Tchernov N.V.. Sarmanaev S.Kh., Akhmetov I.R., Kondrashova S.R., Salmanov A.A, Bessolitzina A.M., Akhmerova O.R, Teregulova Z.S.
Ufa (Russia).
The interest to acute poisonings by searing liquids in Russia in the recent decade (1,2,3) has been caused by a high mortality rate, which stays at the same level as in previous years (4,5,6)
A retrospective study of mortality of the deceased due to acute poisonings in the Republic of Bashkortostan (Russia) during 1992-2001 conducted on the material of acts of the Bureau of Forensic Medicine Analysis and medical charts of 18079 patients of the Ufa Toxicological Center for the same period.
The rate mortality caused by acute poisonings in Republic of Bashkortostan during the last decade amounts to 14274. The mortality rate in cases of acute searing liquids poisonings amounts to 469. More than a half of these were poisonings by acetic acid - 284. Hospitalization for the 10 years equals 18079 patients. Hospitalization of people with acute poisonings by searing liquids is 1106. Lethal outcome is registered in 133 cases (out of these, 85 were acetic acid poisonings).
Tissue and plasma determination of 4-methyl-pyrazole in methanol acute poisoning
Wallemacq P.. Di Fazio V., Vanbinst R., Kônig J.5 Hantson Ph.Laboratory of Toxicology and Intensive Care Unit, University Hospital St Luc, UCL, B-1200 Brussels, Belgium
Four patients (3 male/1 female), admitted in intensive care unit for acute methanol poisoning between December 1999 and November 2001, were treated by fomepizole or 4-methylpyrazole (4-MP), an alcohol dehydrogenase inhibitor, administered either orally or iv. They displayed on admission methanol blood levels ranging from 0.4 to 3,3 g/L. Loading doses of 15 mg/kg 4-MP (ranging from 700-1300 mg) were administered iv or orally. Iterative doses were given at 12 hours interval for a maximum of 3 days. During hemodialysis, a continuous infusion of 4-MP was proposed at a rate of 1 mg/kg/h. A minimum of 12 blood samples were collected for each patient during the treatment, for 4-MP plasma determinations, and a sample of hepatic tissue (160 mg) was removed during the autopsy of one of the patients death 34 h after admission. Samples were kept frozen until analysis. A gas chromatographic method has been developed for 4-MP determinations, with a splitless capillary injector and a nitrogen phosphorus detector. The injec-tor and detecinjec-tor T° were 280 and 350° C respectively. The carrier gas was helium. The extraction was obtained by addition of K2C03, propylphenazone (PP) as internal standard, and ethyl acetate to 300 uL of plasma sample. 2 pL of the upper organic layer were injected into the system. Retention times of 4-MP and PP were 3.98 and 9.56 min. The analytical performances of the method showed a LOD around 1 pg/mL, and coefficient of variations < 6.34 % within the range of 5-50 pg/mL. Plasma determinations of 4-MP displayed concentrations ranging from 1.4-21.6 pg/mL. Peak concentration (mean±sd) was 18.5±2.6 pg/mL, without significant difference according to the route of administration (po or iv) confir-ming the high oral bio-availability of 4-MP. Elimination half-life's (mean±sd) observed during either the first administration (non steady state and during hemodialysis), or the second administration were 6.78±2.9 h and 17.2±3.0 h respectively. Interestingly, 4-MP hepatic concentration was 12 pg/g of hepatic tissue. At that time of sampling - when the patient died - plasma concentration was <1 pg/mL. Since methanol is mainly oxidised within the liver, hepatic 4-MP concentration should better reflect the enzy-matic inhibition. The tissue level observed would suggest that tissue redistribution occurs slowly and that even though 4-MP plasma level decreased below the active concentration of 1 fJg/mL, enzymatic inhibi-tion may last several hours later.
Annales de Toxicologie Analytique, vol. XTV, n° 3, 2002
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Detection of massive cephazolin concentrations in C S F associated with neurotoxicity
Wailemacq P.(1). Di Fazio V.(!>, Carlier E.(2>, Govaerts D.( î )(1) Laboratory of Toxicology, University Hospital St Luc, UCL, B-1200 Brussels, Belgium (2) Intensive Care Unit, and Laboratory, CHU A Vesale, Montigny-le-Tilleul
A 35 year-old man, underwent in June 2001 an open surgical removal of the nucleus pulposus (left L5).
He developed during the recovery period an intense pain rapidly followed by epileptic seizures associated with encephalopathy without any identified cause, except a potential toxicity of cephazolin used for pro-phylaxis during surgery (cephazolin 2g iv and lg topical into the surgical wound). To test this hypothesis, blood and CSF samples were drawn at different times post operative for cephazolin concentration deter-minations: during 4 days for blood, and the day following surgery for CSF. Samples were kept frozen until analysis. Cephazolin determinations were obtained by HPLC-UV, using cefepim as internal standard. The chromatographic conditions consisted of a mixture of 83 % 1 -octane sulfonate buffer/17 % acetonitrile as mobile phase, adjusted to a flow rate of 1 mL/min through a C18 25 cm column maintained at 35° C.
Detection was obtained at 260 nm. The performances of the analytical procedure displayed LOD and LOQ around 0.5 and 1 pg/mL respectively, and CV < 10 % in the analytical range of 1-50 pg/mL. Plasma cepha-zolin concentrations varied between 52 and 14 pg/mL, displaying rebounds and secondary peaks, preven-ting us therefore to determine pharmacokinetic parameters such as the elimination rate constant. The day following surgery, the cephazolin CSF/plasma ratio reached value up to 135, with CSF antibiotic concen-trations > 4500 pg/mL. This represents huge amounts of drug never reported in the literature so far. Since, cephazolin iv does not appreciably diffuse into the CSF being highly bound to plasma proteins, such mas-sive amounts arise from in loco administration, and are expected to contribute to the observed rebounds in the concentrations and to the prolonged elimination phase. It is concluded that the local administration of cephazolin during neurosurgery most likely caused the severe neurological disorders observed post opera-tively in this patient, and should definitely be avoided.
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