Epidemiology
Between 1995 and 2004 in the United States, an average of 1560 cold-related emergency department visits occurred per year and in the years 1999 to 2004, an average of 647 people died per year due to hypothermia. Of deaths reported between 1999 and 2002 in the US, 49% of those affected were 65 years or older and two-thirds were male. Most deaths were not work related (63%) and 23% of affected people were at home. Hypothermia was most common during the autumn and winter months of October through March. In the United Kingdom, an estimated 300 deaths per year are due to hypothermia, whereas the annual incidence of hypothermia-related deaths in Canada is 8000. History
Hypothermia has played a major role in the success or failure of many military campaigns, from Hannibals loss of nearly half his men in the Second Punic War (218 B.C.) to the near destruction of Napoleons armies in Russia in 1812. Men wandered around confused by hypothermia, some lost consciousness and died, others shivered, later developed torpor, and tended to sleep. Others too weak to walk fell on their knees; some stayed that way for some time resisting death. The pulse of some was weak and hard to detect; others groaned; yet others had eyes open and wild with quiet delirium.
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.