The effect of preoperative different dexamethasone regimens on postoperative glycemic control in patients with type 2 diabetes mellitus undergoing total joint arthroplasty: a retrospective cohort study

Type 2 diabetes mellitus (DM) is an age-related disease and accounts for nearly 90% of the approximately 537 million global diabetic cases [1]. The rising worldwide incidence of DM is obvious, which is estimated to rise to 783 million by 2045 [2]. Total joint arthroplasty (TJA) including total hip arthroplasty (THA) and total knee arthroplasty (TKA) is conventionally performed in elderly patients diagnosed with end-stage arthropathies to alleviate pain and restore joint function. The prevalence of DM in TJA patients is estimated to surpasses 15% for THA and 21% for TKA [3]. And the prevalence of DM and perioperative hyperglycemia correlate with increased postoperative complications, including prosthetic joint infection (PJI) and wound complications [4, 5]. Studies have identified postoperative blood glucose levels ≥ 200 mg/dl (11.1 mmol/L) as a risk factor for surgical site infections, even in patients with preoperatively well-controlled blood glucose levels [6, 7]. Hence, postoperative blood glucose levels should be well-managed to avoid adverse events in diabetic patients undergoing TJA.

However, TJA intervention and anesthesia may induce metabolic disorders, resulting in poorly controlled postoperative blood glucose, particularly in diabetic patients [8, 9]. Additionally, operation-related soft tissue injury can trigger systemic inflammatory response and insulin resistance to exacerbate challenges in glycemic control [10]. Dexamethasone, a potent and long-acting glucocorticoid, is routinely administered intravenously preoperatively in TJA patients to attenuate perioperative acute phase response and alleviate postoperative pain, nausea, and vomiting [11‐13], which were beneficial for glycemic control. But, dexamethasone inherently induces hyperglycemia [4], inhibits the inflammatory phase of wound healing [14], and suppresses the immune system [15], which potentially increase the risk of postoperative hyperglycemia and surgical site infections. The dual nature of dexamethasone, with both positive and negative effects, prompts an exploration of its comprehensive impact on glycemic control in type 2 DM patients undergoing TJA. Several studies have discussed the relationships of dexamethasone to blood glucose in diabetic patients undergoing TJA and they preliminarily concluded that an initial increase in blood glucose was observed after dexamethasone administration, yet there was no increase in the rate of infection [9, 16‐19]. However, the current studies were limited by different dexamethasone administration ways [16], different dexamethasone doses [18], small sample size [9, 16, 17], non-diabetic patients included [16, 18], and oversight of food effects [19]. Consequently, further study was needed to identify the effect of dexamethasone on blood glucose levels in diabetic patients undergoing TJA.

This study aimed to evaluate the influence of preoperative intravenous administration of different doses of dexamethasone on postoperative blood glucose levels in diabetic patients undergoing TJA. Furthermore, we determined the risk factors associated with elevated blood glucose levels (≥ 11.1 mmol/L) during the admission period. We hypothesized that compared to the non-dexamethasone group, preoperative intravenous dexamethasone yielded transient effects on increasing the blood glucose levels and dexamethasone administration was not associated with blood glucose levels ≥ 11.1 mmol/L.

The elevated blood glucose levels were associated with complications after TJA, particularly in diabetic patients [9, 18, 19]. Consequently, the orthopedic surgeons have exhibited reluctance in intravenously administering dexamethasone to patients during the perioperative period. This study aimed to evaluate the correlations between preoperative different dexamethasone administration and postoperative blood glucose levels in diabetic patients undergoing TJA. Additionally, the study also identified the risk factors for postoperative hyperglycemia. The principal finding was that preoperative intravenous administration of 5 mg or 10 mg dexamethasone in diabetic patients undergoing TJA would lead to a transient increase in FBG. However, this increase did not yield clinically significant difference and promptly normalized during the subsequent assessments. Furthermore, no differences were found on the rates of PJI and wound complications within 90 days postoperatively. Our study also found that increased HbA1c and preoperative high FBG, but not preoperative dexamethasone administration, worked as the predictive indicators for postoperative hyperglycemia.

Anesthesia and surgery can lead to stress response and contribute to marked neurophysiological changes characterized by the releases of many hormones, such as cortisol, glucagon, and growth hormone, which can elevate the glucose levels and augment insulin resistance [24]. Additionally, diabetic patients often presented with disruptions in glucose metabolism. So, the use of dexamethasone in diabetic patients undergoing TJA may precipitate postoperative hyperglycemia and substantial changes in blood glucose levels. Postoperative hyperglycemia was associated with poor postoperative outcomes in orthopedic surgery including infection, mortality, and poor rehabilitation [24, 25]. Currently, several studies have focused on the effect of dexamethasone on glycemic control in diabetic patients after TJA. Nurok et al. [16] found that there was no evidence of an association between dexamethasone administration and the odds of postoperative glucose levels ≥ 200 mg/dl or higher maximum glucose levels. Park et al. [9] further confirmed that patients with a preoperative HbA1c level of ≥ 7.05% may necessitate alterations in diabetic medication after TKA, regardless of intravenous dexamethasone administration. And Godshaw [18] et al. demonstrated perioperative intravenous dexamethasone did not increase the rate of PJI. Moreover, Allen et al. [17] and Arraut et al. [19] concluded that dexamethasone was associated with transient increase in blood glucose among diabetic patients after TJA, yet this unfavorable effect may not outweigh the known clinical benefits of perioperative glucocorticoids. In our study, we also found preoperative administration of 5 mg or 10 mg dexamethasone to diabetic patients was linked to an initial increase in blood glucose after TJA. Importantly, this increase does not increase the rates of PJI and wound complications within the 90-day postoperative period. Discrepancies with Nurok et al. [16], we found that dexamethasone would lead to higher maximum glucose levels in diabetic patients after TJA. Because Nurok et al. [16] included many non-diabetic patients in dexamethasone group and the diabetic individuals were more likely to experience disturbance of glucose metabolism after TJA. Also, Nurok et al. [16] also acknowledged that their findings may not be generalizable to patients having different baseline characteristics or procedures. So, these may be the reasons why our results were different.

The degree of metabolic disorders correlated with the dose of glucocorticoid [26]. So, whether intravenous 10 mg dexamethasone can result in greater metabolic disturbance than 5 mg dexamethasone in diabetic patients after TJA? Several studies have reported the effect of dexamethasone on FBG levels in diabetic patients after TJA. Allen et al. [17] found that there was no statistically significant association between preoperative 8 mg dexamethasone administration and maximum blood glucose levels within 24 h after surgery. Additionally, Park et al. [9] reported that 10 mg dexamethasone transiently increased blood glucose levels in diabetic patients on POD 0 and POD 1, but had no effect beyond POD 1. Godshaw et al. [18] demonstrated that although diabetic patients experienced significantly higher glucose levels than non-diabetic ones after administration of 12 mg dexamethasone, this was unaffected by the administration of dexamethasone. So, dexamethasone can elevate blood glucose levels in diabetic patients after TJA. Arraut et al. [19] further compared the effects of intravenous 10 mg dexamethasone with 20 mg dexamethasone on glucose levels in diabetic patients and they found that patients after administration of 20 mg dexamethasone trended towards slightly higher mean postoperative blood glucose levels at 24–36 h postoperatively. But, there was no significant difference on maximum blood glucose levels within 72 h. And there were no differences on postoperative glucose levels over 200 mg/dL. So, higher dose of dexamethasone would be more likely to elevate postoperative blood glucose. But, this transient tendency did not lead to clinical difference. Similarly, our study also found that preoperative dexamethasone can elevate FBG levels within POD 1 and there were no differences on postoperative mean FBG levels.

Intravenous dexamethasone can reduce postoperative pain, opioid consumption, nausea/vomiting for patients undergoing TJA [27]. Since glucocorticoid may potentially disturb the blood glucose, the studies evaluating the effect of dexamethasone in TJA excluded the diabetic patients due to the concern of possibly excessive blood glucose fluctuations. Evidence-based guidelines for dexamethasone use in TJA advocated for further research exploring the safety aspects of its administration in patients with DM [27]. Multiple studies have showed that blood glucose levels ≥ 200 mg/dl (11.1 mmol/L) can increase the risk of postoperative infetion and wound complications [9, 17‐19]. Therefore, it was important to distinguish the risk factors for blood glucose levels ≥ 11.1 mmol/L. Allen et al. [17] identified elevated HbA1c and advancing age as risk factors for blood glucose levels ≥ 11.1 mmol/L. Similarly, Park et al. [9] demonstrated that high preoperative HbA1c levels increased and high body mass index decreased the postoperative blood glucose levels. Additionally, Nurok et al. [16] reported no evidence of an association between preoperative pain or postoperative pain and the odds of postoperative blood glucose levels ≥ 11.1 mmol/L. All these studies concluded that preoperative dexamethasone did not increase the occurrence of postoperative blood glucose levels ≥ 11.1 mmol/L. Consistent with these findings, our study also revealed that high preoperative HbA1c increased the risk of postoperative hyperglycemia, while there was no association between preoperative administration of 5 mg or 10 mg dexamethasone and blood glucose levels ≥ 11.1 mmol/L. Notably, if the preoperative HbA1c level was more than 7.15%, the patients may be susceptible to blood glucose levels ≥ 11.1 mmol/L. Moreover, we firstly reported that high preoperative FBG contributed to a high risk of blood glucose levels ≥ 11.1 mmol/L. High preoperative FBG can reflect the poor control of recent blood glucose levels. And postoperative blood glucose may be more likely influenced by the surgery and so on. This may be the reason why high preoperative FBG was associated with postoperative hyperglycemia.

PJI, a devastating complication associated with increased morbidity and mortality, necessitates subsequent multiple operations and requires substantial health-care funds [28]. And wound complications are the predominant causes of readmission in Asian population [29]. Wound problems can result in disastrous consequence and how to achieve effective wound healing in TJA is essential to improve satisfaction levels. Therefore, it’s important to avoid PJI and wound complications after TJA. But for diabetic patients scheduled to TJA, DM has been identified as an independent risk factor for PJI with study showing 2–3 times the risk [18]. Moreover, diabetic individuals were more likely to experience wound complication [30]. Given these considerations, orthopedic surgeons may hesitate to inject dexamethasone intravenously for diabetic patients due to safety concerns. Previously, scholars have studied the safety aspects of perioperative administration of glucocorticoids including dexamethasone and methylprednisolone in non-diabetic patients undergoing TJA. They concluded that glucocorticoids did not increase the rates of PJI and wound complications [31‐34]. Moreover, other scholars examined the influence of dexamethasone on PJI and wound complications in diabetic patients undergoing TJA [18, 19]. Their findings indicated that both the incidences of PJI and wound complication were low, with no difference between the dexamethasone and non-dexamethasone groups within 90 days postoperatively. Our results showed that only 5 patients encountered wound complications and 2 patients encountered PJI within 90 days postoperatively, all of which were from non-dexamethasone group. And no differences were observed among the three cohorts. Our study has come to the same conclusion regarding the PJI and wound complications. Furthermore, in a larger cohort receiving dexamethasone, we firstly demonstrated there were no differences on the postoperative complications in preoperative administration of 5 mg or 10 mg dexamethasone.

The study has several limitations. First, this study relied on retrospective analysis of discharge records, potentially introducing biases associated with data quality. High-quality studies such as RCTs about the effect of dexamethasone on FBG levels in diabetic patients undergoing TJA should be conducted in the further to provide more reliable conclusions. Second, we just reported the clinical outcomes within 90 days postoperatively. And we did not acknowledge whether the rates of PJI and wound complications would undergo changes. Third, as our postoperative management has evolved, our hospital stay was short. This limited the data that were available for postoperative time points regarding blood glucose levels in our study. So, we can’t get the FBG changes in the subsequent time. We think with the establishment of national joint registration systems and further development of monitoring devices on blood glucose, these two limitations can be resolved in the further. Last, high-dose and repetitive dose administration of steroids in TJA patients was gradually common [35, 36], but our study was limited to administration of single and relatively low-dose dexamethasone. Moreover, if the study was conducted with other types and dose of steroids, the results might be different.

Preoperative intravenous administration of 5 mg or 10 mg dexamethasone to diabetic patients has transient effects on increasing the blood glucose levels after TJA. Notably, patients with a preoperative HbA1c level of ≥ 7.15% and elevated preoperative FBG may be associated with postoperative glucose levels ≥ 200 mg/dl, regardless of dexamethasone administration and the dose. In this study population, preoperative intravenous administration of 5 mg or 10 mg dexamethasone to diabetic patients undergoing TJA may not increase the rates of PJI and wound complications within 90 days postoperatively.