The Effect of Renal Replacement Therapy in a Patient with Mercaptopurine Toxicity: Time to Revise Guidelines.

INTRODUCTION: Mercaptopurine, a thiopurine, is used in various disorders of immune regulation, such as autoimmune hepatitis. Thiopurine metabolism is complex with risk for overdosing, especially when metabolism is impaired by liver dysfunction. Hepatotoxicity may be due to mercaptopurine overdose and is often reversible after prompt cessation of the drug. CASE PRESENTATION: Treatment of thiopurine toxicity is mainly supportive and literature on enhanced elimination by renal replacement therapy is ambiguous. CONCLUSION: In this case of thiopurine toxicity, a patient with autoimmune hepatitis presents with abdominal pain, nausea, vomiting, and diarrhea. We show in this case report that renal replacement therapy had no effect on total body clearance of mercaptopurine.

Treatment of a life-threatening dapsone intoxication.

The case report describes a case of a severe dapsone (more than 200 tablets dapsone 100 mg) and mild methotrexate intoxication (10 tablets methotrexate 10 mg) as an attempt to commit suicide, resulting in severe cyanosis with elevation in methemoglobin concentration, treated with methylene blue, ascorbic acid, folinic acid, multidose activated charcoal and hemodialysis. Measurements of blood gases, dapsone and methotrexate levels were performed. Furthermore a hepatitis, pulmonary artery thrombus and a strange taste sensation were diagnosed, probably related to dapsone. The patient recovered and was discharged from hospital after five days. Acute intoxication from excessive dapsone intake is uncommon and clear treatment guidelines are lacking. We here report the treatment modalities as a result of a dapsone intoxication, including the effects on the overall condition of the patient.

Does formative assessment help students to acquire prescribing skills?

PURPOSE: Formative assessments can help motivate students and ease students' learning through feedback. There is a pressing need for improvement of clinical pharmacotherapy (CPT) education since junior doctors make many prescribing errors. The aim of this study was to determine whether a formative assessment with personalized narrative feedback helps medical students to increase their prescribing skills. METHODS: This retrospective cohort study was conducted among masters' medical students at Erasmus Medical Centre, The Netherlands. Students made a formative and a summative skill-based prescription assessment, both during clerkships as part of their regular curriculum. Errors in both assessments were categorized by type and possible consequence and compared with each other. RESULTS: A total of 388 students made 1964 errors in the formative assessment and 1016 in the summative assessment. Most improvements after the formative assessment were seen for mentioning the weight of a child on the prescription (n = 242, 19%). Most new and repeated errors in the summative assessment were missing usage instructions (n = 82, 16% and n = 121, 41%). CONCLUSIONS: This formative assessment with personalized and individual narrative feedback has helped students to increase the technical correctness of their prescriptions. However, errors repeated after the feedback were predominantly errors showing that only one formative assessment has not yet enhanced the clinical prescribing enough.

Case report on postmortem fentanyl measurement after overdose with more than 67 fentanyl patches.

PURPOSE: Fentanyl is an analgesic that is frequently prescribed, which resulted in non-intentional as well as intentional misuse and deaths. Here, we present a postmortem case of a patient who clearly died of a fentanyl overdose due to an extensive number of fentanyl patches combined with oral intake of fentanyl and cocaine. We aimed to show how postmortem analysis can be used to interpret postmortem fentanyl concentrations in unique cases like the one we present. CASE DESCRIPTION: A 23-year-old male was found dead in his bedroom with 67 non-prescribed patches of fentanyl on his body. In the room, there also were fentanyl tablets of 100 µg and cocaine powder, which had possibly also been taken by the deceased. To confirm the cause of death, urine and subclavian blood were retrieved to perform a standard postmortem toxicology screening. The toxicological screening revealed the presence of several drugs, including cocaine, fentanyl, lidocaine and paracetamol. Further analysis of the quantitative postmortem values of fentanyl with ultra-performance liquid chromatography-tandem mass spectrometry revealed a fentanyl concentration of 57.9 µg/L. Considering several issues around postmortem drug analyses, this value seemed to be in line with concentrations found in previously reported postmortem cases. CONCLUSION: We were able to confirm the expected cause of death with an extensive toxicological screening in combination with the circumstantial evidence. We identified fentanyl as most important cause for the fatal outcome in this specific case and simultaneously contributed to the limited availability of knowledge on postmortem fentanyl concentrations.

Potential therapies for sodium azide intoxication; a case report and review of the literature.

Intoxications with sodium azide are rare and in almost all cases lethal in doses above 700 mg or 10mg/kg. We report a case of a patient who ingested 2 grams of sodium azide as a suicide attempt. Sodium azide irreversible blocks cytochrome C oxidase by inhibiting oxidative phosphorylation leading to cell death. There is currently no antidote available. Our patient was treated with a range of therapies, on site, in the emergency department and in the intensive care unit, such as sodium thiosulphate, methylene blue, intralipid, extensive gastric lavage, whole bowel irrigation combined with pro-kinetics, hydroxocobalamin and exchange transfusion. During the clinical course the patient developed cardiac failure, for which veno-arterial ECMO and an intra-aortic balloon pump was placed. However, cardiac function did not recover, leading to discontinuation of treatment after 7 days. As literature on sodium azide intoxication is scarce, we conducted a review to present potential treatment options.

Quantification of beta-lactam antibiotics cefuroxime and flucloxacillin in human synovial fluid, using ultra-performance convergence chromatography-tandem mass spectrometry.

Total hip- and knee arthroplasty generally result in successful outcomes. A small percentage of patients however suffer from periprosthetic joint infections (PJI) postoperatively, often with severe consequences. The standard treatment of chronic PJIs consists of a staged arthroplasty exchange during which antibiotic therapy plays a crucial role. For successful antibiotic treatment, adequate concentrations at the infection site are a prerequisite. Regarding the treatment of PJIs, knowledge is lacking with respect to the relationship between administered dosages and plasma- and infection site concentrations of the antibiotics. To gain insight into the antibiotic exposure at the infection site, validated analytical methods for analysis of the antibiotics in matrices at the site of the PJI are essential. We describe a validated ultra-performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS) method for quantification of the beta-lactam antibiotics cefuroxime and flucloxacillin in synovial fluid. This method was successfully validated for antibiotic quantification in synovial fluids according to the EMA guidelines and consists of a simple sample preparation. For both antibiotics, the accuracy and precision were within requirements (RSD < 15%). In addition, matrix effects and recovery were within the range of 80-120%. Carry over was less than 20% and stability in -80 °C was at least 2 months for standards and quality controls. The limits of quantification were adequate (1-100 mg/L) to cover potential cefuroxime and flucloxacillin concentrations in synovial fluid as described in literature (r > 0.995). The method has a run time of 4.5 min and 50 µL synovial fluid is needed and the validated method will be applied during a PK/PD study to determine the exposure of the study antibiotics in synovial fluid at the site of PJIs.

A diagnostic tool for self-poisoned patients: Analysis of gastric content and lavage fluids.

Approximately 500 patients per year are admitted to the emergency department (ED) of the Erasmus University Medical Center presenting with intoxications with medication. For adequate treatment, it is sometimes important to know which drugs in which quantities were ingested. This can require laboratory analysis of blood or urine samples; however, these samples do not provide information about the possible effects that can still be expected. We performed toxicological screening on the gastric content of three patients admitted to our ED in January and February 2018. These patients underwent gastric lavage or received a gastric tube as part of routine care. The gastric fluid was analysed via UPLC-MS/MS using the Waters method for toxicological screening. In all three patients, we successfully determined drugs in the gastric content. In two patients, we identified more different drugs in the gastric content than in blood plasma. In the other patient, admitted approximately six hours after a severe autointoxication with the betablocker metoprolol, we found significant amounts of metoprolol in the gastric content acquired by gastric lavage. We therefore believe that analysis of gastric content after an intoxication can have multiple applications; for example, it may provide information about symptoms of intoxication that can be expected, it may aid patient care and may provide insight in the toxicokinetics of different drugs. In conclusion, we demonstrate that toxicological screening and quantification of drug levels in gastric content is possible and has potential as an adjunct in patient care, but limitations need to be addressed before implementation in clinical practice.

Symptomatic rebound methaemoglobinaemia after treatment with dapsone.

A 28-year-old female patient was admitted to our hospital with severe dyspnoea and hypoxemia due to methaemoglobinaemia caused by dapsone. The patient recovered completely after repeated infusions of methylene blue and cessation of dapsone. However, 12 days after cessation of dapsone, the patient was readmitted due to recurrence of symptoms based on a relapse of methaemoglobinaemia. Toxicological analysis revealed a toxic dapsone level at readmission and no other explanation for methaemoglobinaemia. Several possible mechanisms as explanation for the recurrence of methaemoglobinaemia are listed and additional tests were performed. In addition to supportive care, treatment consisted of methylene blue; furthermore, cimetidine and ascorbic acid were added. An overview of the pathophysiology, diagnostics, treatment, and possible explanations for this relapse of methaemoglobinaemia caused by dapsone are given. This case shows the importance of considering the possibility of a late rebound methaemoglobinaemia after discontinuation of dapsone.

Cardiac arrest following chloroquine overdose treated with bicarbonate and lipid emulsion.

We describe a 27-year-old female with repeated episodes of pulseless electrical activity due to intoxication with a substance that was unidentified at presentation. Severe QRS widening was observed and empiric treatment with sodium bicarbonate and intravenous lipid emulsion was administered. In this case, intraosseous administration of lipid emulsion failed to improve haemodynamic parameters, suggesting that this dose remained in the bone marrow compartment. We recommend that physicians become aware of this possibility and to avoid intraosseous administration of lipid emulsion.

Central nervous system involvement in a rare genetic iron overload disorder.

In most genetic iron overload disorders the diagnosis can be rejected when transferrin saturation is low. We describe a patient and her family with hyperferritinaemia and low transferrin saturation with iron accumulation in the central nervous system (CNS) and liver due to hereditary aceruloplasminaemia. In this rare genetic iron overload disorder oxidation of iron is disturbed, resulting in storage of iron in the CNS and visceral organs.