Prolonged Tourniquet Application in Total Knee Arthroplasty Leads to Increased Pro-Inflammatory and Procoagulant Markers Linked to Ischemia/Reperfusion Injury—A Randomized Controlled Trial

Background: Currently, the duration of tourniquet time in total knee arthroplasty is chosen by the surgeons and varies between 0 and 120 minutes. Studies evaluating the effect of tourniquet time in this operation are lacking. The purpose of this study was, therefore, to determine whether the duration of tourniquet-induced limb ischemia during total knee arthroplasty influences reperfusion injury, resulting in pain, swelling and the release of proinflammatory markers. Methods: In 40 patients undergoing total knee arthroplasty, tourniquet was applied for up to 30 minutes (group A, short tourniquet) or 90-120 minutes (group B, long tourniquet). Postoperative pain and swelling served as primary outcome parameters. The levels of pro- and anti-inflammatory markers (D-dimers, C3a, C5a, TAT, fetuin-A, PAI-I/tPA complexes, CK-MM, IP10, M-CSF, MIG, MIP-1α, and sC5b9) before surgery and 4 hours, 24 hours and 48 hours after surgery, were used as secondary outcome parameters. Results: Patients in group B, with the long tourniquet time, required patient-controlled intravenous analgesia more frequently than group A patients (47% versus 5%, group B vs. group A, p < 0.0001). However, there were no differences in numeric rating pain scale (NRS) scores and calf circumference between groups A and B. In group B, a significantly higher increase of C3a levels between 4 h and 48 h, a significantly higher increase for MIG between 4 h and 48 h as well as 24 h and 48 h, and a significantly higher increase in M-CSF levels between 24 h and 48 h were observed when compared to group A. Conclusions: Tourniquet times between 90 and 120 minutes, despite currently being accepted in the clinical setting, were associated with an increased need for intravenous analgesia and higher increase of the pro-inflammatory markers C3a, MIG, and M-CSF, suggesting a more pronounced ischemia/reperfusion injury with tourniquet times longer than 90 minutes.