Table 3.
Clinical studies for proposed treatments for POCD.
| Treatment | Published clinical studies and relevant findings | Registered ongoing clinical trials (if applicable) |
|---|---|---|
| ANTI-INFLAMMATORY | ||
| COX-2 inhibitors | Zhu et al. (152): intraoperative and postoperative parecoxib vs. placebo in total knee arthroplasty (reduction in POCD at 1 week but not 3 months postoperatively) Zhu et al. (153): 1 week of preoperative celecoxib vs. placebo in total knee arthroplasty (reduction in POCD at postoperative day 7) | none |
| Minocycline | none | NCT02928692: preoperative minocycline vs. no treatment in colorectal surgery |
| Dexamethasone | Ottens et al. (154): intraoperative dexamethasone bolus vs. no treatment during cardiac surgery (no difference in cognitive performance at 1 and 12 months postoperatively) | NCT01332812: intraoperative dexamethasone bolus vs. no treatment in general surgery |
| Cholinergic agents | Doraiswamy et al. (155): 12-week course of donepezil >6 months vs. no treatment after CABG (improved memory recall, no improved cognition) | NCT02419352: sugammadex vs. neostigmine/atropine at end of general anesthesia NCT02927522: donepezil vs. placebo for 7 days following general surgery |
| Targeted cytokine inhibition | None | None |
| ANTIOXIDATIVE | ||
| Statins | Das et al. (156): postoperative statin vs. placebo in off-pump CABG (reduced POCD on postoperative day 6) | None |
| N-acetylcysteine | None | PANACEA trial ACTRN12614000411640: NAC vs. placebo twice daily for 4 days beginning on day of non-cardiac surgery |
| Edaravone | None | None |
| PRO-NEURONAL | ||
| Dexmedetomidine | Li et al. (157): dexmedetomidine bolus and intraoperative infusion vs. saline in laparoscopic cholecystectomy (reduced POCD on postoperative day 1) Chen et al. (158): correlation between reduction of pro-inflammatory cytokines and reduced POCD on postoperative day 1 in general surgery | NCT02275182: intraoperative dexmetedomidine vs. placebo in general surgery NEUROPRODEX trial 2013-000823-15: intraoperative dexmetedomidine vs. placebo in cardiac and abdominal surgery NCT03480061: intraoperative dexmedetomidine bolus and postoperative infusion vs. standard sedation in cardiac surgery NCT02923128: postoperative dexmedetomidine vs. sufentanil infusion in elective non-cardiac surgery |
| Amantadine | None | NCT03527134: five-day postoperative amantadine vs. no treatment in general surgery |
| Enhancing cognitive reserve | None | NCT02747784: three-month postoperative cognitive training regimen vs. no treatment in breast/urogynecological surgery |
| VARIOUS TARGETS | ||
| Local anesthetics | Wang et al. (159): lidocaine bolus and intraoperative infusion in CABG surgery (improved working memory, verbal associative learning compared to saline controls) Chen et al. (160): lidocaine bolus and intraoperative infusion in spinal surgery (slight improvement in cognitive function) | NCT00975910: lidocaine bolus and intraoperative infusion vs. placebo in supratentorial craniotomy NCT02848599: bupivacaine vs. morphine PCA for 72 h following general surgery |
| Ketamine | Hudetz et al. (161): ketamine bolus at anesthetic induction during cardiac surgery (improved memory/executive function) Nagels et al. (162): ketamine bolus and intraoperative infusion following anesthetic induction during cardiac surgery (no change in POCD compared to placebo) | NCT02892916: ketamine bolus following anesthetic induction vs. placebo in elective orthopedic surgery |
| Lipid mediators | none | None |
| Cannabinoid receptors | none | none |
| Melatonin | Hansen et al. (163): melatonin 6 mg/kg daily for 3 months improved sleep but had no effect on POCD in women having breast cancer surgery Fan et al. (164): melatonin 1 mg/kg daily for 6 days improved sleep and improves MMSE scores in patients undergoing hip arthroplasty | none |
| Turmeric | none | none |
| Acupuncture | Gao et al. (165): Electroacupuncture preserved MMSE scores 2 and 4 days following general surgery. Lin et al. (166): Electroacupuncture preserved MMSE scores on day 3 following intestinal surgery for cancer. (167): Electroacupuncture preserved MMSE scores in elderly patients on day 3 following colorectal surgery for cancer. | none |
CABG, coronary artery bypass graft; MMSE, Mini-Mental State Exam; NAC, N-acetylcysteine; PCA, patient-controlled analgesia.