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| Methanol TOXBASEŽ - Updated 08/2005
Solvent, antifreeze, windscreen wash
Methyl alcohol, carbinol, wood alcohol, wood spirit CAS 67-56-1 UN 1230
Toxic by ingestion, inhalation and skin absorption. Ingestion of 10 mL of pure methanol has resulted in blindness, 30 mL has resulted in death. The UK exposure limit (short-term) is 250 ppm. Note that model engine fuels that contain methanol may also contain nitromethane. This may interfere with the Jaffe Reaction assay for creatinine, resulting in a falsely high creatinine levels (Booth et al., 1999, Mullins and Hammett-Stabler, 1998, DeLeacy et al. 1989). Nitromethane does not interfere with measurement of creatinine through enzymatic assays. Note and contain toxicologically insignificant amounts of methanol - see appropriate TOXBASE entries Methanol - features and management Updated 3/2005
Ataxia, drowsiness, dysarthria, nystagmus may occur within 30 minutes of ingestion, followed by a latent period of 12-24 hours before metabolic toxicity becomes apparent. Poor prognostic features include convulsions, coma, shock, persistent acidosis, bradycardia and renal failure. Central Nervous System:Headache, confusion and vertigo occur with mild to moderate toxicity. Convulsions and coma are seen in severe toxicity Extrapyramidal features may develop in patients who survive severe toxicity. This is due to necrosis in the putamen and subcortical white matter, which can often be shown by MRI scan. Visual:Common features include blurred vision, with the appearance of a " snow field", and photophobia. Optic disc and retinal oedema occur with diminished pupillary light response. The extent of these features appears to correlate with the severity of toxicity. Patients may be left with persistent visual impairment including optic atrophy, diminished visual acuity, loss of colour vision, central scotoma or blindness. Blindness is usually permanent, but in some cases a degree of recovery may occur over a period of months. Gastrointestinal:Common features include nausea, vomiting and abdominal pain. Acute pancreatitis can occur and a small, transient rise in liver transaminases may be seen. Metabolic: A severe metabolic acidosis with an increased anion and osmolal gap is usually seen. Renal failure may develop in severe cases.
1. Ensure clear airway and adequate ventilation, particularly if there is depression of conscious level. 2. Consider gastric aspiration if the patient presents within 1 hour of ingestion. Charcoal is of no use since it does not adsorb methanol. 3. Observe for at least 12 hours after ingestion. 4. Monitor pulse, blood pressure, respiratory rate, cardiac rhythm and urine output. 5. Measure urea and electrolytes, liver function tests, glucose, albumin and osmolality. Arterial blood gases should be performed in all cases of suspected overdose. Measurement of amylase is indicated if patients have severe abdominal pain. 6. Methanol concentration should be measured in all cases of overdose. This assay is not readily available and you should discuss this with a local biochemist or with the National Poisons Information Service 0870 600 6266 (in Ireland NPIC (01) 809 2566).If methanol concentration is not available the diagnosis should be considered if there is a history of suspected ingestion and a severe metabolic acidosis with a large osmolal gap and high anion gap. These are not, however, specific to methanol ingestion and can occur with ethylene glycol ingestion or with other clinical conditions (diabetic or alcoholic ketoacidosis, renal failure, multi-organ failure etc). Absence of an elevated osmolal gap does not exclude serious poisoning since the osmolal gap begins to fall once methanol is metabolised and may therefore not be elevated in the later stages of poisoning. Methanol metabolism to formate, and to a lesser extent lactate, contribute to the high anion gap. 7. If arterial pH is less than 7.3 (hydrogen ion concentration >50 nmol/L) give 250 mL of 1.26% sodium bicarbonate i.v. in an adult and repeat as necessary ( 250 mL of 1.26% contains 37.5 mmol sodium bicarbonate). Alternatively 50 mL of 8.4% contains 50 mmol sodium bicarbonate but caution is advised when given by a peripheral venous line as it is irritant to veins and can cause skin necrosis in cases of extravasation. Large amounts of bicarbonate may be required to correct the metabolic acidosis. Monitor electrolytes regularly since there is a risk of hypernatraemia.
Early treatment with an antidote is advised if the patient has ingested a significant amount of methanol since the onset of clinical features may be delayed. 8. There are two potential antidotes for managing this poisoning. Ethanol and fomepizole both act by inhibiting alcohol dehydrogenase, the enzyme responsible for metabolising ethylene glycol to glycolaldehyde. Ethanol is widely available and relatively cheap. The majority of experience in managing this poisoning is using ethanol. A new antidote, fomepizole, has recently been introduced in the UK. Clinical evidence of the effectiveness of fomepizole is accruing, but its exact place in management is uncertain. It is not appropriate for fomepizole to be widely stocked by individual hospitals, but supplies are available from regional centres or the NPIS ( 0870 600 6266). Fomepizole should only be used after discussion with the National Poisons Information Service 0870 600 6266 (in Ireland NPIC (01) 809 2566). Details of antidotes and doses are given below.Indications for treatment with an antidote include:
OR
9. Give folinic acid 1mg/kg intravenously (up to a maximum of 50 mg) 6 hourly for 48 hours. 10. Control convulsions with intravenous diazepam (0.1-0.3 mg/kg body
weight) or lorazepam (4 mg). 12. Severe poisoning should be treated by haemodialysis. Haemofiltration is less effective than dialysis but high flow haemofiltration should be considered if haemodialysis is unavailable. Peritoneal dialysis is unlikely to be effective in view of low clearances of methanol by this route. Indications for haemodialysis include:
Dialysis should be continued until:
Updated 3/2005 Fomepizole is a competitive inhibitor of alcohol dehydrogenase.
Licenced for use in ethylene glycol poisoning. There is emerging evidence of its benefit in the management of methanol poisoning but there is still limited clinical information of its use. Fomepizole may be preferable to the use of ethanol as an antidote in
the following situations: 2. Co-ingestion of other drugs that may cause CNS depression (e.g. opioids, sedatives, antidepressants, anticonvulsants, antihistamines, hypnotics, muscle relaxants) 3. Patients taking disulfiram or metronidazole 4. Hepatic disease 5. Pregnancy, particularly during the first trimester when ethanol is contra-indicated . However, there are no data to support this. 6. Children - less likely to develop hypoglycaemia associated with use of ethanol 7. Inability of local laboratory to measure repeated ethanol concentrations 8. Lack of local availability of a facility to monitor the patient closely such as intensive care or high dependency unit.
Formerly produced as Antizol by IDIS Ltd World medicines. Currently produced by Orphan in France. Two suppliers have so far been identified: Durbin plc, 240 Northolt Road, South Harrow, Middlesex HA2 8TL Tel: 020 8869 6500 Fax: 020 8869 6582. The existing stock has a shelf-life of 12 months and Durbin are prepared to replace any unused stock at the end of the expiry date. Laboratoire Isotec, 10 Avenue Ampere, Montigny le Bretonneux BP 220 78051, St Quentin en Yvelines, Cedex-France.
Supplies are available from some (Belfast, Birmingham, Cardiff, Edinburgh 0870 600 6266). Discuss with the NPIS before use (0870 600 6266).
Fomepizole 5 mg/mL in a 5 x 20 mL pack If solid, the solution should be liquified by running the vial under warm water. Aseptically draw the appropriate dose from the vial with a syringe and inject into at least 100 mL of sterile sodium chloride injection or 5% dextrose injection. Mix well.
The safety and effectiveness in children and during pregnancy has not been established.
All doses should be administered as slow intravenous infusion for 30 minutes Loading dose: 15 mg/kg IV diluted in 100mls saline or dextrose over 30 minutes
Fomepizole dosing during haemodialysis
Fomepizole should be continued until :
Hypersensitivity to fomepizole or other pyrazoles.
The rate of elimination of ethanol is reduced by approximately 40% by fomepizole therapeutic doses. Ethanol decrease the rate of elimination of fomepizole by approximately 50%. drugs that affect the P-450 system may alter blood levels of fomepizole.
Fomepizole is generally well tolerated with few adverse effects. During clinical trials the most commonly reported features were nausea, dizziness and headaches. Less common features included vomiting, diarrhoea, tachycardia, hypotension, vertigo, nystagmus, slurred speech, skin rashes, eosinophilia and transient rise in liver transaminases. These effects occurred at doses much greater than the therapeutic dose. Pain and inflammation may occur at the injection site.
No cases reported. Nausea, dizziness and vertigo were noted in healthy volunteers receiving 50 and 100 mg/kg. These effects lasted up to 30 hours in one subject.
Updated 10/05 Ethanol has a much greater affinity for alcohol dehydrogenase than
ethylene glycol or methanol, therefore competitively inhibits the
metabolism.
Ethanol should be used with caution in the following situations: 1. Patients with depressed conscious level 2. Co-ingestion of other drugs that may cause CNS depression (e.g. opioids, sedatives, antidepressants, anticonvulsants, antihistamines, hypnotics, muscle relaxants) 3. Patients taking disulfiram or metronidazole - may cause hypotension and flushing (in such patients fomepizole may be a better choice) 4. Hepatic disease 5. Pregnancy- the use of alcohol in the first trimester is controversial. Adverse effects on the foetus are unlikely to occur if alcohol is used as an antidote in the second and third trimesters. 6. Children - children are more susceptible to developing hypoglycaemia during treatment with ethanol.
1. Hypoglycaemia, particularly in children and the malnourished patient 2. Clinical features of alcohol intoxication 3. Respiratory and CNS depression 4. Local phlebitis with use of hyperosmolar IV solutions
Give a loading dose of 600-800 mg/kg absolute (100%) ethanol. This can be given in the form of whisky, gin or vodka (40% ethanol) in a dose of 2 mL/kg body weight (about 150 mL spirits for a 70 kg adult). NB If using gin check the ethanol concentration as this may be less than 40% v/v. Proportionally larger doses may be required (e.g. 35% v/v gin: dose = 40/35 or 1.14 x 2 mL/kg = 2.25 mL/kg). Alternatively, give a loading dose 7.5 ml/kg of 10% ethanol in water, IV over 30 minutes. Solutions stronger than 10% should NOT be used for parenteral administration unless appropriately diluted. Dextrose is the preferred diluent. 10% solutions are hyperosmolar and irritant to the veins and are best given via a central venous catheter.
Continue with maintenance infusion according to the chart below Monitoring Blood ethanol concentrations should be monitored every 1-2 hours initially until a concentration of 1-1.5 g/L (100-150 mg/dL) is reached and every 2-4 hours thereafter. Ethanol concentration should be repeated 1 hour after any change of rate. Patients treated
with ethanol require close monitoring preferably in a critical care area
because of the risk of CNS and respiratory depression.
Ethanol doses
Ethanol can be added to peritoneal dialysate fluid at a concentration of 1-2 g/L of dialysate. Duration of treatment Ethanol should be continued until:
OR Updated 5/2002
This product is expected to be pH neutral but may be irritating to the eyes causing an immediate stinging and burning sensation with lachrymation.
If symptomatic, immediately irrigate the affected eye thoroughly with water or 0.9% saline for at least 10-15 minutes. If symptoms persist check for corneal damage by instillation of fluorescein and refer for ophthalmological assessment if necessary. End |
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