ACUTE LIVER FAILURE

A CUTE LIV ER FA ILURE Joe Heit, MSc, MD, FACP A CUTE LIV ER FA ILURE (A LF) - DEFINITIONS - •the onset of encephalopathy and coagulopathy within 26 weeks of jaundice (without preexisting liver disease) •If onset weeks or less (or weeks or less and previous liver disease) - this is defined as fulminant hepatic failure CA USES OF A LF •A-B-C-D-E-F mnemonic –A = hepatitis A, autoimmune hepatitis, alcohol, acetaminophen (most common in USA), aflatoxicosis –B = hepatitis B (most common in Far East) –C = hepatitis C, cryptogenic –D = hepatitis D –E = hepatitis E (most common in India), (esoteric): Wilson’s disease, Budd-Chiari –F = fatty liver (HELLP, AFLP) A LF - GOA LS •Diagnosis •Estimate disease severity •Initiate treatment •Evaluate for possible liver transplant A LF - Diagnosis ALF is a syndrome - the late manifestation of multiple causes of hepatic injury Diagnosis relies on establishing the presence of encephalopathy secondary to underlying liver disease and measurement of hepatic synthetic dysfunction with an elevated INR of >1.5 Hospitalization is recommended for any patient with these findings A LF - Treatment •The optimal treatment strategy is not well defined The support from literature for many aspects of care does not exist •Some accepted treatments: –N-aceylcysteine for acetaminophen toxicity –Acyclovir for HSV associated liver disease –Lamivudine for Hepatitis B associated ALF –Steroids for autoimmune hepatitis (and alcoholic hepatitis) –Pen G for amanita toxicity –Delivery for HELLP/AFLP A LF - TREA TMENT THE ONLY PROVEN THERAPUTIC INTERVENTION FOR ALF (AND FHF) IS TRANSPLANTATION A LF - Complicating issues • • • • • • • Encephalopathy Cerebral edema Coagulopathy Sepsis Gastrointestinal bleeding Acute renal failure Metabolic derangements ENCEPHA LOPA THY •Likely not all secondary to elevated ammonia levels •Treatment options –Lactulose •No data supporting use in ALF •Generally avoid if Gr III-IV encephalopathy •Monitor for gastric distention and volume depletion –Neomycin and Rifaximin (usually started if no change with lactulose in 48 ours) •Avoid if encephalopathic •Potentially nephrotoxic (small amounts are absorbed) –Branched chain amino acids •Supporting literature is mixed Expensive –Low protein diet CEREBRA L EDEMA - •Occurs in up to 80% of those with Grade IV encephalopathy •Mechanisms unknown, but some possibilities –Osmotic abnormalities in astrocytes •Cytotoxic edema from astrocyte edema •Astrocytes metabolize ammonia to glutamine –Altered cellular metabolism (neurons, glial cells) •Increased intracellular osmolality –Alterations in cerebral blood flow - unlikely mechanism •Causing vasogenic edema •Elevated ICP with herniation (brainstem) a common cause of death in ALF NONINV A SIV E TREA TMENT FOR CEREBRA L EDEMA •Elevate head of bed (30-45degrees) •Quiet environment –Agitation and pain elevate ICP -use adequate sedation & analgesia •Avoid fluid overload (CVP 20 (0.25-1 gm/Kg) –Use to keep serum osmolality 310-325?) •Serum osmolality correlates poorly with [mannitol] •Pentobarbital (3-5 mg/Kg load then 1-3 mg/Kg/hr) –How to monitor ? •Avoid hyperventilation except as a rescue intervention NONINV A SIV E TREA TMENT FOR CEREBRA L EDEMA •Prophylactic Dilantin –Subclinical seizures more frequent than often realized –Autopsies studies conflict on whether less cerebral edema with Dilantin use •Iatrogenic hypernatremia –Hypertonic saline to keep serum Na 145-155 –Small study showed ICP lowering –30cc of 23.4% or 2cc/Kg of 7.5% as bolus q 2-3 hrs to target Na •Hypothermia ? •Indomethicin? COA GULOPA THY - •By definition, present in all cases of ALF •Elevated INR –Decreased hepatic synthesis of many procoagulant proteins •Quantitative and qualitative platelet defects •Decreased fibrinogen –Decreased hepatic synthesis –Increased catabolism (ALF hypercatabolic state) •Variable degree of Vitamin K deficiency COA GULOPA THY - •Spontaneous bleeding actually unusual in ALF •Vitamin K prophylaxis acceptable •FFP prophylaxis not recommended •Treat if active bleeding or planned invasive interventions –FFP for elevated INR > 1.5 (IV route recommended) –Platelets if count < 50,000 –Cryoprecipitate (especially if fibrinogen < 100 mg/dl) –Aminocaproic acid an option if hyperfibrinolytic (diffuse mucosal and puncture site bleeding) –rFVIIa if bleeding persists despite using other measures •Thrombotic risk SEPSIS - •Frequent cause of death •Compromised immune function with FHF –Lowered complement levels –Decreased opsonization –Impaired WBC function –Altered Killer cell function •Usual signs of infection (fever, pain, sputum production) may be absent –Worsening encephalopathy and renal function may be only sign –Lung most common source, then urinary –Invasive devices a common source of infection –Most common organisms - strep, staph, enteric GN, fungal species (usually candida) SEPSIS - •Since usual signs of infections may be absent in ALF, frequent surveillance cultures often performed (even daily) •Empiric antibiotics recommended if: –Surveillance cultures with significant growth –Sudden worsening of neurological or renal function –New signs of SIRS –Hypotension not responsive to fluids –If candidate for urgent liver transplant •Antibiotic choice guided by cultures (if positive) and by usual considerations (hospital antibiogram) –Remember frequency of infection with fungal species SEPSIS - Treatment for infection and sepsis should follow usual process (see: Surviving Sepsis Campaign) –Exceptions include: •If pressors needed, try to avoid epinephrine (decreases mesenteric blood flow and likely decreases hepatic blood flow) •If pressors needed, try to avoid vasopressin (can increase ICP by causing cerebral vasodilation) •Some transplant centers still recommend stress dose steroids for sepsis in ALF patients (? If this will change in light of new literature) GI BLEEDING •Correct coagulopathy –Complete reversal of abnormalities likely not possible and not desirable •Appropriate GI prophylaxis should be given all hospitalized patients with ALF –H2 blockade (and PPI by assumption) decrease risk of GI bleeding A CUTE RENA L FA ILURE •Occurs in 40-50% of cases of FHF; 70% if FHF due to agents that are also nephrotoxic •Etiology unclear –May be intra-renal hemodynamic changes similar to Hepato-renal syndrome •Usual preventative strategies –Avoid hypovolemia and nephrotoxic drugs, early recognition and treatment of infection •Differential diagnosis –Usually ATN v HRS (urine Na useful to differentiate) •RRT instituted for the usual indications –CRRT usually tolerated better than intermittent hemodialysis META BOLIC A BNORMA LITIES •Respiratory and metabolic alkalosis early –Treating primary respiratory alkalosis not indicated •Metabolic acidosis (lactate) and respiratory alkalosis later •Hyponatremia –Avoid and treat rapidly as this can increase ICP –ALF patients likely less susceptible to osmotic demyelination so more rapid correction of hyponatremia usually well tolerated •Hypophosphatemia •Hypokalemia NUTRITION IN A LF •Patients with ALF are hypercatabolic –This potentially worsens their immunodeficiency •Attempts to provide nutritional support is a priority –Enteral route preferred –35-40 Kcal/Kg/day and 0.5-1 gm protein/Kg/day are goals –Lipids can be a good source of calories with less volume –Blood glucose levels should be monitored •Hypoglycemia increases mortality •Hyperglycemia can increase ICP –Evidence for improved outcomes with branched chain amino acids is lacking –Monitor volume MECHA NICA L V ENTILA TION IN A LF •Intubate for usual indications –Hypoxemia, hypercarbia, airway compromise due to encephalopathy •Use caution during intubation to avoid increasing ICP –Adequate sedation and consider lidocaine (1.5 mg/Kg) use •Ventilate in usual fashion –Low tidal volume ventilation (6cc/Kg) but monitor pCO2 as elevated pCO2 will increase ICP –Controversy concerning risks of PEEP •High PEEP might elevate ICP •High PEEP might decrease hepatic blood flow ENCEPA LOPA THY GRA DES •Grade I - euphoric or depresed, slurred speech, mild confusion, disturbed sleep; +/- asterixis •Grade II - lethargic, moderately confused; + asterixis •Grade III - marked confusion, lethargic but arousable, incoherent; + asterixis •Grade IV - coma; -asterixis KING’S COLLEGE CRITERIA • Acetaminophen • Non-acetaminophen – INR > 6.5 – pH < 7.3 - or – Grade III or IV encephalopathy, – INR > 6.5 – Creatinine > 3.4 mg/dl - OR - – Any of the 3: • Age < 10 or > 40 years • Acute/subacute presentation • Total bilirubin > 17.6 mg/dl • Unfavorable cause (halothane, idiosyncratic drug, non-A, non-B hepatitis) SCORING SY STEMS FOR TRA NSPLA NTA TION CLICHY CRITERIA (Europe) •Grade III or IV encephalopathy •Factor V < 20% and patient < 30 years old •Factor V < 30% and patient > 30 years old [...]... COLLEGE CRITERIA • Acetaminophen • Non-acetaminophen – INR > 6.5 – pH < 7.3 - or – Grade III or IV encephalopathy, – INR > 6.5 – Creatinine > 3.4 mg/dl - OR - – Any of the 3: • Age < 10 or > 40 years • Acute/ subacute presentation • Total bilirubin > 17.6 mg/dl • Unfavorable cause (halothane, idiosyncratic drug, non-A, non-B hepatitis) SCORING SY STEMS FOR TRA NSPLA NTA TION CLICHY CRITERIA (Europe) •Grade... antibiotics recommended if: –Surveillance cultures with significant growth –Sudden worsening of neurological or renal function –New signs of SIRS –Hypotension not responsive to fluids –If candidate for urgent liver transplant •Antibiotic choice guided by cultures (if positive) and by usual considerations (hospital antibiogram) –Remember frequency of infection with fungal species SEPSIS - 3 Treatment for infection