Management of Hepatic Encephalopathy in the Hospital

Hospitalist Best PracticeJ Rush Pierce Jr, MD, MPH

May 21, 2014

Case• Hx: 45 year old man with cirrhosis and ascites adm

with 2 days of confusion. On lactulose for 1 year, wife doesn’t know if compliant. Wife says no fever, abd pain, cough, diarrhea.

• PE: 100/60, 72, afebrile. Sleepy but arousable. Spiders, jaundice, ascites, edema, 3+ reflexes

• Lab: WBC = 8,000, H/H = 11.8/34, plts = 70K. Na = 129, K = 3.4, Cl = 103, HCO3 = 21; BUN = 7, creat = 0.9. INR = 2.5, bili = 3.9, ALT/AST sl high. NH4 = 65. CXR and UA neg.

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Clinical questions

1. Does this patient have hepatic encephalopathy?

2. Should I order a CT scan of head?3. Should I do a diagnostic paracentesis to

exclude SBP?4. Where should this patient be admitted?5. Will initial therapy be lactulose, rifaximin, or

both?

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Classification of HE

Source: 11th World Congress of Gastroenterology, 1998

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Acute hepatic failure and HE - Special considerations

• Predicts urgency for transplant• At high risk for cerebral edema (70% for

Grade IV)• Benefit from specific treatments of cerebral

edema • More likely to benefit from ICU stay

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Diagnosis of HE1. Identify underlying liver disease

– Acute with severe transaminitis– Chronic - portal HTN

2. Ascertain neuropsychiatric sxs– Sleep disturbance, alteration in level of

consciousness, confusion

3. Elicit neurologic signs – Asterixis, hyperreflexia, clonus, +Babinski

4. Exclude other causes05/21/2014 6Management of Hepatic Encephalopathy in

the Hospital

West Haven Clinical Severity Grades of HE

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Pierce’s simplification of West Haven Criteria

• Grade 0 = normal• Grade 1 = alert but squirrely• Grade 2= drowsy but awake• Grade 3 = asleep but arousable• Grade 4 = asleep and unarousable

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Asterixis

• https://www.youtube.com/watch?v=Or65nOrcz1A

• Also seen in:– Uremia– Severe CO2 retention– Dilation toxicity– Nodding off

Source: Adams and Victor’s Principles of Neurology, Ch 6

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Excluding other causes

Source: J Investig Med 2013;61:695

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Serum NH4 and diagnosing HE

Source: J Hepatology 2003;38:441

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Serum NH4 and following response to therapy of HE

Source: J Hepatology 2003;38:441

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HE management algorithm

• Hemodynamic stabilization• Detect and treat precipitants• Lower blood ammonia• Treat cerebral edema, if present• Manage hyponatremia

Source: Curr Treat Options Neurol 2014;16:297

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Identify and treat precipitating events

Source: Clin Liver Dis 2012;16:73–89

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Dietary recommendations for HE

Source: Hepatology 2013:58:325

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Predicting lactulose failure

Source: European J Gastro Hepatology 2010, 22:526

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Drug treatment of HE

• Lactulose, Lactilol– 2004 meta-analysis – superior to placebo but dop

not improve survival– When only high quality studies included, no effect– Widely used in practice, recommended as first line

rx

• Neomycin, metronidazole– RCT: neomycin vs placebo – no difference– Metonidazole, vancomyin – no RCT

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Treatment of HE - Rifaximin

Source: World J Gastroenterol 2012;18:767

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Treatment of HE - Rifaximin

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RCT – Rifaximin + lactulose vs lactulose

• Blinded prospective RCT, one center in New Delhi, 10/2010 – 09/2011, no drug sponsorship;

• Inclusion: adults, cirrhosis and overt HE• Exclusion: creat > 1.5, active EtOH in 4 wks, HCC, psych

illness, or major comorbidities• All pts had rx of underlying precipitating illness• Lactulose + rifaximin vs. lactulose + placebo; lactulose

titrated to 2 – 3 stools/day• All meds through NG tube• Followed to discharge or death

05/21/2014 21

Source: Am J Gastroenterol 2013;108:1458

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Source: Am J Gastroenterol 2013;108:1458

Main findings• There was a significant decrease in mortality

after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8 % vs. 49.1 % , P < 0.05). [ARR = 25.3%, NNT = 4)

• No diff in side effects (diarrhea, abd pain)• Pts who did not respond in each group had

higher baseline total WBC (7742 vs 6058)• Sepsis related deaths higher in lactulose +

placebo group (17 vs 7)

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Source: Am J Gastroenterol 2013;108:1458

Hyponatremia in HE

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Source: J Hospital Med2012;7:S14

Mayo Clinic recommendations

Source: Mayo Clin Proc. 2014;89(2):24105/21/2014 25Management of Hepatic Encephalopathy in

the Hospital

Mayo Clinic recs (contd)

Source: Mayo Clin Proc. 2014;89(2):24105/21/2014 26Management of Hepatic Encephalopathy in

the Hospital

Mayo Clinic recs (contd)

Source: Mayo Clin Proc. 2014;89(2):24105/21/2014 27Management of Hepatic Encephalopathy in

the Hospital

Advice on discharge (Expert opinion)

• Home on lactulose– All pts with Childs B/C– Childs A and isolated episode, do test sev weeks

after discharge

• Driving – 18 MVA’s in 167 cirrhotic patients in 1 yr– In car driving test

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Source: Mayo Clin Proc. 2014;89(2):241

Review of clinical questions

1. Does this patient have hepatic encephalopathy?

2. Should I order a CT scan of head?3. Should I do a diagnostic paracentesis to

exclude SBP?4. Where should this patient be admitted?5. Will initial therapy be lactulose, rifaximin, or

both?

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System Questions

• Should we grade HE?• Should everyone with HE get a paracentesis?• When should we use rifaximin?• Would an HE care plan be useful?

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