These guidelines were devised for use in the UK. Conditions and practices may vary outside the UK, for example availability and rapidity of laboratory test results, or availability and use of antidote medication or the presence of variations of paracetamol preparations not available in the UK. Therefore these guidelines may not be appropriate for countries outside the UK and Ireland.
Please note, in the USA paracetamol is known as acetaminophen.
Important Information
Those managing patients with acute paracetamol overdosage should be aware that:
1 These guidelines can only give guidance, cannot cover every eventuality and clinical judgement should always prevail. Patients can be unreliable at recalling the time of an overdose and the number of tablets taken. Some will have taken only paracetamol, some will have taken combination tablets containing paracetamol and other ingredients such as codeine or dextropropoxyphene, while others will have taken several different types of tablets, including those containing paracetamol. Some may have taken several different preparations that all contain paracetamol, and history is therefore only an indication of dose. If in ANY doubt check a 4 hour blood paracetamol concentration (see 4 below). These guidelines are intended solely for the management of the paracetamol element of an overdose. Details of any other substances taken must be obtained and treated appropriately.
2 Hepatocellular necrosis is the major toxic effect of paracetamol poisoning. Biochemical evidence of maximal damage may not be attained until 72-96 hours after ingestion of the overdose. Severe liver damage in the context of paracetamol poisoning has been defined as a peak plasma alanine aminotransferase (ALT) activity exceeding 1000 iu/L. Most patients who are clinically unwell have peak ALT activities of several thousand units per litre. For those who do not have ready access to ALTs, aspartate transaminase (AST) may be substituted throughout these guidelines. An AST exceeding 1000 iu/L indicates severe liver damage. In clinical practice a more accurate test for assessing prognosis is the prothrombin time (INR). Acute renal tubular damage and necrosis may occur, usually in association with hepatocellular necrosis, but rarely in the absence of major liver damage.
3 Any patient should be considered at risk of severe liver damage if he/she has ingested more than 150mg paracetamol/kg body weight, or, in adults, more than 12g (24 standard tablets), whichever is the smaller.
4 Early assessment of the risk of liver damage requires urgent measurement of the patient's plasma paracetamol concentration and blood should be taken for this purpose as soon as possible after 4 hours or more have elapsed since the overdose. Plasma concentrations taken within 4 hours should not be requested as they cannot reliably be interpreted because of the possibility of continuing absorption and distribution of the drug.
5 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.
Patients sometimes give inaccurate histories. If there is doubt about the timing or the need for treatment, treat.6 The treatment lines on the accompanying graph are estimates of risk based on the best available clinical evidence. They are critically dependent upon the accuracy of the history with respect to the time of overdose ingestion. Beyond 15 hours, the risk estimates are less reliable and clinical judgement becomes more important in management.
7 Staggered overdose. In patients who have taken several overdoses of paracetamol over a short period of time, the plasma paracetamol concentration will be more difficult to interpret as the treatment graph relates to a single acute ingestion. Such patients should be considered as at serious risk and considered for treatment with N-acetylcysteine (NAC). They can be discharged after NAC treatment or 24 hours from the last paracetamol dose provided they are asymptomatic and the International Normalised Ratio (INR), plasma creatinine and ALT are normal.
8 Enhanced risk. Patients who regularly consume alcohol in excess of currently recommended limits (particularly those who are malnourished), those who regularly take enzyme-inducing drugs (e.g. carbamazepine, phenytoin, phenobarbitone, primidone, St John's Wort and rifampicin) and those with conditions causing glutathione depletion (e.g. malnutrition, eating disorders, malabsorption states and HIV infection) may be at risk of liver damage from lower plasma paracetamol concentrations than others. The plasma paracetamol concentration for such patients should be considered in relation to treatment line B on the graph.
9 Patients who present 15 hours or longer after ingestion are more difficult to treat successfully with an antidote and are at greater risk of developing serious liver damage. Measures to assist in determining the prognosis include the INR, plasma bicarbonate, venous blood acid/base balance, plasma creatinine and liver function tests.
10 All patients taking a deliberate paracetamol overdose should be considered for social and/or psychological assessment prior to discharge.
11 For further advice for hospital staff in the UK & Ireland, for example on staggered overdoses, severe liver damage, persisting abnormalities of liver function, adverse reactions to NAC or any concerns regarding management, contact the National Poisons Information Service (NPIS):
NPIS (UK) 0870 600 6266
or
Dublin 01 837 9964 or 01 809 2566
NPIS advice on paracetamol overdosage is also available to UK hospital departments and general practitioners on TOXBASE at http://www.TOXBASE.org
0 comments:
Post a Comment