RECAPEM

The Critical Gastrointestinal Hemorrhage: Evidence-Based Management

October 4, 2020, by Shahriar Lahouti

CONTENTS

Preface

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Gastrointestinal bleeding (GIB) is a common problem encountered in the emergency department. Patients with GIB may present with blood loss that is visible to the patient or clinician; hence the name overt GIB, or may have no visible evidence of blood loss, (occult blood loss).1

The accurate diagnosis of GI bleeding relies on prompt resuscitation, initial risk evaluation, provisional clinical diagnosis followed by appropriate definitive investigation which enables specific interventions.

In this post, the main focus of discussion is overt GI bleeding with hemodynamic instability. Usually the diagnosis is straightforward, however critical patients often have multiple causes for hemodynamic instability (multifactorial shock). The problem arises when the clinician does not consider other coexisting etiologies for shock, or when resuscitative efforts are delayed or misguided.

Etiology

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The annual incidence of hospitalization for acute UGIB in the United States is approximately 65 per 100,000 individuals and is more common than lower gastrointestinal (GI) bleeding.2

The hospitalization rate for UGIB is estimated to be sixfold higher than for lower GI bleeding.

Acute GIB is a common problem, occurring in the upper GI tract of 100–200 per 100.000 persons annually and in the lower GI tract of 20.5–27.0 per 100.000 persons annually. Although 80%–85% of cases of GI bleeding resolve spontaneously, it can result in massive hemorrhage and death. The most common causes of upper and lower GIB is shown below.{34}

Initial evaluation

Introduction with a clinical scenario

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The initial evaluation of the patients suspected for significant GIB include history, physical exam, monitoring, laboratories, point of care ultrasound, and possibly nasogastric (NG) lavage. The information obtained is used to guide decisions regarding initial resuscitation, medical therapy, diagnostic and therapeutic interventions.

Clinical presentation

Patients can present with the hemorrhagic manifestation of GIB (table below)1 and/or other related symptoms which are suggestive for blood loss.

Other related symptoms include:

  • Syncope or presyncope: By definition, syncope is transient complete loss of consciousness, associated with inability to maintain postural tone, with rapid and spontaneous recovery. The presumed mechanism is cerebral hypoperfusion.There should not be clinical features of other non-syncope causes of loss of consciousness, such as seizure, antecedent head trauma, or apparent loss of consciousness (ie, pseudosyncope). Presyncope is The symptoms before syncope. These symptoms could include extreme lightheadedness; visual sensations, such as “tunnel vision” or “graying out”; and variable degrees of altered consciousness without complete loss of consciousness. Presyncope could progress to syncope, or it could abort without syncope. Presyncope warrants the same approach just like syncope.5
  • Angina: Severe hypovolemia, and hypotension (or conditions other than coronary arterial disease) can cause an imbalance between myocardial oxygen supply and/or demand, resulting to myocardial infarction (type 2; secondary to ischemic imbalance).6
  • Altered mental status: It has a huge list of differential diagnosis. Altered sensorium in the setting of shock can be due to poor cerebral perfusion or metabolic encephalopathy. Patients with advanced liver disease and hepatic encephalopathy are altered at their baseline. Altered mental status is a continuum that begins with agitation, progresses to confusion or delirium, and ends in obtundation or coma.
  • Abdominal pain: presence of abdominal pain is worrisome and in the presence of hemorrhagic manifestation of GIB can suggest1:
    • Perforated peptic ulcer disease
    • Aortoenteric fistula
    • Mesenteric vein thrombosis
    • GI tumors, polyps
    • Colitis (Inflammatory,infectious, ischemic)
  • Other bleeding symptoms: Patients with coagulopathy may presents with other bleeding symptoms such as hematuria, however hematuria is rarely the cause for hemodynamic instability, and an astute clinician is prepared and will search for other possible source of life threatening bleeding which can explain the patient’s hemodynamic instability such as retroperitoneal hemorrhage,GIB, etc.
  • Unresponsiveness: Severe exsanguinating hemorrhagic shock can present with Pseudo-pulseless electrical activity (a.k.a PREM; pulseless with a rhythm and echocardiographic motion). It is a severe shock state and often is due to profound hypovolemia. If not recognized and promptly resuscitated progresses to asystole cardiac arrest.

Past medical and drug history:

Reviewing PMH and DH provide valuable diagnostic information that can potentially influence therapeutic decision making (table 2). Studies have shown that up to 60% of patients with prior history of GIB, are bleeding from the same lesion.

In patients with undifferentiated hypotension, wherein the cause of instability is less clinically apparent, this information is especially helpful and may alter pretest probability of GIB.

Physical examination: The finding may include:

General:

  • Hypotension: Hypotension may be absolute (SBP <90 mmHg; MAP<65 mmHg), relative (eg, a drop in SBP >40 mmHg) or profound (eg, vasopressor-dependent). Patients with adequate hemodynamic reserve (e.g. young patients without comorbid conditions) may be initially hypertensive, or normotensive with mild-moderate volume loss. Conversely, not every patient with hypotension has shock. Patients with cirrhosis are moderately hypotensive at their baseline.
  • Tachycardia (Sinus tachycardia or atrial fibrillation with rapid ventricular response in patients with pre-existing AF rhythm at their baseline): Tachycardia is not sensitive in patients who consume heart rate lowering agents (e.g. beta blockers etc). In patients at extremis (impending to crash), paradoxical bradycardic response may supervene.
  • Shock index (SI): The SI (HR/SBP) is a more helpful way to understand tachycardia within the context of blood pressure. Shock index > 1 suggests significant instability and possible shock.
  • Pulse pressure (PP): Mild volume loss causes high cardiac output state with ‘Wide PP’; whereas moderate to severe volume loss results in ‘Narrow PP’ (low cardiac output state).
  • Tachypnea: It is not a specific sign, but is highly sensitive for the presence of occult critical illness.
  • Cold/clammy extremities: Early sign of vasoconstriction with reduced cardiac output.
  • Mottling: Is a specific (but less sensitive) sign for hypoperfusion, implying endogenous vasoconstriction.
  • Peripheral cyanosis, Increased capillary refill time (in adult>4.5 sec): implies poor peripheral perfusion.
  • Low urine output: urine output below 0.5 cc/kg/hr is worrisome for renal malperfusion, however immediately following foley catheter placement the urine output won’t be known. In this situation scanty and dark urine is worrisome. Patients with preexisting chronic kidney disease have low urine at their baseline.
  • Pulse oximetry: keep in mind that in patients with severe shock, pulse oximetry readings are not reliable.
  • Orthostatic hypotension:Patients with severe volume loss are recognizable! The expected diagnostic value of orthostatic measurements is whether it can recognize patients with moderate volume loss or not?!
    • The answer is No. Roughly 50% of the healthy population have orthostatic changes in measurement at their baseline. In patients with moderate blood loss, PR change had 22% sensitivity, and BP change had 7-27% sensitivity.7 Orthostatic vital signs are unhelpful. (see more on this)
  • Caution: Hemorrhagic shock is notorious for rapid deterioration (in contrast to septic shock which has a slower pace)!

Abdominal exam:

  • Signs of peritonitis (acute abdomen), will raise concern for surgical etiologies, therefore more evaluation may be required prior to endoscopy to exclude conditions like perforation.
  • Ascites: presence of ascites and other stigmata of chronic liver disease (e.g. jaundice, palmar erythema etc.) will raise pretest probability of complications of portal hypertension (esophagogastric varices, portal hypertensive gastropathy).Keep in mind that patients with portal hypertension can have other etiologies for upper GI hemorrhage. In one study, approximately 40% of patients with cirrhosis and UGIB had a cause unrelated to portal hypertension.8
  • A pulsatile abdominal mass: may suggest aortoenteric fistula as a cause for GIB (more on this below).

Skin:

  • Presence of jaundice is suggestive for liver disease and possible variceal source for GIB. Patients with hereditary hemorrhagic telangiectasia (HHT) may have skin lesions (telangiectasiashown below) and this will suggest possible GI vascular abnormalities as a cause of GIB.

POCUS:

Bedside ultrasound evaluation can help clinicians to rapidly diagnose life threatening conditions and narrow the differential diagnosis (especially in undifferentiated hypotension where the state of shock is recognized but the cause is unknown, and in multifactorial shock, wherein a combination of more than one form of shock is present).

  • Hemodynamic evaluation:
    • Hyperkinetic left ventricle plus virtual IVC can suggest absolute volume loss such as GIB or relative volume loss such as non-resuscitated septic shock.
    • A normal or plumped IVC virtually rules out hemorrhagic shock as a cause of patient’s instability unless there are coexisting conditions which increases the right atrial pressure such as pulmonary embolism, pulmonary hypertension, tricuspid regurgitation, pericardial disease.
  • Abdomen: In patients with risk factors for abdominal aortic aneurysm presenting with GIB (especially UGIB) always consider aortoenteric fistula in your differential diagnosis. Examining abdominal aorta for aneurysmal changes can shift the diagnostic paradigm in such patients.
  • Gastric ultrasonography: Its a non-invasive widely available, and rapid method to evaluate both gastric size and content. (see scanning technique). Studies have demonstrated that various contents of the stomach (gas, fluid, and solid) can be differentiated based on their appearance on the ultrasound.9
    • Arguably an empty stomach is against an active bleeding in the esophagus or stomach (e.g. variceal hemorrhage). Alternatively, a distended stomach (especially if heterogeneous internal echogenicity seen) may suggest upper GI hemorrhage if the patient hasn’t recently eaten (figure 2).10
    • For patients undergoing intubation, gastric distension increases the risk of aspiration and NG lavage may be warranted here.

Nasogastric (NG) Lavage

NG tube insertion is one of the most unpleasant and inhumane procedures and should be avoided unless specifically indicated. Regarding evaluation and treatment of GIB, indications for NG tubes differ widely among practitioners. Recent studies reveal that the true clinical value of an NG tube in patients with GI bleeding is probably less than what traditionally was believed. {11, 12, 13}

Diagnostic indications:

Patients with very high clinical suspicion for UGIB (significant amount of proven bloody vomitus) or those with presumptive upper source (e.g. melena, age <50 y/o; hematocrit <30) do not need NGT insertion for diagnosis. On the other hand, in the following conditions NGT insertion may have diagnostic yields:

  • Suspected history of bloody vomitus: a bloody aspirates may confirm UGIB.
  • Hematochezia: Up to 10% of patients with hematochezia have an upper GI source of bleeding. In the presence of findings that are suggestive for upper GI bleeding (e.g. history of UGIB, cirrhosis, BUN/Cr >30, epigastric discomfort), insertion of NGT may be helpful diagnostically. In this situation a bloody lavage signifies an upper source of bleeding and will determine the next appropriate diagnostic approach (upper endoscopy).
  • Hypovolemic shock: In patients presenting with a hemodynamic profile of hypovolemic shock with minimal/no hematemesis, NG tubes can provide the earliest indication of ongoing high-volume esophageal or gastric bleeding and thus they may benefit from an early upper endoscopy.13

Caveats:

An NG aspirate is diagnostically unhelpful, unless frankly bloody fluid is obtained. Small bits of darkish material, bloody mucus, or positive guaiac tests probably represent sequelae of the procedure, whereas a clear appearance and negative tests still miss most bleeding distal to the stomach (sensitivity 50%). Patients with a bleeding pattern indicative of a Mallory-Weiss tear may need neither an NG tube nor endoscopy.

Therapeutic indications:

  1. Reducing risk of aspiration (when endotracheal intubation anticipated): If intubation is indicated in patients with GI bleeding, NG lavage may be helpful in emptying the gastric contents and reducing the risk of aspiration, especially if the stomach is full and vomiting is uncontrolled.
  2. Providing a clear endoscopic field (at discern of gastroenterologist)

Contraindication for NG tubes:

  • Midface injury, basilar skull fracture
  • Coagulopathy
    • In the presence of coagulopathy or midface injury; orogastric placement may be a better option.
    • Notice: Esophageal varices are not a contraindication for NG tube insertion.
  • History of gastric bypass
  • Esophageal stricture or alkali injury

Laboratory evaluation:

CBC: The initial Hb and HCT level in patients with acute GI bleeding is at the patient’s baseline because the patient is losing whole blood.

  • Worrisome finding: A normal Hb in a patient with hemodynamic instability is a worrisome finding. Remember that transfusion of a unit of packed cells should increase Hb by ~1 g/dL. A failure to respond appropriately to transfusion signifies ongoing bleeding and is assumed a worrisome finding.
  • Reassuring finding: A very low Hb (e.g. Hb < 6 g/dL) in an otherwise hemodynamically stable patient with minimal symptoms suggests a chronic bleeding with very low risk of rapid deterioration {a very low Hb in a stable patient should not invoke panic!}. These patients have chronic bleeding (e.g. for days, weeks), meanwhile gradually retaining volume to compensate (isovolemic anemia). The only immediate threat to these patients is iatrogenic, i.e. giving blood products too rapidly will put them in volume overload state. Ideal management may involve gradual replacement of blood often in combination with diuretics.

BMP: Bleeding from the upper GI tract may elevate BUN levels through the digestion and absorption of hemoglobin. A BUN/Cr ratio >30 may suggest UGIB.

LFTs

Serum lactate: Lactate elevation (e.g. >4 mM) suggests shock, but this has a broad differential diagnosis.

Coagulation studies{PT,PTT, and possiblyThromboelastography (TEG)}

Type and Cross

Troponin and EKG: Subsequent anemia from a GI bleed can reduce a patient’s oxygen-carrying capacity. Patients with GI bleeding who are more than 40 year-old, patients with any symptoms of ischemia, and patients with known coronary artery disease should be screened for potential myocardial ischemia.

Differential diagnosis (DDx)

  • The DDx for hematemesis include:
    • Posterior epistaxis
    • Hemoptysis
  • The DDx for hematochezia are:
    • UGIB: 10-15% of patients with severe hematochezia have upper GI source.14 In a meta-analysis, factors that were predictive of a blood coming from upper GI source (table 3) and lower GI source (table 4) were identified.15
    • Bloody diarrhea: Technically it is GI bleeding, though bleeding is not the main problem.
  • The DDx of Hypovolemic hemorrhagic shock (in non-traumatic patients) include:
    • GI bleeding
    • Ruptured aortic aneurysm
    • Ruptured ectopic pregnancy
    • Uterine or vaginal hemorrhage
    • Postpartum hemorrhage
    • Spontaneous retroperitoneal or peritoneal hemorrhage due to bleeding diathesis.Caution: Presence of free peritoneal fluid (on physical or ultrasonographic exam) should also make you consider hemoperitoneum. Spontaneous rupture of spleen has been reported in patients with severe portal hypertension.16
    • Hemorrhagic pancreatitis

Risk stratification:

Clinical, endoscopic,and laboratory features may be useful for risk stratification of patients who present with acute GI bleeding(table 5).{15 17 18 19 20 21 22}

General Management (Resuscitation Basics)

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The principles of management and basic resuscitation of patients with clinically significant GI bleeding and unstable hemodynamic is reviewed here. These patients require bedside cardiac monitoring, close monitoring of the airway, clinical status, urine output, and NGT output (if has been placed).

Access:

IV access: Two large-bore peripheral IV lines (16 gauge or larger) and/or a central access. Patients predicted to need massive transfusion require central access via either multi-lumen access catheter (MAC), or hemodialysis catheter or the standard central line.

Arterial line: For patients undergoing massive transfusion, consider emergent placement of an arterial line (via femoral, or brachial artery). An arterial catheter is invaluable when running a massive transfusion to titrate vasopressors and avoid overshoot hypertension (which may encourage re-bleeding).

Fluid

The goal of hemodynamic resuscitation is to protect effective tissue perfusion. Keep in mind that this does not necessarily translate to (optimizing MAP).

Currently most experts target a MAP of 60 to 65 mmHg. Studies have shown that higher blood pressure targets were not associated with lower mortality in critically ill hypotensive patients. In contrast, a higher MAP (e.g. >70 mmHg) may contribute to worsening of GI bleeding by establishing a higher driving pressure behind the bleeding site.

Anecdotally patient is given whatever he or she is losing, in this case the blood.Filling the tank with fluid instead of blood can cause several undesired effects such as:

  • Dilutional anemia:The administration of excessive fluids may cause a relative, but not absolute, reduction in Hb concentration, RBC count, or Hct, which is termed ‘dilutional anaemia’. This will result in a loss of RBC-filled capillaries, leading to a reduction in oxygen-carrying capacity and worsening the effective tissue perfusion.{23 24}
  • Dilutional coagulopathy: The adverse effect of liberal fluid administration on coagulation has been well studied in trauma literature. Fluid causes dilutional coagulopathy, clot disruption from increased blood flow; resulting to worsening bleeding diathesis.25
  • Rebound portal hypertension: Patients with cirrhosis are in sodium-avid state (volume overload) at their baseline. Overzealous fluid administration will transiently increase (mean systemic filling pressure; i.e. the driving pressure within the venous system). A fraction of this increased venous pressure is translated to the portal vein and contributes to worsening portal hypertension.26

Patients with frankly severe ongoing blood loss should be transfused immediately with type O blood (women of childbearing age should be transfused with O negative blood), while being typed and cross-matched for blood transfusion.

If you choose crystalloid, just give a small amount! Extrapolated from trauma literature, volume replacement of 1.5 L or more in emergency department has been shown to be an independent risk factor for mortality in trauma patients.27

Red-cell Transfusion

GI bleeding is a frequent indication for red cell transfusion because acute blood loss can decrease oxygen carrying capacity of the blood and therefore impaires tissue perfusion.

  • Unstable massive (exsanguinating) GI bleeding: These patients require a blood transfusion from the very early of their presentation.
  • Stable but active GI bleeding: In patients with active bleeding who become hemodynamically stable, indications for blood transfusion is hemoglobin < 7 mg/dL, except for patients with active acute coronary syndrome, where the Hb threshold for transfusion is < 9 mg/dL.

This recommendation is based on a randomised trial which showed liberal transfusion (transfusion threshold with Hb <9mg/dL) is associated with increased mortality compared to a restrictive strategy (transfusion threshold with Hb<7mg/dL).{28, 29}

GI bleeding can rapidly decompensate. If you’re worried that the patient will deteriorate, request 4 units of PRBC on hold in the blood bank.

Does balanced transfusion (1:1:1 ratio of PRBC:FFP:PLT)improve the outcome in patients who require less than three units of blood within an hour?

  • No. In patients who by definition are not candidates for massive transfusion protocol (see below), administration of FFP, PLT does not improve morbidity and mortality. Therefore if a patient requires two units of blood, administration of FFP, and PLT are not warranted.

Massive transfusion (MT)

It is historically defined as the transfusion of > 10 unit packed red blood cells per 24 hours, and was shown to be associated with multiple hemostatic and metabolic complications.

This definition is retrospective and arbitrary. Alternative definitions accounting for rate and timing will provide a more accurate conceptual framework. Accordingly, the critical administration threshold (CAT) redefined MT as three units of red blood cells over one hour.30 It allows early identification of critical patients at greater risk of death from bleeding compared to traditional MT.

Massive transfusion protocol is activated in situations such as:

  • More than 3-4 units of blood is administered within an hour
  • Massive exsanguinating bleeding from the sites that is difficult to access immediately
  • Severe instability (vasopressor-dependent) from hemorrhagic shock

When MTP is activated, blood products will be provided with a 1:1:1 ratio of PRBC:FFP:PLT (balanced resuscitation).31

Preparation and considerations for patients requiring massive transfusion include:

  • Central access preferentially via multi-lumen access catheters or hemodialysis catheters.
  • Arterial line to closely monitor blood pressure, since overly aggressive resuscitation can increase the risk of rebleeding.
  • Cryoprecipitate, calcium (IV) may be considered.

Coagulopathy

There are several key points to consider in approach to patients with coagulopathy and major bleeding (algorithm 1):

  1. Assess severity of bleeding:32By definition, if there were ≥ 1 of the following factors, the bleed is classified as Major:
  • Critical Site Bleeds: Are bleeds that compromise the organ’s function. Intracranial hemorrhage and other central nervous system bleeds (e.g. intraocular, spinal) and thoracic, intra-abdominal, retroperitoneal, intra-articular, and intramuscular bleeds are considered critical as they may cause severe disability and require surgical procedures for hemostasis. Intraluminal gastrointestinal (GI) bleeding is not considered a critical site bleed; however, it can result in hemodynamic compromise.
  • Hemodynamic Instability
  • Overt Bleeding With Hemoglobin Drop ≥2 g/dL or Administration of ≥2 units of Packed RBCs
  1. Determine pertinent comorbidities and all medications that can contribute to bleeding: Critically ill patients often have multiple coagulopathies. Obtain full history and physical exam and coagulation studies to get a global sense of how coagulopathic the patient is.
    • Comorbidities that can contribute to bleeding may include: Uremia, thrombocytopenia, cirrhosis, malignancies, hereditary coagulopathic disorder.The coagulopathy of cirrhosis is more complicated and is discussed separately (more on this below).
    • Review all medications that the patient is taking which may affect coagulation.
    • Determine the doses of medications and the last time a dose was taken.
  2. Determine the etiology for which the patient was initially anticoagulated: As a principal, always consider the indication for which the patient is consuming anticoagulants (e.g. atrial fibrillation) and weight against the severity of the bleeding (major GIB, vs non-major GI bleeds) to determine how aggressively to reverse anticoagulation.
    • Most patients are anticoagulated for atrial fibrillation or deep vein thrombosis. These are low risk conditions wherein short term interruption is not problematic.
    • Some patients are anticoagulated for higher-risk conditions such as mechanical valve prosthesis (which has a higher risk for thrombosis).This may shift the risk/benefit ratio.
  3. Assess for requirement of reversing anticoagulation: Life-threatening bleeding requires aggressive normalization of coagulation parameters, but minor bleeding may respond to local measures.

The common coagulation factor products which may be used in coagulopathic patients with life threatening bleeding are mentioned below (table 6).

Non-cirrhotic coagulopathic patients with life threatening bleeding and INR > 2 should generally be transfused with prothrombin complex concentrate (PCC) or FFP (plus vitamin k in the case of warfarin overanticoagulation).33 (table 6,7)

For patients with thrombocytopenia,uremia, antiplatelet consumption: Consider DDAVP, and platelet transfusion (if PLT<50.000u/L).

Medications

Proton Pump Inhibitors (PPI):

Patients with possible acute upper GI bleeding are given PPI. However the benefit of PPI administration ‘before endoscopy’ is still unclear (Does patients with variceal bleeding benefit from PPI too??). At the current time most experts agree on administration of PPI for acute UGIB.

Administration protocol: Evidence showed that intermittent IV bolus is comparable to continuous infusion.34 The recommended dose for patients with acute UGIB is to give a high dose IV bolus (e.g. 80 mg pantoprazole), then 40mg IV q12hr.

Octreotide:

The benefit of octreotide administration in variceal GI bleeding is relatively clear. It decreases portal vein pressure, therefore theoretically reduces variceal bleeding. In non-variceal upper GI hemorrhage, there are some weak evidence that octreotide administration was associated with a reduced risk of continued bleeding.35

In patients with possible variceal bleeding, octreotide is given as 50 mcg bolus followed by a continuous infusion at a rate of 50 mcg/hr.

Tranexamic acid

There is not compelling evidence for its role in the treatment of GI bleeding. In a recent randomized trial (HALT-IT)36 use of tranexamic acid did not improve death due to bleeding within 5 days in patients with acute GI bleeding.

Antibiotics

Patients with cirrhosis and portal hypertension have a favorite milieu for gastrointestinal bacterial translocation and infection especially during the decompensated stage.37 Several trials have shown that antibiotic administration is associated with reduced mortality in patients with variceal hemorrhage.38

The recommended agent is usually ceftriaxone 1 gram IV daily.

Approach to upper GI bleeding

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Upper endoscopy is often the first line option for both diagnostic and therapeutic purposes in patients with acute UGIB. The severity of bleeding may determine the optimal time to endoscopy. Patients with initial hemodynamic instability deserve more urgent intervention. (EM:RAP: timing of endoscopy for acute UGIB)

Risks of upper endoscopy:

It’s relatively a safe procedure. The complications include pulmonary aspiration, GI perforation, and increasing bleeding while attempting therapeutic intervention.

Patients should be optimally resuscitated and hemodynamically stable before undergoing endoscopy (since they may crash during the procedure).Data suggests that most patients do not need to have a normal hematocrit in order to safely undergo endoscopy.39Anticoagulation reversal should not delay urgent endoscopy. Evidence shows that endoscopy is safe in patients who are mildly to moderately anticoagulated (e.g. INR<2.5).40

Endotracheal intubation:

Intubation may be indicated when there are high risk features for aspiration such as for unconscious patients unable to protect their airway or patients with massive upper GI bleeding (possibly variceal hemorrhage). Studies have shown that endotracheal intubation is not a benign procedure in patients with GI bleeding and is associated with worse outcomes.41 Be prepared for hemodynamic decompensation and massive aspiration.

  • First resuscitate: Optimize hemodynamics.Consider initiation of vasopressor before intubation, to avoid hemodynamic collapse.
  • Reduce the risk of aspiration: If gastric ultrasound shows distention, the following measures may reduce the risk of aspiration:
    • NG suction
    • Prokinetic agents: may consider erythromycin or metoclopramide to promote gastric emptying prior to procedure. Erythromycin can be given as 3 mg/kg IV infusion over 5 minutes, 15 minutes prior to procedure.42

Procedural sedation for upper endoscopy in non-intubated patients

If you were asked to provide sedation for endoscopist, consider the following:

  • Pretreatment with antiemetic such as ondansetron
  • Provide short-acting titratable drugs with both analgesic properties (fentanyl) and sedative properties (midazolam or propofol)43
  • For unstable patients may consider cardiostable drugs such as ketamine, etomidate
  • Patients with alcoholism may be ketamine resistant, which can be overcome by using higher doses
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

Complications of portal hypertension

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Portal hypertension develops when there is resistance to portal blood flow. The etiologies for portal hypertension (figure 3)44 can be classified to prehepatic (e.g. portal vein thrombosis), intrahepatic (e.g. cirrhosis), post-hepatic (eg, Budd-Chiari syndrome). Portal hypertension is often asymptomatic until complications such as ascites and variceal bleeding develop.45

Portal hypertension can cause upper GI bleeding via several distinct pathologic lesions including esophageal varices, portal hypertensive gastropathy, gastric varices, and ectopic varices. However, it should be kept in mind that patients with portal hypertension and cirrhosis can develop UGIB from sources unrelated to portal hypertension (eg, peptic ulcer disease). Since the most common cause of portal hypertension is cirrhosis, the focus of the following discussion is centered on cirrhotic patients.

Esophagogastric variceal hemorrhage

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Patients with variceal hemorrhage present with hematemesis, melena, hematochezia (brisk bleeders) similar to that seen in patients with GI bleeding from non-variceal lesions. Successful resuscitation of these patients requires understanding the basic mechanism and pathophysiology of variceal hemorrhage.

Pathophysiologic principles of portal hypertension and varix formation and rupture in patients with cirrhosis

In cirrhotic patients portal hypertension results from the combination of both abnormally high portal venous blood flow and increased resistance to flow through the cirrhotic liver. Over time the high pressure system within the portal vein gives rise to the formation of varices by dilating portosystemic venous connections.46

Once varices formed; the variceal hemorrhage can be caused by a wide range of factors including topical, portal hemodynamic, and systemic factors (figure 4).Portal pressure plays the most crucial role in the pathophysiology of variceal hemorrhage among the list (figure 5).

Clinical implication:

As explained in figure 5; the increasing intra-variceal pressure (which approximately equals to portal pressure) plays a pivotal role in variceal hemorrhage.Unlike most other GI bleeders, variceal one is from the venous side. Over-resuscitation of patients with variceal bleeding will increase the central venous pressure and this will directly increase portal venous pressure.47

Keeping in mind that cirrhotic patients usually have low MAP at their baseline (chronic vasodilation); so a borderline hypotension is preferable to higher MAPs (avoiding large-volume resuscitation).48

Pathophysiologic principles of coagulopathy in cirrhotic patients

The coagulopathies in cirrhosis are complex. Most procoagulants (clotting factors) and endogenous anticoagulants are synthetized in the liver. In advanced liver diseases, levels of all these proteins are reduced to a similar extent. This leads to ‘rebalanced hemostasis’ wherein the clotting tendency is close to normal (figure 6).

The INR measures the level of several clotting factors (fibrinogen, factors II, V, VII, X; involved in the extrinsic pathway). Since most of these proteins are synthesized in the liver, it is obvious that INR will be elevated. However, the INR is only evaluating half of the picture!

An increased INR in this setting gives the false impression of heightened bleeding risk(reduced clotting factors), while in fact anticoagulant proteins synthesis is reduced as well, and a rebalanced hemostasis is reached.

Pathophysiology hyperfibrinolysis in cirrhosis: Liver synthesizes fibrinogen, and also clear the blood from endogenous fibrinolytics (e.g. tissue plasminogen activator) too. In advanced liver disease, both fibrinogen level is reduced and clearance of endogenous fibrinolytics are elevated, resulting to hyperfibrinolysis.49

Clinical implication:

The concept of rebalanced hemostasis explains some otherwise puzzling findings in cirrhosis.This explains why the INR fails to predict bleeding following procedures and also how patients may experience portal vein thrombosis or deep vein thrombosis despite an elevated INR.

In patients with cirrhosis, INR is not an accurate measure for hemostasis, and therefore INR elevation in cirrhosis is meaningless and doesn’t necessarily correlate with actual coagulation tendency. Thromboelastography (TEG) is more accurate here.

  • In hemodynamically stable cirrhotic patients with inactive GI bleeding (e.g. melena): Perform ‘TEG’. Elevated INR is meaningless. The routine administration of PCC or FFP is not recommended.(50 51 )
  • In unstable cirrhotic patients with active massive bleeding (e.g. massive hematemesis, hematochezia), regardless of INR; one may be more likely to administer FFP or PCC (especially when there is evidence of true hypocoagulopathy on TEG).
  • No recommendations can be given regarding platelet transfusion in patients with variceal hemorrhage.52 however some experts recommend to keep PLT count > 50.000 in patients with active bleeding.
  • May consider cryoprecipitate transfusion for bleeding cirrhotic patients to increase the fibrinogen level over 150 mg/dL.53

Pathophysiologic principles of infection in cirrhotic patients and its relation with bleeding and coagulopathy

Liver dysfunction will impose cirrhotic patients at increased risk of bacterial infection.54

Several studies have shown the importance of infection in pathophysiologic mechanisms in cirrhosis and its association with variceal hemorrhage{55,56}, abnormalities in coagulation57 ,vasodilatation

of the systemic vasculature58, and worsening liver function.59

Patients with cirrhosis and portal hypertension have a favorite milieu for gastrointestinal bacterial translocation and infection especially during the decompensated stage.37 There’s a close relationship between bacterial infection, bleeding and coagulopathy (figure 7).

Clinical implication:

Trials have shown that antibiotic administration is associated with reduced mortality in patients with variceal hemorrhage.38

Patients require a thorough work up to determine possible etiologies for decompensated chronic liver disease (e.g. infection, mesenteric vein thrombosis,etc).

Blackmore tube placement

Patients with UGIB due to esophageal variceal hemorrhage often have advanced liver disease and can arrive at the ED with airway compromise, hemodynamic instability, thrombocytopenia, and coagulopathy. Managing these patients can be a formidable challenge in ED. Endoscopy by a gastroenterologist remains the “gold standard” for the diagnosis and treatment of acute variceal hemorrhage. However sometimes endoscopy cannot be performed in unstable patients with exsanguinating bleeding or the consultant physicians are unavailable and medical therapy has failed to stop the bleeding and stabilize the patient’s hemodynamics.

Therefore, it is significantly important that clinicians have the required skills to temporary stop the bleeding. Balloon tamponade of esophageal varices often can be done quickly in ED with high success rates in controlling the initial hemorrhage.

 

 

Copy right with permission at EM:RAP. Please note that these material have been peer reviewed and for reference only. When treating a patient, this material should be checked against other references and local practice.

Abdominal paracentesis: It has been shown that total volume paracentesis in patients with tense ascites will improve portal hemodynamics and will decrease variceal pressure, size and wall tension.60

Review: Clinical pearl in management of cirrhotic patients with variceal bleeding:

  • In patients with exsanguinating variceal hemorrhage and unstable hemodynamic; aggressive mindful resuscitation is warranted to optimize tissue perfusion.
  • Emergent endoscopy for unstable actively bleeding patients is recommended.
  • If endoscopy fails, the second step is often Transjugular Intrahepatic Portosystemic Shunting (TIPS). Blackmore tube may be used as a last-ditch effort (e.g. to bridge an exsanguinating patient to TIPS)61
  • Hematologic management:
    • Activate MTP for actively bleeding patients who require 3-4 unit PRBC per hour.
    • In hemodynamically stable patient, the trigger of red cells transfusion is hemoglobin <7mg/dL.62
    • INR is misleading in cirrhotic patients and oftentimes trying to normalize the INR in hemodynamically stable patients with FFP, PCCis futile and a wrong move. 63
    • Platelet transfusion may be considered in actively bleeding patients with PLT count < 50.000.
    • May consider cryoprecipitate transfusion for bleeding cirrhotic patients to increase the fibrinogen level over 150 mg/dL.
  • Measures that reduce portal vein pressure is helpful adjuvants to stop bleeding in patients with active variceal hemorrhage:
    • Octreotide: Initial IV bolus of 50 micrograms (can be repeated in the first hour if ongoing bleeding), then continuous IV infusion of 50 µg/hr for two to five days.
    • Vasopressin 64:Continuous IV infusion: 0.2‐0.4 U/min; can be increased to 0.8 U/min for 24 hour.
    • Abdominal paracentesis
  • Antibiotics: Ceftriaxone 1gr IV
  • Evaluate for infection
  • Be prepared for hepatic encephalopathy as UGIB is the common precipitator. Have a low threshold to initiate lactulose +/- rifaximin for patients who develop delirium

Approach to lower GI bleeding (LGIB)

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The hemorrhagic manifestations of LGIB are clot per rectum and hematochezia. As explained earlier, hematochezia is due to lower GI bleeding in almost 85% of the time.65

Hematochezia originates from an upper GI source in 10-15% of patients, whereas it indicates brisk upper GI bleeding and may be associated with unstable hemodynamic and or hematemesis. The general diagnostic approach to LGIB is explained (algorithm 1). 66

  • Hematochezia in the presence of favoring features for upper GI source (table 3): NGT lavage, upper endoscopy should be performed.
  • Hematochezia in the presence of features favoring lower GI source (table 4):
    • Exsanguinating bleeding (extremely severe bleeding): Invasive angiography should be performed (is both diagnostic and therapeutic).
    • Less severe bleeding: Multidetector CT angiography has replaced the traditional technetium-labeled red cell scans. CT angiography has a sensitivity and specificity of nearly 100% for detecting active or recent GI bleeding and is about 93% accurate in determining the site of bleeding.{67 68}

Advantages of CT Angiography:

  • Can be performed rapidly
  • Localizes bleeding lesions anywhere within the GI tract with high diagnostic accuracy for wide range of pathologic lesions
  • Provides a map prior to treatment with conventional angiography especially in unstable patients

Therapeutic intervention:

Interventional radiology: It plays a pivotal role for exsanguinating lower GI bleeding

Colonoscopy: is less useful in active bleeding state, as active bleeding impairs the ability to clear the bowel, making colonoscopy difficult.

Surgery: May be considered for refractory bleeding. The reported proportion of patients requiring surgery varies from 5% to 25%.69

Aortoenteric Fistula (AEF)

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Aortoenteric fistula (AEF) is a devastating and life-threatening condition, which is as difficult to diagnose as it is to treat. It is an abnormal communication between the aorta and an adjacent loop of the bowel.

Two types are recognized: primary and secondary.

  • Primary: fistulas occur de novo between the aorta and bowel, most commonly duodenum.However, it may involve other portions of the GI tract such as the stomach (aortogastric fistula), jejunum (aortojejunal fistula), ileum (aortoilial fistula), or sigmoid colon (aortosigmoid fistula)
  • Secondary: fistulas occur between an aortic graft and a segment of bowel.

Risk factor: Abdominal aortic aneurysm (AAA) remains the most common risk factor of AEF. The AEF must be kept in mind as a possible etiology of gastrointestinal bleeding in any patient with known AAA or prior aortic intervention, no matter how long ago.

Clinical manifestation:

  • GIB: is the most common initial manifestation, but may not always present. It may be a minor episode of bleeding (herald bleed), or a life threatening overt bleed. GIB may be accompanied by abdominal pain. Most common hemorrhagic presentations are hematemesis, hematochezia.70
    • The classic triad of GIB, abdominal pain, and palpable mass occurs in only 6% to 12% of patients found to have AEF.
  • Other presentations: Graft thrombosis with lower extremity ischemia, overt sepsis, malaise, weight loss.

Diagnosis: It requires a high index of suspicion in patients who present with either signs of GI bleeding (especially UGIB) or infection. Early diagnosis is essential for a successful outcome because of the lethal nature of AEF. The management approach to patients with high suspicion for AEF(known AAA, prior aortic intervention) is as following:

  • Hemodynamically unstable patients with massive bleeding and known AAA should be taken directly to the operating room to make the diagnosis and perform the repair.
  • For patients with acute GIB, who become stabilized, the first-line diagnostic study is CT angiography.

For those in whom a diagnosis of AAA is unknown, but suspected by risk factors, ultrasonography may identify the presence of the aneurysm but will not identify the AEF.

Differential Diagnosis: The differential diagnosis of AEF includes other pathologies causing GIB. Keep in mind the following points:

  • Patients with known history of AAA, or aortic intervention can develop GIB due to other common pathologies e.g. peptic ulcer disease, etc.
  • If another etiology for GIB is found, this does not necessarily rule out the presence of AEF.

Management: It is a uniformly fatal disease if not rapidly recognized and treated.

  • Hemodynamic resuscitation
  • Consult: Immediately consult the appropriate surgical subspecialist if the patient has a history of known AAA or aortic intervention and there is concern for AEF.
    • Aortic repair: via open surgical or endovascular options.71
  • Antibiotics: Consult with infectious disease service. A reasonable regimen includes vancomycin plus an agent with activity against gram-negative organisms (ceftriaxone or a fluoroquinolone or piperacillin-tazobactam).

RECAP:

  • Orthostatic measurements are not sensitive for identifying patients with moderate volume loss.
  • Treatment modalities which ‘Improve Mortality’ in UGIB are:
    • Antibiotic prophylaxis in cirrhotic patients
    • Restrictive transfusion strategy (transfuse if Hb < 7 g/dL)
  • Treatments that ‘Do Not’ improve mortality in UGIB:
    • NG lavage
    • Somatostatin analogue: It does not reduce mortality in UGIB from esophageal varices, but may reduce blood transfusion requirements.
    • PPIs: It does not improve mortality neither in undifferentiated UGIB nor in peptic ulcer bleeding. PPI treatment in peptic ulcer bleeding reduces rebleeding and surgical intervention rates.
  • PPIs drip has not been proven to be more beneficial than bolus.
  • Patients with cirrhosis and GIB are considered to have variceal bleeding until proven otherwise. When they develop hemorrhagic shock, their hemodynamic indices may not best fit to the typical hemorrhagic shock profile. This is due to their chronic vasodilation and volume overload state at their baseline.
  • In cirrhotic patient in shock state: Consider hemorrhagic shock, and septic shock.
  • Over Resuscitation with fluid and blood products increase mortality and complications. In hemodynamically stable patients transfuse to a hemoglobin >7 g/dL.
  • The coagulopathy in non-cirrhotic patients with life threatening GI bleeding should be corrected emergently. FFP, PCC, cryoprecipitate, and platelets are considered as indicated. In patients with life threatening GIB who use warfarin, administration of vitamin k is probably the key therapeutic measure, since the coagulation factor products wear off by 6-8 hours. Once bleeding has been controlled, risk assessment for thrombosis will be done and if required, anticoagulants can be restarted.
  • Efforts to correct INR in cirrhotic patients with FFP, or PCC is a wrong move.
  • Tagged RBC scan is essentially replaced by CT angiography in assessment of hematochezia.
  • In patients with history of aortic repair or known AAA, always consider aortoenteric fistula if they present with GI bleeding (especially UGIB) or look septic.

Going further

GIB review

Intubation:

Coagulopathy:

Medications:

Gastric ultrasound:

CTA:

Post Peer Reviewed By: Mojtaba Chardoli. MD, Darab Zohri. MD

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Shahriar Lahouti

Founder, Chief Editor
I am Shahriar Lahouti and RECAP EM is my primary FOAMed project. The philosophy of RECAP EM is to promote critical thinking and enlightening the mindsets with most rational, current evidence towards a safer practice.

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