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Biomedical subjects

P Harry

Publications and source records attributed to P Harry.

At least 19 recordsLinked to original sources

[Benzodiazepine poisoning in a neonate: clinical and toxicokinetic evaluation following enterodialysis with activated charcoal].

CASE REPORT: A pregnant woman who was a regular user of anxiolytics was admitted to the maternity ward at 38 weeks and 4 days amenorrhea after a massive overdose of clorazepate dipotassium, a benzodiazepine. The exact quantity ingested was undetermined. The infant, born at 39 weeks, presented no spontaneous breathing and tracheal intubation was necessary in the delivery room. The neonatal blood concentrations of the clorazepate metabolites were very high at delivery (26 mg/l nordiazepam and 3.5 mg/l oxazepam) and showed little change over the next 5 days (16 mg/l nordiazepam and 2.1 mg/l oxazepam, with an apparent half-life of 168 h for nordiazepam and 160 h for oxazepam). By day 6, the infant was still dependent on ventilator support and enterodialysis was begun with repeated doses of activated charcoal (1 g/kg every 6 h by gastric tube). Treatment was continued for 5 days and a spectacular diminution in the serum concentrations of the two metabolites was noted on day 11: 1.5 mg/l nordiazepam and less than 0.1 mg/l oxazepam. The nordiazepam and oxazepam half-lifes were reduced to 42 h and 30 h respectively. The concomitant clinical improvement authorized the weaning from ventilation on day 12. CONCLUSION: This is the first report of the use of enterodialysis to treat severe benzodiazepine poisoning in a neonate. Depuration of the toxin was accelerated and the duration of intensive care was shortened thanks to this technique.

Adult↗

Fatal acute poisoning by bentazon.

A case of fatal suicidal bentazon poisoning is presented along with a description of the different analytical methods involved. A 56-year-old farmer was examined by the family doctor 1 h after voluntarily ingesting 500 mL of FIGHTER (bentazon, 480 g/L water). He presented a Glasgow score of 15, polypnea, diarrhea, and vomiting. During transport by ambulance to the hospital, he tossed, sweated, and suddenly presented breathing difficulty followed by heart failure. Tracheal intubation was impossible (H1.5) despite use of different diameter cannulas because of extreme general muscle rigidity. All attempts at resuscitation failed, and the patient died within 2 h postingestion. Blood and urine samples were taken just before death. General basic and neutral drug screening by high-performance liquid chromatography-diode-array detection and gas chromatography-nitrogen-phosphorus detection showed no strychnine or other drugs or toxics except for citalopram (< 0.1 mg/L) and bentazon, but this weak acidic molecule (pKa3.3) was badly extracted in alkaline conditions. Plasma and urine levels, measured after acidic extraction, protein precipitation, or simple dilution, were 1500 and 1000 mg/L, respectively. Bentazon (M.W. 240) was confirmed by its basic mass spectrum (ESI-, m/z 239, 197, 175, 132) or by that of methylated derivative (El+, m/z 254, 212, 175). An hydroxylated metabolite (ESI-, m/z 255, 213, 191, 148; El+, m/z 284, 242, 163) and the N1-glucuronide conjugate of bentazon (ESI-, m/z 415, 239) were also detected in urine. (Quantitation ions are underlined.) This first case of bentazon poisoning with available analytical data revealed the high toxicity of this compound after large dose ingestion with early and heavy symptoms such as muscle rigidity probably related to muscular toxicity. Comparison with another nonfatal case and with toxicological data on animals is discussed.

Benzothiadiazines↗

Determination of LSD and its metabolites in human biological fluids by high-performance liquid chromatography with electrospray tandem mass spectrometry.

A liquid chromatographic procedure with electrospray ionization tandem mass spectrometric detection has been developed and validated for LSD and iso-LSD determination. A one-step liquid-liquid extraction on 1 ml blood or urine was used. The lower limit for quantitative determination was 0.02 microg/l for LSD and iso-LSD. The analytical procedure has been applied in two positive cases (case 1: LSD=0.31 microg/l, iso-LSD=0.27 microg/l in plasma and LSD=1.30 microg/l, iso-LSD=0.82 microg/l in urine; case 2: LSD=0.24 microg/l, iso-LSD=0.6 microg/l in urine). LSD metabolism was investigated using MS-MS neutral loss monitoring for the screening of potential metabolites. The main metabolite was 2-oxo-3-hydroxy-LSD (O-H-LSD) present in urine at the concentrations of 2.5 microg/l and 6.6 microg/l, respectively, for case 1 and 2, and was not present in plasma. Nor-LSD was also found in urine at 0.15 and 0.01 microg/l levels. Nor-iso-LSD, lysergic acid ethylamide (LAE), trioxylated-LSD, lysergic acid ethyl-2-hydroxyethylamide (LEO) and 13 and 14-hydroxy-LSD and their glucuronide conjugates were detected in urine using specific MS-MS transitions.

Adult↗

[Pesticide poisoning].

Pesticide intoxications are mainly accidental with a benign course, such as ingestions of diluted fertilizers or low concentration antivitamin K rodenticides, ant-killing products or granules of molluscicides containing 5% metaldehyde. Voluntary intoxications by chloralose, strychnine, organophosphorus or organochlorine insecticides, concentrated anti-vitamin K products, herbicides such as paraquat, chlorophenoxy compounds, glyphosate or chlorates may be severe. Toxicity is due to active substances but also to solvents or surfactants included in the composition. Analysis done in a toxicology laboratory help in establishing diagnosis, prognosis and treatment. Poison centres may be called constantly to help for the evaluation of these intoxications.

Acetaldehyde↗

Acute metobromuron poisoning with severe associated methemoglobinemia. Identification of four metabolites in plasma and urine by LC-DAD, LC-ESI-MS, and LC-ESI-MS-MS.

A case of self poisoning with metobromuron, a urea derivative used as a herbicide, is reported. Severe methemoglobinemia observed at the admission (80%) disappeared only at day 11, and hemolysis appeared at day 4 and decreased slowly to day 12. Metobromuron was analyzed by liquid chromatography with diode-array detection. Initial plasma concentration and elimination half-life were 4.9 mg/L and 5 h, respectively. Several metabolites were also detected, and four of those were identified by liquid chromatography-electrospray mass spectrometry. Normetobromuron, bromophenylurea, and bromoacetanilide were detected in plasma, but only N-methyl bromophenylurea was detected in urine. Bromoacetanilide probably results from acetylation of the intermediate bromoaniline. Methemoglobinemia could result from metabolization of metobromuron to bromoaniline and bromoacetanilide.

Acetanilides↗

[Evaluation of intravenous immunotherapy with purified F(ab')2 fragments (Viperfav)].

OBJECTIVES: To assess early clinical and biological prognosis factors in viper envenomings, and assess efficacy of Viperfav immunotherapy. Viperfav contains purified F(ab')2 fragments of equine antibodies. PATIENTS AND METHODS: A retrospective case review study of viper envenomings collected by two poison centers in France, treated or not treated by Viperfav, was conducted. Two hundred seven cases of viper bites including 119 moderate or severe envenomings (Grade II and III, recorded in adults and children and collected from 1992 to 1997 were included. Before treatment, clinical gradation and early biological severity criteria were collected. After treatment, or grade II and III envenomings, the two treatment groups were compared concerning severity and frequency of complications and sequelae, duration of hospitalization in intensive care unit (ICU) and duration of total hospital stay. RESULTS: Before treatment, both groups were not significantly different. In the Viperfav treatment group, there was a significantly lower incidence of complications (4% vs. 21%, p = 0.02) and sequelae (0% vs 14%, p = 0.006). ICU stay greater than 3 days occurred in 28% of patients in the symptomatic treatment group and no case was recorded in the Viperfav group (p = 0.0002). Total hospital stay was reduced significantly in the Viperfav group versus symptomatic treatment group (3.3 vs. 8.7 days, p = 0.000002). CONCLUSIONS: Viperfav immunotherapy was safe and effective for rapidly counteracting venom toxicity and improved markedly the prognosis of viper envenomations. The studied clinical and biological prognosis factors are valuable tools for predicting moderate or severe envenomings and are helpful for early prescription of Viperfav antivenom.

Adult↗

[Snake bite by European vipers. A multicenter study of tolerance to Viperfav, a new intravenous antivenom].

OBJECTIVES: To evaluate the tolerance and the effectiveness of i.v. Viperfav, a new antivenom containing F(ab')2 fragments of equine antibodies, for the treatment of European viper envenomed patients. STUDY DESIGN: Open, multicentre field trial, associated with a cohort study. PATIENTS: The study included 46 patients of either gender, nine aged less then 10 years, eight between 10 and 15 years, and 28 adults, who sustained a moderate or severe viper envenomation (Grade 2 or 3). METHOD: At the inclusion, a single infusion of Viperfav was given. Depending on the clinical course, up to four additional infusions were to have been administered at 4-hour intervals. To evaluate tolerance, all symptoms were recorded. There were three effectiveness evaluation criterion (duration of hospitalisation, course of the severity grade, recovery (sequelae)) and one subjective criteria (value of the antivenom as ascertained by investigators). RESULTS: In the 46 included patients, 79 infusions were administrated. Concerning tolerance, six mild symptoms were associated to the antivenom infusions. No severe reaction occurred. The mean duration of hospitalisation was 4 days 19 hours +/- 13 hours. A severity grade decrease by at least one point was observed in 35 patients, and all were discharged without sequelae. For the investigators the antivenom was inefficient in only two patients (grade 3 with tissue lesions). CONCLUSIONS: In comparison with literature data (5 to 10% of severe reactions attributable to the antivenom), the tolerance of Viperfav can be considered as satisfactory. As all criteria were in favour of a positive benefit to risk ratio, the authors recommend the use of Viperfav i.v. for the grade 2 and 3 envenomations instead of the current less purified antivenom, which can only be administered by the intramuscular route.

Adolescent↗

Ethylene glycol poisoning in a child treated with 4-methylpyrazole.

OBJECTIVE: The alcohol dehydrogenase inhibitor 4-methylpyrazole (4-MP) is a new antidote of ethylene glycol (EG) intoxication. The purpose of the present case report was to demonstrate 4-MP efficiency in EG poisoning in a 4-year-old child. METHOD AND RESULTS: 4-MP Treatment was performed 7 hours after EG ingestion. Plasma EG and 4-MP concentrations were measured 2 hours after each infusion of 4-MP. Plasma 4-MP concentrations were in the range of the values reported to block EG metabolism. The efficiency of 4-MP treatment was confirmed by the rapid correction of metabolic acidosis without alkalization and by the increase in EG half-life. No adverse effect of 4-MP was observed. CONCLUSION: This child ingested a potentially lethal dose of EG despite a high concentration of bittering agent in antifreeze. EG poisoning was treated efficiently by 4-MP without recourse to hemodialysis.

Antidotes↗

High-performance liquid chromatographic determination of 4-methylpyrazole in plasma and in dialysate.

A rapid method for the determination of 4-methylpyrazole (4-MP) levels in plasma and in dialysate by isocratic reversed-phase high-performance liquid chromatography with UV detection is described. The internal standard was the 3-methylpyrazole (3-MP). Plasma sample preparation consisted of a protein precipitation. Dialysate samples were injected without preparation. The method was linear up to 30 mg l(-1) in plasma and up to 5 mg l(-1) in dialysate. The within-day precisions (C.V.) were less than 4% in plasma and were less than 2% in dialysate. The day-to-day precisions (C.V.) were less than 7% in plasma and were less than 3% in dialysate. This method is easy to perform and has practical interest for clinicians who need to monitor in emergency 4-MP levels in ethylene glycol and methanol poisonings.

Alcohol Dehydrogenase↗

[Acute poisoning by new psychotropic drugs].

New tricyclic antidepressants such as amineptine and tianeptine have mild toxic effects while amoxapine is very toxic. Poisoning with new selective serotonin reuptake inhibitor antidepressants or monoamine-oxidase inhibitors type A (toloxatone, moclobemide) is usually not severe, but life-threatening serotonin syndromes may appear in case of drug combination with antidepressants. Loxapine and clozapine poisoning may lead to death while risperidone intoxication has usually a rather benign course. Substituted benzamide neuroleptics (amisulpride, sultopride) may induce seizures, QT prolongation and torsades de pointes. New hypnotics such as zolpidem and zopiclone have a mild toxicity similar to that of benzodiazepines, but coma and respiratory depression are observed if other drugs or ethanol are ingested or in case of chronic hepatic or respiratory insufficiency.

Acute Disease↗

Gas gangrene.

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Aged↗

4-Methylpyrazole and hemodialysis in ethylene glycol poisoning.

CASE REPORTS: Two patients severely intoxicated with ethylene glycol became anuric and were treated by hemodialysis and the antidote, 4-methylpyrazole. On admission, their plasma ethylene glycol concentrations were 0.42 and 3 g/L respectively and no alcohol was detected. The elimination of 4-methylpyrazole in the dialysate represented 45% of the total body elimination. Clearances of 4-methylpyrazole by hemodialysis were 80 mL/min and 52 mL/min respectively. RESULTS: In such cases, the authors propose infusion of a 4-methylpyrazole loading dose of 10-20 mg/kg before dialysis and intravenous infusion of 1-1.5 mg/kg/h during the 8-12 hours of hemodialysis to compensate the loss in dialysate.

Adult↗

Hemodynamic changes in acute adrenal insufficiency.

OBJECTIVE: Acute adrenocortical insufficiency is an unusual cause of isolated shock. The purpose of this study is to describe the cardiovascular changes in 6 patients with acute adrenal insufficiency presenting with hemodynamic instability. DESIGN: Retrospective and prospective study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: 6 patients studied by right cardiac catheterization. MEASUREMENTS AND RESULTS: Results before glucocorticoid treatment show two possible hemodynamic states: 1) myocardial depression with hypovolemia in 3 patients, and 2) hyperdynamic shock with high cardiac output and diminished systemic arterial resistance in 3 other patients. The 3 patients presenting hyperdynamic shock were all given intravenous fluid therapy of over 20 ml/kg before the first hemodynamic measurement. For 2 other patients with low cardiac index and high systemic arterial resistance studied prospectively, 20 ml/kg intravenous fluid therapy transformed the hemodynamic state to hyperdynamic shock. The cardiovascular effect of glucocorticoid treatment studied in 4 patients was resulted in an improvement in the left ventricular systolic work index. CONCLUSIONS: Diagnosis of acute adrenocortical insufficiency must be considered if clinical manifestations are present suggesting septic shock without any obvious infectious cause in patients having undergone considerable intravenous fluid therapy as an initial course of treatment.

Acute Disease↗