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Study Demonstrates 3-Doses of Hydrocortisone May Help Reduce Complications in Bilateral Total Knee Replacement

Patients having both knees replaced at the same time are at greater risk for serious complications including increased inflammatory reaction, more pain, and possible lung injury.

Now, a collaboration of HSS surgeons and anesthesiologists has found that administering a specific regimen of three doses of hydrocortisone steroids to patients undergoing the procedure – which is known as bilateral total knee arthroplasty (TKA) – may help reduce these risks.

The patients who received the three steroid doses had significantly reduced inflammatory reactions, as well as less prevalence of fever, lowered visual analog pain scores, and improved knee motion. The patients also had significantly lower values of desmosine in their urine samples, suggesting that the three dose treatment may be protective against lung injury.

Three Doses Work When Two Didn’t

Bilateral TKA is known to create higher levels of post-surgical inflammatory reaction than occurs after single knee replacement. The marker of greater inflammation is detecting higher levels of interleukin-6 (IL-6) in the blood. IL-6 is a cytokine, which is a specific kind of cellular messenger that signals for increased inflammatory processes by the immune system. More IL-6 in the blood means more signals for inflammation and a greater inflammatory reaction.

Increased inflammation triggered by higher IL-6 levels can result in acute respiratory distress syndrome with postoperative confusion and fever – all known risks after bilateral TKA.

In an earlier study, the research team had investigated whether administering two 100 mg doses of the steroid drug, hydrocortisone might help reduce the IL-6 levels after surgery, thus reducing inflammation and the accompanying negative reactions. The two doses did not significantly reduce IL-6 levels.

However, in this most recent study, the team found that administering three 100 mg doses, eight hours apart, did reduce IL-6 levels after bilateral TKA.

Double-blind Study

Thirty-four patients scheduled for bilateral TKA were enrolled in the double-blind, randomized, placebo-controlled trial. 17 of the patients received three doses of intravenous hydrocortisone (100 mg) given eight hours apart. 17 patients received 3 "doses" of a placebo at the same intervals.

Urinary desmosine levels were obtained at baseline, and at one and three days postoperatively. The level of IL-6 was measured at baseline and at six, ten, twenty-four, and forty-eight hours postoperatively. Pain scores, presence of fever, and functional outcomes were also recorded.

Steroids Decreased Inflammatory Markers

While all 34 patients experienced an increased level of IL-6 after their surgeries, the patients receiving placebo doses demonstrated significantly higher IL-6 levels than the patients receiving the steroids. Urinary desmosine levels significantly increased by twenty-four hours in the placebo group, but remained unchanged in the hydrocortisone group

Pain scores at twenty-four hours were significantly lower in the steroid group as was the presence of fever. Only 11.8% of the steroid group experienced fever, while 47.1% of the placebo group did. Range of motion at the knee was significantly greater in the group receiving steroids.

Elevated levels of desmosine in the urine following surgery can indicate potential lung injury. The significantly lower values of desmosine in the steroid group suggests that the three-dose treatment may help protect against lung injury, a known risk associated with bilateral TKA.

With the benefits of the three-dose hydrocortisone regimen having been shown in this well-controlled study, doctors could consider using this therapy for patients who might require bilateral TKA.


Kethy M. Jules-Elysee, MD
Assistant Attending Anesthesiologist, Hospital for Special Surgery
Clinical Assistant Professor of Anesthesiology, Weill Cornell Medical College

Sarah E. Wilfred, BA
Hospital for Special Surgery

Stavros G. Memtsoudis, MD, PhD
Attending Anesthesiologist, Hospital for Special Surgery
Clinical Professor of Anesthesiology, Weill Cornell Medical College
Clinical Professor of Public Health, Weill Cornell Medical College

David H. Kim, MD
Attending Anesthesiologist, Hospital for Special Surgery
Clinical Instructor in Anesthesiology, Weill Cornell Medical College

Jacques T. Ya Deau, MD, PhD
Associate Attending Anesthesiologist, Hospital for Special Surgery
Clinical Associate Professor of Anesthesiology, Weill Cornell Medical College

Michael K. Urban, MD, PhD
Associate Attending Anesthesiologist, Hospital for Special Surgery

Michael L. Lichardi, DPM, PA-C
Hospital for Special Surgery

Alexander S. McLawhorn, MD
Hospital for Special Surgery

Headshot of Thomas P. Sculco, MD
Thomas P. Sculco, MD
Director, Complex Joint Reconstruction Center
Surgeon-in-Chief Emeritus, Hospital for Special Surgery

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