Liver failure

Liver failure Hyper - acute liver failure Acute liver failure Greatest risk of cerebral oedema, CVS failure Greatest chance of spontaneous survival Sub - acute liver failure Lowest risk of cerebral oedema/ encephalopathy Easily confused with CLD Ascites Lowest chance of spontaneous survival Principle Causes of Acute Liver Failure Cause Viral Drug related Agent responsible Hepatitis A, B, D E, others Idiosyncratic and dose related Toxins Vascular events Other Carbon tetrachloride, Phosphorous Amanita phalloides Ischemic hepatitis, Budd-Chiari, VOD, heat shock liver Pregnancy related, Wilson disease, lymphoma No previous liver disease Various definitions Jaundice or symptoms to encephalopthy • Decompensated chronic liver disease – Decompensation with sepsis · Bacterial peritonitis : Rx as “peritonitis” · Bacteraemia, chest, urine – Variceal bleed : frequently septic, endoscopic skills ± TIPS – Encephalopathy – Hepatorenal failure – Alcoholic hepatitis : steroids, pentoxifylline, feed, delta bilirubin Differential with ALF : History Pattern of LFT‟s Imaging : ultrasound, CT scan Biopsy : vary rarely indicated • Liver trauma Multi system disease Coagulopathy · INR important prognostic indicator in established ALF · Platelet dysfunction DIC - rare Metabolic · Insulin resistance : Clarke et al Hepatology · Hyperlactataemia :Bernal et al Lancet 2002 : useful to track · Liver net producer of lactate Murphy et al Crit Care Med 2001 · P04, Mg, Na, glucose, K, pH · High incidence of pancreatitis Nutrition · Frequent poor recent oral intake ± vomiting · No evidence for protein restriction in either acute or CLD · Gastric prophylaxis · Increased metabolic requirements Walsh et al CCM 2000;28(3):649-54 Renal failure • Common 45% of all cases • Multifactorial - frequently pre renal, ATN rather than HRS • Role of intra-abdominal pressure • Specific associations with viral disease, alcohol, auto-immune • CRRT or slow haemodialysis is ideal • Anticoagulation – epoprostenol, heparin, regional anticoagulation, citrate Infection : ALF • • Impaired innate and cellular immunity Bacterial infection 335 of 887 patients (550 episodes) • Severe sepsis 58% mortality • • Septic shock 98% mortality Fungal infection 99 of 887 : 11% : 64% mortality • Rolando et al Hepatology 2000 32:734, 31(4):872 • Components of SIRS associated with encephalopathy • Rolando et al Hepatology 2000;32:734-9, Vaquero et al Gastroenterology 2003;125:755-64, Shawcross D et al J Hepatol inpress • Cultures +++ • • Antibiotics : broad initially - 5/7 course • Antifungals No benefit to routine prophylaxis or Selective gut decontamination Rolando et al Semin Liver Dis 1996;16:389-402, Rolando et al Liver Trans Surg 1996;2:8-13 Vasopressors in ALF • What mean arterial pressure ? – Clinical examination ….invasive – Determined by JV saturation and ICP : autoregulating or not ? Which drug? – Determine fluid responsiveness initially · · Whatever you can get your hands on increases splannchnic V02 : glucose turnover Meier Hellman et al 1997 Crit care Med • – In sepsis and MOF epinephrine may be detrimental – Phenylephrine : decreased flow with decrease in spl V02 Reinelt Crit Care Med 1999,27:325 – Norepinephrine as first choice – Vasopressin may be potentially detrimental : cerebral complications and potential splanchnic ischaemia Results stratified according to blood pressure on day of SST Harry et al Hepatology 2002 –57% of patients have abnormal synacthen response –hypotension associated with lower baseline and increment (p<0.05) 1500 NS 1000 P<0.01 P <0.05 500 Marik 2005 CCM 53;1254 • LDL cholesterol did separate groups – 8.2±7.6 vs 28.4±14 • Mortality 39% vs 56% • 75% of those on pressors had abnormal response 0 * P<0.001 mortality associated with lower baseline and increment (p<0.05) –correlates with APACHE III and SAPS –No correlate with other parameters other than cholesterol Baseline Increment Peak Encephalopathy Portal Systemic Encephalopathy Portal systemic shunt – spontaneous collateral – Surgical – TIPPS Not at risk of cerebral oedema Precipitating factors – Sepsis · SBP Rx fluids ++ · Albumin HE of Acute Liver Failure Hepatocellular failure · Avoid renal failure Rapid onset Cerebral oedema – CNS active drugs – Electrolyte abnormalities Myoinositol levels not reduced Cytotoxic and vasogenic – Diuretics - over use – Gastrointestinal bleeding Hepatic encephalopathy in CLD • • • • Not a cause of death ……. Providing the airway is managed Association of SIRS with encephalopathy Feed - std protein, high calorie, fibre content ideally vegetable based Lactulose and enemas - cleaning or acidification – Als-Nielson BMJ 2004 ; 328: 1064 Non-absorbable antibiotics Decreasing ammonia therapies – (i) ornithine and (ii) benzoate Benzodiazepine antagonists - no efficacy Pomiers-Layrargues Hepatology 1989 10;969 Sedation - real risk in ward environment – Yes, they are a menace : up all night, climbing into the wrong • Treat precipitating cause : sepsis screen, fluids……. • • • • Incidence of cerebral oedema Reviewed 229 patients Grade III/IV coma 1999-2002 Incidence Hyperacute : 24% Acute : 23% Subacute : 9% Progressive neuropsychiatric syndrome, progressive neural inhibition Occurs in both acute and chronic liver disease Clinical state may change very rapidly NH4 Neurosteroids Inflammatory response Shawcross Lancet 365 2005 Larsen Neurochem International 2004 (44) Increased ammonia in cerebral deaths : splanchnic ammonia production Larsen et al Hepatology 1998 NH4 cut off 124 .pH, cerebral oedema + NH4 predict outcome Bhatia V Gut 2005 Partial pressure NH4 correlates with level of encephalopathy Kramer Hepatology 2000:21 CBF variable : loss of autoregulation to pressure Terlipressin in ALF Shawcross et al; Hepatology 2004;39(2):464-70 N=14 Jalan et al Gastroenterology o 2004;27:1338 Cooled to 32-33 C ICP CBF CPP CI PRE POST n=7 45 (25-49) 16 (13-17) * 103 (25-134) 44 (24 -75) * 45 (37-56) 70 (60-78) * 9.8 (7-13) 5.1 (4.3-6.1) * •Arterial NH4 343 (109 - 490) to 259 (100•Uptake 2.6 ( 0.6-6.3) to -0.3 (-3.1 - 1.4) Reduced risk of intracranial hypertension (p<0.05) Reduction in ICP in treatment group (p<0.005) Murphy et al Hepatology 2004;39(2):464-70 • Agitation and airway management – Grade III : Intubate ventilate and sedate with opiate and propofol – Control ventilation - avoid alkalosis • Position - 10 to 20 degrees head up • Insert reverse jugular line: JV sat 55 to 80% • Tight control of glucose, K, pH, Na (145-150 mmol/L) Murphy et al Hepatology 2004;39(2):464-70 • Ammonia : early CRRT • MAP >65 : frequently not autoregulating - need to measure ICP • Treat “ICP” - pupillary abnormalities – Mannitol 150 ml 20% (osmolarity < 320) or hypertonic NaCl (30%) : 20 ml Indomethacin 0.5 mg/kg • Hyperventilation - only for ICP in association with high JV satn • ICP trigger:– JV saturation, ammonia >150, pressors, fever, hyperacute and acute, pupilllary abnormalities • Temperature - avoid fever : hypothermia should not be undertaken routinely Currently available… Phase III study with BAL Demetriou et al Ann Surg 2004;239 660-670 MARS Therapy Mitzner et al Liver Transpl 2000;6:277-286, Heemann et al Hepatology 2002;36:949-58 24 patients with CLD and „acute liver injury‟ • MARS group: reduced bile acids, bilirubin, encephalopathy • Controls: biochemistry static, worsening encephalopathy – MARS 11/12 , SMT 6/12 (P<0.05) – 6 mnth survival 6/12 MARS vs 4/11 Coagulopathy and MARS treatment in CLD Doria et al Clinical transplantation 2004;18:365 Single Pass Albumin Dialysis (SPAD) Clearance of bilirubin, bile acids, NH4 : improved Sauer Hepatology 2004;39:1048 MARS Nathan et al Liver Transplant 2004;10:1109 Lai W et al Int Care Med 2005 • • 18 patients with alcohol related AoCLD randomized to MARS or SMT over 7 days Significant improvement in encephalopathy • • No change in renal function or creatinine No change in ammonia or cytokine levels (TNF, IL-6, IL-10, IL-8), MDA, MELD fell in both groups 10 patients with ALF grade III/IV coma Treated 8 hours on 2 consecutive days Increase SVRI on first Rx 1114±196 to 1432±245, changes not significant by end of second Rx No change in ICP 14.5 (7-25) to 14 (3-25) MARS+ SMT vs. SMT Acute on Chronic Liver Disease n=70 Significant improvements in encephalopathy grade No differences in survival Hassanein et al AASLD 2004 Outcome of CLD in ITU Wehler et al Hepatology 2001;34:255-261 143 patients :observational study, Apache III>90, pressors, Clinical jaundice > 92% 1month Mortality vs 11% in those with < 3 criteria 420 patients Gildea Chest 2004;126:1598 30 patients with HRF 8/30 30 day survival (median 21) Ventilated survival 0/15 Non-ventilated survival 8/15 No difference INR/alb/pressors J Gastroenterology and Hepatology Witzke et al 2004 19;1369 Accuracy of ICU scoring systems Child Pugh 0.72 MELD 0.72 APACHE II 0.78 SOFA 0.80 Graphical representation of LITU mortality and the Sequential Organ Failure Assessment System. 100 90 80 70 60 Mortality 50 (Percent) 40 30 20 10 0 1 2 3 4 5 6 No. of organ failure PSE+CVS+RENAL failure = 98% Mortality SOFA score cut off : 13 363 patients with CLD admitted to LITU Guidelines for referral Paracetamol Non-Paracetamol Arterial pH < 7.30 or HC03 < 18 pH < 7.30 or or HC03 < 18 INR > 3.0 day 2 or > 4.0 thereafter INR >1.8 oliguria and/or elevated creatinine oliguria/renal failure altered conscious level encephalopathy hypoglycaemia hypoglycaemia shrinking liver size Children - coagulopathy Budd Chiari Pregnancy related < 1000 ml need OLT Na < 130 mmol/L Bilirubin > 300 µmol/l Paracetamol pH < 7.30 all 3 of the following within 24 hrs PT > 100 INR > 6.5 Creatinine > 300 µmol/l grade 3 - 4 encephalopathy Non-Paracetamol pH<7.3 INR > 6.5 Liver volume Low P04 : good prognosis Alpha feta protein Lactate : 4 hrs > 3.5 OR 43 p<0.001 Lactate : 12 hrs > 3.5 OR 63 p<0.001 Children - coagulopathy INR > 4.5 Budd Chiari : renal failure + HE any 3 of : seronegative hepatitis or drug related / halothane Bilirubin > 300 µmol/l INR > 3.5 Age < 10 yrs or > 40 yrs J - E > 7 days MELD > 30 Encephalopathy + Factor V < 20% or < 30% if > 30 yrs of age The future: Increasing liver disease alcohol, HCV, NAFLD HCC Treatment changing Innovative treatment options liver support systems - further Controlled trials required Transplantation is a real option Early discussion Assume fluid deplete: time is tissue Infection is common Agitation=HE Close observation julia.wendon@kcl.ac.uk