Toxic megacolon and Ogilvie’s syndrome

Ogilvie’s or acute colonic pseudo-obstruction

The clinical features of Ogilvie’s syndrome include abdominal distention, with or without abdominal pain, in hospitalized or institutionalized patients with serious underlying medical and surgical conditions. ^{, ,} Patients usually present with constipation; however, passage of flatus or stool is reported in up to 40% of patients. Bowel sounds may be normal, diminished, or hyperdynamic. Leukocytosis and fever are more common in patients with ischemia or perforation, but also occur in those who have not developed these complications. According to Laplace’s law, the pressure required to stretch the walls of a hollow viscus decreases in inverse proportion to diameter. Therefore progressive colonic distention causes the highest tension in the wall of the cecum and is most likely to be the site of perforation. The risk of cecal perforation increases sharply when cecal diameter is greater than 12 cm and when this distention has been present for longer than 6 days. A diameter of 9–12 cm has been suggested as a sign of impending perforation. ^, Institutionalized patients with chronic constipation or chronic dysmotility can have a chronically distended cecum with diameter over 12 cm without clinical manifestation. The 12-cm diameter warning must therefore be individualized. If the diagnosis and treatment are delayed, progressive distention may cause peritoneal signs, abdominal compartment syndrome, respiratory compromise, sepsis, ischemia, perforation, MOF, and death.

Toxic megacolon

Toxic megacolon is the late, life-threatening complication of inflammatory or infectious colitis. Patients present with fever, leukocytosis, abdominal distention, and tenderness, with or without signs of local or generalized peritonitis. Both IBD and infectious colitis classically present with diarrhea, but constipation may herald the onset of megacolon, delaying diagnosis. In addition to these findings, patients may present with dehydration, altered consciousness, electrolyte disturbances, hypoalbuminemia, and hypotension. In severe cases, septic shock and MOF may ensue. ^, Factors that may trigger or predispose to the development of toxic megacolon have been identified; these include severe hypokalemia; discontinuation or rapid tapering of corticosteroids, sulfasalazine, or mesalazine; use of antidiarrheal agents; and use of antidepressants. Barium enema and colonoscopy may cause worsening distention that further impairs colonic blood supply, leading to worsening ischemia and perforation. Colonoscopy and barium enema are contraindicated in patients with clinical or radiographic features of toxic megacolon because of the risk of perforation.

Colonic ileus and ogilvie’s syndrome

The pathophysiology of Ogilvie’s syndrome is not fully understood. Current literature suggests an imbalance in autonomic regulation of the colonic motor function, leading to excessive parasympathetic suppression and sympathetic stimulation. This results in an aperistaltic colon. ^, In addition to autonomic dysregulation, neurotransmitters (e.g., substance P and vasoactive intestinal polypeptide [VIP]), inflammatory mediators (e.g., tumor necrosis factor [TNF], interleukin-1 [IL-1]), metabolic derangements, and pharmacologic interventions also play a crucial role in the development of Ogilvie’s syndrome. Electrolyte disturbances are common and often multifactorial. For example, the inflamed colon loses its capacity to reabsorb salt and water, and the rate of potassium excretion into the lumen may be markedly increased because of inflammatory diarrhea. Metabolic alkalosis secondary to volume depletion and potassium loss is associated with poor prognosis. Metabolic acidosis suggests the presence of ischemic colitis.

Postoperative motility disturbances are inevitable after abdominal surgery and result from a complex interaction of neurogenic and inflammatory mechanisms. The extent of parasympathetic suppression and sympathetic activation depends on the amount of surgical stimulation, as demonstrated by Bueno and colleagues in experimental studies in dogs. Surgical manipulation triggers two different, distinct phases of postoperative ileus. The first or early phase is neurally mediated and is activated during and immediately after surgery. During this phase, intestinal manipulation initiates release of norepinephrine via the sympathetic nerves from the spinal cord, in addition to nitric oxide (NO) and VIP release via vagal nerve stimulation, abolishing the motility of the entire gastrointestinal tract. ^, This phase ceases once the abdomen is closed. The second, long-lasting phase of postoperative ileus involves the inflammation of the intestinal muscularis. During this phase, activation of peritoneal mast cells triggers release of vasoactive and proinflammatory substances, such as histamine and proteases, which recruit leukocytes and temporarily increase mucosal permeability. This allows luminal bacteria or bacterial products to enter the lymphatics. This likely represents the key event that triggers the next stage of the inflammatory cascade: activation of resident macrophages. Once activated, resident macrophages release cytokines such as TNF and subsequent upregulation of inducible nitric oxide synthetase (iNOS) and cyclooxygenase-2 (COX-2), further blunting the contractile response of the inflamed tissues. In addition, in vivo animal studies have demonstrated that endogenous opioids released peripherally can modulate gastrointestinal (GI) motor and secretory functions. Opioid receptors are stimulated by endogenous opioids, which are secreted locally upon stress. Once activated, they inhibit acetylcholine release from motor neurons and promote transmitter release from inhibitory neurons. In addition to stimulation by endogenous opioids, exogenous opioids, commonly used for analgesia, also act upon peripheral opioid receptors in the GI tract, inhibiting GI motility.

CIRCI may be related to circulating bacteria or bacterial products and/or proinflammatory cytokines, following a similar mechanism as previously described. Colonic ileus also has been associated with ischemia-reperfusion injury, causing energy deficit, functio laesa, and oxidant-mediated tissue damage. Finally, distal colonic distention induces inhibition of proximal colonic motility, the so-called colo-colonic reflex, thereby perpetuating a vicious cycle.

Ogilvie’s syndrome

ACPO was first described by Sir William Heneage Ogilvie’s in two patients who had retroperitoneal tumors invading the celiac plexus, which led him to suggest sympathetic deprivation as the etiology of the massive distention. The vast majority of patients presenting with Ogilvie’s syndrome have the syndrome in association with a predisposing factor. Clinical factors predisposing to Ogilvie’s syndrome are summarized in Box 92.1 . ^{, ,} In a large retrospective series of 400 patients, Vanek and Al-Salti reported the most common predisposing conditions associated with Ogilvie’s syndrome were nonoperative trauma (11%), infections (10%), and cardiac disease (10%). Although nonsurgical factors predisposing to Ogilvie’s syndrome are frequent, surgical operations remain the most common cause of this syndrome. Of these, Ogilvie’s syndrome is most likely to occur after obstetric/gynecologic, abdominal/pelvic, trauma, orthopedic/spine, and cardiac procedures. These procedures account for 50%–60% of all Ogilvie’s cases. Exogenous catecholamines have dose-dependent effects on intestinal motility; low doses promote and high doses suppress motility. α-Adrenergic agonists and dopamine are stronger inhibitors of acetylcholine release than β-adrenergic agents. Dopamine, in addition to inhibiting upper GI motility, inhibits distal colonic motility. Antipsychotic agents such as clozapine, haloperidol, and olanzapine have been associated with life-threatening forms of Ogilvie’s syndrome. One explanation of these gastrointestinal side effects is their antimuscarinic properties. Opioids suppress GI motility through activation of mu-opioid receptors, which inhibit the release of acetylcholine from the myenteric plexus. The outcome of this interaction is the decreased levels of cyclic adenosine monophosphate (cAMP) and calcium with a reduction in excitatory neurotransmitter release that ultimately leads to decreased peristalsis. ^, Opioid agonists inhibit GI wall motility, impair reabsorption of fluid from the lumen, and impair relaxation of the internal anal sphincter. Additional predisposing factors such as severe metabolic derangements, sepsis, GI infections, and spinal cord injuries have also been implicated in the development of Ogilvie’s syndrome.