Gastro-Intestinal Vascular Emergencies

Best Practice & Research Clinical Gastroenterology 27 (2013) 709–725

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Gastro-Intestinal Vascular Emergencies Olivier Corcos, MD, Associate Professor *, Alexandre Nuzzo, MD, Assistant Professor 1 Department of Gastroenterology, IBD, Nutritional Support and Intestinal Transplantation, Beaujon Hospital Clichy, Paris VII University, 100 Boulevard du General Leclerc, 92110 Clichy, France

a b s t r a c t Keywords: Acute mesenteric ischaemia Intestinal stroke Intestinal ischaemic injury Non-occlusive Intestinal failure Short bowel syndrome Revascularization Superior mesentery artery Translocation Ischaemic colitis

Gastro-Intestinal Vascular Emergencies include all digestive ischaemic injuries related to acute or chronic vascular and/or haemodynamic diseases. Gastro-intestinal ischaemic injuries can be occlusive or non-occlusive, arterial or venous, localized or generalized, superficial or transmural and share the risks of infarction, organ failure and death. The diagnosis must be suspected, at the initial presentation of any sudden, continuous and unusual abdominal pain, contrasting with normal physical examination. Risk factors are often unknown at presentation and no biomarker is currently available. The diagnosis is confirmed by abdominal computed tomography angiography identifying intestinal ischaemic injury, either with vascular occlusion or in a context of low flow. Recent knowledge in the pathophysiology of acute mesenteric ischaemia, clinical experience and existing recommendations have generated a multimodal and multidisciplinary management strategy. Based on the gastro-intestinal viability around a simple algorithm, and coordinated by gastroenterologists, the dual aim is to avoid large intestinal resections and death. Ó 2013 Elsevier Ltd. All rights reserved.

* Corresponding author. Tel.: þ33 140875616; fax: þ33 140874575. E-mail address: [email protected] (O. Corcos). 1 Tel.: þ33 140875616; fax: þ33 140874575. 1521-6918/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bpg.2013.08.006

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Introduction Gastro-Intestinal Vascular Emergencies (GIVE) result from ‘gastro-intestinal ischaemic injury’ (Gi3). Recent works on the pathophysiology of intestinal perfusion and ischaemia, from the onset of a vascular event to the development of bowel necrosis, suggest that each involved mechanism-vascular and digestive- should be known, recognized and treated specifically, not only by digestive and vascular surgeons and intensivists, but also gastroenterologists and interventional radiologists. In the absence of powerful biomarkers the time, between symptom onset and an irreversible ischaemia is unpredictable, thus all suspicions of GIVE should lead to an urgent diagnostic and therapeutic strategy. Although controlled trials in mesenteric ischaemia are almost unfeasible, a new management strategy, coordinated by gastroenterologists, has been proposed with the dual goal to avoid death and large intestinal resections.

Pathophysiology of gastro-intestinal ischaemic injury Gastro-intestinal ischaemic injury (Gi3) represents acute digestive ischaemia with systemic consequences, due to an interruption or decrease of splanchno-mesenteric blood flow. Gi3 is a multistep process starting with splanchno-mesenteric occlusion or low flow, leading to bowel necrosis, multiorgan failure and death [1,2]. Acute mesenteric ischaemia (AMI) itself is one step of Gi3 process and occurs in the first moments after vascular or haemodynamic injury. If the phenomenon prolongs, AMI extends in depth until necrosis. When a main proximal artery or regional blood flow are interrupted, ischaemia becomes rapidly transmural and gangrenous, while an intramural arteriolar occlusion leads to superficial ischaemia. The systemic consequences of bowel necrosis are lethal in most patients in the absence of curative treatment [3,4]. This multi-step process, described in numerous literature articles, is resumed Fig. 1 [5–12]. Several theories have explained how non-infectious diseases such as vascular occlusion or low flow states could lead to sepsis and multi-organ failure. In the model of intestinal origin of sepsis the gut was hypothesized to be the ‘motor’ of multi-organ failure [9,13–15]. Aside from its barrier function, the gut contains growth factors, adenosine, and hormones, which have emerged as potential tools for the

Fig. 1. The multi-step pathophysiology of Gi3.

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modulation of intestinal inflammation and repair due to their roles in cellular proliferation, differentiation, migration, apoptosis and autophagy [16–20]. Physiologically the gut could initiate and propagate sepsis by the ability of bacteria, endotoxins, and other antigens to translocate, along with the production of pro-inflammatory cytokines and toxins [9]. In The ‘Three Hits Model’ Deitch et al added the phenomenon of ischaemia and reperfusion [21]. In the ‘Gut-Lymph’ theory, bacteria, cellular components, inflammatory, immune cells, cytokines and chemokines generated by the injured gut travel via the lymphatics to reach the pulmonary circulation, activating alveolar macrophages, and contributing to acute lung injury, acute respiratory distress syndrome and multi-organ failure [22–24]. Diagnosis of gastro-intestinal ischaemic injuries (Gi3) and vascular emergencies Positive diagnosis of GIVE is based on the association of a Gi3 and vascular disorders (occlusion and/ or low flow). Main pathological conditions, considered as GIVE and leading to Gi3 are illustrated Fig. 2. However, vascular pathologies not usually encountered by gastroenterologists, such as aortic dissections and traumatic lesions, will not be discussed here. Presentation of Gi3 Abdominal pain is almost constant. The association with athero-thrombo-embolic risk factors, and a reassuring abdominal examination is very evocative. Associated manifestations include: nausea, vomiting, diarrhoea, bleeding, concomitant ischaemic stroke, ileus, bleeding and systemic inflammatory response syndrome (SIRS). The pain onset, should be considered as the countdown and without specific treatments, leads to intestinal necrosis and death [25–28]. Confirmation of Gi3 Multidetector abdominal computed tomography angiography (CT scan) CT-scan has become the new gold standard for positive diagnosis of GIVE with 96% and 94% for sensitivity and specificity, respectively [29]. All suspected subjects should have an initial CT scan, unenhanced followed by two sequences at the arterial and portal phases, to confirm the diagnosis, evaluate severity and the modalities of endovascular treatment [30,31]. Scanographic features of Gi3 include: intestinal wall thickening, abnormal or delayed mucosal enhancement, bowel dilation, mesenteric stranding, ascites or solid organ infarcts. These attributes are not specific of the severity or stage of intestinal injury. Haematomas, pneumatosis intestinalis, aeroportia can be also observed.

Fig. 2. Causes of Gastro-Intestinal Vascular Emergencies (GIVE).

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Digestive endoscopy GI endoscopies are not mandatory for the diagnosis of acute mesenteric ischaemia, except for ischaemic colitis. Upper endoscopy may detect lesions of coeliac artery involvement: Stress ulcers, haemorragic gastropathy, gastroduodenal ischaemic ulcers or necrotic ulcerations [2]. If AMI diagnosis has already been established, except for ischaemic colitis, in our opinion ileocolonoscopy should not be performed. If colonoscopy is performed for non-specific digestive manifestations, intestinal ischaemic lesions although non-specific, can be observed (deep ulcerations, with sharp edges, following arterial territories). In this situation, ileocolonoscopy should always be completed with CT-scan. Biomarkers of Gi3 The complex histological structure of the intestinal wall, the overlapping protein expression of both liver and gut, together with hepatic metabolism through the portal blood explain the lack of a useful early biochemical marker of Gi3 [32,33]. The more studied biomarkers lack sufficient accuracy (leukocytosis, CRP, acidosis, LDH, ASAT, CPK) or specificity (D-dimere, pancreatic proteins, neurotensin, calcitonin, interleukin 6, TNF) for diagnosis. Others are rapidly cleared by the liver through the portal circulation (somatostatin, VIP and substance P) or are late findings (Hexodesaminidase, L-lactate) [27,32,34–36]. Some recent markers have been studied with greater interest: D-Lactate is a byproduct of bacterial fermentation, neither produced nor metabolized by human cells, that translocates after ischaemic injury, increased intestinal permeability, or bacterial overgrowth [37]. In rodent models, D-lactate plasma levels significantly increased 2 hours suggesting an early release after ligation of superior mesenteric artery (SMA), intra-abdominal pressure, or bowel obstruction, compared with controls [38]. In the clinical setting, this was corroborated in the plasma of AMI patients, in comparison to other causes of abdominal surgery. However, conflicting results were recently reported in a pig model of intestinal ischaemia [37]. Fatty acid binding proteins (FABP): FABP are cytosolic proteins which three isoforms are expressed in enterocytes: intestinal FABP (I-FABP), ileal bile acid binding protein (I-BABP) and liver FABP (L-FABP). I-FABP is uniquely located at the tips of the intestinal mucosal villi and normally undetectable in peripheral circulation [33]. In experimental studies of AMI, serum I-FABP seemed a sensitive and organ specific marker of intestinal damage. Significant increased levels were shown in a recent and original human experimental model of ischaemia-reperfusion [39]. In clinical settings, I-FABP measured in peritoneal fluid, plasma and urine were significantly higher in patients with intestinal ischaemia than in healthy controls [40]. Thuijls et al confirmed these findings showing that plasma and urine I-FABP, LFABP and urine I-BABP allowed differentiation of intestinal ischaemia from other abdominal emergencies in 50 patients with high suspicion of AMI [41]. Alpha gluthatione S-transferase (alphaGST): Gluthathione S-transferases are enzymes involved in the detoxication of a wide variety of compounds by conjugation to gluthatione. In the clinical setting, alphaGST showed a significant increase in 12/24 AMI in comparison with 12 other unclear acute abdominal pain suspected for being ischaemic, with a negative predictive value of 100 per cent [42]. Citrulline: Citrulline is an amino acid mainly synthesized from glutamine by the enterocyte. Plasma concentration depends on gut synthesis and renal degradation and decreases in short bowel conditions [43]. The decreased plasma concentration in the first hours of shock in critically ill patients, was correlated with mortality, suggesting an association with gut ischaemia [44]. Ischaemia modified albumin: During acute ischaemic conditions, albumin’s metal binding capacity is reduced giving rise to a metabolic variant known as ischaemic modified albumin. It is a sensitive, non-specific marker of myocardial, muscle ischaemia pulmonary embolism and stroke [45,46]. In the rabbit model of intestinal ischaemia, ischaemic modified albumin was significantly and early increased whereas contradictory results are reported in a rat model [47,48]. In clinical settings, significant increased levels were found at admission of 7 patients with AMI compared to healthy controls. A preliminary study reported a sensitivity of 100% and 86% specificity in detection of 12 AMI in preoperative plasma of 26 patients scheduled for laparotomy with AMI suspicion [49]. Limitations: Several limitations could be highlighted from these findings. In animal models obtained by endovascular embolization or per-laparotomy ligation of SMA, antigens of specific proteins may vary significantly between species and most controls are healthy animals. In the clinical setting,

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most studies were performed in small populations, with high pre-test probability due to high suspicion of intestinal ischaemia and at late stage with need for exploratory laparotomy. Characterization of Gi3 As illustrated in Figs. 3 and 4 acute Gi3 can be characterized as early or late, occlusive or nonocclusive or following the digestive involvement. Early and late Gi3 Two presentations -early and late Gi3- correlated with distinct prognosis should be distinguished [50]:  Late Gi3 indicate the onset of complications, defined by the presence of one of the three following criteria: (1) organ failure, (2) hyperlactatemia, (3) intestinal necrosis at CT scan. Scanographic features of intestinal necrosis are: (1) perforation (pneumoperitoneum, extra-digestive gas), (2) peritonitis (peritoneal enhancement, collections), (3) total absence of mucosal enhancement with loss of continuity within a thinned gut wall («ghost bowel»).  Early Gi3 are defined by the absence of all these three criteria.

Digestive involvement The topographic localization of ischaemic lesions indicate vascular involvement (Fig. 4). Occlusive and non-occlusive Gi3 Occlusive Gi3 The distinctive particularities between arterial thrombosis, emboli and non-occlusive Gi3 are illustrated Table 1. Atherosclerosis and thrombosis. In proximal SMA thrombosis, Gi3 appears confluent, without jejunal, ileal or right colonic sparing [30]. Without a prompt revascularization, after one or successive intestinal resection procedures, survivors of thrombotic occlusive mesenteric ischaemia often present with short

Fig. 3. Characterization of gastro-intestinal ischaemic injuries. Abbreviations: SMA Superior mesenteric artery, GI Gastro-Intestinal.

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Fig. 4. Vascular involvement according to digestive injury.

bowel syndrome with remnant proximal duodeno-jejunum and less than 70% of the colon. These patients require specialized management in Intestinal Failure Centres [51,52]. Arterial Embolism. Numerous cardiac conditions have been proposed as potential sources of embolism. The more common are atrial fibrillation, recent myocardial infarction, mechanical prosthetic valve, Table 1 Distinctive features between thrombotic, embolic or non-occlusive Gi3. Arterial thrombosis

Arterial emboli

Non-occlusive mesenteric ischemia

Medical context and history

 Atherom risk factors  Medical history of atherom disease

 Cardio-aortic embolic disease  Medical history of embolic events (30%)

    

Onset Physical particularities

 Progressive or sudden  Malnutrition from alimentary fear  Mesenteric angor previous to AMI  Vascular murmur  No pulses

 Sudden  Simultaneous embolic events (20%)  Atrial fibrillation or embolic heart disease (75%)

    

Gut involvement

 Continuous and extensive  All small bowel/right colon in SMA occlusion

 Discontinous and Segmental  Median small bowel

Vascular involvement

    

 Division branches of SMA (50%)  Multiples emboli

     

 Atheromatous arteries



Aggravating factors

SMA CT IMA No collaterals Previous surgery

 Organ failure onset

 Consecutive to vascular occlusion and Gi3



ICU patient Medications Toxics Low-flow states, shock Hypovolemiant treatments, vasoconstrictors, mechanical ventilation, cocaine Insidious or sudden Abdominal distension Oral/enteral intolerance Tenderness Low arterial pressure, fever, digestive bleedings, vomiting, diarrhoea Stress ulcers Ischemic cholangitis Small bowel Ischemic colitis Systemic circulation Coeliomesenteric low flows Insufficient etiological treatment Surgery as first line treatment Prior to Gi3

Abbreviations: ICU: Intensive Care Unit, AMI: Acute mesenteric ischaemia, SMA: superior mesenteric artery, CT: celiac trunk, IMA: inferior mesenteric artery, Gi3: gastro-intestinal ischaemic injury.

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dilated myocardiopathy, and mitral rheumatic stenosis. Other sources of cardioembolism include infective and non infective endocarditis, atrial myxoma, patent foramen ovale, atrial septal aneurysm, atrial or ventricular septal defects, calcific aortic stenosis, and mitral annular calcification [30]. An oblique origin from visceral aortic artery explains why SMA is often involved, even if concomitant peripheral embolus has been demonstrated in autopsy in over 2/3 of patients [53]. Depending on the size of thromboemboli, the occlusion can concern the origin (15%) or beyond the first jejunal branches (50%), distal to the middle colic artery to create a classic pattern of ischaemia that spares the first portion of the small intestine, ileocecal valve and the ascending colon [30]. Spontaneous isolated dissection of the SMA. Isolated dissection of the SMA is a rare and potentially fatal condition and is not associated with aortic dissection [54]. Isolated dissection of SMA can be detected incidentally, but may also cause acute abdominal pain or complications such as bowel infarction and haemorrhage [54,55]: Briefly the natural course of SMA dissection includes: (1) limited progression with thrombosis of the false lumen, (2) progressive dissection to distal branches of the SMA, (3) rupture through the adventitia, or (4) rapidly expanding false lumen resulting in the obliteration of the true lumen [56,57]. The dissection seems located at the anterior wall and around the convex curvature of the SMA. Except in the rare case of medial fibrodysplasia the exact cause of isolated superior mesenteric artery dissection has not been identified. The reported available potential risk factors include hypertension, smoking, hyperlipidaemia, coronary heart disease, atherosclerosis, diabetes mellitus, traffic trauma with seat belt, and iatrogenic trauma. Healthy patients without clear risk factors are reported to be more prevalent with no obvious etiologic factor [55]. Mesenteric venous thrombosis. Mesenteric venous thrombosis (MVT) represent about 15% of AMIs and leads to intestinal ischaemia in 4–58% of cases [58,59]. The mortality associated with intestinal resection is currently 20–60% while severe disability may result from either short bowel syndrome or post-ischaemic intestinal stenoses [59]. Acute porto-mesenteric thrombosis is diagnosed by doppler ultrasonography and/or CT scan. Portal obstruction may be primitive, due to endovascular thrombus, or consecutive to invasion of the portal vein. Early symptoms of acute thrombosis are abdominal pain and SIRS with portal hypertension and biliary complications (cavernoma) observed later. Associated conditions to MVT are (1) general (prothrombotic affection, myeloproliferative disease, prothrombin gene mutation or antiphospholipid syndrome, cancer, nocturnal paroxystic haemoglobinuria, Behçet’s disease, celiac disease and hereditary thrombophilia) or (2) local (pancreatitis, cholangitis, diverticulitis, cholecystitis, IBD, CMV, surgery, cirrhosis) [59]. In acute MVT intestinal infarction may occur in relation to relative decreased arterial flow. In a recent study of 57 patients with MVT patients with or without intestinal resection were compared: diabetes, metabolic syndrome or intestinal injury at initial evaluation were correlated with bowel resection (Elkrief et al in preparation). Ancient studies demonstrated that acute MVT was followed by a spasm with initial reduction of blood flow in the SMA [60,61]. This data suggests that in MVT an associated arterial disease could be responsible for severe i3 requiring intestinal resection. Further studies are needed to confirm this hypothesis. Vasculitides. Vasculitides are defined by the presence of inflammatory cells in vessel walls with reactive damage and subsequent loss of vessel [62]. Primary systemic vasculitides are classified according to the size and type of involved vessels [63,64]. Main digestive manifestations-ischaemia, infarction, perforation, peritonitis, haemorrhages – are common to all vasculitides. Otherwise, some are more specific: granulomatous ileo-colitis or gastritis in granulomatosis with polyangiitis, eosinophilic gastroenteritis in eosinophilic granulomatosis with polyangiitis, venule vasculitis and thrombosis extent to mesenteric and portal veins and/or ischaemic perforation of ileocolic deep ulcers (Behçet’s disease), typical angiographic micro-aneurysms in polyarteritis nodosa and the increasingly reported coexistence of inflammatory bowel disease in Takayasu’s arteritis [65]. In a review of 62 small to medium sized vasculitides, severe manifestations, significantly associated with mortality, such as bowel ischaemia, intestinal occlusion, peritonitis and acute pancreatitis occurred in 34% of patients [66]. The recently revised Five-Factor Score, established in 1108 patients integrated these severe abdominal complications [67]. Endoscopic and radiographic lesions are typically focal and segmental and not linked with gut vasculature.

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Non-occlusive Gi3 Non-occlusive mesenteric ischaemia. During systemic or regional low flow states-i.e shocks, haemorrhage, surgery, dialysis, sepsis, hypovolaemia, cardiogenic injuries, treatments, intoxications or intense exercise, the activation of the renin-angiotensin-aldosterone pathway accentuates splanchnic vasoconstriction which decreases regional blood flow under the critical threshold [68–70]. The impairment of bowel perfusion may be severe up to a point where blood flow is virtually unmeasurable. Stress ulcers. Critical illness can contribute to splanchnic hypoperfusion, playing a major role in the pathogenesis of gastric stress ulcers. Stress-related mucosal damage occurs in many critically ill ICU patients often within 24 h of admission. This type of mucosal damage worsens prognosis [71]. Factors involved in the pathogenesis of stress ulcers include gastric acid secretion, significant decrease in visceral blood flow and gastrointestinal motor dysfunction [72]. At upper endoscopy stress ulcers include multiple subepithelial petechiae, superficial erosions and in some cases ulcerations, particularly in the gastric fundus. These lesions do not usually perforate and tend to bleed from superficial mucosal capillaries. Ischaemic colitis. Pathophysiology: The colon is predisposed to ischaemia due to a relatively low blood flow and less developed microvasculature compared to the small bowel [73–75]. Inversely the colon is protected from ischaemia by a collateral blood supply via a system of arcades connecting the two major arteries, IMA and SMA. The anatomy is highly variable and certain areas are more vulnerable in some people. The splenic flexure and sigmoid colon are regions where two circulations meet each other, have more limited collateral networks and therefore the sites of ischaemic injury. Ischaemic injury of the rectum is rare because of a dual blood supply from the mesenteric and iliac arteries. The left colon is predominantly affected in 75% of patients (with splenic flexure in approximately 25 %) whereas isolated right colon ischaemia occurs in about 10–25% of cases [76]. Right colonic ischaemia is associated with more severe colitis and a worse outcome, it should be considered as an acute mesenteric ischaemia [77]. Anatomically, ischaemic colitis (IC) may be classified into gangrenous (15%) and nongangrenous (85%) [74,75]. The latter can also be subdivided into transient (50%) and chronic (30– 40%) with a poor prognosis in elderly patients [73]. Predisposing factors of non-occlusive ischaemic colitis (Table 2): IC is the most frequent and benign intestinal ischaemic injury, and in the majority of cases from a non-occlusive mechanism, although occlusive conditions may predispose patient to impaired colonic perfusion and IC [5,73,78]. Diagnosis: As with other GIVE, ischaemic colitis displays both features of Gi3 and vascular/haemodynamic insufficiency. Nevertheless the clinical presentation is non-specific and varies, depending on the severity and extent of the disease. The triad that associates a sudden crampy abdominal pain, diarrhoea and rectal bleeding accounts for 40% of cases. Triphasis CT scan should be performed first to (1) exclude AMI, (2) confirm colonic injury sparing the rectum, (3) clarify the occlusive or nonocclusive mechanism, (4) search for complications and contra-indication to flexible sigmoïdoscopy (necrosis, perforation, peritonitis), (5) identify the cause and eliminate differential diagnosis [73,77]. Flexible sigmoidoscopy or complete colonoscopy are crucial for positive diagnosis, to eliminate infectious colitis and to determine the severity of IC. Endoscopies should be performed carefully, in case of left and early IC and before 48 h. Bowel preparation is not recommended. A left ulcerative colitis with sharp limits sparing the rectum is very evocative with three endoscopic stages [78]:

 Stage 1: alternating normal mucosae with mild mucosal lesions  Stage 2: longitudinal ulcers with clear limits, typically purple with bleeding submucosae.  Stage 3: grey-black appearance of the mucosa and extensive necrosis of the lamina propria. Avoid biopsies with this stage.

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Table 2 Predisposing factors of ischemic colitis. Vascular Occlusion Hypoperfusion states Mechanical colonic obstruction Medications

Iatrogenic

Coagulability disorders

Idiopathic In young patients

 Superior mesenteric artery occlusion: right Ischaemic colitis  Inferior mesenteric artery: Thrombosis, emboli, surgical ligation  Congestive heart failure, arrhythmia, transient hypotension, strenuous physical activity, shocks  Tumours, adhesions, volvuli, hernias, diverticulitis, prolapse, fecaloma  Antibiotics, appetite suppressants, chemotherapy agents (alkaloids and taxanes), constipation inducing medications, decongestants (pseudoephedrine), cardiac glucosides, diuretics, ergot alkaloids, hormonal therapies, statins, illicit drugs, immunosuppressive agents, laxatives, nonsteroidal anti-inflammatory drugs, psychotropic medications, serotonin agonists antagonists and vasopressors  Aortic reconstruction, abdominal aortic aneurysm repair, coronary artery bypass surgery, complication of colonic surgery or colonoscopy  Deficiencies of protein C, protein S, and antithrombin III, factor V Leiden and prothrombin mutation, antiphospholipid antibodies, Protein Z deficiency, JAK2 mutation  Negative aetiologic work-up  Vasculitis, oestrogens, cocaine and methamphetamine use, psychotropic drugs, sickle cell disease, long-distance running and heritable disorders of coagulation

As with all GIVE, gangrenous and non-gangrenous IC may be classified as early and late i3. Nongangrenous (early) IC patients do not have organ failure, high lactate levels or complications (perforation, peritonitis, necrosis) consecutive to i3. As all predisposing factors of IC may also be complications it is fundamental to determine the chronologic onset between digestive and low-flow symptoms. Fig. 5 illustrates the diagnosis algorithm and management of IC. Treatments of GIVE Treatment of gastro-intestinal ischaemic injuries (Gi3) The famous sentence pronounced by Cokkinis about mesenteric ischaemia « the diagnosis is impossible, the prognosis hopeless and the treatment useless » is now obsolete [3]. Until now, AMI has always been considered an abdominal emergency associated with a high mortality rate and often, intestinal failure in survivors [51]. A systematic review of 45 observational studies, including 3692 AMI patients, reported overall in-hospital death rates of about 70% and almost 100% in untreated patients [3]. Recently, Arthurs et al reported an in-hospital survival rate of 36% in patients who successfully underwent endovascular revascularization, compared with 50% in cases of conventional treatment [79]. In the literature, the best survival rates were reported with revascularization and in early AMI [25,26,68,79,80]. Recently we reported the encouraging results of a multidisciplinary and multimodal management of Gi3 patients, taking into account the pathophysiology of intestinal ischaemia [50]. From these results Gi3 should always be considered as a potentially reversible injury. The multidisciplinary and multimodal management of Gi3 From the published literature, available recommendations and our experience in intestinal and vascular failure, we hypothesized that a multidisciplinary and multimodal management, designed to avoid large intestinal resections, permanent intestinal failure, and long-term parenteral nutrition, could improve the prognosis of AMI [50,81]. In our Intestinal Stroke Centre, incorporating gastroenterology, interventional radiology, vascular and digestive surgery, intensive care units, all experienced in GIVE we set out to test the feasibility and effectiveness of a multimodal protocol, focused on intestinal viability. We reported our preliminary results in 18 consecutive patients [50]. This pilot study confirmed that such a strategy was feasible and associated with a significant improvement in survival,

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Fig. 5. Algorithm for management of ischaemic colitis. Abbreviations: CMV cytomegalovirus, IC ischaemic colitis.

compared with historical reports [3,80,82,83]: survival of AMI patients was 89% at 2 years, morbidity 27% without peritonitis or additional resection and only 39% of patients needed intestinal resection. Resection lengths and time in ICU were significantly shorter in revascularized patients and early Gi3 with a trend for survival, compared with late AMI. At follow-up evaluation, 17% of patients needed long-term parenteral nutrition [50]. According to these results contemporaneous multidisciplinary and multimodal management of Gi3 should associate three approaches:  Preservation of non necrotic small bowel with revascularization and specific medical treatment  Resection of all necrotic small bowel  Prevention of multiorgan failure The fundamental cornerstone of this approach is to offer an aggressive strategy not only in severely injured patients, but especially in early patients without complications or organ failure. A pathophysiological-based medical protocol associated with radiological or surgical revascularization, organized around a simple algorithm, should be proposed without any delay [50]. The algorithm of this multimodal, multidisciplinary management is illustrated Fig. 6 The Gi3Medical Protocol Immediately after diagnosis of AMI is suspected, and throughout the initial management, patients should receive a pathophysiological-based medical protocol (Fig. 7 and Table 3), associated with etiological treatment. Radiological revascularization With the exception of venous mesenteric thrombosis and IC, radiological revascularization should be performed whenever technically possible, especially in case of early Gi3, during angiography, under curative heparin, anti-platelet and proton pump inhibitors therapies [50,68]. The mechanisms of Gi3 determine the techniques of revascularization (Table 4) [5,25,79,81,84,85]. Despite low levels of evidence (grade C) the American Societies of Surgery and Vascular Medicine and the Societies of Cardiology’s (AHA) edited recommendations (Class IIb) for percutaneous revascularization in selected patients with acute intestinal ischaemia caused by arterial obstructions [81]. Surgical Management The main risks of AMI are intestinal necrosis and death. Surgical management should concern both vessels and intestine, thus performed by vascular and digestive specialized surgeons. If clinical complications suspected (perforation, peritonitis, necrosis) urgent laparotomy must be performed without

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Fig. 6. Algorithm of Multimodal and Multidisciplinary Management of Gi3. Legend : Late stage ¼ presence of at least one of 3 criteria: (1) organ failure, (2) hyperlactatemia, (3) intestinal necrosis/Early stage ¼ 0 criteria.

delay. A median large incision is often necessary for careful exploration of the entire digestive tract, for revascularization and resection of necrotic territories.  Surgical revascularization Whenever possible, vascular surgery should precede intestinal procedure, to preserve the maximum length of small bowel. Surgical techniques of revascularization are guided by the mechanisms and consequences of Gi3 preferably established before surgery (Table 4).  Intestinal resection In extensive intestinal necrosis requiring large resections, an aggressive strategy of resection and resuscitation should be offered if long-term home parenteral nutrition or intestinal transplantation are envisaged. Viable segments are placed in common stoma, without anastomosis for surveillance and future elective continuity reestablishment. Ischaemic, but not necrotic, intestinal segments should be revascularized without intestinal resection, but with systematic second look. Treatment of specific vascular/haemodynamic disorders GIVE require interaction between gastroenterologists, interventional radiologists, digestive and vascular surgeons and ICU specialists. Each specialist should treat or refer patients for optimal and

Fig. 7. Pathophysiological-based Medical protocole of Gi3. Abbreviations: O2: oxygen therapy, PPI: proton pump inhibitors, Revasc: revascularization, IV: intravenous, i3: Intestinal ischaemic injury.

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Table 3 Principles and modalities of medical treatment of gastro-intestinal ischemic injury (Gi3). Mandatory medical protocol

1. Complete oral/enteral resting 2. Blood volume resuscitation even in conserved hemodynamic conditions 3. Heparin therapy for anti-Xa activity maintained in 0.5–0.8 range, even in case of moderate digestive bleeding 4. Oral Digestive Decontamination:  Oral gentamycine 80 mg/d  Oral Metronidazole 1.5 g/d 5. Oxygen therapy 6. IV Proton pump inhibitors

Conditional medical protocol

7. IV aspirin 100 mg/d if arterial occlusion (compression, thrombosis, emboli) and if a revascularization is considered 8. IV antibiotics Piperacilline-tazobactam IV 3  4 grams/d if SIRS or organ failure or surgery 9. Gastric aspiration if vomiting or ileus 10. Blood transfusion if Hb <9 g/dl

Abbreviations: IV intravenous, SIRS systemic inflammatory response syndrome.

adaptable management. Furthermore, we consider that all GIVE share a common pathophysiology, justifying establishing a common medical protocol for Gi3, to avoid and prevent digestive necrosis and death. Non-occlusive Gi3 In the absence of vascular occlusion the CT scan diagnosis is often misleading, although the association of at-risk conditions with intestinal injury requires confirmation. In non-occlusive Gi3, first line treatment should not be surgical. Priority is to reestablish a splanchno-mesenteric perfusion flow according to Fig. 8 [68,81]. If medical management fails, intra-arterial vasodilation should be discussed as recommended. When intra-arterial papaverin was performed, reported mortality rates were below 50%, with or without laparotomy [26,68]. Surgery should be offered after treatment failure or deterioration. Ischaemic colitis As in all Gi3 prompt medical management is mandatory to avoid colonic necrosis or complications. Surgery is necessary in about 20% of patients with high mortality [26]. Whatever the presentation,

Table 4 Radiological and surgical techniques of revascularization in Intestinal Ischaemic Injuries. Radiological revascularization

Surgical revascularization

Thrombosis

     

Thrombolysis Angioplasty Thrombo-aspiration Mechanical deobstruction Stenting Vasodilation?

    

Emboli

   

Thrombolysis Thrombo-aspiration Mechanical deobstruction Vasodilation?

 Mechanical deobstruction  Bypass

Non-occlusive ischemia

 Intra-arterial vasodilation

 Intra-arterial vasodilation associated with life saving intestinal resection

Mechanical deobstruction Arterial reimplantation Endarterectomy Bypass Patching

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Fig. 8. Principles of management of non-occlusive Gi3.

gangrenous or not, late or early, treatment should include bowel rest, blood volume resuscitation, cessation of promoting factors, improvement of haemodynamic and cardiac conditions and antibiotics targeting both anaerobic and aerobic bacteria. In occlusive IC, aspirin and eventually anticoagulant should be discussed although no evidence is available in the literature. Surgery should be reserved for refractory organ failure, perforation or peritonitis, sepsis, persistent fever, refractory pain, massive bleeding, severe protein-losing enteropathy, pneumoperitoneum or endoscopically-proved extensive gangrene. In chronic IC, symptomatic strictures are indications for resection, but endoscopic dilation may also be an option [73]. Arterial dissections Although isolated SMA dissection often has a favourable prognosis with conservative medical treatment (including antalgics, alimentary resting, anti-hypertensive therapy with or without anticoagulants), patients with refractory symptoms or complications may be candidates for endovascular stenting or surgery [25,55]. Mesenteric venous thrombosis When acute mesenteric thrombosis is diagnosed early, anticoagulant therapy for six months prevents the extension of thrombosis and the risk of mesenteric infarction. After 6 months or in the case of portal vein cavernoma, anticoagulation should be continued if the cause is still present, or if the thrombosis has extended to the mesenteric vein. Later, when a cavernoma is present, prevention of bleeding according to current guidelines is recommended. Increased use of early anticoagulation in patients with acute MVT has been accompanied by a decreasing incidence of intestinal infarction from 33% in patients not receiving anticoagulation, to 2% in a study where 95% of patients received anticoagulation [59]. Mesenteric threatening syndromes Chronic mesenteric ischaemia manifests as post-prandial abdominal pain with alimentary fear, weight loss and often cachexia. When patients are unable to nourish orally or when abdominal pain becomes nocturnal or permanent, the risk of infarction increases. Patients require specific treatment, taking into account other pathological conditions: renal insufficiency, malnutrition, peripheric arterial diseases. Treatment requires an optimal strategy between surgical or endovascular repermeabilization and nutritional support [86,87]. Conflicts of interest None.

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Research agenda:  Early and specific biomarkers of gastro-intestinal ischaemic injury need to be identified  Survivors of gastro-intestinal ischaemic injuries should be studied to identify predictive factors of intestinal resection and short-bowel syndrome  Specific splanchno-mesenteric vasoactive agents need to be developed in ischaemia-related vasospasm  Further development of morphological techniques to determine digestive viability

Summary Gastro-Intestinal Vascular Emergencies are most often misunderstood by gastroenterologists and may occur with or without digestive vascular occlusion. Whatever the involved mechanisms the incidence is increasing and the prognosis could be improved by an innovative multimodal and multidisciplinary management initiated at early presentation. Diagnosis must be suspected with any sudden, continuous and unusual abdominal pain, contrasting with normal physical examination at the initial stage. Thrombo-athero-embolic risk factors are often unknown at presentation and no biochemical test is specific. Absence of individual risk factors or normal biology might not deny or delay the diagnosis, which should be confirmed by abdominal computed tomography angiography identifying gastro-intestinal ischaemic injury, with or without vascular occlusion. Gastroenterologists have a major role in the management, in order to avoid death and large intestinal resections, by initiating and coordinating a multidisciplinary and multimodal management incorporating a medical protocol, revascularization of viable digestive segments and resection of non-viable intestine. Therapeutic strategy depends on the presence of at least one of three criteria (necrosis, organ failure, or elevated serum lactate). In the early stages, patients without surgical complication, organ failure or high lactate levels should be treated medically with endovascular revascularization whenever possible. At later stages, surgical management requires both resection and revascularization. Any factor that may have contributed to this ischaemic stroke (i.e atherosclerosis, cardiac embolism or thrombophilia) should be investigated and treated, with particular reference to ischaemic colitis and non-occlusive mesenteric ischaemia. Acknowledgements Amy Whereat and Pamela Heuer for writing assistance. References [1] Ackland G, Grocott MP, Mythen MG. Understanding gastrointestinal perfusion in critical care: so near, and yet so far. Crit Care (London, England) 2000 Jan 1;4(5):269–81. [2] Veenstra RP, Geelkerken RH, Verhorst PM, Huisman AB, Kolkman JJ. Acute stress-related gastrointestinal ischemia. Digestion 2007;75(4):205–7. [3] Schoots IG, Koffeman GI, Legemate DA, Levi M, van Gulik TM. Systematic review of survival after acute mesenteric ischaemia according to disease aetiology. Br J Surg 2004 Jan 5;91(1):17–27. [4] Kassahun WT, Schulz T, Richter O, Hauss J. Unchanged high mortality rates from acute occlusive intestinal ischemia: six year review. Langenbecks Arch Surg 2008 Jan 3;393(2):163–71. [5] Kolkman J-J, Bargeman M, Huisman A-B, Geelkerken R-H. Diagnosis and management of splanchnic ischemia. World J Gastroenterol 2008 Dec 28;14(48):7309–20. [6] Otte JA, Huisman AB, Geelkerken RH, Kolkman JJ. Jejunal tonometry for the diagnosis of gastrointestinal ischemia. Feasibility, normal values and comparison of jejunal with gastric tonometry exercise testing. Eur J Gastroenterol Hepatol 2008 Jan 1;20(1):62–7. [7] Eltzschig H, Carmeliet P. Hypoxia and inflammation. New Engl J Med 2011 Feb 17:1–10. [8] Demir IE, Ceyhan GO, Friess H. Beyond Lactate: is there a role for serum lactate measurement in diagnosing acute mesenteric ischemia. Dig Surg 2012;29(3):226–35. [9] Clark JA, Coopersmith CM. Intestinal crosstalk: a new paradigm for understanding the gut as the “motor” of critical illness. Shock 2007 Oct 1;28(4):384–93.

O. Corcos, A. Nuzzo / Best Practice & Research Clinical Gastroenterology 27 (2013) 709–725

723

[10] Bennion RS, Wilson SE, Williams RA. Early portal anaerobic bacteremia in mesenteric ischemia. Arch Surg (Chicago, Ill 1960) 1984 Feb;119(2):151–5. [11] Oostdijk EAN, de Smet AMGA, Kesecioglu J, Bonten MJM. The role of intestinal colonization with Gram-negative bacteria as a source for intensive care unit-acquired bacteremia*. Crit Care Med 2011 May;39(5):961–6. [12] Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immuno 2009 Nov 1;9(11):799–809. Nature Publishing Group. [13] Puleo F, Arvanitakis M, van Gossum A, Preiser J-C. Gut failure in the ICU. Semin Respir Crit Care Med 2011 Oct 11;32(05):626–38. [14] Berg RD, Garlington AW. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun 1979 Feb;23(2):403–11. [15] Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV. Multiple-organ-failure syndrome. Archives Surgery (Chicago, Ill 1960) 1986 Feb;121(2):196–208. [16] Eltzschig HK, Sitkovsky MV, Robson SC. Purinergic signaling during inflammation. N Engl J Med 2012 Dec 13;367(24): 2322–33. [17] Kaser A, Blumberg RS. Autophagy, microbial sensing, endoplasmic reticulum stress, and epithelial function in inflammatory bowel disease. YGAST 2011 May 1;140(6):1738–1747.e2. Elsevier Inc. [18] Linden J. Role of adenosine in response to vascular inflammation. Arterioscler Thromb Vasc Biol 2012 Apr;32(4):843–4. [19] Colgar SP, Taylor CT. Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroenterol Hepatol 2010 May; 7(5):281–7. [20] Glover LE, Colgan SP. Hypoxia and metabolic factors that influence inflammatory bowel disease pathogenesis. YGAST 2011 May 1;140(6):1748–55. Elsevier Inc. [21] Deitch EA. Gut-origin sepsis: evolution of a concept. Surgeon 2012 Dec;10(6):350–6. [22] Senthil M, Brown M, Xu D-Z, Lu Q, Feketeova E, Deitch EA. Gut-lymph hypothesis of systemic inflammatory response syndrome/multiple-organ dysfunction syndrome: validating studies in a porcine model. J Trauma 2006 May;60(5):958–65 discussion965–7. [23] Deitch EA, Xu D, Kaise VL. Role of the gut in the development of injury- and shock induced SIRS and MODS: the gut-lymph hypothesis, a review. Front Biosci 2006;11:520–8. [24] Badami CD, Senthil M, Caputo FJ, Rupani BJ, Doucet D, Pisarenko V, et al. Mesenteric lymph duct ligation improves survival in a lethal shock model. Shock 2008 Dec;30(6):680–5. [25] Park WM, Gloviczki P, Cherry KJ, Hallett JW, Bower TC, Panneton JM, et al. Contemporary management of acute mesenteric ischemia: factors associated with survival. J Vasc Surg 2012 Apr 21;35(3):445–52. [26] Brandt LJ, Boley SJ. AGA technical review on intestinal ischemia. American Gastrointestinal Association. Gastroenterology 2000 May 1;118(5):954–68. [27] Kurland B, Brandt LJ, Delany HM. Diagnostic tests for intestinal ischemia. Surg Clin North Am 1992 Feb;72(1):85–105. [28] Oldenburg WA, Lau LL, Rodenberg TJ, Edmonds HJ, Burger CD. Acute mesenteric ischemia: a clinical review. Arch Intern Med 2004 May 24;164(10):1054–62. [29] Oliva IB, Davarpanah AH, Rybicki FJ, Desjardins B, Flamm SD, Francois CJ, et al. ACR appropriateness criteria(Ò) imaging of mesenteric ischemia. Abdom Imaging 2013 Jan 9. [30] Wyers MC. Acute mesenteric ischemia: diagnostic approach and surgical treatment. Seminar Vasc Surg 2010 Apr 11;23(1):9–20. [31] Furukawa A, Kanasaki S, Kono N, Wakamiya M, Tanaka T, Takahashi M, et al. CT diagnosis of acute mesenteric ischemia from various causes. Am J Roentgenology 2009 Feb 1;192(2):408–16. [32] Evennett NJ, Petrov MS, Mittal A, Windsor JA. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World J Surg 2009 Jul;33(7):1374–83. [33] Derikx JP. Non-invasive markers of gut wall integrity in health and disease. World J Gastroenterol 2010;16(42):5272. [34] Acosta S, Nilsson T. Current status on plasma biomarkers for acute mesenteric ischemia. J Thromb Thrombolysis 2011 Nov 13;33(4):355–61. [35] Chiu Y-H, Huang M-K, How C-K, Hsu T-F, Chen J-D, Chern C-H, et al. D-dimer in patients with suspected acute mesenteric ischemia. Am J Emerg Med 2009 Oct;27(8):975–9. [36] Martin C, Boisson C, Haccoun M, Thomachot L, Mege JL. Patterns of cytokine evolution (tumor necrosis factor-alpha and interleukin-6) after septic shock, hemorrhagic shock, and severe trauma. Crit Care Med 1997 Nov;25(11):1813–9. [37] Nielsen C, Mortensen FV, Erlandsen EJ, Lindholt JS. L- and D-lactate as biomarkers of arterial-induced intestinal ischemia: an experimental study in pigs. Int J Surg 2012;10(6):296–300. [38] Duzgun AP, Gulgez B, Ozmutlu A, Ertorul D, Bugdayci G, Akyurek N, et al. The relationship between intestinal hypoperfusion and serum d-lactate levels during experimental intra-abdominal hypertension. Dig Dis Sci 2006 Dec;51(12): 2400–3. [39] Derikx JPM, Matthijsen RA, de Bruïne AP, van Bijnen AA, Heineman E, van Dam RM, et al. Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation. PLoS One 2008; 3(10):e3428. [40] Kanda T, Tsukahara A, Ueki K, Sakai Y, Tani T, Nishimura A, et al. Diagnosis of ischemic small bowel disease by measurement of serum intestinal fatty acid-binding protein in patients with acute abdomen: a multicenter, observer-blinded validation study. J Gastroenterol 2011 Feb 5;46(4):492–500. [41] Thuijls G, van Wijck K, Grootjans J, Derikx JPM, van Bijnen AA, Heineman E, et al. Early diagnosis of intestinal ischemia using urinary and plasma fatty acid binding proteins. Ann Surg 2011 Feb;253(2):303–8. [42] Delaney CP, O’Neill S, Manning F, Fitzpatrick JM, Gorey TF. Plasma concentrations of glutathione S-transferase isoenzyme are raised in patients with intestinal ischaemia. Br J Surg 1999 Oct;86(10):1349–53. [43] Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology 2000 Dec 1;119(6):1496–505. [44] Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou J-C, et al. Plasma citrulline kinetics and prognostic value in critically ill patients. Intensive Care Med 2010 Apr;36(4):702–6. [45] Hietbrink F, Besselink MGH, Renooij W, de Smet MBM, Draisma A, van der Hoeven H, et al. Systemic inflammation increases intestinal permeability during experimental human endotoxemia. Shock 2009 Oct;32(4):374–8.

724

O. Corcos, A. Nuzzo / Best Practice & Research Clinical Gastroenterology 27 (2013) 709–725

[46] Keating L, Benger JR, Beetham R, Bateman S, Veysey S, Kendall J, et al. The PRIMA study: presentation ischaemia-modified albumin in the emergency department. Emerg Med J 2006 Oct;23(10):764–8. [47] Dundar ZD, Cander B, Gul M, Karabulut KU, Girisgin S. Serum ischemia-modified albumin levels in an experimental acute mesenteric ischemia model. Acad Emerg Med 2010 Nov;17(11):1233–8. [48] Uygun M, Yilmaz S, Pekdemir M, Duman C, Gürbüz YS. The diagnostic value of ischemia-modified albumin in a rat model of acute mesenteric ischemia. Acad Emerg Med 2011 Apr;18(4):355–9. [49] Gunduz A, Turedi S, Mentese A, Karahan SC, Hos G, Tatli O, et al. Ischemia-modified albumin in the diagnosis of acute mesenteric ischemia: a preliminary study. Am J Emerg Med 2008 Feb;26(2):202–5. [50] Corcos O, Castier Y, Sibert A, Gaujoux S, Ronot M, Joly F, et al. Effects of a multimodal management strategy for acute mesenteric ischemia on survival and intestinal failure. Clin Gastroenterol Hepatol 2013 Feb 1;11(2):158–165.e2. Elsevier Inc. [51] Amiot A, Messing B, Corcos O, Panis Y, Joly F. Determinants of home parenteral nutrition dependence and survival of 268 patients with non-malignant short bowel syndrome. Clin Nutr 2012 Sep 15:1–7. Elsevier Ltd. [52] Messing B, Joly F. Guidelines for management of home parenteral support in adult chronic intestinal failure patients. YGAST 2006 Feb;130(2 suppl 1):S43–51. [53] Acosta S, Björck M. Acute thrombo-embolic occlusion of the superior mesenteric artery: a prospective study in a well defined population. Eur J Vasc Endovascular Surg Off J Eur Soc Vasc Surg 2003 Aug 1;26(2):179–83. [54] Katsura M, Mototake H, Takara H, Matsushima K. Management of spontaneous isolated dissection of the superior mesenteric artery: case report and literature review. World J Emerg Surg 2011;6:16. [55] Min S-I, Yoon K-C, Min S-K, Ahn SH, Jae HJ, Chung JW, et al. Current strategy for the treatment of symptomatic spontaneous isolated dissection of superior mesenteric artery. J Vasc Surg 2011 Aug;54(2):461–6. [56] Park YJ, Park KB, Kim D-I, Do YS, Kim D-K, Kim Y-W. Natural history of spontaneous isolated superior mesenteric artery dissection derived from follow-up after conservative treatment. J Vasc Surg 2011 Sep 23. [57] Jung SC, Lee W, Park E-A, Jae HJ, Chung JW, Park JH. Spontaneous dissection of the splanchnic arteries: CT findings, treatment, and outcome. Am J Roentgenology 2013 Jan;200(1):219–25. [58] Amitrano 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 Nov;102(11):2464–70. [59] Plessier A, Rautou PE, Valla D-C. Management of hepatic vascular diseases. J Hepatol 2012;56(suppl 1):S25–38. [60] Curd LH, Conrad MC. Role of sympathetics in the response to acute venous occlusion. Am J Physiol 1977 Aug;233(2):H264–8. [61] Colombato LA, Albillos A, Groszmann RJ. Temporal relationship of peripheral vasodilatation, plasma volume expansion and the hyperdynamic circulatory state in portal-hypertensive rats. Hepatology 1992 Feb;15(2):323–8. [62] Morgan MD, Savage COS. Vasculitis in the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2005 Apr;19(2):215–33. [63] Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised international chapel hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013:1–11. [64] Pagnoux C, Mahr A, Guillevin L. Abdominal and digestive manifestations in systemic vasculitides. Ann de médecine interne 2003 Nov;154(7):457–67. [65] Ha HK, Lee SH, Rha SE, Kim JH, Byun JY, Lim HK, et al. Radiologic features of vasculitis involving the gastrointestinal tract. Radiographics 2000 May;20(3):779–94. [66] Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, wegener granulomatosis, churg-strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine (Baltimore) 2005 Mar;84(2):115–28. [67] Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Le Toumelin P, et al. The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore) 2011 Jan;90(1):19–27. [68] Kozuch PL, Brandt LJ. Review article: diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy. Aliment Pharmacol Ther 2005 Feb 1;21(3):201–15. [69] Trompeter M, Brazda T, Remy C, Vestring T, Reimer P. Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy. Eur Radiol 2002 May 1;12(5):1179–87. [70] Björck M, Wanhainen A. Nonocclusive mesenteric hypoperfusion syndromes: recognition and treatment. Seminar Vasc Surg 2010 Apr 11;23(1):54–64. [71] Stollman N, Metz DC. Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care 2005 Mar; 20(1):35–45. [72] Bardou M, Barkun AN. Stress ulcer prophylaxis in the ICU. Crit Care Med 2013 Mar;41(3):906–7. [73] Theodoropoulou A. Ischemic colitis: clinical practice in diagnosis and treatment. World J Gastroenterol 2008;14(48):7302. [74] O’Neill S, Yalamarthi S. Systematic review of the management of ischaemic colitis. Colorectal Dis 2012 Oct 9;14(11):e751– 63. [75] Brandt LJ, Feuerstadt P, Blaszka MC. Anatomic patterns, patient characteristics, and clinical outcomes in ischemic colitis: a study of 313 cases supported by histology. Am J Gastroenterol 2010 Jun 8;105(10):2245–52. [76] Flobert C, Cellier C, Berger A, Ngo A, Cuillerier E, Landi B, et al. Right colonic involvement is associated with severe forms of ischemic colitis and occurs frequently in patients with chronic renal failure requiring hemodialysis. Am J Gastroenterol 2000 Jan;95(1):195–8. [77] Fujita T. Variability in pathogenesis and treatment of ischemic colitis. Am J Gastroenterol 2011 Apr;106(4). 800–0. [78] Glauser PM, Wermuth P, Cathomas G, Kuhnt E, Käser SA, Maurer CA. Ischemic colitis: clinical presentation, localization in relation to risk factors, and long-term results. World J Surg 2011 Nov;35(11):2549–54. [79] Arthurs ZM, Titus J, Bannazadeh M, Eagleton MJ, Srivastava S, Sarac TP, et al. A comparison of endovascular revascularization with traditional therapy for the treatment of acute mesenteric ischemia. J Vasc Surg 2011 Mar;53(3):698–704 discussion704–5. [80] Ryer EJ, Kalra M, Oderich GS, Duncan AA, Gloviczki P, Cha S, et al. Contemporary results of revascularization for acute mesenteric ischemia. J Vasc Surg Society Vascular Surgery 2012 Apr 11;55(6):1682–9.

O. Corcos, A. Nuzzo / Best Practice & Research Clinical Gastroenterology 27 (2013) 709–725

725

[81] Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease. Circulation 2006 Mar 21;113(11):e463–654. [82] Gupta PK, Natarajan B, Gupta H, Fang X, Fitzgibbons Jr RJ. Morbidity and mortality after bowel resection for acute mesenteric ischemia. Surgery Mosby, Inc. 2011 Oct 1;150(4):779–87. [83] Kougias P, Lau D, Sayed el HF, Zhou W, Huynh TT, Lin PH. Determinants of mortality and treatment outcome following surgical interventions for acute mesenteric ischemia. J Vasc Surg 2007 Sep;46(3):467–74. Elsevier. [84] Resch TA, Acosta S, Sonesson B. Endovascular techniques in acute arterial mesenteric ischemia. Semin Vasc Surg 2010 Mar; 23(1):29–35. [85] Sarac TP, Altinel O, Kashyap V, Bena J, Lyden S, Sruvastava S, et al. Endovascular treatment of stenotic and occluded visceral arteries for chronic mesenteric ischemia. J Vasc Surg 2008 Mar 1;47(3):485–91. [86] van Noord D, Kuipers EJ, Mensink PBF. Single vessel abdominal arterial disease. Best Pract Res Clin Gastroenterol 2009 Jan 1;23(1):49–60. [87] Mensink PB, Moons LM, Kuipers EJ. Chronic gastrointestinal ischaemia: shifting paradigms. Gut 2010 Nov 29.