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This project tested whether oxidative stress (OS) related to extended tourniquet application during total knee arthroplasty (TKA) and subsequent ischemic reperfusion contributed to CRPS outcomes up to 6 month following TKA. Blood samples were obtained in 90 osteoarthritis patents (63.3% female; 95.6% Non-Hispanic White) undergoing TKA prior to tourniquet placement (T1), 45 minutes after tourniquet inflation (T2), and 15 minutes following tourniquet removal (T3). Plasma levels of F2-isoprostanes (IsoPs) and isofurans (IsoFs), the most specific measures of in vivo OS, were quantified. The primary OS measure was Combined OS (IsoPs+ IsoFs/2), which most accurately captures upstream OS processes independent of oxygen tension. CRPS outcomes included a continuous measure of CRPS symptom extent (CRPS Severity Score; CSS) and dichotomous CRPS diagnoses based on 2012 IASP diagnostic criteria. CRPS outcomes were assessed at 6 week and 6 month post-TKA follow-up. Results indicated that greater variability in Combined OS across T1-T3 predicted higher CSS scores at 6 week follow-up (p<.02). A CRPS diagnosis at 6 week follow-up was predicted by greater perioperative OS at T3 (p<.01), greater OS change from T1-T2 (p<.02), higher average OS across T1-T3 (p<.006), higher maximum OS across T1-T3 (p<.006), and greater variability in OS across T1-T3 (p<.02). Extent of CRPS symptoms at 6 month follow-up, which are more clearly interpretable as reflecting clinical CRPS, were predicted by greater increases in OS from T1 to T2 (p<.03), with a similar marginal trend (p<.08) for baseline pre-incision (T1) OS levels. Perioperative OS did not significantly predict CRPS diagnosis at 6 months. Results indicate that elevated perioperative OS status in patients undergoing TKA may increase risk for CRPS particularly in the early postoperative period. These findings implicate OS as a potential novel mechanism of CRPS risk in the surgical setting. R01AG048915 (SB) R01GM112871 (FTB) UL1 TR000445.
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