management of hepatic encephalopathy in the hospital
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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.
05/21/2014 2Management of Hepatic Encephalopathy in the Hospital
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?
05/21/2014 3Management of Hepatic Encephalopathy in the Hospital
Classification of HE
Source: 11th World Congress of Gastroenterology, 1998
05/21/2014 4Management of Hepatic Encephalopathy in the Hospital
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
05/21/2014 5Management of Hepatic Encephalopathy in the Hospital
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
05/21/2014 7Management of Hepatic Encephalopathy in the Hospital
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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05/21/2014 9Management of Hepatic Encephalopathy in the Hospital
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
05/21/2014 10Management of Hepatic Encephalopathy in the Hospital
Excluding other causes
Source: J Investig Med 2013;61:695
05/21/2014 11Management of Hepatic Encephalopathy in the Hospital
Serum NH4 and diagnosing HE
Source: J Hepatology 2003;38:441
05/21/2014 12Management of Hepatic Encephalopathy in the Hospital
Serum NH4 and following response to therapy of HE
Source: J Hepatology 2003;38:441
05/21/2014 13Management of Hepatic Encephalopathy in the Hospital
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
05/21/2014 14Management of Hepatic Encephalopathy in the Hospital
Identify and treat precipitating events
Source: Clin Liver Dis 2012;16:73–89
05/21/2014 15Management of Hepatic Encephalopathy in the Hospital
Dietary recommendations for HE
Source: Hepatology 2013:58:325
05/21/2014 16Management of Hepatic Encephalopathy in the Hospital
Predicting lactulose failure
Source: European J Gastro Hepatology 2010, 22:526
05/21/2014 17Management of Hepatic Encephalopathy in the Hospital
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
05/21/2014 18Management of Hepatic Encephalopathy in the Hospital
Treatment of HE - Rifaximin
Source: World J Gastroenterol 2012;18:767
05/21/2014 19Management of Hepatic Encephalopathy in the Hospital
Treatment of HE - Rifaximin
05/21/2014 20Management of Hepatic Encephalopathy in the Hospital
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
05/21/2014 22Management of Hepatic Encephalopathy in the Hospital
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)
05/21/2014 23Management of Hepatic Encephalopathy in the Hospital
Source: Am J Gastroenterol 2013;108:1458
Hyponatremia in HE
05/21/2014 Management of Hepatic Encephalopathy in the Hospital 24
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
05/21/2014 Management of Hepatic Encephalopathy in the Hospital 28
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?
05/21/2014 29Management of Hepatic Encephalopathy in the Hospital
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?
05/21/2014 30Management of Hepatic Encephalopathy in the Hospital
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