PARACETOMOL OVERDOSE: PARACETOMOL OVERDOSE PowerPoint Presentation: 1893: Paracetamol was Discovered 500mg Paracetamol tablets introduced to the UK 1956 1963 Paracetamol Introduced as an over the counter medicine Paracetamol: A History 1948: Brodie and Axelrod discover Paracetomol as a Urinary metabolite ‘Happy 100th Birthday’ Paracetamol Combinations: Paracetamol Combinations Codeine Dihydrocodeine Dextropropoxyphene Oral Decongestants PowerPoint Presentation: PARACETAMOL ~ FIGURES Reduction in Mortality Figures from 1999-2000 Reduction on mortality is in part due to reduction on pack size Paracetomol is used by 30 million people in the UK every year 1 in 10 liver transplants in children is due to paracetamol toxicity there are 30000 admissions to hospital every year for paracetamol overdose 1000 patients are on the waiting list for heart, liver and lung transplant PowerPoint Presentation: Absorption of Paracetamol at 1- 2 hours Absorption and Distribution complete by 4 hours CYTOCHROME P450 OXIDATIVE PATHWAY PARACETOMOL NABPQI Conjugation with Glutothionine Low Dose High dose Binding to Liver Proteins Peroxidation of Lipid Membrane 1st pass metabolism via Gut Paracetomol Metabolism and Toxicity Organs Affected: Organs Affected Liver Kidney Heart Pancreas Organs which contain P450 Cytochrome System At Risk Patients: At Risk Patients Induction of P450 Enzymes - Drugs - Alcohol Depletion of Glutothionine Systemic Effects of Overdose: Systemic Effects of Overdose HEPATOTOXICITY Renal Toxicity Metabolic Acidosis Cardiac Problems PowerPoint Presentation: Liver Histology PowerPoint Presentation: Macroscopic Pathology - Paracetomol Overdose PowerPoint Presentation: Normal Liver Histology CENTRAL VEIN BILE CANANICULUS BILE DUCT PowerPoint Presentation: Histological Injury with Paracetamol There is extensive hepatocyte necrosis seen here in a case of acetaminophen overdose. The hepatocytes at the left are dead, and those at the right are dying. PowerPoint Presentation: Massive Centrilobular Necrosis of the Liver Large portions of the lobule are lost and only small groups of periportal liver cells are preserved Clinical Presentation: Clinical Presentation 1. Stage I (Day 1) anorexia, lethargy, malaise, nausea & vomiting, pallor 2. Stage II (Day 2) Stage I symptoms disappear hepatic necrosis begins: abdominal pain and tenderness, hepatomegaly 3. Stage III (Days 3-4) Stage I symptoms reappear hepatic necrosis peaks: jaundice, encephalopathy, acute renal failure, bleeding, hypoglycemia 4. Stage IV (after Day 4) resolution of symptoms and hepatic dysfunction INVESTIGATIONS: INVESTIGATIONS Plasma Paracetamol Levels FBC Coagulation Studies U+E Blood Glucose LFT’s Determination of Risk: Determination of Risk Late Presentation Prognostic Indicators Rising PT between day 3 and 4 PT > 100 secs Associated Renal Failure Significant Acidosis Hepatic Encephalopathy PowerPoint Presentation: Suspected Paracetamol Overdose < 16 hours from the ingestion >=16hours from ingestion time or time of ingestion uncertain or staggered overdose Take blood for paracetamol level minimum 4 hours from ingestion (if >4 hours from ingestion and >150mg/kg taken, commence NAC immediately while awaiting level Below treatment line Above Treatment Line Commence NAC infusion Stop NAC( If already started) Discharge when seen Psych. Take blood for INR/LFT/U+E’s/Clotting/Glucose minimum 24 hours from approximate time of ingestion. INR>1.2 or ALT>45 NORMAL Continue NAC: Further Management Algorithm 1. N.B High Risk Patients Ascertain High Risk PowerPoint Presentation: FURTHER MANAGEMENT OF PARACETOMOL OVERDOSE Following abnormal LFT/ INR Give IV 5% dextrose to maintain urine output >100ml per hour Insert urinary catheter if necessary Monitor blood glucose 4 hourly Check ABGs/U+E’s/Clotting/INR 12 hourly INR rising further INR falling or creatinine rising Renal function stable or pH <7.3 pH >7.3 Consider transfer to ITU depending on advice from hepatologists Continue to monitor INR Continue NAC at 16 hourly until INR<1.5 Discharge when psychiatrically fit Treatment of Hepatotoxicity: Treatment of Hepatotoxicity Poor Prognostic Indicators - Referral to Liver Unit Rising PT between day 3 and 4 PT > 100 secs Associated Renal Failure Significant Acidosis Hepatic Encephalopathy All Patients with Acute Hepatotoxicity should Receive NAC Other Problems to Treat: Other Problems to Treat Acute Renal Failure Hypoglycaemia Hepatic Encephalopathy Prognosis: Prognosis Prognostic Indicators 0Treatment within 8 hours Patients who present at > 8hours Mortality of < 10 % in those with Hepatotoxicity Overall Mortality is < 0.5% No Long Term Follow up with full recovery PowerPoint Presentation: ANY QUESTIONS ?