Perioperative Oxidative Stress Prospectively Predicts CRPS-Related Outcomes in the 6 months Following Total Knee Arthroplasty

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.