CONTENTS

GI hemorrhage

• Rapid Reference: Overview & Checklist 🚀
• Investigations
  • Diagnosis & bedside evaluation
  • Risk stratification
• Resuscitation basics
• Causes
• Specific bleeding location/types
  • Approach to upper GI bleed
  • Variceal bleed
  • Hematochezia and (presumed) lower GI bleed

stress ulcer prophylaxis

• SUP (stress ulcer prophylaxis)
• PPI pharmacology
• Famotidine pharmacology

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rapid reference: Critical GI bleed checklist

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history & physical 

• History:
  • NSAID use? Abdominal pain?
  • Alcoholism? Liver disease?
  • Surgical history: Gastric bypass surgery? AAA repair?
  • Prior GI bleeds? Prior upper endoscopy or colonoscopy?
  • Anticoagulant medications (including aspirin)? Last dose taken?
• POCUS examination:
  • (1) Hemodynamics & volume status.
  • (2) Ascites?
  • (3) Gastric distension?

labs

• Complete blood count, electrolytes, liver function tests.
• INR, PTT, fibrinogen.
• TEG if cirrhosis or complex coagulopathy (e.g., DIC).
• Type & Crossmatch.
• Iron studies (ferritin, iron, TIBC, transferrin saturation).

medications & blood transfusion

• Blood transfusion
  • Hemodynamically stable: target HgB >7 mg/dL.
  • Extremely unstable: may require massive transfusion protocol: 📖.
• Coagulation optimization:
  • 🩸 Reverse anticoagulant medications. 📖
  • 🩸 Thrombocytopenia: Consider platelet transfusion to target a platelet count >50. 📖
  • 🩸 Hypofibrinogenemia: Cryoprecipitate transfusion to target fibrinogen level >150 mg/dL.
  • 🩸 Consider DDAVP 0.3 mcg/kg if uremic, or if on anti-platelet drugs for soft indications. 📖
  • 🛑 Avoid giving fresh frozen plasma to patients with INR elevation due to cirrhosis. 📖
• Upper GI bleed:
  • Proton pump inhibitor 40 mg IV q12hr.
  • Erythromycin 250 mg IV infused over 5-30 minutes before intubation/endoscopy (especially if ultrasonography reveals gastric distension).📖
    • ⚠️ Contraindicated in QT prolongation.
• If cirrhosis is known/suspected:
  • Octreotide (50 mcg bolus, then 50 mcg/hr infusion).
  • Ceftriaxone 1 gram.
• Review medication list:
  • Discontinue anticoagulants.
  • Discontinue antihypertensives.
• IV iron: Consider intravenous iron repletion with folate for iron deficiency anemia. 📖

procedures: vascular access & source control 

• Access:
  • Ideally, two 18G IVs.
  • For patients undergoing massive transfusion, consider A-line & large-bore central access. 📖
• Source control:
  • Suspected upper GI bleed: Consult GI for EGD (esophagogastroduodenoscopy).
  • Suspected lower GI bleed: NG lavage plus CT angiogram (algorithm below).

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diagnosis & bedside evaluation

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interpretation of various manifestations of GI bleeding

• Hematemesis (vomiting blood)
  • Nearly 100% specific for upper GI bleed (vs. swallowed blood from posterior epistaxis).
  • Implies active bleeding & need for urgent EGD (esophagogastroduodenoscopy).
  • Hematemesis is the most worrisome manifestation of GI bleeding.
• Coffee Ground Emesis
  • In the context of a known GI bleed, coffee ground emesis is highly specific for an upper GI bleed (vs. swallowed blood from posterior epistaxis).
  • The presence of coffee ground emesis implies less active bleeding compared to hematemesis (blood had time to congeal in stomach).
  • Be careful about over-calling the presence of coffee ground emesis (sometimes emesis has some dark particulate material that isn't blood).
• Melena (black tarry stool)
  • Strongly suggestive of upper GI bleed.
  • However, can result from right-sided colonic bleed with slow transit.
  • Other causes of dark stool include oral iron supplementation.
• Hematochezia (bright red blood per rectum)
  • Generally implies a lower GI bleed.
  • However, ~10% of cases result from a massive upper GI bleed with rapid transit of blood through the GI tract (usually such patients will have hemodynamic instability).
  • The clinical approach to severe hematochezia is below. 📖
• Clots per rectum: Very strongly suggestive of a lower GI bleed (Likelihood Ratio of 20 for lower GI source)

differential diagnosis of GI bleed:

• GI hemorrhage is usually easy to diagnose, but consider:
• Posterior epistaxis can cause patients to swallow blood, mimicking an upper GI bleed. This can cause hemorrhagic shock.
• Bloody diarrhea (e.g., due to mesenteric ischemia or infectious colitis) can be misleading. Although this is technically a GI bleed, bleeding isn't the main problem.

POCUS exam: 

• Hemodynamic evaluation
  • Collapsed inferior vena cava and hyperkinetic left ventricle suggest volume depletion from bleeding.
  • If a normal or distended IVC is seen in a patient with shock, this argues against hemorrhagic shock as the cause of the patient's instability. In this scenario, initiating a massive transfusion protocol is inadvisable.
• Ascites
  • Ascites can easily be evaluated with a FAST exam (or an abbreviated exam including the right & left upper-quadrant FAST views).
  • Presence of ascites suggests cirrhosis, with a potential benefit from octreotide and antibiotics. However, note that hemoperitoneum should be considered if there aren't clear signs of gastrointestinal hemorrhage. Occasionally patients will present with splenic laceration due to trivial trauma or splenic pathology.(23569554, 6619401)
• Gastric distension
  • Gastric ultrasonography is a simple, validated approach to evaluate gastric size and contents. 🌊
  • A collapsed stomach argues against active bleeding in the esophagus or stomach (e.g., variceal hemorrhage). Alternatively, a distended stomach may suggest upper GI hemorrhage if the patient hasn't recently eaten.(29487770)
  • For patients undergoing intubation, gastric distension increases the risk of aspiration.

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risk stratification

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factors to consider for initial risk stratification

• Past medical history
  • 👍 Recent endoscopy without any high-risk lesion.
  • 👎 Known cirrhosis and/or varices.
  • 👎 Severe chronic cardiac disease (e.g., cardiomyopathy, aortic stenosis, pulmonary hypertension).
• Hemoglobin
  • 👍 Profound anemia with hemodynamic stability: This implies a subacute or chronic bleed, with low risk of rapid deterioration. These patients have been bleeding for days, meanwhile gradually retaining volume to compensate (isovolemic anemia). The only immediate danger to these patients is iatrogenic: if given blood too rapidly they will develop volume overload. Ideal management isn't to slam in several units of blood, but rather to provide gradual transfusion (often in combination with diuresis).
  • 👎 Normal hemoglobin with unstable hemodynamics: Hemoglobin takes time to fall in response to bleeding, so normal hemoglobin plus shock implies a very brisk bleed.
• Hemodynamics
  • 👍 Shock index (HR/SBP) <~0.9 (31656568)
  • 👎 Shock index (HR/SBP) >~0.9
  • 👎 Frank hypotension, syncope, poor capillary refill.
• POCUS
  • 👍 IVC is full, gastric antrum is empty.
  • 👎 IVC is empty, gastric antrum is full.
• Coagulation:
  • 👍 Easy-to-fix coagulopathy (e.g., supratherapeutic INR).  The presence of an easily reversible coagulopathy is a reassuring sign (e.g., markedly supratherapeutic INR from warfarin). If the patient has survived living with an INR of 10, then they will do much better once their INR is normalized. So although the INR elevation can invoke panic, it's actually a favorable prognostic sign.
  • 👎 Hard-to-fix coagulopathy (e.g., NOAC).
• Signs of ongoing bleeding
  • 👍 No active evidence bleeding (no recent bowel movements).
  • 👎 Active hematochezia with suspected lower GI bleed: This is worrisome, but lower GI bleeds have a reduced mortality compared to upper GI bleeds.
  • 👎 👎 Active hematemesis: This indicates an active upper GI bleed.
  • 👎👎👎 Active hematemesis plus hematochezia: This indicates a very brisk upper GI bleeding, with rapid transit through the GI tract.

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resuscitation basics

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red blood cell transfusion

• The hemoglobin target should be >7 g/dL (>70 g/L) in nearly all cases.(23281973) Exceptions include:
  • Massive bleed with hemodynamic instability.
  • Acute coronary syndrome (target hemoglobin >8 g/dL).
• If you're really worried that the patient will open up, request 4 units PRBC on hold in the blood bank. Don't transfuse to a high hemoglobin to “tank up” the patient.
• RCTs and meta-analyses have demonstrated that conservative transfusion causes reduced mortality and reduced rebleeding (e.g., figure below).(28397699)
• Massive transfusion protocol (MTP): For severe instability (e.g. vasopressor dependence) consider activation of a massive transfusion protocol. 📖

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causes of GI hemorrhage

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upper GI bleed (~75%)

• Peptic ulcer disease.
• Esophagitis.
• Mallory-Weiss tear.
• Portal hypertension:
  • Variceal bleed (esophageal or gastric).
  • Portal gastropathy.
• Nasogastric tube irritation.
• Aortoenteric fistula.
• Malignancy.
• Hemobilia (e.g., liver abscess, trauma, liver biopsy).
• Hemosuccus pancreaticus (e.g., pancreatitis, pseudocysts, malignancy).
• Miscellaneous:
  • Dieulafoy's lesion.
  • AVMs (arteriovenous malformations).
  • GAVE (gastric antral vascular ectasia).

 small intestine (~4%)

• Most common cause depends on age:
  • >40-50 years old:  Vascular malformations (e.g., arteriovenous malformations).
  • 25-40 years old:  Neoplasms (e.g., leiomyoma, adenocarcinoma, lymphoma, carcinoid, metastases).
  • <25 years old:  Meckel's diverticulum.
• Crohn disease.
• Isolated ulcers in the small bowel due to NSAIDs, ischemia, or vasculitis.
• Infections (CMV, histoplasmosis, tuberculosis).

lower GI bleed (~30%)

• Most common cause depends on age:
  • <50 years old:  Infectious colitis, anorectal disease, inflammatory bowel disease.
  • >50 years old:  Diverticulosis, arteriovenous malformations, malignancy, ischemic colitis.
• Vascular lesions:
  • Diverticular hemorrhage.
  • AVMs (arteriovenous malformations).
• Colitis (this usually includes bloody diarrhea):
  • Ischemic colitis.
  • Inflammatory bowel disease.
  • Infectious colitis (e.g., bacterial, CMV).
  • NSAID-induced colitis.
• Colon cancer, or post-polypectomy bleeding.
• Colorectal varices.
• Anorectal pathology:
  • Hemorrhoids.
  • Stercoral ulcer.

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approach to upper GI bleed

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initial sequence of interventions

• (1) Emergent upper endoscopy is usually first line, although there are a few exceptions:
  • (a) For a patient with a history of aortic surgery within the past ~5 years, it might be better to start with a CT angiogram to evaluate for aortoenteric fistula.
  • (b) For a patient with exsanguinating bleeding from a duodenal ulcer (e.g., diagnosed based on active extravasation on CT angiography), it could be preferrable to go directly to interventional radiology. Posterior duodenal ulcers can be difficult to manage endoscopically in the face of torrential bleeding.
• (2) If endoscopy identifies source of bleeding but fails to achieve hemostasis, interventional radiology is generally next step.
  • Ideally endoscopy will localize the bleed, which helps direct interventional radiology towards the appropriate arteries to embolize.
  • If endoscopy doesn't show any source of bleeding, consider CT angiography to evaluate for a lower GI bleed.
• (3) If all else fails, surgery is a last-ditch option (with modern endoscopy & IR techniques, this is rarely needed).

PPI (proton pump inhibitor)

• If an upper GI hemorrhage possible, give IV proton pump inhibitor.
• There's no evidence that a continuous infusion is superior to intermittent IV bolus therapy (e.g., 40 mg pantoprazole IV q12hr). (25201154)

erythromycin 💊

• IV erythromycin promotes gastric emptying prior to procedures (e.g., intubation or upper endoscopy). This could facilitate a successful procedure, while reducing the risk of aspiration. Erythromycin is recommended in the 2021 AGA guidelines on upper gastrointestinal hemorrhage, based on RCTs demonstrating that it reduced the need for repeat endoscopy and reduced the hospital length of stay (table below).(33929377)
• The usual dose is 250 mg infused over 5-30 minutes, followed by endoscopy 20-90 minutes later.(33929377, 26083537)
• When not to use erythromycin:
  • (1) The main risk of erythromycin is torsade de pointes, so erythromycin should be avoided in patients with prolonged QTc interval.
  • (2) If gastric ultrasonography demonstrates an empty stomach, there is little rationale for erythromycin.
• Erythromycin may take a long time for the pharmacy to reconstitute, so order it early.

intubation?

• Intubating the GI bleeder isn't a benign intervention. Intubation is associated with worse outcomes, but it's unclear whether this is truly a causal relationship.(28011279)
• Indications for intubation include:(36936565)
  • Altered mental status or agitation, with inability to tolerate a procedure.
  • Severe hematemesis.
• These are high-risk intubations, with a risk of hemodynamic decompensation or massive aspiration:
  • Consider resuscitation and initiation of vasopressor infusion before intubation, to avoid hemodynamic collapse.
  • Gastric ultrasonography may be helpful to detect gastric distension. Consider NG suction to reduce the risk of aspiration (varices aren't a contraindication to NG tube placement). However, NG drainage may not be 100% effective due to occlusion by clots.

post-endoscopy risk stratification & disposition

• The type of bleeding lesion seen on endoscopy determines the risk of re-bleeding. This can assist with patient disposition, for example:
  • Visible vessel: higher risk of re-bleeding.
  • Adherent clot: intermediate risk.
  • Clean-based ulcer or “flat spot”: low risk of re-bleeding (patient can be sent home or to ward).

management of re-bleeding

• This will depend on the lesion seen initially. However, the usual sequence of events is as follows:
  • 1st line: Repeat endoscopy.
  • 2nd line: Interventional radiology.
  • 3rd line: Surgery.

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variceal bleed

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try to keep the portal venous pressure low

• Octreotide should be provide immediately on an empiric basis if varices are considered a possibility.
  • If a variceal hemorrhage is possible, give octreotide (50 microgram bolus followed by 50 mcg/hr infusion). This is safe, when in doubt just give it.
• Variceal bleeding is from a venous source, so any fluid will increase the central venous pressure and directly promote bleeding. These patients often live at a low blood pressure (e.g., 80-90 mm systolic), so borderline hypotension is preferable to large-volume resuscitation.
  • When in doubt, try to avoid massive transfusion in patients with variceal hemorrhage. This can rapidly devolve into a vicious cycle which promotes ongoing bleeding and worsening coagulopathy. 🌊

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antibiosis & infection evaluation

antibiotic

• Antibiotic administration has been shown to improve mortality among patients with GI bleed and cirrhosis. This is often thought of as “SBP prophylaxis,” but that's not entirely true. There is a close relationship between infection, coagulopathy, and bleeding among cirrhotic patients. In some patients, GI bleed may be a manifestation of occult underlying infection which triggers coagulopathy.
• Antibiotics should be given to any patient with cirrhosis plus GI bleeding (this is what the evidence has proven).
  • It doesn't matter whether or not it is a variceal bleed.
  • It doesn't matter whether or not the patient has ascites.
• The usual therapy is ceftriaxone 💉 1 gram IV for seven days.(17030175). 

evaluate for infection

• Given the close relationship between bleeding, coagulopathy, and infection there should be a high index of suspicion for underlying infection.
• If significant ascites is present, this should be sampled to exclude spontaneous bacterial peritonitis. Therapeutic paracentesis may decrease the portal pressure and thereby decrease bleeding.(8985265)
• Additional investigation may be indicated if there are signs of infection (e.g., chest X-ray, blood cultures).

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management of cirrhotic coagulopathy 

• This is discussed in the chapter on cirrhotic coagulopathy: 📖

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procedural options

esophageal varices

• Often can be treated via upper endoscopy with banding (rubber bands are used to occlude the varices).
• If endoscopy fails, the second step is often Transjugular Intrahepatic Portosystemic Shunting (TIPS).

gastric varices 

• Endoscopic therapy often doesn't work well for gastric varices (due to the anatomy of the stomach).
• BRTO procedure (balloon-occluded retrograde transvenous obliteration of gastric varices): If the patient has a gastrorenal shunt, this may be used as a passageway for interventional radiology to reach the varices (figure below). This procedure is technically challenging and not widely available. BRTO won't exacerbate hepatic encephalopathy, but it may increase portal vein pressures and thereby worsen ascites or esophageal varices.(28348478)
• TIPS is more commonly used for gastric varices than BRTO. TIPS has the opposite complication pattern of BRTO (TIPS may worsen hepatic encephalopathy, but it will alleviate ascites and esophageal varices).

blakemore tube placement

• ⚠️ Blakemore tube insertion is not supported by any high-quality evidence. This is a high-risk procedure that should probably be limited to exsanguinating cirrhotic patients who lack other immediate treatment options (e.g., to bridge an exsanguinating patient to TIPS).(32004196) Blakemore tubes predominantly work by impairing blood flow through varices, so their use in nonvariceal bleeds is dubious. An overview of the procedure is as follows:
• (1) Insert the tube through the mouth to a depth of 50 cm (these patients will be intubated already).
• (2) Confirm that tube is in the stomach (e.g. either visualization with ultrasonography or withdrawal of gastric contents via gastric port).
• (3) Inflate the gastric balloon with 50 ml of air.
• (4) Confirm placement within the stomach using either an X-ray or gastric ultrasonography.
• (5) Inflate the gastric balloon with 200 ml of additional air for a total volume of 250 ml.
• (6) Put traction on the tube (using either a pulley system plus a liter bag of saline or by attaching it to the ETT securement device).
• (7) Start by inflating only the gastric balloon to avoid esophageal ischemia. With traction, this may occlude veins which are feeding the esophageal varices.
• (8) If bleeding persists, inflate the esophageal balloon to 30 mm. If bleeding is controlled, try gradually reducing pressure in the esophageal balloon promptly to avoid esophageal necrosis.
• (9) After the patient has stabilized for ~12 hours, start weaning. Deflate the balloons and observe for re-bleeding. If the patient remains stable, the tube may be removed.

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be prepared for hepatic encephalopathy

• Upper GI bleeding is a common precipitant for hepatic encephalopathy.📖
• There should be a low threshold for initiation of lactulose and rifaximin for patients who develop delirium.

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hematochezia & lower GI bleed

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general approach

• Hematochezia is due to a lower GI bleed ~85% of the time, but it can also be due to a massive upper GI bleed with rapid transit through the gut.
  • Hematochezia due to an upper GI bleed is usually associated with hemodynamic instability. Other features that help sort this out are shown in the figure above.(28296600)
• The traditional approach to hematochezia was always to start with an upper endoscopy to exclude upper GI bleed. However, 85% of the time this is an unnecessary procedure that will only delay appropriate management. This has been replaced by newer algorithms which involve risk stratification, NG lavage, and CT angiography. 🌊(26925883)

NG tube with gastric lavage

• Diagnostic performance:
  • Sensitivity for upper GI bleed is ~50%, so negative lavage doesn't exclude upper GI bleed.
  • Bloody lavage has high specificity for an upper GI bleed.
• Historically, gastric lavage has been applied broadly to patients with minimal benefit. This has given gastric lavage a poor reputation as an ineffective and unnecessary procedure.
• Gastric lavage can be useful in the patient with a probable lower GI bleed, because this helps direct whether the patient should receive an upper endoscopy versus CT angiogram of the abdomen (see algorithm above).

expanding role of CT angiography

• Improvements in multi-detector CT technology are making this a front-line test for lower GI bleeds (replacing the tagged RBC scan). Advantages of CT angiography include the following:
  • Can be performed rapidly (e.g., no oral contrast, no delays waiting for radio-tracer dye).
  • Localization of bleeding lesions anywhere in the GI tract (e.g., upper GI bleed, lower GI bleed, hemobilia).
  • Diagnosis of broad range of abdominal pathologies which can present with bleeding (e.g., ischemic colitis, aortoenteric fistula).
  • Imaging the vascular anatomy creates a map to guide subsequent procedures by interventional radiology.
  • Risk stratification based on amount of blood extravasation.
• Timing is essential:
  • Lower GI bleeds have a maddening tendency to stop and start. In order to be helpful, the scan must be obtained while the patient is bleeding briskly.
  • If the patient is actively bleeding, obtain a STAT CT angiography.
  • If the patient has clearly stopped bleeding, it may be wise to follow the patient carefully. If bleeding resumes, order a CT angiogram immediately.
• Make sure the scan is protocoled correctly:
  • CT angiography is not the same thing as simply a “contrast CT abdomen/pelvis.” CT angiography actually involves three different CT scans which are timed around a bolus of contrast, in order to watch contrast pass through the abdominal vasculature.
  • If there is any confusion about which test to order, call the radiologist and make sure the test is protocoled correctly.

interventional radiology is usually the key intervention

• Colonoscopy is rarely useful for severe lower GI bleeds (with the possible exception of a post-polypectomy bleed).
  • Brisk bleeding impairs the ability to clear the bowel, making colonoscopy difficult. The endoscopist will be buried in blood, feces, or both.
• Interventional radiology with embolization is generally the most useful therapy.
• Surgery may be considered for refractory bleeding if it can be definitively localized to a specific region of bowel.

common mistakes to avoid:

• Consulting GI and doing nothing until they provide recommendations.
  • Gastroenterology will rarely be able to urgently intervene on a patient with hematochezia (unless the patient has upper GI bleeding, in which case emergent upper endoscopy is needed).
  • Consulting GI and waiting for them to see the patient will typically delay care by several hours. If you believe that the patient has lower GI bleeding and their NG lavage is negative, it's probably best to order a CT angiogram without delay.
• Ordering a tagged RBC scan:
  • Tagged RBC scans are slightly more sensitive than CT angiography, but they are nonspecific. The scan tends to provide a fuzzy image that doesn't definitively identify the source of bleeding.
  • Unlike CT angiography, a tagged RBC scan doesn't provide precise guidance for IR to perform angiography. Likewise, a tagged RBC scan isn't accurate enough to confidently direct a surgeon towards which part of the bowel should be resected.

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SUP (stress ulcer prophylaxis)

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SUP (stress ulcer prophylaxis) is a perpetually controversial topic. The following approach is based on the 2024 SCCM/ASHP guidelines. (39007570) 

pharmacological SUP: indications

• [1] The patient is truly critically ill (e.g., not simply boarding in the ICU).
  • Many studies used intubation as a surrogate for critical illness. However, mechanical ventilation alone doesn't necessitate SUP. (39007570)
• -PLUS-
• [2] One of the following. The precise definition of these terms is not universally agreed upon, so clinical judgment is required:
  • Shock.
  • Coagulopathy.
  • Chronic liver disease.
  • Neurocritical care patient (primarily in terms of elevated intracranial pressure).

pharmacological SUP: preferred agent & dosing

• Proton pump inhibitors (PPI) are generally preferred, with the following doses:
  • Esomeprazole or omeprazole 40 mg/day.
  • Lansoprazole 30 mg/day.
• Either the IV or PO route is fine.
  • Most PPI tablets cannot be crushed and administered via an enteral tube.
  • Lansoprazole or pantoprazole oral suspension can be given via a feeding tube.
• Reasons that PPIs are preferred over H2-receptor antagonists:
  • [1] PPIs are more effective than H2RAs in preventing stress ulcers. (PEPTIC trial) The greater efficacy of PPIs for gastrointestinal hemorrhage is well established overall. For example, would you ever consider giving an H2RA to a patient with an active gastrointestinal hemorrhage? Of course not.
  • [2] PPIs are safe. They are available over-the-counter and used by millions of patients. RCTs among critically ill patients have demonstrated that PPIs do not cause C. difficile, pneumonia, or death. (SUP-ICU trial, REVISE trial, 39007570)
  • [3] PPIs have less risk of inducing delirium as compared to H2-receptor antagonists. Famotidine is on the Beers List of medications to avoid in elderly patients due to its propensity to cause delirium.
  • [4] PPI dosing doesn't require adjustment for renal failure.
  • [5] Pantoprazole has superior oral bioavailability than famotidine (~40-50%), which facilitates enteral administration of pantoprazole.
  • (Further discussion of evidence behind PPIs in ICU: 🌊)
• H2-receptor antagonists are also acceptable for SUP. SCCM/ASHP guidelines indicate that either option can be used. (39007570)

pharmacological SUP: documentation & cessation

• The indication for medical therapy should be documented in the chart, e.g.:
  • “Chronic outpatient PPI – continue.”
  • “PPI for SUP risk incurred by shock.”
• Medications for SUP should be discontinued as soon as they are no longer indicated (e.g., resolution of critical illness or resolution of shock). Documenting the indication for therapy will clarify when treatment should be stopped.

early enteral nutrition

• Enteral nutrition is recommended to reduce clinically significant stress ulceration. (39007570) Early enteral nutrition is generally beneficial for other reasons as well.  

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proton pump inhibitors (PPIs)

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contraindications, drug interactions, side effects 👎

side-effects

• PPIs cause remarkably few adverse effects and have a strong safety record. (Goodman & Gillman 13e)
• Common side effects include nausea, headache, constipation, and diarrhea.
• Discontinuation may cause a rebound increase in gastric acidity, with dyspepsia.

drug interactions

• Loss of gastric acidity may affect the bioavailability of some medications:
  • Azoles (itraconazole, posaconazole, ketoconazole).
  • Atazanavir and other protease inhibitors.
  • Tyrosine kinase inhibitors (e.g., erlotinib).
  • Mycophenolate mofetil.
  • Digoxin (increases digoxin absorption).
• CYP enzymes:
  • Omeprazole inhibits CYP2C19 and induces CYP1A2.
  • Lansoprazole is a moderate inhibitor of CYP2C19.
  • Pantoprazole may be less likely to cause CYP drug-drug interactions.

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indications, advantages 👍

• PPIs are generally regarded as the most effective medication to suppress gastric acid production and treat or prevent peptic ulceration.
• Additional reasons to select PPIs for stress ulcer prophylaxis are explored in the section above.

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dosing

• Stress ulcer prophylaxis:
  • Esomeprazole, pantoprazole, or omeprazole 40 mg/day.
  • Lansoprazole 30 mg/day.
• Gastrointestinal hemorrhage: Esomeprazole, pantoprazole, or omeprazole 40 mg q12hr.

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pharmacology, mechanism of action

• Absorption:
  • Enteral PPIs are absorbed in the alkaline environment of the small bowel. Oral bioavailability is very good.
  • ⚠️ Lansoprazole: administration after a meal may decrease absorption by 50-70%. Lansoprazole should be taken 30-60 minutes before a meal.
• Distribution:
  • Pantoprazole: Vd of 10-20 liters with 98% protein binding to albumin.
  • Lansoprazole: Vd of ~15 liters with 97% protein binding to albumin.
• Metabolism:
  • Pantoprazole, Lansoprazole: Primarily metabolized by CYP2C19, with a moderate effect from CYP3A4.
• Elimination:
  • Inactive metabolites are mostly cleared by the kidneys.
  • The half-life is approximately 0.5-3 hours. However, due to the irreversible inactivation of the proton pumps, this results in a biological duration of action of 24-48 hours.
• Mechanism of action:
  • Causes irreversible inhibition of the gastric H/K ATPase (aka proton pump), causing an 80-95% reduction in gastric acidity.

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famotidine

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contraindications, drug interactions, side effects 👎

contraindications

• Renal dysfunction (may increase drug levels, with promotion of delirium).
• Elderly patients may be at increased risk of confusion.

side effects

• Minor side effects (diarrhea, headache, constipation, muscle pain).
• Delirium (confusion, hallucinations, slurred speech).
• Tachyphylaxis/tolerance may occur over several days, limiting their ongoing efficacy (due to receptor up-regulation).

drug interactions

• Famotidine may affect the bioavailability of drugs that depend on gastric acid for absorption. These drugs are listed in purple font in the section above under proton pump inhibitors.
• Famotidine has minimal effect on hepatic CYP enzymes. However, some sources suggest that it may have a mild inhibitory effect on CYP1A2, which could potentially increase tizanidine levels.

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indications, advantages 👍

• Stress ulcer prophylaxis (2nd line agent after PPIs).

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dosing for stress ulcer prophylaxis

• 20 mg IV/PO q12 hours.
• GFR 30-50 ml/min: 20 mg IV/PO q24 hrs.
• GFR <30 ml/min or hemodialysis: 10 mg IV/PO q24 hours.
  • ⚠️ Famotidine is not significantly removed by hemodialysis, so it may accumulate.

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pharmacology, mechanism of action

• Absorption:
  • Oral administration: rapidly absorbed.
  • Oral bioavailability is ~40-50%.
• Distribution:
  • Hydrophilic with a LogP of -0.6 and Vd is 1-1.3 L/kg.
  • Little protein binding (15-20%).
• Metabolism:
  • Hepatic metabolism accounts for a small fraction of clearance.
• Elimination:
  • Elimination occurs mostly by renal (65-70%) and metabolic (30-35%) routes.
  • Excreted unchanged by the kidney via filtration and renal tubular secretion.
  • The elimination half-life is normally ~2-4 hours.
  • Not cleared significantly by hemodialysis or peritoneal dialysis.
• Mechanism of action:
  • H2RA reversibly compete with histamine for binding to H2 receptors on the basolateral membrane of parietal cells.

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questions & discussion

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• Don't panic in response to a patient who walks into the emergency department with a hemoglobin of 4 mg/dL. Profound anemia in a hemodynamically stable patient implies chronicity, not acuity.
• Don't waste your time with orthostatic vital signs.
• Overtransfusion increases mortality and complications. For a hemodynamically stable patient, transfuse to a hemoglobin >7 g/dL (>70 g/L).
• The severe hematochezia algorithm has changed recently. Tagged RBC scans have largely been replaced by CT angiography. Most patients can avoid getting an upper endoscopy. The new algorithm streamlines evaluation, treatment, and disposition.
• A variceal bleed is a venous bleed, so over-resuscitation can dramatically increase the driving pressure of the bleed (roughly equal to the central venous pressure). Consider a cautious resuscitation strategy with tolerance of soft blood pressures (noting that patients with cirrhosis often live at a low blood pressure).
• Don't try to “correct” the INR among patients with cirrhosis using fresh frozen plasma or PCC. This is futile and potentially harmful.

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