title: Steroid modulation of cytokine release and desmosine levels in bilateral total knee replacement: a prospective, double-blind, randomized controlled trial.
abstract: BACKGROUND
  The perioperative inflammatory response as measured by elevated levels of interleukin-6 (IL-6) has been linked to acute respiratory distress syndrome, postoperative confusion, and fever. Because of the extent of surgery,patients undergoing bilateral total knee arthroplasty may be at high risk of complications. We had found a significant decrease in IL-6 in patients having bilateral total knee replacement who received two doses of 100 mg of hydrocortisone eight hours apart; however, by twenty-four hours, IL-6 levels were equal to those in the group that received a placebo. In the present study, we investigated whether the administration of three doses would reduce IL-6 levels at twenty-four hours and affect other outcomes such as desmosine level, a marker of lung injury.
  
  
  METHODS
  After institutional review board approval, a total of thirty-four patients (seventeen patients and seventeen control subjects) were enrolled in this double-blind, randomized, placebo-controlled study. Three doses of intravenous hydrocortisone (100 mg) or placebo were given eight hours apart. 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 recorded.
  
  
  RESULTS
  The level of IL-6 increased in both groups, but was significantly higher in the control group, peaking at twenty-four hours (mean and standard deviation, 623.74 ± 610.35 pg/mL versus 148.13 ± 119.35 pg/mL; p = 0.006). Urinary desmosine levels significantly increased by twenty-four hours in the control group, but remained unchanged in the study group (134.75 ± 67.88 pmol/mg and 79.45 ± 46.30 pmol/mg, respectively; p = 0.006). Pain scores at twenty-four hours were significantly lower in the study group (1.4 ± 0.9 versus 2.4 ± 1.2; p = 0.01) as was the presence of fever (11.8%versus 47.1%; p = 0.03). Range of motion at the knee was significantly greater in the study group (81.6 ± 11.6 versus 70.6 ± 14.0 in the right knee [p = 0.02] and 81.4 ± 11.3 versus 73.4 ± 9.4 in the left knee [p = 0.03]).
  
  
  CONCLUSIONS
  Hydrocortisone (100 mg) given over three doses, each eight hours apart, decreased and maintained a lower degree of inflammation with bilateral total knee replacement as measured by IL-6 level. Corticosteroids decreased the prevalence of fever, lowered visual analog pain scores, and improved knee motion. The significantly lower values of desmosine in the study group suggest that this treatment may be protective against lung injury.
authors.affiliation: Department of Anesthesiology, 535 East 70th Street, New York, NY 10021, USA. JulesElyseeK@hss.edu
authors.forename: Kethy M
authors.initials: KM
authors.lastname: Jules- Elysee
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Wilfred
authors.forename: Stavros G
authors.initials: SG
authors.lastname: Memtsoudis
authors.forename: David H
authors.initials: DH
authors.lastname: Kim
authors.forename: Jacques T
authors.initials: JT
authors.lastname: YaDeau
authors.forename: Michael K
authors.initials: MK
authors.lastname: Urban
authors.forename: Michael L
authors.initials: ML
authors.lastname: Lichardi
authors.forename: Alexander S
authors.initials: AS
authors.lastname: McLawhorn
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sculco
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000517:prevention & control*; D000368:Aged; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects / Q000379:methods*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003895:Desmosine / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D011183:Postoperative Complications / Q000097:blood / Q000517:prevention & control; D011300:Preoperative Care / Q000379:methods; D011446:Prospective Studies; D016059:Range of Motion, Articular / Q000187:drug effects; D012016:Reference Values; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D003895:Desmosine; D006854:Hydrocortisone