levoleucovorin and Poisoning

While there is seldom need for most anti-poisoning agents and antidotes, they should be quickly available, when needed. Local worst-case scenarios, regional staggering of the treatment, and distances must be taken into account at the health care unit level. Hospitals are fairly well equipped with the recommended antidotes. Replenishment of the stocks is complicated by continual disruptions in supply of antidotes. New antidotes in the updated recommendation include calcium folinate (leucovorin) for methanol poisoning and octreotide for the treatment of hypoglycemia caused by intoxications resulting from antidiabetics of the sulfonyl urea group.

Topics: Antidotes; Humans; Leucovorin; Octreotide; Poisoning

Methanol poisoning is not frequently observed in children; however, without treatment, serious intoxication can be complicated by visual impairment, coma, metabolic acidosis, respiratory and circulatory insufficiency and death. Treatment in a paediatric intensive care is therefore compulsory. Methanol is metabolised in the liver by alcohol dehydrogenase to the toxic metabolites formaldehyde and formic acid. Classically, ethanol is given as a competitive inhibitor in order to avoid the formation of these compounds. We report on the use of fomepizole (4-methylpyrazole),a new and potent inhibitor of alcohol dehydrogenase, in a 3-year-old boy after the intake of a toxic amount of methanol. The course was uneventful and the use of fomepizole was not accompanied by any side-effects. An overview is given of all cases of paediatric poisoning in which fomepizole was used.. Fomepizole seems to be a safe and valid alternative to ethanol in cases of paediatric methanol poisoning.

Topics: Antidotes; Child, Preschool; Drug Therapy, Combination; Fomepizole; Humans; Leucovorin; Male; Methanol; Poisoning; Pyrazoles; Solvents

Almost all cases of acute methanol toxicity result from ingestion, though rarely cases of poisoning have followed inhalation or dermal absorption. The absorption of methanol following oral administration is rapid and peak methanol concentrations occur within 30-60minutes.. Methanol has a relatively low toxicity and metabolism is responsible for the transformation of methanol to its toxic metabolites. Methanol is oxidized by alcohol dehydrogenase to formaldehyde. The oxidation of formaldehyde to formic acid is facilitated by formaldehyde dehydrogenase. Formic acid is converted by 10-formyl tetrahydrofolate synthetase to carbon dioxide and water. In cases of methanol poisoning, formic acid accumulates and there is a direct correlation between the formic acid concentration and increased morbidity and mortality. The acidosis observed in methanol poisoning appears to be caused directly or indirectly by formic acid production. Formic acid has also been shown to inhibit cytochrome oxidase and is the prime cause of ocular toxicity, though acidosis can increase toxicity further by enabling greater diffusion of formic acid into cells.. Methanol poisoning typically induces nausea, vomiting, abdominal pain, and mild central nervous system depression. There is then a latent period lasting approximately 12-24 hours, depending, in part, on the methanol dose ingested, following which an uncompensated metabolic acidosis develops and visualfunction becomes impaired, ranging from blurred vision and altered visual fields to complete blindness.. For the patient presenting with ophthalmologic abnormalities or significant acidosis, the acidosis should be corrected with intravenous sodium bicarbonate, the further generation of toxic metabolite should be blocked by the administration of fomepizole or ethanol and formic acid metabolism should be enhanced by the administration of intravenous folinic acid. Hemodialysis may also be required to correct severe metabolic abnormalities and to enhance methanol and formate elimination. For the methanol poisoned patient without evidence of clinical toxicity, the first priority is to inhibit methanol metabolism with intravenous ethanol orfomepizole. Although there are no clinical outcome data confirming the superiority of either of these antidotes over the other, there are significant disadvantages associated with ethanol. These include complex dosing, difficulties with maintaining therapeutic concentrations, the need for more comprehensive clinical and laboratory monitoring, and more adverse effects. Thus fomepizole is very attractive, however, it has a relatively high acquisition cost.. The management of methanol poisoning includes standard supportive care, the correction of metabolic acidosis, the administration of folinic acid, the provision of an antidote to inhibit the metabolism of methanol to formate, and selective hemodialysis to correct severe metabolic abnormalities and to enhance methanol and formate elimination. Although both ethanol and fomepizole are effective, fomepizole is the preferred antidote for methanol poisoning.

Topics: Ethanol; Fomepizole; Formates; Humans; Leucovorin; Methanol; Poisoning; Practice Guidelines as Topic; Pyrazoles; Renal Dialysis

There is little data on the frequency of adverse events following acute methotrexate ingestions in pediatric patients. Likewise, recommendations for observation length, site and management strategies in this population are not well established. Therefore, most recommendations are modeled after management of chronic overdose in patients with underlying medical conditions.. The primary objective of this study is to determine the frequency of acute toxicity after acute methotrexate accidental unsupervised ingestions in patients less than six years. In addition, we describe the frequency of late toxicity and characterize the management site and approaches.. This is a retrospective cohort study of pediatric accidental unsupervised methotrexate ingestions reported to six poison centers in the United States over a 16 year period. Demographic information, exposure details, signs, symptoms, treatments, length and location of observation and outcomes were collected.. 103 patients met inclusion criteria. Methotrexate dose was reported in 86 patients (84%) and ranged from 1.3 mg-75 mg. The majority of cases (97%) ingested a dose ≤20 mg. The significant majority of cases experienced no clinical effects (99 of 103 cases; 96%). Three children experienced minor outcome (3%). There were no patients with a major outcome or death.. The incidence of toxicity from pediatric single, acute ingestions of methotrexate is rare and when it occurs is generally limited to no or only minimally concerning effects. Because concentrations from single ingestions were consistent with low subtoxic exposures, we believe that home monitoring without hospital referral and without methotrexate specific therapy is reasonable in those with acute ingestions up to 20 mg.

Topics: Antidotes; Antimetabolites, Antineoplastic; Charcoal; Child; Child, Preschool; Cohort Studies; Female; Humans; Incidence; Infant; Leucovorin; Male; Methotrexate; Poisoning; Resuscitation; Retrospective Studies; Treatment Outcome; United States

Single-patient methanol intoxications are a common clinical presentation, but outbreaks are rare and usually occur in settings in which there is limited access to ethanol and methanol is consumed as a substitute. In this case report, we describe an outbreak of methanol intoxications that was challenging from a public health perspective and discuss strategies for managing such an outbreak.

Topics: Acid-Base Equilibrium; Acidosis; Adult; Antidotes; Disease Outbreaks; Eating; Fomepizole; Humans; Hydraulic Fracking; Leucovorin; Male; Manitoba; Methanol; Middle Aged; Nausea; Poisoning; Pyrazoles; Renal Dialysis; Sodium Bicarbonate; Solvents; Vomiting; Young Adult

To present a case of survival without visual and central nervous system sequelae at a formate concentration of twice the reported lethal level.. This was a case of a 33-year-old man who ingested 1 liter of a toxic mixture of methanol and ethanol. Upon admission, he presented with anxiety, tachycardia and hypertension and had a serum formate level of 1,400 mg/l (normal range 0.9-2.1 mg/l), a methanol level of 806 mg/l (normal range 2-30 mg/l), an undetectable ethanol concentration and a normal lactate level. A 10% solution of ethanol and folinic acid was administered intravenously and two 8-hour sessions of intermittent hemodialysis were performed. The patient was discharged on the fifth day without sequelae of poisoning. The follow-up examinations 3 months and 2 years later revealed no damage to the basal ganglia. The patient had normal visual-evoked potential and findings on optical coherence tomography. The genetic analysis revealed a rare minor allele for the gene coding CYP2E1 enzyme of the microsomal ethanol oxidizing system.. The patient survived acute methanol poisoning without long-term sequelae despite a high serum level of formic acid upon admission.

Topics: Adult; Ethanol; Formates; Humans; Leucovorin; Male; Methanol; Poisoning; Renal Dialysis

We report the case of a 16 years old female patient, with a pregnancy history of 11.4 weeks by ultrasound and intrauterine fetal death. In a private clinic were prescribed methotrexate 500 mg intramuscular single dose, and vaginal misoprostol. She had a clinical feature of five days of evolution characterized by fever of 39 degrees C, nausea, general attack and vomiting. The initial diagnosis was severe sepsis secondary to septic abortion, oral candidiasis and acute poisoning by methotrexate. After that, she was referred to the Instituto Nacional de Perinatologia, where stayed with fever for four days, and was managed with hydration, antibiotics, folinic acid and alkalizing. Her recovery was gradual. She was discharged after 12 days with significant clinical improvement. The literature review describes that the use of methotrexate for abortion purpose with therapeutic-dose presents a similar adverse effects to those found in our patient, however there are no case reports that describe the use of this drug in macrodosis for the same purpose, and their cytotoxic effects. We present this case because the patient used a macrodosis of this antimetabolite and due to the premature and empirical management with folinic acid, joined with alkalinization of urine, is the ideal treatment and as it is illustrated in our case.

Topics: Abortifacient Agents; Abortion, Induced; Abortion, Missed; Abortion, Septic; Administration, Intravaginal; Adolescent; Anti-Bacterial Agents; Antidotes; Candidiasis, Oral; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Injections, Intramuscular; Leucovorin; Methotrexate; Misoprostol; Neutropenia; Poisoning; Pregnancy; Recombinant Proteins; Vomiting

Topics: Antidotes; Antimetabolites, Antineoplastic; Child; Fluid Therapy; Folic Acid; gamma-Glutamyl Hydrolase; Hemoperfusion; Humans; Infusions, Intravenous; Leucovorin; Male; Methotrexate; New York City; Poison Control Centers; Poisoning; Renal Dialysis; Thymidine; Treatment Outcome; Vitamin B Complex

A series of eight cases of methyl alcohol poisoning resulting from consumption of adulterated alcohol is presented. Most of the patients had blurring of vision followed by coma, metabolic acidosis and hemodynamic unstability (SBP < 90 mmHg) on admission to medical ICU. Early recognition and prompt initiation of treatment lead to successful recovery in five of these patients. Analysis of correlation between clinical and biochemical indicators of severity and indication for various therapeutic interventions are discussed.

Topics: Adolescent; Adult; Female; Humans; Intensive Care Units; Leucovorin; Male; Methanol; Middle Aged; Poisoning; Renal Dialysis

We report a case of wood alcohol (methylated spirits) poisoning in a 40-year-old chronic alcoholic. The initial diagnosis of state of drunkenness was supported by the increased plasma level of ethanol (4.66 g.L-1) obtained with enzymatic method. The confirmation, using gas chromatography (GC), showed an unexpected peak with a retention time at 1.19 min, characteristic of methanol (0.41 g.L-1). The GC analysis of the absorbed beverage revealed a 5% methanol content. The osmolal gap was 115 mOsm.kg-1, with 13 mOsm.kg-1 due to methanol and 90 mOsm.kg-1 to ethanol. Seven hours after the ingestion, the anion gap was at 13 mmol-1. This result reflected the inhibition of methanol oxidation by alcohol-dehydrogenase, when the plasma ethanol concentration was above 1 g.L-1. This concentration was maintained by continuous intravenous administration of (Curéthyl-A) a 95% ethanol containing solution, until methanol concentration decreased below 0.2 g.L-1. The outcome was favourable without neurological and ophthalmological sequelae.

Topics: Acid-Base Equilibrium; Adult; Alcohol Dehydrogenase; Alcoholic Beverages; Alcoholic Intoxication; Chromatography, Gas; Enzyme Inhibitors; Ethanol; Humans; Leucovorin; Male; Methanol; Osmolar Concentration; Oxidation-Reduction; Poisoning

Methotrexate is a chemotherapy antimetabolite, folic acid antagonist, that inhibits the enzyme dihydrofolate reductase resulting in decreased levels of tetrahydrofolate in the cells. This in turn blocks synthesis of thymidylate, a nucleotide necessary for DNA synthesis. It is readily absorbed from the gastrointestinal tract. Toxicity from overdose can affect multiple organ systems including bone marrow, liver, intestinal tract, kidneys, lungs, skin, and blood vessels, resulting in death in severe cases. Methotrexate is widely used to treat neoplastic disease, dermatologic disorders (psoriasis), and rheumatologic disorders (severe rheumatoid arthritis). As its indications for use increase, more accidental overdoses can be expected. We present the treatment and clinical course of one such case, that of a 2-year-old who accidentally took her grandmother's arthritis pills. Her initial serum level was 10 times greater than that needed to cause toxicity. She was treated with gastric lavage, activated charcoal, leucovorin rescue, and ICU admission. Her clinical course was unremarkable, and the only evidence of toxicity was a mild elevation in a liver-associated enzyme that resolved without any clinical sequela. Leucovorin at a dose equal to or greater than the possible ingestion should be given as soon as possible in methotrexate overdoses.

Topics: Antidotes; Antimetabolites, Antineoplastic; Antirheumatic Agents; Emergency Treatment; Folic Acid Antagonists; Gastric Lavage; Humans; Leucovorin; Methotrexate; Poisoning

Topics: Acid-Base Equilibrium; Acidosis; Adult; Ethanol; Humans; Leucovorin; Male; Methanol; Osmolar Concentration; Poisoning; Renal Dialysis; Solvents

Ingestion of over 60 g of formic acid by an adult is potentially fatal. We report a case of a 36-year-old woman with a history of depression who ingested 110 g of formic acid. She survived a complicated intensive care hospitalization following usage of intravenous folinic acid, urinary alkalinization, intravenous furosemide and supportive care. We suggest a management protocol aimed at minimizing formate toxicity by enhancing hepatic formate degradation via the folinic acid 'one carbon pool' and by enhanced renal elimination of formate.

Topics: Adult; Female; Formates; Furosemide; Humans; Hydrogen-Ion Concentration; Infusions, Intravenous; Kidney; Leucovorin; Poisoning; Suicide, Attempted

Significant toxicity can result from intentional methanol inhalation. We report seven cases, involving four patients, of intentional inhalation of CARB-MEDIC carburetor cleaner containing toluene (43.8%), methanol (23.2%), methylene chloride (20.5%), and propane (12.5%). Patients arrived at the emergency department with central nervous system depression, nausea, vomiting, shortness of breath, photophobia, and/or decreased visual acuity. Treatment included correction of acidosis, leucovorin and/or folic acid, ethanol infusions, and supportive care. Hemodialysis was necessary in three cases. Measured blood methanol levels ranged from 50.4 to 128.6 mg/dL. Blood formic acid levels were 120, 193, and 480 micrograms/mL, respectively, in three patients. Ophthalmic examinations revealed hyperemic discs and decreased visual acuity in one patient. One individual was found pulseless with several CARB-MEDIC cans nearby. Attempts at revival were unsuccessful. Clinicians should be aware that significant blood methanol and formic acid levels may occur after inhalation of methanol.

Topics: Administration, Inhalation; Adult; Ethanol; Folic Acid; Humans; Leucovorin; Male; Methanol; Poisoning; Substance-Related Disorders

Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Therapy, Combination; Humans; Leucovorin; Methotrexate; Neoplasms; Poisoning; Renal Dialysis

Methotrexate toxicity is rare but extremely severe. When complete, it consists of ulcerations of the gastrointestinal mucosae responsible for necrotizing enteritis, erythroderma, bone marrow aplasia, interstitial pneumonia, hepatitis and organic renal failure with diuresis. Toxicity is facilitated by pre-existing renal impairment, third sector and abstention or underdosage of foliculinic acid prescribed as antagonist. The diagnosis rests on serum assays, the results of which must be interpreted taking into account the assay method and the time elapsed between the injection of methotrexate and its assay in serum. The multivisceral pathology observed may totally regress, as in the case reported here. Treatment is based on symptomatic measures, starting with maintenance of an abundant and alkaline diuresis, and on the parenteral administration of folinic acid in doses that vary with the authors.

Topics: Acute Kidney Injury; Chemical and Drug Induced Liver Injury; Dermatitis, Exfoliative; Enteritis; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Osteosarcoma; Poisoning; Pulmonary Fibrosis

Topics: Accidents, Home; Aspartate Aminotransferases; Child, Preschool; Emergencies; Humans; L-Lactate Dehydrogenase; Leucovorin; Male; Methotrexate; Poisoning; Time Factors

Topics: Animals; Blood Chemical Analysis; Body Weight; Dogs; Drug Combinations; Female; Folic Acid; Hemodynamics; Leucovorin; Male; Organ Size; Poisoning; Pyrimethamine