The reaction is probably mediated by chloroacetaldehyde, one of the breakdown products of the ifosfamide molecule, which has chemical properties similar to acetaldehyde and chloral hydrate. The symptoms of ifosfamide encephalopathy can range from mild (difficulty concentrating, fatigue), to moderate (delirium, psychosis), to severe (nonconvulsive status epilepticus or coma). In children, this can interfere with neurological development. Apart from the brain, ifosfamide can also affect peripheral nerves. The severity of the reaction can be classified according to either the National Cancer Institute or the Meanwell criteria (grade I–IV). Previous brain problems and low levels of albumin in the blood increase the likelihood of ifosfamide encephalopathy. In most cases, the reaction resolves spontaneously within 72 hours. If it develops during an infusion of the drug, discontinuing the infusion is advised. The most effective treatment for severe (grade III–IV) encephalopathy is an intravenous solution of methylene blue, which appears to shorten the duration of encephalopathy; the exact mechanism of action of methylene blue is unclear. In some cases, methylene blue may be used as a prophylaxis before further doses of ifosfamide are administered. Other treatments include albumin and thiamine, and dialysis as a rescue modality.Ifosfamide may also cause a normal anion gap acidosis, specifically renal tubular acidosis type 2. References
External links
ACS Drug Guide: Ifosfamide
Harvard Medical School Health Information on Ifosfamide
BC Cancer Agency Ifosamide Information (Professional)
RxList Online Drug Index Ifosamide Listing
"Ifosfamide". Drug Information Portal. U.S. National Library of Medicine.
In the EU classification of dangerous substances it is harmful (Xn) while more toxic substances are classified as toxic (T) or very toxic (T+). The U.S. Environmental Protection Agency generally puts substances which are lethal at more than 30 g to adults in Toxicity Class III.Ethylene glycol has a low vapor pressure; it does not evaporate readily at normal temperatures and therefore high concentrations in air or intoxication are unlikely to occur following inhalational exposures. There may be a slight risk of poisoning where mists or fogs are generated, although this rarely leads to poisoning as ethylene glycol causes irritation and coughing when breathed in, alerting victims to its presence. Ethylene glycol is not well absorbed through skin meaning poisoning following dermal exposure is also uncommon. Diagnosis
As many of the clinical signs and symptoms of ethylene glycol poisoning are nonspecific and occur in many poisonings the diagnosis is often difficult. It is most reliably diagnosed by the measurement of the blood ethylene glycol concentration. Ethylene glycol in biological fluids can be determined by gas chromatography. Many hospital laboratories do not have the ability to perform this blood test and in the absence of this test the diagnosis must be made based on the presentation of the person. In this situation a helpful test to diagnose poisoning is the measurement of the osmolal gap.