Perioperative hyperglycemia and postoperative periprosthetic joint infection (PJI) after total knee and hip arthroplasty

Peri-prosthetic joint infection (PJI) is not only a serious individual health problem requiring long-term use of antibiotics or sometimes staged-revision surgery, but also a serious public health problem increasing national healthcare cost [1,2] as well. Diabetes mellitus (DM) is known to be one of the risk factors for PJI and its prevalence is on an increasing trend in the general population [3]. There are some reports showing the relationship between postoperative glucose levels and postoperative infections in the fi eld of cardiothoracic surgery [4-7]. These studies suggested that postoperative hyperglycemia might be one of the risk factors for postoperative infection or wound complications in the cardiothoracic surgery. Therefore, we hypothesized that post-operative hyperglycemia might be also one of the risk factors of PJI. However, the quantitative relationship between the peri-operative blood glucose levels and PJI has not been fully established. The aim of this study is to fi nd the relationship between peri-operative hyperglycemia and PJI.


Introduction
Peri-prosthetic joint infection (PJI) is not only a serious individual health problem requiring long-term use of antibiotics or sometimes staged-revision surgery, but also a serious public health problem increasing national healthcare cost [1,2] as well. Diabetes mellitus (DM) is known to be one of the risk factors for PJI and its prevalence is on an increasing trend in the general population [3]. There are some reports showing the relationship between postoperative glucose levels and postoperative infections in the fi eld of cardiothoracic surgery [4][5][6][7]. These studies suggested that postoperative hyperglycemia might be one of the risk factors for postoperative infection or wound complications in the cardiothoracic surgery.
Therefore, we hypothesized that post-operative hyperglycemia might be also one of the risk factors of PJI. However, the quantitative relationship between the peri-operative blood glucose levels and PJI has not been fully established.
The aim of this study is to fi nd the relationship between peri-operative hyperglycemia and PJI. patients. The diagnosis in THA patients was osteoarthritis in 1 patient and epiphyseal dysplasia in one patient. The mean preoperative C-reactive protein levels were 0.25±0.5 mg/dL (range; 0 to 4.34 mg/dL). All patients were followed up for a minimum of 1year postoperatively.

Materials and Methods
Of the 234 patients, 32 (14.0%) had a history of type II DM before surgery. Preoperatively, the fasting blood glucose (FBG) levels and plasma hemoglobin A1c (HbA1c) were measured within two months before surgery. Three patients (9.4%) of the 32 DM patients required insulin control of diabetes, 24 patients (75.0%) in oral medicine and 5 patients in diet only. Table 2 shows the diabetes-related characteristics. Every patient received intravenous antibiotics (cefazolin) for two days postoperatively. Every patient restarted to eat next morning after the operations.
We measured the blood glucose levels for two days postoperatively before each meal for all patients who underwent TKA and THA using self-monitoring of blood glucose (SMBG) meters (ARKRAY, Co., Ltd., Tokyo, Japan). We took their blood and measured the fasting blood glucose (FBG) levels at 1,2 and 3 weeks after operations. We used the rapid-acting insulin according to our protocol of sliding scale insulin when the blood glucose levels before each meal were over 200 mg/dL for two days postoperatively. We used 4 units of the rapid-acting insulin from 200 to 250 mg/dL, 6 units from 250 to 280 mg/dL, 8 units from 280 to 300 mg/dL, and 10 units over 300 mg/dL. PJI was diagnosed based on the criteria for defi ning a surgical site infection (SSI) [8]. For data analysis, fi rst, the patterns of the blood glucose levels for these two days and FBG levels at 1, 2 and 3 weeks after operation were identifi ed for each patient, and the blood glucose levels were compared between the infected and non-infected groups. Second, the risk factors of PJI were investigated.
All statistical analyses were performed in Ekuseru-Toukei 2012 (Social Survey Research Information Co., Ltd., Tokyo, Japan). Correlations were considered signifi cant when the p value was less than 0.05. Correlations among the comparison of the background between the infected group and the noninfected group were determined using Wilcoxon rank sum test and Fisher's exact test. Correlations among the blood glucose levels between in the infected group and in the non-infected group were also determined using Wilcoxon rank sum test and Fisher's exact test.

Results
The overall incidence of PJI among the 234 patients was 1.2% (n=3). All three PJI (two women, one men), occurred after TKA.
One woman underwent TKA of the right side due to the primary osteoarthritis. She had required insulin control of diabetes. On 64th days after the operation, her knee was swollen and became  Table 3 shows that the comparison of the background between the infected group and the non-infected group. In this study, the rate of PJI was signifi cantly higher in patients with higher preoperative FBG values in TKA patients. Blood glucose levels for the two postoperative days tended to be higher in the infected than in the non-infected group, although the differences were not statistically signifi cant (Figure 1). FBG levels at 1 week after operation also tended to be higher in   Table 6).

Discussion
The number of DM patients who need to undergo THA or TKA have been increasing [9]. As many literatures have stated the associations between the postoperative infections and DM or a high level of HbA1c in the fi eld of cardiothoracic surgery [4][5][6][7], it was also reported that the patients that underwent total joint arthroplasty with DM had a signifi cantly higher risk of postoperative PJI than that of the patients without DM [10][11][12][13][14][15]. For example, Hwang et al. reported that the patients with the preoperative blood glucose levels >200 mg/dL and HbA1c levels >8.0 mg/dl were at the risk for wound complications after total knee arthroplasty [13]. Tarabichi et al. reported that the HbA1c level over 7.7 mg/dL was associated with a higher risk of postoperative PJI [15]. Although it has been reported that it is important to control the postoperative glucose levels to decrease the rate of PJI [10], there are few reports about the association with hyperglycemia and PJI. This motivated us to study the postoperative blood glucose levels after TJA.
The highlight of our study was fi rst that the peri-operative blood glucose values at Day 1 and 2 were tended to be higher in infected patients than those of the non-infected group, and the average blood glucose levels increased to about 200 mg/dL in the afternoon of Day 1 and 2 in the infected group. It also showed that PJI patients were higher blood glucose level at 1 week after operation than not-infected patients.
Two reports about the relationship between the hyperglycemia and the postoperative PJI were introduced as follows [14,16]. Stryker et al. [14], reported that patients with a mean postoperative glucose >200 mg/dL are at the risk for wound complications after total joint arthroplasty. Mraovic et al. reported the perioperative blood glucose levels at Day 1 morning in infected patients who underwent TJA were signifi cantly higher than that in not-infected patients [16]. Mravoic also reported the glucose values at Day 1 morning over 200mg/dL was a signifi cant risk factor for infection with an over two-fold increased rate of the infection comparing with the glucose levels under 200ml/dL [16].
Compared with these literatures we introduced, the blood glucose levels in the afternoon were higher than that in the morning and evening in the infected group from the fi gure in our study. Moreover, there was only one patient with the blood glucose levels over 200 mg/dL at Day 1 morning and that patient was not infected. From those results, we hypothesized that it would be more important to measure the blood glucose levels in the afternoon than in the morning. Our study suggested that the postoperative blood glucose level over 200 mg/dL in the afternoon at Day 1 and 2 was a predictive factor of PJI.
Most investigators rarely pay attention to the glucose level after one week postoperatively although they pay attention to   Table 4: Cross-sectional analysis results with maximum blood glucose levels before each meal in two days postoperatively.