Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled Clinical Trial

Abstract

Background There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to suppress postoperative neuroinflammation, this study hypothesized and investigated whether minocycline might have a preventive effect on postoperative cognitive dysfunction after noncardiac surgery. Methods This study included patients aged more than 60 yr undergoing total knee arthroplasty under general anesthesia. They were randomly assigned to minocycline and placebo groups, to orally receive 100 mg of minocycline or placebo twice daily from the day before surgery until the seventh day after surgery. Cognitive function was evaluated before surgery, and 1 week and 3 months after surgery, using a battery of four cognitive function tests, including Visual Verbal Learning Test, Trail Making Test, Stroop Color and Word Test, and Letter–Digit Coding Task. Additionally, 30 healthy volunteers were subjected to the same tests as the patients to examine the learning effect of repeated tests. The occurrence of postoperative cognitive dysfunction was judged from the results of the neurocognitive test battery, with consideration of the learning effect. The secondary endpoints were the effects of minocycline on postoperative delirium and postoperative pain. Results A total of 100 patients were randomized to the minocycline group, and 102 were randomized to the placebo group. The average age of patients was 75 yr. Evaluation showed no significant difference in the incidence of postoperative cognitive dysfunction between the minocycline and placebo groups at both 1 week (8 of 90 [8.9%] vs. 4 of 95 [4.2%]; odds ratio, 2.22 [95% CI, 0.64 to 7.65]; P = 0.240) and 3 months (15.3 of 90 [17.0%] vs. 15.3 of 95 [16.1%]; odds ratio, 1.07 [95% CI, 0.49 to 2.32]; P = 0.889) postoperatively. Missing data 3 months after surgery were corrected by the multiple imputation method. There were no differences between the two groups in postoperative delirium and postoperative pain. Conclusions Minocycline is likely to have no preventive effect on postoperative cognitive dysfunction. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Itaconate alleviates anesthesia/surgery-induced cognitive impairment by activating a Nrf2-dependent anti-neuroinflammation and neurogenesis via gut-brain axis

“…A series of specific and potent anti-inflammatory therapeutic drugs and methods have been identified and developed, including specific pro-resolving inflammatory mediators (such as Maresin 1 [ 39 ]) and cholinergic agonists (such as nicotine [ 40 ]). Despite extensive basic research exploring various small molecule neuroprotective agents and approaches targeting inflammation for the prevention and treatment of POCD over the past few decades, the clinical translation progress has been slow [ 35 , 41 ].…”

Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation

“…Due to its anti-inflammatory properties, multiple reports have focused on minocycline’s therapeutic effect on cognitive dysfunction. However, in 2023, Takazawa et al examined minocycline’s effect on POCD in elderly individuals administered total knee arthroplasty and found that 200 mg of minocycline daily from the day before surgery until the seventh day after surgery did not decrease POCD incidence, contradicting many preclinical studies [ 51 ]. The negative results of this study may be related to the short dosing period.…”

IL-1β, the first piece to the puzzle of sepsis-related cognitive impairment?

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