Search

A new assay was developed to measure the concentration of remimazolam besylate (CNS7056B) and its major carboxylic acid metabolite (CNS7054X) in human plasma. For this new assay method, midazolam-d4 maleate was used as an internal standard. After setting up a previously described assay method, using CNS7056-d4 and CNS7054-d4 as internal standards, analytical results of both methods were compared. For the new analytical method, ultra-high-performance liquid chromatography (UHPLC) with tandem mass spectrometry was applied. A purification method, using solid phase extraction, was developed and validated. The chromatographic separation of the analytes was achieved with a mobile phase gradient using a Water Acquity™ UHPLC-System. The Kinetex™ biphenyl 50 × 2.1 mm UHPLC column was used with a particle diameter of 1.7 μm (Phenomenex, Germany). A measuring range of 0.6–2,000 ng/mL for CNS7056B and of 6–20,000 ng/mL for CNS7054X could be achieved with this new assay. The lower limit of quantification was 0.6 ng/mL for CNS7056B and 6 ng/mL for CNS7054X. The assay was validated according to US Food and Drug Administration guidelines. The new method showed an accuracy of 96.9–110.4% and a precision of 2.1–6.7% for both analytes.

Background Patient-controlled analgesia (PCA) is a common method for postoperative pain therapy, but it is characterized by large variation of plasma concentrations. PCA with target-controlled infusion (TCI-PCA) may be an alternative. In a previous analysis, the authors developed a pharmacokinetic model for hydromorphone. In this secondary analysis, the authors investigated the feasibility and efficacy of TCI-PCA for postoperative pain therapy with hydromorphone. Methods Fifty adult patients undergoing cardiac surgery were enrolled in this study. Postoperatively, hydromorphone was applied intravenously during three sequential periods: (1) as TCI with plasma target concentrations of 1 to 2 ng/ml until extubation; (2) as TCI-PCA with plasma target concentrations between 0.8 and 10 ng/ml during the following 6 to 8 h; and (3) thereafter as PCA with a bolus dose of 0.2 mg until the next morning. During TCI-PCA, pain was regularly assessed using the 11-point numerical rating scale (NRS). A pharmacokinetic/pharmacodynamic model was developed using ordinal logistic regression based on measured plasma concentrations. Results Data of 43 patients aged 40 to 81 yr were analyzed. The hydromorphone dose during TCI-PCA was 0.26 mg/h (0.07 to 0.93 mg/h). The maximum plasma target concentration during TCI-PCA was 2.3 ng/ml (0.9 to 7.0 ng/ml). The NRS score under deep inspiration was less than 5 in 83% of the ratings. Nausea was present in 30%, vomiting in 9%, and respiratory insufficiency in 5% of the patients. The EC50 of hydromorphone for NRS of 4 or less was 4.1 ng/ml (0.6 to 12.8 ng/ml). Conclusion TCI-PCA with hydromorphone offered satisfactory postoperative pain therapy with moderate side effects.

Background Continuous non-invasive arterial pressure measured with CNAP™ (CNAP) has been shown to be superior to intermittent oscillometric measurements during procedural sedation and spinal anaesthesia. We assessed the performance of CNAP during general anaesthesia by analysis of agreement with invasive measurements of arterial pressure (AP). Methods Eighty-eight patients undergoing elective abdominal surgery, cardio-, or neurosurgery were included in the study. Systolic, diastolic, and mean AP measured by an intra-arterial catheter in the radial artery (IAP) were compared with those obtained by CNAP from the same arm. Data were analysed to determine the precision (i.e. measurement error) and accuracy (i.e. systematic error) of beat-to-beat CNAP values with respect to IAP. Also, we compared the frequency of fast changes in AP (FCAP) and hypotension (IOH) by both methods. Results CNAP precision of 4.5, 3.1, and 3.2 mm Hg (systolic, diastolic, and mean AP, respectively) was not significantly different from IAP precision, and CNAP accuracy was +6.7, −5.6, and −1.6 mm Hg. The frequency of AP pairs having a difference within the calculated limits of agreement was 81%, 64%, and 76% for systolic, diastolic, and mean AP, respectively. The calculated limits of agreement were ±17.6, ±11.4, and ±12.0 mm, Hg, respectively. CNAP and IAP detected simultaneously to 82.1% FCAP and to 84.6% IOH. Conclusions CNAP provides real-time estimates of arterial pressure comparable with those generated by an invasive intra-arterial catheter system during general anaesthesia.

The objective was to compare two methods for assessing eating disorder psychopathology in pre-gastric banding surgery patients. 93 morbidly obese patients were assessed with the German versions of the Eating Disorder Examination (EDE) and the Eating Disorder Examination-Questionnaire (EDE-Q). The EDE and the EDE-Q were significantly correlated on the restraint, eating concern, shape concern and weight concern subscales, although the questionnaire scores were significantly higher. Frequencies of objective bulimic episodes were slightly but significantly correlated and the difference between EDE and EDE-Q was not significant. When participants were classified as binge eaters based on a cut-off of two binges per week on average in the last 28 days, the concordance between EDE and EDE-Q was moderate. The EDE-Q seems well-suited in assessing eating disorder psychopathology in obese pre-gastric banding patients. Yet, for the assessment of binge eating episodes the use of the questionnaire alone can not be recommended.

The objective was to compare two methods for assessing eating disorder psychopathology in pre-gastric banding surgery patients. 93 morbidly obese patients were assessed with the German versions of the Eating Disorder Examination (EDE) and the Eating Disorder Examination-Questionnaire (EDE-Q). The EDE and the EDE-Q were significantly correlated on the restraint, eating concern, shape concern and weight concern subscales, although the questionnaire scores were significantly higher. Frequencies of objective bulimic episodes were slightly but significantly correlated and the difference between EDE and EDE-Q was not significant. When participants were classified as binge eaters based on a cut-off of two binges per week on average in the last 28 days, the concordance between EDE and EDE-Q was moderate. The EDE-Q seems well-suited in assessing eating disorder psychopathology in obese pre-gastric banding patients. Yet, for the assessment of binge eating episodes the use of the questionnaire alone can not be recommended.