4 Aetiology of Acute Liver Failure in UK and Europe. UK Europe Paracetamol hepatotoxicity 54.1% 2%Viral % 70%HAV % 4%HBV + HDV 9.0% 45%Other % 3%Indeterminate % 18%Drug reaction 6.9% 14.5%Miscellaneous 3.9% 12
5 Paracetamol as cause of acute liver failure Commonest cause of ALF in UK (>50%)Usually taken with suicidal intent8% due to unintentional overdosing in ‘high risk’ patientsALF occurs in 2-5% of patients who present following paracetamol ODMedian dose 40g (range 5-210g)
6 Paracetamol Nausea/vomiting (after 24hours) RUQ pain/tenderness Liver damage maximal 3-4 days after ingestionEncephalopathy, haemorrhage, hypoglycaemia, sepsis, cerebral oedema and death
12 Case 2 35yr male 60 paracetamol taken 24hours ago O/E vomiting, abdo tenderP 120/min, BP 120/80What else do you want to know?What are you going to do?
13 Case 2 Blood glucose ABG, lactate PT U&Es, LFTs, Amylase Paracetamol levelUrine outputOther medication?Suicidal intent?, family support?
14 Case 2PT 24Bili 30, ALP 130, ALT 9000, Alb 40Na 145, K 3.0, Ur 19, Cr 190Glu 3.5pH 7.38, O2 13, CO2 3, HCO3 12Lactate 3.0
15 Management of paracetamol overdose Monitor paracetamol levels > 4 hours after ingestionIf below treatment line, repeat levelGive NAC if over treatment line?high risk lineTreatment lines not valid for staggered ODIf in doubt, give NAC! Don’t wait!
16 Monitor PT, creatinine, amylase, lactate, pH, LFTs daily If abnormal, PT twice dailyiv fluids – patients will be dry!Seek precipitating factors for overdose
17 Other managementIf features of liver failure develop, continue N-acetylcysteinePPICareful monitoring of fluid balance (CVP/U.O), haemodynamicsBroad spectrum antibiotics (anti-fungals)Monitor and correct electrolytes (Ca, Mg, PO4)Monitor glucoseLook for signs of confusion
18 Acute liver failure Support CNS Respiration Circulation Renal CoagulationInfectionMetabolism
19 Indications for liver transplant pH < 7.3lactate > 3.2PT > 180creatinine > 300+PT >100 +grade 3 or 4 coma prognosis very poor
21 Alcohol Withdrawal Signs and symptoms range widely tremulousness (shakes), insomnia, anxiety, hyperreflexia, mild autonomic hyperactivity, and GI upsetDelerium Tremens usually > 48 hours after cessation of drinkingDisorientation, agitation, and hallucinations; with severe autonomic hyperactivity (tremulousness, tachycardia, tachypnoea, hyperthermia)HallucinationsPersecutory, auditory, or (most commonly) visual and tactile hallucinationsSeizures
22 History Physical symptoms Moods/state of mind Morning drinking habits Degree (and longevity) of drinkingAny suggestion of withdrawal symptoms
24 CAGE questionnaireHave you ever felt you should cut down on your drinking?Have people annoyed you by criticising your drinking?Have you ever felt bad or guilty about your drinking?Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (eye-opener)?
25 Chlordiazepoxide Benzodiazepine Controls symptoms of alcohol withdrawalPatients admitting to >10u per day are likely to require treatmentDose/level and length of treatment will depend on severity of dependence and on patient factors
27 Adverse effects Drowsiness, sedation Unsteadiness, ataxia Confusion Dizziness, vertigo, syncopeUsually dose relatedMore common in elderly or in patients with liver disease
28 Wernicke’s encephalopathy Thiamine deficiencyClassic triad of encephalopathy, ataxia, and ophthalmoplegia (10%)Consider diagnosis:long-term alcohol abuse or malnutritionacute confusion, decreased conscious level, ataxia, ophthalmoplegia, memory disturbance, hypothermia with hypotension, and delirium tremens
29 Wernicke’s encephalopathy Beware of administering dextrose in a thiamine-deficient stateExacerbates the process of cell death by providing more substrate for biochemical pathways that lack sufficient amounts of coenzymesStart thiamine concurrently or priorIv pabrinex (vitamins B + C)2 pairs tds for 3 daysThiamine 100mg tdsVitamin B co forte 2 tabs daily
30 Korsakoff psychosisCharacterized by retrograde amnesia (inability to recall information),Inability to assimilate new informationDecreased spontaneity and initiativeConfabulation.Other manifestations of thiamine deficiencyWet beri beriNutritional polyneuropathy
31 Chronic liver disease What pain relief can I give? Diuretics The confused liver patientWhat do I doRole of sedatives?
32 Case You are called to see the following man who is c/o abdominal pain 48yr man, alcoholic liver diseaseBili 150, Alb 30, PT 16Ascites
33 What concerns me? What is the cause of his pain? Renal function? Has SBP been excluded?Would a paracentesis relieve his pain?Renal function?Varices?Encephalopathy?
34 Consider the analgesic options Paracetamol?NSAIDS?Codeine?Stronger Opiates?
35 Analgesia in chronic liver disease ParacetamolSafe in small quantitiesProbably the safest analgesic for these patients!!!!Reduce maximum daily intake and avoid regular dosing for >5 days)ie 500mg – 1g qds prn (max 2g daily)
36 NSAIDs Codeine/Tramadol NEVER! Variceal haemorhage, renal failure Risk of encephalopathyNeed to balance risk versus need for analgesiaCo-prescribe lactuloseUse lower doses, avoid regular dosing
37 Stronger opiatesNever without consultation with consultant in charge of patientHigh risk of over-sedation and encephalopathyEffects may be delayed/prolonged
38 Diuretics Why do we prescribe? To control ascites? Why do we need to control ascites?Patient comfort!(Rarely respiratory distress)REMEMBER:Ascites does not kill patients, but diuretics can!
39 Which diuretic and why? Spironolactone Dose is 100 -200 mg once daily Liver disease is a cause of secondary hyperaldosteronismAldosterone inhibitorDose is mg once dailyNo need to split dosesContraindications?Hyperkalaemia, hyponatraemiaRenal impairmentUse cautiously and monitor closely!
40 The Confused Liver Patient Consider:EncephalopathyGrades 1-4 (daytime somnolence, agitation, liver flap, decreased conscious level, coma)Alcohol withdrawalSub-dural haematoma or other neurological event
41 Encephalopathy - causes Drugs (including alcohol)Check drug chart for night sedation, opiates, chlordiazepoxideElectrolyte abnormalitiesLow sodium, low potassium, dehydrationHypoglycaemiaSepsis (including SBP)Constipation (Give lactulose + enemas)GI bleeding
43 Take home points (Paracetamol OD) Para OD = ParvolexPT is most sensitive indicator of liver injuryCareful attention to fluid balanceEarly discussion!
44 Take home points (Alcohol withdrawal) Take a proper alcohol historyThink about alcohol withdrawal before symptoms developMonitor patient daily and review dosage of chlordiazepoxide!All dependent patients must receive Pabrinex and vitamin B.
45 Take home points (Analgesia in CLD) Paracetamol is safe in small quantities and should be first choiceCaution with other groupsDiureticsThink carefully before prescribingNo urgency in this situationMonitor electrolytes and renal function
46 Confused liver patients Management of encephalopathy is usually straightforward if you remember the checklist!Check for sepsisLactuloseFluidsReplace electrolytesCheck drug chartDo not sedate them!!