Acute Mesenteric Ischaemia

Stefan Acosta

Address for correspondence:

Department of Clinical Sciences Malmö, Lund University. E-mail: stefan.acosta@med.lu.se

Senior Consultant. Department of Cardio-Thoracic and Vascular Surgery, Skåne University Hospital. Ruth Lundskogsg 10, SE – 205 02 Malmö, Sweden.

Acute mesenteric ischaemia (AMI) is one of the deadliest acute diseases. The spectrum of disease encompasses acute mesenteric arterial occlusion, but also mesenteric venous thrombosis, and non-occlusive mesenteric ischaemia. AMI is not uncommon. It is simply not diagnosed in time and a large proportion will die undiagnosed. The contemporary incidence of acute mesenteric arterial occlusion in population-based studies is underestimated, mainly due to the low autopsy rate. The evolution of high-resolution CT has had an impact on the diagnosis of acute mesenteric occlusive ischaemia. It is important that CT protocols for acute abdomen are optimal for imaging of the mesenteric vessels. The rate of intervention for intestinal revascularization is very low in acute mesenteric arterial occlusion and needs to be better to improve outcomes. Patients managed by vascular surgeons are highly selected, and may undergo intestinal revascularisation; their prognosis will be better than for those managed simply by bowel resection or only palliative treatment. It is desirable that patients with AMI should have access to treatment in a hybrid theatre, and by a clinical team able to offer a full range of open, hybrid or endovascular interventions during a single procedure.

Acute mesenteric ischaemia (AMI) is regarded as one of the deadliest acute diseases. Despite rapid technical evolution of computed tomography (CT) scanners available around the clock in high-income countries, prognosis remains poor. In acute mesenteric arterial occlusion, intestinal revascularisation is necessary due to development of ischaemia of the jejunum, ileum, and colon, and is a prerequisite for survival in half of the patients¹Acosta S, Ögren M, Sternby N-H, Bergqvist D, Björck M: Clinical implications for the management of acute thromboembolic occlusion of the superior mesenteric artery. Autopsy findings in 213 patients. Ann Surg 2005; 241: 516 – 22.. The development of a pathway to increase awareness for early diagnosis, and hybrid operation rooms for open and endovascular technique are steps forward to improve revascularisation rates, and outcomes in a few highly specialised vascular centres around the world. In acute mesenteric venous thrombosis, development towards transmural intestinal infarction is slower and the extent of intestinal ischaemia is more limited than mesenteric arterial occlusion, allowing timely diagnosis with CT more often for successful treatment with anticoagulation therapy alone. Prognosis for mesenteric venous thrombosis has improved over the last decades. Non-occlusive mesenteric ischaemia (NOMI), often secondary to heart failure or multiple organ failure, has on the other hand, a continued dismal prognosis.

Three main branches of the abdominal aorta vascularise the gastro-intestinal tract: the coeliac artery (CA), the superior mesenteric artery (SMA) and the inferior mesenteric artery (IMA). The CA provides blood supply to the stomach, liver, part of pancreas and the proximal part of the duodenum. The SMA provides blood supply to the distal duodenum, small bowel and up to the mid transverse colon. Blood supply to the distal colon is provided by the IMA, which is relatively small compared to the CA and SMA. Collaterals connect the three main branches, and these can exist within one mesenteric artery or between two mesenteric arteries.

The mesenteric venous system is localized parallel to the mesenteric arterial system. The superior mesenteric vein (SMV) receives venous blood from the duodenal, pancreatic, right gastroepiploic, jejunal, ileal, right colic and middle colic veins. The splenic vein and SMV drain into the portal vein (PV).The CA receives 800 ml blood/minute and the SMA 500 ml/minute, increasing up to 1100 ml/min and 1400 ml/min after a meal, respectively¹Kolkman JJ, Mensink P. Non-occlusive mesenteric ischaemia: a common disorder in gastroenterology and intensive care. Best Pract Res Clin Gastroenterol 2003; 17: 457 – 473.. Branches of these arteries enter the serosa on the mesenteric side to form a serosal vascular plexus around the gut. The blood is directed to the submucosal plexus and finally to the mucosa.

Originally, the term AMI was defined as occurrence of acute mesenteric thromboembolic arterial occlusion, acute mesenteric venous thrombosis or NOMI resulting in bowel injury within the distribution of the superior mesenteric vessels¹Kaleya RN, Boley SJ. Acute mesenteric ischaemia. Crit Care Clin 1995; 11: 479 – 512.. In the more contemporary literature, the diagnosis of NOMI includes clinical scenarios such as colonic ischaemia, usually left-sided, following repair of abdominal aortic aneurysm²Björck M, Koelemay M, Acosta S, Bastos Goncalves, Kölbel T, Kolkman JJ, et al. Management of the diseases of mesenteric arteries and veins. Eur J Vasc Endovasc Surg 2017; 53: 460 – 510.. The left colon is not supplied by the SMA, and isolated left-sided, sometimes mild and transient, colonic ischaemia³Brandt LJ, Feuerstadt P, Longstreth GF, Boley S. ACG Clinical Guideline: Epidemiology, Risk factors, patterns of presentation, diagnosis and management of colon ischemia (CI). Am J Gastroenterol 2015; 110: 18 – 74., or the misnomer “ischaemic colitis”, secondary to a vascular disorder, are not included in the definition of NOMI or AMI in the ESVS Guidelines⁴Björck M, Koelemay M, Acosta S, Bastos Goncalves, Kölbel T, Kolkman JJ, et al. Management of the diseases of mesenteric arteries and veins. Eur J Vasc Endovasc Surg 2017; 53: 460 – 510.. Patients who die from causes other than colon infarction, but who terminally develop moderate mucosal ischaemia in the colon without small bowel ischaemia found at autopsy are labelled as colonic ischaemia⁵Acosta S, Ögren M, Sternby N-H, Bergqvist D, Björck M. Fatal colonic ischaemia: A population-based study. Scand J Gastroenterol 2006; 41: 1312 – 1319..

History

Acute occlusion of the superior mesenteric artery (SMA) has been recognized as a cause of abdominal catastrophe since 1875, based on an experimental work on the effects of ligature of the mesenteric vessels¹Litten M. Uber die Folgen des Verschlusses der Arteria Mesaraica Superior. Arch Pathol Anat 1875; 63: 289.. Recovery following bowel resection of infarcted intestine secondary to mesenteric vessel occlusion was first reported in 1895²Elliott JW. The operative relief of gangrene of the intestine due to occlusion of the mesenteric vessels. Ann Surg 1895; 21: 9.. The first reported successful embolectomy of the SMA was performed in 1951³Stewart GD, Sweetman WR, Westphal K, Wise RA. Superior mesenteric artery embolectomy. Ann Surg 1960; 151: 274., successful thrombendarterectomy in 1958⁴Shaw RS, Maynard EP. Acute and chronic thrombosis of the mesenteric arteries associated with malabsorption. N Engl J Med 1958; 258: 874 – 878., aorto-mesenteric by-pass in 1973⁵Ribet M, Quandalle P, Wurtz A. Ischémies aigues coelio-mésenteriques; interventions de revascularization. Ann Chir 1973; 27: 626 – 30. and local intra-arterial thrombolysis in 1979⁶Jamieson AC, Thomas RJ, Cade JF. Lysis of a superior mesenteric artery embolus following loc al infusion streptokinase and heparin. Aust N Z J Surg 1979; 49: 355 – 356..

Pathophysiology

In AMI, whatever the cause, the infarction starts from the mucosa side and outwards to the serosa side⁷Haglund U, Bulkley GB, Granger DN. On the pathophysiology of intestinal ischaemic injury. Acta Chir Scand 1987; 153: 321 – 324.. This means that visible signs of intestinal infarction at laparotomy appear later than on the mucosa side. Infarction may be much more extensive on the mucosa than on the serosa side and the surgeon performing a bowel resection with anastomosis needs to be aware of this difference.

Epidemiology

Incidence and mortality estimates for AMI can only be determined from population-based studies with a high autopsy rate⁸Acosta S. Epidemiology of mesenteric vascular disease: clinical implications. Semin Vasc Surg. 2010 Mar;23(1):4 – 8.. In a population-based study with an autopsy rate of 87%, conducted between 1970 and 1982 in Malmö, Sweden, 79% of patients with occlusive arterial AMI were diagnosed at autopsy. The incidence was 8.6 (95% CI 7.6 – 9.7)/100 000 person years and mortality rate was 93%⁹Acosta S, Ögren M, Sternby NH, Bergqvist D, Björck M. Incidence of Acute Thrombo-Embolic Occlusion of the Superior Mesenteric Artery—A Population-based Study. Eur J Vasc Endovasc Surg 2004; 27: 145 – 150.. The overall incidence was higher among women, 10.1 (95% CI 8.5 – 11.6)/ 100 000 person years, compared to men, 7.1 (95% CI 5.7-8.4)/100 000 person years.

In a more contemporaneous population-based study with an autopsy rate of 32%, conducted between 2006 and 2015 in Helsinki, Finland, 29% were diagnosed post-mortem. The overall incidence rate was 3.1 (95% CI 2.8 – 3.3)/100 000 person years and overall 90-day mortality was 83%¹⁰Lemma A, Tolonen M, Vikatmaa P, Mentula P, Kantonen I, But A, Leppäniemi A, Sallinen V. Epidemiology, diagnostics and outcomes of acute occlusive arterial mesenteric ischaemia – a population-based study. Eur J Vasc Endovasc Surg 2022; 64: 646 – 653..

Diagnosis

The diagnosis should be considered when there is severe abdominal pain with initially minimal abdominal signs (pain out of proportion) in an elderly patient. Suspicion of mesenteric arterial embolic occlusion must be considered if there is co-existing atrial fibrillation or history of arterial embolism or synchronous embolism. Mesenteric arterial thrombotic occlusion is more likely in a patient with history of atherosclerotic disease. A patient with pre-existing symptoms of chronic mesenteric ischaemia such as weight loss, postprandial abdominal pain and gastrointestinal complaints/food fear, suggests the diagnosis is AMI due to mesenteric arterial thrombosis¹¹Terlouw LG, Moelker A, Abrahamsen J, Acosta S, Bakker OJ, Baumgartner I, et al. European guidelines on chronic mesenteric ischaemia – joint United European Gastroenterology, European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Gastrointestinal and Abdominal Radiology, Netherlands Association of Hepatogastroenterologists, Hellenic Society of Gastroenterology, Cardiovascular and Interventional Radiological Society of Europe, and Dutch Mesenteric Study group clinical guidelines on the diagnosis and treatment of patients with chronic mesenteric ischaemia. United European Gastroenterology Journal 2020; 8: 371 – 395.. Pain out of proportion, accompanied by rapid and often forceful bowel evacuation, and a source of embolus/previous history of embolism has been termed the clinical triad of early acute embolic occlusion¹²Kaleya RN, Sammartano RJ, Boley SJ. Aggressive approach to acute mesenteric ischaemia. Surg Clin North Am 1992; 72: 157 – 182.. These symptoms sometimes fade, leaving the patient falsely improved until necrosis of the bowel and peritonitis develop.

There are no accurate plasma biomarkers for AMI¹³Nuzzo A, Guedj K, Curac S, Hercend C, Bendavid C, Gault N, et al. Accuracy of citrulline, I-FABP and D-lactate in the diagnosis of acute mesenteric ischaemia. Sci Rep 2021; 11: 18929.. A normal D-dimer at presentation most likely excludes the diagnosis¹⁴Acosta S, Nilsson TK, Björck M. D-dimer testing in patients with suspected acute thromboembolic occlusion of the superior mesenteric artery. Br J Surg 2004; 91: 991 – 4.. There are diagnostic laboratory pitfalls that may mislead clinicians away from the diagnosis of AMI, such as elevated troponin I, pancreas amylase and normal plasma lactate¹⁵Acosta S, Block T, Björnsson S, Resch T, Björck M, Nilsson T. Diagnostic pitfalls at admission in patients with acute superior mesenteric artery occlusion. J Emerg Med 2012; 42: 635 – 41..

Computed tomography with intravenous contrast enhancement and imaging in the arterial phase is highly accurate for the diagnosis of acute mesenteric arterial occlusion. Clinical suspicion of AMI in the radiology request letter optimises the CT protocol, resulting in better diagnostic accuracy¹⁶Anglaret S, Dallongeville A, Beaussier H, Touloupas C, Boulay I, Tardivel AM, et al. Influence of clinical suspicion on CT accuracy of acute mesenteric ischemia: Retrospective study of 362 patients. Eur J Radiol 2021; 138: 109652.. A tailored CT protocol may be used in patients with an acute abdomen to improve diagnostic accuracy for AMI, even if it is not suspected clinically. CT can accurately visualize the location of mesenteric arterial occlusion and evaluate secondary signs of intestinal ischaemia. Timely diagnosis is when there is visible mesenteric arterial occlusion without any signs of intestinal ischaemia¹⁷Wadman M, Block T, Ekberg O, Syk I, Elmståhl S, Acosta S. Impact of MDCT with intravenous contrast on the survival in patients with acute superior mesenteric artery occlusion. Emerg Radiol 2010; 17: 171 – 178..

Treatment and Management

The SMA is almost exclusively the target artery for revascularization. Intestinal revascularization is necessary in most patients since the extent of intestinal infarction involves the jejunum. ileum and colon in 50% of the patients, and at least two of these intestinal segments in 82%¹⁸Acosta S, Ögren M, Sternby N-H, Bergqvist D, Björck M: Clinical implications for the management of acute thromboembolic occlusion of the superior mesenteric artery. Autopsy findings in 213 patients. Ann Surg 2005; 241: 516 – 22.. From pre-operative clinical evaluation it has to be determined if the patient has peritonitis or not, and from the CT angiography it should be determined whether the patient has an embolic or thrombotic occlusion. Then the patient should preferably be treated in a vascular centre with a hybrid operating room. If peritonitis, the patient should undergo laparotomy for evaluation of severity and extent of intestinal ischaemia (Fig 1). Open, endovascular or hybrid revascularisation should precede bowel surgery if there is no bowel perforation. Completion imaging with angiography or transit time flow measurement should be considered¹⁹Björck M, Koelemay M, Acosta S, Bastos Goncalves, Kölbel T, Kolkman JJ, et al. Management of the diseases of mesenteric arteries and veins. Eur J Vasc Endovasc Surg 2017; 53: 460 – 510.. Vascular surgery should be tailored based on whether laparotomy is indicated or not, whether the occlusion is embolic or thrombotic, and local expertise (Fig 1). Open SMA embolectomy for embolic occlusion and stenting for thrombotic occlusion are main options for intestinal revascularisation in centres that can offer both open and endovascular therapy. Local SMA thrombolysis with, or without adjunctive aspiration thromboembolectomy is an excellent method if used on patients without peritonitis²⁰Björnsson S, Björck M, Block T, Resch T, Acosta S. Thrombolysis for acute occlusion of the superior mesenteric artery. J Vasc Surg 2011; 54: 1734 – 1742.. Aspiration²¹Liu YR, Tong Z, Hou C-B, Cui S-J, Guo L-R, Qi Y-X. Aspiration therapy for cute embolic occlusion of the superior mesenteric artery. World J Gastroenterol 2019; 25: 848 – 858. or mechanical dissolution²²Freitas B, Bausback Y, Schuster J, Ulrich M, Bräunlich S, Schmidt A, et al. Thrombectomy devices in the treatment of acute mesenteric ischemia: Initial single-center experience. Ann Vasc Surg 2018; 51: 124 – 131. of thromboembolic clots with, or without subsequent need for laparotomy can be useful endovascular techniques. Retrograde open mesenteric stenting (ROMS) (Fig 2-3) is a useful approach after laparotomy, which also can be used when percutaneous transfemoral or brachial-first access with recanalization to the distal SMA fails²³Oderich G, Macedo R, Stone DH, Woo EY, Panneton JM Resch T. Multicenter study of retrograde open mesenteric artery stenting through laparotomy for treatment of acute and chronic mesenteric ischaemia. J Vasc Surg 2018; 68: 470 – 480.. ROMS can be performed with considerable shorter operative times than bypasses to the SMA in AMI²⁴Andraska E, Haga L, Li X, Avgerinos E, Singh M, Chaer R, et al. Retrograde open mesenteric stenting should be considered as the initial approach to acute mesenteric ischemia. J Vasc Surg 2020; 72: 1260 – 8.. It is easier to recanalize the SMA from within the exposed SMA than from peripheral arterial access sites. Open vascular surgery for acute thrombotic SMA occlusion has not been proven to have inferior outcomes than endovascular therapy or ROMS, and procedures like thrombendartectomy of the SMA, reimplantation of the SMA and aorto-iliac bypasses to the SMA are valid options²⁵Hou L, Wang T, Wang J, Zhao J, Yuan D. Outcomes of different acute meenteric ischemia therapies in the last 20 years: A meta-analysis and systematic review. Vascular 2021 Jun 21; 17085381211024503.. The concepts of second look laparotomy and damage control surgery should be considered in patients with peritonitis undergoing intestinal revascularisation²⁶Ding W, Wang K, Liu B, Fan X, Wang S, Cao J, et al. Open abdomen improves survival in patients with peritonitis secondary to acute superior mesenteric artery occlusion. J Clin Gastroenterol 2017; 51: e77 – e82.. The intestinal revascularisation rate is presently too low, 3%²⁷Beaulieu RJ, Arnaoutakis KD, Abularrage CJ, Efron DT, Schneider E, Black JH. Comparison of open and endovascular treatment of acute mesenteric ischemia. J Vasc Surg 2014;59 : 159–64. according to nationwide register studies in the US, and needs to be increased considerably to have an impact on lowering bowel morbidity and mortality rates.

Figure 1. Suggested simplified modern management of acute mesenteric arterial ischaemia. ROMS = Retrograde open mesenteric stenting.

Figure 2. Hybrid approach in a patient with acute thrombotic occlusion of the SMA. Computed tomography angiography with sagittal reconstruction showing a heavily calcified occlusive lesion at the ostium of the superior mesenteric artery (white arrow), a thrombotic lesion superimposed of on the atherosclerosis at the ostium (black line), and contrast filling in a stenotic part of the superior mesenteric artery (white line) (A). After laparotomy, the SMA was exposed followed by retrograde puncture of the SMA, passage of a guidewire across the occlusive lesion, which was first dilated with a 2 mm balloon, followed by passage of a 4 Fr Cobra slip catheter downstream to the infra-renal aorta. After retrograde puncture in the right common femoral artery, a long introducer and a snare (B) were brought up to catch the guidewire (C) introduced from the SMA, to establish through-and-through wire access (D) by bringing the guidewire out of the introducer that was inserted in the groin. The introducer was then advanced into the proximal SMA, followed by antegrade stenting with a short balloon expandable stent, followed by a longer self-expandable stent extension (E).

Figure 3. Laparotomy showed extensive small bowel ischaemia with appearance of cyanosis, poor peristalsis, and slight dilatation of small bowel loops (A). Rapid recovery of normal color of the small bowel loops and peristalsis was noted before closing the abdomen (B). The patient had an uneventful recovery.

Prognosis and Follow Up

Prognosis is highly dependent on study era, evolving diagnostic methods and autopsy rate in patient series. Short-term overall mortality is above 80% in population-based studies²⁸Lemma A, Tolonen M, Vikatmaa P, Mentula P, Kantonen I, But A, Leppäniemi A, Sallinen V. Epidemiology, diagnostics and outcomes of acute occlusive arterial mesenteric ischaemia – a population-based study. Eur J Vasc Endovasc Surg 2022; 64: 646 – 653.. In patients surviving AMI, secondary prevention including smoking cessation, statin therapy, and antiplatelet therapy for patients with thrombotic occlusion, and anticoagulation treatment in patients with embolic occlusion, is recommended²⁹Björck M, Koelemay M, Acosta S, Bastos Goncalves, Kölbel T, Kolkman JJ, et al. Management of the diseases of mesenteric arteries and veins. Eur J Vasc Endovasc Surg 2017; 53: 460 – 510..

History

Mesenteric venous thrombosis (MVT) was recognised as a cause of intestinal gangrene in 1895 by Elliott, who treated the infarcted bowel by resecting it, creating two stomas, and reanastomosing them two weeks later¹Elliott JW. The operative relief of gangrene of the intestine due to occlusion of the mesenteric vessels. Ann Surg 1895; 21: 9.. There was a delay in recognizing MVT as a distinct cause of AMI, differentiated from acute mesenteric arterial occlusion; the first report was in 1935 by Warren an Eberhard²Warren S, Eberhard TP. Mesenteric venous thrombosis. Surg Gynecol Obstet 1935; 61: 102 – 21.. Following the development of heparin, anticoagulants were first used to treat MVT in 1940³Strohl EL, Lasner J. Mesenteric venous occlusion. Arch Surg 1950; 60: 339 – 42., and were shown to be associated with improved outcome in 1965 by Naitove and Weisman⁴Naitove A, Weismann RE. Primary mesenteric venous thrombosis. Ann Surg 1965; 161: 516 – 23.. The first open thrombectomy was described in 1974 by Bergentz⁵Bergentz SE, Erticsson B, Hedner U, Leandoer L, Nilsson IM. Thrombosis in the superior mesenteric and portal veins: report of a case treated with thrombectomy. Surgery 1974; 76: 286 – 90., and the first use of percutaneous transhepatic local thrombolysis was reported in 1988 by Yankes⁶Yankes JR, Uglietta JP, Grant J, Braun SD. Percutaneous transhepatic recanalization and thrombolysis of the superior mesenteric vein. AJR Am J Roentgenol 1988; 151: 289 – 90..

Pathogenesis

There are three major pathways for the pathogenesis of MVT:

1. Direct injury including abdominal trauma, surgical procedures such as splenectomy and bariatric surgery, acute pancreatitis, and inflammatory bowel disease.
2. Local venous congestion such as portal hypertension/liver cirrhosis, severe congestive heart failure and morbid obesity.
3. Acquired thrombophilia such as especially pancreatic cancer, and oral contraceptive use. Inherited thrombophilia such as Factor V Leiden mutation⁷Zarrouk M, Salim S, Elf J, Gottsater A, Acosta S. Testing for thrombophilia in mesenteric venous thrombosis – Retrospective study and systematic review. Best Pract Res Clin Gastroenterol 2017; 31: 39 – 48..

MVT causes stasis of the mesentery and impaired venous run-off from a typically limited segment of bowel, resulting in localised mesenteric oedema, swollen bowel, and discoloration of the most affected small bowel. The intestinal infarction is often limited to the jejunum and/or ileum⁸Acosta S, Ögren M, Sternby NH, Bergqvist D, Björck M. Mesenteric venous thrombosis with transmural intestinal infarction: A population-based study. J Vasc Surg 2005; 41: 59 – 63.. When dividing the adjacent mesentery to the infarcted intestinal segment at surgery, thrombotic material will be seen originating from minor vein branches.

Epidemiology

The relative ratio between MVT and acute SMA occlusion was less than 1:4 in a population-based study⁹Acosta S. Epidemiology of mesenteric vascular disease: clinical implications. Semin Vasc Surg. 2010 Mar;23(1):4 – 8.. The estimated overall population-based incidences of MVT in Malmö 1970 to 1982¹⁰Zarrouk M, Salim S, Elf J, Gottsater A, Acosta S. Testing for thrombophilia in mesenteric venous thrombosis – Retrospective study and systematic review. Best Pract Res Clin Gastroenterol 2017; 31: 39 – 48., and 2000 – 2006 were similar¹¹Acosta S, Alhadad A, Svensson P, Ekberg O. Epidemiology, risk and prognostic factors in mesenteric venous thrombosis. Br J Surg 2008; 95: 1245 – 1251.: 1.8 (95% CI 1.3 – 2.2)/100 000 and 2.7 (95% CI 2.0 – 3.5)/100 000 person years, respectively, with equal incidences in both sexes.

Diagnosis

Clinical diagnosis is most challenging and imaging requests to radiology seldom include suspicion of MVT (or AMI)¹²Salim S, Ekberg O, Elf J, Zarrouk M, Gottsäter A, Acosta S. Clinical implications of CT findings in mesenteric venous thrombosis at admission. Emerg Radiol 2018; 25: 407 – 413.. Acute onset of abdominal pain will typically occur within 1 – 3 days of thrombus formation, whereas there is a sub-acute type that may present over days or weeks with nonspecific symptoms. The pain of acute MVT is mid abdominal and colicky, suggesting an origin from the small bowel. Melaena, haematemesis, or rectal bleeding occur in only 15%, whereas occult bleeding may be present in 50% of patients¹³Kumar S, Sarr MG, Kamath PS. Mesenteric venous thrombosis. N Engl J Med 2001; 345: 1683 – 8.. Fever and sign of peritonitis suggest progression of ischaemia towards intestinal infarction¹⁴Hmoud B, Singal AK, Kamath PS. Mesenteric venous thrombosis. J Clin Exp Hepatol 2014; 4: 257 – 63.. The presence of MVT is associated with symptoms related to intestinal ischaemia in the overwhelmingly majority of patients, whereas patients with isolated portal vein thrombosis without extension of thrombosis to the SMV very seldom have symptoms of intestinal ischaemia¹⁵Amitrano L, Guardascione MA, Scaglione M, Pezzullo L, Sangiuliano N, Armellino MF, et al. Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol 2007; 102: 2464 – 70.. The insidious onset of abdominal pain over days in MVT, together with the availability of high-resolution CT scanners around the clock in high-income countries has had a tremendous impact on the early detection of MVT before transmural intestinal infarction and the need for bowel resection¹⁶Amitrano L, Guardascione MA, Scaglione M, Pezzullo L, Sangiuliano N, Armellino MF, et al. Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol 2007; 102: 2464 – 70.. The CT should be performed with intravenous contrast enhancement and imaging in the portal phase.

Treatment and Management

Timely diagnosis means no peritonitis at CT diagnosis; the condition is then manageable with anticoagulation therapy alone, and is successful in most patients¹⁷Salim S, Zarrouk M, Elf J, Gottsäter A, Ekberg O, Acosta S. Improved prognosis and low failure rate with anticoagulation as first-line therapy in mesenteric venous thrombosis. World J Surg 2018; 42: 3803 – 3811. (Fig 4). Direct oral anticoagulants, vitamin K antagonists or low molecular weight heparin may be tailored to the individual patient. Direct oral anticoagulants have been shown to be equally effective with the same rate of bleeding complications¹⁸Salim S, Ekberg O, Elf J, Zarrouk M, Gottsäter A, Acosta S. Evaluation of direct oral anticoagulants and vitamin K antagonists in mesenteric venous thrombosis. Phlebology 2019; 34: 171 – 178.. Patients with no strong permanent trigger factor for MVT such as intra-abdominal cancer should undergo blood screening for inherited and acquired thrombophilia¹⁹Acosta S, Salim S. Management of acute mesenteric venous thrombosis: A systematic review of contemporary studies. Scand J Surg 2021; 110: 123 – 129..

Figure 4. Suggested management of acute MVT.

Late presentation²⁰Feldman Z, Wang J, Chou EL, Latz CA, Sumpio BJ, Eagleton MJ, et al. Venous mesenteric ischemia carries high procedural burden and elevated mortality in patients with severe presentation. J Vasc Surg Venous Lymphat Disord 2021; 9: 1479 – 1487., failure of anticoagulation therapy or late diagnosis will be drivers for laparotomy and bowel resection, and endovascular intervention. Peritonitis means laparotomy and bowel resection. In eleven contemporary published series, the bowel resection rate was 44%²¹Acosta S, Salim S. Management of acute mesenteric venous thrombosis: A systematic review of contemporary studies. Scand J Surg 2021; 110: 123 – 129., which means that bowel resection is a very important treatment option for many patients. There are a variety of endovascular thrombolysis-based procedures that may be used in patients responding poorly to anticoagulation therapy²²Acosta S, Salim S. Management of acute mesenteric venous thrombosis: A systematic review of contemporary studies. Scand J Surg 2021; 110: 123 – 129.. Percutaneous transhepatic (Fig 5A) and percutaneous transjugular intrahepatic portosystemic shunt (Fig 5B) are the most important access routes to the SMV for subsequent thrombolysis.

Figure 5A-B. Schematic drawings of various ways of local delivery of thrombolysis for MVT. In Salim S. On Acute Mesenteric Venous Thrombosis. Lund: Lund University; 2020. Figures reused by permission from Robin Tran. A. Percutaneous hepatic access. B. Percutaneous transjugular intrahepatic portosystemic shunt including stentgraft placement in the shunt.

Prognosis and Follow Up

The 30-day mortality rate is often lower than 10% in modern series²³Salim S, Zarrouk M, Elf J, Gottsäter A, Ekberg O, Acosta S. Improved prognosis and low failure rate with anticoagulation as first-line therapy in mesenteric venous thrombosis. World J Surg 2018; 42: 3803 – 3811.,²⁴Feldman Z, Wang J, Chou EL, Latz CA, Sumpio BJ, Eagleton MJ, et al. Venous mesenteric ischemia carries high procedural burden and elevated mortality in patients with severe presentation. J Vasc Surg Venous Lymphat Disord 2021; 9: 1479 – 1487., but is likely to be higher in patients requiring intervention²⁵Feldman Z, Wang J, Chou EL, Latz CA, Sumpio BJ, Eagleton MJ, et al. Venous mesenteric ischemia carries high procedural burden and elevated mortality in patients with severe presentation. J Vasc Surg Venous Lymphat Disord 2021; 9: 1479 – 1487.. Small bowel wall oedema at CT was an independent predictor associated with need for bowel resection²⁶Salim S, Ekberg O, Elf J, Zarrouk M, Gottsäter A, Acosta S. Clinical implications of CT findings in mesenteric venous thrombosis at admission. Emerg Radiol 2018; 25: 407 – 413.. Mid-term mortality will be worse in patients with higher comorbidity²⁷Feldman Z, Wang J, Chou EL, Latz CA, Sumpio BJ, Eagleton MJ, et al. Venous mesenteric ischemia carries high procedural burden and elevated mortality in patients with severe presentation. J Vasc Surg Venous Lymphat Disord 2021; 9: 1479 – 1487., renal insufficiency²⁸Salim S, Zarrouk M, Elf J, Gottsäter A, Ekberg O, Acosta S. Improved prognosis and low failure rate with anticoagulation as first-line therapy in mesenteric venous thrombosis. World J Surg 2018; 42: 3803 – 3811.and cancer²⁹Feldman Z, Wang J, Chou EL, Latz CA, Sumpio BJ, Eagleton MJ, et al. Venous mesenteric ischemia carries high procedural burden and elevated mortality in patients with severe presentation. J Vasc Surg Venous Lymphat Disord 2021; 9: 1479 – 1487.. Life-long anticoagulation therapy will be necessary for those without a temporary trigger factor (Fig 4).

Definition

Non-occlusive mesenteric ischaemia (NOMI) is defined as a hypoperfusion syndrome that occurs when severe ischaemia of the intestines develops, despite the mesenteric arteries being patent. It is caused by either mesenteric vasoconstriction secondary to conditions such as heart failure, vasoconstrictive medication, repair of abdominal aortic aneurysm, and hypovolaemia, or by increased intra-abdominal pressure¹Björck M, Koelemay M, Acosta S, Bastos Goncalves, Kölbel T, Kolkman JJ, et al. Management of the diseases of mesenteric arteries and veins. Eur J Vasc Endovasc Surg 2017; 53: 460 – 510.⁴.

A special situation occurs if a mesenteric artery is occluded or stenosed without resulting in any symptoms before the patient develops hypovolaemia and/or hypotension.

Epidemiology

The overall incidence of autopsy-verified, fatal NOMI was 2.0/100 000 person-years, increasing up to 40/100 000 person-years in octogenarians, in a population with an autopsy rate of 87%²Acosta S, Ögren M, Sternby N-H, Bergqvist D, Björck M. Fatal nonocclusive mesenteric ischaemia: population-based incidence and risk factors. J Intern Med 2006; 259: 305 – 313..

Pathogenesis

Low cardiac output is the main cause of NOMI. In fatal NOMI, 40% had concomitant stenosis of the SMA³Acosta S, Ögren M, Sternby N-H, Bergqvist D, Björck M. Fatal nonocclusive mesenteric ischaemia: population-based incidence and risk factors. J Intern Med 2006; 259: 305 – 313.: Those with stenosis of the SMA were older and more likely to have additional stenosis of the coeliac trunk. Synchronous infarction of the liver, spleen or kidney occurred in 20% of the patients with fatal NOMI⁴Acosta S, Ögren M, Sternby N-H, Bergqvist D, Björck M. Fatal nonocclusive mesenteric ischaemia: population-based incidence and risk factors. J Intern Med 2006; 259: 305 – 313..

Risk factors

In a nested case-control study, matched for sex, age and year of death, risk factors for NOMI were recent surgery, cardiac failure and atrial fibrillation⁵Acosta S, Ögren M, Sternby N-H, Bergqvist D, Björck M. Fatal nonocclusive mesenteric ischaemia: population-based incidence and risk factors. J Intern Med 2006; 259: 305 – 313.. Patients undergoing chronic dialysis are also a high-risk disease group due to dialysis-associated hypotension, haemoconcentration, perhaps due to high-dose recombinant human erythropoietin therapy and mesenteric atherosclerosis, digoxin therapy and hypoalbuminemia⁶Ori Y, Chagnac A, Schwartz A, Herman M, Weinstein T, Zevin D, et al. Non-occlusive mesenteric ischemia in chronically dialyzed patients: A disease with multiple risk factors. Nephron Clin Pract 2005; 101:c87-c93.. Hypotension at the end of dialysis, when coupled with intravascular dehydration and a relatively high haematocrit, may initiate a low flow state in the SMA.

Diagnosis

Clinical suspicion is the mainstay of diagnosis in patients suspected of having NOMI. Of 33 patients with confirmed NOMI after cardiac arrest, 82% were reported to have gastro-intestinal manifestations beforehand⁷Paul M, Bougouin W, Legriel S, Charpentier J, Jaubert P, Savary G, et al. Frequency, risk factors, and outcomes of non-occlusive mesenteric ischaemia after cardiac arrest. Resuscitation 2020; 157: 211 – 218.: Vomiting, haematemesis, rectal bleeding and abdominal distension occurred in 48%, 21%, 18% and 39%, respectively. The location of ischaemia in the gastro-intestinal tract documented by CT and upper- or lower digestive endoscopy were: stomach/duodenum in 45%, jejunum/ileum in 26%, right colon in 36%, left colon in 39% and rectum in 33%. Bed-side laparoscopy in patients with suspected NOMI in intensive care after cardiac surgery has been suggested to improve early diagnosis⁸Bergamini C, Alemanno G, Giordano A, Pantalone D, Fontani G, Di Bella AM, et al. The role of bed-side laparoscopy in the management of acute mesenteric ischemia of recent onset in post-cardiac surgery patients admitted to the ICU. Eur J Trauma Emerg Surg 2022; 48: 87 – 96.. Angiography may be considered the most reliable method to verify the diagnosis due to the four radiological signs of mesenteric vasospasm⁹Siegelman SS, Sprayregen S, Boley SJ. Angiographic diagnosis of mesenteric arterial vasoconstriction. Radiology 1974; 112: 533 – 42..: (i) Narrowing of the origins of multiple branches of the SMA; (ii) Alternate dilatation and narrowing of the intestinal branches; (iii) Spasm of the mesenteric arcades; and (iv) Impaired filling of intramural vessels. It appears that CT angiography can identify these signs as well¹⁰Siegelman SS, Sprayregen S, Boley SJ. Angiographic diagnosis of mesenteric arterial vasoconstriction. Radiology 1974; 112: 533 – 42.. In addition, SMA diameter was found to be smaller in patients with NOMI than in controls¹¹Mazzei M, Guerrini S, Squitieri NC, Vindigni C, Imbriaco G, Gentili F, et al. Reperfusion in non-occlusive mesenteric ischaemia (NOMI): effectiveness of CT in an emergency setting. Br J Radiol 2016; 89: 20150956.. CT may also capture different intestinal abnormalities such as mesenteric fat stranding, bowel wall thickening and high attenuation of the bowel wall on unenhanced CT images to suggest that there is a reperfusion state at the time of CT¹²Mazzei M, Guerrini S, Squitieri NC, Vindigni C, Imbriaco G, Gentili F, et al. Reperfusion in non-occlusive mesenteric ischaemia (NOMI): effectiveness of CT in an emergency setting. Br J Radiol 2016; 89: 20150956.. It is suggested that biphasic CT angiography is as good as angiography and has potential to replace angiography following a comparative study, where angiography was done after CT examinations in 30 patients¹³Kammerer S, Schuelke C, Berkemeyer S, Velasco A, Heindel W, Koehler M, et al. The role of multislice computed tomography (MSCT) angiography in the diagnosis and therapy of non-occlusive mesenteric ischemia (NOMI): Could MSCT replace DSA in diagnosis? PLoS ONE 2018; 13(3): e0193698..

Treatment and Management

Patients with suspected NOMI need best supportive care in intensive care. In patients with known risk factors for intra-abdominal hypertension/abdominal compartment syndrome, intra-abdominal pressure should be assessed using a urinary bladder measurement system. Abdominal compartment syndrome is defined as intra-abdominal pressure > 20 mm Hg and new onset organ dysfunction. Decompressive laparotomy should be performed to prevent NOMI¹⁴Kirkpatrick AW, Robert DJ, De Waele J, Jaeschke R, Malbrain M, De Keulenaer B, et al. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive care Med 2013; 39: 1190 – 206.. Patients with peritonitis need a laparotomy for resection of transmural intestinal infarction for survival. Identified stenoses of the mesenteric arteries¹⁵Acosta S, Ögren M, Sternby N-H, Bergqvist D, Björck M. Fatal nonocclusive mesenteric ischaemia: population-based incidence and risk factors. J Intern Med 2006; 259: 305 – 313. should be treated by stenting, where possible, followed by continuous local intra-arterial administration into the SMA of vasodilators such as papaverine, nitroglycerine, prostaglandin E1, or glucagon¹⁶Trompeter M, Brazda T, Remy CT, Vestring T, Reimer P. Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy. Eur Radiol 2002; 12: 1179 – 87.,¹⁷Kozuch PL, Brandt LJ. Review article: diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy. Aliment Pharmacol Ther 2005; 21: 201 – 15.. Papaverine may be given as a bolus dose of 80 mg directly into the SMA, followed by 30 – 60 mg/hour of catheter-directed local continuous infusion for 24 – 72 hours.

Prognosis

Prognosis is poor in NOMI and the outcomes depends on individual patient characteristics. Independent predictors for mortality are preoperative low blood pressure and low base excess¹⁸Suzuki S, Kondo H, Furukawa A, Kawai K, Yukaya T, Shimazui T, et al. Prognostic factors of preoperative examinations for non-occlusive mesenteric ischemia: A Multicenter retrospective project study conducted by the Japanese Society for abdominal emergency medicine. World J Surg 2020; 44: 3687 – 3694.. Prompt administration of continuous local intra-arterial of vasodilator therapy into the SMA after CT diagnosis has in a univariate analysis been associated with improved survival¹⁹Miyazawa R, Kamo M. What affects the prognosis of NOMI patients? Analysis of clinical data and CT findings. Surg Endosc 2020; 34: 5327 – 5330.. The mortality rate after emergency laparotomy for NOMI is reported to be 30%²⁰Nakamura F, Yui R, Muratsu A, Onoe A, Nakajima M, Takahashi H, et al. A strategy for improving the prognosis of non-occlusive mesenteric ischemia (NOMI): a single-center observational study. Acute Medicine & Surgery 2019; 6: 365 – 370.- 52%²¹Käser SA, Müller TC, Guggemos A, Nitsche U, Späth C, Maurer CA, et al. Outcome after surgery for acute right-sided colonic ischemia without feasible vascular intervention: a single center experience of 58 patients over 6 years. BMC Surg 2015 Mar 21; 15: 31. doi: 10.1186/s12893-015-0018-0., and after cardiac arrest, the mortality rate increased to 96%²²Paul M, Bougouin W, Legriel S, Charpentier J, Jaubert P, Savary G, et al. Frequency, risk factors, and outcomes of non-occlusive mesenteric ischaemia after cardiac arrest. Resuscitation 2020; 157: 211 – 218..

AMI is an important differential diagnosis in middle-aged and elderly patients with an acute abdomen. Early diagnosis of occlusive AMI relies heavily on performance of CT using intravenous contrast and an optimal protocol. Collaboration between general and vascular surgeons is very important, and timely intestinal revascularisations is possible in a variety of ways, preferably in a hybrid operating suite. The intestinal revascularisation rate needs to be improved in acute arterial mesenteric ischaemia to improve outcomes.