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.

Performance of three point-of-care urinalysis test devices for drugs of abuse and therapeutic drugs applied in the emergency department.

BACKGROUND: Point-of-care tests for toxicological screening of patients for drugs of abuse and therapeutic drugs may be helpful in the emergency department (ED) to assist in a rapid diagnosis. OBJECTIVES: In this prospective study, the performance of TesTcard9® (Varian; Middelburg, Netherlands), Syva RapidTest d.a.u. 10® (Dade Behring; Leusden, Netherlands), and Triage TOX Drug Screen® (Biosite; Bunnik, Netherlands), when applied on-site in the ED by physicians and nurses, was evaluated. METHODS: Patients in the ED were included in the study when a physician thought the patient could benefit from a toxicological screen. Urine samples were screened utilizing the three point-of-care tests. All three tests simultaneously determined the presence of amphetamines, methamphetamine, opiates, methadone (except for TesTcard9), cocaine, cannabis, barbiturates, benzodiazepines, tricyclic antidepressants, and phencyclidine. The same urine specimen was analyzed in the pharmacy department using Syva EMIT II immunoassay and chromatographic confirmation. The results were compared for agreement. RESULTS: During the 6-month study period, 80 urine samples were screened. In total, 62 (78%) specimens were found positive for at least one drug. Amphetamines (n = 16), cocaine (n = 27), cannabis (n = 25), benzodiazepines (n = 25), and opiates (n = 8) were the most frequently found. The sensitivity and specificity of all three devices were higher than 93% for these compounds, with the exception of the sensitivity for cannabis with the TesTcard9 (88%) and the sensitivity for benzodiazepines with the Syva RapidTest d.a.u. 10 (88%) and TesTcard9 (80%). CONCLUSION: In the ED setting, the Triage TOX Drug Screen performed better than the other point-of-care tests, probably due to its more objective reading system and its adequate quality controls.

Presence of tobramycin in blood and urine during selective decontamination of the digestive tract in critically ill patients, a prospective cohort study.

INTRODUCTION: Tobramycin is one of the components used for selective decontamination of the digestive tract (SDD), applied to prevent colonization and subsequent infections in critically ill patients. Tobramycin is administered in the oropharynx and gastrointestinal tract and is normally not absorbed. However, critical illness may convey gut barrier failure. The aim of the study was to assess the prevalence and amount of tobramycin leakage from the gut into the blood, to quantify tobramycin excretion in urine, and to determine the association of tobramycin leakage with markers of circulation, kidney function and other organ failure. METHODS: This was a prospective observational cohort study. The setting was the 20-bed closed format-mixed ICU of a teaching hospital. The study population was critically ill patients with an expected stay of more than two days, receiving SDD with tobramycin, polymyxin-E and amphotericin-B four times daily in the oropharynx and stomach. Tobramycin concentration was measured in serum (sensitive high performance liquid chromatography - mass spectrometry/mass spectrometry (HLPC-MS/MS) assay) and 24-hour urine (conventional immunoassay), in 34 patients, 24 hours after ICU admission, and in 71 patients, once daily for 7 days. Tobramycin leakage was defined as tobramycin detected in serum at least once (> 0.05 mg/L). Ototoxicity was not monitored. RESULTS: Of the 100 patients with available blood samples, 83 had tobramycin leakage. Median highest serum concentration for each patient was 0.12 mg/L; 99% of the patients had at least one positive urinary sample (> 0.5 mg/L), 49% had a urinary concentration ≥ 1 mg/L. The highest tobramycin serum concentration was significantly associated with vasopressor support, renal and hepatic dysfunction, and C-reactive protein. At binary logistic regression analysis, high dopamine dose and low urinary output on Day 1 were the significant predictors of tobramycin leakage. Nephrotoxicity could not be shown. CONCLUSIONS: The majority of acute critically ill patients treated with enteral tobramycin as a component of SDD had traces of tobramycin in the blood, especially those with severe shock, inflammation and subsequent acute kidney injury, suggesting loss of gut barrier and decreased renal removal. Unexpectedly, urinary tobramycin was above the therapeutic trough level in half of the patients. Nephrotoxicity could not be demonstrated.

Simple and sensitive method for quantification of low tobramycin concentrations in human plasma using HPLC-MS/MS.

After oral administration of tobramycin, as part of selective decontamination of the digestive tract (SDD) in critically ill patients, absorption of tobramycin from the gut into the blood may take place. To quantify low concentrations of tobramycin in human plasma, we developed and validated a simple (sample pre-treatment consisting of protein precipitation with acetonitrile using 200microl plasma), rapid (runtime 3min using a Pathfinder MR reversed-phase column) and sensitive (concentration range of 0.05-1.0mg/l using MS/MS detection) method.