RESUMO
The benzodiazepine, midazolam, is one of the most frequently used sedatives in intensive care medicine, but it has an unfavorable pharmacokinetic profile when continuously applied. As a consequence, patients are frequently prolonged and more deeply sedated than intended. Due to its distinct pharmacological features, including a cytochrome P450-independent metabolization, intravenous lormetazepam might be clinically advantageous compared to midazolam. In this retrospective cohort study, we compared patients who received either intravenous lormetazepam or midazolam with respect to their survival and sedation characteristics. The cohort included 3314 mechanically ventilated, critically ill patients that received one of the two drugs in a tertiary medical center in Germany between 2006 and 2018. A Cox proportional hazards model with mortality as outcome and APACHE II, age, gender, and admission mode as covariates revealed a hazard ratio of 1.75 [95% CI 1.46-2.09; p < 0.001] for in-hospital mortality associated with the use of midazolam. After additionally adjusting for sedation intensity, the HR became 1.04 [95% CI 0.83-1.31; p = 0.97]. Thus, we concluded that excessive sedation occurs more frequently in critically ill patients treated with midazolam than in patients treated with lormetazepam. These findings require further investigation in prospective trials to assess if lormetazepam, due to its ability to maintain light sedation, might be favorable over other benzodiazepines for sedation in the ICU.
RESUMO
Objective: Age-related disorders, such as dementia, significantly contribute to the global burden of disease. Adequate screening in the primary care setting is critical for early detection and proper management. The Addenbrooke's Cognitive Examination III (ACE-III) is an open-source neuropsychological test with superior diagnostic quality in comparison to the Mini-Mental State Examination (MMSE). Our aim was to perform a guideline-conform English-German translation and cultural adaptation of the ACE-III in order to enable implementation in German-speaking countries. Methods: The translation and cultural adaptation were performed in accordance with the "Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes (PRO) Measures" from the International Society for Pharmacoeconomics and Outcome Research (ISPOR) (Wild et al. 2005). Four separate English-German translations were compiled into one German consensus translation, which was then translated back into English and compared to the original English version. After comparison, the German consensus translation was revised with emphasis on the identified differences between the English original version and the English translated version. This revised German consensus translation was subsequently evaluated for clinical applicability on a 5-point scale (0 - not applicable; 5 - applicable without any restrictions) by 20 practitioners experienced in the field of neuropsychological testing, using an anonymized, paper-based 22-item survey. Results: Nineteen of the 20 practitioners (95.0%) rated the German ACE-III translation as overall applicable. The median rating was 4.0 [IQR (4.0/5.0)]. When evaluating survey items assessing the applicability of the individual 19 subtests of the ACE-III, all of them (100%) were rated as applicable with a median rating of 4.5 [IQR (4.1/4.9)]. Conclusion: The German ACE-III translation in its current form is generally applicable and can be utilized for clinical and scientific purposes.
