Acute mesenteric ischemia: Pathophysiology, diagnosis, and treatment

Abstract

Ischemia has been traditionally defined as an insufficiency of oxygen delivery by the blood. Lately it has become clear that such a view is too restrictive. Hypoperfusion may be caused by both anatomic and functional impediments to either inflow to or outflow from an organ. Furthermore, the pathophysiologic consequences are likely to involve not only cellular hypoxia, but also a restricted supply of nutrients and other important molecules, and an abnormal elimination of physiologic wastes such as carbon dioxide. Acute mesenteric ischemia (AMI) is, therefore, a severe anatomic or functional limitation of the splanchnic circulation, resulting in a dual defect of intestinal hypoxia and cellular hypercarbia. It is a complex syndrome that includes three related processes: occlusive mesenteric ischemia, nonocclusive ischemia, and sepsis-induced splanchnic ischemia. Acute occlusive mesenteric ischemia is caused by a local impairment of splanchnic blood flow. Arterial occlusion is usually caused by embolism rather than thrombosis. Mesenteric vein thrombosis is responsible for 20% of acute occlusive mesenteric ischemia. This condition is termed primary when no predisposing factors can be identified. Secondary mesenteric vein thrombosis may occur in portal hypertension, intraabdominal infection, and carcinomatosis (particularly gastrointestinal and pancreatic). Nonocclusive mesenteric ischemia is caused by the nonobstructive reduction in oxygen delivery below the critical level where oxygen consumption becomes supply dependent and tissues resort to anaerobic metabolism. Nonocclusive mesenteric ischemia has been observed in shock syndromes, low-flow states, drug-induced vasoconstriction, hypotension complicating vasodilator therapy, and other conditions. Preexisting vascular disease such as diabetes with small vessel disease or arteriosclerosis will predispose to nonocclusive ischemia. Visceral hypoxia is characterized by a reduction in synthesis and an acceleration of the catabolism of adenosine triphosphate. Ischemia finally occurs because either oxygen consumption is reduced or oxygen demand is excessive, or a combination of both. Depressed mesenteric oxygen consumption generally develops because of diminished oxygen delivery. It may also be the consequence of severely reduced cellular oxygen uptake, or an abnormal oxygen utilization apparatus. Excessive acid is produced and buffered, thereby generating CO 2 anaerobically. The increase in CO 2 production, coupled with a reduction in CO 2 removal due to a reduced or absent blood flow, forms the basis for cellular, tissue, and venous hypercarbia. Splanchnic flow is sensitive to numerous factors including the autonomic nervous system, hormones, endogenous mediators, and various drugs. Reperfusion injury is the secondary damage that occurs to ischemic tissues after the reestablishment of blood flow. It is characterized by intense vasospasm and ischemic injury of the intestinal mucosa. This may be due to oxygen-derived free-radical-mediated cellular damage. This secondary nonocclusive transformation of an occlusive ischemia provides a rationale for vasodilatory therapy of occlusive splanchnic ischemia. Sepsis is intricately associated with mesenteric ischemia. The evolution of primary AMI is almost always complicated by sepsis due to enteric organisms. Sepsis-induced gastrointestinal tract dysfunction appears due to visceral ischemia, probably caused by uncontrolled inflammation. When sepsis occurs in AMI, it usually marks the point at which the local disease process acquires a multisystemic dimension, heralding the syndrome of multisystem organ failure with its dismal prognosis. The difficulty of an early diagnosis is probably the most important cause of the high mortality, which varies from 60% to 90%. The diagnosis is particularly difficult in the elderly because of the lack of specificity and the paucity of symptoms. The diagnosis of AMI must be made on the basis of a high index of suspicion. Clinical clues include nausea, vomiting, and diffuse abdominal pain that is out of proportion to symptoms. The difficult diagnosis is compounded by the paucity of revealing laboratory data, which are often nonspecific and consist of a moderate leukocytosis, hyperamylasemia, and lactic acidosis. Rarely, a plain film of the abdomen may suggest the diagnosis. Angiography may demonstrate vasospasm, arterial occlusion, and venous obstruction. Other diagnostic modalities under investigation include mucosal tonometry, ultrasonic duplex scanning, flexible endoscopy, laparoscopy, surface oximetry, infrared photoplethysmography, and 31P magnetic resonance spectroscopy. Most cases of AMI are diagnosed long after the episode has started. The treatment of mesenteric ischemia has two major goals: the prevention of mesenteric infarction and the forestallment of sepsis and sepsis-induced multisystem organ failure. Management of established AMI involves treating the local intestinal injury as well as the systemic consequences, including sepsis. There are three types of care: resuscitative, operative, and nonoperative.