A 20 mg dose of dexamethasone does not reduce the proportion of joint replacement patients needing rescue analgesia: a matched cohort study

Introduction

Optimizing pain management for patients after total joint replacement (TJR) surgery is an ongoing effort. Uncomfortable postoperative pain is detrimental to the patients recovery and may cause anxiety, sleep disturbance, delayed mobilisation, prolonged length of hospital stay and increased opioid use (1,2). Postoperative pain control following a TJR procedure has improved considerably with the introduction of multi-modal analgesic protocols (3). However, a predictable and consistent amount of pain after TJR has not yet been fully achieved.

Corticosteroids (dexamethasone, methylprednisolone) play an important role within the multi-modal analgesic approach (4). Systematic reviews on this topic show positive effects on length of hospital stay, on postoperative pain, on opioid consumption and on postoperative nausea and vomiting but also that the quality of evidence is moderate to low (5-7). Various placebo controlled randomized trials have demonstrated the efficacy of corticosteroids in controlling postoperative pain, with significantly less pain during the early post-operative phase after TJR if dexamethasone is used (7). However, timing of administration of these corticosteroid varies widely, ranging from a single dose given one week before TJR surgery, a single intravenous (IV) injection immediately before surgery to two doses (one immediately before surgery and one 24 hours later) (8-10). Besides timing, the optimal dose of corticosteroids for postoperative pain control is still unknown, with dexamethasone dosing varying from 8 mg up to 40 mg preoperative (5,11). A meta-analysis by Hannon et al. showed strong evidence for intravenous dexamethasone but insufficient evidence on optimal dose or number of doses (12). Of their 16 included studies using dexamethasone the low dose was 0.1 and 0.2 mg/kg for high dose, ranging in clinical practice from 6–10 mg (low dose) to 12–20 mg/kg (high dose). Only two included studies compared the effects of different doses of dexamethasone, limiting their ability to draw any conclusions regarding the optimal dose, urging them to call for further research on the safest and most efficacious dose and number of doses.

Therefore the primary aim of this study was to determine if a higher (20 mg compared to 8 mg), single preoperative dose of dexamethasone results in a reduced need for rescue analgesics during the first 24 hours after joint replacement surgery. For the reporting of this study, we adhered to the STROBE reporting checklist (available at https://aoj.amegroups.com/article/view/10.21037/aoj-22-34/rc) (13).

Methods

Study design

We conducted a matched cohort study. The Regional Medical Ethical Review Board (Medisch Ethische Commissie Máxima Medisch Centrum) approved the study (No. N20.119) and individual consent for this retrospective analysis was waived. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). All consecutive patients without diabetes, planned for an elective TJR procedure between June 2019 and March 2020 and who were managed by the anaesthesiologist involved in this study (KV) were given a 20 mg dose [high dose group (HDG)]. This dose was administered intravenously just prior to incision. After the HDG group was completed, each HDG patient was matched with a patient who received a standard 8 mg dose [standard dose group (SDG)] in the same hospital. SDG patients were operated between December 2015 and March 2020. Patients and observers were not blinded for the administered dose of dexamethasone. For matching, the following items were used: type of arthroplasty [primary total hip arthroplasty (THA) or total knee arthroplasty (TKA)], gender, age (±10 years), type of anaesthesia (general or spinal) and level of pre-operative pain during activity (±1 point on pain Numeric Rating Scale). Patients with opioid use before surgery were excluded. Besides the difference in dexamethasone dose, all patients were managed with our standard perioperative multimodal analgesia protocol for joint replacement surgery: paracetamol (1,000 mg, 4 times per day for 7 days, followed by 1,000 mg 3 times per day as needed, for another 7 days), celebrex (200 mg 2 times per day for 7 days, followed by 200 mg 2 times per day as needed, for another 7 days), oxycontin (5 or 10 mg 2 times per day for 3 days) and oxynorm (5 mg as needed 4 times per day for 4 days). Additionally, pantoprazole (40 mg once per day for 14 days) and movicolon (once per day for 4 days) are given. Local Infiltration Analgesia [LIA, 150 mL ropivacaine 0.2% with epinephrine (10 mg mL)] was perioperative administered in case of total knee replacement but not with total hip replacement. No adductor canal or femoral nerve blocks were used. We included patients who had either general or spinal anaesthesia during TJR surgery.

Per protocol, the aim is to postoperatively control the NRS pain to <4. If patients experience uncomfortable pain with a NRS score >3 after surgery, opioids are given if the Ramsay sedation score is <4, breathing frequency is >10/minute and the systolic blood pressure is >100 mmHg (14). Pain is reassessed after 60 minutes. In case the NRS score is still ≥4 and there are no side effects, a second 5 mg dose of oxynorm can be given with a maximum of 10 mg within 6 hours. Patients were not informed about this postoperative pain protocol but daily three rounds of scoring pain levels is standard care on our orthopedic ward. Of course, patient who experienced high pain levels between pain scoring rounds were able to contact a nurse for further pain management.

For all patients the following data was collected: (I) involved joint and type of anaesthesia (general or spinal); (II) use of rescue analgesics (number and total dosage) during hospitalization; (III) Numeric Rating Scale (NRS) scores for knee or hip pain, routinely collected three times per day (8 am, 3 pm and 10 pm) during hospital admission; (IV) all complications and readmissions within 90 days. Primary outcome of the study was the proportion of patients who needed oxynorm after TJR during their stay at the nursing ward. Secondary outcomes were rescue analgesia on the post-anesthesia care unit (general anesthesia patients only), length of stay (LOS, measured from time admitted in hospital to discharge time) and complications (number and severity).

Statistical analysis

For sample size calculation we used an online tool (powerandsamplesize.com) comparing two proportions (two independent samples, two sided equality). The study was powered to detect a reduction of 25% (from 80% to 55%) in the proportion of patients needing rescue analgesics after the arthroplasty procedure (β=0.8, α=0.05). This resulted in 52 patients per group.

Descriptive statistics were used to present patient demographics and surgery details. Data was checked for distribution and outcomes with normally distributed data were tested with a 2-sided Student t-test, non-parametric data with a Mann-Whitney U test Binominal outcomes were tested with the Chi-Square test. All analysis was performed using SPSS (IBM SPSS statistics version 25) with P<0.05 considered statistically significant.

Results

A total of 59 patients who received a single preoperative dose of 20 mg dexamethasone (HDG, n=59) were matched to 59 patients who received a standard dose of 8 mg dexamethasone (SDG, n=59) (Table 1). On the nursing ward 54 patients (91.5%) from the HDG needed oxynorm versus 58 (98.3%) in the SDG (Chi square test: P=0.09, odds ratio 0.19 with 95% confidence interval: 0.21–1.65). HDG patients received a median of 5 mg [interquartile range (IQR): 0] oxynorm, SDG patients received a median of 5 mg (IQR: 0) oxynorm (P=0.70). See Table 2 and Table 3 for all outcomes.

Discussion

We found that on the nursing ward a high number of patients received rescue analgesics, both in the HDG and the SDG. This questions the efficacy of our multimodal analgesic protocol. Compared to the multimodal analgesic protocol presented in the study by Kardash et al., ours does without morphine which might explain the higher need for rescue analgesics (15). The multimodal analgesic protocol in the study by Lunn et al. combined gabapentin, acetaminophen and celecoxib with LIA (11). In the first postoperative 24 hours, their median cumulative use of rescue analgesics was 20 mg of oxycodone, quite a bit more than the median 5 mg oxycodone which our HDG patients received during their postoperative stay in hospital.

Key findings

This study investigated the effect of a high (20 mg) perioperative dose of dexamethasone versus a standard (8 mg) dose. There was no difference between the HDG and the SDG regarding the number of patients needing rescue analgesics. Also, given doses of rescue analgesics did not differ between both groups. There were no differences in any of the secondary outcomes. Our results do not demonstrate any beneficial effect of a higher (20 mg) dose of dexamethasone compared to a standard 8 mg dose.

Strengths and limitations

This study has several limitations. First of all it is a non-randomized design, possibly introducing bias. Moreover, the number of included patients is limited. However, the absolute differences between the groups were small, which makes a type 2 error due to limited number of patients less likely. Strong points are that we were able to include a group of patients matched on an extensive number of details and the observational character extends the clinical validity of our results.

Comparison with similar researches

Quite a number of systematic reviews elaborate on positive effects of dexamethasone with regards to pain, LOS and post operative nausea and vomiting (5,6,16,17). The included studies almost exclusively use a dose of 5 to 10 mg corticosteroids, comparable to our standard dose of 8 mg. Four studies used a higher dose. In a randomized controlled with 50 THA patients, Kardash et al. tested 40 mg dexamethasone against placebo and found a prolonged suppressive effect on the inflammatory response and a significant decrease of pain on mobilisation in the first 24 postoperative hours (15). Their reported mean NRS pain scores at rest during the first 24 hours for patients who received dexamethasone were comparable to the pain scores found in our study. Lunn et al. used methylprednisolone (equivalent to 25 mg dexamethasone) versus placebo (11). Their reported median pain scores on a NRS at rest with methylprednisolone ranged from 1.5 to 2 points during the first 24 hours, only slightly lower than the mean 2.2 (HDG) and 2.4 (SDG) found in our study. These differences are minimal and clinically not relevant. Nielsen et al. found improved analgesic and functional outcomes when using 1 mg·kg dexamethasone compared to 0.3 mg·kg a in a double blind randomized controlled trial (18). In contrast to our study, only high pain responders undergoing total knee replacement were included. Gasbjerg et al. found in a double blind randomized controlled trial reduced pain and morphine consumption 48 hours after total knee replacement with a second 24 mg dose of dexamethasone compared to placebo and to a single 24 mg dose (19).

Explanations of findings

Although intuitively a higher dose of analgesics implies increased postoperative pain reduction, the potential hazards of administering higher doses of corticosteroids should be taken into account. Corticosteroids have an immunosuppressive action, raising concern that postoperative wound infections are more likely with higher doses (20). In our study we did not observe postoperative wound infection in either group. Furthermore, corticosteroids can deregulate the glucose balance, with a measurable raise of postoperative blood glucose that is however without clinical significance in regard to postoperative complications (20). Since diabetes mellitus is a common co-morbidity of arthroplasty patients, this should be taken into consideration (21).

Implications and actions needed

Randomized controlled trials, preferably blinded, are needed to further investigate the effect of different dosages of glucocorticoids on postoperative pain in TJR.

Conclusions

In conclusion, we did not find better postoperative pain control in our patients who preoperatively received 20 mg dexamethasone compared to our arthroplasty patients who received 8 mg dexamethasone.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://aoj.amegroups.com/article/view/10.21037/aoj-22-34/rc

Data Sharing Statement: Available at https://aoj.amegroups.com/article/view/10.21037/aoj-22-34/dss

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoj.amegroups.com/article/view/10.21037/aoj-22-34/coif). WvdW reports support from Avania for attending and traveling to 2022 TOPRA meeting and is a board member of European Hip Society Scientific Committee and Commissie Wetenschap en Innovatie Nederlandse Orthopaedische Vereniging. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The Regional Medical Ethical Review Board (Medisch Ethische Commissie Máxima Medisch Centrum) approved the study (No. N20.119) and individual consent for this retrospective analysis was waived. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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