Polypharmacy and potentially inadequate medication as risk factors for the development of postoperative delirium in elderly patients

Introduction: Postoperative delirium (POD) is a common postoperative disorder with increased complication and mortality rates. The aetiology is multifactorial. The elderly (>/= 65 years) are particularly at risk because of high cerebral vulnerability and the interaction of predisposing and precipitating risk factors. Polypharmacy and potentially inadequate medications (PIMs) can have an indirect or direct delirogenic effect. This paper investigates a possible association between preoperative polypharmacy and potentially inadequate medication (according to the PRISCUS list and the EU(7)PIM list) and the development of POD in elderly patients. Methods: This investigation was conducted as a part of the multicenter study "Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)" at the location Charité Universitätsmedizin Campus Virchow Klinikum (CVK). Patients aged >/= 65 years with major elective surgery (>/= 60 minutes) were included. The primary endpoint was the incidence of POD within 7 days postoperatively, assessed using the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-5) and/or the Nursing Delirium Screening Scale (NuDESC) and/or the Confusion Assessment Method (CAM) and/or the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and/or chart review. The long-term medication of the study participants was tested for polypharmacy (>/= 5 drugs) and screened for potentially inadequate medication using the PRISCUS list and EU(7)PIM list. The data were analysed using logistic regression analysis. The following confounding variables were considered: age, gender, education level, nutritional status, surgical area, duration of anaesthesia, comorbidities (according to Charlson Comorbidity Index) and activities of daily living (ADL). Results: From October 2015 to April 2017 394 study participants (median age 73 years, 49.7% women) were included, of whom 25.1% developed POD. In the study group suffering from POD, more study participants showed polypharmacy (54.5% vs. 40.3%) and PIMs according to the EU(7)PIM list (70.7% vs. 54.9%) or PRISCUS list (12.1% vs. 10.5%). In the regression analysis no association between polypharmacy or PIM and POD could be demonstrated. The already known influence of the confounders age, educational status and duration of anaesthesia was confirmed. Conclusion: Polypharmacy and PIMs according to the PRISCUS list or EU(7)PIM list have not been shown to be independent risk factors for the development of POD. This study is currently the only one investigating the influence of PIMs on POD when considering the international study situation. Because polypharmacy and PIMs generally increase the risk of side effects, drug interactions and serious adverse events, they should be considered in future studies on POD and in the context of delirium prevention.Das postoperative Delir (POD) ist eine häufige postoperative Erkrankung mit erhöhten Komplikations- und Mortalitätsraten. Die Ätiologie ist multifaktoriell. Betagte Menschen (≥ 65 Jahre) sind aufgrund des Zusammenwirkens prädisponierender und präzipitierender Risikofaktoren besonders gefährdet. Polypharmazie und potentiell inadäquate Medikamente (PIMs) können mittelbar oder unmittelbar delirogen wirken. Ziel dieser Arbeit ist es, einen Zusammenhang zwischen präoperativer Polypharmazie oder potentiell inadäquater Medikation (PIM) gemäß der PRISCUSListe oder der EU(7)PIM-Liste und der Entwicklung eines POD bei älteren Patienten aufzuzeigen. Methoden Die vorliegende Arbeit fand im Rahmen der multizentrischen Studie „Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)“ am Standort Charité Universitätsmedizin Berlin Campus Virchow Klinikum (CVK) statt. Es wurden Patient*innen ≥ 65 Jahre mit größerem elektivem Eingriff (≥ 60 Minuten) eingeschlossen. Den primären Endpunkt bildete die Inzidenz von POD innerhalb von 7 Tagen postoperativ, erhoben anhand der Diagnostic and Statistical Manual of Mental Disorders-Kriterien (DSM-5) und/oder der Nursing Delirium Screening Scale (NuDESC) und/oder der Confusion Assessment Method (CAM) und/oder der Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) und/oder Chart-Review. Die Dauermedikation der Studienteilnehmer*innen wurde auf Polypharmazie (≥ 5 Medikamente) geprüft und mittels PRISCUS-Liste und EU(7)PIM List auf PIMs untersucht. Die Auswertung der Daten erfolgte über eine logistische Regressionsanalyse. Dabei wurden folgende Störgrößen berücksichtigt: Alter, Geschlecht, Bildungsstand, Ernährungsstatus, Operationsbereich, Anästhesiedauer, Komorbiditäten (nach Charlson Comorbidity Index) und Aktivitäten des täglichen Lebens (ADL). Es wurden 394 Studienteilnehmer*innen (Altersmedian 73 Jahre, 49,7 % Frauen) eingeschlossen, von denen 25,1% ein POD entwickelten. In der an POD erkrankten Studiengruppe zeigten mehr Studienteilnehmer*innen eine Polypharmazie (54,5% vs. 40,3%) und PIMs gemäß EU(7)PIM-Liste (70,7% vs. 54,9%) oder PRISCUS-Liste (12,1 % vs. 10,5 %). In der Regressionsanalyse konnte kein Zusammenhang zwischen Polypharmazie oder PIM und POD nachgewiesen werden. Es bestätigte sich der bereits bekannte Einfluss der Störgrößen Alter, Bildungsstatus und Anästhesiedauer. Schlussfolgerung Als unabhängige Risikofaktoren für die Entwicklung von POD konnten Polypharmazie und PIMs gemäß PRISCUS-Liste oder EU(7)PIM-Liste nicht bestätigt werden. Diese Studie ist bei Betrachtung der internationalen Studienlage die derzeit einzige, die den Einfluss von PIMs auf POD untersucht. Da Polypharmazie und PIMs das Risiko für Nebenwirkungen, Arzneimittelinteraktionen und schwere unerwünschte Ereignisse im Allgemeinen erhöhen, sollten sie auch in zukünftigen Studien zum POD und im Kontext der Delirprävention berücksichtigt werden

Preoperative medication use and development of postoperative delirium and cognitive dysfunction

Postoperative delirium (POD) and postoperative (neuro-)cognitive disorder (POCD) are frequent and serious complications after operations. We aim to investigate the association between pre-operative polypharmacy and potentially inappropriate medications and the development of POD/POCD in elderly patients. This investigation is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental State Examination score less than or equal to 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method (for the intensive care unit [ICU]), and a patient chart review. POCD was assessed 3 months after surgery with a neuropsychological test battery. Pre-operative long-term medication was evaluated in terms of polypharmacy (≥5 agents) and potentially inappropriate medication (defined by the PRISCUS and European list of potentially inappropriate medications [EU(7)-PIM] lists), and associations with POD and POCD were analyzed using logistic regression analysis. Eight hundred thirty-seven participants were included for analysis of POD and 562 participants for POCD. Of these, 165 patients (19.7%) fulfilled the criteria of POD and 60 (10.7%) for POCD. After adjusting for confounders, pre-operative polypharmacy and intake of potentially inappropriate medications could not be shown to be associated with the development of POD nor POCD. We found no associations between pre-operative polypharmacy and potentially inappropriate medications and development of POD and POCD. Future studies should focus on the evaluation of drug interactions to determine whether patients benefit from a pre-operative adjustment

Preoperative medication use and development of postoperative delirium and cognitive dysfunction

Postoperative delirium (POD) and postoperative (neuro-)cognitive disorder (POCD) are frequent and serious complications after operations. We aim to investigate the association between pre-operative polypharmacy and potentially inappropriate medications and the development of POD/POCD in elderly patients. This investigation is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental State Examination score less than or equal to 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method (for the intensive care unit [ICU]), and a patient chart review. POCD was assessed 3 months after surgery with a neuropsychological test battery. Pre-operative long-term medication was evaluated in terms of polypharmacy (≥5 agents) and potentially inappropriate medication (defined by the PRISCUS and European list of potentially inappropriate medications [EU(7)-PIM] lists), and associations with POD and POCD were analyzed using logistic regression analysis. Eight hundred thirty-seven participants were included for analysis of POD and 562 participants for POCD. Of these, 165 patients (19.7%) fulfilled the criteria of POD and 60 (10.7%) for POCD. After adjusting for confounders, pre-operative polypharmacy and intake of potentially inappropriate medications could not be shown to be associated with the development of POD nor POCD. We found no associations between pre-operative polypharmacy and potentially inappropriate medications and development of POD and POCD. Future studies should focus on the evaluation of drug interactions to determine whether patients benefit from a pre-operative adjustment