title: Does limb preconditioning reduce pain after total knee arthroplasty? A randomized, double-blind study.
abstract: BACKGROUND
  Total knee arthroplasty (TKA) can be associated with considerable postoperative pain. Ischemic preconditioning of tissue before inducing procedure-related underperfusion may reduce the postoperative inflammatory response, which further may reduce associated pain.
  
  
  OBJECTIVE
  In this prospective, randomized study, we aimed at evaluating the impact of ischemic preconditioning on postoperative pain at rest and during exercise; use of pain medication; levels of systemic prothrombotic and local inflammatory markers; and length of stay and achievement of physical therapy milestones.
  
  
  METHODS
  Sixty patients undergoing unilateral TKA under tourniquet were enrolled with half (N = 30) being randomized to an episode of limb preconditioning before induction of ischemia for surgery (tourniquet inflation). Pain scores, analgesic consumption, markers of inflammation (interleukin-6 [IL-6], tumor necrosis factor [TNF]-α in periarticular drainage), and periarticular circumference were measured at baseline and during 2 days postoperatively. Changes in prothrombotic markers were evaluated.
  
  
  RESULTS
  Patients in the preconditioning group had significantly less pain postoperatively at rest (mean difference = -0.71, 95% confidence interval [CI] = -1.40 to -0.02, p = 0.043) and with exercise (mean difference = -1.38, 95% CI = -2.32 to -0.44, p = 0.004), but showed no differences in analgesic consumption. No differences were seen between the study and the control group in terms of muscle oxygenation and intraarticular levels of IL-6 and TNF-α as well as levels of prothrombotic markers. No differences were found between groups in regard to hospitalization length and time to various physical therapy milestones.
  
  
  CONCLUSIONS
  Ischemic preconditioning reduces postoperative pain after TKA, but the treatment effect size we observed with the preconditioning routine used was modest.
  
  
  CONCLUSIONS
  Given the ease of this intervention, ischemic preconditioning may be considered as part of a multimodal analgesic strategy. However, more study into the impact of different preconditioning strategies, elucidation of mechanisms, safety profiles, and cost-effectiveness of this maneuver is needed.
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, Weill Medical College of Cornell University, 535 East 70th Street, New York, NY, 10021, USA, memtsoudiss@hss.edu.
authors.forename: Stavros G
authors.initials: SG
authors.lastname: Memtsoudis
authors.forename: Ottokar
authors.initials: O
authors.lastname: Stundner
authors.forename: Daniel
authors.initials: D
authors.lastname: Yoo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gonzalez Della Valle
authors.forename: Friedrich
authors.initials: F
authors.lastname: Boettner
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Bombardieri
authors.forename: Kethy
authors.initials: K
authors.lastname: Jules-Elysee
authors.forename: Lazaros
authors.initials: L
authors.lastname: Poultsides
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sculco
mesh_terms: D000368:Aged; D000700:Analgesics / Q000627:therapeutic use; D000990:Antithrombin III; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000295:instrumentation; D007902:Length of Stay; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009519:New York City; D059408:Pain Management / Q000295:instrumentation / Q000379:methods*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D011446:Prospective Studies; D011516:Prothrombin; D020127:Recovery of Function; D012039:Regional Blood Flow; D013582:Synovial Fluid / Q000378:metabolism; D013997:Time Factors; D014111:Tourniquets; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000700:Analgesics; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases