Efficacy and safety of perioperative intravenous dexamethasone in type 2 diabetes mellitus patients undergoing total hip arthroplasty: a prospective randomized controlled trial

Abstract

Purpose

This study aimed to evaluate the efficacy and safety of perioperative intravenous dexamethasone (Dexa) in patients with type 2 diabetes mellitus (T2DM) undergoing total hip arthroplasty (THA).

Methods

In this prospective, single-blind randomized trial (Registration No.: MR-45-23-047982; Registration Date: December 7, 2023), 60 T2DM patients undergoing THA were assigned to either the Dexa or control group. Outcomes included white blood cell count (WBC), C-reactive protein (CRP), visual analogue scale (VAS) scores, blood glucose, nausea and vomiting, medication requirements, complications, and hospital stay.

Results

Compared with controls, the Dexa group had lower WBC on postoperative days 2 ~ 3 (day 2: 9.20 ± 1.28 vs.10.56 ± 2.34 × 10⁹/L, P = 0.007; day 3: 8.02 ± 1.34 vs. 9.22 ± 1.49 × 10⁹/L, P = 0.002)and reduced CRP on days 1 ~ 3 (day 1: 38.20 vs. 63.50 mg/L, P = 0.040; day 2: 86.00 vs. 101.50 mg/L, P = 0.010; day 3: 78.00 vs. 95.20 mg/L, P = 0.044). Transient hyperglycemia was observed in the Dexa group on postoperative day 1, with higher median blood glucose (8.90 vs. 8.35 mmol/L, P < 0.01) and peak glucose (11.80 vs. 10.35 mmol/L, P = 0.031) but showed no differences thereafter. VAS pain scores at rest and during activity were lower in the Dexa group on postoperative days 1 ~ 2 (all P < 0.01). Dexa reduced the need for rescue tramadol (4 vs. 12 patients, P = 0.020) and metoclopramide (1 vs. 8 patients, P = 0.026), and lowered PONV incidence (3.33% vs. 23.30%, P = 0.026). Hospital stay was shorter in the Dexa group (5.67 ± 1.13 vs. 6.70 ± 1.29 days, P = 0.002), with no differences in 90-day complications (all P > 0.05).

Conclusion

Perioperative Dexa administration improves early recovery outcomes in patients with T2DM undergoing THA without compromising short-term safety, although it may cause transient hyperglycemia. However, the relatively small sample size, limited follow-up period, and lack of systematic evaluation of potential complications highlight the need for larger, longer-term studies to further strengthen these observations.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13018-026-06808-1.

Introduction

Total hip arthroplasty (THA) is one of the most common orthopedic procedures performed today in the field of orthopedic surgery, THA is widely regarded as one of the most successful surgical procedures of the 20th century due to its remarkable efficacy. However, factors such as surgical trauma and anesthesia can lead to postoperative pain, nausea, vomiting, and other discomfort, significantly impacting patient satisfaction and recovery outcomes. These symptoms can result in prolonged hospital stays and increased healthcare costs, imposing a significant burden on patients [1].

With the advancement of enhanced recovery after surgery (ERAS) protocols, glucocorticoids have been increasingly used in the perioperative management of non-cardiac surgery patients to alleviate postoperative nausea, vomiting, and other symptoms. Studies have demonstrated that perioperative administration of dexamethasone (Dexa) can reduce the risk of postoperative nausea and vomiting (PONV) by 26% [2]. Dexamethasone, a potent and long-acting glucocorticoid, was developed by Philip Showalter Hench and colleagues in 1957 through structural modification of existing glucocorticoids [3]. Due to its significant efficacy and low mineralocorticoid activity, dexamethasone was rapidly approved for the treatment of various diseases [4], Its development marked a new era in glucocorticoid therapy, offering effective treatment options for a wide range of inflammatory and immune disorders [5]. Furthermore, studies have demonstrated that perioperative administration of Dexa in joint replacement surgery can alleviate pain, reduce inflammation, and lower the risk of postoperative nausea and vomiting (PONV) [6]. Consequently, Dexa has been increasingly utilized in the perioperative management of THA in recent years [7, 8].

However, most previous investigations of perioperative dexamethasone use in total hip arthroplasty (THA) have primarily focused on non-diabetic patients, resulting in a paucity of high-quality evidence in this high-risk population with diabetes. According to global epidemiological data, the prevalence of type 2 diabetes mellitus (T2DM) continues to rise and is projected to reach 783 million by 2045 [9], Correspondingly, contemporary arthroplasty cohorts indicate that patients with T2DM account for more than 15 ~ 20% of individuals undergoing THA [6, 10]. Patients with T2DM are known to have an increased risk of adverse postoperative outcomes, and poor perioperative glycemic control has been associated with worse prognosis following THA. Notably, elevated perioperative blood glucose levels represent a well-established independent risk factor for surgical site infection (SSI) and periprosthetic joint infection (PJI), even among patients with apparently well-controlled preoperative glycemia [11] .A large multicenter retrospective analysis of 90,830 primary THA patients demonstrated that elevated preoperative blood glucose was independently associated with an increased risk of PJI, with diabetic patients exhibiting a 2.60-fold higher adjusted odds when preoperative glucose levels exceeded 277 mg/dL [12]. Currently, research evidence on the safety of Dexa in T2DM patients undergoing THA, especially concerning perioperative glycemic variability and the associated risk of infection, is still limited. Although retrospective studies, such as that by Williams et al. [13], have suggested that perioperative dexamethasone administration may be associated with reduced hospital length of stay in patients with T2DM undergoing total hip arthroplasty, these findings are inherently limited by retrospective design, non-randomized treatment allocation, and potential residual confounding. In addition, perioperative glycemic monitoring and infection-related outcomes were not uniformly predefined or systematically assessed in prior studies. Therefore, a prospective randomized controlled trial is required to provide more robust evidence regarding the causal effects and safety of dexamethasone use in this high-risk population. By standardizing perioperative management and systematically evaluating blood glucose variability and postoperative complications, the present study aims to address key evidence gaps left by previous retrospective analyses and to better inform perioperative management strategies.

Materials and methods

Object of study

In this study, 60 patients from the Department of Joint Surgery at The People’s Hospital of Guangxi Zhuang Autonomous Region were enrolled. The inclusion criteria were: a preoperative diagnosis of osteonecrosis of the femoral head (ONFH), osteoarthritis (OA), or developmental dysplasia of the hip (DDH), in combination with a prior diagnosis of type 2 diabetes mellitus (T2DM). This randomized controlled trial was conducted and reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. The study received approval from the hospital’s ethics committee (approval number: KY-ZC-2022-109) and was registered with both the National Health Information Security Platform and the Medical Research Registration and Filing Information System (www.medicalresearch.org.cn, registration number: MR-45-23-047982, December 7, 2023). The trial flow diagram is presented in Fig. 1.

Fig. 1.

Flow diagram of the trial

Inclusion and exclusion criteria

Inclusion criteria

1. Patients with insulin-dependent type 2 diabetes mellitus who meet the diagnostic and therapeutic criteria for primary total hip arthroplasty.

2. Absence of any contraindications to anesthesia.

3. Written informed consent obtained from both the patients and their families prior to participation in the study

Exclusion criteria

1. Patients with a documented history of glucocorticoid allergy.

2. Patients who abuse alcohol or substance abuse.

3. Patients aged < 18 years or > 75 years.

4. Patients who received glucocorticoid therapy within 3 months prior to surgery.

5. Patients who used strong opioids within 1 week before surgery.

6. Patients diagnosed with rheumatic system diseases.

7. Patients with abnormal adrenocortical function were excluded based on preoperative morning serum cortisol testing or a documented history of adrenal disorders.

8. Patients with a history of gastrointestinal ulcer or bleeding who underwent anticoagulation treatment within 1 week before surgery.

9. Patients with immunodeficiency diseases.

Case grouping

A prospective, single-blind, randomized controlled trial was conducted. Eligible patients were randomly assigned in a 1:1 ratio to either the Dexa group or the control group using a computer-generated random number sequence with variable block sizes. The allocation sequence was generated by an independent statistician who was not involved in patient recruitment. The group allocation information was concealed in sequentially numbered, opaque, sealed (SNOS) envelopes. The envelopes were prepared by a research nurse not involved in the trial and were opened immediately prior to surgery by an anesthesiologist who was not part of the research team. Throughout the study, patients remained blinded to their group assignment.

To ensure strict adherence to the study protocol and patient safety, all intravenous injections were administered by a qualified anesthesiologist following verification with the attending surgeon.In the Dexa group, patients received an intravenous injection of 10 mg Dexa sodium phosphate before anesthesia induction, followed by an additional 10 mg dose administered intravenously 3 h after the initial dose. In the control group, patients received an intravenous injection of 2 mL of normal saline before anesthesia induction, followed by an equivalent volume of normal saline administered intravenously 3 h after the initial dose.

The dosing regimen of 10 mg Dexa administered twice intravenously was selected based on previous randomized trials in joint arthroplasty, which demonstrated that split-dose regimens provide superior anti-inflammatory and analgesic effects compared with a single higher dose [14]. Given concerns about glycemic control in diabetic patients, we adopted two moderate doses rather than a single larger dose, balancing efficacy with safety [15, 16].

Perioperative management

In this study, all surgical procedures were performed by senior joint surgeons within the same team, utilizing a standardized surgical approach. Each patient received a diabetes-specific diet and nutritional education from a certified nutritionist. Subcutaneous injections of insulin aspart were administered using an insulin pen before each meal, while long-acting insulin injections were administered subcutaneously before bedtime to maintain glycemic control. The therapeutic dosage of insulin was dynamically adjusted based on the patient’s blood glucose levels. Both groups adhered to the principles of ERAS for perioperative management. This included measures such as prevention of surgical site infection, intraoperative temperature management, postoperative analgesia, prevention of PONV, and prophylaxis against deep vein thrombosis (DVT).

Preoperative management

All enrolled patients received standardized perioperative management. Preemptive analgesia was administered with oral etoricoxib 200 mg (100 mg tablets, Jiangsu Hengrui Pharmaceuticals) prior to surgery. Capillary blood glucose levels were monitored before and after each meal and at bedtime. To maintain perioperative glycemic control, insulin aspart (300 units/pen, Novo Nordisk) was administered via subcutaneous injection before each meal, and insulin degludec (300 units/pen, Novo Nordisk) was administered at bedtime. Insulin dosages were dynamically adjusted according to blood glucose levels, with the target range set at 6.7 ~ 10.0 mmol/L. All patients received individualized dietary counseling by nutritionists, who developed personalized diabetic diets based on metabolic status and glycemic profiles. Comorbid conditions were managed under specialist guidance to ensure perioperative safety. All patients received standardized preoperative education following institutional ERAS protocols, including instruction on postoperative functional exercises (e.g., ankle pump, quadriceps strengthening), nutritional counseling (diabetic diet, protein supplementation), and perioperative precautions.

Intraoperative management

All procedures were performed under neuraxial or general anesthesia determined by the anesthesiologist based on patient characteristics and ASA classification. patients received intravenous tranexamic acid (15 mg/kg) and prophylactic antibiotics (cefuroxime 1.5 g). Intraoperative fluid administration was guided by estimated blood loss and hemodynamic status. Active warming measures (e.g., forced-air warming blanket, fluid warmers, ambient temperature maintained at approximately 24 °C) were applied to maintain core temperature ≥ 36 °C, which was monitored continuously via axillary temperature. A urinary catheter was inserted after anesthesia and removed 1 ~ 2 days postoperatively upon recovery of bladder function. All surgeries were performed by senior surgeons using a standardized anterolateral approach with cementless prosthesis implantation. Wound closure was performed in layers over a drain.

Postoperative management

1. Postoperative pain management

After returning to the ward, patients received local ice pack application at the surgical site for approximately 12 h to reduce swelling and pain. Pain intensity was assessed using the Visual Analogue Scale (VAS, 0 to 10). On the day of surgery and postoperative day 1, patients were administered intravenous parecoxib sodium 40 mg (40 mg per vial, Emeishan Tonghui Pharmaceutical) diluted in 10 mL of 0.9% sodium chloride solution every 12 h. From postoperative day 2, patients received oral etoricoxib 200 mg every 12 h. For VAS scores of 4 ~ 6, oral hydrocodone-acetaminophen 10 mg (5 mg per tablet, SpecGx LLC, USA) was administered every 8 h. For VAS scores above 6, intramuscular tramadol hydrochloride 100 mg (100 mg per vial, Grante Pharmaceuticals, Germany) was given.

• 2.Management of postoperative nausea and vomiting

The severity of nausea was assessed using a Visual Analogue Scale (VAS, 0 ~ 10), with 0 indicating no nausea and 10 indicating the most severe nausea; higher scores corresponded to greater intensity. For VAS scores exceeding 4, intramuscular metoclopramide hydrochloride 10 mg (10 mg per vial, Shanghai Hefeng Pharmaceutical) was administered as the first-line antiemetic. If nausea persisted after 30 min, intravenous ondansetron hydrochloride 5 mg (5 mg per vial, Hangzhou Minsheng Pharmaceutical) was given as a rescue antiemetic.

• 3.Prophylactic anticoagulation

Patients received subcutaneous injection of nadroparin calcium 4,100 IU (4,100 IU per vial, Zhaoke Pharmaceutical) 6 h postoperatively, repeated every 24 h until discharge. After discharge, patients were instructed to take oral rivaroxaban 10 mg (Jiangsu Zhongbang Pharmaceutical) once daily until postoperative day 35.

• 4.Prophylactic antibiotic therapy

For patients without signs of postoperative infection, prophylactic antibiotics were administered within 24 h after surgery. Specifically, 1.5 g of cefuroxime sodium (0.75 g per vial, Zhejiang Huidisen) diluted in 100 mL of 0.9% sodium chloride solution was given intravenously twice daily to prevent infection.

• 5.Postoperative rehabilitation

Surgical drains were removed when output was < 50 mL within 24 ~ 48 h postoperatively. Following drain removal, patients initiated early mobilization with a walker and received additional rehabilitation exercises under the guidance of a physical therapist,

• 6.Postoperative diet and glycemic management

Postoperative nutritional management included a personalized diabetic diet designed by a nutritionist. For patients with hypoalbuminemia (serum albumin < 30 g/L), oral protein supplements were initiated, with intravenous human albumin administered if levels remained below the threshold. Glycemic control followed the same protocol as described in the preoperative Sect.  (Preoperative management).

Discharge criteria

The primary discharge criteria were as follows: (1) Normal body temperature. (2) Well-healed surgical incision with no signs of infection. (3) VAS pain score of less than 6 points, both at rest and during activity. (4) Ability to walk more than 50 m with the assistance of a walker. (5) Adequate control of comorbid conditions.

Observe and record indicators

To minimize potential bias in data collection, we used standardized case report forms (CRFs), and all investigators underwent uniform training before study initiation. Data entry was performed independently by two researchers with cross-validation to ensure accuracy. The following parameters were prospectively collected: (1) preoperative WBC, CRP, and HbA1c levels; (2) postoperative WBC and CRP values at 24 h, 48 h, and 72 h; (3) perioperative blood glucose levels (from 1 day before surgery to 3 days after surgery); (4) VAS pain scores at rest and during hip flexion at 45°from preoperative day to postoperative day 3; (5) postoperative VAS nausea scores, number of nausea episodes, and incidence of PONV within 3 days after surgery; (6) cumulative doses of analgesics or antiemetics used for pain or PONV control; (7) length of postoperative hospital stay; (8) postoperative complications, such as surgical site complications, gastrointestinal bleeding, deep vein thrombosis, or urinary tract infection; (9) readmission within 90 days after surgery. (10) surgical duration; (11) perioperative estimated blood loss (PEBL); (12) preoperative and postoperative hemoglobin levels; (13) preoperative and postoperative serum creatinine levels.

Sample size calculation

The sample size was calculated a priori based on the primary outcome of postoperative pain during walking on postoperative day 1 (VAS score), as this is a standard patient-centered endpoint in ERAS protocols [17]. We anticipated a mean reduction of 1.35 points in the Dexa group compared to the control group. Based on preliminary data, the standard deviation in the control group was estimated to be 1.51 points. A two-sided significance level (α) of 0.05 and a statistical power (1-β) of 90% were set, with a 1:1 allocation ratio between groups. The sample size per group was calculated using the formula N=(Zα + Zβ)² × 2σ²/δ², where Zα = 1.96 (for α = 0.05, two-sided), Zβ = 1.28 (for β = 0.10, power = 90%), σ = 1.51, and δ = 1.35. The calculation yielded approximately 26 patients per group. To account for a potential dropout rate of 15%, we increased the sample size to 30 patients per group, resulting in a total of 60 patients. Therefore, 30 patients in each group were required for this trial.

Statistical analysis

This was a single-blind trial in which patients were blinded to group allocation. Data collectors and statisticians were also blinded to treatment assignment to minimize assessment and analysis bias. Statistical analysis was performed using SPSS 27.0 software. Initially, the normality of the measurement data was assessed. Data conforming to a normal distribution were expressed as mean ± standard deviation( ± s)and analyzed using the independent samples t-test. For data that did not conform to a normal distribution, the non-parametric Mann-Whitney U test was applied, and results were expressed as median (interquartile range) [M (P25, P75)]. Categorical data were analyzed using the Pearson chi-square test or Fisher’s exact test, as appropriate. A p-value of < 0.05 was considered statistically significant.

Results

General data analysis results of two groups of patients

After screening according to the study protocol, a total of 65 patients met the inclusion criteria. Of these, 5 patients were excluded based on the exclusion criteria, resulting in 60 patients being enrolled in the study. The enrolled subjects were randomly allocated into the Dexa group (n = 30) and the control group (n = 30). As detailed therein, all 30 participants randomly assigned to the Dexa group and all 30 assigned to the control group received the intended intervention and were analyzed for the primary outcome. There were no losses to follow-up. No significant differences were observed between the two groups in terms of age, sex, body mass index (BMI), primary diagnosis, anesthesia method, ASA physical status score, preoperative WBC, preoperative CRP levels, blood glucose levels, hemoglobin A1c (HbA1c), preoperative resting VAS pain score, or preoperative activity VAS pain score (Table 1). Moreover, key perioperative and surgical parameters, including operative duration, estimated blood loss, postoperative hemoglobin levels, and postoperative creatinine concentrations, were similar between the groups (all P > 0.05), indicating the homogeneity of the cohorts in terms of procedural stress and baseline physiological conditions.(Supplement table).

Table 1.

Analysis of baseline characteristics of the two groups [M(P25,P75)]/N(%)

		Dexa group	Control group	t/z/χ² value	P Value
Sex	Male	16(53.3%)	15(50.0%)	0.067	0.769
	Female	14(46.7%)	15(50.0%)
Age(year)		65.5(60.8,72.0)	60.33(55.0,67.5)	− 1.895	0.067
Height(cm)		162.5(155.8,168.0)	161.0(155.8,168.0)	− 0.104	0.917
Weigh(Kg)		60.0(54.5,70.0)	62.0(52.8,66.0)	− 0.222	0.824
BMI(Kg/m2)		23.4(21.6,27.1)	22.3(21.0,27.0)	− 0.710	0.478
Main diagnosis				2.471	0.295
	ONFH	10(33.3%)	15(50.0%)
	OA	19(63.3%)	15(50.0%)
	DDH	1(3.3%)	0(0.0%)
Anesthesia				0.373	0.542
	intravertebral anesthesia	24(80.0%)	22(73.3%)
	general anesthesia	6(20.0%)	8(26.7%)
ASA Classification				1.926	0.165
	I	0(0.0%)	0(0.0%)
	II	7(23.3%)	12(40.0%)
	III	23(76.7%)	18(60.0%)
	IV	0(0.0%)	0(0.0%)
Preoperative white blood cell count(109/L)		7.52 ± 1.82	7.88 ± 1.93	− 0.742	0.461
Preoperative C-reactive protein(mg/L)		7.15 (5.00,17.10)	10.95 (5.00,19.73)	− 0.514	0.607
Preoperative blood glucose(mmol/L)		7.80(6.40,9.30)	7.45(6.18,9.00)	− 1.059	0.290
Preoperative HbA1c		6.65(6.25,8.23)	6.65(5.80,7.65)	33.58	0.387
Preoperative Resting VAS pain score		4.00(3.75,6.00)	4.00(4.00,5.00)	− 0.070	0.945
Preoperative activity VAS pain score		6.00(5.00,7.00)	7.00(6.00,7.00)	− 1.709	0.087

BMI, body mass index; ASA, American society of anesthesiologists; ONFH, osteonecrosis of the femoral head; OA, osteoarthritis; DDH, developmental dysplasia of the hip; WBC, white blood cell count; CRP, C-reactive protein; HbA1c, hemoglobin A1c; VAS, visual analogue scale

Analysis of postoperative white blood cell count

On postoperative day 1, the mean WBC count in peripheral blood was (11.56 ± 2.43) × 10⁹/L in the Dexa group and (10.81 ± 3.33) × 10⁹/L in the control group, with no significant difference between the two groups (P = 0.326). On postoperative day 2, the mean WBC count was (9.20 ± 1.28) × 10⁹/L in the Dexa group and (10.56 ± 2.34) × 10⁹/L in the control group, indicating a significantly higher WBC count in the control group compared to the Dexa group (P = 0.007). By postoperative day 3, the mean WBC count was (8.02 ± 1.34) × 109/L in the Dexa group and (9.22 ± 1.49) × 10⁹/L in the control group, with the control group again showing a significantly higher WBC count than the Dexa group (P = 0.002).Compared to preoperative levels, the postoperative peripheral blood WBC counts in both groups increased, peaking on the first postoperative day, and then demonstrated a declining trend from day 1 to day 3 after surgery (Fig. 2).

Fig. 2.

Comparison of postoperative white blood cell count between the two groups (*: P = 0.326, **: P = 0.007, ***: P = 0.002)

Analysis of C-reactive protein level after operation

On postoperative days 1~3, the median peripheral blood CRP levels in the Dexa group were 38.20 (25.38,54.00) mg/L, 86.00 (69.00,110.00) mg/L, and 78.00 (60.00,97.00) mg/L, respectively, while those in the control group were 63.50 (44.25,95.50) mg/L, 101.50 (88.25,120.00) mg/L, and 95.20 (70.00,107.50) mg/L. CRP levels in the Dexa group were significantly lower than those in the control group (P = 0.040, P = 0.010, and P = 0.044, respectively). Notably, CRP levels peaked on postoperative day 2 and began to decline by day 3 (Fig. 3).

Fig. 3.

Comparison of postoperative C-reactive protein levels between the two groups (*: P = 0.040, **: P = 0.010, ***: P = 0.044; POD1, Postoperative day 1; POD2, Postoperative day 2; POD3, Postoperative day 3)

Postoperative blood glucose and maximum blood glucose levels

The median postoperative blood glucose level on day 1 was significantly higher in the Dexa group compared with the control group (P  < 0.01). On the day of surgery, as well as on postoperative days 2 and 3, no significant differences were observed between the two groups (P  = 0.877, P = 0.474, and P  = 0.069, respectively; Table 2).

Table 2.

Comparison of postoperative blood glucose and maximum glucose levels between the two groups [M(P₂₅, P₇₅)] mmol/L

	Dexa group	control group	Z	P
Postoperative blood glucose
POD0	8.30(7.30,9.80)	8.40(7.08,10.15)	− 0.155	0.877
POD1	8.90(7.90,10.43)	8.35(7.10,10.10)	− 3.317	< 0.01*
POD2	8.30(7.08,9.83)	7.90(6.70,9.30)	− 0.716	0.474
POD3	7.95(6.50,9.13)	8.05(6.78,9.73)	− 1.819	0.069
Maximum blood glucose level
POD0	10.40(8.93,12.35)	9.70(8.875,11.57)	− 0.155	0.877
POD1	11.80(10.65,13.37)	10.35(9.18,12.7)	− 2.160	0.031*
POD2	10.35(9.35,12.57)	10.30(8.88,12.80)	− 0.444	0.657
POD3	11.10(9.70,12.85)	10.50(8.90,13.98)	− 0.303	0.167

*P < 0.05, POD0, Postoperative day 0; POD1, Postoperative day 1; POD2, Postoperative day 2; POD3, Postoperative day 3

Regarding the highest daily blood glucose levels within the first three postoperative days, patients in the Dexa group exhibited significantly higher peak glucose levels on postoperative day 1 compared with the control group (P  = 0.031). However, on the day of surgery and on postoperative days 2 and 3, the differences between the two groups were not statistically significant (P  = 0.877, P  = 0.657, and P  = 0.167, respectively; Table 2). Transient hyperglycemia observed on postoperative day 1 was managed with short-acting insulin titration according to the predefined protocol. Blood glucose levels subsequently returned to the target range, and no episodes of severe hypoglycemia or ketoacidosis occurred.

Analysis of postoperative resting VAS score

On postoperative days 1 and 2, the median VAS pain scores in the Dexa group were 5.00 (4.00, 6.00) and 3.00 (3.00, 4.00), respectively, which were significantly lower than those in the control group [6.00 (6.00, 7.00) and 4.00 (3.00, 5.00); P < 0.01]. On postoperative day 3, no significant difference was observed in VAS scores between the Dexa and control groups (P  =  0.159; Fig. 4).

Fig. 4.

Comparison of postoperative resting VAS scores between the two groups (*: P  < 0.01,**: P  = 0.014, ***: P  = 0.159; POD1,Postoperative day 1;POD2, Postoperative day 2; POD3, Postoperative day 3)

VAS score analysis of postoperative activity status

On postoperative day 1 and day 2, the median VAS pain scores during activity in the Dexa group were 6.00 (6.00,7.00) and 5.00 (3.75,5.00), respectively, which were significantly lower than those in the control group [7.00 (6.75,8.00) and 5.00 (4.00,6.00); P  = 0.002 and P  < 0.001, respectively]. On postoperative day 3, no significant difference was observed between the Dexa and control groups in activity-related VAS pain scores (P  = 0.443) (Fig. 5).

Fig. 5.

Comparison of postoperative activity VAS scores between the two groups (*: P  = 0.02, **: P  = 0.006, ***: P  = 0.443, Postoperative day 1; POD2, Postoperative day 2; POD3, Postoperative day 3)

Analysis of postoperative analgesic and antiemetic drug use in two groups

The number of patients requiring tramadol hydrochloride injection and metoclopramide hydrochloride injection, as well as the total dosage of these medications used within the first 3 postoperative days, were significantly lower in the Dexa group compared to the control group (P  < 0.05). However, there were no significant differences between the two groups in the number of patients requiring oxycodone-acetaminophen tablets or tropisetron hydrochloride injection, nor in the total dosage of these medications used (P  > 0.05) (Table 3).

Table 3.

Comparison of postoperative analgesic and antiemetic requirements between the two groups

	Dexa group	Control group	Z/χ2	P
Oxycodone & acetaminophen tablet(mg)
Number of users	17/30	19/30	0.278	0.792
Total drug dose(mg)	310	340	− 1.372	0.170
Tramadol Hydrochloride injection
Number of users	4/30	12/30	5.455	0.020*
Total drug dose(mg)	600	1600	− 2.142	0.032*
Metoclopramide hydrochloride injection
Number of users	1/30	8/30	6.405	0.026*
Total drug dose(mg)	10	80	− 2.260	0.024*
Tropisetron hydrochloride injection
Number of users	0	1	1.017	0.500
Total drug dose(mg)	0	5	− 1.000	0.317

*P < 0.05

Clinical efficacy and complications

In this study, no allergic reactions occurred in the perioperative patients. the incidence of nausea and PONV in the Dexa group was significantly lower than that in the control group, with statistical significance (P < 0.05) (Table 4).

Table 4.

Clinical efficacy and complications N(%)

	Dexa group	Control group	χ 2	P
PONV	1(3.33%)	8(23.30%)	6.405	0.026*
Nausea	1(3.33%)	9(30.00%)	7.680	0.006*
UTI	2(6.67%)	0(0.00%)	2.069	0.492
DVT	3(10.00%)	2(6.70%)	0.218	1.000
PJI	0(0.00%)	0(0.00%)	–	–
SSI	1(3.33%)	0(0.00%)	1.017	1.000
WE	2(6.67%)	3(10.00%)	0.218	1.000
GB	0(0.00%)	0(0.00%)	–	–
Postoperative hospital stay	5.67 ± 1.13	6.70 ± 1.29	− 3.307	0.002*
Admission within 90 days	1(3.33%)	0(0.00%)	1.017	1.000

*P < 0.05

Regarding postoperative complications, no cases of prosthetic joint infection(PJI) or gastrointestinal bleeding (GB) were observed in either group. Additionally, there were no significant differences in the incidence of other postoperative complications, such as urinary tract infections(UTI), DVT, surgical site infection(SSI), or wound exudate(WE), between the two groups. The postoperative hospital stay in the Dexa group was significantly shorter than that in the control group, while no significant difference was observed in the 90-day readmission rate between the two groups (Table 4).

Discussion

Patients undergoing THA may experience postoperative pain, nausea, vomiting, and other physiological discomforts, which can significantly hinder rapid recovery, impair the hospitalization experience, and increase both psychological and economic burdens. To address these issues, numerous studies have explored the perioperative use of dexamethasone in THA patients. However, due to its potential to elevate blood glucose levels, Dexa is rarely used in diabetic patients. Currently, there is limited research on the perioperative application of Dexa in THA patients with T2DM, and the effects of short-term Dexa use on perioperative blood glucose levels and postoperative complications in these patients remain unclear. This study demonstrated that perioperative intravenous administration of dexamethasone in patients with T2DM undergoing THA effectively attenuates systemic inflammatory responses, reduces pain scores and the incidence of postoperative nausea and vomiting, decreases the need for antiemetic and analgesic medications, and shortens postoperative hospital stay. Importantly, these benefits were achieved without increasing the risk of postoperative complications. These findings provide clinically meaningful guidance for enhanced recovery in this special population of patients with T2DM undergoing THA.

Dexa inhibits inflammatory response

Surgical trauma can induce edema at the surgical site and trigger the release of numerous inflammatory mediators, lowering the pain receptor threshold and increasing pain sensitivity [18]. Thus, reducing the inflammatory response at the surgical site in THA patients can indirectly alleviate postoperative pain and is a critical measure for promoting rapid recovery. As a long-acting glucocorticoid, Dexa exerts potent anti-inflammatory effects by inhibiting inflammatory signaling pathways and the expression of E-selectin, chemokines, and integrins, thereby reducing leukocyte recruitment [19]. Lei et al. [14] conducted a randomized controlled trial involving 165 THA patients and demonstrated that CRP and IL-6 levels in the perioperative Dexa group were significantly lower than those in the placebo group within the first 3 postoperative days. Additionally, the study concluded that multiple small-dose intravenous injections of Dexa were more effective than a single higher-dose injection. In the present study, CRP levels in THA patients treated with Dexa were significantly lower than those in the control group within 3 days postoperatively (P < 0.05), consistent with the findings of Lei et al.

A notable difference in our study is the inclusion of WBC count as an inflammatory marker. The results showed that WBC counts in the Dexa group were significantly lower than those in the control group on postoperative days 2 and 3 (P = 0.007 and P = 0.002, respectively). This aligns with the results of a randomized, double-blind study by Gądek et al. [20], which investigated the effects of perioperative glucocorticoid use on WBC counts (P < 0.05). Since WBCs spend most of their lifespan in storage and have a circulating lifespan of approximately 2 to 16 days after release into peripheral tissues, this explains the rapid increase in WBC counts due to postoperative stress in THA patients and their subsequent decline after 2 days.

Although the absolute differences in WBC and CRP levels between groups were modest, these changes were statistically significant and consistent across multiple postoperative time points. Importantly, they coincided with clinically meaningful improvements in pain scores, PONV incidence, and length of hospital stay. Therefore, the observed reductions in inflammatory markers should be interpreted as indicators of systemic inflammatory modulation rather than isolated laboratory changes. Collectively, these studies and theoretical evidence strongly support the efficacy of Dexa in reducing the inflammatory response following THA in diabetic patients.

Analgesic effect of Dexa

It is reported that 30% to 77% of patients experience moderate to severe pain after surgery [21], Postoperative pain is a common cause of prolonged hospital stays in THA patients. It not only diminishes patient satisfaction but also extends hospitalization duration and increases both financial and physiological burdens. Most perioperative pain in THA patients is inflammatory in origin, making the inhibition of the inflammatory response a critical measure for pain relief.

In the perioperative analgesic management of THA patients, opioids are highly effective. While they provide significant pain relief and benefits, they also carry risks such as gastrointestinal reactions, psychiatric complications, readmissions, and the need for postoperative revisions [22, 23].

Steroid receptors are present in both the central and peripheral nervous systems. Free steroids can cross the blood-brain barrier and act on various tissues, playing a key regulatory role in inflammatory and neuropathic pain. In recent years, the perioperative use of steroids in THA patients has demonstrated superior analgesic effects, reducing the need for additional analgesic medications. Some studies suggest that the analgesic effect of Dexa may be linked to its ability to alleviate local inflammation. Dexa exerts its analgesic effects by inhibiting prostaglandin synthesis and reducing vascular permeability, thereby mitigating local tissue edema [24]. Kelly et al. [25] conducted a retrospective analysis of 376 THA patients and found that those receiving Dexa had significantly lower pain scores and morphine requirements compared to untreated patients. Additionally, Dexa-treated patients had significantly shorter postoperative hospital stays. Arraut et al. [26] performed a retrospective study on 2,256 patients undergoing primary elective THA and found that patients receiving two doses of Dexa required significantly fewer opioids within 72 h postoperatively than those receiving a single dose. This suggests that, within a safe range, multiple small-dose intravenous injections of Dexa provide better analgesic effects than a single dose.

In this study, the VAS pain scores and rescue medication requirements in the Dexa group were significantly lower than those in the control group on the first and second postoperative days (P < 0.05), consistent with the findings of the aforementioned studies. These results indicate that Dexa can effectively alleviate postoperative pain in diabetic THA patients and reduce opioid use. However, the optimal timing, dosage, and administration regimen of Dexa for perioperative THA patients remain unclear, necessitating further clinical studies to provide additional evidence.

The role of Dexa in preventing PONV

PONV is a common adverse reaction among surgical patients. The incidence of PONV is reported to range from 25% to 30% in the general postoperative population, with the rate increasing to as high as 80% in high-risk groups [27]. Specifically, patients undergoing total THA or total knee arthroplasty (TKA) have been found to experience PONV at a frequency of 20–83% [28]. Persistent PONV significantly impairs patients’ dietary intake and comfort, prolongs hospital stays, increases healthcare costs, and causes considerable distress [29]. The physiological and pathological mechanisms of PONV are complex and multifactorial, involving intricate neuroanatomical pathways. The chemoreceptor trigger zone (CTZ) and the nucleus tractus solitarius (NTS) contain a high density of emetic receptors. When the body is exposed to emetic stimuli or medications with vomiting side effects, changes in the activity of these receptors send signals to the vomiting center, triggering a vomiting response [30]. Recent studies have identified multiple perioperative factors influencing the occurrence of PONV [31, 32]. By comprehensively understanding these factors, clinicians can stratify patients based on their individual risk profiles and implement targeted preventive measures to reduce PONV incidence. The perioperative use of Dexa plays a significant role in PONV prevention.Bustos et al. [33] conducted a retrospective study involving over 800 joint replacement patients, comparing a Dexa group with a control group. They found that the Dexa group required significantly fewer antiemetic medications (e.g.,ondansetron) than the control group. Similarly, Jeffrey et al. [34] demonstrated that the combination of ondansetron and Dexa was more effective in preventing PONV than ondansetron alone, and that multiple doses of Dexa were more effective than a single dose.

In this study, the incidence of PONV and nausea within the first 3 postoperative days was significantly higher in the control group than in the Dexa group (P < 0.05). Additionally, the total dose of metoclopramide hydrochloride required in the control group was significantly higher than that in the Dexa group (P < 0.05). These findings indicate that Dexa effectively reduces the incidence of PONV and nausea in THA patients, further underscoring its critical role in perioperative PONV prevention for diabetic patients undergoing THA.

The effect of Dexa on blood glucose and its safety

As a glucocorticoid, Dexa promotes glucose production in hepatocytes by antagonizing insulin response, reduces glucose uptake in skeletal muscle and white adipose tissue, and can lead to transient elevations in blood glucose levels and insulin resistance [35]. Additionally, Dexa has immunosuppressive effects, which may theoretically increase the risk of PJI. Mou et al. [36] conducted a study involving 1,216 diabetic patients undergoing joint replacement and found that preoperative Dexa administration resulted in a transient increase in immediate postoperative blood glucose levels upon returning to the ward and in fasting blood glucose levels on the first postoperative morning. However, Dexa had no significant effect on blood glucose levels on the second and third postoperative days. Furthermore, while preoperative Dexa led to higher mean and maximum postoperative blood glucose levels, it did not significantly impact wound complications or the incidence of PJI. Allen et al. [15] observed that preoperative intravenous Dexa in diabetic THA patients was associated with an initial increase in blood glucose and higher insulin demand on postoperative day 0. However, no significant effects on blood glucose levels or average blood glucose were observed 24 h after surgery. These studies collectively indicate that perioperative Dexa use can transiently elevate blood glucose levels in diabetic THA patients, with higher doses having a more pronounced effect. However, this effect is typically limited to the first 24 h postoperatively.

In this study, blood glucose levels in both groups of THA patients were higher on the first postoperative day compared to preoperative levels, likely due to the surgical stress response. Notably, the median blood glucose and maximum blood glucose levels in the Dexa group were significantly higher than those in the control group on the first postoperative day, suggesting a correlation between Dexa and transient blood glucose elevation. However, this effect was limited to the first postoperative day, as no significant differences in blood glucose levels were observed between the two groups on the second and third postoperative days (P = 0.474 and P = 0.069, respectively). These findings are consistent with the results of previous studies.

It is important to consider whether postoperative blood glucose fluctuations in THA patients increase the risk of PJI. Studies by Maradit et al. [37] and Stryker et al. [11] found that perioperative hyperglycemia in THA patients was associated with an increased incidence of PJI, raising concerns among orthopedic surgeons regarding the perioperative use of Dexa in THA. To further investigate the safety of Dexa in perioperative THA patients, Heckmann et al. [38] conducted a study involving approximately 470,000 THA patients. They found no significant differences in SSI or hematoma rates between Dexa and non-Dexa groups. However, the incidence of postoperative complications such as PJI, sepsis, pulmonary embolism, and lower extremity venous embolism was significantly lower in the Dexa group. Notably, the incidence of PJI in diabetic patients was also significantly lower in the Dexa group compared to the non-Dexa group. Jones et al. [39] performed a retrospective study on over 110,000 joint replacement patients, 31.0% of whom had diabetes. The study revealed that fasting blood glucose levels on the first postoperative morning were significantly higher in the Dexa group and positively correlated with Dexa use. However, patients receiving perioperative intravenous Dexa had a significantly lower risk of PJI, SSI, and other non-surgical site infections within 90 days postoperatively compared to the control group. Additionally, other studies have not found an increased risk of PJI associated with perioperative Dexa use [40, 41]. These studies collectively suggest that while intravenous Dexa may cause a transient increase in postoperative blood glucose levels in diabetic THA patients, it does not significantly elevate the risk of PJI.

In this study, the use of Dexa in diabetic THA patients did not increase the risk of PJI, consistent with the findings of previous studies. Additionally, There were no significant differences in the incidence of UTI, DVT, GB, or SSI between the two groups within 90 days postoperatively (P > 0.05), supporting the short-term safety of perioperative glucocorticoid use in this population. Importantly, the clinical benefits of dexamethasone observed in this study were confined to the early postoperative period. This finding should be interpreted within the context of ERAS principles, which prioritize early pain control, reduction of PONV, and accelerated mobilization to facilitate functional recovery and shorten hospital stay. In this setting, short-term improvements may translate into meaningful clinical and economic advantages, even in the absence of long-term differences in complication rates. Nevertheless, dexamethasone is known to have potential neuropsychiatric adverse effects, including sleep disturbance, mood changes, and delirium, particularly in elderly patients [42]. Although no such events were observed in our cohort, neurocognitive outcomes were not systematically assessed, and therefore subtle or transient mental health effects cannot be excluded. This should be taken into consideration when extrapolating our findings to older or more vulnerable populations.

Limitations

Several limitations of this study should be acknowledged. First, the sample size was relatively small, which may limit the statistical power to detect rare complications such as PJI and may also affect the accuracy of effect size estimates for secondary outcomes, including blood glucose. Second, this was a single-center study with a follow-up period of 90 days, therefore, potential long-term metabolic or functional effects of perioperative dexamethasone could not be evaluated. Third, although no neuropsychiatric adverse events were observed, standardized assessments for delirium or cognitive dysfunction were not performed, and thus subtle mental health effects, particularly in elderly patients, may have been underestimated. Fourth, this study included only insulin-dependent T2DM patients with relatively well-controlled diabetes, as evidenced by the basal-bolus insulin regimen required for perioperative glycemic control. While this homogeneous population strengthens the internal validity of our findings and demonstrates the safety of dexamethasone in this higher-risk subgroup, it also limits the generalizability of our results to non-insulin-dependent T2DM patients or those with poor glycemic control, who may have different β-cell function, baseline inflammatory status, and glycemic responses to glucocorticoid exposure; Finally, the dosing regimen used in this study represents only one of several possible approaches, and the optimal dose and timing of dexamethasone in diabetic patients undergoing THA remain to be determined.

Conclusion

In this prospective randomized trial involving patients with T2DM undergoing THA, perioperative intravenous dexamethasone was significantly associated with reduced early postoperative inflammation markers (WBC and CRP), lower pain scores during the first two postoperative days, and a significant reduction in the incidence of PONV. These benefits translated into a decreased need for rescue analgesics and antiemetics, as well as a shorter hospital stay. Importantly, the impact of dexamethasone on blood glucose was transient, primarily limited to the first postoperative day, and was effectively managed with a standardized insulin protocol. With our limited sample size and follow-up, we found no association between perioperative dexamethasone use and short-term complications.

However, these findings should be interpreted with consideration of the study’s limitations. The relatively small sample size limits definitive conclusions regarding secondary outcomes such as blood glucose variability and rare adverse events such as PJI. Additionally, the potential impact of dexamethasone on the psychological health of diabetic patients (e.g., delirium) remains unclear. The single-center design and relatively short follow-up period also limit the generalizability of the results and the ability to assess long-term metabolic or safety outcomes.

In conclusion, this study suggests that perioperative split-dose dexamethasone can significantly improve early recovery outcomes, including pain control, PONV, and hospital stay, in T2DM patients undergoing THA. The effect on blood glucose is transient and manageable. Therefore, dexamethasone holds potential as an effective perioperative management tool for T2DM patients, particularly within ERAS protocols. However, despite these promising short-term effects, the long-term impact of dexamethasone on the psychological health of elderly diabetic patients and other outcomes remains uncertain. Given the limitations of this study, its widespread use in high-risk clinical populations should be approached with caution. Further studies with larger sample sizes, multi-center designs, and extended follow-up periods are needed to confirm these benefits and assess long-term safety.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

THA

Total hip arthroplasty

ERAS

Enhanced recovery after surgery

PONV

Postoperative nausea and vomiting

Dexa

Dexamethasone

T2DM

Type 2 diabetes mellitus

SSI

Surgical site infection

PJI

Periprosthetic joint infection

ONFH

Osteonecrosis of the femoral head

OA

Osteoarthritis

DDH

Developmental dysplasia of the hip

CONSORT

Consolidated standards of reporting trials

SNOS

Sequentially numbered, opaque, sealed

DVT

Deep vein thrombosis

ASA

American society of anesthesiologists

VAS

Visual analogue scale

WBC

White blood cell count

CRP

C-reactive protein

HbA1c

Hemoglobin A1c

CRFs

Case report forms

BMI

Body mass index

POD

Postoperative day

TKA

Total knee arthroplasty

CTZ

Chemoreceptor trigger zone

NTS

Nucleus tractus solitarius

PEBL

Perioperative estimated blood loss

UTI

Urinary tract infection

GB

Gastrointestinal bleeding

Author contributions

Wen-hui Liu, Zheng-liang Li and Dong Yin established the study design; Wen-hui Liu and Zheng-liang Li wrote the draft of the manuscript; Fu-lin Li, Xiao Huang and Wen-wen Huang contribute to the protocol conception and to the acquisition, analysis, and interpretation of the data. All authors read and approved the final manuscript.

Funding

This work is supported by Guangxi Science and Technology Major Project (Grant Nos. AA23023004); Guangxi Health Commission Plan Project (Z-A20220109, Z20200911); Beijing Medical and Health Public Welfare Foundation Project (YWJKJJHKYJJ-B20128DS).

Data availability

The data are not available due to privacy or ethical reasons.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of the People's Hospital of Guangxi Zhuang Autonomous Region (Approval No.: KY-ZC-2022-109). Prior to enrollment, all participants provided written informed consent. The trial was registered with the National Health Information Security Platform and the Medical Research Registration and Filing Information System (Trial Registration No.: MR-45-23-047982).

Consent for publication

Written informed consent for publication of the clinical details was obtained from the patient.

Competing interests

The authors declare no competing interests.