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P Hantson

Publications and source records attributed to P Hantson.

At least 19 recordsLinked to original sources
PubMed2005

Formate kinetics in methanol poisoning.

OBJECTIVE: The objective is to describe the kinetics of formate, the main toxic metabolite of methanol, in a series of consecutive patients treated in the same intensive care unit for severe methanol poisoning. METHODS: The charts of the patients admitted between 1987 and 2001 were reviewed. Inclusion criteria were: a history of deliberate methanol ingestion, with a blood methanol concentration greater than 20 mg/dL (6.2 mmol/L) or a high anion gap metabolic acidosis. Indications for hemodialysis were: blood methanol concentration >50 mg/dL (15.8 mmol/L), metabolic acidosis (bicarbonate <15 mmol/L, arterial pH <7.30), visual toxicity. Antidotal therapy included ethanol administration in 22 cases, and fomepizole in three cases. Serial blood measurements were obtained for pH, bicarbonate, methanol and formate. Endogenous and hemodialysis elimination half-lives were calculated as t1/2 =0.693/Ke. Fick principle was applied for hemodialysis clearance calculation. RESULTS: The records of 25 methanol poisoned patients were analysed. Among them, 18 patients had sufficient data to allow accurate determinations of formate kinetics. Formate half-life elimination during hemodialysis was 1.80+/-0.78 h, which was statistically different from the values observed before or in the absence of dialysis (6.04+/-3.26 h, P =0.004). The mean hemodialysis formate clearance rate calculated in eight cases was 176+/-43 mL/min. A rebound in plasma formate concentration was observed in three patients after the discontinuation of hemodialysis. CONCLUSIONS: In accordance with previous isolated case reports and in contrast with a recent case series, our data document that hemodiaysis is effective in reducing formate elimination half-life. The impact on clinical outcome is still debatable.

Adult↗
PubMed2001

Treatment of acute methanol poisoning with fomepizole.

OBJECTIVE: To assess the efficacy and safety of fomepizole, a competitive alcohol dehydrogenase inhibitor, in methanol poisoning and to test the hypothesis that fomepizole obviates the need for hemodialysis in selected patients. DESIGN AND SETTING: Retrospective clinical study in three intensive care units in university-affiliated teaching hospitals. PATIENTS: All methanol-poisoned patients admitted to these ICUs and treated with fomepizole from 1987-1999 (n=14). MEASUREMENTS AND RESULTS: The median plasma methanol concentration was 50 mg/dl (range 4-146), anion gap 22.1 mmol/l (11.8-42.2), arterial pH 7.34 (7.11-7.51), and bicarbonate 17.5 mmol/l (3.0-25.0). Patients received oral or intravenous fomepizole until blood methanol was undetectable. The median cumulative dose was 1250 mg (500-6000); the median number of twice daily doses was 2 (1-16). Four patients underwent hemodialysis for visual impairment present on admission. Four patients with plasma methanol concentrations of 50 mg/dl or higher and treated without hemodialysis recovered fully. Patients without pretreatment visual disturbances recovered, with no sequelae in any case. There were no deaths. Fomepizole was safe and well tolerated, even in the case of prolonged treatment. Analysis of methanol toxicokinetics in five patients demonstrated that fomepizole was effective in blocking methanol's toxic metabolism. CONCLUSIONS: Fomepizole appears safe and effective in the treatment of methanol-poisoned patients. If our results are confirmed in prospective analyses, hemodialysis may prove unnecessary in patients presenting without visual impairment or severe acidosis.

Adolescent↗
PubMed2001

Fomepizole (orphan medical).

Orphan Medical has developed fomepizole as a potential treatment for both ethylene glycol and methanol poisoning. The drug was launched as Antizol in January 1998 for the treatment of ethylene glycol poisoning [273949] after US marketing approval was grantedin December 1997 [271563]. It has also received US approval for methanol poisoning [393217] and UK approval for ethylene glycol poisoning [329495]. In 1999, Orphan Medical's partner, Cambridge Laboratories, intended to pursue European approval under the mutual recognition procedure [329495]. However, by September 2000, Cambridge Laboratories had discontinued their involvement with fomepizole and IDIS World Medicines had licensed the rights to distribute the drug in the UK [412142]. In February 2000, the Canadian Therapeutic Products Programme (TPP) granted fomepizole Priority Review, provided that an NDA was submitted by March 14, 2000 [354665]. In August 2000, the TPP accepted this NDA and set a target date for approval in the fourth quarter of 2000 [379474]. The TPP granted fomepizole a Notice of Compliance permitting the sale of fomepizole in Canada in December 2000. The company's marketing partner in Canada, Paladin Labs had launched fomepizole by January 2001 [396953]. In June 2000, Tucker Anthony Cleary Gull stated that the Orphan Drug status which Orphan Medical had obtained for fomepizole would provide marketing exclusivity through December 2004. The analysts also stated that fomepizole had accounted for 40% of Orphan Medical's revenue in financial year 1999, although +/- 30% of sales were estimated to be due to stockpiling [409606].

Journal Article↗
PubMed2000

A case of fatal diquat poisoning: toxicokinetic data and autopsy findings.

CASE REPORT: A 37-year-old man ingested in a suicide attempt 300 mL of a diquat solution (equivalent to 60 g diquat ion). The initial diquat serum concentration was 64 microg/mL 4 hours after poisoning. The clinical course was characterized by a progressive anuria and by neurological disorders (coma and seizures). The patient died 26 hours after poisoning from refractory cardiocirculatory collapse. Extracorporeal techniques removed 1.09 g of diquat which could be considered as significant in regard to the total amount that was likely absorbed, but they did not influence the clinical outcome. There was marked renal tubular damage at autopsy and the highest diquat tissue concentration was found in the kidneys.

Adult↗
PubMed2000

Pancreatic injury following acute methanol poisoning.

BACKGROUND: Methanol ingestion is a cause of potentially life-threatening poisoning with numerous systemic manifestations. Clinicians may overlook the possibility of acute pancreatitis in this setting. The objective of this paper is to document the incidence of this complication in a series of 22 patients and to discuss the respective role of methanol and ethanol in its pathogenesis. CASE REPORT: A 54-year-old woman developed acute necrotizing pancreatitis following acute methanol poisoning. She was treated by hemodialysis, ethanol infusion, and folinic acid, but, despite maximal supportive therapy, she died from multiple organ failure 54 hours after the ingestion. CASE SERIES: In a series of 22 consecutive patients admitted with a diagnosis of acute methanol poisoning, we found evidence of pancreatic damage in 11 patients. The abnormalities were present from admission and before ethanol therapy in 7 cases and developed after ethanol therapy in 4 cases. Seven patients had a history of chronic ethanol abuse, but no patient had previously suffered from acute or chronic pancreatitis. Three patients presented moderate-to-severe acute pancreatitis according to clinical and radiological criteria and required aggressive supportive therapy including peritoneal dialysis. One patient died from the direct consequences of acute necrotizing pancreatitis and 2 fully recovered from this event. Three patients evolved to brain death; autopsy revealed hemorrhagic lesions in the pancreas in only 1 case. CONCLUSIONS: Clinical, biological, and radiographic signs of acute pancreatic injury may be more common than previously realized. Acute methanol poisoning appears to produce pancreatic injury, although antidotal treatment with ethanol or prior chronic ethanol abuse may be contributing factors. Because ethanol treatment may complicate the pancreatic injury, fomepizole (4-methylpyrazole) may be the preferable antidote in acute methanol poisoning.

Acute Disease↗
PubMed2000

Determination of formic acid tissue and fluid concentrations in three fatalities due to methanol poisoning.

Three fatalities caused by methanol ingestion are reported. Admission blood methanol concentrations ranged from 0.28 to 4.6 g/L. Two patients had been admitted after a significant delay (>20 hours), and one patient was observed within 90 minutes following ingestion. Formic acid levels were determined in blood samples at admission and ranged from 302 to 680 mg/L. The patients died 44, 55, and 82 hours after poisoning. Formic acid determinations in postmortem tissues were performed by a gas chromatograph method. The authors found great variability in formic acid distribution among the patients and among organs.

Acidosis↗
PubMed2000

Survival with extremely high blood methanol concentration.

Fatalities are still reported following methanol poisoning. Methanol is extensively metabolized by alcohol dehydrogenase to formaldehyde and by aldehyde dehydrogenase to formic acid which is the main toxic metabolite. Survival with extremely high blood methanol concentration is possible provided that aggressive symptomatic and specific therapy is applied. This is illustrated by the clinical observation of a 27-year-old man who was admitted 22 hours after poisoning and presented a peak blood methanol concentration of 12.9 g/l. Treatment included correction of metabolic acidosis, ethanol infusion, haemodialysis and peritoneal dialysis. The patient survived with moderate visual sequelae and oesophageal stenosis. The range of toxicity of methanol according to blood levels determination is discussed.

Adult↗
PubMed2000

Spontaneous haemoperitoneum from surreptitious ingestion of a rodenticide.

Superwarfarins have progressively replaced warfarin as rodenticides as they are more potent and have a longer anticoagulant activity. Human exposure may be complicated by spontaneous haemorrhage in various sites. We report the case of a 51-year-old woman who was admitted with spontaneous haemoperitoneum and intramural haematoma along the small intestine. After the evidence of a deficit of vitamin K1-dependent clotting factors (II, VII, IX, X), the patient admitted that she was chronically ingesting difenacoum. She was successfully treated with fresh frozen plasma and vitamin K1. Follow-up was not accepted.

4-Hydroxycoumarins↗
PubMed2000

Antimony excretion in a patient with renal impairment during meglumine antimoniate therapy.

Meglumine antimoniate was administered to a patient with visceral leishmaniasis with normal renal function. Soon after the first intramuscular administration of meglumine antimoniate 20 mg/kg, equivalent to 510 mg antimony (Sb), the patient developed septic shock with oliguria. Creatinine clearance decreased to 23 ml/minute. Treatment was discontinued, and Sb urinary excretion was measured. After the initial dose, 500.25 mg Sb was recovered in urine over 8 days, corresponding to 98% of the amount of Sb given intramuscularly (66% eliminated within first 48 hrs). Nine days after the dose, meglumine antimoniate was reintroduced at a dosage of 11.7 mg/kg (equivalent to 300 mg Sb) every 48 hours with good tolerance. At that time creatinine clearance had returned to 87.8 ml/minute. By day 14 of therapy the interval was reduced to daily administration of the same dose; the dosage was increased to 16.6 mg/kg/day (equivalent to 425 mg Sb) from day 17 to day 31. The patient eventually completely recovered and was discharged with normal renal function. Although no specific guidelines exist for dosage adjustment in renal failure, monitoring of Sb urinary excretion indicates that the kidneys are the almost exclusive route of elimination.

Antimony↗
PubMed2000

Prospective analysis of aneurysm treatment in a series of 103 consecutive patients when endovascular embolization is considered the first option.

OBJECT: The aim of this study was to evaluate prospectively the results of treating cerebral aneurysms with coil embolization (CE) or with surgical clipping when CE was considered the first option. METHODS: Whenever an aneurysm was to be treated, CE was first considered by our neurovascular team. Surgical clipping was reserved for cases excluded from CE or cases in which CE failed. The study consisted of 103 consecutive patients with 132 aneurysms, of which 127 were treated. Coil embolization was performed using Guglielmi detachable coils, and surgery was performed using Zeppelin clips. Three groups were defined: Group A consisted of 64 aneurysms that were treated by CE (neck/sac ratio < 1:3); Group B, 63 aneurysms that were surgically clipped; and Group C, 12 aneurysms that failed to be satisfactorily (> or = 95%) embolized and were subsequently clipped. The percentages of residual aneurysm were 31.2% in Group A, 1.6% in Group B, and 0% in Group C. The percentages of patients with poor Glasgow Outcome Scale (GOS) scores (GOS Scores 1-3) were 13.3% in Group A, 6.1% in Group B, and 8.3% in Group C. The percentages of poor outcome (GOS Scores 1-3) in patients with good clinical status before treatment were 10.7% in Group A, 0% in Group B, and 8.3% in Group C. CONCLUSIONS: Even with preselection, CE remains associated with a significant number of treatment failures and poor outcomes, even in patients with good preoperative clinical status. Surgical clipping can offer better results than CE, even for more complex aneurysms of the anterior circulation, especially for those involving the middle cerebral artery cases. However, because CE can be effective and causes less stress and invasiveness for the patient, it should be considered first in aneurysms strictly selected by a neurovascular team.

Adult↗
PubMed1999

[Smoke poisoning].

SYSTEMIC AND LOCAL EFFECT: Smoke inhalation causes systemic and local, mainly respiratory, toxicity due to the asphyxiant and irritant properties of toxic gases. OXYGEN DEPRIVATION AND INTOXICATION: The syndrome of oxygen deprivation and intoxication by asphyxiant gases is caused by combustion-induced oxygen deprivation and exposure to carbon monoxide (CO) and cyanide (CN), but also to other toxic gases. A loss of consciousness is a good sign of systemic toxicity; however, the respective role of CO, CN and other toxic gases cannot be determined. The presence of apnea, lactic acidosis, and severe cardiovascular disturbances is consistent with CN poisoning. A correlation exists between blood CO concentration determined on a sample obtained at the site of the fire, and the occurrence and severity of the clinical disorders. IRRITANT GASES INTOXICATION: This syndrome explains the mucosal injury affecting the eyes and the lungs. These complications are better diagnosed by clinical examination rather than by various investigations such as chest X-ray or fiberoptic bronchoscopy. Dysphonia is always a sign of severe poisoning. CLINICAL COURSE: In non-burned victims, delayed neurological and respiratory complications can be observed. Oxygen administration is the cornerstone supportive therapy. Hyperbaric oxygen should be discussed according to the severity of the syndrome of oxygen deprivation and intoxication by asphyxiant gases. In case of cyanide poisoning, a safe and effective antidote should be given; hydroxocobalamine seems to be the drug of choice. Supportive treatment is efficient to treat respiratory failure. Endotracheal intubation should be considered in patients exhibiting early dysphonia associated with dyspnea.

Asphyxia↗