1. Management of Hepatic Encephalopathy in the Hospital
Hospitalist Best Practice
J Rush Pierce Jr, MD, MPH
May 21, 2014

2. Management of Hepatic Encephalopathy in the Hospital
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
Management of Hepatic Encephalopathy in the Hospital

3. Management of Hepatic Encephalopathy in the Hospital
Clinical questions
Does this patient have hepatic encephalopathy?
Should I order a CT scan of head?
Should I do a diagnostic paracentesis to exclude SBP?
Where should this patient be admitted?
Will initial therapy be lactulose, rifaximin, or both?
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

4. Management of Hepatic Encephalopathy in the Hospital
Classification of HE
Source: 11th World Congress of Gastroenterology, 1998
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

5. 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
Management of Hepatic Encephalopathy in the Hospital

6. Management of Hepatic Encephalopathy in the Hospital
Diagnosis of HE
Identify underlying liver disease
Acute with severe transaminitis
Chronic - portal HTN
Ascertain neuropsychiatric sxs
Sleep disturbance, alteration in level of consciousness, confusion
Elicit neurologic signs
Asterixis, hyperreflexia, clonus, +Babinski
Exclude other causes
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

7. West Haven Clinical Severity Grades of HE
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

8. 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
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

9. Management of Hepatic Encephalopathy in the Hospital
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

10. Management of Hepatic Encephalopathy in the Hospital
Asterixis
Also seen in:
Uremia
Severe CO2 retention
Dilation toxicity
Nodding off
Source: Adams and Victor’s Principles of Neurology, Ch 6
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

11. Excluding other causes
Source: J Investig Med 2013;61:695
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

12. Serum NH4 and diagnosing HE
Source: J Hepatology 2003;38:441
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

13. Serum NH4 and following response to therapy of HE
Source: J Hepatology 2003;38:441
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

14. 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
Management of Hepatic Encephalopathy in the Hospital

15. Identify and treat precipitating events
Source: Clin Liver Dis 2012;16:73–89
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

16. Dietary recommendations for HE
Source: Hepatology 2013:58:325
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

17. Predicting lactulose failure
Source: European J Gastro Hepatology 2010, 22:526
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

18. Management 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
Management of Hepatic Encephalopathy in the Hospital

19. Treatment of HE - Rifaximin
Source: World J Gastroenterol 2012;18:767
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

20. Treatment of HE - Rifaximin
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

21. 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
Source: Am J Gastroenterol 2013;108:1458
05/21/2014

22. Management of Hepatic Encephalopathy in the Hospital
Source: Am J Gastroenterol 2013;108:1458
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

23. Management of Hepatic Encephalopathy in the Hospital
Main findings
There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8 % vs % , 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)
Source: Am J Gastroenterol 2013;108:1458
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

24. Management of Hepatic Encephalopathy in the Hospital
Hyponatremia in HE
Source: J Hospital Med
2012;7:S14
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

25. Mayo Clinic recommendations
Source: Mayo Clin Proc. 2014;89(2):241
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

26. Mayo Clinic recs (contd)
Source: Mayo Clin Proc. 2014;89(2):241
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

27. Mayo Clinic recs (contd)
Source: Mayo Clin Proc. 2014;89(2):241
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

28. 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
Source: Mayo Clin Proc. 2014;89(2):241
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

29. Review of clinical questions
Does this patient have hepatic encephalopathy?
Should I order a CT scan of head?
Should I do a diagnostic paracentesis to exclude SBP?
Where should this patient be admitted?
Will initial therapy be lactulose, rifaximin, or both?
05/21/2014
Management of Hepatic Encephalopathy in the Hospital

30. Management 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
Management of Hepatic Encephalopathy in the Hospital