DR J HARTY / DR CM RITCHIE / DR M GIBBONS

Transcription

1 CLINICAL GUIDELINES ID TAG Title: Author: Speciality / Division: Directorate: Paracetamol Poisoning DR J HARTY / DR CM RITCHIE / DR M GIBBONS Medicine Acute Date Uploaded: 16 th September 2014 Review Date 1 st July 2016 Clinical Guideline ID CG0015

2 PARACETAMOL POISONING MANAGEMENT OF OVERDOSE Doctors managing acute paracetamol overdose should be aware that: Paracetamol in acute overdose is hepatotoxic and nephrotoxic, but toxicity takes 3-4 days to reach a peak. Any patient should be considered a risk of severe liver damage if he/she has ingested more than 150mg paracetamol/kg body weight or 12 g or more in total. Severe liver damage is defined as persisting acidosis despite resuscitation, INR > 3.0 or the presence of encephalopathy. Only 60% of untreated patients whose paracetamol levels lie above the treatment line (see Figure 1) will develop severe liver damage. Patients who consume alcohol in excess or who regularly take drugs which induce liver micros omal enzymes (carbamazepine, phenytoin, phenobarbitone, primidone and rifampicin) are at risk from lower plasma paracetamol concentrations than those whose enzymes are not induced. Patients who present 12 hours or more after ingestion tend to be more severely poisoned and are at greater risk of serious liver damage. The time interval since ingestion is critical in assessing whether treatment is required, but is often difficult to establish. Detailed questioning of the patient and others is necessary. If there is any doubt about the timing or the need for treatment, treat. If there is a history of a staggered overdose/ ingestion then treatment should be initiated irrespective of levels. Early assessment of the risk of liver damage requires urgent measurement of the patient s plasma paracetamol concentration. Plasma concentrations taken within 4 hours of ingestion cannot be reliably interpreted because of the possibility of continued drug absorption and distribution. Patients with conditions causing glutathione depletion (malnutrition, AIDS) may also be at risk from lower concentrations. Intravenous N-acetylcysteine (NAC, acetylcysteine) is an effective antidote for the management of paracetamol overdose.

3 MANAGEMENT OF PATIENTS WHO PRESENT WITHIN 8 HOURS OF INGESTION Consider emptying the stomach or giving activated charcoal if more than 150 mg/kg paracetamol has been taken. These measures are of little value after 4 hours. Take blood for paracetamol estimation after 4 hours. Take appropriate action as defined by the treatment line (see Figure 1). If paracetamol level is not available within 8 hours of ingestion and 12 g or more have been take n, start treatment. Provided the antidote is started within 8 hours of ingestion, patients may be discharged after treatment is completed. There is no merit in keeping then in hospital simply to monitor liver function. Patients should, however, be advised to return if vomiting or abdominal pain recur. Give a discharge note to the patient with instructions and also a letter to the GP. Check the INR and serum creatinine before discharge.

4 MANAGEMENT OF PATIENTS WHO PRESENT 8-15 HOURS AFTER INGESTION Urgent action is required because the efficacy of antidotes declines progressively from 8 hours after ingestion. Give N-acetylcysteine without waiting for the paracetamol concentration measurement if more than 150 mg/kg body weight or 12 g or more has been ingested or if the history is vague or if the overdose / ingestion has been staggered. Take blood for estimation of plasma paracetamol concentration for assessment of the risk of the patient developing severe liver damage using the treatment line (see Figure 1). If the patient is not at risk; Stop antidote if level is well below the treatment line (see Figure 1). Patient can be discharged after the infusion if the INR and creatinine are normal. If abnormal, further monitoring is required. Vitamin K should be given if INR is increased but fresh frozen plasma and clotting factors are only indicated for active bleeding. MANAGEMENT OF PATIENTS WHO PRESENT HOURS AFTER INGESTION Measure the paracetamol level on admission. Start all patients on N-acetylcysteine. The infusion can be stopped if: (a) Patient is asymptomatic and (b) The INR and plasma creatinine are normal and (c) The plasma paracetamol is less than 10 mg/1 (0.07 mmol/l) 24 hours after ingestion provided the time of ingestion is known and this has not been a staggered overdose. Further monitoring is required if (a), (b) or (c) do not apply. INR and creatinine should be measured before discharge whether or not they have received N- acetylcysteine. MANAGEMENT OF PATIENTS WHO PRESENT LONGER THAN 24 HOURS AFTER INGESTION Management is controversial. Check INR, plasma creatinine and arterial ph. Discuss case with a specialist liver unit, after discussion with Consultant Physician on-call. The following abnormalities indicating severe liver damage will be taken into account in decisions regarding the need for transfer to a specialist unit:- (a) INR > 3.0

5 (b)creatinine is elevated. (c) Acidosis is present. (d) Encephalopathy or hypotension is present. (e) There is pre-existing liver disease. EXCESSIVE CHRONIC INGESTION Excessive chronic ingestion could be defined as ingestion of greater than the maximum daily dose of 4 g, but less than 7.5 g at any one time, for 24 hours or greater. There are no conclusive data on the proper evaluation and management of patients chronically Ingesting paracetamol in excess of the recommended doses. As there are no established guidelines for determining the risk of hepatotoxicity in such patients, factors that should be considered are: (a) The number and timing of doses. (b) The amount ingested in each dose and the total overall dose. (c) Regular excess alcohol consumption or patient on enzyme-inducing drugs (eg carbamazepine, phenobarbitone, phenytoin and rifampicin). If paracetamol levels are below the level of detection and liver enzyme and or PT are not elevated, further treatment is unnecessary. If liver function tests are abnormal and paracetamol overdose is suspected, consider treatment with N-acetylcysteine. DOSAGES AND ROUTES OF ADMINISTRATION ACTIVATED CHARCOAL The adult oral dose of activated charcoal is g and is usually given with 20 ml lactulose to prevent constipation. N-ACETYLCYSTEINE N-acetylcysteine (Parvolex ) is given intravenously as follows: 150 mg/kg in 200 ml 5% dextrose over 60 minutes. Followed by: 50 mg/kg in 500 ml 5% dextrose over 4 hours. Then 100 /kg in 1000 ml 5% dextrose over 16 hours. A ceiling weight of 110 kg should be used when calculating the dosage for obese patients. DO NOT calculate an individual dose. Weigh the patient and dose them according to their dosing band in the following table.

6 Acetylcysteine (Parvolex ) administration in adults & children >12 years and over 40Kg. Dose of acetylcysteine to be administered via IV infusion: Prescribed dose must be prescribed in grams Volume of acetylcysteine to be added to infusion fluid & infusion rate has also been detailed below Regimen THREE BAGS TO BE GIVEN IN CONSECUTIVE ORDER 1 st Bag 2 nd Bag 3 rd Bag 150mg/kg acetylcysteine 50mg/kg acetylcysteine 100mg/kg acetylcysteine Duration of infusion Infusion fluid Patient weight (kg) 1 hour 4 hours 16 hours 200ml 5% glucose or sodium chloride 0.9%* Dose Ampoule Infusion volume rate (ml) (ml/hour) 500ml 5% glucose or sodium chloride 0.9%* Dose Ampoule Infusion volume rate (ml) (ml/hour) 1000ml 5% glucose or sodium chloride 0.9%* Dose Ampoule Infusion volume rate (ml) (ml/hour) g g g g g g g g g g g g g g g g g g g g g / maximum dosage 16.6g g g *In adolescents ( 16) weighing < 40kg there is a significant risk of inducing hyponatremia. 0.9% saline and a more concentrated solution should be made up. Each Parvolex ampoule = 200mg/ml Acetylcysteine

7 Children and Adolescents ( 16) In adolescents weighting < 40kg there is a significant risk of inducing hyponatremia. 0.9% saline and a more concentrated solution should be made up. The full course of treatment with N-acetylcysteine comprises 3 consecutive intravenous infusions: First infusion Initial loading dose of 150 mg/kg infused over 1 hour (150 mg/kg/hr). Given as a 50 mg/ml solution at a rate of 3 ml/kg/hr. Second Infusion Dose: 50 mg/kg infused over 4 hours (12.5 mg/kg/hr). Given as a 6.25 mg/ml solution at a rate of 2 ml/kg/hr. Third Infusion Dose: 100 mg/kg infused over 16 hours (6.25 mg/kg/hr). Given as a 6.25 mg/ml solution at a rate of 1 ml/kg/hr. Preparation of the solution NB. See a full worked example in appendix one. Dose 1 Prepare a 50 mg/ml solution. Dilute each 10ml ampoule of N-acetylcysteine (200mg/ml) with 30 ml glucose 5% or sodium chloride 0.9% to give a total volume of 40 ml. Dose 2 Prepare a 6.25 mg/ml solution. Dilute each 10 ml ampoule of N-acetylcysteine (200 mg/ml) with 310 ml glucose 5% or sodium chloride 0.9% to give a total volume of 320 ml. Dose 3 Prepare a 6.25 mg/ml solution. Dilute each 10 ml ampoule of N-acetylcysteine (200 mg/ml) with 310 ml glucose 5% or sodium chloride 0.9% to give a total volume of 320 ml. Administration Weigh the child. DO NOT calculate an individual dose; dose the patient according to their dosing band in the following table. Determine the total volume of solution to be infused (infusion fluid + N-acetylcysteine prepared as above) into the child from the table. A separate volume will be required for each of the three infusion periods. For example for a child weighing 12 kg, 38mL of solution is required for Dose 1, 100mL for Dose 2 and 208mL for Dose 3. For further details see Infuse intravenously according to the weight of the child (see table). For example for a child weighing 12 kg, Dose 1 is infused at 38ml/hr over 60 minutes, Dose 2 would be infused at 25ml/hr and Dose 3 at 13ml/hr. Doses should be administered sequentially with no break between the doses.

8 Acetylcysteine (Parvolex ) administration in children <12 years and adults under 40Kg. Dose of acetylcysteine to be administered via IV infusion: Prescribed dose must be prescribed in milligrams Each ampoule should be diluted as detailed and the correct volume of the resulting solution infused at the rate stated for the patient s weight Regimen THREE BAGS TO BE GIVEN IN CONSECUTIVE ORDER 1 st Bag 2 nd Bag 3 rd Bag Infusion preparation Patient weight (kg) 3ml/kg/hr for 1 hour (150mg/kg) *Dilute each 10ml amp with 30ml infusion fluid = 50mg/ml solution Dose (mg) Total infusion volume (ml) Infusion rate (ml/hr) 2ml/kg/hr for 4 hours (50mg/kg) *Dilute each 10ml amp with 310ml infusion fluid = 6.25mg/ml solution Dose (mg) Total infusion volume (ml) Infusion rate (ml/hr) 1ml/kg/hr for 16 hours (100mg/kg) *Dilute each 10ml amp with 310ml infusion fluid = 6.25mg/ml solution Dose (mg) Total infusion volume (ml) Infusion rate (ml/hr) *In adolescents ( 16) weighing < 40kg there is a significant risk of inducing hyponatremia. 0.9% saline and a more concentrated solution should be made up. Each Parvolex ampoule = 200mg/ml Acetylcysteine

9 N-acetylcysteine may cause adverse effects which may be localised to the area surrounding the infusion site or more generalised and usually occur during the first 30 minutes of administration when large amounts of the antidote are being given rapidly. They include nausea, flushing, itching, erythematomacular rashes, urticaria, angioedema, bronchospasm and rarely, hypotension or hypertension. Infusion of N-acetylcysteine should be stopped and an antihistamine given. Once the adverse effects have settled, infusion can usually be resumed at the lowest infusion rate (100 mg/kg over 16 hours). ADVICE SHOULD BE SOUGHT FROM A SPECIALIST LIVER UNIT IF ANY OF THE FOLLOWING APPLY: The INR is greater than 3.0. There is an elevated creatinine (>200 µmol/l). There is evidence of encephalopathy. Mean arterial blood pressure is < 60 mmhg (following volume resuscitation). There is evidence of metabolic acidosis, ph < 7.3 (following volume resuscitation). FURTHER INTERVENTIONS PRIOR TO TRANSFER TO LIVER UNIT Once decision to transfer has been made patient should be moved to HDU/ITU environment for stabilisation and preparation Grade III (agitation or aggression) or IV (deep coma, decorticate or decerebrate) encephalopathy require elective intubation and ventilation prior to transfer. Avoid sedatives if possible Commence prophylactic PPI Commence prophylactic broad spectrum antibiotic and anti-fungal cover Monitor blood glucose hourly and change iv fluid accordingly Give FFP only if active bleeding or invasive procedure planned (insertion of CVP line not an indication) QUESTIONS THAT A LIVER UNIT ARE LIKELY TO ASK - Arterial ph Creatinine level and recent urine output. INR and or prothrombin time Blood glucose measurements, evidence of hypoglycaemia Any evidence of sepsis (ie temperature and WCC)

10 Level of encephalopathy Fluid status Platelet count ORGANISING TRANSFER See separate Intranet guidelines on Patient Transfer and ECRs ( extracontractual referrals) King s College Hospital telephone and ask to page Liver ITU SpR Disclaimer: Whilst every care has been taken to ensure that the format of this guideline is correct, the Trust can accept no responsibility whatsoever for the actual content of the guideline. DEVELOPED BY: DR CM RITCHIE / DR M GIBBONS UPDATED BY : DR J HARTY / DR CM RITCHIE / DR M GIBBONS UPDATED BY : DR J HARTY / DR U BRADLEY/ AISLING O HAGAN (ED PHARMACIST) JULY REVIEW DATE: JULY 2016

11 APPENDIX ONE. A WORKED EXAMPLE OF ACETYLCYSTEINE TREATMENT IN A 32KG CHILD. First bag 4900mg (4.9 g) is the dose to be administered over one hour. The ready reckoner tells us that we need to run in 98ml of a 50mg/ml solution over one hour I.e. 98ml x 50mg/ml = 4900mg. To make the 50mg/ml solution; The ready reckoner tells us; dilute each 10ml amp of acetylcysteine 200mg/ml (2000mg/10ml) with 30ml infusion fluid. This will give us 2000mg in 40ml = 50mg/ml. But we need 4900mg, therefore dilute 3 amps of acetylcysteine 200mg/ml with 90ml infusion fluid. This will give us 6000mg in 120ml = 50mg/ml. But we only need 4900mg, so if we run in 98ml at a rate of 98ml/hr, this will give us the correct dose of 4900mg. 22ml of our infusion solution will remain at the end of one hour; this can be discarded. Second bag 1625mg (1.625 g) is the dose to be administered over 4 hours. The ready reckoner tells us that we need to run in 260ml of a 6.25mg/ml solution over 4 hours (65ml/hr). I.e. 260ml x 6.25mg/ml = 1625mg. (total dose to be given over 4 hours) To make the 6.25mg/ml solution; The ready reckoner tells us; dilute each 10ml amp of acetylcysteine 200mg/ml (2000mg/10ml) with 310ml infusion fluid. This will give us 2000mg in 320ml = 6.25mg/ml. As we only need 1625mg, one amp will be sufficient. We only need 1625mg from our 2000mg/320ml solution, so if we run in 260ml at a rate of 65ml/hr, this will give us the correct dose of 1625mg in total over the 4 hours. I.e. 6.25mg/ml x 65ml/hr x 4hr = 1625mg. 60ml of our infusion solution will remain at the end of four hours; this can be discarded.

12 Third bag 3300mg (3.3 g) is the dose to be administered over 16 hours. The ready reckoner tells us that we need to run in 528ml of a 6.25mg/ml solution over 16 hours (33ml/hr). I.e. 528ml x 6.25mg/ml = 3300mg. (total dose to be given over 16 hours) To make the 6.25mg/ml solution; The ready reckoner tells us; dilute each 10ml amp of acetylcysteine 200mg/ml (2000mg/10ml) with 310ml infusion fluid. This will give us 2000mg in 320ml = 6.25mg/ml. But we need 3300mg, therefore dilute 2 amps of acetylcysteine 200mg/ml with 620ml infusion fluid. This will give us 4000mg in 640ml = 6.25mg/ml. We only need 3300mg from our 4000mg/640ml solution, so if we run in 528ml at a rate of 33ml/hr, this will give us the correct dose of 3300mg in total over the 16 hours. I.e. 6.25mg/ml x 33ml/hr x 16hr = 3300mg. 112ml of our infusion solution will remain at the end of sixteen hours; this can be discarded.