- Email: [email protected]
TREATMENT OF MESENTERIC EMBOLISM WITH DEXTRAN 40
567 reliance should be placed on exclusion of the condition by a negative result. In other populations and in other regions a positive serological result may be of greater significance. Whereas none of the sera from patients with chronic non-specific ulcerative colitis gave positive results, antibodies were present in all those with ulcerative postdysenteric colitis following acute amoebic dysentery. Distinction between these forms of colitis by clinical and other means may be extremely difficult (Powell and Wilmot 1966) but it is evident that serological distinction is possible. Whilst much disagreement exists regarding the pathogenicity of E. histolytica there is no doubt that the consequences of bowel infection vary greatly. In many instances the amoeba seems to be no more than a commensal and in others tissue invasion is so slight that symptoms, if not entirely absent, bear a doubtful relationship to the organism. In yet other instances infection results in a relatively mild and chronic form of diarrhoea or dysentery. It should be stressed that amoebic dysentery in our patients is a severe disease with considerable tissue invasion. We do not know if our serological findings are
applicable
to
patients
with
only mildly symptomatic
infections. The incidence of antibodies in asymptomatic cyst-passers has been found to be higher than in the random local African population (Maddison et al. 1965) but we do not have information on those forms of intestinal amoebiasis associated with vague symptoms and chronic ill-health which are commonly reported. In general, the presence of antibodies is an indication of past or present tissue invasion by E. histolytica. Although the amoebic gel-diffusion precipitin-test appears slightly less sensitive in dysentery than in liver abscess, the results are much more consistent than those obtained by the complement-fixation test (Elsdon-Dew and Maddison 1952). The test should be of some value in distinguishing between those patients in whom invasive amoebae are the direct cause of symptoms and those in whom the presence of E. histolytica and symptoms are merely coincidental.
Summary The results of the amoebic gel-diffusion precipitin-test have been evaluated in 526 patients with dysentery. Whereas the incidence of antibodies in bacillary dysentery was the same as that of a control group of 371 patients without dysentery or evidence of amoebiasis (16%), 92% of those with proved acute amoebic dysentery, and 35 % of those with dysentery of undetermined aetiology were positive. All the patients with ulcerative post-dysenteric colitis were positive and all with chronic non-specific ulcerative colitis were negative. Although the test has less clinical value in acute amoebic dysentery than in amoebic liver-abscess it should be of use when tissue invasion of the bowel by E. histolytica is
suspected. We thank Prof. E. B. Adams and our colleagues in the department of medicine of the University of Natal for their cooperation; Dr. R. Wright, Radcliffe Infirmary, Oxford, for supplying sera; and Dr. R. Nupen, acting medical superintendent, King Edward VIII Hospital, Durban. The Amcebiasis Research Unit is sponsored by the South African Council for Scientific and Industrial Research, the Natal Provincial Administration, the University of Natal, and the United States Public Health Service (grant no. AI 01592). REFERENCES
Elsdon-Dew, R., Maddison, S. E. (1952) J. trop. Med. Hyg. 55, 208. Maddison, S. E. (1965) Expl Parasit. 16, 224. — Powell, S. J., Elsdon-Dew, R. (1965) Am. J. trop. Med. Hyg. 14, 554. Powell, S. J., Maddison, S. E., Wilmot, A. J., Elsdon-Dew, R. (1965) Lancet, ii, 602. Wilmot, A. J. (1966) Unpublished. -
TREATMENT OF MESENTERIC EMBOLISM WITH DEXTRAN 40 W. J. DANIEL Melb., F.R.C.S.E.
M.B.
REGISTRAR IN SURGERY
M.B.
S. D. MOHAMED Glasg., M.R.C.P.E., M.R.C.P.
SENIOR REGISTRAR AND CLINICAL TUTOR IN MEDICINE
Ch.M.
N. A. MATHESON Aberd., F.R.C.S.E., F.R.C.S.
SENIOR LECTURER IN SURGERY
From the and
University Departments of Surgery and Materia Medica Therapeutics and the Royal Infirmary, Aberdeen
LOW-MOLECULAR-WEIGHT dextran (dextran 40, ’Rheomacrodex ’), a dextran fraction with a mean molecular weight of 40,000, was introduced into clinical use as a substance with important biorheological properties. In particular, dextran 40 seems to counteract aggregation of red blood-cells in vitro (Thorsen and Hint 1950) and there is evidence to support the claim of Gelin and Ingelman (1961) that a similar effect operates in vivo. Since the viscosity of blood is increased by red bloodcell aggregation (Dintenfass 1962), reversal of intravascular aggregation is likely to improve tissue perfusion. But the clinical implications of intravascular red blood-cell aggregation are still uncertain and, although dextran 40 has been advised in a wide variety of conditions in which tissue perfusion may be impaired (Bergentz et al. 1961), its usefulness is still imprecisely defined. There is no doubt, however, that in dogs dextran 40 can afford definite protection against infarction when a segment of small bowel is deprived of its arterial bloodsupply (D’Angelo et al. 1963). Similarly, Lepley et al. (1962) have reported convincing evidence of benefit from dextran 40 after acute occlusion of the superior mesenteric vein in dogs. Yet the use of dextran 40 in the treatment of mesenteric vascular occlusion in man has seldom been described. Serjeant (1965) described 1 patient in whom the clinical features strongly supported a presumptive diagnosis of mesenteric embolism and whose symptoms were rapidly ameliorated with dextran 40. The present report concerns a patient, treated with dextran 40, in whom extensive and severe ischasmia of the gut, consequent on mesenteric embolism, was confirmed at laparotomy. At re-exploration 2 days later there was evidence of improved intestinal perfusion and, despite the development of acute renal failure the patient recovered completely. Subsequent studies of intestinal function showed no notable abnormality.
Case-report A 71-year-old man, with a previous history of gastroenterostomy for duodenal ulcer in 1956, a myocardial infarction in 1958, and deep-vein thrombosis and pulmonary embolism in 1961, was readmitted on March 23,1965, with severe anginal pain. He showed cardiomegaly and auricular fibrillation and there was electrocardiographic evidence of previous anterior and posterior myocardial infarcts. Urinalysis showed no abnormality; the blood-urea was 40 mg. per 100 ml. It was considered likely that further ischasmic myocardial damage had been sustained; treatment was symptomatic. 6 days later he complained of vague abdominal pain and on the next day mild tenderness and signs of peritoneal irritation were elicited to the left of the mid-abdomen. He vomited twice; and the stool contained occult blood. Mesenteric embolism was diagnosed. At operation, the proximal five feet of jejunum was normally
568
perfused; thereafter, the small intestine and proximal colon were discoloured and cyanosed. Pulsation could not be seen in the subserosal vessels from a point five feet from the duodenojejunal flexure to a point just distal to the hepatic flexure of the colon. It was judged that an embolus had lodged in the superior mesenteric artery at the origin of the ileocolic artery. The anaesthetist advised that the patient’s general condition was against embolectomy and, since the situation was similar that in which dextran 40 had been shown to be of definite benefit in dogs, we decided to use this substance and to reexplore the abdomen 48 hours later so that infarcted bowel could be removed. The proximal limit of absent pulsation in subserosal vessels was marked with a seromuscular silk suture. A gastrostomy was fashioned for gastrointestinal decompression, and the abdomen was closed. On the day of operation (day 1) 2 litres of dextran 40 in dextrose was infused and treatment with 100% oxygen by an Aviator ’ mask and intravenous heparin in doses controlled by the clotting-time was started. On day 2, 1 litre of dextran 40 in dextrose was infused. On day 3, abdominal tenderness was still present. At re-exploration all of the small intestine was viable and the colour of its distal part seemed to have improved. The proximal limit of absent pulsation was unchanged but pulsation could now be seen in the subserosal vessels supplying the caecum; in addition, the subserosal vessels of the terminal ileum were clearly filled with well-oxygenated blood. At the end of the second operation the patient’s general condition was very poor with periods of intermittent mild hypotension and moderate hypoxxmia from sputum retention. Acute renal failure was considered as a possible complication and 1 litre of 10% mannitol was infused, besides 1 litre of dextran 40, resulting in a urinary output of 1100 ml. Sputum retention was treated with physiotherapy and endoscopic aspiration, and 30% oxygen by a Venturi mask was substituted for 100% oxygen. On day 4, 1 litre of dextran 40 was infused and the urine volume was 400 ml.; on day 5, during which 700 ml. of dextran 40 was given, the urine volume fell to 40 ml. despite infusion of a further 500 ml. of 10% mannitol. Thereafter the patient was anuric for 4 days. An arteriovenous shunt was inserted and hsemodialysis was carried out on three occasions before the diuretic phase became established on the 19th day. His subsequent progress was uneventful. 7 weeks after the mesenteric embolisation investigations to detect any residual defect in small-bowel function were undertaken. The haemoglobin was 60% (Sahli), the packed-cell volume (P.c.v.) 29%, and the mean corpuscular hxmoglobin concentration (M.c.H.c.) 32%. The serum-iron and the total iron-binding capacity (Ramsay 1957) were 71 {g. per 100 ml. and 270 g. per 100 ml. respectively. The serum-calcium and serum-alkaline-phosphatase were normal at 4-6 mEq. per litre and 13 and 10 King-Armstrong units respectively. Serumalbumin was 3-9 g. per 100 ml. and there was slight elevation of the oe2-globulin (16%) and y-globulin (21%). Daily excretion of faecal fat over three 3-day collection periods averaged 3-2, 2-9, and 1-9 g. respectively. Duplicate D-xylose excretion tests gave 3-2 g. and 4-1 g. for the 0-5 hour samples and 3-2 g. and 1-6 g. for the 5-24 hour samples; the cumulative excretion for 24 hours was normal at 6-4 and 5-7 g. Hepatic surface radioactivity after an oral test dose (0-55 (J.C, 0-55 g.) of "Co-labelled vitamin B12 (Mohamed and Tulloch 1966) was 1700 counts per minute per C of the dose (normal, more than 900 counts per minute per µC) and the serum-vitaminB12 activity for Lactobacillus leichmannii was 632 pg. per ml. (normal 160-190 pg. per ml.) 8-hour excretions of histidine metabolites after a 15 g. histidine load (Mohamed and Roberts 1965, Roberts and Mohamed 1965) were: formiminoglutamic acid, 40 mg. (normal, less than 30 mg.) and urocanic acid 20 mg. (normal less than 15 mg.). A barium meal and followthrough examination showed a normal small-bowel mucosal pattern. Oral iron was given and, 4 weeks later, the haemoglobin had risen to 85% (Sahli) though the normal pretreatment M.c.H.C. and serum-iron values were in accord with a dyshaemopoietic to
’
pr6cess from failure of iron utilisation due to the prolonged and complicated illness. 2 months later, he had gained 11 lb. in weight and the haemoglobin had risen to 92% (p.c.v. 40% M.C.H.c. 33.5%). He has remained well and entirely symptomfree. In November, 1965, further detailed tests of small-bowel absorptive function gave normal results. The blood values were
haemoglobin 110% (Sahli),
P.c.v.
49%,
M.c.H.c.
32,7%,
and reticulocytes 1-2%. The serum-proteins had reverted to normal and a repeat histidine load test showed normal excretions of formiminoglutamic and urocanic acids.
Discussion
This case-report describes an elderly unfit man who had acute and extensive intestinal ischxmia, from occlusion of the superior mesenteric artery. The diagnosis was confirmed at operation and the patient was treated with dextran 40, heparin, and oxygen. 48 hours later, at a second operation, intestinal perfusion seemed to have improved. Subsequently, after a complicated clinical course, the patient recovered completely, gained weight, and showed no notable residual defect of intestinal function. Experimentally, the mucosa and submucosa bear the brunt of intestinal ischxmia (Klein 1921) and malabsorption from intestinal vascular insufficiency has often been recognised (Joske et al. 1958, Shaw and Maynard 1958, Heard et al. 1963). Shaw (1958), however, could not produce malabsorption in experimental animals with chronic mesenteric arterial insufficiency. Heard et al. (1963) suggested that absorptive defects perhaps occurred only when acute and severe ischaemia had persisted long enough to cause serious intestinal injury before relief. Thus, the absence of small-bowel absorptive defects during convalescence in the present patient suggests that amelioration of the initial acute ischaemia occurred before sufficient intestinal injury had been sustained. Although it cannot definitely be concluded that dextran 40 was solely responsible for the restoration of intestinal perfusion, the favourable outcome in the present case, taken together with the experience of Serjeant (1965) in similar circumstances, suggests that beneficial effects similar to those observed in the dog may also obtain in acute mesenteric vascular insufficiency in man. Ideally, there is a need for a controlled trial of dextran 40 in clinical mesenteric occlusion but the practical considerations and the ethical problems in an otherwise often lethal disease are formidable. Meantime, the outcome, favourable or otherwise, in patients such as the present one, where treatment with dextran 40 was dictated by the patient’s poor general condition, should be fully reported. The observed effects of dextran 40 after mesenteric occlusion in the dog have generally been attributed to disaggregation of red blood-cells with resulting improvement of blood-flow in adjacent tissue. The relative inefficiency of dextran 80 (Swedish-American clinical dextran) in mesenteric venous occlusion in dogs (Lepley et al. 1962) favours this explanation and detracts from the possibility that either plasma-volume expansion or antihxmostatic properties of dextran are wholly responsible. Finally, acute renal failure during treatment with dextran 40 merits comment. 5 patients who developed acute oliguric renal failure in association with the administration of dextran 40 have been described (Gracey 1966, Wilkinson 1966). However, the xtiological factors of
oliguric renal failure in any particular patient are often obscure and dextran 40 is often used in patients who, by the nature or severity of their antecedent illness, In all but 1 of the are liable to develop renal failure. acute
569
patients previously described, and in the present patient, there was adequate cause for renal failure without attributing it to dextran 40. Present evidence is inadequate to incriminate dextran 40
as a cause
of
acute
renal failure.
Summary with mesenteric embolism and intestinal ischsemia, confirmed at laparotomy, was treated with low-molecular-weight dextran. 48 hours later, at re-exploration, the previously ischasmic bowel was still viable and there was evidence of improved perfusion. Despite the complication of acute renal failure the patient recovered completely and detailed studies did not show any residual defect in small-bowel A
71-year-old
extensive
man
acute
congestive cardiac failure due to mitral stenosis and auricular fibrillation, suddenly developed severe abdominal pain with localised tenderness to the left of the umbilicus. The stool contained occult blood. A distal segmental occlusion of the superior mesenteric artery was diagnosed and the patient was treated with dextran 40 and heparin: the abdominal symptoms were relieved within 3 hours and convalescence was uneventful. REFERENCES
Bergentz, S.-E., Gelin, L.-E., Rudenstam, C.-M., Zederfeldt, B. (1961) Acta chir. scand. 122, 343. D’Angelo, G. J., Ameriso, L. M., Tredway, J. B. (1963) Circulation, 27, 662. Dintenfass, L. (1962) Circulation Res. 11, 233. Gelin, L.-E., Ingelman, B. (1961) Acta chir. scand. 122, 294. Gracey, L. (1966) in Reports of Symposia on Rheomacrodex; vol. 1, p. 50. London.
absorption.
Joske, R. A., Shamma’A, M. H., Drummey, G. D. (1958) Am. J. Med. 25,
We thank Dr. A. A. Dawson for the serum-vitamin-B12 estimation and Dr. M. B. Roberts for help with the histidine-load tests. Requests for reprints should be addressed to Mr. N. A. Matheson, Department of Surgery, University Medical Buildings, Foresterhill, Aberdeen.
Heard, G., Jefferies, J. D., Peters, D. K. (1963) Lancet, ii, 975. Klein, E. (1921) Surgery Gynec. Obstet. 33, 385. Lepley, D., Mani, C. J., Ellison, E. H. (1962) J. surg. Res. 2, 403. Mohamed, S. D., Roberts, M. (1966) J. clin. Path. (in the press). Tulloch, M. (1966). Unpublished. Ramsay, W. N. M. (1957) Clin. chim. Acta, 2, 214, 221. Roberts, M., Mohamed, S. D. (1965) J. clin. Path. 18, 214. Serjeant, J. C. B. (1965) Lancet, i, 139. Shaw, R. S. (1958) New Engl. J. Med. 259, 347. Maynard, E. P. (1958) ibid. 258, 874. Thorsen, G., Hint, H. (1950) Acta chir. scand. suppl. 154. Wilkinson, R. (1966) in Reports of Symposia on Rheomacrodex; vol. 2, p. 21. London.
Addendum
Since the above report was submitted, another patient with mesenteric embolism has been treated with dextran 40. This patient, a woman aged 61, while recovering from
Preliminary Communications
for aneurysms
arising from that blood-vessel, 4 had had bleeding which had proved fatal in 2. We had
therefore decided that direct attack on the lesion method of choice.
was
the
The figures are not significant statistically, but they do reflect the bad results in aneurysms of the anterior communicating and middle cerebral arteries. Yet the morbidity and mortality of surgical treatment must in the end be TABLE I-OPERATIVE RESULTS IN INTRACRANIAL ANEURYSMS
preferable
-
-
TABLE II-OPERATIVE RESULTS WITH THE DREW
CIRCULATORY ARREST IN NEUROSURGERY IN 1961 we reviewed the results of operation in 100 consecutive cases of intracranial aneurysm that had been referred to this centre-these were out of 198 referred cases (table i). We had become convinced that proximal ligation in these cases was unsatisfactory. Out of 17 patients who had undergone ligation of the carotid artery recurrent
449.
to the risk of disaster from future haemorrhage if the lesion is left untreated. We had had the impression, for instance, that the outlook was better in untreated cases of aneurysm of the anterior communicating artery, but all our patients who had been refused operation over a two-year period had died of recurrent hxmorrhage. The bad results of surgery in patients whose condition was otherwise satisfactory were often due to operating in areas where severe haemorrhage was a constant danger. Temporary occlusion of the carotid and vertebral arteries in the neck had proved inadequate. Temporary occlusion of small intracranial blood-vessels, too, was ineffective; the requisite dissection was disastrous, largely because of
TECHNIQUE
the perforating vessels, quite apart from temporary permanent damage to the vessel walls. The great success of the Drew1 technique of profound hypothermia in cardiac surgery led us to adopt this method for obtaining a perfectly dry field. This method consists of a double extracorporeal circulation bypassing each ventricle, the patient’s lungs being used as the oxygenating mechanism. The heparinised blood is cooled outside the body by means of a heat exchanger in the systemic circuit. A temperature of 15°C in the brain can be obtained with this method, and total arrest of the circulation can be tolerated for forty-five to fifty minutes, during which the intracranial lesion can be treated. 8 patients underwent this treatment (table 11). They were all in the worst operative group, but the results were bad, not only because of bleeding due to heparin but also from the added morbidity and mortality arising from the artificial circulation. We decided this method was not applicable to intracranial surgery. Our dissatisfaction was tempered by the knowledge that we needed only a few minutes to deal with the vascular anomaly in a dry field. We returned therefore to the principle of moderate surface cooling to a temperature of about 30°C.
damage
to
or
METHOD
Whilst the craniotomy was in progress the chest was opened by a vertical sternotomy, and at the moment that ischsmia was required the great vessels arising from the aorta were clamped. To our amazement this had little effect on haemorrhage from the vascular lesion, and we concluded that the anastomotic circulation through the superior intercostal vessels and the induced peripheral hypertension were the cause of this failure. We therefore decided to use circulatory arrest by the method 1.
Drew, C. E., Keen, G., Benazon, D.
B.
Lancet, 1959, i, 745.
applicable
to
patients
with
only mildly symptomatic
infections. The incidence of antibodies in asymptomatic cyst-passers has been found to be higher than in the random local African population (Maddison et al. 1965) but we do not have information on those forms of intestinal amoebiasis associated with vague symptoms and chronic ill-health which are commonly reported. In general, the presence of antibodies is an indication of past or present tissue invasion by E. histolytica. Although the amoebic gel-diffusion precipitin-test appears slightly less sensitive in dysentery than in liver abscess, the results are much more consistent than those obtained by the complement-fixation test (Elsdon-Dew and Maddison 1952). The test should be of some value in distinguishing between those patients in whom invasive amoebae are the direct cause of symptoms and those in whom the presence of E. histolytica and symptoms are merely coincidental.
Summary The results of the amoebic gel-diffusion precipitin-test have been evaluated in 526 patients with dysentery. Whereas the incidence of antibodies in bacillary dysentery was the same as that of a control group of 371 patients without dysentery or evidence of amoebiasis (16%), 92% of those with proved acute amoebic dysentery, and 35 % of those with dysentery of undetermined aetiology were positive. All the patients with ulcerative post-dysenteric colitis were positive and all with chronic non-specific ulcerative colitis were negative. Although the test has less clinical value in acute amoebic dysentery than in amoebic liver-abscess it should be of use when tissue invasion of the bowel by E. histolytica is
suspected. We thank Prof. E. B. Adams and our colleagues in the department of medicine of the University of Natal for their cooperation; Dr. R. Wright, Radcliffe Infirmary, Oxford, for supplying sera; and Dr. R. Nupen, acting medical superintendent, King Edward VIII Hospital, Durban. The Amcebiasis Research Unit is sponsored by the South African Council for Scientific and Industrial Research, the Natal Provincial Administration, the University of Natal, and the United States Public Health Service (grant no. AI 01592). REFERENCES
Elsdon-Dew, R., Maddison, S. E. (1952) J. trop. Med. Hyg. 55, 208. Maddison, S. E. (1965) Expl Parasit. 16, 224. — Powell, S. J., Elsdon-Dew, R. (1965) Am. J. trop. Med. Hyg. 14, 554. Powell, S. J., Maddison, S. E., Wilmot, A. J., Elsdon-Dew, R. (1965) Lancet, ii, 602. Wilmot, A. J. (1966) Unpublished. -
TREATMENT OF MESENTERIC EMBOLISM WITH DEXTRAN 40 W. J. DANIEL Melb., F.R.C.S.E.
M.B.
REGISTRAR IN SURGERY
M.B.
S. D. MOHAMED Glasg., M.R.C.P.E., M.R.C.P.
SENIOR REGISTRAR AND CLINICAL TUTOR IN MEDICINE
Ch.M.
N. A. MATHESON Aberd., F.R.C.S.E., F.R.C.S.
SENIOR LECTURER IN SURGERY
From the and
University Departments of Surgery and Materia Medica Therapeutics and the Royal Infirmary, Aberdeen
LOW-MOLECULAR-WEIGHT dextran (dextran 40, ’Rheomacrodex ’), a dextran fraction with a mean molecular weight of 40,000, was introduced into clinical use as a substance with important biorheological properties. In particular, dextran 40 seems to counteract aggregation of red blood-cells in vitro (Thorsen and Hint 1950) and there is evidence to support the claim of Gelin and Ingelman (1961) that a similar effect operates in vivo. Since the viscosity of blood is increased by red bloodcell aggregation (Dintenfass 1962), reversal of intravascular aggregation is likely to improve tissue perfusion. But the clinical implications of intravascular red blood-cell aggregation are still uncertain and, although dextran 40 has been advised in a wide variety of conditions in which tissue perfusion may be impaired (Bergentz et al. 1961), its usefulness is still imprecisely defined. There is no doubt, however, that in dogs dextran 40 can afford definite protection against infarction when a segment of small bowel is deprived of its arterial bloodsupply (D’Angelo et al. 1963). Similarly, Lepley et al. (1962) have reported convincing evidence of benefit from dextran 40 after acute occlusion of the superior mesenteric vein in dogs. Yet the use of dextran 40 in the treatment of mesenteric vascular occlusion in man has seldom been described. Serjeant (1965) described 1 patient in whom the clinical features strongly supported a presumptive diagnosis of mesenteric embolism and whose symptoms were rapidly ameliorated with dextran 40. The present report concerns a patient, treated with dextran 40, in whom extensive and severe ischasmia of the gut, consequent on mesenteric embolism, was confirmed at laparotomy. At re-exploration 2 days later there was evidence of improved intestinal perfusion and, despite the development of acute renal failure the patient recovered completely. Subsequent studies of intestinal function showed no notable abnormality.
Case-report A 71-year-old man, with a previous history of gastroenterostomy for duodenal ulcer in 1956, a myocardial infarction in 1958, and deep-vein thrombosis and pulmonary embolism in 1961, was readmitted on March 23,1965, with severe anginal pain. He showed cardiomegaly and auricular fibrillation and there was electrocardiographic evidence of previous anterior and posterior myocardial infarcts. Urinalysis showed no abnormality; the blood-urea was 40 mg. per 100 ml. It was considered likely that further ischasmic myocardial damage had been sustained; treatment was symptomatic. 6 days later he complained of vague abdominal pain and on the next day mild tenderness and signs of peritoneal irritation were elicited to the left of the mid-abdomen. He vomited twice; and the stool contained occult blood. Mesenteric embolism was diagnosed. At operation, the proximal five feet of jejunum was normally
568
perfused; thereafter, the small intestine and proximal colon were discoloured and cyanosed. Pulsation could not be seen in the subserosal vessels from a point five feet from the duodenojejunal flexure to a point just distal to the hepatic flexure of the colon. It was judged that an embolus had lodged in the superior mesenteric artery at the origin of the ileocolic artery. The anaesthetist advised that the patient’s general condition was against embolectomy and, since the situation was similar that in which dextran 40 had been shown to be of definite benefit in dogs, we decided to use this substance and to reexplore the abdomen 48 hours later so that infarcted bowel could be removed. The proximal limit of absent pulsation in subserosal vessels was marked with a seromuscular silk suture. A gastrostomy was fashioned for gastrointestinal decompression, and the abdomen was closed. On the day of operation (day 1) 2 litres of dextran 40 in dextrose was infused and treatment with 100% oxygen by an Aviator ’ mask and intravenous heparin in doses controlled by the clotting-time was started. On day 2, 1 litre of dextran 40 in dextrose was infused. On day 3, abdominal tenderness was still present. At re-exploration all of the small intestine was viable and the colour of its distal part seemed to have improved. The proximal limit of absent pulsation was unchanged but pulsation could now be seen in the subserosal vessels supplying the caecum; in addition, the subserosal vessels of the terminal ileum were clearly filled with well-oxygenated blood. At the end of the second operation the patient’s general condition was very poor with periods of intermittent mild hypotension and moderate hypoxxmia from sputum retention. Acute renal failure was considered as a possible complication and 1 litre of 10% mannitol was infused, besides 1 litre of dextran 40, resulting in a urinary output of 1100 ml. Sputum retention was treated with physiotherapy and endoscopic aspiration, and 30% oxygen by a Venturi mask was substituted for 100% oxygen. On day 4, 1 litre of dextran 40 was infused and the urine volume was 400 ml.; on day 5, during which 700 ml. of dextran 40 was given, the urine volume fell to 40 ml. despite infusion of a further 500 ml. of 10% mannitol. Thereafter the patient was anuric for 4 days. An arteriovenous shunt was inserted and hsemodialysis was carried out on three occasions before the diuretic phase became established on the 19th day. His subsequent progress was uneventful. 7 weeks after the mesenteric embolisation investigations to detect any residual defect in small-bowel function were undertaken. The haemoglobin was 60% (Sahli), the packed-cell volume (P.c.v.) 29%, and the mean corpuscular hxmoglobin concentration (M.c.H.c.) 32%. The serum-iron and the total iron-binding capacity (Ramsay 1957) were 71 {g. per 100 ml. and 270 g. per 100 ml. respectively. The serum-calcium and serum-alkaline-phosphatase were normal at 4-6 mEq. per litre and 13 and 10 King-Armstrong units respectively. Serumalbumin was 3-9 g. per 100 ml. and there was slight elevation of the oe2-globulin (16%) and y-globulin (21%). Daily excretion of faecal fat over three 3-day collection periods averaged 3-2, 2-9, and 1-9 g. respectively. Duplicate D-xylose excretion tests gave 3-2 g. and 4-1 g. for the 0-5 hour samples and 3-2 g. and 1-6 g. for the 5-24 hour samples; the cumulative excretion for 24 hours was normal at 6-4 and 5-7 g. Hepatic surface radioactivity after an oral test dose (0-55 (J.C, 0-55 g.) of "Co-labelled vitamin B12 (Mohamed and Tulloch 1966) was 1700 counts per minute per C of the dose (normal, more than 900 counts per minute per µC) and the serum-vitaminB12 activity for Lactobacillus leichmannii was 632 pg. per ml. (normal 160-190 pg. per ml.) 8-hour excretions of histidine metabolites after a 15 g. histidine load (Mohamed and Roberts 1965, Roberts and Mohamed 1965) were: formiminoglutamic acid, 40 mg. (normal, less than 30 mg.) and urocanic acid 20 mg. (normal less than 15 mg.). A barium meal and followthrough examination showed a normal small-bowel mucosal pattern. Oral iron was given and, 4 weeks later, the haemoglobin had risen to 85% (Sahli) though the normal pretreatment M.c.H.C. and serum-iron values were in accord with a dyshaemopoietic to
’
pr6cess from failure of iron utilisation due to the prolonged and complicated illness. 2 months later, he had gained 11 lb. in weight and the haemoglobin had risen to 92% (p.c.v. 40% M.C.H.c. 33.5%). He has remained well and entirely symptomfree. In November, 1965, further detailed tests of small-bowel absorptive function gave normal results. The blood values were
haemoglobin 110% (Sahli),
P.c.v.
49%,
M.c.H.c.
32,7%,
and reticulocytes 1-2%. The serum-proteins had reverted to normal and a repeat histidine load test showed normal excretions of formiminoglutamic and urocanic acids.
Discussion
This case-report describes an elderly unfit man who had acute and extensive intestinal ischxmia, from occlusion of the superior mesenteric artery. The diagnosis was confirmed at operation and the patient was treated with dextran 40, heparin, and oxygen. 48 hours later, at a second operation, intestinal perfusion seemed to have improved. Subsequently, after a complicated clinical course, the patient recovered completely, gained weight, and showed no notable residual defect of intestinal function. Experimentally, the mucosa and submucosa bear the brunt of intestinal ischxmia (Klein 1921) and malabsorption from intestinal vascular insufficiency has often been recognised (Joske et al. 1958, Shaw and Maynard 1958, Heard et al. 1963). Shaw (1958), however, could not produce malabsorption in experimental animals with chronic mesenteric arterial insufficiency. Heard et al. (1963) suggested that absorptive defects perhaps occurred only when acute and severe ischaemia had persisted long enough to cause serious intestinal injury before relief. Thus, the absence of small-bowel absorptive defects during convalescence in the present patient suggests that amelioration of the initial acute ischaemia occurred before sufficient intestinal injury had been sustained. Although it cannot definitely be concluded that dextran 40 was solely responsible for the restoration of intestinal perfusion, the favourable outcome in the present case, taken together with the experience of Serjeant (1965) in similar circumstances, suggests that beneficial effects similar to those observed in the dog may also obtain in acute mesenteric vascular insufficiency in man. Ideally, there is a need for a controlled trial of dextran 40 in clinical mesenteric occlusion but the practical considerations and the ethical problems in an otherwise often lethal disease are formidable. Meantime, the outcome, favourable or otherwise, in patients such as the present one, where treatment with dextran 40 was dictated by the patient’s poor general condition, should be fully reported. The observed effects of dextran 40 after mesenteric occlusion in the dog have generally been attributed to disaggregation of red blood-cells with resulting improvement of blood-flow in adjacent tissue. The relative inefficiency of dextran 80 (Swedish-American clinical dextran) in mesenteric venous occlusion in dogs (Lepley et al. 1962) favours this explanation and detracts from the possibility that either plasma-volume expansion or antihxmostatic properties of dextran are wholly responsible. Finally, acute renal failure during treatment with dextran 40 merits comment. 5 patients who developed acute oliguric renal failure in association with the administration of dextran 40 have been described (Gracey 1966, Wilkinson 1966). However, the xtiological factors of
oliguric renal failure in any particular patient are often obscure and dextran 40 is often used in patients who, by the nature or severity of their antecedent illness, In all but 1 of the are liable to develop renal failure. acute
569
patients previously described, and in the present patient, there was adequate cause for renal failure without attributing it to dextran 40. Present evidence is inadequate to incriminate dextran 40
as a cause
of
acute
renal failure.
Summary with mesenteric embolism and intestinal ischsemia, confirmed at laparotomy, was treated with low-molecular-weight dextran. 48 hours later, at re-exploration, the previously ischasmic bowel was still viable and there was evidence of improved perfusion. Despite the complication of acute renal failure the patient recovered completely and detailed studies did not show any residual defect in small-bowel A
71-year-old
extensive
man
acute
congestive cardiac failure due to mitral stenosis and auricular fibrillation, suddenly developed severe abdominal pain with localised tenderness to the left of the umbilicus. The stool contained occult blood. A distal segmental occlusion of the superior mesenteric artery was diagnosed and the patient was treated with dextran 40 and heparin: the abdominal symptoms were relieved within 3 hours and convalescence was uneventful. REFERENCES
Bergentz, S.-E., Gelin, L.-E., Rudenstam, C.-M., Zederfeldt, B. (1961) Acta chir. scand. 122, 343. D’Angelo, G. J., Ameriso, L. M., Tredway, J. B. (1963) Circulation, 27, 662. Dintenfass, L. (1962) Circulation Res. 11, 233. Gelin, L.-E., Ingelman, B. (1961) Acta chir. scand. 122, 294. Gracey, L. (1966) in Reports of Symposia on Rheomacrodex; vol. 1, p. 50. London.
absorption.
Joske, R. A., Shamma’A, M. H., Drummey, G. D. (1958) Am. J. Med. 25,
We thank Dr. A. A. Dawson for the serum-vitamin-B12 estimation and Dr. M. B. Roberts for help with the histidine-load tests. Requests for reprints should be addressed to Mr. N. A. Matheson, Department of Surgery, University Medical Buildings, Foresterhill, Aberdeen.
Heard, G., Jefferies, J. D., Peters, D. K. (1963) Lancet, ii, 975. Klein, E. (1921) Surgery Gynec. Obstet. 33, 385. Lepley, D., Mani, C. J., Ellison, E. H. (1962) J. surg. Res. 2, 403. Mohamed, S. D., Roberts, M. (1966) J. clin. Path. (in the press). Tulloch, M. (1966). Unpublished. Ramsay, W. N. M. (1957) Clin. chim. Acta, 2, 214, 221. Roberts, M., Mohamed, S. D. (1965) J. clin. Path. 18, 214. Serjeant, J. C. B. (1965) Lancet, i, 139. Shaw, R. S. (1958) New Engl. J. Med. 259, 347. Maynard, E. P. (1958) ibid. 258, 874. Thorsen, G., Hint, H. (1950) Acta chir. scand. suppl. 154. Wilkinson, R. (1966) in Reports of Symposia on Rheomacrodex; vol. 2, p. 21. London.
Addendum
Since the above report was submitted, another patient with mesenteric embolism has been treated with dextran 40. This patient, a woman aged 61, while recovering from
Preliminary Communications
for aneurysms
arising from that blood-vessel, 4 had had bleeding which had proved fatal in 2. We had
therefore decided that direct attack on the lesion method of choice.
was
the
The figures are not significant statistically, but they do reflect the bad results in aneurysms of the anterior communicating and middle cerebral arteries. Yet the morbidity and mortality of surgical treatment must in the end be TABLE I-OPERATIVE RESULTS IN INTRACRANIAL ANEURYSMS
preferable
-
-
TABLE II-OPERATIVE RESULTS WITH THE DREW
CIRCULATORY ARREST IN NEUROSURGERY IN 1961 we reviewed the results of operation in 100 consecutive cases of intracranial aneurysm that had been referred to this centre-these were out of 198 referred cases (table i). We had become convinced that proximal ligation in these cases was unsatisfactory. Out of 17 patients who had undergone ligation of the carotid artery recurrent
449.
to the risk of disaster from future haemorrhage if the lesion is left untreated. We had had the impression, for instance, that the outlook was better in untreated cases of aneurysm of the anterior communicating artery, but all our patients who had been refused operation over a two-year period had died of recurrent hxmorrhage. The bad results of surgery in patients whose condition was otherwise satisfactory were often due to operating in areas where severe haemorrhage was a constant danger. Temporary occlusion of the carotid and vertebral arteries in the neck had proved inadequate. Temporary occlusion of small intracranial blood-vessels, too, was ineffective; the requisite dissection was disastrous, largely because of
TECHNIQUE
the perforating vessels, quite apart from temporary permanent damage to the vessel walls. The great success of the Drew1 technique of profound hypothermia in cardiac surgery led us to adopt this method for obtaining a perfectly dry field. This method consists of a double extracorporeal circulation bypassing each ventricle, the patient’s lungs being used as the oxygenating mechanism. The heparinised blood is cooled outside the body by means of a heat exchanger in the systemic circuit. A temperature of 15°C in the brain can be obtained with this method, and total arrest of the circulation can be tolerated for forty-five to fifty minutes, during which the intracranial lesion can be treated. 8 patients underwent this treatment (table 11). They were all in the worst operative group, but the results were bad, not only because of bleeding due to heparin but also from the added morbidity and mortality arising from the artificial circulation. We decided this method was not applicable to intracranial surgery. Our dissatisfaction was tempered by the knowledge that we needed only a few minutes to deal with the vascular anomaly in a dry field. We returned therefore to the principle of moderate surface cooling to a temperature of about 30°C.
damage
to
or
METHOD
Whilst the craniotomy was in progress the chest was opened by a vertical sternotomy, and at the moment that ischsmia was required the great vessels arising from the aorta were clamped. To our amazement this had little effect on haemorrhage from the vascular lesion, and we concluded that the anastomotic circulation through the superior intercostal vessels and the induced peripheral hypertension were the cause of this failure. We therefore decided to use circulatory arrest by the method 1.
Drew, C. E., Keen, G., Benazon, D.
B.
Lancet, 1959, i, 745.