Hello, and welcome to the SCCM Neurocritical Care Review course. I am Sudhir Dattar, faculty here at Wake Forest Baptist Medical Center, and today I will be talking to you about GI issues in the neuroICU. I don't have any disclosures. The objectives of today's talk include a review of the evaluation and management of upper and lower GI bleed, to describe the causes, presentation, and management of medical and surgical abdominal syndrome, such as ileus, bowel perforation, and mesenteric ischemia, and to summarize the clinical features, presentation, and management of liver failure and pharmacological implications of altered hepatic clearance. There are several risk factors for acute GI hemorrhage, and in our patient population that includes acute CNS injury, for example, traumatic brain injury, or poor grade aneurysmal subarachnoid hemorrhage, or following craniotomy, or due to lesions particularly involving the posterior fossa. Increased ICP due to any cause can also lead to gastric ulcers, and they are called Cushing's ulcers, named after the neurosurgeon Harvey Cushing, who first described them. Other risk factors, as outlined here, include mechanical ventilation, coagulopathy, sepsis, previous NSAIDs, and aspirin use, and alcohol abuse, particularly binge drinking. The lesions that can lead to acute GI hemorrhage could either be erosions or ulcers. Erosions are usually minor, they're confined to the mucosa, and seldom lead to a large hemorrhage. Ulcers, on the other hand, extend into the submucosa and beyond, sometimes penetrating the whole thickness of the gut and causing perforation along with life-threatening hemorrhage. The source of acute hemorrhage could be either upper or lower GI tract. Upper GI hemorrhage could be variceal due to esophageal and gastric varices in a serotic patient with portal hypertension, or non-variceal, such as due to peptic ulcer disease or Malory-Weiss tears, which are mucosal tears at the gastroesophageal junction and are often precipitated by forceful vomiting, however, can occur due to any cause of increased intra-abdominal pressure. Aspirin and alcohol abuse are often predisposing factors, but these tears seldom lead to a large life-threatening hemorrhage. Some of the causes of lower GI hemorrhage include diverticular disease, such as diverticulitis, hemorrhoids, ulcerative colitis or Crohn's disease, rectal ulcers or tears, sometimes due to fecal management systems, colorectal malignancy, and in certain situations, an upper GI source can mimic a lower GI source if there is rapid transit of blood, and that can happen in situations where there is massive outpouring of blood in the gut, such as due to a ruptured varix or due to a bleeding ulcer with an arterial base. Development of melanin typically takes about 100 cc or more of blood that slowly transits the gut over several hours, about 10-12 hours or so. However, if there is a large volume of blood with rapid transit, that can present as bright red blood per rectum, even when the source is upper GI, and that is typically associated with hemodynamic compromise, shock, and hematemesis. Some of the early symptoms of acute GI hemorrhage include nausea, excessive sweating, and pallor, and when enough volume is lost, then signs of hypovolemia, such as tachycardia, drop in urine output, and then eventually shock develop. Of note, hemoglobin or hematocrit are not reliable indicators of the degree of blood loss, and that is because a drop in hemoglobin following acute hemorrhage typically occurs due to redistribution of body fluids and dilution, and that can take several hours, sometimes up to 72 hours to fully manifest. In addition, occult blood testing on a nasogastric aspirate sample or feces is also not helpful for detecting clinically significant blood loss, because supportive devices such as NG tubes or otogastric tubes or fecal management systems can cause subtle mucosal trauma, and that can lead to occult blood in those samples. Blood is a cathartic, so if it is present in the gut in any significant amount, it will manifest through one end or the other. This table outlines the clinical manifestation and its associated significance. As you can see here, hematemesis or vomiting blood and coffee ground emesis are nearly 100% specific for upper GI source. On the other hand, clots per rectum are very strongly suggestive of lower GI bleed. Melanin or black tarry stool and hematocasia or bright red blood per rectum suggest upper and lower GI bleed, respectively, except for the caveats that we have talked about. Talking about treatment strategies for acute GI hemorrhage, first and foremost is placement of large-bore IV lines and volume resuscitation using crystalloids and vasopressors as needed for hemodynamic support. As soon as available, replacement of the lost blood with PRBC transfusions is initiated with a hemoglobin goal of 8 grams per deciliter for most patients, and for those with active cardiovascular disease, a higher goal can be chosen. Monitoring of dilutional coagulopathy and thrombocytopenia while transfusing multiple units of packed red blood cells is essential. Correction may be needed with fresh frozen plasma and platelet transfusions. In addition, the citrate in stored blood is a calcium chelator, and with multiple transfusions can lead to a significant drop in plasma-free calcium concentration. Also of importance is correction of any underlying existing coagulopathy, which may be due to either a qualitative or quantitative platelet dysfunction or due to impairment of the coagulation cascade from pathologic processes like DIC or iatrogenic from oral anticoagulants. Patients with peptic ulcer disease should be tested for active infection with H. pylori, and if present, should be treated with appropriate antibiotic regimen. There are several antibiotic regimens to choose from, and the choices are typically guided by the presence of risk factors for macrolide resistance and penicillin allergy. For uncontrolled variceal bleeding, use of somatostatin analogs such as octreotide or vasopressin is recommended with continued infusions for up to 2 to 5 days. Nasogastric tube placement, if possible, can aid in decompression of the stomach prior to intubation and reduce the risk of aspiration. In addition, it can also help in the initial confirmation of upper GI sores before frank hematemesis is observed. The route of endoscopy, upper or lower, depends upon the most likely suspected source. For patients admitted with acute upper GI bleed, endoscopy is recommended early, within 24 hours of presentation. Thermocoagulation, sclerosant injections, or placement of clips are options for controlling the hemorrhage during endoscopy. Placing is preferred for esophageal varices. A detailed review of endoscopic treatment options is beyond the scope of this course. If endoscopy is unsuccessful, for example, in cases of posterior deodorant ulcers, which may be difficult to manage endoscopically, angiographic evaluation and embolization of the bleeding source or surgical intervention are options. Proton pump inhibitor is the mainstay of medical management of patients admitted to the hospital with acute upper GI bleed. Options include using IVPPI every 12 hours at a dose of 40 milligrams, which is our practice, or starting a continuous infusion following a bolus loading dose. Patients with cirrhosis who present with upper GI bleed need prophylactic antibiotics, preferably before endoscopy. We typically use broad-spectrum antibiotics, such as ceftriaxone 1 gram intravenously daily for seven days. If the patient is discharged before seven days, then they can be transitioned to an oral antibiotic regimen, such as suprafloxacin 500 milligrams every 12 hours. As with any other disease, prevention is always better than cure. Patients at high risk of GI bleed should be started on acid suppression for stress ulcer prophylaxis. High risk factors include coagulopathy, chronic liver disease, mechanical ventilation, lack of internal nutrition, sepsis, and several others as outlined here. In addition, traumatic brain or spinal cord injury and burns also increase the risk of GI hemorrhage. Comparing PPIs and H2 receptor blockers for stress ulcer prophylaxis, PPIs probably seem to do better. This meta-analysis involving nearly 40,000 patients showed that PPIs resulted in a greater reduction of clinically important GI bleed events compared with H2 blockers. This risk reduction was highest in patients at high risk of bleeding. Also, there was no important increase in the risk of pneumonia. Several other studies comparing PPIs to H2 blockers produced mixed results, either showing no important difference or, as in case of some, favoring PPIs. This clinical practice guideline published in 2020 suggests using PPI for stress ulcer prophylaxis with H2 blockers as a reasonable choice. Delayed gastric emptying is a common occurrence in the critically ill and is linked to aspiration pneumonia and adverse outcomes. Alias occurs when there is functional inhibition of bowel propulsive activity. Some of the common causes are outlined here. Some degree of alias is physiologic following abdominal surgery, with a rapid return of gastric and small bowel function within hours and return of colonic function by 2-5 days. If the alias gets prolonged beyond that, it is considered pathologic. Of the neurologic disorders to note are Guillain-Barre syndrome and spinal cord injury, both of which lead to autonomic dysregulation and impaired gut motility. Some of the commonly seen culprits for alias in the ICU are medications, particularly opiates and anticholinergic drugs, as well as electrolyte imbalances, particularly hypokalemia. If the alias goes unchecked, it can lead to substantial preventable complications, such as abdominal distention, bowel perforation, and Compadre-Pitt syndrome. Common symptoms of alias include abdominal discomfort, nausea, and vomiting. Exam findings include discomfort or pain on palpation, distention of the abdomen with a tympanic note, no visible peristalsis, and silence on auscultation. A couple of abdominal x-rays are shown here and they reveal distended loops of small and large bowels. Involvement of the cecum, ascending and transverse colon are common. Also of importance is to look for any free peritoneal air that may suggest bowel perforation has occurred. When a combination of history, exam findings, and plain radiography cannot distinguish alias from small bowel obstruction, CT scan of the abdomen is recommended and with oral contrast has a high sensitivity and specificity in distinguishing alias from complete small bowel obstruction. Management includes treatment of the underlying cause, if known, and that may include discontinuation of the offending drugs, particularly opiates, when possible. Correction of electrolyte disturbances, particularly potassium, is crucial. NPO and upper GI tract is decompressed with nasogastric tube to intermittent wall suction. Those who have substantial NG tube output are at risk of dehydration, which can be addressed with adequate use of balanced crystalloids to prevent hypovolemia. Bowel rest is preferred initially and with signs of return of bowel function, trickle feeds can be started and advanced as tolerated. In cases of severe colonic distention, rectal tube placement may be necessary to decompress the colon. Enteral feeding is the most preferred route. However, in very prolonged cases of alias, total parenteral nutrition can be considered, but it is usually best avoided. A subtype of colonic alias is Ogilvy syndrome or acute colonic pseudo obstruction. This is characterized by acute dilation of the colon without obstruction that usually involves the cecum and the right hemicolon, although occasionally can extend to the rectum. Initial management is conservative with frequent monitoring given clinical risk of colon ischemia and perforation. In severe cases, options include pharmacologic management with neostigmine, colonoscopy and decompression or surgical decompression with cecostomy or colectomy. In our experience, neostigmine is reasonably effective and according to this meta-analysis, including 127 patients, a single dose was effective in resolving colonic pseudo obstruction in 89% of the cases. Let's switch gears and now talk about acute mesenteric ischemia. Intestinal ischemia, which can affect the small or large intestine, can be caused by any process that reduces intestinal blood flow, and that process may be occlusive, such as arterial occlusion, venous occlusion, or non-occlusive, such as arterial vasospasm or a low flow state. Arterial occlusion can be either embolic, and the source is often the heart, or thrombotic and commonly affects the superior mesenteric artery. In patients with acute mesenteric ischemia, abdominal examination may be normal initially or show subtle nonspecific findings, such as mild extension, but no signs of peritoneal inflammation. Patients often complain of severe abdominal pain, which is typically out of proportion to physical exam findings. However, as bowel ischemia progresses, the abdomen becomes grossly distended, bowel sounds disappear, and eventually peritoneal signs develop. A feculent odor to the breath may also be appreciated. Eventually, signs of sepsis and shock signal a deteriorating course. Mesenterism is the most common source of arterial emboli to the gut. Other risk factors include aortic surgery or instrumentation, such as cardiac catheterization, aortography, or endovascular aortic interventions. Patients with atherosclerotic disease of the celiac artery, superior mesenteric artery, or inferior mesenteric artery are at increased risk for intestinal ischemia. This can lead to a low flow state to the intestinal circulation, leading to non-occlusive ischemia. Vasoconstructive meds, including illicit drugs, have also been implicated in the development of non-occlusive ischemia. Laboratory studies are nonspecific and findings may include marked leukocytosis with neutrophilic predominance, elevated hematic rate consistent with hemo concentration, and metabolic acidosis. A general rule of thumb is that any patient presenting with acute abdominal pain and metabolic acidosis has intestinal ischemia until proven otherwise. Some other laboratory values have also been examined, which include lactate, which carries a sensitivity of 80 to 90%, but a very low specificity of around 44%. Also, serum amylase has been studied and elevated levels have been observed in just approximately half of the patients. Abdominal radiographs may be nonspecific and completely normal. When abnormal, they may reveal ileus with distended loops of bowel, thickening of the bowel wall, or presence of gas within the bowel wall, referred to as pneumatosis intestinalis, marked by arrowheads in this abdominal radiograph here. If a perforation has occurred, then x-rays reveal free air under the diaphragm on upright films or free air over the liver or spleen in lateral decubitus position. In this supine film here, the big arrows mark the free intraperitoneal air. For patients presenting with classic clinical manifestations and abdominal films revealing signs of advanced ischemia or findings of free air suggesting perforation, a STAT surgical consultation for urgent laparotomy is warranted. For a stable patient with persistent signs or symptoms, additional imaging with abdominal CT scan with IV contrast is often pursued. In this example here, the big arrow on the left marks the free intraperitoneal air, and the small arrows on the right show pneumatosis intestinalis or gas in the bowel wall. The arrowheads in the left image show the presence of hepatic portal venous gas, which is correlated strongly with transmural bowel infarction. If the CT scan is inconclusive and the suspicion remains high, then mesenteric angiogram would be the next step. Initial management includes resuscitation with intravenous fluid therapy, vasopressors if needed for treatment of shock, empiric broad-spectrum antibiotic therapy, and gastric decompression. In the absence of any active bleeding or other contraindications, systemic anticoagulation can be considered. With signs of advanced ischemia, emergency surgical consultation is warranted for laparotomy. Abdominal compartment syndrome refers to organ dysfunction caused by intraabdominal hypertension. Abdominal perfusion pressure equals mean arterial pressure minus intraabdominal pressure, a concept similar to the cerebral perfusion pressure. Normal IAP, or intraabdominal pressure, is 5 to 7 mmHg, however, that number can be variable, and in patients with high BMI, IAP of 9 to 14 mmHg can be observed. Abdominal hypertension, or IAH, is defined as sustained elevation in IAP greater than 12 mmHg and is further classified into four grades as outlined in the table here. From a research standpoint, abdominal compartment syndrome is defined as sustained elevation in IAP to greater than 20 mmHg with new organ dysfunction. However, from a clinical standpoint, ACS, or abdominal compartment syndrome, is defined as IAH that produces new organ dysfunction. A general rule of thumb is that patients with a pressure less than 10 are unlikely to have ACS, and patients with a pressure greater than 25 are quite likely. There is a strong correlation between bladder pressure and IAP, and therefore, measurement of bladder pressure is what is used for diagnosis. Abdominal compartment syndrome can be caused by increased abdominal volume from gut dilation, malignancy, or ascites, decreased wall compliance due to surgery with tight closures, or wall bleeding, or a combination of these factors. Additionally, massive resuscitation for septic shock, burns, and abdominal infections can also lead to ACS. Increased intra-abdominal pressure can cause multi-organ dysfunction that includes acute renal failure due to vascular compromise, gut ischemia, decreased cardiac output from impairment of venous return to the heart, and extrinsic pulmonary compression through the diaphragm causing increased respiratory pressures or decreased volumes depending on the mode of mechanical ventilation. Of particular relevance in our patient population, ACS can increase intracranial pressure and lead to further neurological complications. Management includes evacuation of intra-abdominal contents with nasogastric decompression, colon decompression, drainage of ascites, or removal of fluid with either diuresis or renal replacement therapy. Other strategies include adequate analgesia and sedation to relax the abdominal wall, and in severe cases, neuromuscular paralysis. The aim is to maintain abdominal perfusion pressure greater than 60 millimeters of mercury for adequate perfusion of intra-abdominal organs. And finally, surgical decompression is often necessary for these patients, especially when the intra-abdominal pressure is greater than 25 millimeters of mercury. Fulminant hepatic failure is defined as acute onset of encephalopathy with a new coagulopathy without pre-existing liver disease with an illness course that is less than 26 weeks. In the 1980s, acute viral hepatitis used to be the most common cause, however, that is now taken over by acetaminophen toxicity as the most common cause worldwide. Other causes are outlined here. The most feared complication from a neurologic perspective is development of cerebral edema causing increased ICP and brain herniation. Hyperammonemia is thought to be the common underlying pathway. Under normal circumstances, ammonia is produced in the gut and is metabolized by the liver to urea and glutamine. However, when the liver fails, ammonia starts building up and is then metabolized in other tissues such as the brain where astrocytes are the sites of ammonia detoxification. Here, ammonia is converted to glutamine and glutamine being osmotically active causes the astrocytes to swell. This slide outlines the grades of hepatic encephalopathy, which can go anywhere from minimal without clinical evidence of mental status change all the way to grade 4, which is a comatose state. Ammonia level of greater than 100 micrograms per liter is associated with high-grade hepatic encephalopathy, and a level of greater than 200 is strongly associated with development of cerebral edema. ICP monitoring is useful, although often challenging because these patients have concomitant coagulopathy, making placement of ICP monitoring devices difficult. The principles of treatment of cerebral edema in these patients are similar to the treatment of cerebral edema due to other conditions and includes the use of osmotic agent sensitization. Renal replacement therapy, either as intermittent hemodialysis or CRRT, can help temporize ammonia. However, the definitive management is liver transplantation, and patients may need to be transferred to a transplant center. Patients with cirrhosis are susceptible to a variety of complications, and the survival can be reduced when they occur. Outlined here is a list of major complications, and when one of these occur, patients are considered to have developed decompensated cirrhosis. Portal vein thrombosis and cardiomyopathy are also other major complications. However, they are not included in the criteria for decompensated cirrhosis. Risk factors for decompensation include bleeding, infection, alcohol intake, hepatotoxic medications, dehydration, and obesity, among others. Once decompensation occurs, patients should be considered for liver transplantation. Liver is responsible for selective uptake, concentration, metabolism, and excretion of most drugs. There are several mechanisms of hepatic drug clearance, and liver impairment could alter one or more of those pathways, including alterations of hepatic blood flow, portal shunting, changes in cytochrome P450 activity, hypoalbuminemia, and increase in free levels of the drug. In addition, cholestasis and impaired renal clearance can also affect drug metabolism. Those adjustments are needed to prevent toxicity or inadequate efficacy, depending on the individual drug. That's all I have. Thank you so much for listening and I hope you enjoyed the talk.

neuroICU

upper GI bleeding

lower GI bleeding

abdominal syndrome

mesenteric ischemia

liver failure