European viper envenomation recorded by French poison control centers: A clinical assessment and management study.

INTRODUCTION: Immunotherapy is the gold standard treatment for patients bitten by European vipers in France; it significantly decreases morbidity, frequency and severity of complications and length of stay. A national prospective study was performed by all Poison Control Centers (PCC) to validate the emergency protocol for viper envenomations. METHODS: This prospective study included all cases of viper bites in France, treated or not with Viperfav(®) in 2013. RESULTS: In 2013, 277 cases of viper bites were collected: ratio M/F 2.1; mean aged 43 years (<15 years 25% 15-65 63% > 65 12%). The final severity was divided into 68 grades 0, 58 grades I, 62 grades IIA, 71 grades IIB and 18 grades III. One death was reported. Five patients had neurological signs. For the 114 patients who received Viperfav(®), all systemic signs disappeared in 5 h and in 24 h for biological and neurological signs. No severe anaphylactic reaction with Viperfav(®) was reported. Late Viperfav(®) administration increased the risk of functional impairment 15 days after the bite (OR = 3.21 p = 0.043). The administration of Low Molecular Weight Heparin (LMWH) increased the frequency of functional impairment to 15 days after the bite (OR = 6.38 p = 0.064), although Viperfav(®) was given in the first 18 h. DISCUSSION: This study confirms the efficiency, safety and recommendation of an early administration of a single dose of Viperfav(®), LMWH should not be used. It also shows the extension of neurotoxic venom of vipers in France.

Effect of age and gender on the pharmacokinetics of R667, a novel agent for the treatment of emphysema, in healthy volunteers.

The purpose of the present study was to assess the impact of age and gender on the pharmacokinetics (PK) of R667. Thirty six healthy male and female volunteers (12 m 18-45 years; 12 m and 12 f > or = 65 years) received a single 1 mg oral dose of R667. Serial blood samples were collected for determination of plasma R667 and metabolite concentrations. The PK parameters of R667 were similar between elderly males and young males (Cmax = 9.8 vs 9.8 ng/mL; AUC(0-last) = 50.9 vs 47.3 ng x h/mL, respectively). Exposure of R667 increased in elderly females compared to elderly males (Cmax = 13.1 vs 9.8 ng/mL; AUC(0-last) = 60.8 vs 47.3 ng x h/mL, respectively). When the CL/F was corrected for BSA and V/F corrected for weight these differences were no longer evident. In conclusion these exposure differences are not considered clinically relevant, and no dose adjustment of R667 is required based on gender or age.

Fatal overdosage with nefopam (Acupan).

This paper presents a fatality due to massive, intravenous self-administration of nefopam (Acupan), a non-opiate central analgesic, in a 37-year-old female. Nefopam was measured in various postmortem samples by means of high-pressure liquid chromatography coupled to mass spectrometry via an ionspray interface. Heart blood concentration was 4.38 microg/mL and exceeded by approximately 30 times the highest therapeutic levels with the usual reservations concerning possible postmortem redistribution. This is only the third case of death following nefopam overdose reported in the literature.

Determination of blood cyanide by HPLC-MS.

An original high-performance liquid chromatographic-mass spectrometric (HPLC-MS) procedure was developed for the determination of cyanide (CN) in whole blood. After the addition of K13C15N as internal standard, blood was placed in a microdiffusion device, the inner well of which was filled with a mixture of taurine (50mM in water)/naphthalene-2,3-dicarboxaldehyde (NDA, 10mM in methanol)/methanol/ concentrated (approximately 20%) ammonia solution (25:25:45:5, v/v). Concentrated H2SO4 was added to the blood sample, and the microdiffusion chamber was sealed. After 30 min of gentle agitation, 2 microL of the contents of the inner vial were pipetted and directly injected onto a NovaPak C18 HPLC column. Separation was performed by a gradient of acetonitrile in 2mM NH4COOH, pH 3.0 buffer (35-80% in 10 min). Detection was done with a Perkin-Elmer Sciex API-100 mass analyzer with an ionspray interface, operated in the negative ionization mode. MS data were collected as either TIC or SIM at m/z (299 + 191) and (301 + 193) for the derivatives formed with CN and 13C15N, respectively. Inspired by previous works dealing with the complexation of CN by NDA + taurine to form a 1-cyano [f] benzoisoindole derivative analyzed by HPLC-fluorimetry, this method appears simple, rapid, and extremely specific. Limits of detection and quantitation for blood CN are 5 and 15 ng/mL, respectively. The use of 13C15N as internal standard allows the quantitation of CN with elegance and accuracy in comparison with previously reported methods.