Oral vs Intravenous Dexamethasone in Total Knee Arthroplasty (TKA)

The Role of Dexamethasone in Total Knee Arthroplasty: Effects of Oral and Intravenous Administration on Early Postoperative Pain and Mobilization

This prospective observational cohort study aims to evaluate the association between perioperative dexamethasone administration and early postoperative recovery following primary total knee arthroplasty. In routine clinical practice, dexamethasone may be administered orally, intravenously, or not administered, depending on the surgeon's established perioperative protocol.

The primary objective is to assess early postoperative recovery in terms of pain intensity, functional mobility, and knee joint range of motion. Secondary objectives include evaluation of inflammatory response, postoperative metabolic changes, opioid requirement, and the severity of postoperative nausea and vomiting (PONV).

Group allocation is non-randomized and determined solely by the standard perioperative management approach routinely applied by the surgeon selected by the patient. No additional interventions are introduced for research purposes. All outcomes are assessed prospectively during the early postoperative period.

Study Overview

• Status: Recruiting
• Conditions: Knee Osteoarthritis; Gonarthrosis; Primary; Total Knee Arthroplasty
• Intervention / Treatment: Other: Routine perioperative management

Detailed Description

Total knee arthroplasty (TKA) is an effective treatment for advanced knee osteoarthritis; however, early postoperative recovery may be influenced by pain severity, limited functional mobility, systemic inflammatory response, metabolic alterations, and postoperative nausea and vomiting. Optimization of perioperative medical management is therefore a key component of enhanced recovery pathways.

Dexamethasone is frequently incorporated into perioperative care due to its anti-inflammatory, analgesic, antiemetic, and metabolic effects. Despite widespread use, variability persists in routine clinical practice regarding route of administration and dosing strategies. Comparative real-world data evaluating oral and intravenous administration within standardized care pathways remain limited.

This study is designed as a single-center, prospective observational cohort investigation evaluating early postoperative recovery parameters associated with routine perioperative dexamethasone strategies. The study does not introduce experimental interventions, randomization, or alterations to established treatment protocols.

Participants are assigned to cohorts according to the routine perioperative management approach of the operating surgeon selected by the patient. Each participating surgeon follows a predefined dexamethasone protocol that was implemented prior to initiation of this study. Treatment allocation is therefore independent of the research process and reflects real-world clinical practice.

The exposure of interest is perioperative dexamethasone administration as part of routine clinical care. Exposure status is defined according to the route of administration applied within the surgeon's established perioperative protocol: intravenous dexamethasone, oral dexamethasone, or no dexamethasone.

The standard institutional regimens consist of 8 mg administered preoperatively and 4 mg administered on postoperative day one, delivered either intravenously or orally depending on routine practice. Patients receiving no dexamethasone serve as the comparison cohort. Exposure classification is determined prior to postoperative outcome assessment.

All surgical procedures are performed using standardized institutional techniques for primary total knee arthroplasty. Postoperative management follows a multimodal analgesic protocol consistent across cohorts. Rescue opioid administration is provided when clinically indicated, and cumulative tramadol dose is recorded. Laboratory monitoring and clinical assessments are performed according to routine perioperative care standards.

Outcome data are collected prospectively using standardized and validated measurement tools during the early postoperative period. Baseline demographic and clinical variables are documented to account for potential confounding factors. Statistical analyses will include appropriate parametric or non-parametric tests depending on distributional assumptions. Repeated measurements will be evaluated using repeated-measures analysis or mixed-effects modeling, with multivariable adjustment to account for baseline differences between cohorts. Statistical significance is defined as p < 0.05.

The study is conducted in accordance with the Declaration of Helsinki and has received institutional ethics committee approval. All participants provide written informed consent prior to enrollment. Participation does not alter standard clinical management.

• Study Type: Observational
• Enrollment (Estimated): 270

Contacts and Locations

• Study Contact: Name: Atahan Eryilmaz, Resident Physician; Phone Number: +90 552 609 9055; Email: dratahaneryilmaz@gmail.com
• Study Contact Backup: Name: Mehmet Ersin, Associate Professor; Phone Number: +90 507 788 60 54; Email: drmehmetersin@gmail.com

Study Locations

• Turkey (Türkiye)
  • Istanbul
    • Istanbul, Istanbul, Turkey (Türkiye), 34200
      • Recruiting
      • Sultangazi Haseki Training and Research Hospital
      • Contact: Mehmet Ersin, Associate Professor; Phone Number: +90 507 788 60 54; Email: drmehmetersin@gmail.com
      • Contact: Atahan Eryilmaz, Resident Physician; Phone Number: +90552 609 9055; Email: atahanerylmaz@yahoo.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients aged 50 to 80 years with a diagnosis of primary knee osteoarthritis who are scheduled to undergo elective primary total knee arthroplasty at Istanbul Sultangazi Haseki Training and Research Hospital. Eligible participants have an ASA physical status of I or II and are able to ambulate independently prior to surgery. All participants are capable of understanding the study procedures and providing written informed consent.

Patients are managed according to the routine perioperative dexamethasone protocols of the surgeon selected by the patient. Group allocation is based on the standard clinical practice of the chosen surgeon and not assigned by the investigators. Participants are followed prospectively to evaluate postoperative pain, inflammatory response, functional mobility, postoperative nausea and vomiting, and analgesic requirements during the early postoperative period.

Description

Inclusion Criteria:

• Age between 50 and 80 years
• Diagnosis of primary knee osteoarthritis (primary gonarthrosis)
• Scheduled for elective primary total knee arthroplasty
• ASA physical status I or II
• Ability to ambulate independently (with or without assistive devices) preoperatively
• Ability to understand study procedures and complete pain and functional assessments
• Provision of written informed consent

Exclusion Criteria:

• Revision total knee arthroplasty
• History of knee joint infection
• Inflammatory arthritis (e.g., rheumatoid arthritis)
• Chronic systemic corticosteroid use
• Uncontrolled diabetes mellitus
• Known endocrine disorders affecting glucose metabolism
• Active infection at any site
• Known hypersensitivity to corticosteroids
• Severe hepatic, renal, or cardiac disease
• Neurological or musculoskeletal disorders affecting gait or balance
• Inability or unwillingness to comply with study procedures

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intravenous Dexamethasone Group; Patients undergoing primary total knee arthroplasty who receive dexamethasone intravenously according to the routine perioperative protocol of the operating surgeon (8 mg IV preoperatively and 4 mg IV postoperatively).	Other: Routine perioperative management; This is a prospective observational cohort study. No intervention is assigned by the investigators. Patients are managed according to the routine perioperative dexamethasone protocols of the surgeon chosen by the patient. One cohort receives intravenous dexamethasone (8 mg preoperatively and 4 mg postoperatively), one cohort receives oral dexamethasone (8 mg preoperatively and 4 mg postoperatively), and a control cohort receives no dexamethasone. All other perioperative and postoperative treatments are provided according to standard institutional practice and are not influenced by study participation.
Oral Dexamethasone Group; Patients undergoing primary total knee arthroplasty who receive dexamethasone orally according to the routine perioperative protocol of the operating surgeon (8 mg oral preoperatively and 4 mg oral postoperatively).	Other: Routine perioperative management; This is a prospective observational cohort study. No intervention is assigned by the investigators. Patients are managed according to the routine perioperative dexamethasone protocols of the surgeon chosen by the patient. One cohort receives intravenous dexamethasone (8 mg preoperatively and 4 mg postoperatively), one cohort receives oral dexamethasone (8 mg preoperatively and 4 mg postoperatively), and a control cohort receives no dexamethasone. All other perioperative and postoperative treatments are provided according to standard institutional practice and are not influenced by study participation.
Control Group (No Dexamethasone); Patients undergoing primary total knee arthroplasty who do not receive dexamethasone as part of the routine perioperative management.	Other: Routine perioperative management; This is a prospective observational cohort study. No intervention is assigned by the investigators. Patients are managed according to the routine perioperative dexamethasone protocols of the surgeon chosen by the patient. One cohort receives intravenous dexamethasone (8 mg preoperatively and 4 mg postoperatively), one cohort receives oral dexamethasone (8 mg preoperatively and 4 mg postoperatively), and a control cohort receives no dexamethasone. All other perioperative and postoperative treatments are provided according to standard institutional practice and are not influenced by study participation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain Intensity Measured with Visiual Analog Scale (VAS)	Postoperative pain intensity will be assessed using the Visual Analog Scale (VAS), a validated 0 to 10 numeric rating scale, where 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores represent greater pain intensity and therefore a worse outcome. Pain will be evaluated both at rest and during ambulation.	Measuring once in the preoperative period and every 6 hours during the first 48 hours after surgery.
Functional Mobility (Timed Up and Go Test)	Functional mobility will be evaluated using the Timed Up and Go (TUG) test, which measures the time (in seconds) required for a participant to stand up from a seated position, walk three meters, turn, walk back, and sit down. Shorter completion times indicate better functional mobility, whereas longer times indicate poorer performance.	Preoperatively and daily during the first 2 postoperative days.
Nausea and Vomiting (PONV) Score	Severity of postoperative nausea and vomiting will be assessed using a 0 to 10 Numeric Rating Scale (NRS), where 0 indicates no symptoms and 10 indicates the most severe nausea or vomiting imaginable. Higher scores represent worse symptoms.	Assessed daily during the first 2 postoperative days.
Postoperative Opioid Requirement	Requirement for rescue opioid analgesia following routine postoperative analgesic protocol consisting of scheduled paracetamol (4 doses per day) and NSAIDs (2 doses per day). Total opioid consumption and proportion of patients requiring opioid analgesia will be recorded. Cumulative tramadol dose administered as rescue analgesia will be recorded in milligrams (mg) during the first 48 hours after surgery. Higher values indicate greater postoperative analgesic requirement.	During the first 48 hours after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Range of Motion - Flexion and Extension Angles	Knee range of motion will be measured in degrees (°) using a standard universal goniometer aligned with anatomical landmarks (greater trochanter, lateral femoral epicondyle, and lateral malleolus). Measurements will be performed by trained personnel following a standardized protocol to minimize inter-observer variability. Greater flexion angles indicate improved joint mobility, whereas higher extension deficit values indicate reduced extension capacity.	Preoperatively and daily during the first 2 postoperative days.
White Blood Cell Count	Systemic inflammatory response will be assessed by measuring white blood cell (WBC) count, expressed in ×10³/µL. Higher values indicate greater inflammatory response.	Preoperatively and daily during the first 2 postoperative days.
C-Reactive Protein Level	ystemic inflammatory response will also be assessed by measuring C-reactive protein (CRP) levels, expressed in mg/L. Higher values indicate greater inflammatory response.	Preoperatively and daily during the first 2 postoperative days.
Postoperative Glycemic Response	Serum blood glucose levels will be measured in mg/dL using standard hospital laboratory methods. Daily postoperative values will be recorded to evaluate metabolic response and potential dexamethasone-associated hyperglycemia. Higher values indicate increased glycemic response.	Preoperatively and daily during the first 2 postoperative days.
Postoperative Mobilization Status	Postoperative mobilization status will be assessed using a categorical (ordinal) scoring system at postoperative day 0, day 1, and day 2. Patients will be classified into three categories based on their level of mobilization: 0 = Immobilized (no mobilization); = Independently mobilized (without assistance); = Assisted mobilization (with support) This classification is used to describe functional recovery status. Independent mobilization (score 1) represents the best functional outcome, assisted mobilization (score 2) represents moderate recovery, and immobilization (score 0) represents the poorest outcome. All patient groups (intravenous dexamethasone, oral dexamethasone, and control) will be evaluated daily using this scale.	Postoperative Day 0, Day 1, and Day 2

Collaborators and Investigators

• Sponsor: Haseki Training and Research Hospital
• Investigators: Principal Investigator: Mehmet Ersin, Associate Professor, Sultangazi Haseki Training and Research Hospital

Publications and helpful links

General Publications

• Chan TCW, Cheung CW, Wong SSC, Chung AYF, Irwin MG, Chan PK, Fu H, Yan CH, Chiu KY. Preoperative dexamethasone for pain relief after total knee arthroplasty: A randomised controlled trial. Eur J Anaesthesiol. 2020 Dec;37(12):1157-1167. doi: 10.1097/EJA.0000000000001372.
• De Oliveira GS Jr, Almeida MD, Benzon HT, McCarthy RJ. Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2011 Sep;115(3):575-88. doi: 10.1097/ALN.0b013e31822a24c2.
• Chen J, He Y, Deng T, Li Y, Wang X, Zhao M, Li F, Wang C, Tian H. Effects of Dexamethasone on Nausea, Vomiting, and Inflammatory Indexes After Total Knee Arthroplasty. Orthop Surg. 2025 Oct;17(10):2862-2868. doi: 10.1111/os.70139. Epub 2025 Aug 13.
• Liang S, Xing M, Jiang S, Zou W. Effect of Intravenous Dexamethasone on Postoperative Pain in Patients Undergoing Total Knee Arthroplasty: A Systematic Review and Meta-Analysis. Pain Physician. 2022 Mar;25(2):E169-E183.
• Xu B, Ma J, Huang Q, Huang ZY, Zhang SY, Pei FX. Two doses of low-dose perioperative dexamethasone improve the clinical outcome after total knee arthroplasty: a randomized controlled study. Knee Surg Sports Traumatol Arthrosc. 2018 May;26(5):1549-1556. doi: 10.1007/s00167-017-4506-x. Epub 2017 May 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Total Knee Arthroplasty; Knee Osteoarthritis; Gonarthrosis; Intravenous Dexamethasone; Multimodal Analgesia
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 194-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to institutional policies, patient privacy considerations, and the observational nature of this single-center study. The collected data are intended solely for the purposes of this research and related academic publications.

Drug and device information, study documents

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