

1.  

2. Parking Lot Care?

3. Case • 54 yr old F, 3D hx of N/V/D and abdo pain • no fever • no GI bleeding • confused today • Hx HTN • metoprolol and ASA

4. Case • T 36.1 P 62 BP 99/60 RR 28 Sat 92% • lethargic, weak, sl. confused • dry MM, JVP flat, PPP • abdo diffusely tender, no guarding/rebound • midline scar ? hx • stools OB +ve, no melena/blood

5. Case Differential Diagnosis • gastroenteritis with dehydration • ischemic gut • intra-abdominal sepsis • urosepsis

6. Case • chemstrip • monitored bed • IV’s • NS bolus/infusion • analgesic/antiemetic • Labs: CBC/CH6, coags, LFT’s/lipase, lactate

7. Case glc 0.8 CBC • Hb 160 • plt 30 • WBC 24 (neuts) lytes • Na 141 • K 5.2 • Cl 96 • CO2 8 creatinine 123 lactate 22 LFTs • ALT >3000 • Bili 42 • ALP 105 Coags • INR >9 • PTT >150

8. Acute Liver Failure Cathy Dorrington MD FRCPC

10. Objectives • define, diagnose and to list common etiologies of Acute Liver Failure (ALF) • describe appropriate emergency management of ALF • be knowledgeable regarding predictors of prognosis in patients with ALF

11. ALF Definition Pt with labs c/wHEPATITIS (15X N ALT) + COAGULOPATHY = INR >1.5 + Any ENCEPHALOPATHY + NO PRE-EXISTING liver disease + DURATION < 26 wks Polson and Lee. Hepatology 2005

12. ALF Differential Diagnosis • Sepsis with DIC • Disease process involving brain and liver • SLE • TTP • Acute decompensation of chronic liver disease

13. Prognosisoverall survival 65%1998-2001 N=308 Ostapowicz. Ann Intern Med 2002

14. Etiology • Metabolic • Wilson’s • Drugs / Toxins • OTC - Tylenol • Prescription • Herbals • Illicit - Ecstasy • Amanita • Pregnancy • HELLP • Fatty Liver ACUTE LIVER FAILURE Autoimmune • Viral • HAV • HBV / HDV • Non-A-E • Infiltrative • Lymphoma • Melanoma • TB • Vascular • Budd-Chiari • Ischemic

15. Etiology of ALF1998-2001 N=308 Ostapowicz. Ann Intern Med 2002

16. Etiology Prescription Drugs* • isoniazid (16%) • propylthiouracil (9%) • phenytoin (7%) • valproic acid (7%) *unlikely if taken > 2 years Ostapowicz. Ann Intern Med 2002

17. Investigations post diagnosis ALF • ammonia • fibrinogen level • APAP level /toxicology screen • viral hepatitis serology • anti-HAV IgM, HBsAg, anti-HBcIgM, anti-HEV, anti-HCV • ceruloplasmin level (Wilson’s) • autoimmune markers • ANA, ASMA, immunoglobulin levels • HIV - rapid Polson and Lee. Hepatology 2005

18. Investigations Imaging • ultrasound abdomen with doppler • Budd-Chiari • malignant infiltration • tumour • cirrhosis (acute on chronic)

19. Management • etiologic specific therapy • NAC in non-APAP ALF • metabolic disturbances • hemodynamics • management of complications • transplant consideration

20. Management Etiology known • APAP -> NAC • autoimmune -> steroids • Budd-Chiari ->TIPS • malignant infiltration -> chemo • Hep B -> antivirals* • Amanita Phalloides ->silibinin/Pen G NOT recommended

21. Management NAC in non-acetominophen ALF • improves microcirculatory tissue perfusion • inotrope • antioxidant • vasodilator • improves cerebral perfusion pressure

22. Management NAC in non-APAP ALF: Gastroenterology 2009 • RCT 173 adult pts with ALF • excluded shock, malignancy, pregnancy • 72 hr infusion

23. Management • 3wk survival similar • Transplant rate similar • transplant-free survival improved • 40% vs. 27% • benefit confined to Grade I/II : NNT 5

24. Metabolic Disturbances • hypoglycemia • K+,  Mg++,  Na+, PO4 • lactic acidosis

25. Hemodynamics of ALF • volume depletion • hyperdynamic circulation • maintenance of MAP >60 to CPP • pressor of your choice

26. Coagulopathy • significant bleeding in 10-20% • upper GI • nasopharynx • skin puncture sites

28. CoagulopathyNon-Bleeding Patients INR • DO NOT CORRECT with FFP unless planned invasive procedure • best prognostic feature • triage for transplant • Vitamin K 10mg for all Platelets • invasive procedures >50 • otherwise <10

29. CoagulopathyBleeding Patient FFP • correct INR to ≤ 1.5 Vitamin K Platelets • correct to 50 Activated Factor VIIa • consider if INR not correcting with FFP Fibrinogen • cryoprecipitate if < 1 • 10 units

30. CoagulopathyBleeding Patient ? Octaplex • not studied in this patient population • relative contraindication • risk of peri-operative thrombus • absolute contraindication • co-existent DIC

31. Encephalopathy Grades of Encephalopathy I - Changes in behavior with minimal change in level of consciousness II - Gross disorientation, drowsiness, possibly asterixis, inappropriate behavior III - Marked confusion, incoherent speech, sleeping most of the time but arousable to vocal stimuli IV - Comatose, unresponsive to pain, decorticate or decerebrate posturing

32. Encephalopathy • cerebral edema/increased ICP >> toxins • mental status -> tremor/asterixis • important predictor of survival • triage tool for transplant • CT head in altered pts to r/o bleed

33. Encephalopathy Cerebral Edema • leading cause of death and disability • 50-85% in grades III/IV encephalopathy • poorly understood • cytotoxic accumulation of substances normally cleared by liver • vasogenic

34. Ammonia & Cerebral Edema • metabolized by astrocytes to glutamine • accumulates in astrocytes to cause cell swelling Blei. Hepatology 2000

35. Encephalopathy Lactulose • ? small increase in survival time • no change in degree of encephalopathy • no change in overall outcome Alba. J Hepatol 2002

36. Management • bowel distension -> challenge to transplant

37. Encephalopathy Sedation – avoid in Grade I/II • Benzos •  T½ -> encephalophathy evaluation • Propofol • first choice • ?decrease ICP • smaller doses as  T½

38. Encephalopathy Seizures • phenytoin • low dose benzos during phenytoin load • no benefit to prophylactic administration Ellis. Hepatology 2000

39. Encephalopathy Cerebral Edema (assume in Grade III/IV) • HOB 30° • barbituates (thiopental) • mannitol/hyperventprn • steroids not beneficial • ? cooling (32-34 C) • ?ICP monitor Polson and Lee. Hepatology2005

40. Infection • 80% develop bacterial infection • 25% of exclusion for transplant • 40% post-transplant deaths • SIRS  worsening encephalopathy • fever worsens ICH Rolando. Hepatology 1990

42. Infection • prophylactic antibiotics •  rate of infection (61% vs. 32%) •  but not stat sig Δ in mort (45% vs. 67%) • consider, low threshold for empiric tx • gut decontamination with po antibiotics • no change in rate of infection or outcomes Rolando. Hepatology 1993

43. Infection • screening • culture all • asceptic technique • lines etc. • empiric if suspected • ceftriaxone plus vanco

44. Renal Dysfunction • 42% - 82% of ALF • 75% APAP overdose • etiology • hypotension, hypovolemia • TNF, endotoxins • renal vasoconstriction • unfavourableprognosis

45. Renal Dysfunction • replace/maintain volume • avoid nephrotoxic drugs • avoid contrast or NAC prior

46. Disposition • ICU • hepatology consult • +/- transfer to transplant center Predicting prognosis and decision to transfer

47. Prognosisoverall survival 65%1998-2001 N=308 Ostapowicz. Ann Intern Med 2002

48. Prognosis • etiology • lab values

49. Prognosis Etiologies with poor outcome = <25% spontaneous recovery • mushroom poisoning and Wilson’s: 0% • idiosyncratic drug injury • acute hepatitis B • autoimmune • Budd-Chiari syndrome • indeterminate Polson and Lee. Hepatology 2005

50. Prognosis Etiologies associated with better outcomes = >50% spontaneous recovery • APAP (85%) • HAV • shock liver • pregnancy related Polson and Lee. Hepatology 2005