Can emergency department clinicians diagnose gamma-hydroxybutyrate (GHB) intoxication based on clinical observations alone?

OBJECTIVES: Gamma-hydroxybutyrate (GHB) is a drug of abuse with central depressing effects, which may cause coma with a GCS score as low as 3. A rapid diagnosis 'GHB intoxication' may prevent unnecessary diagnostic work-up and may lead to guided, less invasive, treatment. The aim of this study was to evaluate if ED physicians' clinical evaluation were sufficient for diagnosis in patients with suspected GHB-intoxication. METHODS: Patients presenting at the ED with a GCS<15 and a potential intoxication with drugs of abuse for whom urine toxicology screen was performed were included consecutively. After a first assessment, the ED physician registered the most likely initial diagnosis in the hospital information system. Urine of these patients was tested with a validated gas chromatography analytical method for GHB (confirmation test). The initial diagnoses were compared for agreement with the results of the confirmation test. RESULTS: A total of 506 patients were included, 100 patients tested positive for GHB and 406 patients tested negative for GHB. Sensitivity and specificity of the ED physicians compared with the confirmation test to diagnose GHB intoxications were 63% (95% CI 52 to 73) and 93% (95% CI 90 to 95), respectively. The positive predictive value was 67% (95% CI 60 to 77) and the negative predictive value was 92% (95% CI 88 to 94). CONCLUSION: Physicians underestimate the presence of GHB intoxication and can fail to diagnose GHB intoxication based on clinical observations alone. In the future, a rapid reliable initial analytical GHB test in addition to clinical judgement could be valuable to reduce false negative diagnosis.

Prospective Investigation of the Performance of 2 Gamma-Hydroxybutyric Acid Tests: DrugCheck GHB Single Test and Viva-E GHB Immunoassay.

BACKGROUND: Gamma-hydroxybutyric acid (GHB) is a recreational drug with central nervous system depressing effects that is often abused. A urine GHB point-of-care test can be of great diagnostic value. The objective of this prospective study was to determine the performance of the new DrugCheck GHB Single Test and the Viva-E GHB immunoassay for urine samples in emergency department patients. METHODS: Patients presented to the emergency department of the OLVG hospital in Amsterdam with a Glasgow Coma Scale score <15 and potential drug of abuse intoxication were included in the study. Between June 2016 and October 2017, 375 patients were included. Using the DrugCheck GHB Single Test (Express Diagnostics Int'l, Blue Earth, MN) and the Viva-E GHB immunoassay (Siemens Healthineers, The Hague, the Netherlands), patients' urine samples were tested for GHB (cutoff for a positive result, 10 or 50 mcg/mL GHB). To ensure quality, the results obtained were compared with those generated using a validated gas chromatography method. The tests were considered reliable if specificity and sensitivity were both >90%. Possible cross-reactivity with ethanol was investigated by analyzing ethanol concentrations in patients' samples. RESULTS: Seventy percentage of the included patients was men, and the median age was 34 years old. The DrugCheck GHB Single Test's specificity and sensitivity were 90.0% and 72.9%, respectively, and using 50 mcg/mL as a cutoff value, its specificity and sensitivity improved to 96.7% and 75.0%, respectively. Serum and urine ethanol levels in the false-positive group were significantly higher compared with those in the true-negative group. The specificity and sensitivity of the Viva-E GHB immunoassay (cutoff value of 50 mcg/mL and excluding samples with ethanol levels ≥2.0 g/L) were 99.4% and 93.5%, respectively. CONCLUSIONS: The DrugCheck GHB Single Test's specificity was sufficient, whereas its sensitivity was poor, making it unsuitable for use at point-of-care. Contrarily, using 50 mcg/mL as the cutoff value and excluding samples with ethanol levels ≥2.0 g/L, the Viva-E GHB immunoassay showed acceptable results to detect clinically relevant GHB intoxications.

Effects of unbound mycophenolic acid on inosine monophosphate dehydrogenase inhibition in pediatric kidney transplant patients.

BACKGROUND: Mycophenolic acid (MPA) is a key immunosuppressive drug that acts through inhibition of inosine monophosphate dehydrogenase (IMPDH). MPA is commonly measured, as part of therapeutic drug monitoring, as the total concentration in plasma. However, it has been postulated that the free (unbound) fraction of MPA (fMPA) is responsible for the immunosuppressive effects. In this study, a sensitive low volume high-performance liquid chromatography (HPLC) assay was developed to measure fMPA concentrations to explore the relationship between fMPA and IMPDH activity. METHODS: To obtain fMPA concentrations, plasma samples were filtrated using Centrifree ultrafiltration devices. The ultrafiltrate was analyzed by HPLC using a Kinetex C18 column (2.6 µm, 3.0 × 75 mm). fMPA concentrations were compared with the total MPA concentrations available in 28 pediatric kidney transplant patients at 3 consecutive occasions after transplantation. The relationship between fMPA and IMPDH activity was analyzed using an Emax model. RESULTS: The HPLC assay, using 25 µL of the ultrafiltrates, was validated over a range from 2.5 to 1000 µL with good accuracy, precision, and reproducibility. Total and free MPA concentrations were well correlated (R = 0.85, P < 0.0001), although large intraindividual and interindividual variability in the bound MPA fractions was observed. The overall relationship between fMPA concentrations and IMPDH inhibition using the Emax model was comparable with that of total MPA, as previously reported. The model estimated EC50 value (164.5 µL) is in good agreement with reported in vitro EC50 values. CONCLUSIONS: This study provides a simple HPLC method for the measurement of fMPA and a pharmacologically reasonable EC50 estimate. The good correlation between the total and free MPA concentrations suggests that routine measurement of fMPA to characterize mycophenolate pharmacokinetic and pharmacodynamic does not seem warranted, although the large variability in the bound fractions of MPA warrants further study.