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

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

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

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

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

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

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

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

Management 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 Management of Hepatic Encephalopathy in the Hospital

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

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

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

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

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

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

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

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

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

Treatment of HE - Rifaximin 05/21/2014 Management 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 Source: Am J Gastroenterol 2013;108:1458 05/21/2014

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

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

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

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

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

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

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

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