788

INTRAVENOUS AMINOACIDS AND INTRAVENOUS HYPERALIMENTATION AS PROTEIN-SPARING THERAPY AFTER MAJOR SURGERY A Controlled Clinical Trial C. B. OXBY

J. P. COLLINS G. L. HILL

University Departments of Surgery and Medical Physics, General Infirmary, Leeds LS1 3EX

Summary

A solution of aminoacids without a calorie source was infused postoper-

in ten patients undergoing proctocolectomy or rectal excision and the results were compared with those in ten matched controls and ten patients who received intravenous hyperalimentation. Aminoacid infusion prevented the nitrogen and potassium loss that occurred in the untreated group but no clinical advantage could be seen. Nitrogen and potassium loss was also prevented in the patients treated with intravenous hyperalimentation but these patients had significantly fewer postoperative complications than either the controls or those given aminoacid infusion. It is suggested that aminoacid infusion is of very little benefit after major surgery. On the other hand the skilled administration of intravenous hyperalimentation to patients after major surgery can be of real benefit.

atively

Fig. 4-Total integrated hormonal response to a (expressed as percentage of normal) in patients

test-meal with un-

treated cceliae disease.

(fig. 4) may prove to be a useful complementary tool with which to detect new cases of coeliac disease; it may also be useful for monitoring the return to normal of the functional abnormalities. We thank Mr T. E. Adrian, Miss W. Czaykowska, Miss P. Dayus and the Dietetic Department, Hammersmith Hospital for their help; and the Well come Trust, the British Diabetic Association, and the Institut National de la Sante et de la Recherche Médicale for financial support. REFERENCES 1. Stewart, J. S. Clins Gastroent. 1974, 3 (1), 109. 2. Stewart, J. S. Postgrad. med. J. 1968, 44, 632. 3. Booth, C. C. Br. med. J. 1970, iii, 725 and iv, 14. 4. Schedl, H. P., Clifton, J. A. Nature, 1963, 199, 1264. 5. Silk, D. B. A., Kumar, P. J., Webb, J. P. W., Lane, A. E., Clark, M. L., Dawson, A. M. Gut, 1975, 16, 261. 6. Bernier, J. J., Soule, C., Galian, A. Archs fr. mal. app. Dig. 1975, 64, (6), 495. 7. Read, N. W., Levin, R. J., Holdsworth, C. D. Gut, 1976, 17 (6), 444. 8. Schedl, H. P., Pierce, C. E., Rider, A., Clifton, J. A. J. clin. Invest. 1968,

47, 417. Elias, E., Mackinnon, A. M., Short, M. D., Dowling, R. H. Eur. J. clin. Invest. 1973, 3, 226. 10. Mackinnon, A. M., Short, M. D., Elias, E., Dowling, R. H. Am. J. dig. Dis. 1975,20,835. 11. Wormsley, K. D. Scand. J. Gastroent. 1970, 5, 353. 12. Worning, H., Mullertz, S., Hess Thaysen, E., Bang, H. O. ibid. 1967, 2, 81. 13. Di Magno, E. P., Go, V. L. W., Summerskill, W. H. J. Gastroenterology, 1969, 56, 1149. 14. Russell, R. C. G., Bloom, S. R., Fielding, L. P., Bryant, M. G. Postgrad. med. J. 1976, 52, 645. 15. Adrian, T. E., Bloom, S. R., Besterman, H. S., Barnes, A. J., Cooke, T. J. C., Russell, R. C. G., Faber, R. G. Lancet, 1977, i, 1961. 16. Häcki, W. H., Greenberg, G. R., Bloom, S. R. in Gut Hormones (edited by S. R. Bloom); Edinburgh, p.182, 1978. 17. Bloom, S. R., Turner, R. C., Ward, A. S. Gastroenterology, 1977, 72, A-3/813. 18. Thomson, J. P. S., Bloom, S. R. Clin. Sci. molec. Med. 1976, 51, 177. 19. Blackburn, A. M., Bloom, S. R., Ebeid, F. H., Ralphs, D. N. Gut (in the 9.

press). 20. Polak, J. M., Pearse, A. G. E., van Noorden, S., Bloom, S. R., Rossiter, M. A. ibid. 1973, 14, 870. 21. Bloom, S. R., Patel, H. R., Johnston, D. I. ibid. 1976, 17, 812. 22. Rhodes, R. A., Chey, W. Y., Tai, H. H., Escoffery, R. Clin. Res. 1976, 24, 290A. 23. O’Connor, F. A., McLoughlin, J. C., Buchanan, K. D. Br. med. J. 1977, i, 811. 24. Hooft, C., Devos, E., van Damme, J. Lancet, 1969, ii, 161. 25. Walker-Smith, J. A., Gigor, W. ibid. i, 1021. 26. Birbeck, J. A. ibid. ii, 496. 27. Day, G., Evans, K., Wharton, B. Archs Dis. Childh. 1973, 48, 41. 28. Creutzfeldt, W., Ebert, R., Arnold, R., Frerichs, H., Brown, J. C. Diabetolo-

gia, 1976, 12, 279. 29. Bloom, S. R. Gut, 1972, 13, 520. 30. Jacobs, L. R., Polak, J., Bloom, S. R.,

1976, 50, 14P.

Introduction INFUSION of dextrose-free aminoacid solution

was

pro-

posed as a method with fewer technical and metabolic problems than intravenous hyperalimentation (LV.H.) for sparing body nitrogen in postoperative patients.’ Others2-6 have confirmed that in postoperative patients nitrogen balance is improved, at least to some extent, by such

However, all these studies have been patients after moderate surgery and the

treatment.

in

mainly nitrogen spared over the study period is a very small proportion (about 2-3%) of the total-body nitrogen. The clinical usefulness of this treatment in major surgery where nitrogen losses are large needs to be determined. Does aminoacid infusion (A.A.L) conserve body nitrogen after major surgery when losses of nitrogen would otherwise be large? Does A.A.I. shorten hospital stay and enhance wound healing in such patients, and how do these effects compare with those obtained from a full course Of I.V.H.? Patients and Methods

patients awaiting abdominoperineal excision of the panproctocolectomy were interviewed and their informed consent to the study was obtained. These patients were then allocated to three groups (controls, A.A. I., and I.V.H.) to achieve matching for sex, age, weight, degree of weight-loss, preoperative diagnosis, and extent of planned operation (table i). In each case the extent of the subsequent surgery was the same as that planned. There were originally thirty-three patients in the trial. One patient who was in the A.A.I. group had abdominal wound dehiscence on the 5th postoperative day and his surgeon was unhappy with him continuing in the trial. The control patient and the I.V.H. patient with whom he was Adult

rectum or

matched were also withdrawn from the trial.

Body-composition Measurements Dowling,

R. H. Clin. Sci. molec. Med.

Body composition

was

investigated immediately before sur-

789 TABLE I-PATIENT DATA BEFORE OPERATION IN THREE MATCHED GROUPS

*Difference between pre-illness weight (as stated by patient) and measured weight. tRectal excision + small-bowel resection.

F.:.=fa;ca! incontinence.

ulcerative colitis. c.D. = Crohn’s disease.

p=proctocolectomy.

u.c.

=

c.R. R.P.

rectal carcinoma. =radiation proctitis. =

R.E.=rectal excision.

gery and 15 days after surgery. The patients were weighed and the thickness of the mid-biceps, mid-triceps, and subscapular skinfolds were measured 3 times with a Holtain skinfold calliper. The skinfold thickness was the sum of the means of the 3 measurements at these 3 sites. Total-body nitrogen (T.B.N.) was measured by in-vivo neutron-activation analysis.’ The patient was exposed to fast neutrons and immediately after this he was transferred to a whole-body counter where both the induced radioactivity (T.B.N.) and the naturally occurring radioactivity from 40K (total-body potassium [T.B.K.]) were measured. The coefficient of variation of repeated measurements of a subject of constant body composition is 2.6% for T.B.N. and 2.1% for T.B.K. The absolute error is believed to be small for T.B.K. and it is less than 10% for T.B.N.

litre of nutrient solution contained 500 ml of freamine n and 500 ml of 500 g/1 dextrose. To each litre of nutrient solution was added 40-50 mmol sodium, 20-40 mmol potassium, 8-15 mmol magnesium, and 12-18 mmol phosphate (as potassium acid salt). In addition 1 ampoule of a multivitamin preparation (’Multibionta’, Merck) was administered daily in the nutrient solution as well as appropriate intramuscular doses of folate, vitamin K, and vitamin B,2. The A.A.I. group received intravenously 0.23±0-02 g nitrogen/kg/day over an average period of 12.5+1.4 days and the I.V.H. group received intravenously 36-5+3-5 kcal/kg/day and 0.23+0.03 g nitrogen/kg/day over an average period of

Surgery

patient in the aminoacid group axillary-vein thromdeveloped on the 13th postoperative day, which settled spontaneously when the catheter was removed. There were no other complications from either of the intravenous techniques. No major surgical complications occurred in any of the thirty patients. Student’s t test was used to see whether the changes within each group were significantly different from zero. This test was also used to see whether the mean changes between groups were significantly different.

All the patients were managed in a similar manner. Before surgery each received intramuscular injections of antibiotics (gentamicin 80 mg, lincomycin 600 mg) with anaesthetic premedication and these antibiotics were given again 8 h later. The patients with inflammatory bowel disease received hydrocortisone over the perioperative period according to a standard protocol. The perineal wounds were managed by the method of primary suture of perineum and pelvic peritoneum described by Irvin and Goligher. Primary wound healing was said to have occurred if, on the 12th postoperative day, the wound was intact with no serous or pus leakage. In those perineal wounds in which healing was delayed the wound was described as healed when complete epithelialisation had occurred.

Nutrition After surgery all patients were allowed free voluntary food intake as soon as this could be tolerated. This was usually between the 4th and 6th day. In six control patients and six A.A.I. patients oral intake was assessed by the precise weighing technique at 7 days and again at 14 days after surgery. At 7 days the controls ate an average of 22 kcal/kg/day (range 13-42) and the A.A. patients ate an average of 20 kcal/kg/day (range 2-29). At 14 days the controls ate an average of 29 kcal/kg/day (range 9-44) and the A.A.I. patients ate an average of 28 kcal/kg/day (range 13-45). The patients in the control group received no intravenous nutrition therapy and were maintained in fluid balance by intravenous electrolyte solutions (1-8g/1 saline with 40 g/1 dextrose or 9 g/1 saline) until sufficient oral intake was achieved. On the 2nd postoperative day all patients in the other two groups had a central venous catheter inserted. They were then given 2-3 1 of an intravenous nutrient solution every 24 h. For the A.A.I. group each litre of nutrient solution contained 500 ml of an 85 g/1 solution of synthetic aminoacids (’Freamine 11’, McGaw) and 500 ml of water and for the i.v.H. group each

13.4:t2.5days.

Complications In

one

bosis

Results

Body Composition Mean changes in body-weight, skinfold thickness, T.B.N., and

T.B.K.

for the three groups before and 15

days after surgery are shown in table n. Weight, skinfold thickness, T.B.N., and T.B.K. were significantly lower atter 15days in the control group, but with the exception of weight these measurements did not change significantly in patients receiving either i.v.H. or A.A.I. The mean change in weight after surgery was significantly lower in the A.A.I. group and significantly higher in the I.V.H. group. The mean changes observed in the control from group were all significantly different (P