What Is the Normal Trajectory of Interleukin-6 and C-reactive Protein in the Hours and Days Immediately After TKA?

Background Some patients with early periprosthetic joint infection (PJI) can be treated successfully using open débridement with polyethylene exchange rather than two-stage revision; however, the challenge is to diagnose PJI early. In late infection, C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated, but shortly after surgery, CRP is difficult to interpret because it may be elevated even in the absence of infection, and we know little about the normal trajectory of IL-6 immediately after arthroplasty. If a deviation of biomarkers from their normal trajectory is seen, it may help guide the clinician toward early knee aspiration.

Questions/purposes We studied the normal trajectories of IL-6 and CRP in the immediate hours and days after uncomplicated TKA and examined whether one or the other normalizes more quickly.

Methods We studied serum IL-6 and CRP levels in 50 patients undergoing primary TKA at five time points: 12 hours preoperatively and postoperatively at 12 hours, 48 hours, 4 days, and 2 weeks. One surgeon operated on all patients using the same approach and postoperative management. The same laboratory methods were used each time. Results are presented as median and range. Repeated-measures analysis was done using Friedman’s (nonparametric) test. No patient showed any clinical sign of infection during our study period. All patients were followed up until 1 year with no evidence of infection and good knee scores.

Results IL-6 showed a sharp rise from its baseline with a preoperative median value of 6 pg/mL (range, 3-17 pg/mL) to a peak of median value of 133 pg/mL (range, 15-359 pg/mL) at 12 hours postoperatively. At 48 hours, IL-6 had declined to a median value of 82 pg/mL (range, 12-309 pg/mL). At 4 days, it had further declined to a median value of 22 pg/mL (range, 5-67 pg/mL). At 2 weeks, IL-6 reached a median value of 7 pg/mL (range, 3-14 pg/mL), which was not different from the baseline median value with the numbers available (p = 0.455). CRP showed a gradual rise from its baseline preoperative median value of 2 mg/L (range, 1-17 mg/L) to a median value of 15 mg/L (range, 2-111 mg/L) at 12 hours postoperatively, which peaked at 48 hours to a median value of 125 mg/L (range, 22-247 mg/L). At 4 days postoperatively, CRP levels had declined to a median value of 69 mg/L (range, 21-234 mg/L). At 2 weeks, CRP had reached a median value of 12 mg/L (range, 1-72 mg/L), which was still higher than the baseline median value with available numbers (p < 0.001).

Conclusions We found that after uncomplicated TKA, IL-6 showed a sharp rise to peak at 12 hours, then fell rapidly to near baseline levels by 4 days and returned to the baseline level at 2 weeks. CRP showed a gradual rise to peak at 48 hours, then fell gradually, remaining elevated at 4 days and higher than baseline level at 2 weeks. Future studies can help define more definitive thresholds for IL-6 and CRP; ideally, these should derive from large, multicenter studies. With such data, any deviation from a known normal trajectory can facilitate a quicker decision to perform knee aspiration to diagnose early PJI more promptly.

Level of Evidence Level III, diagnostic study.