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ALTERD

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Section IconAssess
Chief Complaint
Consider the diagnosis of hepatic encephalopathy in any patient presenting with altered mental status, particularly one with known liver disease.
History-May be difficult to obtain from patient, be sure to incorporate family, caregiver, NH staff, etc.
Past Medical History, with consideration for previous liver disease, alcoholism, or recent TIPS procedure
Medications, such as
Non-adherence with Rifaximin or lactulose
Recent/current antibiotics
Benzodiazepines
Opioid
Diuretics
Valproic Acid
Diet
High protein loads
Review of Systems
Changes in bowel patterns
  • Diarrhea
  • Constipation
  • Melena/Hematochezia
Signs of infection
Signs & Causes
Signs/Causes of Dehydration
Signs of neuromuscular decline
Section IconLook
Physical Exam, with particular attention to
Fetor hepaticus (musty breath), sign of severe disease
Nystagmus
Ascites
Abdominal tenderness
Caput medusa
Testicular atrophy
Muscle atrophy
Asterixis in hands
Jaundice
Spider nevi
Palmar erythema
Bruising
Ataxia
Hyperactive deep tendon reflexes
Laboratory Testing
Labs
  • BMP
LFT’s
CBC
PT/INR
Blood alcohol level, if indicated
Ammonia level
Toxicology screen, if indicated
  • Drug Levels (based on history or med list)
    • Digoxin
    • Acetaminophen
    • Salicylates
Radiology
  • RUQ sono with Doppler
Other
  • Consider lumbar puncture
  • Consider diagnosis paracentesis to evaluation for spontaneous bacterial peritonitis (SBP); as many as 10% of patients with overt hepatic encephalopathy also have SBP.
Section IconTreatment
Goal of HE treatment
The goal of HE treatment is to induce remission of OHE by purging the colon of bacterial contents and then to maintain remission from future HE episodes via secondary prophylaxis given the high risk of recurrence.
Treat common conditions associated with HE
Infections (SBP, pneumonia, UTIs, bacteremia)
GI bleeding (variceal and nonvariceal)
Electrolyte abnormalities (particularly hypokalemia and hyponatremia)
Acute kidney injury and hypovolemia/dehydration
Sedating medications or intoxication
Portal vein thrombosis
Constipation and HE therapy noncompliance
Section IconEvaluate Risk
West Haven Criteria (WHC) Grade 1: Changes in behavior with minimal change in level of consciousness
No treatment
WHC Grade 2: Gross disorientation, drowsiness, possibly asterixis, inappropriate behavior
Lactulose PO or NG* route: 30 mL (20 grams) to 45 mL (30 grams) PO or NG q1h until large BM, several small BMs, and/or improvement in mental status
*Presence of varices or unknown varices status is not a contraindication to NGT placement
WHC Grade ≥ 3, unable to take PO, or contraindication to PO administration: Marked confusion, incoherent speech, sleeping most of the time but arousable to vocal stimuli or Comatose, unresponsive to pain; decorticate or decerebrate posturing
If intubated, can administer lactulose as above via NGT
  • PEG-3350 4 liters can be administered via NGT as adjunctive therapy
If not intubated, lactulose rectal 200 grams (300mL lactulose in 700mL sodium chloride 0.9%) via rectal tube hourly until large BM, several small BMs, and/or improvement in mental status
Treatment following stabilization of new or recurrent OHE episode in the ED at admission or upon discharge
Goal: Maintain remission from OHE and prevent future episodes of HE via secondary prophylaxis given high risk of recurrence
West Haven Criteria (WHC) Grade 1
No treatment or continue home treatment with lactulose with or without rifaximin (dosing listed below).
Initial WHC Grade 2, 3 or 4
Lactulose PO or NG: 30 mL (20 grams) q1-2 hours until 2 – 4 soft bowel movements per day.
In addition to lactulose, consider adding Rifaximin 550 mg PO BID once able to take PO
Rationale:
  • Addition of rifaximin to lactulose increases efficacy of therapy and decreases mortality and lowers readmission rates for hepatic encephalopathy at 180 days6,7
  • Rifaximin added to placebo has been shown to maintain remission
Medication Information
Lactulose 10 g/15 mL Oral Solution:
  • Contraindications:
    • Lactulose contains galactose; contraindicated in those who cannot take galactose in diet
  • Adverse effects:
    • Bloating, epigastric pain, flatulence, nausea, vomiting
    • Hypernatremia, hypokalemia
  • Safety Considerations:
    • Pregnancy: Although lactulose does not cross the placenta, there have not been adequate and well-controlled studies of lactulose in pregnant women conducted. Administer lactulose to pregnant women only if clearly indicated.
    • Breastfeeding: Evidence is inconclusive for determining infant risk when used in breastfeeding mother. Exercise caution when administering lactulose to a nursing woman.
Rifaximin (Xifaxan) 550mg oral tablet
  • Give with or without food.
  • Contraindications:
    • Avoid in patients with hypersensitivity to rifaximin or any component of the drug or to other rifamycin antibiotics e.g., rifampin, rifabutin.
    • Avoid use in diarrhea complicated by fever or blood in stool or due to pathogens other than Escherichia coli.
  • Adverse effects
    • Peripheral edema
    • Abdominal pain, nausea, dizziness, headache, fatigue
  • Safety Considerations:
    • Pregnancy: It is unknown whether rifaximin crosses the placenta. Thus, administer during pregnancy only if the benefit justifies the risk to the fetus and inform the patient of the potential for harm. Breastfeeding: Evidence is inconclusive for determining infant risk when used in breastfeeding mother. Exercise caution when administering rifaximin to a nursing woman.
  • Cost Considerations:
References
  1. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guidelines by AASLD and EASL. Hepatology. 2014 Aug;60(2):715-35.
  2. Patidar KR, Bajaj JS. Covert and overt encephalopathy: diagnosis and management. Clin Gastroenterol Hepatol. 2015 Nov;13(12):2048-61.
  3. Gerber T, Schomerus H. Hepatic encephalopathy in liver cirrhosis: pathogenesis, diagnosis, and management. Drugs. 2000;60:1353-70.
  4. Gundling F, Zelihic E, Seidl H, et al. How to diagnose hepatic encephalopathy in the emergency department. Ann Hepatol. 2012;12(1):108-14.
  5. Rahimi RS, Singal AG, Cuthbert JA, et al. Lactulose vs. polyethylene glycol 3350-electrolyte solution of treatment of overt hepatic encephalopathy. The HELP randomized clinical trial. JAMA Intern Med 2014 Nov;174(11):1727-33.
  6. Naderian M, Akbari H, Saeedi M, et al. Polyethylene glycol and lactulose versus lactulose alone in the treatment of hepatic encephalopathy in patients with cirrhosis: a non-inferiority randomized controlled trial. Middle East J Dig Dis 2017 Jan;9(1):12-9.
  7. Wang Z, Chu P, Wang W. Combination of rifaximin and lactulose improves clinical efficacy and mortality in patients with hepatic encephalopathy. Drug Design, Development, and Therapy 2019;13:1-11.
  8. Courson A, Jones GM, Twilla JD. Treatment of acute hepatic encephalopathy: comparing effects of adding rifaximin to lactulose on patient outcomes. J Pharm Pract 2016;29(3):212-7.
  9. Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362:1071-81.
Section IconReassess
Screen for social needs prior to discharge.
For low resource facilities, a referral for health plan or community case manager or social worker to follow up within 24 hours of discharge. These actions are not required of the physician but could be performed by other ED staff. For the patient discharged from the ED, provide written instructions to support adherence to treatment. Click here for a sample screening tool and discharge instructions (PDF).
Section IconDisposition
Concept
Spectrum of disposition options from low to high intensity to match patient needs.
Covert HE and unrelated reason for visit: Discharge home with recommended PCP follow up within 14 days
Target patient: West Haven score 1, no metabolic disarray or complications
If patient does not have PCP use local processes for referral to establish primary care and/or gastroenterology referral.
Covert HE and related reason for visit: Discharge home with expedited specialty clinic (GI/Liver) (if available) follow up within 7 days
Target patient: West Haven score currently 1 but could be 2 at other times, no metabolic disarray or complications.
Consider discharge prescription for rifaximin; if ED does not have good access to specialty clinic follow up, maintain a low threshold for gastroenterology consultation
Established history of HE and patient’s primary reason for visit to ED related to liver disease and its complications: Short outpatient hospitalization (e.g., ED observation unit or observation in an inpatient area)
Target patient: West Haven score 1 with barriers to outpatient follow up or West Haven 2 with near normal mental status and/or mild metabolic disarray or complications such as abdominal ascites requiring therapeutic paracentesis with anticipated length of stay less than two midnights.
Consider starting rifaximin in ED, correction of metabolic disturbances, GI consult, CIWA for patients with alcohol abuse history (need CIWA <9 to be eligible for observation care); upon discharge from ED observation recommend GI/hepatology clinic (if available) follow up within 3-5 days.
ED observation protocol should state inclusion/exclusion criteria (e.g., GCS >12, no clinical concern for variceal bleeding or sepsis, nursing care needs appropriate for level of observation unit staffing), typical observation interventions (testing/treatments/consultations) and endpoints for discharge home (e.g., GCS 15, new oral medication regimen established and well tolerated, no other diagnoses identified warranting inpatient care) with outpatient follow up plan versus inpatient admission.
Overt HE: Inpatient hospitalization on general medical or GI service
Target patient: West Haven score 2-3, arousable and redirectable, minimal or moderate metabolic disarray or complications.
Recommend GI consult and consider starting rifaximin in ED.
Overt HE: Medical ICU hospitalization
Target patient: West Haven score 4, obtundation and severe metabolic disarray or complication (e.g., sepsis, GI bleed); patient unlikely to be able to take PO meds
Recommend GI consult.
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Acknowledgments

Developed by the ACP Expert Panel on Hepatic Encephalopathy.
Reviewed by the ACEP Clinical Resource Review Committee.

CONTRIBUTORS
Arun B. Jesudian, MD, co-chair Stanley C. Thompson, MD, co-chair Christopher W. Baugh, MD, MBA William Ford, MD Christi Anne Jen, PharmD, BCPS, FAzPA James Neuenschwander, MD, FACEP Edgar Ordonez, MD, FACEP Rebecca A. Perez, RN, BSN, CCM

 

ACEP Staff
Jerry Anderson Riane V. Gay, MPA, CAE Liz Muth Lillian Renner

 

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