Mesenteric ischaemia

This is a common enough event in the ICU that one might have expected a serious discussion of ischaemic gut to appear in the exam with some frequency, and indeed it has now appeared four times:

• Question 13 from the second paper of 2022
• Question 8 from the second paper of 2021
• Question 1 from the first paper of 2021
• Question 12 from the first paper of 2017

These SAQs asked for a detailed exploration of mesenteric ischaemia, specifically asking candidates to "outline the pathophysiology, diagnosis and treatment". Additionally, Question 8 from the second paper of 2021 went into some considerable detail about vascular supply anatomy and the difference between venous and arterial ischaemia.

What does an intensivist need to know about this for their day-to-day practice? Not much, if Oh's Manual is anything to go by. Mesenteric ischaemia comes up once as a quarter-page discussion in Jamie Cooper's chapter on lactic acidosis (p/160 of the 7th edition), where much is made of how difficult it is to diagnose, and how one must have a high index of suspicion. Nothing in the way of concrete recommendations or instructions is offered, which is characteristic of the Manual (and defies the definition of a manual).

For good quality reading on this topic, the time-poor candidate is directed to either this 2014 review by Schofield et al or this NEJM article by Clair and Beach (2016). Each has helpful exam-ready headings like "Pathophysiology" and "Diagnosis". These articles were remixed into the summary which follows. Most of the discussion will be about acute mesenteric ischaemia as it is seen more commonly in critical care environments, but chronic mesenteric ischaemia is also a thing - more akin to claudication of the gut - which will receive some minimum of attention here. For more detail about this very different beast, the exam candidate with infinite time resources is directed to the excellent review by Pecoraro et al (2012), or to the Guidelines of the World Society of Emergency Surgey (Bala et al, 2017)

Mesenteric blood supply

The splanchnic circulation is described in greater detail in the CICM First Part Exam study notes. In summary:

The major vessels and their branches are:

• Coeliac trunk
  • Left gastric artery
  • Common hepatic artery
  • Splenic artery
• Superior mesenteric artery
  • Inferior pancreaticoduodenal artery
  • Intestinal (jejunal and ileal) arteries
  • Ileocolic artery
  • Right colic artery
  • Middle colic artery
• Inferior mesenteric artery
  • Left colic artery
  • Sigmoid arteries
  • Superior rectal artery

The structures supplied by each major branch are:

• Coeliac trunk:
  • Abdominal part of the oesophagus
  • Stomach
  • Superior half of the duodenum
  • Liver
  • Superior half of the pancreas
  • Spleen
• Superior mesenteric artery:
  • Intestine, from the lower half of the duodenum down to the splenic flexure of the large intestine
• Inferior mesenteric artery:
  • Colon, from the splenic flexure down to the sigmoid and superior portion of the rectum

Territories most susceptible to ischaemia

The mesenteric circulation enjoys extensive collateral blood supply, which generally means that it is resistant to ischaemia. For example, anastomoses between arteries from different parts of the mesenteric circulation mesh freely and form a shared capillary network. Thus, none of these arteries are end-arteries, which means they should be relatively resistant to emboli. Still, emboli can be highly destructive if they block a proximal large vessel. 

• The SMA is particularly susceptible to emboli due to the acute angle of its take-off from the aorta and its higher blood flow rate.
• This tends to spare the projimal jejunum and colon, as most of the emboli lodge 3 to 10 cm distal to the origin of the SMA (Bala et al, 2017)

Also, the areas of greatest collateralisation are areas which are the most susceptible to non-occlusive mesenteric ischaemia (NOMI). These watershed areas are:

• The neck of the pancreas, a watershed between the coeliac trunk and SMA 
• The splenic flexure (Griffth's Point), a watershed between the branches of the SMA and IMA
• The rectosigmoid junction (Sudek's Point), a watershed between the IMA and the superior rectal artery (Amini & Nagalli, 2020)

Pathophysiology of mesenteric ischaemia

There are several major ways this thing can happen:

• Acutely:
  • Arterial embolism (40% of cases)
  • Arterial thrombosis from ruptured atheroma (20-35% of cases)
  • Arterial dissection (<5% of cases)
  • Non-occlusive mesenteric hypoperfusion (10-15% of cases)
  • Venous infarction (5-15% of cases)
• Chronically
  • Gradual onset of arterial insufficiency

Occlusive mesenteric ischaemia

• This is in an acute occlusion of the vessels
• Embolic (thrombotic) occlusion: 
  • The origin of the thrombus is typically the heart
  • AF is the main cause, but other possibilities exist (eg. LV apical thrombus, a large abdominal aortic aneurysm, or cholesterol emboli after angiography or IABP insertion)
• Occlusion due to a rupture of a mesenteric or aortic atheroma:
  • 75% of these patients have pre-existing chronic mesenteric ischaemia; in 90% of cases the acute ischaemia is due to a progressive atheromatous narrowing at the origin of the mesenteric vessels.

Non-occlusive mesenteric ischaemia

• The mesenteric circulation is a vascular bed with highly variable vascular resistance
• Any increase in mesenteric vascular resistance can lead to mesenteric hypoperfusion
• Typically this is seen in patients requiring high-dose vasopressors, or those who are shocked and secreting their own
• The watershed areas mentioned above are the most susceptible.

Venous mesenteric infarction

• This is basically a DVT of the gut, with resulting oedema and diminished perfusion.
• Risk factors include portal hypertension, hypercoagulability, thrombocytosis and any sort of local inflammation (eg. pancreatitis or diverticulitis).

Chronic mesenteric arterial insufficiency

• Atherosclerosis of mesenteric vessels leads to chronically diminished flow through the mesenteric circulation
• Generally speaking, this leads to the development of extensive collateral circulation
• The collateral circulation allows a major visceral arterial occlusion to be clinically silent, and to go virtually unnoticed

Risk factors for mesenteric ischaemia

Obviously, the risk factors for different kinds of mesenteric ischaemia are going to be different. 

Occlusive acute mesenteric ischaemia tends to result from embolic phenomena or atheroma rupture, so the risk factors tend to be things which create mobile thrombi or which agitate atheromae. Some risk factors, like cardiac surgery, are a source of both emboli (eg. air bubbles) as well as atheroma fragmentation (eg. when the surgeon stabs your aorta).

• Angiography
• Intra-aortic balloon pump counterpulsation
• VA ECMO
• Cardiac surgery
• Infective endocarditis
• Atrial fibrillation
• Large areas of infarcted LV or LV aneurysms (mural thrombi)
• Infective endocarditis

Non-occlusive acute mesenteric ischaemia is a phenomenon where an otherwise relatively normal mesenteric vascular rbed is subjected to some sort of sudden increase in vascular resistance, or a sudden decrease in blood flow, or some combination of both. 

• Shock states, especially those with increased SVR (eg. cardiogenic or obstructive shock)
• High dose vasopressors, eg. noradrenaline and vasopressin

Venous mesenteric ischaemia due to mesenteric venous thrombosis has risk factors which resemble the risk factors for DVT and VTE in general. Additionally, there are a few risk factors unique to the mesenteric venous circulation which are probably of interest to the intensivist. Hmoud et al (2014) list quite a number of different risk factors, which can be arbitrarily grouped into these two categories:

• Generic clot risk factors
  • Factor V Leiden, prothrombin mutation, protein C or S deficiency
  • Antiphospholipid syndrome 
  • Malignancy
  • Oral contraceptives
• Specific mesenteric venous risk factors
  • Inflammatory bowel disease
  • Abdominal surgery, especially splenectomy
  • Portal hypertension
  • Pancreatitis
  • Abdominal trauma

Diagnosis of mesenteric ischaemia

History 

• History of atherosclerosis
• Hypercoagulable background
• AF
• Vasculitis
• Recent abdominal surgery
• Historical features associated with chornic mesenteri ischaemia, eg:
  • Postprandial pain ("mesenteric angina"), 30-60 minutes after eating
  • Weight loss
  • Diarrhoea or constipation
  • Early satiety

Examination

• Classic “pain out of proportion to examination”
• Epigastric bruit
• Peritonism
• Clinical features of shock

Biochemistry

• Features of organ system dysfunction, eg. rising creatinine
• Raised lactate
• Neutrophilia

Imaging

• Doppler ultrasound of the mesenteric vessels
• CT with IV contrast, two-phase to detect venous thrombosis
• Catheter angiography (also allows thrombolysis)

Clinical characteristics of different types of mesenteric ischaemia

The World Society of Emergency Surgery suggest that "severe abdominal pain out of proportion to physical examination findings should be assumed to be AMI until disproven". This does not seem to be specific to any particular cause of ischaemia. According to Park et a (2002), the presenting features usually are:

• Abdominal pain (95% of patients)
• Nausea (44%)
• Vomiting (35%)
• Diarrhoea (35%)
• PR bleeding (16%)

The clinical scenario is said to differentiate the causes of mesenteric ischaemia, as the clinical findings are typically similar for all of them (wait long enough and ultimately everything starts looking like severe septic shock and multiorgan system failure). In short, the abdomen is usually the same on examination, and the way you come to the conclusion that this must be embolic or venous, is by discovering that the patient is in AF, or has recently had a bowel resection for a colonic carcinoma, or something along those lines. Still, Hmoud et al (2014) were able to create this table of clinical findings and historical features which may help differentiate arterial and venous mesenteric ischaemia:

	Arterial mesenteric ischaemia	Venous mesenteric ischaemia
Risk factor	Acute intra-abdominal process	Atrial fibrillation
	Thrombophilia	Cardiomyopathy and CHF
	Malignancy	Valvular heart disease
	Cirrhosis
History of DVT	Absent	Present in 20–40%
CT	Diagnostic in 40–50% only	In more than 90%
Angiogram	Diagnostic in most	In 50–60% only
Acute presentation	Most of the time	Can be subacute or chronic
Bowel infarction	Likely if not relieved in 12 h	Not usual if diagnosed and AC started
Treatment	Embolectomy or IA papaverine	Anticoagulation, possible thrombolysis, systemic or directed
Need for surgery	Frequent	Less likely if AC started early
Ischemic to normal transition	Abrupt	Gradual
Mortality	More common	Less common with CT and AC availability
Chronicity	Rare	Can occur with portal hypertension and varices

Management of mesenteric ischaemia in the ICU

Broadly, one could outline the management in a simplified way, but one would also have to admit that a slightly different strategy would be required depending on what sort of mesenteric ischaemia is involved.

Specific management:

• Occlusive mesenteric ischaemia:
  • Endovascular repair
  • Open repair with or without vascular bypass
  • Catheter-directed clot aspiration or  thrombolysis
  • Stenting of dissected segments
• Non-occlusive mesenteric ischaemia:
  • Management of the shock state which focuses on maximising splanchnic blood flow (eg. decreased doses of vasopressors, increased inodilators
  • Catheter-directed vasodilators may be an option (eg. papeverine)
  • Stenting could be an option if chronic SMA stenosis is making this condition worse
• Venous mesenteric ischaemia:
  • Anticoagulation
  • Endovascular clot retrieval
• In all cases
  • Bowel resection of the infarcted bowel may be the only option

Supportive management

• Airway protection may be required (high risk of aspiration)
• Mechnical ventilation (increased work of breathing due to acidosis)
• Circulatory support (vasodilated shock state)
• Analgesia and anaesthesia (opiates may actually be preferred, as they "rest the gut" by paralysing its motility)
• Neuromuscular junction blockers may help organ perfusion by their effect on abdominal compartment pressure
• Electrolyte correction (particularly correction of acdi-base balance)
• Fluid resuscitation (extensive third-space losses are to be expected)
• Abdominal compartment pressure - serial measurements 
• Parenteral nutrition (the patient should remain fasted)
• Antibiotics of a broad spectrum, eg. piperacillin/tazobactam or meropenem

Prognosis of mesenteric ischaemia

Like with everything in ICU, the prognosis of mesenteric ischaemia is mainly related to whatever else is going on. The prognosis of a promptly detected arterial embolic event in a patient with AF and nothing else is obviously going to be different to the prognosis of the patient who developed mesenteric ischaemia in the course of severe septic shock with multiorgan system failure. Looking at an undifferentiated case series of 780 patients, Leone et al (2018) found an in-ICU mortality rate of 58%. They could not determine which was occlusive or which was venous; but they assumed that the 14% of patients who survived with conservative management probably had the venous version, which generally does better. On the other hand, where the ischaemia is non-occlusive and due to something like cardiogenic shock, it should be viewed as uniformly fatal: nobody is going to operate on these people to remove the infarcted bowel, which means they will surely die. Thus, it would be rather difficult to produce precise numbers to describe the mortality for each subtype of mesenteric ischaemia.