Suicide Mortality, Suicidal Ideation and Psychological Problems in Dutch Anaesthesiologists

Previous studies reveal an elevated suicide rate for anaesthesiologists. We sought to examine anaesthesiologist suicide mortality and its underlying explanatory factors. Two studies were conducted in order to establish the suicide mortality figures among Dutch anaesthesiologists and to investigate life events, workrelated stress, psychological problems and alcohol- and drug abuse in relation to suicidal ideation. The results suggest that suicide mortality in anaesthesiologists in The Netherlands is elevated, and comparable to that in other Western countries, but small numbers prevent robust testing of this difference. Anaesthesiologists are more likely than the general population to experience sleeping problems and suicidal ideation; male anaesthesiologists are more likely to suffer from depression. The prevalence of suicide among this population may be related to a high prevalence of psychological problems, in addition to the knowledge and availability of means. Areas of suicide prevention among this group are discussed.Security and Global Affair

Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide

Perioperative Medicine: Efficacy, Safety and Outcom

The association of polypharmacy with functional decline in elderly patients undergoing cardiac surgery

Aims: Identifying preoperative risk factors in older patients becomes more important to reduce adverse functional outcome. This study investigated the association between preoperative medication use and functional decline in elderly cardiac surgery patients and compared polypharmacy as a preoperative screening tool to a clinical frailty assessment.Methods: This sub-study of the Anaesthesia Geriatric Evaluation study included 518 patients aged ≥70 years undergoing elective cardiac surgery. The primary outcome was functional decline, defined as a worse health-related quality of life or disability 1 year after surgery. The association between polypharmacy (i.e. ≥5 prescriptions and Results: Functional decline was reported in 284 patients (55%) and preoperative polypharmacy and excessive polypharmacy showed higher risks (adjusted relative risk 1.57, 95% confidence interval [CI] 1.23-1.98 and 1.93, 95% CI 1.48-2.50, respectively). Besides cardiovascular medication, proton-pump inhibitors and central nervous system medication were significantly associated with functional decline. Discrimination between models with polypharmacy or frailty was similar (area under the curve 0.67, 95% CI 0.61-0.72). The net reclassification index improved when including polypharmacy to the basic model (17%, 95% CI 0.06-0.27).Conclusion: Polypharmacy is associated with functional decline in elderly cardiac surgery patients. A preoperative medication review is easily performed and could be used as screening tool to identify patients at risk for adverse outcome after cardiac surgery.Pharmacolog

Total bodyweight and sex both drive pharmacokinetic variability of fluconazole in obese adults

Background Fluconazole is commonly used to treat or prevent fungal infections. It is typically used orally but in critical situations, IV administration is needed. Obesity may influence the pharmacokinetics and therapeutic efficacy of a drug. In this study, we aim to assess the impact of obesity on fluconazole pharmacokinetics given orally or IV to guide dose adjustments for the obese population. Methods We performed a prospective pharmacokinetic study with intensive sampling in obese subjects undergoing bariatric surgery (n = 17, BMI >= 35 kg/m(2)) and non-obese healthy controls (n = 8, 18.5 <= BMI < 30.0 kg/m(2)). Participants received a semi-simultaneous oral dose of 400 mg fluconazole capsules, followed after 2 h by 400 mg IV. Population pharmacokinetic modelling and simulation were performed using NONMEM 7.3. Results A total of 421 fluconazole concentrations in 25 participants (total bodyweight 61.0-174 kg) until 48 h after dosing were obtained. An estimated bioavailability of 87.5% was found for both obese and non-obese subjects, with a 95% distribution interval of 43.9%-98.4%. With increasing total bodyweight, both higher CL and V-d were found. Sex also significantly impacted V-d, being 27% larger in male compared with female participants. Conclusions In our population of obese but otherwise healthy individuals, obesity clearly alters the pharmacokinetics of fluconazole, which puts severely obese adults, particularly if male, at risk of suboptimal exposure, for which adjusted doses are proposed.Pharmacolog

Dose recommendations for gentamicin in the real-world obese population with varying body weight and renal (dys)function

Background: The impact of weight on pharmacokinetics of gentamicin was recently elucidated for (morbidly) obese individuals with normal renal function.Objectives: To characterize the pharmacokinetics of gentamicin in real-world obese patients, ultimately to develop dose recommendations applicable across the entire obese population.Methods: In two Large Dutch hospitals, all admitted patients with BMI >= 25 kg/m(2) with at Least one gentamicin administration, at Least one gentamicin and at Least one creatinine serum concentration measurement were included. Data from one hospital, obtained from electronic health records, combined with prospective data of non-obese and morbidly obese people with normal renal function, served as the training dataset, and data from the second hospital served as the external validation dataset.Results: In the training dataset [1187 observations from 542 individuals, total body weight (TBW) 52-221 kg and renal function (CKD-EPI) 5.1-141.7 mL/min/1.73 m(2)], TBW was identified as a covariate on distribution volume, and de-indexed CKD-EPI and ICU stay on clearance (all P< 0.001). Clearance was 3.53 L/h and decreased by 0.48 L/h with each 10 mL/min reduction in de-indexed CKD-EPI. The results were confirmed in the external validation (321 observations from 208 individuals, TBW 69-180 kg, CKD-EPI 5.3-130.0 mL/min/1.73 m(2)).Conclusions: Based on the study, we propose specific mg/kg dose reductions with decreasing CKD-EPI values for the obese population, and extension of the dosing interval beyond 24 h when CKD-EPI drops below 50 mL/min/1.73 m(2). In ICU patients, a 25% dose reduction could be considered. These guidelines can be used to guide safe and effective dosing of gentamicin across the real-world obese population.Pharmacolog