Early Cognitive Changes After Same-day Discharge Hip and Knee Arthroplasty

Overview

The goal of this observational study is to explore early cognitive changes in patients aged 70 years or older undergoing same-day discharge after hip or knee replacement surgery. The main question it aims to answer is: Does patients experience cognitive changes in cognitive test performance from before surgery to the first day after surgery? Participants will: * Complete a cognitive test batteri vitually about 14 days before surgery, and on the first and seventh day after their operation. * Record pain levels and pain medicine use during the first week after surgery

Introduction Background Postoperative cognitive dysfunction (POCD) is a prevalent complication in elderly patients and has significant clinical and socioeconomic consequences, delayed recovery, decreased quality of life, persistent neurocognitive disorders and increased morbidity and mortality within the first year of surgery (1, 2). The pathogenesis remains poorly understood, partly due to varying diagnostic approaches and methodologies. Nevertheless, there is consensus that POCD is multifactorial influenced by factors such as advanced age, sleep disturbances, and inadequate perioperative pain management (3) . Sleep deprivation, in particular, can exacerbate hyperalgesia, impair cognition, and lead to increased respiratory and cardiac risks due to REM sleep rebound (4). Fast-track surgical protocols, which emphasize multimodal rehabilitation-including regional anesthesia, opioid-sparing analgesia, and early mobilization-have been shown to reduce postoperative pain, sleep disturbances, and the risk of delirium (5, 6). These protocols have reduced the average length of hospital stays worldwide (7) . In Denmark length of hospital stay after total hip arthroplasty (THA), total knee arthroplasty (TKA) and unicompartmental knee (UKA) is now only one day and an increasing number of patients are discharged on the day of surgery. Same-day discharge enable earlier return to a familiar environment and potentially enhanced pathophysiological recovery (8). No studies have described early postoperative cognitive test performance in elderly patients undergoing same-day discharge hip and knee arthroplasty. This study therefore aims to address this knowledge gap by examining early cognitive changes in patients aged ≥70 years after same-day discharge hip and knee arthroplasty. Aim The primary aim of this study is to report early cognitive changes measured with Symbol Digit Modality Test (SDMT) (9) in patients over 70 years undergoing same-day discharge THA, TKA and UKA. Secondary, to report cognitive changes using the Stroop Color Test and verbal fluency test as well as patient's perceived cognitive function. As patients return home on the day of surgery in this contemporary same-day discharge arthroplasty setting, we hypothesize that early postoperative changes in cognitive performance will be limited compared with earlier fast-track studies with a longer median length of stay (LOS) (6). Methods Study design A prospective cohort study design has been chosen over a randomized controlled trial (RCT) due to its suitability for addressing complex perioperative outcomes. While randomized controlled trials are the gold standard for evaluating interventions, their use in perioperative research is often constrained by difficulties in standardizing multifactorial variables (10, 11). Furthermore, same-day discharge surgery is already established as the standard of care in modern fast-track settings, and the planned study do not aim to investigate it as an intervention but rather to describe patients' pathophysiological responses to surgery in a same-day discharge setting and to provide observational data on potential limiting factors for improved recovery after same-day discharge hip and knee arthroplasty. Setting The study will be conducted at Odense University Hospital-Svendborg where same-day discharge surgery after hip and knee arthroplasty is the standard of care in about 50% of patients (Danielsen et al. 2026). Patients will be included in the study from May 2026 to October 2026. This center has followed a published protocol for same-day discharge surgery including well defined eligibility and criteria for discharge on day of surgery (12) and it has been the standard clinical practice since September 2022. The cognitive tests: The cognitive tests will be administered by two research assistants with prior research experience. Both assistants received structured, on-site training in test administration by a neuropsychologist (AV). In addition, pilot test cases were completed prior to recruiting participants to confirm consistency and reliability in the test administration. Eligible participants will be recruited from the outpatient clinic. Testing will be performed virtually with the patients being at home. The patients will receive instructions to complete all sessions in the same quiet room and on the same device, to keep environmental stimuli (lighting, background noise, screen distance, seating, posture, and internet conditions) constant and thereby reduce within-subject variance and practice effects. The baseline test will be administered 14 days +- 3 days prior to surgery to avoid preoperative anxiety effects. Postoperatively, testing will be carried out on postoperative day 1 and day 7. More frequent testing is avoided to reduce practice effects. Remote virtual testing is chosen as it is more feasible in these patient populations, and this also holds in today's developing health care system where telecommunication is taking a greater role in the health care setting (13). SDMT, Stroop color test and verbal fluency test administered remotely has shown that it yields scores highly concordant with in-person testing (14) (15) (16, 17) . Participants Patients will be eligible for inclusion if they are 70 years of age or older, scheduled for elective unilateral total hip or knee arthroplasty, and planned discharge on the day of surgery according to current eligibility criteria for same-day discharge (table 1). Patients will be excluded if they do not provide informed consent, are unable to comply with study procedures or follow-up visits, are not discharged on the day of surgery, have a diagnosis of dementia or another cognitive disorder, or present with a Brief Assessment of Impaired Cognition (BASIC) ≤20 at baseline(18). Patients with Parkinson's disease or other neurological conditions causing functional impairment will also be excluded, as will those with a history of alcohol abuse (≥35 units/week) or daily use of anxiolytics or hypnotics. Additionally, all participants must be native Danish speakers (Table 2) Surgery and anesthesia Only patients receiving spinal anesthesia will be included to minimize confounding from general anesthesia and to reflect current fast-track practice, in which most (about 70%) primary hip and knee arthroplasties are still performed under spinal anesthesia (19). Furthermore, local practice, as approximately 90% of primary total hip and knee arthroplasties in our unit are performed under spinal anesthesia, leaving the general-anesthesia group too small for adequately powered comparisons (20). Spinal anesthesia is administered using a relatively short-acting blockade bupivacaine 5 mg/mL, 2.5 mL (15 mg) in THA, while for primary TKA and UKA, bupivacaine 5 mg/mL, 2 mL (10 mg) (13). Standard local infiltration analgesia (LIA) will be used with 150 mL ropivacaine 2 mg/mL in knee arthroplasties but not in hip arthroplasties (21). Peripheral nerve blocks are not used. Patients will also receive methylprednisolone 125 mg and 1 gr tranexamic acid intravenously immediately prior to skin incision. Postoperative pain management and other medication Postoperative pain management will follow a standardized multimodal, opioid-sparing regimen. All patients will receive paracetamol (1 g × 4) in combination with ibuprofen 400 mg × 3 (7 days) for THA patients in and 400 mg × 4 (14 days) for TKA and UKA patients, unless contraindicated. Opioids will be reserved as rescue medication, administered only on an "as needed" basis. Morphine 10 mg tablets will be used as first-line rescue analgesia, with oxycodone 5 mg as an alternative for patients who do not tolerate morphine. Outcome Primary outcome: • Change in SDMT score from baseline (14 days preoperatively) to postoperative day 1 (POD1). The SDMT is a validated neuropsychological tool that measures processing speed, attention, and visual scanning (22). The SDMT will be administered virtually as an oral 90-second test. The primary metric will be the SDMT score, defined as the number of correct digit substitutions completed within 90 seconds Secondary outcomes: * Change in SDMT score from baseline to POD7. * Change in Stroop Color-Word Test score from baseline to POD1. The Stroop Color-Word Test is a validated measure of selective attention and susceptibility to interference (9). The primary metrics will be completion time (seconds) and number of errors recorded for each session. * Change in Stroop Color-Word Test score from baseline to POD7. * Change in Verbal fluency assessment score from baseline to POD1. Verbal fluency assessment is a validated test which assesses executive function, semantic memory, and language (23). In our test a semantic (animal naming) and a phonemic (letter S) fluency task were used, each administered for 60 seconds. Number of correct responses for each task will be registered. * Change in Verbal fluency assessment score from baseline to POD7. * Reporting patient-reported cognitive function on POD1. A brief two-item subjective cognitive questionnaire will be administered to assess patient's perceived cognitive changes and to identify any discrepancy between subjective experience and objective neuropsychological test performance. * Change in patient-reported cognitive function from POD1 to POD7. Perioperative descriptive data and potential confounders (covariates): * Cumulative In-hospital postoperative morphine consumption, measured in milligrams \[Time frame: end of surgery until discharge from the hospital on the day of surgery (DOS)\]. Data will be obtained from the hospital electronic medication record. * Cumulated postoperative morphine consumption in milligrams \[Time frame: POD1 to - POD7\]. Patients will receive a medication log in which they will record their daily analgesic intake, including both scheduled and rescue medication, with specific documentation of any opioid use. * Postoperative pain intensity during rest once a day \[Time frame: POD1 - POD7\]. Patients will record pain intensity using an 11-point numeric rating scale (NRS, 0-10) in a pain diary. * Postoperative pain intensity during activity once a day \[Time frame: POD1 - POD7\]. Patients will record pain intensity using an 11-point numeric rating scale (NRS, 0-10) in a pain diary. Pain will be assessed defined as a standardized 5-m walk test (24). Data Source: A REDCap database has been established in collaboration with the Open Patient Data Explorative Network (OPEN) at Odense University Hospital (25). Patients scheduled for hip and knee arthroplasty at Svendborg hospital and included in the planned study will be enrolled in the database following informed consent. Patient's baseline database will be registered on comorbidities and medication use entered by trained research staff. Statistics and sample size Although this is an exploratory study, the sample size was guided by considerations from both the literature and our pilot planning. Because the design is paired, each participant serves as their own control (baseline vs. postoperative assessment). For the SDMT we assumed a minimal clinically important difference (MCID) of 4 points (26, 27), a within-subject correlation of 0.85 between baseline and postoperative scores, and a standard deviation of 7.5 (9). With a two-sided alpha of 0.05 and 80% power, this corresponds to approximately 14 participants with complete paired measurements per subgroup (THA, TKA, and UKA) if analyses are performed separately. To account for anticipated dropout/non-same-day discharge (15%), we will aim to enroll 16 patients per subgroup to obtain 14 participants with complete paired measurements. Continuous variables will be summarized as mean with standard deviation (SD) and range if approximately normally distributed; otherwise as median with interquartile range (IQR) and range. Categorical variables will be described using absolute and relative frequencies (n, %) The primary endpoint (change in cognitive test performance from baseline to the first postoperative assessment) will be analyzed using a linear mixed-effects (multilevel) regression model with time (baseline, POD1, POD7) included as a categorical fixed effect and a random intercept for each participant. The primary effect estimate will be the marginal mean difference from baseline to POD1 with a corresponding 95% confidence interval (CI). In addition, marginal means at each time point and the marginal mean difference from baseline to POD7 (95% CI) will be reported. The same modeling framework will be applied to all continuous secondary outcomes. Patient involvement Patients who have previously undergone hip or knee arthroplasty were involved in the design process. Their feedback informed the research questions and outcome measures, ensuring relevance and patient-centeredness. During pilot testing, participating patients also provided input on the planned assessment procedures and overall feasibility, which further informed methodological adjustments. Ethics and registration All participants will provide written informed consent and may withdraw at any time. An application was submitted to the Research Ethics Committee for the Region of Southern Denmark (S-20252000-31). The committee determined that the project is not subject to formal approval requirements under Danish law. The project has also been registered in the Region of Southern Denmark's internal record of data processing activities for research and quality purposes (25/49880). Table 1. Inclusion and exclusion criteria for planned discharge on day of surgery Inclusion criteria • Unilateral elective primary THA, TKA, or UKA Exclusion criteria * Acute myocardial infarction, cerebrovascular accident, transient ischemic attack, or coronary atherosclerotic disease within last 3 months * Unstable ischemic heart disease * Ejection fraction \< 40% * Glomerular filtration rate \< 60 mL/min/1.73 m2 * Chronic obstructive pulmonary disease with home oxygen * Insulin-dependent diabetes mellitus * Sleep apnea requiring mechanical treatment * CFS ≥ 4 a * 2 or more falls within last 3 months * Body mass index \< 18.5 or \> 40 * Not interested in discharge on day of surgery * No adult present at home during the initial postoperative night \* a CFS = Clinical Frailty Scale (28) . \* This criterion was inadvertently omitted from the protocol paper but has consistently been applied across all centers. Table 2. Study-specific inclusion and exclusion criteria Inclusion criteria * Eligible for same-day discharge criteria (Table 1) * Age ≥70 years * Elective unilateral THA, TKA, or UKA * Native Danish speaker * Spinal anesthesia Exclusion criteria * Inability or unwillingness to provide informed consent * Inability to comply with virtual study procedures or follow-up sessions, including because of visual or hearing impairment * Known dementia or other diagnosed cognitive disorders or Basic score ≤20 * Parkinson's disease or other neurological conditions causing functional impairment * History of alcohol abuse (≥35 units per week) * Daily use of anxiolytics or hypnotics * Not discharged on the day of surgery References 1. Joris J, Kehlet H, Slim K. Postoperative cognitive dysfunction: time for enhanced recovery after surgery programmes. Eur J Anaesthesiol. 2022;39(9):733-4. 2. Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Aceto P, Audisio R, et al. 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