PRINGLE : POST-VAGOTOMY SIDE-EFFECTS

SIDE-EPPBCT

Loss of appetite Bilious vomiting Diarrhoea Vasomotor syptoms Loss of weig t Iron-defiaency anaemia

POST-VAGOTOMY SIDE-EFFECTS AND BLOOD-GROUP SUBSTANCES

BY ROBERT PRINGLE DEPARIhlBNI OF SURGERY, QUBB”S COLLEGE, DUNDHB

I 4 3 35 2 0 0 25 I 4 3

BILATERAL vagotomy and gastrojejunostomy for chronic duodenal ulcer is followed in some patients by symptoms which are related to the physiological disturbances produced by section of the vagus nerves, the presence of a gastro-enterostomy, or, as is more likely, the combination of the two procedures. These side-effects are loss of appetite, bilious vomiting, diarrhoea, vasomotor symptoms, loss of weight, and iron-deficiency anaemia.

A considerable difference of opinion exists as to the incidence of these sequelae of operation. Taking vasomotor symptoms as an example, Walters, Lynn, and Mobley (1957) found this side-effect in 3 per cent of their patients, Hoerr (1955) 48 per cent, Austen and Edwards (1961) 6 per cent, Holt and Lythgoe (1961) 6 per cent, Lloyd-Davies (1956) 11 per cent, Cox and Kerr (1957) 12 per cent, Feggetter and Pringle (1963) 13.3 per cent, and Burge and Pick (1958) 16 per cent. There are many possible explana- tions of this disparity. Variations in the technique of vagotomy and gastrojejunostomy, the diligence with which postoperative symptoms are sought at interview, and biological differences between patients are some of the many possible factors.

The purpose of this study is to consider the blood group and secretor status in a series of patients who have had bilateral vagotomy and gastrojejunostomy for chronic duodenal ulcer and to determine their effect, if any, on the incidence of postoperative side- effects.

This simple classification was adopted, as it was thought that any attempt to define intermediate grades would make assessment more diffcult or even impossible.

ABO groups and secretor status were determined in all of these patients. The determination of secretor status was carried out using the method of Boyd and

Table DISTRIBUTION OF SIDE-EFFECTS I I

Total No. of patients with side-effm I 56 I 3 2 0

Shapleigh (1954) in which a saline extract of Ulex europaeus is titrated against the patient’s saliva with suitable group 0 cells as an indicator. The ABO groups were determined by standard tube methods.

RESULTS Of the 175 patients, 119 (68 per cent) had no

symptoms of any kind, and 56 (32 per cent) had side- effects (see Table I). The distribution of blood groups and secretor status in these patients is shown in

Table zz.-INCIDENCB OF SIDE-EFFECTS ACCORDING TO BLOOD GROUP AND SECRETOR STATUS

IA I I N S

Totalingroup 175

Per c&t with side effects

= r F 3

33’3 33‘3 5 0 0 - S = Secretor; NS = Non-secretor.

MATERIAL AND METHODS The series consists of 175 patients who had bilateral

vagotomy and gastrojejunostomy for chronic duodenal ulcer, and in whom the results were assessed after 10 years or more. Full details of this series are reported elsewhere (Feggetter and Pringle, 1963). At interview each patient was allowed to state his symptoms with- out prompting. If it became obvious that the patient was unaware of the side-effects of the operation then leading questions were asked. On this basis symptoms were called ‘mild’ when obtained only by careful questioning, and ‘ severe ’ if volunteered by the patient.

Table IZ. Statistically there is no significant association between blood group and secretor status and the overall occurrence of side-effects.

Each side-effect has been examined separately to determine if an association exists between the parti- cular symptom and any particular blood group, and secretor and non-secretor state. No significance was found in respect of appetite, bilious vomiting, vaso- motor symptoms, and loss of weight.

Diarrhoea occurred in 35 (30.2 per cent) secretors and in only 8 (13.6 per cent) non-secretors (xa ‘4997, P<o-o5). This is statistically significant (Table ZZZ).

42 BRIT. J. SURG., 1968, Vol. 55, No. I, JANUARY

Iron-deficiency anaemia occurred more often than expected in individuals belonging to blood group A (x2 =487, P<005). This is also significant (Table In.

This study suggests that there is a statistical cor- relation between the secretor status and the occurrence of diarrhoea following vagotomy and gastroentero- stomy for chronic duodenal ulcer. An association between blood group A and postoperative iron- deficiency anaemia has also been found. These findings would seem to indicate that the occurrence of diarrhoea and anaemia following operation concerns

by the fact that the quantity of blood-group substances present in saliva is not related to the secretor status and/or the ABO grouping (Evans, 1960).

Moreover Witebsky and Neter (1935) demonstrated blood-group-substance-destroying factors in the terminal ileum and colon. These factors extended to the jejunum and upper ileum in 2 cases of intestinal obstruction. They postulated that the mucopoly- saccharide destructive activity might be organismal in origin, as bacteria migrate into the upper intestinal tract in obstruction.

The functional significance of the production and destruction of blood-group substances in the gastro- intestinal tract is unknown, but it seems reasonable to

Table ZZZ.-INCIDENCE OF DIARRHOEA ACCORDING TO BLOOD GROUP AND SECRETOR STATUS

S = Secretor; NS = Non-secretor.

Table Iv.-INCIDENCE OF IRON-DEFICIENCY ANAEMIA ACCORDING TO BLOOD GROUP AND SECRETOR STATUS

~~~

Percentwithanaemia 143 I 293 I I 4 3 I - 1 - S = Secretor; NS = Non-secretor.

the biological make-up of the patient rather than minor variations in technique of the operation itself.

The blood-group substances are complex muco- polysaccharides and are unique in that they are the only substances in the body containing the mono- saccharide L-fucose.

The blood-group substances A, By H, LC, and Leb are present in the tissue fluids. The secretor gene exerts its influence by determining whether Leb is present in addition to LC, and also by ensuring the presence of the A, By H antigens in the saliva and gastric juice.

This leads to a considerable individual variation in the mucopolysaccharide composition of the fluids bathing the gastro-intestinal mucosa, e.g., a group A Lewis positive secretor has A, H, LC, and Leb substances present; a group AB Lewis positive secretor has A, By H, W, and Leb; a group 0 Lewis positive secretor has H, LC, and Leb. Lewis positive non-secretors of blood group A, AB, B, or 0 have only LC present in the secretions. Further differences exist in the case of Lewis negative subjects. Approxi- mately 95 per cent of the population are Lewis positive, and 76 per cent of the population are secretors. The situation is made even more complex

assume that disease of the gastro-intestinal tract and surgical intervention may upset the balance.

The present investigation suggests that there may be an interaction between the presence or absence of the various blood factors and the liability of patients to develop diarrhoea and iron-deficiency anaemia following vagotomy and gastroenterostomy for chronic duodenal ulcer. More detailed investigations are required of the incidence of post-vagotomy side- effects in each of the many possible combinations of ABO blood groups, secretor status, and Lewis type, and of the possible mechanisms of action involved.

SUhmmRY The incidence of side-effects occurring in 175

patients, 10 years or more following bilateral vago- tomy and gastrojejunostomy for chronic duodenal ulcer, was determined.

The distribution of ABO blood-groups and secretor status in these patients was also examined.

This study suggests that diarrhoea occurs with greater frequency in patients who are secretors and that iron-deficiency anaemia is more common in blood-group A individuals.

OWEN-SMITH : PROPHYLAXIS OF EXPERIMENTAL GAS GANGRENE 43

Acknowledgements.-I am grateful to Mr. G. Y. Feggetter for his encouragement and for permission to review these patients, all of whom were under his care in the Royal Victoria Inlirmary,Newcastle upon Tyne. My thanks are also due to Miss D. E. A. Strevens of the Department of Mathematics, Queen’s College, Dundee. for her helr, with the statistical analysis.

REFERENCES AUSTEN, W. G., and EDWARDS, H. C. (1961), Gut, 2,158. BOYD, W. C., and SHAPLEIGH, E. (1954), Blood, 9, 1195.

BURGE, H., and PICK, E. J. (1958)~ Br. med.J., I, 613. Cox, H. T., and KBRR, D. F. (1957), Zbid., I, 1211. EVANS, D. A. P. (1g6o),J. Lab. clm. Med., 55, 386. FEGGETTER, G. Y., and PRINOLE, R. (1963), surgery Gynec.

Obsret., 116, 175. Horn, S. 0. (1955), Surgety, St Louis, 38, 149. HOLT, R. L., and LYTHGOB, J. P. (1g61), Br. 3. Surg., 49,

255.

Gastroenterology, 35,685.

LLOYD-DAVIES, J. A. (1956), Br. med.J., 2, 1086. WALTBRS, W., LYNN, T. E., and MOBLEY, J. E. (1g57),

WITEBSKY, E., and NGTBR, E. (1935),3. exp. Med., 62,589.

ANTIBIOTICS AND ANTITOXIN THERAPY IN THE PROPHYLAXIS OF EXPERIMENTAL GAS GANGRENE

BY M. S. OWEN-SMITH DEPARTMEW OP MILITARY SURGERY, ROYAL ARMY MEDICAL COLLBGE, LONDON

MACLENNAN AND MACFARLANE ( I~M) , in a study of nearly 500 cases of established human gas gangrene in war wounds, were convinced that antitoxin therapy and early surgery after diagnosis of the cause of the toxaemia were the most important factors in the reduction of the fatality-rate which was obtained as experience accumulated. Reactions to the antiserum used were few and of minor importance.

Little was known of the prophylactic, as opposed to the therapeutic, effect of antitoxin in preventing gas gangrene, but when penicillin was introduced and used in war wounds there was some evidence of its beneficial effect. Fisher, Williams, Grimson, and Florey (1945)~ in a study of 3907 war wounded, showed that if those patients with wounds thought to carry a high risk of developing gas gangrene (as de- fmed by the War Wounds Committee of the Medical Research Council) were given penicillin prophylac- tically then the incidence of this complication was nil. Of those patients treated concurrently without penicillin, 0.14 per cent developed gas gangrene.

Penicillin alone, given up to g hours after wound- ing, has been completely effective in the prophylaxis of gas gangrene of the high-velocity bullet wound in sheep (Owen-Smith and Matheson, 1968).

Garrod (1958) demonstrated that the tetracycline group of drugs were more effective than penicillin against Clostridia in vitro. Oral tetracycline was chosen in preference to penicillin injections for self- aid packs for soldiers in the jungles of Borneo, because of ease of supply and administration. Self- treatment was begun immediately after wounding with the object of reducing sepsis, and in the hope of preventing gas gangrene (Wheatley, 1967).

The study reported here was undertaken to evaluate the prophylactic effect of tetracycline therapy on the standard contaminated bullet wound of sheep’s muscle. Antitoxin therapy was also investigated and the results of these forms of treatment were com- pared with that of penicillin.

h%ATERIALS AND METHODS Sheep.-The animals used were mostly ewes

aged 5 7 years, as well as a few rams, and weighed 45-80 kg. They were starved, but not deprived of

water, in open-fronted pens for 48 hours before commencing the experiment. This was to reduce the risk of inhalation of vomit following regurgitation common in the ruminant.

Anaesthesia.-The sheep were anaesthetized with a 6 per cent solution of sodium pentobarbitone administered into the cephalic vein. The dose used was approximately 10 mg. per kg. total body-weight. They were then placed on their right sides on an operating table, a cuffed endotracheal tube was passed, and they breathed air spontaneously.

Wound.-This was the standard sheep leg prepara- tion of Hopkinson and Watts (1963). In this prepara- tion a 0.22-in. bullet was fired from a fixed rifle, the muzzle of which was 3m. away from the animal’s hind leg. The bullet passed through the leg from lateral to medial side and was aimed so that it traversed the centre of the quadriceps femoris muscle. The striking velocity was approximately 16ooft. per second, the remaining velocity approximately 1200 ft. per second, and the energy dissipated in the tissues creating the wound was go-120ft. per lb. The maximum diameter of the temporary cavity formed in the limb was about 9 cm., or roughly the size of a cricket ball. Great care was taken to see that the wound track passed deeply through the thigh muscle.

Gas Gangrene Contaminant (Thoresby and Watts, 1967).-A suspension of spores of Clostridium oedema- tiens ( 5 x 10’) spores per ml.) was used, the spores being checked for viability. One millilitre of the suspension was evenly spread over approximately 4 sq. in. of battledress cloth, which was then fixed over the target spot on the ‘entrance’ surface of the sheep’s closely clipped thigh.

Dressiqgs.-No dressings were used on the small entry and exit wounds.

Recwery and Progress.-After wounding, the sheep awoke in 3040 minutes, and began to get up and walk around soon after. About 24 hours later, those animals developing fatal gas gangrene began to look ill and would not eat. Although there was little to be observed in the way of local changes at the wound site, except for some swelling, they developed a progressive toxaemia, and death ensued within 48 hours.