635

VALUE OF BILE-ACID BINDING AGENTS IN POST-VAGOTOMY DIARRHŒA T. V. TAYLOR

Department of Clinical Surgery, Royal Infirmary,

Edinburgh EH3 9YW H. B. TORRANCE

M. E. LAMBERT

two and six weeks. They were then of aluminium hydroxide (’Aludrox’) course four-week given 10 ml three times a day and again reviewed at two and six weeks. 8 patients, 4 in each group were given propranolol (’Inderal’) 20 mg three times a day. The trial was not,double-blind largely because of the difficulty in matching the pharmaceutical agents; in addition, we felt that the palatability of aludrox compared with that of cholestyramine was an important factor to be considered. Patients were assessed in terms of drug acceptance, side-effects, and bowel habit.

times

a

day and reviewed at

a

Manchester Royal Infirmary, Manchester M13 9WL

Results increases the incidence of post-vagotomy diarrhœa. The effect of agents which either bind bile acids or prevent their action on the colonic mucosa has been studied in 31 patients with post-vagotomy diarrhœa—15 had had vagotomy and pyloroplasty alone and 16 vagotomy and pyloroplasty and cholecystectomy. Cholestyramine was particularly useful after the combined operation. Aluminium hydroxide in large doses has a similar mechanism of action to cholestyramine and is cheaper and more palatable, but propranolol was of no value. This study suggests that the excretion and chemical composition of bile and the handling of bile acids by the small intestine is of fundamental importance in the pathogenesis of post-vagotomy diarrhœa.

Summary

Cholecystectomy

Introduction

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THE cause of post-vagotomy diarrhoea remains unknown. An association between cholecystectomy and the incidence of post-vagotomy diarrhoea’ supports the theory that the excretion of bile acids, their chemical composition, and their handling by the small bowel may be important in the pathogenesis of post-vagotomy diarrhoea. Since bile-acids produce diarrhoea by a direct action on the colonic mucosa, agents which either bind them or prevent their action on the colon should improve the diarrhoea. The small-intestinal transit and absorption of bile-acids must also influence the quantity and rate at which they come into contact with the colonic mucosa. Cholestyramine is said to be of value in the treatment of post-vagotomy diarrhoea .2,3 Aluminium hydroxide also has bile-acid binding properties in vitro’* and is less expensive and more palatable than cholestyramine. Propranolol which inhibits the bile-acid stimulation of rabbit colonic adenyl cyclase in vitr05.6may also be of value; moreover it allays anxiety and psychogenic factors which may play a role in post-vagotomy diarrhrea.7 This’prospective study was undertaken to investigate the value of these three pharmaceuticals in post-vagotomy diarrhoea. Methods 31 patients (16 who had undergone vagotomy, pyloroplasty, and cholecystectomy and 15 vagotomy and pyloroplasty alone) with post-vagotomy diarrhoea were included in the trial. Postvagotomy diarrhoea was defined as a postoperative change in bowel habit amounting to the passage of three or more loose motions per day which were usually exacerbated by food and heralded by lower abdominal colic but may have been episodic; if episodic, urgency or occasional incontinence should have been present. All patients stopped any previous medication and were given a four-week course of cholestyramine (’Questran’) 4 g three

In the combined tients improved on

operation group (v.p.c.’ ), 12 of 16 pacholestyramine but 3 could not toler-

the

drug, and in 1 the symptoms worsened. In the patients who had had vagotomy and pyloroplasty (v.p.) only, 6 improved on cholestyramine, 7 found the drug to be of no value, and 2 could not tolerate it:

ate

15

Operation V+P+C V+P

No. 16 15

Improved 12

6

Worse 1 2

Could not tolerate

3 2

The improvement in patients who had had the combined operation was greater than that in those who had had vagotomy and pyloroplasty alone (P=0-044). Symptoms recurred soon after cessation of treatment but in several patients symptoms could subsequently be controlled by a reduced dose of 4 g daily taken in the morning. 11 patients complained of occasional nausea, 6 of vomiting, and 5 could not tolerate cholestyramine. The results with aludrox 10 ml three times a day, were less impressive-5 of 16 in the v.p.c. group but only 1 of 15 in the v.p. group improved. No patients had side-effects with aludrox, and all those whose symptoms improved with aludrox had also responded to cholestyramine. 5 of the 8 patients given propranolol had stopped taking the drug at the 2-week review because their symptoms had worsened and the other 3 had found no improvement at this stage. The drug was therefore

abandoned. In those patients who responded to medication, the greatest improvement was in frequency of bowel action and consistency of the motion; episodic bouts of diarrhoea with urgency were most difficult to control. Discussion confirm those of other workers2,3 that is effective in the treatment of some cases of post-vagotomy diarrhoea; and its greater effectiveness in patients who had undergone ct olecystectomy plus vagotomy and pyloroplasty (P=0-044) supports the concept of bile-acid mediated diarrhoea. After vagotomy, the altered chemical composition of bile may increase the incidence of gallstones.8 Allan9 has reported increased f2ecal bile-acid excretion in post-vagotomy diarrhoea. When cholecystectomy is added to vagotomy, concentrated bile acids are no longer rapidly emptied from a distended gallbladder in response to food; instead, a continuous trickling of bile leads to unbuffered bile acids of different chemical composition entering the gut all the time. Increased peristalsis on eating may hurry unbuffered bile acids into the colon where they would cause diarrhoea by inhibition of colonic absorption of potassium, sodium, and water."*’" Consequently Our

findings cholestyramine

636

cholecystectomy might be expected to heighten the role played by bile acids in the pathogenesis of post-vagotomy diarrhoea.It bile-acid secretion is the only xtiological factor then sufficient quantities of agents which bind these acids should control the diarrhoea. Although cholestyramine improves symptoms in some patients, in others it has little effect; its effect appears to be best in those who have had a cholecystectomy. We suggest that whilst bile acids play an important role in post-vagotomy diarrhoea other factors such as motility disturbances (similar to those seen in the irritable bowel syndrome2) may also be present. The poorer response obtained with aluminium hydroxide in this study is probably a reflection of the dose used. The patients who responded to aluminium hydroxide were those who had also responded to cholestyramine. Our impression is that if the dose were to be doubled or trebled results similar to those with cholestyramine could be achieved-a larger dose is effective after

Preliminary Communications BLOOD-TRANSFUSION IN GROUP-B STREPTOCOCCAL SEPSIS ANN O. SHIGEOKA ROBERT T. HALL HARRY R. HILL Division

of Clinical Immunology, Department of Pediatrics, University of Utah, Salt Lake City; and Children’s Mercy Hospital, University of Missouri, Kansas City, Missouri, U.S.A. and Department of Pathology,

Transfusion of fresh whole blood was evaluated as a means of supplying and opsonins lessening the high mortality of group-B streptococcal sepsis in neonates. Pre-transfusion and post-transfusion sera from 22 infants were examined for the presence of opsonins against group-B organisms. Opsonic activity rose only when donor blood containing heat-stable antibody was administered in high volume (>40% of blood-volume). 9 of 9 infants transfused with

Summary

containing antibody to their infecting strain surseptic episodes. 3 of 6 who received blood lacking antibody to their infecting strain died. blood vived

INTRODUCTION

GRoUp-B streptococci, despite their sensitivity to several antibiotics, are a major cause of morbidity and mortality in neonates and in other patients with comdefence mechanisms.1-7 Patients in whom group-B streptococcal sepsis develops usually lack opsonic antibody to their infecting strain;8 and Lancefield and co-workers9 have shown that mice are protected against such infections by administration of antibody to the organisms. For these reasons we have examined the effects of fresh whole-blood transfusion on serum opsonic activity and on mortality in group-B

promised

streptococcal sepsis. Organisms Reference

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for

reprints should

be addressed

to

T. V. T.

REFERENCES

1.

Taylor,

T. V.,

Lambert,

M.

E., Quereshi, S., Torrance, B. Lancet, 1978,i,

295.

Ayulo, J. A. Am. J. Gastroent. 1972, 57, 207. 3. Duncombe, V M., Bolin, T. D., Davis, A E. Gut, 1977, 18, 531. 4. Sali, A., Murray, W. R., Blackwood, A., Mackay, C. Br J. Surg 1977, 64, 296. 5. Coyne, M. J., Bonorris, G. G., Chung, A., Conley, D. R., Croke, J., Schoenfield, L. H. Gastroenterology, 1976, 71, 68. 6. Conley, D., Coyne, M , Chung, A., Bonorris, G., Schoenfield, L. J. ibid. 71, 72. 7. Johnstone, E. C J psychosom. Res. 1974, 18, 205. 8. Fagerberg, S., Grevsten, S., Johanssen, H., Krauss, U. Gut, 1970, 11, 789. 9 Allan, J. G., Gerskowitch, V. P., Russell, R. I. ibid. 1973, 14, 423. 10. Mekhjian, H. S., Phillips, S. F. Gastroenterology, 1970, 59, 120. 11. Mekhjian, H. S., Phillips, S. F., Hoffman, A. F. J. clin. Invest. 1971, 50, 1569. 12. Sali, A, Watkinson, G., MacKay, C. Gut, 1977, 18A, 419 2.

infected patients were cultured at 37°C in Todd-Hewitt broth for 18 h.8 The organisms were washed and then adjusted to an optical density of 0.9nm (S x 10$to 1 x 109 colony-forming units per ml) in phosphate-buffered saline (P.B.s.). Serum Serum was used immediately after collection or frozen at —70°C. To ensure an intact classical complement pathway we added 0-025 ml of whole human complement (Cordis Laboratories, Miami, Florida), which maximally enhances antibodymediated

opsonisation