An enzymatic assay with formate oxidase for point-of-care diagnosis of methanol poisoning.

Gas chromatographic analysis for quantification of plasma methanol requires laboratory equipment and personnel, and it is typically unavailable in short time notice, especially in low- and middle-income countries. Detection of formate with the enzyme formate oxidase (FOX) is a promising method that can make the diagnosis of methanol poisoning simple and fast. The aims of this study were to test the sensitivity and specificity of a modified FOX-enzyme and to test the specificity of a point-of-care (POC)-model containing FOX-enzyme with samples from patients with metabolic acidosis. The sensitivity and specificity of FOX-enzyme in aqueous solution were evaluated with a spectrometer and by visual detection for colour change. Formate concentrations between 1 and 20 mmol/L were used to test sensitivity, and 18 potentially interfering substances were tested for specificity. The sensitivity of the FOX-enzyme was 100% and the specificity 97%. When specificity of the POC-model was tested, no false positives were detected. As such, the sensitivity and specificity of this modified FOX-enzyme for detection of formate were high. The results with this enzyme confirm the potential for its use in formate analysis as a fast diagnosis of methanol poisoning.

A survey of the antidote preparedness in Norwegian hospitals.

OBJECTIVES: Antidotes are an important part of the emergency preparedness in hospitals. In the case of a major chemical accident or a fire, large quantities of antidotes may be needed within a short period of time. For time-critical antidotes it is therefore necessary that they be immediately available. We wanted to evaluate the antidote preparedness in Norwegian hospitals as regards the national recommendations and compare this with other international guidelines. METHODS: A digital survey was sent to the 50 hospitals in Norway that treat acute poisonings. Of these, four hospitals are categorised as regional hospitals, 15 as large hospitals and 31 as small hospitals. Each hospital was asked which antidotes they stockpiled from a list of 35 antidotes. The financial costs (low, moderate, high) were added to an established efficacy scale to illustrate the cost-effectiveness of the different antidotes. RESULTS: The response rate was 100%. Eleven of fifty (22%) hospitals stockpiled all antidotes recommended for their hospital size. All four regional hospitals had all the recommended antidotes. Large hospitals which were not regional hospitals had the least availability of antidotes, and only one large hospital stockpiled all antidotes recommended for this hospital size. CONCLUSIONS: We found varying compliance with the national recommendations for antidote storage in hospitals. To strengthen antidote preparedness, we recommend standardised European guidelines to support national guidelines.

Formate test for bedside diagnosis of methanol poisoning.

Methanol poisoning kills thousands of people every year and remains a diagnostic challenge, especially where the resources are scarce, but also in high-income countries worldwide. We are in the course of developing a bedside strip to detect formate - the toxic metabolite of methanol. We hereby present the first clinical methanol case where formate was detected bedside from a drop of blood: The patient, a 61-year-old male, was admitted with a suspect methanol poisoning and severe metabolic acidosis. The test strip was positive after 3 minutes. Sodium bicarbonate (500 mmol/L), fomepizole, dialysis and folinic acid were given based on the positive test. The diagnosis was some hours later confirmed by GC-MS, showing a methanol concentration of 62 mmol/L (200 mg/dL) and a formate concentration of 19 mmol/L. Implementation of this technology into routine clinical use can potentially offer an opportunity for a step change in the management of methanol poisoning.

Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug-metabolizing enzymes.

Paracetamol has a good safety profile, but pharmacogenetic differences in drug-metabolizing enzymes may have an impact on its risk of hepatotoxicity. We present a case of fatal acute liver failure (ALF) after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy, where pharmacogenetic screening was conducted. This 30-year-old man was electively admitted for a tracheostomy. A total of 14.5 g paracetamol was given over four days. He developed a severe ALF and died 11 days after admission. Pharmacogenetic screening showed absent CYP2D6 metabolism and increased CYP1A2 activity, which may have increased the formation of toxic intermediate metabolite, N-acetyl-p-benzo-quinone imine (NAPQI). He also had decreased function of UGT2B15, which increases the amount of paracetamol available for metabolism to NAPQI. Having a reduced muscle mass and thus a reduced glutathione levels to detoxify produced NAPQI may add to the risk of toxicity. This case may indicate that pharmacogenetic variability is of potential relevance for the risk of paracetamol-induced hepatotoxicity in patients with neuromuscular diseases. Further studies should investigate if pharmacogenetic screening could be a tool to detect potentially increased risk of hepatotoxicity in these patients at therapeutic doses of paracetamol and hence provide information for selection of analgesic treatment.

Long-term stability of extemporaneously prepared captopril oral liquids in glass bottles.

PURPOSE: The long-term stability of captopril in extemporaneously prepared oral liquids was studied. METHODS: Captopril solutions of 1 and 5 mg/mL were prepared in sterile water for irrigation with sorbitol, disodium edetate, and sodium benzoate. The samples were stored in 100-mL amber glass bottles with a headspace of air at 22 degrees C for 12 months. The captopril concentration was determined by high-performance liquid chromatography at 0, 3, 6, 9, and 12 months. The pH of the solutions was also measured, and the physical appearance was recorded. The stability of the 1-mg/mL captopril preparation during 1 month of simulated use when stored at 2-8 degrees C was tested at the start and the end of the 12-month study period. Chemical stability was defined as retention of at least 90% of the initial captopril concentration. The microbiological quality of the preparations was tested at 0, 6, and 12 months (1 mg/mL) and 0 and 12 months (5 mg/mL). RESULTS: Throughout the 12-month study period, the captopril concentration in the oral liquids exceeded 90% of the initial concentration. The lowest concentration (98.5%) was detected in the 5-mg/mL preparation after 3 months of storage. The 1-mg/mL preparation was stable during 1 month of simulated use, both at the start and the end of the 12-month study period. No microbiological growth was observed in any of the samples tested. CONCLUSION: Extemporaneously prepared oral liquid formulations of captopril 1 and 5 mg/mL were chemically stable when stored in glass bottles at room temperature for 12 months when stabilized with 0.1 mg/ mL disodium edetate at a low pH.