Effects of Propofol, Dexmedetomidine, and Midazolam on Postoperative Cognitive Dysfunction in Elderly Patients: A Randomized Controlled Preliminary Trial
Postoperative cognitive dysfunction (POCD) is a significant complication following surgery, particularly in elderly patients. This condition, characterized by subtle disturbances in thought processes, can affect various cognitive domains such as memory, attention, and language comprehension. The choice of anesthesia technique is a modifiable risk factor for POCD. This study aimed to evaluate the effects of three commonly used sedatives—dexmedetomidine, propofol, and midazolam—on the incidence of POCD in elderly patients undergoing hip or knee replacement under spinal anesthesia.
The study was a prospective randomized controlled trial conducted at the China-Japan Friendship Hospital from July 2013 to December 2014. A total of 164 patients aged 65 years or older, scheduled for elective unilateral total hip or knee replacement, were included. Additionally, 41 non-surgical controls were recruited from the community. Patients were randomized into three groups in a 1:1:1 ratio to receive one of the three sedatives during combined spinal-epidural anesthesia (CSEA). The sedative dose was adjusted to achieve light sedation, as indicated by a bispectral index (BIS) score between 70 and 85.
All participants, including controls, underwent a battery of five neuropsychological tests before and seven days after surgery. The tests included the Montreal Cognitive Assessment (MoCA), Stroop Color-Word Test (SCWT), Digit Span Test, Digit Symbol Test, and Associative Learning and Memory Test. One year postoperatively, patients and controls were interviewed using the MoCA 5-minute protocol over the telephone.
The primary outcome was the incidence of POCD seven days after surgery, defined using the reliable change index (RCI). POCD was diagnosed if the RCI score was less than -1.96 on two or more tests or if the combined z score was less than -1.96. The secondary outcome was the incidence of POCD one year after surgery.
Seven days postoperatively, 60 of 164 patients (36.6%) were diagnosed with POCD. The incidence of POCD was significantly lower in the propofol group (18.2%) compared to the dexmedetomidine (40.0%) and midazolam (51.9%) groups. One year postoperatively, the incidence of POCD was 14.0%, 10.6%, and 14.9% in the dexmedetomidine, propofol, and midazolam groups, respectively, with no significant differences among the groups.
The neuropsychological test results revealed that patients in the propofol group had better scores in the associative learning test and SCWT compared to the other groups. The SCWT measures executive functions such as attention and information processing. Lower scores in the dexmedetomidine and midazolam groups indicated deficits in these areas. The associative word learning test, related to semantic memory, showed better performance in the propofol group, suggesting a lesser inhibitory effect on the left hemisphere language function.
The study also examined the effects of the sedatives on specific cognitive domains. The overall MoCA score and the clock-drawing subtest score showed significant differences among the groups. Patients in the dexmedetomidine group had higher D values (postoperative minus preoperative scores) for the overall MoCA score and clock-drawing score compared to the propofol and midazolam groups. This suggests that dexmedetomidine might have a protective effect on visuospatial abilities.
Hypotension during surgery, a known risk factor for POCD, was monitored and managed. There were no significant differences in the duration of hypotension or the type and dose of vasoactive drugs administered among the three groups. This indicates that the treatment of hypotension did not influence the occurrence of POCD.
Pain management, another risk factor for POCD, was standardized across all groups using patient-controlled epidural analgesia (PCEA). Postoperative pain scores and complications were similar among the groups, suggesting that effective pain management minimized its contribution to POCD.
The study’s findings highlight the differential effects of sedatives on cognitive function in elderly patients. Propofol demonstrated a significant advantage in reducing the short-term incidence of POCD, while midazolam was associated with the highest incidence. Dexmedetomidine showed potential protective effects on specific cognitive domains, particularly visuospatial abilities. However, the long-term incidence of POCD one year postoperatively was independent of the sedative type.
The study’s strengths include its randomized controlled design, homogeneous patient population, and comprehensive neuropsychological test battery. However, the single-institution setting and the small number of patients receiving blood transfusion limit the generalizability of the results.
In conclusion, among dexmedetomidine, propofol, and midazolam sedation in elderly patients, propofol has the least impact on cognitive function, while midazolam impairs it the most. The effect on POCD one year after arthroplasty was independent of the sedative type. These findings suggest that the choice of sedative can influence the short-term cognitive outcomes in elderly patients undergoing major surgery.
doi.org/10.1097/CM9.0000000000000098
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