Fluoxetine for Reducing Postoperative Cognitive Dysfunction in Elderly Patients After Total Knee Replacement: Study Protocol for a Single-centre, Double-blind, Randomised, Parallel-group, Superiority, Placebo-controlled Trial

Overview

Journal BMJ Open

Specialty General Medicine

Date 2022 Jun 29

PMID 35768113

Authors

Daoyi Lin

Lulu Yu

Jiaxin Chen

Hong Ye

Yushan Wu

Yusheng Yao

Affiliations

Soon will be listed here.

Abstract

Introduction: Postoperative cognitive dysfunction (POCD) is a common complication following major surgical procedures. The underlying pathophysiology is poorly understood, but the role of neuroinflammation is strongly implicated. Given the antineuroinflammatory and neuroprotective effects of fluoxetine, we hypothesise that fluoxetine may reduce the cumulative incidence of POCD in elderly patients undergoing total knee arthroplasty (TKA).

Methods And Analysis: This is a prospective, randomised, double-blind, parallel-group, placebo-controlled, superiority trial. Five hundred elderly patients undergoing unilateral TKA will be randomly assigned to the fluoxetine and placebo groups. The fluoxetine group will receive fluoxetine 20 mg daily 8 weeks preoperatively, and the placebo group will receive placebo capsules daily 8 weeks preoperatively. The primary outcome is the cumulative incidence of POCD at 1 month postoperatively. The secondary outcomes include the occurrence of delirium, the area under the curve of the Numeric Rating Scale pain scores over time, and sleep disturbance. Data on all the results, risk factors and adverse events will also be collected and analysed.

Ethics And Dissemination: The Fujian Provincial Hospital Ethics Board has approved the protocol for this trial (identifier number: K2021-01-009). All participants will be required to provide written informed consent before any protocol-specific procedures.

Trial Registration Number: ChiCTR2100050424.

Citing Articles

The multifaceted effects of fluoxetine treatment on cognitive functions.

Ampuero E, Luarte A, Flores F, Soto A, Pino C, Silva V Front Pharmacol. 2024; 15:1412420.

PMID: 39081952 PMC: 11286485. DOI: 10.3389/fphar.2024.1412420.

Preoperative mild cognitive impairment as a risk factor of postoperative cognitive dysfunction in elderly patients undergoing spine surgery.

Park S, Kim J, Ha Y, Kim K, Yi S, Koo B Front Aging Neurosci. 2024; 16:1292942.

PMID: 38282693 PMC: 10811182. DOI: 10.3389/fnagi.2024.1292942.

Fluoxetine alleviates postoperative cognitive dysfunction by attenuating TLR4/MyD88/NF-κB signaling pathway activation in aged mice.

Yao Y, Lin D, Chen Y, Liu L, Wu Y, Zheng X Inflamm Res. 2023; 72(6):1161-1173.

PMID: 37188940 DOI: 10.1007/s00011-023-01738-8.

References

Yue T, Li Q, Wang R, Liu Z, Guo M, Bai F . Comparison of Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in Evaluating Anxiety and Depression in Patients with Psoriatic Arthritis. Dermatology. 2019; 236(2):170-178. DOI: 10.1159/000498848. View

Mowla A, Mosavinasab M, Pani A . Does fluoxetine have any effect on the cognition of patients with mild cognitive impairment? A double-blind, placebo-controlled, clinical trial. J Clin Psychopharmacol. 2007; 27(1):67-70. DOI: 10.1097/JCP.0b013e31802e0002. View

Ren S, Yuan F, Yuan S, Zang C, Zhang Y, Lang B . Early Cognitive Dysfunction in Elderly Patients after Total Knee Arthroplasty: An Analysis of Risk Factors and Cognitive Functional Levels. Biomed Res Int. 2022; 2022:5372603. PMC: 8881138. DOI: 10.1155/2022/5372603. View

Lim C, Kim S, Park J, Kim C, Yoon S, Lee J . Fluoxetine affords robust neuroprotection in the postischemic brain via its anti-inflammatory effect. J Neurosci Res. 2008; 87(4):1037-45. DOI: 10.1002/jnr.21899. View

Chollet F, Tardy J, Albucher J, Thalamas C, Berard E, Lamy C . Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011; 10(2):123-30. DOI: 10.1016/S1474-4422(10)70314-8. View

Atallah M, Demian A, Shorrab A . Development of a difficulty score for spinal anaesthesia. Br J Anaesth. 2004; 92(3):354-60. DOI: 10.1093/bja/aeh073. View

Steinmetz J, Christensen K, Lund T, Lohse N, Rasmussen L . Long-term consequences of postoperative cognitive dysfunction. Anesthesiology. 2009; 110(3):548-55. DOI: 10.1097/ALN.0b013e318195b569. View

Inouye S, van Dyck C, Alessi C, Balkin S, Siegal A, Horwitz R . Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990; 113(12):941-8. DOI: 10.7326/0003-4819-113-12-941. View

Liu Q, Sun Y, Huang H, Chen C, Wan J, Ma L . Sirtuin 3 protects against anesthesia/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation. J Neuroinflammation. 2021; 18(1):41. PMC: 7863360. DOI: 10.1186/s12974-021-02089-z. View

10.

Moller J, Cluitmans P, Rasmussen L, Houx P, Rasmussen H, Canet J . Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998; 351(9106):857-61. DOI: 10.1016/s0140-6736(97)07382-0. View

11.

Deng Y, Wang R, Li S, Zhu X, Wang T, Wu J . Methylene blue reduces incidence of early postoperative cognitive disorders in elderly patients undergoing major non-cardiac surgery: An open-label randomized controlled clinical trial. J Clin Anesth. 2020; 68:110108. DOI: 10.1016/j.jclinane.2020.110108. View

12.

Monk T, Weldon B, Garvan C, Dede D, van der Aa M, Heilman K . Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2007; 108(1):18-30. DOI: 10.1097/01.anes.0000296071.19434.1e. View

13.

Bohnen N, Twijnstra A, Jolles J . Performance in the Stroop color word test in relationship to the persistence of symptoms following mild head injury. Acta Neurol Scand. 1992; 85(2):116-21. DOI: 10.1111/j.1600-0404.1992.tb04009.x. View

14.

Deiner S, Silverstein J . Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009; 103 Suppl 1:i41-46. PMC: 2791855. DOI: 10.1093/bja/aep291. View

15.

Harrison D, Langham B . Spinal anaesthesia for urological surgery. A survey of failure rate, postdural puncture headache and patient satisfaction. Anaesthesia. 1992; 47(10):902-3. DOI: 10.1111/j.1365-2044.1992.tb03161.x. View

16.

Lu J, Chen G, Zhou H, Zhou Q, Zhu Z, Wu C . Effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy: A randomized double blinded controlled trial. J Clin Anesth. 2017; 41:30-34. PMC: 5558812. DOI: 10.1016/j.jclinane.2017.06.004. View

17.

Johnson T, Monk T, Rasmussen L, Abildstrom H, Houx P, Korttila K . Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology. 2002; 96(6):1351-7. DOI: 10.1097/00000542-200206000-00014. View

18.

Vela Vasquez R, Pelaez Romero R . Aspirin and spinal haematoma after neuraxial anaesthesia: Myth or reality?. Br J Anaesth. 2015; 115(5):688-98. DOI: 10.1093/bja/aev348. View

19.

Yu L, Buysse D, Germain A, Moul D, Stover A, Dodds N . Development of short forms from the PROMIS™ sleep disturbance and Sleep-Related Impairment item banks. Behav Sleep Med. 2012; 10(1):6-24. PMC: 3261577. DOI: 10.1080/15402002.2012.636266. View

20.

Alboni S, Poggini S, Garofalo S, Milior G, El Hajj H, Lecours C . Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment. Brain Behav Immun. 2016; 58:261-271. DOI: 10.1016/j.bbi.2016.07.155. View