Inducing inflammation after a surgical procedure is a natural healing response. Several studies have demonstrated a significant increase in inflammatory markers after surgery. However, they do return to normal levels over time. In certain circumstances, these markers can remain elevated for prolonged periods. Their persistent elevated levels could point towards an occult infection or instability. It is well known that these markers peak within the first few days after surgery and gradually decrease over time as the wound heals and the body's hemostasis returns to normal. If these markers persist or increase beyond the expected time frame, it may indicate a complication such as infection or prolonged inflammation. Several studies have evaluated CRP and ESR postop levels after a traditional total knee replacement. This study is the first to evaluate five expected inflammatory marker levels after robotic-assisted total knee arthroplasty. Additionally, we are comparing their levels in patients who underwent unilateral vs bilateral TKA's.
The C-reactive protein is an acute-phase protein produced by the liver in response to ongoing inflammation. This is the most commonly used inflammatory marker to assess healing progress following knee replacement. According to Baretto et al., CRP levels increase until the third day following surgery, reaching a mean value of 111.9 mg/L, a median value of 75.9 mg/L, and tapering off [11]. According to the study, only one-third of the patients returned to normal levels after three weeks. During the immediate postoperative period, CRP levels were not correlated with body mass index, age, gender, blood transfusion, or complications. A study by Shen H et al. reported that CRP is an extremely sensitive and specific marker for predicting complications, with a sensitivity of 86% and specificity of 92%. According to our study, in the bilateral group, CRP values increased immediately after surgery compared to the unilateral group.
Compared to preoperative values, they remained 24 hours, 48 hours, and 60 hours after surgery. The peak was reached at 60 hours postoperatively, with no downward trend until 96 hours. A significant difference in CRP titers was observed between the two groups at 24, 48, and 60 hours, with bilateral groups having significantly higher levels. This study provides baseline values for robotic knee replacement using the medial parapatellar approach and the importance of diligently selecting patients for bilateral knee replacement per the inclusion criteria.
A peak in ESR was observed in the bilateral group 60 hours after surgery and in the unilateral group 48 hours after surgery. It was evident that there was a significant difference between the two groups preoperatively and 24,48 and 60 hours postoperatively, with significantly higher values in the bilateral group. The ESR measures the rate at which red blood cells settle in a test tube over time. Often, it is used to indirectly measure increased acute phase reactants as a nonspecific haematological marker. Previously, Honwsawek et al. reported an increase in ESRs two weeks after TKA, with a peak value reaching 26 weeks following the procedure. Two weeks after surgery, they returned to preoperative levels [6].
On the other hand, CRP levels were elevated on the first postoperative day and decreased to their preoperative levels two weeks after surgery. Mercurio M. et al. reported that the median CRP level was 3.2 mg/l preoperatively, 57.6 mg/l postoperatively, and 5.3 mg/l thirty days postoperatively [12]. As a result of our study, ESR values tended to rise continuously and peaked in the 48 hours following surgery, whereas CRP values peaked at 60 hours following surgery. ESR and CRP can indicate a propensity towards prolonged inflammation if the levels are continuously higher beyond five days.
To our knowledge, no study has studied IL-6, LDH and AST levels in patients who underwent TKA. Paradoxically, depending on the context and the specific conditions in the body, it has been shown to have both pro-inflammatory and anti-inflammatory effects. As 1L-6 stimulates the synthesis of CRP from hepatocytes, it increases before CRP [13,14]. In this study, postoperatively, the peak of IL 6 was observed 12 hours after surgery, and the level of IL 6 began to decline 60 hours after surgery. Significant differences between unilateral and bilateral groups were observed after 12, 24, and 48 hours. These findings are significant because they correlate with the degree of intervention. Since there is usually a downward trend as early as 60 hours postoperatively, they may reflect any deviation from normal very early. According to Honwsawek et al., in their 49 unilateral total knee replacements study, serum IL-6 levels peak at 24 hours postoperatively and return to preoperative levels after two weeks. After primary total knee replacement, Maniar RN et al. examined the average levels of IL-6 and CRP in 50 patients who underwent surgery using a midvastus approach with navigation. A peak in CRP levels was observed at 48 hours, and a return to baseline occurred after two weeks. IL-6 levels peak at 12 hours postoperatively, decline after four postoperative days and return to preoperative levels within two weeks [15]. A study by Huang ZY et al. examined IL6 and CRP levels in patients who underwent conventional unilateral primary total knee replacement with enhanced recovery at 12 hours, 48 hours, 72 hours, and two weeks after surgery [16].
In contrast, IL-6 levels peak 48 hours postoperatively and begin to decline within 72 hours, while CRP levels peak at 72 hours and return to normal within two weeks. Their study's late rise in IL-6 was due to not using the tourniquet to prevent reperfusion injury and enhance recovery, as opposed to using the tourniquet to prevent reperfusion injury [16]. According to Xu JZ et al., in conventional and robotic total knee replacements, CRP, ESR, IL-6, neutrophil to lymphocyte ratio, and creatine kinase were measured preoperatively and at the first and third postoperative days. A lower level of the inflammatory marker was found in the robotic group compared to the traditional group on the third postoperative day [17].
The present study found that both groups showed significant increases in LDH levels immediately following the procedure and increased slightly between 24 and 48 hours afterward. After 48 hours of postoperative surgery, the peak was reached and then began to decline. Furthermore, this study showed no significant difference between the unilateral and bilateral groups at any point in time. The extent of tissue damage may not directly correlate with the level of LDH.
According to Niki Y et al., different inflammatory markers were detected following conventional total knee arthroplasty and minimally invasive knee replacement. There is a minor peak in levels of AST on postoperative day one and a prominent peak on day seven [10]. The present study showed a rise in postoperative AST levels following surgery in both groups, followed by a drop. We cannot comment on further peak levels because we only analysed maximum day seven data.
Despite its uniqueness, the study has several limitations and drawbacks. Firstly, in many cases, the final blood draw was performed on the day of the discharge, as the patient's length of stay varies from patient to patient. However, we obtained at least 4 samples, including the one collected in the preop period, and analysed them to obtain meaningful data.
Second, we identified statistically significant differences in sex, preoperative haemoglobin, tourniquet time, Diabetes, rheumatoid arthritis, and length of hospital stay. However, due to the small sample size and lack of homogeneity, these results were not found to be significant at a larger institution with a larger sample size. Despite this, the study brings out important statistically pertinent facts beyond trends.
A baseline study designed for a specific cohort of consecutive patients operated with Robotic technology without violating the intramedullary canal and with lesser soft tissue dissection [ as proclaimed by proponents of technology] is likely helpful for future comparisons [18]. Similarly, comparing the trends of markers in bilateral and unilateral may guide surgeons in making the appropriate choice based on preoperative levels.