BackgroundAppropriate utilization of vancomycin is important to attain therapeutic targets while avoiding clinical failure and the development of antimicrobial resistance. Our aim was to observe the use of vancomycin in an intensive care population, with the main focus on achievement of therapeutic serum concentrations (15–20 mg/l) and to evaluate how this was influenced by dose regimens, use of guidelines and therapeutic drug monitoring.MethodsA prospective observational study was carried out in the intensive care units at two tertiary hospitals in Norway. Data were collected from 83 patients who received vancomycin therapy, half of these received continuous renal replacement therapy. Patients were followed for 72 h after initiation of therapy. Blood samples were drawn for analysis of trough serum concentrations. Urine was collected for calculations of creatinine clearance. Information was gathered from medical records and electronic health records.ResultsLess than 40% of the patients attained therapeutic trough serum concentrations during the first 3 days of therapy. Patients with augmented renal clearance had lower serum trough concentrations despite receiving higher maintenance doses and more loading doses. When trough serum concentrations were outside of therapeutic range, dose adjustments in accordance to therapeutic drug monitoring were made to less than half.ConclusionThe present study reveals significant challenges in the utilization of vancomycin in critically ill patients. There is a need for clearer guidelines regarding dosing and therapeutic drug monitoring of vancomycin for patient subgroups.

PurposeTo investigate the extent of medication discrepancies (MDs) revealed by medication reconciliation (MR) and to assess the potential clinical relevance of the MDs for the patients in a short-term and long-term perspectives.MethodsPatients ≥18 years admitted to five internal medicine wards were included in this prospective study. MDs between the medication list obtained by physicians at hospital admission and medication list obtained by a structured MR process by pharmacists were identified and assessed for clinical relevance by an expert team. Clinical relevance was assessed in two ways as (a) if they were not acted upon during the hospital stay (short term) or (b) if they persisted after discharge from the hospital (long term).ResultsIn total 262 patients, age 19–98 (SD 18.94, mean 73.4 years), 58.8% female, were included. 79.4% of the patients had at least one MD with a mean of 3.2 MDs/patient. 80.7% of the MDs were discussed with the physician, and 95.5% of these were acted upon. Of the 438 MDs evaluated by the expert panel, 35.2% and 71.2% were assessed to be of moderate, major or extreme clinical relevance in the short-term and long-term perspectives, respectively.ConclusionsBy using a structured approach, MDs were identified for 80% of the patients and the majority of the MDs were evaluated to possibly harm the patient in a long-term perspective. The results emphasise that structured MRs may improve patient safety.Trial registration number2011/542.

The Peppermint Initiative seeks to inform the standardisation of breath analysis methods. Five Peppermint Experiments with gas chromatography-ion mobility spectrometry (GC-IMS), operating in the positive mode with a tritium 3H 5.68 keV, 370 MBq ionisation source, were undertaken to provide benchmark Peppermint Washout data for this technique, to support its use in breath-testing, analysis, and research. Headspace analysis of a peppermint-oil capsule by GC-IMS with on-column injection (0.5 cm3) identified 12 IMS responsive compounds, of which the four most abundant were: eucalyptol; β-pinene; α-pinene; and limonene. Elevated concentrations of these four compounds were identified in exhaled-breath following ingestion of a peppermint-oil capsule. An unidentified compound attributed as a volatile catabolite of peppermint-oil was also observed. The most intense exhaled peppermint-oil component was eucalyptol, which was selected as a peppermint marker for benchmarking GC-IMS. Twenty-five washout experiments monitored levels of exhaled eucalyptol, by GC-IMS with on-column injection (0.5 cm3), at t=0 min, and then at t+60, t+90, t+165, t+285 and t+360 min from ingestion of a peppermint capsule resulting in 148 peppermint breath analyses. Additionally, the Peppermint Washout data was used to evaluate clinical deployments with a further five washout tests run in clinical settings generating an additional 35 breath samples. Regression analysis yielded an average extrapolated time taken for exhaled eucalyptol levels to return to baseline values to be 429 ± 62 min (± 95% confidence-interval). The benchmark value was assigned to the lower 95 % confidence-interval, 367 min. Further evaluation of the data indicated that the maximum number of volatile organic compounds (VOC) discernible from a 0.5 cm3 breath sample was 69, while the use of an in-line biofilter appeared to reduce this to 34.

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.

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.

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.

BackgroundFomepizole is the preferred antidote for treatment of methanol and ethylene glycol poisoning, acting by inhibiting the formation of the toxic metabolites. While very effective, the price is high, and the availability limited. Its availability is further challenged in situations with mass poisonings. Therefore, a fifty percent reduced maintenance dose for fomepizole during continuous renal replacement therapy (CRRT) was suggested in 2016, based on pharmacokinetic data only. Our aim was to study whether this new dosing for fomepizole during CRRT gave plasma concentrations above the required 10 µmol/L. Secondly, we wanted to study the elimination kinetics of fomepizole during CRRT, which has never been studied before. MethodsProspective observational study of adult patients treated with fomepizole and CRRT. We collected samples from arterial line (pre-filter) = plasma concentration, post-filter and dialysate for fomepizole measurements. Fomepizole was measured using high-pressure liquid chromatography with a reverse phase column. ResultsTen patients were included in the study. Seven were treated with continuous veno-venous hemodialysis (CVVHD) and three with continuous veno-venous hemodiafiltration (CVVHDF).Ninety-eight percent of the plasma samples were above the minimum plasma concentration of 10 µmol/L. Fomepizole was removed during CRRT with a median saturation/sieving coefficient of 0.85 and dialysis clearance of 28 mL/min. ConclusionFomepizole was eliminated during CCRT. The new dosing recommendations for fomepizole and CRRT appeared safe, by maintaining the plasma concentration above the minimum value of 10 µmol/L.Based on these data the fomepizole maintenance dose during CRRT could be reduced to half as compared to intermittent hemodialysis.

Introduction and Aims. Methanol poisonings pose a major risk especially where illegal alcohol is consumed. The source of the methanol in the drinks are debated. We aimed to evaluate whether home distillation of alcohol made from rice was capable of producing toxic amounts of methanol. Design and Methods. Twenty households with homemade alcohol production in Phu Tho province in Vietnam were included in this pilot study. We followed the whole production process and an alcohol sample from each household was analysed for methanol content. Results. 17 (85%) of the samples contained detectable levels of methanol. The median concentration was 9 mg/L (range 2-37 mg/L). To develop clinical symptoms of methanol poisoning from the sample with the highest concentration would require drinking more than 424 L. Discussion and Conclusions. Homemade alcohol from rice did not contain sufficient amount of methanol to cause toxicity in our study. This supports the theory of methanol being added to ethanol post production for economical purposes as the main source of mass poisonings. [Lao Y, Pham BD, Le HT, Nguyen Van H, Hovda KE. Methanol content in homemade alcohol from a province in North Vietnam. Drug Alcohol Rev 2019;38:537-542]