factors or dietary ignorance, which fre- quentIy result in a reIative avitaminosis. Among these are seIf-imposed diets for the reIief of symptoms, proIonged ad- herence to diets prescribed by physicians for the treatment of such diseases as ulcer, coIitis, aIIergic states and many others, and such eccentricities in diet as excess of carbohydrates and aIcoho1.

Even when the diet is adequate there are many conditions which increase the need of the body and it is we11 to recaI1 that in periods of increased growth, pregnancy and Iactation, with increased work, with increased metabolism, and during infectious states and in conva- lescence the need for most, if not aI1, of the vitamins is greatIy augmented.

Diminished absorption of vitamins oc- curs with vomiting, diarrhea, aIteration of the gastrointestina1 mucous membrane, aIteration of the gastrointestina1 secretions and any aIterations of gastrointestina1 continuity (postoperative).

AIthough vitamins may be we11 absorbed and adequateIy present in the diet of a given individua1, changes in gastro-

intestinal secretions and in the bacteria1 composition of the gastrointestina1 tract may bring about increased destruction of vitamins and resuIt in a state of partia1 avitaminosis.

FinaIIy there is a factor of diminished utiIization of vitamins in the body which may resuIt in a vitamin deficiency state even though intake and absorption are within norma Iimits. This occurs in the presence of advanced hepatic disease, advanced pancreatic disease and in certain forms of gastric disease. In this connection recent work by Patek16 indicates that a high vitamin intake, pIus iron, may be of vaIue in the treatment of advanced hepatic cirrhosis.

THERAPEUTIC OUTLINE

Vitamin probIems met in surgica1 prac- tice are in many respects different from those met by the internist. The physician frequently meets instances of a deprivation of one vitamin producing a recognizabIe cIinica1 entity. The surgeon is more Iikely to meet iII-defmed states of poor heaIth due to the deprivation of many or a11 of the vitamins, which can onIy be cIassified cIinicaIIy as a state of maInutrition, cachexia or by some simiIar vague term. These debilitated individuaIs are the con- cern of the surgeon from the standpoint of adequate preoperative preparation and postoperative care.

For these reasons muItipIe vitamin therapy wiI1 find a greater usefuIness in the hands of surgeons than in other groups. It is of the greatest importance that adequate dosage of vitamins be given to make up compIeteIy an existing deficit. CarefuI anaIysis of the dietary histories of debiIitated patients wiI1 not serve as an accurate guide in the caIcuIation of vitamin deficits. Even when the amounts of vitamins ingested are known, the factors of absorption and utiIization are of equa1 and at times greater importance in the body economy. For these reasons it is wiser to give an excess over and above

354 American Journal of Surgery Vorhaus-Hypervitamin Therapy NOVEMBER, 1938

the calculated amounts of the different vitamins.

In contempIating the administration of Iarge doses of vitamins-hypervitamin therapy-the question of toxic effects of overdosage may present itseIf to the surgeon. A carefuI survey of the vitamin Iiterature reveaIs that in onIy one instance, Vitamin D, is there evidence pertaining to the question of over dosage and toxicity.27 For this reason in a muItipIe vitamin pIan of therapy, Vitamin D administration shouId be kept down we11 within the Iimits of possibIe toxic effects.

For the purpose of preparing a “run- down” or debiIitated patient for operation it is desirabIe not onIy to give vitamins in adequate amounts but also to give certain minerals. Anemia is so frequentIy present in debiIitated states that it is noted as a frequent concomitant to avitaminosis. Vitamins themseIves, particuIarIy that group derived from Iiver extract, are active hematopoietic substances. An a11 incIusive therapeutic regime, however, must include the administration of iron, preferably in the ferrous state, and in adequate amounts. AIso the administration of smaI1 amounts of caIcium and phos- phorus is often of vaIue in cachectic individuaIs.

Taking a11 of these facts into considera- tion a therapeutic outIine is presented to the surgeon for routine use in surgica1 practice. It is suggested that multipIe vitamin and minera therapy be given preoperativeIy for the preparation of the surgica1 patient. The Iength of time during which this hypervitamin therapy shouId be instituted wiI1 always be the individua1 probIem of the surgeon. Therapy for from five to ten days before operation wiI1 suffice in many cases, but there are unquestionably many instances where the individua1 surgeon wiI1 prefer to maintain this high vitamin and minera IeveI for a Ionger period of time. The daily vitamin intake during the period of hypervitamin therapy should incIude the foIlowing vita- mins in these minimum dosages:

Vitamin A. . . . 30,000 U. S. P. units Vitamin D . . ..__.......... 2,000 U. S. P. units Vitamin B l............... 1,500 International units Vitamin c.. . . . . 500 InternationaI units Vitamin G compIex (as Iiver

extract) 100 gamma equivaIent

of riboflavin Vitamin rz.. . . Trace Iron (as ferrous saIt). . . Dicakium phosphate.. . . .

60 mg.

50 mg.

Such a vitamin-minera mixture as described in this outIine of hypervitamin therapy has been employed in the pre- operative preparation of patients in many cIinics. It is too earIy to evaIuate sta- tisticaIIy the modifications in operative mortaIity and postoperative morbidity foIIowing this regime. In our experience there has been sufficient change to justify a feehng of optimism and a determina- tion to continue to employ this form of therapy.

The same circumstances which hoId true for preoperative hypervitamin therapy are of great significance in the post- operative states. Depending upon the type of operation, as soon as the gastro- intestinal function permits, this program of hypervitamin therapy may be instituted. It is impossibIe to state empiricaIIy how Iong this pIan of hypervitamin therapy shouId be continued. It can onIy be expressed in cIinica1 terms by stating that muItipIe vitamin and minera intake shouId be maintained at maximum IeveIs as Iong as compIete recovery has not yet taken pIace. When the strength of the individua1 has returned to normaI and the patient’s capacity to ingest a com- pIeteIy baIanced diet has been attained, this form of suppIementary therapy may be discontinued at the discretion of the surgeon.

There has been an increasing use of suIfaniIamide and its derivatives in the treatment of surgica1 infections. In many instances a sudden change is noted in the toxicity of a given case. AIthough, dramatic improvement may be noted in the infec- tion, the toxic effect upon the Iiver and other tissues is often disproportionate to the improved cIinica1 picture. Such

NEW SERIES VOL. XLII, No. z Vorhaus-Hypervitamin Therapy American ~~~~~~~ or surgery 344

patients often represent a state of relative multiple avitaminosis. In addition, the effect of sulfanilamide upon the hemato- poietic system, combined with the influ- ence of the infection, results in an anemia which requires adequate amounts of iron and other hematinic agents. In those patients recovering from infections, suc- cessfully treated with sulfanilamide, this plan of hypervitamin therapy is of special value. It is hoped that the routine applica- tion of this plan of hypervitamin therapy now in use by a few clinics, will earn the enthusiastic approval of an increasing number of surgeons.

SUMMARY AND CONCLUSIONS

A brief outline of recent contributions in vitamin investigations has been pre- sented with special emphasis upon their application to general surgery. The multi- ple avitaminoses associated with anemia, which are so frequently encountered in surgical practice, require hypervitamin administration. A therapeutic outline is presented with details of minimum daily dosage of each vitamin and of the essential minerals.

Hypervitamin therapy is indicated in routine preoperative preparation of all cases as we11 as in debilitated and mal- nourished individuals. Patients requiring gastrointestinal or biliary tract surgery present special indications for hyper- vitamin therapy. Its value is stressed in infectious conditions and in hyperthyroid- ism. The vitamin and mineral content of the hypervitamin therapeutic plan provides adequate dosage for postoperative and convalescent needs. The routine use of hypervitamin therapy in postoperative and convalescent patients is recommended.

REFERENCES

I. AMBROSI, F. Policlinico (sez. cbir.), 44: 273-2ar (June) 1937.

2.

7.

a.

9.

IO.

II.

12.

13.

14.

‘5.

16.

17.

Ia.

19. 20. 21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

BESSEY, 0. A., and WOLBACH, S. B. J. A. M. A., 110: 2072-20a0 (June Ia) Ig3a.

BRODIE, J. B., and MACLEOD, F. L. J. Nutrition,

10: 179, 1935. BRULL, L. Bruxelles M&l., 17: 1557-1566 (Aug. 29)

1937. BUTT, H. R., and SNELL, A. M. Proc. Staj’ Meet.,

Mayo Clin., 13: 74-80 (Feb. 2) 1938. DESSY, G., and CATAGNI, F. Diagnosi, 16: I IO

(April) 1936. ELLIS, L. N., and Z~IACHINSKY, A. Science, 86:

245-246 (Sept. IO) 1936. FREEMAN, W., and GLASS, W. E. Am. J. Clin.

Path., 8: 197-205 (March) 1938. HEIPZDRICHS, W. A. Am. J. Pbysiol., rag: 678-683

(June 17) 1933. HOGAN, A. G. J. A. M. A., I IO: 1188-r 193 (April

9) 1938. IVY, A. C. Surg., Gynec. ti Obst., 66: 209-217

(March) 1938. JEANS, P. C., BLANCHARD, E., and ZENTMIRE, Z.

J. A. M. A., 108: 451-458 (Feb. 6) 1937. MADISON, R. R., and MANWARING, W. H. Proc.

Sot. Exper. Biol. cY Med., 37: 402, 1937. MARTIN, C. L., and MOURSUND, W. H. JR. Am. J.

Roentgenol., 38: 620-624 (Oct.) 1937. OSTERBERG, A. E. Proc. Staff Meet., Mayo Clin.,

13: 72-74 (Feb. 2) 1938. PATEK, A. J. Proc. Sot. Exper. Biol. @ Med., 37:

329-330 (Nov.) 1937. PERLA, D., and MARMORSTON, J. Arch. Path., 23’

543 (April) 1937; 23: 683 0%) 1937. PETERS, G. A., and MARTIN, H. E. Proc. Sot. E.xper.

Biol. & Med., 36: 76-78 (Feb.) 1937. _ PETERS, R. A. Lancet, I: 1161 (May) 1936. PETRI, S. Folia baemat., 56: 159-186, 1936. POLICARD, A. A., and FERRAND, M. Klin. Wcbnscbr.,

16: 3o8-310 (Feb. 27) 1937. RALLI, E. P., FRIEDMAN, G. J., and KASLOW, M.

Proc. Sot. Exper. Biol. c~ Med., 36: 52-56 (Feb.)

1937. SCLARE, I. M. Brit. M. J., 1’ 1249-1251 (June Ig)

1937. SEBRELL, W. H. J. A.M. A., IIO: 1665-1672 (May

14) 1938. SHOHL, A. T. J. A. M. A., III: 614-619 (Aug. 13)

I 938. SPENGLER, F. Miincben. med. Wcbnscbr., a4:

779-780 0%) 1937. STECK, I. E., DEUTSCH, H., REED, C. I., and

STRUCK, H. C. Ann. Int. Med., IO: 951-64

(Jan.1 1937. SURE, B., and THEIS, R. M. Proc. Sot. Exper. Biol.

@’ Med., 37: 646, 1937. VORHACS, M. G. Am. J. Digest. Dis., 5: 405-408

(Sept.) 193a. WIDENBAUER, F. Klin. Wcbnscbr. 16: 600 (ApriI

24) 1937. WILLIAMS, R. R., and SPIES, T. D. Vitamin B,.

New York, MacMiIlan. 1938. WOLBACH, S. B. New England J. Med., 215: I 15%

II59 (Dec. 17) 1936.