Abstract
Aging of the central nervous system is accompanied by degenerative changes that affect cognitive function and increase the risk of developing mental disorders such as delirium and dementia. Delirium, emergence delirium, and postoperative cognitive dysfunction are distinct perioperative disorders with overlapping pathophysiological backgrounds that cumulatively affect the patient's attention, environmental awareness, and other cognitive processes, with significant clinical and psychosocial consequences. Furthermore, several studies suggest the existence of a bidirectional relationship between the above conditions and perioperative sleep quality. In the geriatric population, perioperative factors such as the biological stress of the surgery itself, pain, sedation, and electrolyte disturbances increase the risk of developing these conditions. Dexmedetomidine, a selective alpha-2 adrenergic agonist with sedative properties, is being investigated as a pharmacological approach to reduce po ...
Aging of the central nervous system is accompanied by degenerative changes that affect cognitive function and increase the risk of developing mental disorders such as delirium and dementia. Delirium, emergence delirium, and postoperative cognitive dysfunction are distinct perioperative disorders with overlapping pathophysiological backgrounds that cumulatively affect the patient's attention, environmental awareness, and other cognitive processes, with significant clinical and psychosocial consequences. Furthermore, several studies suggest the existence of a bidirectional relationship between the above conditions and perioperative sleep quality. In the geriatric population, perioperative factors such as the biological stress of the surgery itself, pain, sedation, and electrolyte disturbances increase the risk of developing these conditions. Dexmedetomidine, a selective alpha-2 adrenergic agonist with sedative properties, is being investigated as a pharmacological approach to reduce postoperative delirium. Its mechanism of action affects the noradrenergic pathway, inducing sedation with a pattern that resembles natural sleep and reducing the systemic stress response. Additionally, it possesses analgesic properties that contribute to the reduction of intraoperative and postoperative pain, reducing the need for opioid use, which has been linked to an increased risk of delirium. This doctoral thesis examines the effect of dexmedetomidine on the occurrence of postoperative delirium and postoperative cognitive dysfunction in patients undergoing orthopedic surgery under regional anesthesia. It also investigates the effect of this pharmacological intervention on postoperative sleep quality and the development of chronic pain, taking into account risk factors for the development of postoperative delirium, which include the duration of surgery, social characteristics of the participants, as well as the presence of co-morbidities and the use of anticholinergic drugs. A randomized clinical trial was conducted in patients over 65 years of age undergoing total knee or hip arthroplasty under regional anesthesia. Patients were divided into two groups in a 1:1 ratio, the study group receiving dexmedetomidine and the control group receiving propofol as a sedative agent, targeting equivalent levels of sedation. The assessment of the incidence of emergence delirium and postoperative delirium was done using validated scales, Riker Sedation-Agitation and Confusion Assessment Method, respectively. The ISPOCD psychometric test battery was used for the global assessment of cognitive function. Sleep quality was assessed with the self-reported Pittsburgh Sleep Quality Index, while the PainDetect tool was used to identify patients who developed chronic pain. The evaluation of the above parameters was conducted 3 times: before surgery, 48 hours postoperatively, and 3 months postoperatively. A total of 80 patients (41 in the dexmedetomidine group and 39 in the control group) who completed all 3 phases of the evaluation were included in the study. The results showed that the administration of dexmedetomidine was associated with a significant reduction in the incidence of postoperative delirium (4.8% vs. 38.4%, p=0.001) and emergence delirium (2.4% vs. 38.4%, p<0.001). Similarly, the incidence of early postoperative cognitive dysfunction in the first 48 hours postoperatively was reduced (2.4% vs. 56.4%, p<0.001). Furthermore, patients in the dexmedetomidine group reported improvement in their sleep quality in the immediate postoperative period (4.4 ± 0.7 vs. 13.4 ± 0.8, p<0.001) with a lower PSQI score and a lower score on the PainDetect tool at 3 months (2.4 ± 0.9 vs. 5.3 ± 0.9, p=0.023, respectively). The level of sedation achieved intraoperatively did not differ between the two agents (3.9 ± 0.4 vs. 3.9 ± 0.3, p=0.450) according to the Ramsay scale. Episodes of intraoperative bradycardia and hemodynamic instability were more frequent in the dexmedetomidine group, while only one patient developed airway obstruction (2.4% vs. 30.8%, p=0.002) in the dexmedetomidine group. In conclusion, the use of dexmedetomidine as a sedative agent intraoperatively resulted in a reduction in the incidence of postoperative delirium, emergence delirium, and early postoperative cognitive dysfunction, while improving self-reported postoperative sleep quality and reducing chronic pain scores in patients undergoing hip and knee arthroplasty with regional anesthesia and analgesia. It is thus emerging as a promising agent with potential benefits in patient outcomes and in reducing the cost of hospitalization. However, further research is needed to be able to generalize findings to other types of surgical patients.
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