Management of Hepatic Encephalopathy in the Hospital

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

2. 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. Management of Hepatic Encephalopathy in the Hospital

3. 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? Management of Hepatic Encephalopathy in the Hospital

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

6. 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 Management of Hepatic Encephalopathy in the Hospital

7. West Haven Clinical Severity Grades of HE 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 Management of Hepatic Encephalopathy in the Hospital

9. Management of Hepatic Encephalopathy in the Hospital

10. 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 Management of Hepatic Encephalopathy in the Hospital

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

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

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

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

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

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

18. 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 Management of Hepatic Encephalopathy in the Hospital

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

20. Treatment of HE - Rifaximin 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

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

23. 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) Source: Am J Gastroenterol 2013;108:1458 Management of Hepatic Encephalopathy in the Hospital

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

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

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

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

30. 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? Management of Hepatic Encephalopathy in the Hospital