635 TABLE VI-DEATH-RATES RELATED TO PREVIOUS ATTACKS

I

*

I

I

Biochemical or laparotomy evidence of acute pancreatitis on at least 1 TABLE VII-DEATH-RATES I

I

previous occasion.

RELATED TO OPERATION I

*As a precipitating event or for diagnostic or therapeutic reasons.

the apparent cause, and irrespective of the severity of the illness as assessed clinically. This approach was adopted deliberately for the sake of simplicity in a multicentre trial and because exclusions would presuppose special knowledge about the effect of one or other drug. Conclusions may be drawn with some confidence because the randomisation procedure achieved an acceptably even distribution of patients of different categories between the treatment groups. The most important finding is that the chance of dying of acute pancreatitis does not appear to be influenced by glucagon or aprotinin in the doses used. Although it might be argued that subtle effects have been missed in the smaller subgroups, the statisticall5 estimated differences were so small that they can be ever

safely disregarded. The death-rate of 11% may surprise some, because much higher rates have been reported.2 Several factors may explain the apparent discrepancy. First, participation in the trial may have influenced centres to seek patients very actively-possibly increasing the proportion with relatively mild disease. Next, concepts of intensive therapy, both in the ward and in specifically designated units, are being applied with increasing vigour and might be expected to improve the prognosis in a disease with such dramatic effects on metabolism and the cardiorespiratory system. Further, all patients were admitted to the trial, including those with a recurrent attack in whom the death-rate is known to be low.3 The present analysis has concentrated on death-rates and has failed to reveal an effect for either agent. The large store of data will now be analysed for further information. It will be important to see whether eithei drug causes the disease to run a milder and less complicated course in the survivors. The data will also be used to examine the hypothesis4 that patients who will die o] acute pancreatitis can be recognised early in the illnes by the presence of a number of indicators (such as blood pressure below a certain level). The outcome of this trial is useful for at least two rea sons. First, the use of these relatively expensive drugs it acute pancreatitis must now be questioned seriously. Thi

ineffectiveness of aprotinin has recently been confirmed in another trial. Second, although there were no major side-effects in any patient, one patient who had first been exposed to the drug during the trial apparently died of aprotinin hypersensitivity in a subsequent attack." This death emphasises the need for precautionary measures, such as intradermal testing, before this drug is used. The Working Party wishes to thank Miss S. L. Suen and Mrs F. Amirgholy for data-processing assistance, Dr P. Wilding of the Wolfson Research Laboratories, Queen Elizabeth Medical Centre, Birmingham, for advice on the amylase estimation, Bayer Pharmaceuticals Ltd and Eli Lilly & Co. Ltd for the supplies of aprotinin, glucagon, and placebo, and the surgeons and patients of the following centres, and above all the local supervising surgeons: Bangour General Hospital (Mr A. A. Gunn), Belfast City Hospital (Mr R. C. Curry), Bristol Hospitals (Mr R. C. N. Williamson, Mr R. G. Hughes, Mr N. I. Ramus, Mr M. H. Ornstein, Mr B. A. Shorey), Glasgow Western Infirmary (Mr W. R. Murray), North Middlesex Hospital (Mr B. Brara), Manchester Royal Infirmary (Mr D. Allan, Mr R. J. Williams), Newcastle upon Tyne Hospitals (Mr D. C. Britton), Norfolk and Norwich Hospitals (Mr B. Mayou, Mr S. Janvrin), Scarborough Hospital (Miss M.

Evans).

Requests for reprints should be addressed to Mr A. G. Cox, Northwick Park Hospital, Watford Road, Harrow, Middlesex, HA13UJ. F.R.C.S.

REFERENCES 1.

Trapnell, J. E., Rigby, C. C., Talbot, C. H., Duncan, E. H. L. Br. J. Surg. 1974, 61, 177. 2. Condon, J. R., Knight, M., Day, J. L. ibid. 1973, 60, 509. 3. Trapnell, J. E., Duncan, E. H. L. Br. med. J. 1975, i, 179. 4. Ranson, J. H. C., Pasternak, B. S. J. surg. Res. 1977, 22, 79. 5. Imrie, C. W., Bejamin, I. S., Ferguson, J. C., Thomson, W. O., McKay, A. J., Blumgart, L. H. Pancreatic Society of Great Britain and Ireland, Newcastle meeting, 1977. 6. Proud, G., Chamberlain, J. Lancet, 1976, ii, 48.

ALTERATION IN FIBRINOLYTIC CAPACITY AFTER OPERATION

N. J. GRIFFITHS

M. WOODFORD

M. H. IRVING

Department of Surgery, University of Manchester School of Medicine, Hope Hospital, Salford, M6 8HD The fibrinolytic response to 20 min of forearm venous occlusion was studied in patients undergoing major and minor operations. Fibrinolytic capacity, which is defined as the increase in fibrinolytic activity resulting from a period of venous occlusion, was significantly reduced on the first postoperative day after major operations, but not after minor operations. Since venous occlusion results in the release of plasminogen activator from the vascular endothelium into the blood, these findings suggest that the reduction in the level of spontaneous fibrinolytic activity after major operations is the result either of

Summary

636 exhaustion of the vascular endothelium of plasminogen activator or defective synthesis and release of this enzyme from the endothelium.

TABLE II-E.C.L.T. CHANGES AFTER

20

MIN OF FOREARM VENOCS

OCCLUSION ON DAY BEFORE OPERATION AND ON DAY AFTER OPERATION IN PATIENTS UNDERGOING

MAJOR AND MINOR

OPERATIONS

Introduction AFTER trauma and surgical operations, there is a reduction in the level of spontaneous fibrinolytic activity in the blood. This reduction is greatest in the early postoperative period.1,2 It has been suggested that postoperative venous thrombosis is associated with this reduction in systemic fibrinolysis. 1,2 Spontaneous systemic fibrinolytic activity is probably maintained by constant diffusion of the enzyme, plasminogen activator, from the vascular endothelium into the circulation.3 As this enzyme arises predominantly from the venous endothelium,4 a reduction in systemic fibrinolytic activity might reflect either a failure of the endothelium to release this enzyme or exhaustion of the plasminogen-activator content of the cells. Of the various methods used to assess the fibrinolytic response of the endothelium, venous occlusion of a limb is probably the most widely recognised and reproducible. A period of venous occlusion results in the release of plasminogen activatorfrom the vascular endothelium into the occluded venous blood,6 increasing the fibrinolytic activity in the blood. This present study investigates the influence of major and minor operation on the postoperative response to forearm venous occlusion. Materials and Methods We studied twenty patients, all of whom gave informed conbefore the investigations. Ten patients (five men and five women aged between 20 and 66 years) underwent major upper abdominal operations. In this group the type of muscle-relaxant anxsthesia used was the same in each case, but the length of operation varied (mean 100 min, range 40-135 min). The minor-operation group consisted of ten men aged 31-61 years undergoing hernia repair. The mean operation-time in this group was 30 min (range 20-40 min). Again the type of anwsthesia used was identical in each case, but no muscle relaxants were used. Forearm venous occlusion was undertaken at a fixed time on the morning of the day before operation and again on the morning of the first postoperative day. The same arm was used on the two occasions because of the suggested discrepancies between right and left arm.7 The technique of venous occlusion was as described by Robertson et al.7 The patient, after a 5 min rest, had a sphygmomanometer cuff applied around the arm and inflated to a pressure midway between systolic and diastolic for 20 min. Venous samples were taken immediately before the cuff was inflated and then again just before deflation of the cuff. Further venous samples were taken after induction of anwsthesia, at the middle of the operation, and just before reversal of ansesthesia, or, in the case of the group having minor surgery, at the end of the operation. sent

TABLE I-E.C.L.T. CHANGES DURING AND AFTER

i

All

samples

mately

r

were

4°C and the

i

i

i

transported melting ice at approxiwas estimated by the activity fibrinolytic on

euglobulin clot-lysis time (E.C.L.T.) method of Nilsson and Olow8 by means of an automatic clot-lysis time recorder,9 with the results expressed in minutes. Plasma-fibrinogen was measured in all the venous samples by means of the modified technique of Ratnoff and Menzie.1o Because of the uneven distribution of results, all E.C.L.T. results were transformed to the log,o before statistical analysis.

Results

During major operations fibrinolytic activity increased, as demonstrated by a significant fall in the E.C.L.T. from the preoperative value to the mid-operative value (p

Alteration in fibrinolytic capacity after operation.

635 TABLE VI-DEATH-RATES RELATED TO PREVIOUS ATTACKS I * I I Biochemical or laparotomy evidence of acute pancreatitis on at least 1 TABLE VII-DEA...
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