The study was approved by the Institutional Review Board (IRB) of Wake Forest School of Medicine.
We designed this pilot clinical trial to test our hypothesis that improving preoperative physical function using aquatic exercise intervention (AEI) in elderly patients with advanced knee osteoarthritis (KOA) who are undergoing TKA will improve postoperative outcomes.
This was a pilot randomized clinical trial.
We enrolled participants from the Preoperative Assessment Clinic at Wake Forest Baptist Medical Center.
We recruited participants aged 50 years and older who are scheduled for primary TKA. A trained study coordinator screened potential participants for baseline mobility status, using the mobility assessment tool-short form (MAT-sf). Those participants who score at or below the 50th percentile, based on our prior preoperative study data (20), were considered eligible (e.g. MAT scores ≤58 for men and ≤50 for women). Exclusion criteria included patients who were undergoing knee replacement for indications other than osteoarthritis, revision surgery or bilateral surgery, scheduled for emergency surgery; afraid of water or are not willing to undergo water exercise; having major deficits in hearing or vision; currently exercising more than 3 times a week; participating in another clinical trial; or cannot understand the questionnaires and directions due to cognitive impairment or language barriers. Following these tests, participants underwent a standard medical workup at the discretion of the PAC's attending physician, including American Society of Anesthesiologists (ASA) physical status scoring, and Revised Cardiac Risk Index (RCRI) classification. For each participant, information regarding demographic characteristics, comorbidities, medications were gathered. Written informed consent was obtained from all the participants. At the beginning of the study, we only enrolled participants who are ≥ 65 years old who’s scheduled surgery is more than 8 weeks away. However, due to poor enrollment, the enrollment criteria were changed to participants who are ≥50 years old and have scheduled surgery ≥ 4 weeks.
Blood pressure, pulse, height and weight were assessed. All enrolled participants were assessed by a trained study coordinator on 1) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and physical function (13), 2) physical function using the Short Physical Performance Battery (SPPB), 3) self-reported mobility using Mobility Assessment Tool-short form (MAT-sf) 4) depression using Geriatric Depression Scale Short Form (GDS-sf), and 5) cognitive function using Montreal Cognitive Assessment (MoCA). The WOMAC (score 0-96) is a widely used and extensively validated tool to assess pain, stiffness, and physical function in patients with hip and/or knee osteoarthritis. It has three subscales including pain (5 items, score 0-20), stiffness (2 items, score 0-8) and physical function (17 items, score 0-68) (14). The SPPB consists of repeated chair stands, balance testing, and 4-meter walking speed (total score 0-12). It is known to predict subsequent disability, institutionalization, and mortality (15). The MAT-sf is a 10-item computer-based assessment of mobility using animated video clips (17). The 10 items in the MAT-sf cover a broad range of functioning. The items include walking on level ground, a slow jog, walking outdoors on uneven terrain, walking up a ramp with and without using a handrail, stepping over hurdles, ascending and descending stairs with and without the use of a handrail, and climbing stairs while carrying bags. It has been validated against measures of physical function, including the Pepper Assessment Tool for Disability, the Short Physical Performance Battery, and 400-meter walk test among a population of older community dwellers (17). The GDS-sf (score 0-15) is a 15-item screening tool for depression for older adults and it has been validated in the preoperative setting. Score of 0-5 is considered as normal, while a score of >5 suggests depression (16). The Montreal Cognitive Assessment (MoCA) is a widely validated 30 points test that measures several domains of cognitive function, including short-term memory recall tasks, visuospatial abilities, executive function, attention, concentration, working memory, language, and orientation (18). Baseline blood were drawn at the first visit for high-sensitivity-C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and, stored at -80 °C until the completion of the study and all samples were analyzed together.
Data to calculate Charlson comorbidity (19) was obtained by chart review and the score was calculated.
After baseline assessments, all the enrolled participants were randomly assigned 1:1 to the intervention or control group, using a pre-generated randomization list. The AEI were conducted in warm water (a minimum of 90 degrees) at the Wake Forest Baptist Medical Center Therapy Pool, three times a week, and for 60 minutes each session until the scheduled surgery (4-8 weeks). All the sessions were supervised by an aquatic therapist. The AEI was designed to improve 1) range of motion, 2) muscle strength, and 3) resistance, resulting in improvement in mobility in this low-mobility population. The protocol consists of a warm-up (10 minutes); joint range of motion for flexibility and strength (20 minutes); low intensity endurance such as walking to prevent chilling and maintain and/or improve cardiovascular fitness (20 minutes); and end with a cool down (10 minutes). Depending on the participant’s tolerance, resistance equipment, such as a noodle and/or neoprene ankle cuff were added to increase the exercise intensity. The participants’ exercise log was kept by the aquatic exercise director to record the compliance to the protocol. A trained study coordinator called the intervention group participants weekly to assist with problem solving, reinforce progress, and to encourage adherence. Control group participants received a brochure on perioperative nutrition in addition to the standard cares, such as optimization of their underlying medical problems and perioperative infection prevention measures. The principal investigator who assessed the clinical outcomes, and the two designated trained study coordinator who were not supervising the aquatic exercise and were blinded to the randomization status.
Evaluation before surgery
Participants in both groups were evaluated one week prior to their scheduled surgery. Blood pressure, pulse, and weight were assessed. Symptoms of osteoarthritis, self-reported mobility, depression, and cognition using the WOMAC, MAT-sf, GDS-sf and MoCA were assessed by a study coordinator. The SPPB was administered by two designated trained study coordinator who were not supervising the aquatic exercise and were masked to the randomization status. At this time, follow up labs were drawn to measure hs-CRP, TNF-α, and IL-6.
Evaluation after surgery
Participants in both groups were asked to return 4-6 weeks after the scheduled surgery. Blood pressure, pulse, and weight were assessed. Osteoarthritis symptoms, self-reported mobility, depression and cognition, using WOMAC, MAT-sf, GDS-sf and MoCA were assessed by a study coordinator. Physical function was assessed using SPPB by two designated trained study coordinators who were not supervising the aquatic exercise and were masked to the randomization status. Follow up labs were drawn to measure hs-CRP, TNF-α, and IL-6.
The primary outcome of interest was 30 day National Surgical Quality Improvement Project (NSQIP) defined morbidity, including surgical site infection, wound disruption, pneumonia, unplanned intubation, pulmonary embolism, ventilator >48 hours, acute renal failure, urinary tract infection, stroke, coma, peripheral nerve injury, cardiac arrest, myocardial infarction, requirement of transfusion, deep vein thrombosis, sepsis and mortality, hospital length of stay, ICU length of stay, delirium, and institutionalization (30). The secondary outcomes were osteoarthritis symptoms using WOMAC, physical function, measured by SPPB, self- reported mobility measured by MAT-sf, depression, measured by GDS, cognition, measured by MoCA, and inflammatory profiles, including CRP, TNF-α, and IL-6.
Due to the novelty of this project, no previous work was available. This study provides preliminary data for estimating effect size of prehabilitation on different outcomes (and corresponding standard deviations) for future larger studies.
All statistical analyses were performed using SAS software, version 9.4 (SAS Institute, Cary, NC). Sample means and standard deviations were computed for the continuous baseline characteristics and counts and proportions were calculated for the discrete baseline characteristics according to intervention groups. For non-normally distributed characteristics, medians, 1st quartile, and 3rd quartile were also calculated. Logistic regressions were used to examine the associations between anesthesia time and unfavorable outcomes, including postoperative complications, longer hospital stay of over 2 days, disposition to nursing home/rehab after adjusting for intervention groups. Odds ratios (ORs) and their 95% confidence intervals (CIs) were presented. In order to best approximate the conditional normality assumption, the distributions of functional measurements were checked and transformed if needed. Differences in mean values of each functional measurement between intervention groups were estimated using repeated measures analysis of covariance with baseline outcome measure, intervention assignment, visit, and an intervention by visit interaction included in the model. Hypothesis tests for intervention effects at the follow-up visits were performed using contrasts. Overall comparisons between groups across follow-up visits were obtained using a contrast to compare average intervention effects across both follow-up visits. Raw mean and standard deviation were presented at baseline, adjusted least squares means and standard error were presented at post-intervention and post-operative visits.