Circulatory Exercise After Total Knee Replacement

Boosting Venous Return After Knee Replacement: Effects of a Novel Circulatory Exercise on Early Postoperative Inflammation - A Randomized Controlled Trial

Total knee replacement is commonly associated with early postoperative inflammation, edema, pain, and reduced mobility. This randomized controlled trial will evaluate whether adding a simple circulatory exercise program to standard postoperative rehabilitation reduces early limb edema and inflammatory response after unilateral primary total knee replacement. Participants will be randomized to standard rehabilitation alone or standard rehabilitation plus seated and supine knee-extension exercises with alternating ankle dorsiflexion. The primary endpoint is change in limb edema measured by standardized limb circumference at postoperative day 14.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Osteoarthritis; Postoperative Edema; Total Knee Replacement; Postoperative Inflammation
• Intervention / Treatment: Other: standard postoperative TKR rehabilitation; Other: Standard Rehabilitation Plus Circulatory Exercise

Detailed Description

This is a randomized, parallel-group, assessor-blinded controlled clinical trial. Adults undergoing elective unilateral primary total knee replacement for osteoarthritis will be allocated in a 1:1 ratio to either standard postoperative rehabilitation or standard rehabilitation plus a circulatory exercise protocol. The intervention includes supine leg elevation with ankle pump and knee extension, and seated knee extension with alternating ankle dorsiflexion. The exercise will be performed at approximately 15 cycles per minute, 10 sets of 1 minute, with 60 seconds rest between sets, twice daily for 14 postoperative days. Outcomes include limb circumference, pain, functional mobility, quadriceps strength, inflammatory biomarkers, hemostasis markers, analgesic use, patient satisfaction, and adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults ≥ 18 years undergoing elective unilateral primary TKR for osteoarthritis.
• Able to provide informed consent.
• Able to perform the exercise (cognitively and physically) prior to discharge.

Exclusion Criteria:

• Preexisting peripheral vascular disease with severe ischemia or venous insufficiency that limits exercise.
• Contraindication to early active movement per surgeon (e.g., complex surgical fixation limiting motion if present).
• Severe neurological or cognitive impairment preventing instruction adherence.
• Inability to comply with follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard postoperative TKR rehabilitation (hospital protocol)	Other: standard postoperative TKR rehabilitation; Participants will receive standard postoperative total knee replacement rehabilitation according to the local hospital protocol, including early mobilization, ROM exercises, quadriceps activation, ambulation training, and standard pain/edema management as clinically indicated.
Experimental: Circulatory Exercise Protocol (in addition to standard rehab)	Other: Standard Rehabilitation Plus Circulatory Exercise; Participants will receive standard postoperative rehabilitation plus a circulatory exercise protocol including supine leg elevation with ankle pump and knee extension, and seated knee extension with alternating ankle dorsiflexion. The exercise will be performed at approximately 15 cycles/minute, 10 sets of 1 minute, 60 seconds rest between sets, twice daily for 14 postoperative days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in postoperative lower-limb edema between the operated and contralateral limbs measured by standardized limb circumference (cm)	Lower-limb circumference (cm) will be measured bilaterally at standardized anatomical landmarks: 10 cm above the superior border of the patella, at the mid-patellar level, and 20 cm above the superior border of the patella. Measurements will be obtained on both the postoperative limb and the contralateral (sound) limb. Edema will be quantified as the side-to-side difference in circumference and the change from baseline.	Baseline/preoperative to postoperative day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain intensity measured by the Numeric Rating Scale (NRS, 0-10) at rest and during activity	Pain intensity will be assessed using an 11-point Numeric Rating Scale (NRS), where 0 indicates no pain and 10 indicates the worst imaginable pain. Scores will be recorded at rest and during activity.	Baseline/preoperative to postoperative day 14
Functional mobility:	Timed Up and Go (TUG) (go for 3 meter and come back). Record assistance level and gait aids. 3-meter walk test at regular base and fast base.	Baseline/preoperative to postoperative day 14
Analgesic consumption	Opioid consumption: record rescue analgesic use	Baseline/preoperative to postoperative day 14
Quadriceps strength via handheld dynamometry.	Seated 60 Degrees Knee Flexion Patient position Seated on the edge of the table, with feet not in contact with the ground and knee at 60 degrees of flexion. Contact point Posterior aspect of the ankle attachment, at the hook closest to the achilles tendon. Device orientation Horizontal, linked to the ankle strap at one end and anchored to a fixed surface by the cable strap at the other, posterior to the patient's leg being tested. Position of examiner Adjacent to the patient, in a position to situate the DynaMo and instruct the action. Instruction Pull against the DynaMo as hard as you can. 3, 2, 1 - pull, pull, pull and relax. Attachments Tension links, Carabiners, Ankle strap, Tension strap.	Baseline/preoperative to postoperative day 14
Neuromuscular electrical stimulation response	Neuromuscular electrical stimulation response by chattanoga multi-current electrical stimulation.	Baseline/preoperative to postoperative day 14
Patient satisfaction with postoperative recovery measured by a 5-point Likert Scale	Patient satisfaction with postoperative recovery will be assessed on postoperative day 14 using a 5-point Likert Scale, where 1 = very dissatisfied, 2 = dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = satisfied, and 5 = very satisfied.	postoperative day 14
Serum Interleukin-6 (IL-6)	Interleukin-6 is a pro-inflammatory cytokine and an early mediator of the surgical stress response. Serum IL-6 will be quantified from peripheral venous blood by ELISA. Higher concentrations indicate a greater systemic inflammatory response; IL-6 peaks at approximately 24-48 hours postoperatively. Unit: pg/mL · Reference: < 7 pg/mL (assay-dependent)	Baseline (pre-operative), 24-48 hours post-operative (peak IL-6 window), Baseline/preoperative to postoperative day 14.
Hemostasis or clotting tests	PT (Prothrombin Time) APTT (Activated Partial Thromboplastin Time) D-dimer Fibrinogen	Baseline/preoperative to postoperative day 14
Serum C-Reactive Protein (CRP)	C-reactive protein is a hepatically synthesized acute-phase reactant produced in response to IL-6 signaling. Serum CRP will be measured from peripheral venous blood by immunoturbidimetric assay. Higher concentrations indicate greater systemic inflammation; CRP peaks later than IL-6 (~48-72 hours). Unit: mg/L · Reference: < 10 mg/L (hs-CRP: < 1 low, 1-3 moderate, > 3 high cardiovascular risk)	Baseline (preoperative), postoperative 24-48 hours, and postoperative day 14.
Serum Interleukin-10 (IL-10)	Interleukin-10 is an anti-inflammatory cytokine mediating the compensatory anti-inflammatory response to surgical injury. Serum IL-10 will be quantified from peripheral venous blood by ELISA. Higher concentrations indicate a greater compensatory anti-inflammatory response. Unit: pg/mL · Reference: < 10 pg/mL (often < 5 pg/mL; assay-dependent)	Baseline (preoperative), postoperative 24-48 hours, and postoperative day 14.
Serum Tumor Necrosis Factor-alpha (TNF-α)	Tumor necrosis factor-alpha is a pro-inflammatory cytokine released early in the innate immune response to tissue injury. Serum TNF-α will be quantified from peripheral venous blood by ELISA. Higher concentrations indicate a greater pro-inflammatory response. Unit: pg/mL · Reference: < 8.1 pg/mL (commonly < 15-20 pg/mL; assay-dependent)	Baseline (preoperative), postoperative 24-48 hours, and postoperative day 14.
Prothrombin Time (PT)	Prothrombin time assesses the extrinsic and common coagulation pathways. PT will be determined on platelet-poor plasma (peripheral venous blood in 3.2% sodium citrate) by an automated clot-based method using a thromboplastin reagent. A prolonged PT indicates impaired extrinsic/common-pathway function. Unit: seconds · Reference: 11-13.5 seconds (INR 0.8-1.1)	Baseline (preoperative) and postoperative day 14.
Activated Partial Thromboplastin Time (APTT)	Activated partial thromboplastin time assesses the intrinsic and common coagulation pathways. APTT will be determined on citrated platelet-poor plasma by an automated clot-based method. A prolonged APTT indicates impaired intrinsic/common-pathway function. Unit: seconds · Reference: 25-35 seconds	Baseline (preoperative) and postoperative day 14.
D-dimer	D-dimer is a fibrin degradation product reflecting activation of coagulation and fibrinolysis. D-dimer will be measured on citrated plasma by a latex-enhanced immunoturbidimetric assay. Elevated concentrations indicate increased fibrin turnover (hypercoagulable/prothrombotic state or venous thromboembolism). Unit: µg/mL FEU · Reference: < 0.50 µg/mL FEU (< 500 ng/mL FEU)	Frame: Baseline (preoperative) and postoperative day 14.
Fibrinogen	Fibrinogen (coagulation factor I) is the soluble precursor of fibrin and an acute-phase reactant. Plasma fibrinogen will be measured on citrated plasma by the Clauss clot-based method. Elevated concentrations reflect an acute-phase/inflammatory response; low concentrations may reflect consumption or dilution and a bleeding tendency. Unit: mg/dL · Reference: 200-400 mg/dL (2-4 g/L)	Baseline (preoperative) and postoperative day 14.

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Huang ZY, Huang Q, Wang LY, Lei YT, Xu H, Shen B, Pei FX. Normal trajectory of Interleukin-6 and C-reactive protein in the perioperative period of total knee arthroplasty under an enhanced recovery after surgery scenario. BMC Musculoskelet Disord. 2020 Apr 21;21(1):264. doi: 10.1186/s12891-020-03283-5.
• Si HB, Yang TM, Zeng Y, Zhou ZK, Pei FX, Lu YR, Cheng JQ, Shen B. Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty. BMC Musculoskelet Disord. 2017 Jun 17;18(1):265. doi: 10.1186/s12891-017-1597-y.
• Windisch C, Kolb W, Kolb K, Grutzner P, Venbrocks R, Anders J. Pneumatic compression with foot pumps facilitates early postoperative mobilisation in total knee arthroplasty. Int Orthop. 2011 Jul;35(7):995-1000. doi: 10.1007/s00264-010-1091-8. Epub 2010 Jul 22.
• Li H, Zhang W, Lu Q, Wang J, Zhi Y, Zhang L, Zhou L. Which Frequency of Ankle Pump Exercise Should Be Chosen for the Prophylaxis of Deep Vein Thrombosis? Inquiry. 2022 Jan-Dec;59:469580221105989. doi: 10.1177/00469580221105989.
• Lee B, Yoon D, Yim J. Effects of an Early Exercise Program with Cryotherapy on Range of Motion, Pain, Swelling, and Gait in Patients with Total Knee Arthroplasty: A Randomized Controlled Trial. J Clin Med. 2024 Feb 29;13(5):1420. doi: 10.3390/jcm13051420.
• Carnevale Pellino V, Gatti A, Vandoni M, Patane P, Febbi M, Ballarin S, Cavallo C, Marin L. Pneumatic Compression Combined with Standard Treatment after Total Hip Arthroplasty and Its Effects on Edema of the Operated Limb and on Physical Outcomes: A Pilot Clinical Randomized Controlled Study. J Clin Med. 2023 Jun 20;12(12):4164. doi: 10.3390/jcm12124164.
• Incesoy MA, Demirkiran CB, Kaya HB, Geckalan MA, Tak AY, Elmali N, Yildiz F, Uzer G. Natural course of postoperative C-reactive protein and erythrocyte sedimentation rate in unilateral and simultaneous bilateral total knee arthroplasty. BMC Musculoskelet Disord. 2025 Mar 14;26(1):260. doi: 10.1186/s12891-025-08523-0.
• Londhe SB, Shah RV, Doshi AP, Londhe SS, Subhedar K. CRP (C Reactive Protein) level after total knee replacement in Indian population--- does it follow Anglo-Saxon trend? Arthroplasty. 2020 Aug 27;2(1):24. doi: 10.1186/s42836-020-00043-7.

Study record dates

Study Major Dates

• Study Start (Estimated): June 16, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 16, 2027

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: July 3, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Rehabilitation; Total knee replacement; Total knee arthroplasty; Venous return; Postoperative edema; Postoperative inflammation; Circulatory exercise; Ankle pump exercise
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 04-2026-30083

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No