PACT module Acute hepatic failure. Intensive Care Training Program Radboud University Medical Centre Nijmegen

Transcription

1 PACT module Acute hepatic failure Intensive Care Training Program Radboud University Medical Centre Nijmegen

2 Acute Liver Failure Acute on Chronic Liver Failure Acute loss of hepatocellular function in a patient with a previously normal liver function 40% spontaneous recovery 65% overall survival Acute loss of hepatocellular function in a patient with a previously abnormal liver function Acute Wilson disease - reactivation of Hep B - autoimmune hepatitis Distinction often difficult unless liver biopsy confirms absence of cirrhosis Hyperacute liver failure Interval jaundice-encephalopathy 7 days Subacute liver failure Interval jaundice-encephalopathy > 28 days Usually paracetamol good chance of spontaneous recovery Usually idiosyncratic drug reaction low chance of spontaneous recovery

3 Singanayagam A. Curr Opin Crit Care 2015;21:

4 Aetiologies in Western Usually hyperacute with AKI - good outcome world Usually subacute bad outcome Antibiotics (amoxi/clav) NSAIDs Anticonvulsants

5 Outcome Singanayagam A. Curr Opin Crit Care 2015;21:

6 Initial management issues (4) Making a timely diagnosis of ALF in patients with liver dysfunction and altered mental state (DD acutely decompensated chronic liver disease and sepsis) Administer N-acetylcysteine in every ALF patient?

7 Diagnosis Singanayagam A. Curr Opin Crit Care 2015;21:

8 NAC treatment Limits liver injury via repletion of hepatic glutathione Improves systemic hemodynamics and DO2 No overall survival difference at 21 days

9 Initial management issues (4) Transferral to a liver transplant centre? 25% will undergo transplantation, transplant candidacy is extremely difficult, treatment of MOSF INR > 2.0 or grade 2 hepatic encephalopathy With high risk patients (including extremes of age) with any degree of encephalopathy During transport maintain euglycemia and protect the airway

10 Initial management issues (4) Should the patient be listed for orthotopic liver transplantation? King s College Criteria

11 Singanayagam A. Curr Opin Crit Care 2015;21:

12 Causes of death Frequently triggered by infection sometimes by necrotic liver

13 Specific complications Infections Immune dysfunction results in infection in up to 90% of patients Gram + > Gram - > Candida SDD reduces incidence of infections but overall effect inconclusive Low threshold for administering empiric antibiotics in Grade III/IV encephalopathy or renal failure

14 Specific complications Pulmonary Intubate if a patients reaches Grade III encephalopathy Aim at an initial PaCO2 goal of 35 mm Hg Approximately 35% of ALF patients will develop ALI/ARDS

15 Specific complications Cerebral edema and ICP Accounts for 20-25% of deaths Combination of ammonia-glutamine hypothesis and increase in cerebral blood flow Increased risk with hyperacute liver failure, serum ammonia > μmol/l and Gr III/IV encephalopathy ICP measurement controversial although risk for significant bleeding < 5%

16 Detry O. World J Gastroenterol 2006;12:

17 Ammonia-glutamine hypothesis Tofteng F. J Cereb Blood Flow Metab 2006;26:21-27

18 Ammonia-glutamine hypothesis Tofteng F. J Cereb Blood Flow Metab 2006;26:21-27

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20 Specific complications Cardiovascular Systemic arterial vasodilation Portal hypertension, splanchnic sequestration of blood and decreased venous return Norepinephrine preferred vasoconstrictor Vasopressin may increase ICP

21 Specific complications Bleeding Increased PT or INR essential for diagnosis 50-70% platelet count < 150 * 10 9 Clinically significant bleeding in ALF < 5% due to concomitant decrease in anticoagulant proteins Bleeding from varices extremely rare as is spontaneous intracranial bleeding

22 Specific complications Acute renal failure 50% of patients with ALF Acute tubular necrosis or functional renal failure (hepatorenal syndrome) Institute early RRT preferentially by a continuous technique low urine production, increase in serum creatinine 26.5 μmol/l, serum ammonia > μmol/l

23 Hepatorenal Syndrome Turban S.World J Gastroenterol 2007;14:

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25 Specific complications Salvage transplantation 10% of patients with paracetamol induced ALF compared to 30-50% other aetiologies Bleeding during transplantation less than in patients with cirrhosis due to lower degree of PH Death usually due to MOSF or brain stem herniation

26 Molecular Adsorbents Recirculating System 50 kda Sen S. Aliment Pharmacol Ther 2002;16(Suppl. 5):32-38

27 MARS Sen S. Aliment Pharmacol Ther 2002;16(Suppl. 5):32-38

28 MARS Bridge to transplantation Liver support until spontaneous recovery

29 MARS and AoCLF Karvellas CJ. Crit Care 2007;11:215

30 MARS and ALF Karvellas CJ. Crit Care 2007;11:215

31 Schmidt LE. Liver Transplantation 2003;9:

32 MARS Schmidt LE. Liver Transplantation 2003;9:

33 Fulmar trial 6 M N = 102 Saliba F. Ann Intern Med 2013;159:

34 Infection susceptibility in acute-on-chronic liver failure

35 Patient Female, 37 Alcoholic hepatitis Acute-on-chronic liver failure Various infection periods

36 Infections in cirrhosis 50% of all admissions for liver cirrhosis Main precipitant for acute-on-chronic liver failure MODS including hepatic encephalopathy, hepatorenal syndrome, ARDS, vasodilatory shock 30-day mortality > 25%

37 Main mechanisms Systemic translocation of gut-derived organisms Impaired hepatic clearance mechanisms Peripheral immune paresis

38 CD Accumulating circulating immune effector cells in the liver - depletion in the blood

39 Pathophysiology of acute liver failure Acute onset icterus Elevated transaminases Coagulopathy Encephalopathy In patients without hepatopathy

40 Pathophysiology of acute liver failure Marked activation of systemic inflammation MODS High rate of secondary infections

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42 Liver cirrhosis and septic shock - outcome Sauneuf B. Crit Care 2013;17:R78

43 Characteristics Sauneuf B. Crit Care 2013;17:R78

44 Treatment Sauneuf B. Crit Care 2013;17:R78