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Biomedical subjects

Philippe Hantson

Publications and source records attributed to Philippe Hantson.

33 records · Page 2Linked to original sources
PubMed2004

Plasma and tissue determination of 4-methylpyrazole for pharmacokinetic analysis in acute adult and pediatric methanol/ethylene glycol poisoning.

Methanol and ethylene glycol poisoning may result in severe intoxication. The inhibition of alcohol dehydrogenase by ethanol or 4-methylpyrazole (4-MP, fomepizole) is fundamental to their treatment. 4-MP presents several advantages over ethanol therapy and has been recently approved as a specific antidote for both intoxications. The authors have developed a simple gas chromatographic method to determine blood and tissue 4-MP concentrations. This method has been validated for its reproducibility (between-day CV < 6.3%), sensitivity (LOD 0.2 microg/mL), and linearity. It has been used in 4 adult patients intoxicated by methanol and 1 child accidentally intoxicated by ethylene glycol. 4-MP was used for each patient, and its blood levels were monitored every 4 hours over 2-3 days for pharmacokinetics purposes. In the population studied, after repeated administration of 10 mg/kg fomepizole, plasma 4-MP concentrations ranged from 1.4 to 21.6 microg/mL, always above the active level of 0.8 microg/mL. The mean peak concentration observed in the 4 adult patients was 18.5 +/- 2.6 microg/mL and in the child was 18.9 +/- 2.2 microg/mL. Even though 4-MP is characterized by a dose-dependent kinetic profile, under our conditions of dosage and blood sampling, its elimination better fitted a first-order kinetic model. At steady state and without any concomitant therapies, the mean apparent elimination half-life was 14.5 +/- 3 hours. Elimination seemed faster in the child. A trend toward a progessive enhancement of the 4-MP elimination rate is suggested in the pediatric case, with the duration of the treatment resulting in a t(1/2) below 5 hours after 48 hours. One patient died, and samples of blood and hepatic tissue were removed simultaneously during autopsy for 4-MP analysis. Interestingly, when the plasma concentration was subtherapeutic (<1 microg/mL) the tissue concentration observed was still significant with 12 microg/g, supporting an intermittent scheme of administration.

Administration, Oral↗
PubMed2004

Fomepizole alone for severe infant ethylene glycol poisoning.

OBJECTIVE: To report a case of a massive ingestion of ethylene glycol in an infant successfully treated by fomepizole without hemodialysis. DESIGN: Descriptive case report. SETTING: Pediatric intensive care unit. PATIENT: A 5-mo-old boy who ingested 200 mL of an antifreeze solution. INTERVENTIONS: Antidotal therapy with a total of seven doses of fomepizole administered intravenously with an interval of 12 hrs (15 mg/kg as loading dose, then 10 mg/kg). Hemodialysis was not performed. MEASUREMENTS AND MAIN RESULTS: Iterative determination of ethylene glycol concentration was obtained in blood and urine. Kinetics were calculated for ethylene glycol and fomepizole elimination. The infant made a complete recovery with no change in renal function. CONCLUSIONS: Although not yet approved for this indication in the child, fomepizole seemed safe and effective in a case of severe ethylene glycol poisoning, without the need for hemodialysis.

Accidents, Home↗
PubMed2003

Intravenous magnesium sulfate administration in a patient with refractory vasospasm following subarachnoid hemorrhage.

OBJECTIVE: Magnesium sulfate is being investigated for the prevention or treatment of vasospasm following subarachnoid hemorrhage. PATIENT: A 45-year-old woman suffered subarachnoid hemorrhage and developed after 8 days symptomatic vasospasm in the left middle cerebral artery (MCA) while she was receiving nimodipine prophylactically. METHODS AND RESULTS: Transcranial Doppler monitoring was performed. Cerebral autoregulation was abolished in the left MCA. Despite this finding the administration of a bolus dose of MgSO(4), followed by a continuous infusion in order to achieve serum magnesium levels in the range of 4-4.5 mg/dl (1.65-1.85 mmol/l), resulted in a marked decrease (12.2%) of the left MCA mean blood flow velocity, without clinically relevant change in systemic blood pressure (3%). This effect was maintained for at least 4 h. It did not prevent the development of ischemic lesions.

Belgium↗
PubMed2003

Acute arsenic poisoning treated by intravenous dimercaptosuccinic acid (DMSA) and combined extrarenal epuration techniques.

Arsenic poisoning was diagnosed in a 26-year-old man who had been criminally intoxicated over the last two weeks preceding admission by the surreptitious oral administration of probably 10 g of arsenic trioxide (As2O3). The patient developed severe manifestations of toxic hepatitis and pancreatitis, and thereafter neurological disorders, respiratory distress, acute renal failure, and cardiovascular disturbances. In addition to supportive therapy, extrarenal elimination techniques and chelating agents were used. Dimercaprol (BAL) and dimercaptosuccinic acid (DMSA or succimer) were used simultaneously as arsenic chelating agents for two days, and thereafter DMSA was used alone. DMSA was administered by intravenous (20 mg/kg/d for five days, then 10 mg/kg/d for six days) and intraperitoneal route. Intravenous DMSA infusion was well tolerated and resulted in an increase in arsenic blood concentration immediately after the infusion. Continuous venovenous hemofiltration combined with hemodialysis, and peritoneal dialysis were proposed to enhance arsenic elimination. It was calculated that over an 11-day period 14.5 mg arsenic were eliminated by the urine, 26.7 mg by hemodialysis, 17.8 mg by peritoneal dialysis, and 7.8 mg by continuous venovenous hemofiltration. These amounts appeared negligible with regard to the probable ingested dose. The patient died on day 26 from the consequences of multiple organ failure, with subarachnoid hemorrhage and generalized infection caused by Aspergillus fumigatus.

Acute Kidney Injury↗
PubMed2003

Defibrination and systemic bleeding caused by an imported African snakebite.

A 55-year-old man was referred from Burkina Fasso for coagulation disorders with severe spontaneous systemic bleeding. He had been bitten six days before by a snake that could not be definitely identified. No specific treatment had been started in Africa. The patient was admitted with severe anaemia, incoagulable blood with undetectable fibrinogen. Multiple haematomas in the chest and abdomen were found at computed tomography. Blood transfusions and the administration of fresh frozen plasma and fibrinogen did not result in any clinical or biological improvement. The clinical course was dramatically reversed after the infusion of two vials of Pasteur polyspecific antivenom (Echis-Bitis-Naja). According to the geographical distribution of this snake species, it seems very likely that the snakebite was caused by Echis ocellatus. Even given with delay, the antivenom was effective and well tolerated.

Antivenins↗
PubMed2002

Fomepizole therapy for reversal of visual impairment after methanol poisoning: a case documented by visual evoked potentials investigation.

PURPOSE: To illustrate the safety and efficacy of fomepizole in a case of methanol poisoning with initial visual impairment. DESIGN: Interventional case report. METHODS: A 60-year-old man was admitted with blurred vision and changes in color perception 18 hours after ingesting 100 ml methanol. Fomepizole was chosen for antidotal therapy in combination with hemodialysis. Flash electroretinogram (fERG) and flash visual evoked potentials (fVEPs) examinations were obtained at the bedside 2 hours after admission and on days 1 and 8. The monocular pattern-reversal visual evoked potentials (pVEPs) were investigated on days 1 and 8. RESULTS: A complete reversal of visual impairment was achieved within 20 hours. An abnormal b-wave amplitude and an increased peak III latency at VEPs were present on admission and recovered within 24 hours. CONCLUSIONS: Fomepizole appeared safe and effective for a patient who had severe methanol poisoning presenting with visual impairment.

Alcohol Dehydrogenase↗
PubMed2002

Determination of ethylene glycol tissue content after fatal oral poisoning and pathologic findings.

A 23-year-old comatose man who had drunk an unknown amount of ethylene glycol was admitted to the hospital 5 hours after ingestion. The initial plasma ethylene glycol concentration was 116.2 mg/100 ml. A severe metabolic acidosis was present. Despite aggressive therapy with ethanol, hemodialysis, and intensive care support, the patient died 27 hours after poisoning. The plasma ethylene glycol concentration immediately before death was 35.9 mg/100 ml. Brain edema and acute renal tubular necrosis were evident at postmortem examination. Oxalate crystals were identified in both organs. Ethylene glycol content or concentration was determined in tissues and biologic fluids.

Adult↗
PubMed2002

Effervescent paracetamol poisoning: a case report.

Severe poisoning with effervescent paracetamol tablets has never been described in the literature. Indeed, the effervescent formulation contains high amounts of sodium and bicarbonate, both responsible for important emetic properties in the case of massive ingestion. Moreover, dissolving more than 6-8 tablets in the same glass appears to be difficult. We report a well-documented case of a patient with potentially hepatotoxic serum levels after the ingestion of 16 g effervescent paracetamol, apparently without vomiting. We show that the difficulties of a massive oral intake may be overcome by a slow intake. Nevertheless, this case report does not modify the important assertion that effervescent paracetamol use could limit the risk of life-threatening intoxication by a single massive acute overdose.

Acetaminophen↗
PubMedDate not supplied

Acute renal injury following methanol poisoning: analysis of a case series.

The objective of this paper is to document the prevalence of indicators of acute renal injury in a series of methanol-poisoned patients treated in an intensive care unit and to discuss the possible mechanisms. This is a retrospective analysis of the medical records of 25 consecutive patients admitted to the intensive care unit after severe intentional methanol poisoning. Acute renal impairment was defined as a serum creatinine concentration higher than 177 micro mol/L and/or a urinary output on admission and for the first 24 h below 0.5 ml/kg/h. Clinical pathological signs of acute renal injury were found in 15 patients. In comparison with the 10 other patients taken as control group, the patients who developed renal injury had a lower blood pH value on admission, a higher serum osmolality, and a higher peak formate concentration. Two factors contributing to renal injury could be identified: hemolysis and myoglobinuria. The role of osmotic changes (osmotic nephrosis) or of a direct cytotoxic effect of formic acid remains speculative. Analysis of proteinuria suggests that proximal tubular cells may be preferentially affected. Results of histopathological evaluation of the kidney on a limited sample size (n = 5) were inconclusive but suggestive of possible hydropic changes in the proximal tubule secondary to methanol toxicity. Acute renal injury may be associated with other signs of severity in methanol poisoning, but it is almost always reversible in survivors. Indicators of acute renal injury were identified. The pathophysiology of this acute renal injury is multifactorial and far more complex than shock-related tubular necrosis.

Acute Kidney Injury↗