Postoperative delirium (POD) is an acute alteration of mental state, characterized by reduced awareness and attention, occurring up to five postoperative days after recovery from anesthesia. Several original studies and reviews have identified possible perioperative POD risk factors; however, there is no comprehensive review of the preoperative risk factors in patients diagnosed with POD using only validated diagnostic scales. The aim of this systematic review was to report the preoperative risk factors associated with an increased incidence of POD in patients undergoing non-cardiac and non-brain surgery. The reviewed studies included original research papers that used at least one validated diagnostic scale to identify POD occurrence for more than 24 h. A total of 6475 references were retrieved from the database search, with only 260 of them being suitable for further review. Out of the 260 reviewed studies, only 165 that used a validated POD scale reported one or more preoperative risk factors. Forty-one risk factors were identified, with various levels of statistical significance. The extracted risk factors could serve as a preoperative POD risk assessment workup. Future studies dedicated to the further evaluation of the specific preoperative risk factors’ contributions to POD could help with the development of a weighted screening tool.

BACKGROUND: Postoperative delirium (POD), emergence delirium (ED), and postoperative cognitive dysfunction (POCD) are disorders of the neuropsychiatric spectrum affecting the elderly during the postoperative period, potentially sharing a common pathophysiological pathway. Disrupted sleep postoperatively correlates with both POD and POCD, revealing overlapping risk factors. This study investigates the potential of dexmedetomidine anesthesia to reduce the incidence of POD (primary outcome), ED, POCD, impairment of sleep quality, and emergent chronic pain (secondary outcomes) in older adults undergoing major orthopedic surgery under regional anesthesia. METHODS: In this double-blind randomized control trial, patients scheduled for major lower limb orthopedic surgery under regional anesthesia were randomized to receive either dexmedetomidine or propofol for sedation at a 1:1 ratio. POD, ED, and POCD were assessed with the Confusion Assessment Method tool, the Riker Sedation-Agitation scale, and the European Battery of psychometric tests, respectively. Sleep quality was assessed using the Pittsburg Sleep Quality Index and chronic pain with the painDETECT tool. Assessments of all outcome variables were performed before surgery, and at 48 hours and 3 months postoperatively. RESULTS: A total of 80 patients (dexmedetomidine group n = 41) were enrolled in the study and completed the follow-up. POD, ED, and early POCD incidence were significantly lower in dexmedetomidine compared to propofol group (4.8% vs 38.4%, P = .001; 2.4% vs 38.4%, P < .001; 2.4% vs 56.4%, P < .001, respectively). Patients in the dexmedetomidine group reported improved sleep quality in the immediate postoperative period (lower PSQI score) and lower painDETECT scores at 3 months (4.4 ± 0.7 vs 13.4 ± 0.8, P < .001; 2.4 ± 0.9 vs 5.3 ± 0.9, P = .023, respectively). Intraoperative bradycardia and hemodynamic instability episodes were more common in the dexmedetomidine group while a single patient presented airway obstruction (2.4% vs 30.8%, P = .002) in the dexmedetomidine group. CONCLUSIONS: Sedation with dexmedetomidine resulted in a statistically and clinically important reduction in the incidence of POD, ED, and early POCD, while it improved self-reported postoperative sleep quality and reduced chronic pain scores in patients undergoing major elective lower limb surgery under regional anesthesia.

Family B G protein-coupled receptors (GPCRs) belong to the superfamily of GPCRs and play an important role in many physiological and pathophysiological processes. Previous studies revealed the importance of ligands for family B GPCRs as drug targets, thus demonstrating the need for the development of novel ligands with improved pharmacodynamic and pharmacokinetic profiles. A major contribution to the development of novel drugs is the knowledge of the structure and function of their targets. Family B receptors are plasma membrane proteins containing an extracellular N-domain, an intracellular C-tail, seven transmembrane domains (TMs), which are connected to each other with three extracellular (ELs) and three intracellular (ILs) loops. The ELs and the upper parts of TMs form the J-domain of receptors. Peptides bind to family B receptors according to a two-step model. Based on this model, the C-terminal region of peptides first binds to the N-domain of receptor. Interaction of ligands with the N-domain of receptor provides an “affinity-trap” that facilitates the binding of the N-terminal region of peptides to the J-domain. Structural changes associated with peptide binding to the extracellular parts of receptors are transmitted through TMs to the intracellular regions of receptors and are responsible for their interaction with the G proteins and activation of the latter, thus resulting in a biological effect. In this review, we summarize the current structural information for family B GPCRs and their ligands along with the structural determinants of ligand binding and receptor activation, as well as, the physiological and pathophysiological role of these entities.