Predictors of subacute postoperative pain after total knee arthroplasty: A secondary analysis of two randomized trials.

BACKGROUND: Methods for identifying high-pain responders undergoing total knee arthroplasty remain important to improve individualized pain management. This study aimed at evaluating pre- and perioperative predictors of pain on Days 2-7 after total knee arthroplasty. METHODS: This is a secondary analysis of data from 227 patients participating in two randomized trials. Pain outcomes were mean pain during walking on Days 2-7 and on Days 2, 4 and 7. Multivariable linear and logistic regressions were carried out in two steps. First, only preoperative available variables including demographics, comorbidities, pain catastrophizing scale and preoperative pain were evaluated while controlling for trial intervention and recruitment site. In the second step, perioperative variables and pain during walking 24 h postoperatively were added. RESULTS: The model with only preoperative predictors for mean pain Days 2-7 showed preoperative pain (R-squared 0.097) as the only predictor. In the second model, adding postoperative available variables, only pain 24 h postoperatively (R-squared 0.248) was significant, with a significant main effect of recruitment site. Results for the separate day analysis similarly showed preoperative pain and pain during walking 24 h postoperatively as predictors. The overall best sensitivity (60%) and specificity (74%) for predicting a high-subacute postoperative pain response on Days 2-7 was with cut-off values of VAS 45.5 (out of 100) for pain during walking 24 h postoperatively. CONCLUSIONS: Postoperative pain during walking at 24 h is predictive of subacute postoperative pain on Days 2-7 after total knee arthroplasty, while preoperative pain was only a weak predictor. SIGNIFICANCE STATEMENT: This study investigated factors associated with pain after total knee arthroplasty beyond the immediate postoperative period. The analysis revealed significant associations between preoperative pain levels and, particularly, pain 24 h postoperatively, with subsequent subacute pain the following week. These findings can assist in identifying patients who would benefit from enhanced, individualized analgesic interventions to facilitate postoperative recovery.

High dose dexamethasone in high pain responders undergoing total hip arthroplasty: A randomized controlled trial.

BACKGROUND: Postoperative pain after total hip arthroplasty (THA) may delay postoperative mobilization and discharge. Postoperative pain has been shown to be higher in pain catastrophisers and patients receiving opioids. A single dose of glucocorticoid reduces pain after THA, and an increased dose of glucocorticoids has been found to be effective in patients at high risk of postoperative pain after total knee arthroplasty (TKA), however, the ideal dose in THA remains unknown. OBJECTIVE: To evaluate the effect of a high dose (1 mg kg -1 ) vs. intermediate dose (0.3 mg kg -1 ) of dexamethasone on pain after THA. DESIGN: A randomized double-blind controlled study. SETTING: A two-centre study including two large arthroplasty sites in Denmark was conducted from February 2019 to August 2020. PATIENTS: A total of 160 patients undergoing THA by neuraxial block with multimodal analgesia, having a Pain Catastrophising Scale score >20 and/or preoperative opioid use were included. INTERVENTION: Patients were randomly assigned to receive dexamethasone 1 mg kg -1 or 0.3 mg kg -1 before THA. MAIN OUTCOME MEASURES: Primary outcome was percentage of patients experiencing moderate to severe pain (visual analogue scale, VAS > 30 mm on a 0 to 100 mm scale) on ambulating 24 h after surgery. Secondary outcomes included cumulated pain scores, C-reactive protein (CRP), opioid use, postoperative recovery scores, length of stay, complications, and re-admission within 30 and 90 days. RESULTS: No difference was found in percentage of VAS >30 mm 24 h after surgery in the 5-m walk test (VAS > 30/VAS ≤ 30%); 33/42 (44%) vs. 32/43 (43%), relative risk = 1.04 (95% confidence interval 0.72-1.51; P  = 0.814) in 1 mg kg -1vs. 0.3 mg kg -1 respectively. No differences were found in CRP and opioid use between groups. Also, no intergroup differences were found in recovery scores, re-admissions, or complications. CONCLUSION: 1 mg kg -1vs. 0.3 mg kg -1 dexamethasone improved neither postoperative pain nor recovery in THA in a cohort of predicted high pain responders. TRIAL REGISTRATION: ClinicalTrials.gov ID-number NCT03763760 and EudraCT-number 2018-2636-25.

Repeat dose steroid in high pain responders after total knee arthroplasty: A study protocol.

Pain after total knee arthroplasty (TKA) is a well-known clinical problem potentially delaying ambulation and recovery. Perioperative glucocorticoids reduce pain and facilitate early recovery, but the optimal timing and dose are still unknown. High pain catastrophizers have an increased risk of poorly controlled postoperative pain, and moderate to severe pain at 24 h is associated with a risk of pain relapse at 48 h. To evaluate the effect of a repeat moderate dose of glucocorticoids after TKA in high pain catastrophizers presenting with moderate to severe pain 24 h postoperatively, having received preoperative high-dose glucocorticoids. High pain catastrophizers (Pain Catastrophizing Scale > 20) undergoing TKA are screened 24 h postoperatively and are included if they experience moderate to severe pain (VAS > 30) during a 5 m walk test. The included patients will receive either oral 24 mg dexamethasone (n = 55) or placebo (n = 55) on the evening of Day 1 (~30-37 h) after surgery. In addition, patients receive a standard multimodal analgesic regimen, including paracetamol, celecoxib, local infiltration analgesia, and preoperative dexamethasone (1 mg/kg). Patients will fill out a pain diary for 7 days after surgery. The primary outcome is moderate to severe pain (VAS > 30) during a 5 m walk test on the morning of Day 2 after surgery. The secondary outcomes include cumulated pain at rest and during ambulation, cumulated use of rescue analgesics, quality of sleep, lethargy, dizziness, nausea, satisfaction with the analgesic regimen, length of stay, morbidity, mortality, and reasons for readmissions. Follow-up is at 8 and 30 days. The data from this study will provide evidence for the effect of a repeated dose of dexamethasone as an analgesic adjuvant in patients undergoing TKA with a high risk of postoperative pain.

High-dose dexamethasone in low pain responders undergoing total knee arthroplasty: a randomised double-blind trial.

BACKGROUND: Postoperative pain after total knee arthroplasty (TKA) is a continuing problem despite optimised multimodal analgesia. Previous studies have shown preoperative glucocorticoids to reduce postoperative pain, but knowledge about specific doses and effects in specific patient groups is lacking. METHODS: A two-centre, double-blind, two-arm study comparing preoperative dexamethasone (1 mg kg-1vs 0.3 mg kg-1 i.v.) on postoperative pain in 160 planned TKA subjects with low preoperative pain catastrophising and no opioid use. Subjects received multimodal analgesia with paracetamol, cyclooxygenase-2 inhibitors, local anaesthetic infiltration analgesia, and rescue opioids. The primary outcome was percentage of subjects experiencing moderate to severe pain (visual analogue scale >30 mm) upon ambulation at 24 h. Secondary outcomes included pain scores, postoperative inflammation (C-reactive protein), opioid and antiemetics use, and 'Quality of Recovery-15' and 'Opioid-Related Symptom Distress Scale', length of stay, readmissions, and complications up to Day 90. RESULTS: A total of 157 subjects (80 vs 77) were included. No difference was found between groups in the incidence of subjects experiencing visual analogue scale >30 on ambulation 24 h after surgery (56% vs 53%, relative risk =1.07, confidence interval: 0.8-1.4, P=0.65). No differences in other pain outcomes or use of rescue opioids and antiemetics, in Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, length of stay, readmissions, or complications. C-reactive protein values were comparable at 24 h (13 [6-25] mg L-1vs 16 [9-38] mg L-1, P = 0.07), but lower at 48 h (26 [9-52] mg L-1vs 50 [30-72] mg L-1, P<0.01) in the high-dose group. CONCLUSION: Use of 1 mg kg-1vs 0.3 mg kg-1 i.v. dexamethasone in low pain responders after TKA did not improve early postoperative pain or other outcomes in contrast to benefits in a high pain responder population. CLINICAL TRIAL REGISTRATION: NCT03758170 (first registration 29-11-2018).

High-dose steroids in high pain responders undergoing total knee arthroplasty: a randomised double-blind trial.

BACKGROUND: Total knee arthroplasty (TKA) is associated with moderate-to-severe postoperative pain despite multimodal opioid-sparing analgesia. Pain catastrophising or preoperative opioid therapy is associated with increased postoperative pain. Preoperative glucocorticoid improves pain after TKA, but dose-finding studies and benefit in high pain responders are lacking. METHODS: A randomised double-blind controlled trial with preoperative high-dose intravenous dexamethasone 1 mg kg-1 or intermediate-dose dexamethasone 0.3 mg kg-1 in 88 patients undergoing TKA with preoperative pain catastrophising score >20 or regular opioid use was designed. The primary outcome was the proportion of patients experiencing moderate-to-severe pain (VAS >30) during a 5 m walk 24 h postoperatively. Secondary outcomes included pain at rest during nights and at passive leg raise, C-reactive protein, opioid use, quality of sleep, Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, readmission, and complications. RESULTS: Moderate-to-severe pain when walking 24 h postoperatively was reduced (high dose vs intermediate dose, 49% vs 79%; P<0.01), along with pain at leg raise at 24 and 48 h (14% vs 29%, P=0.02 and 12% vs 31%, P=0.03, respectively). C-reactive protein was reduced in the high-dose group at both 24 and 48 h (both P<0.01). Quality of Recovery-15 was also improved (P<0.01). CONCLUSIONS: When compared with preoperative dexamethasone 0.3 mg kg-1 i.v., dexamethasone 1 mg kg-1 reduced moderate-to-severe pain 24 h after TKA and improved recovery in high pain responders without apparent side-effects. CLINICAL TRIAL REGISTRATION: NCT03763734.

Preoperative high-dose Steroids in Total Knee and Hip Arthroplasty - Protocols for three randomized controlled trials.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA)/ total hip arthroplasty (THA) still experience moderate-severe postoperative pain despite optimized pain management regimes. The patients already on opioid treatment and pain catastrophizers (PCs) have a higher risk of postoperative pain. The use of preoperative intravenous high-dose glucocorticoids decreases postoperative pain after TKA and THA, but optimal dose is yet to be found, and the effect on subpopulations at high pain risk is unknown. AIM: To investigate the effect of a higher than previously used dose of glucocorticoids (dexamethasone (DXM)), administered intravenously before surgery, as part of standardized fast-track regimen, on postoperative pain in TKA/THA subgroups. METHOD: Three separate randomized, double-blinded, controlled trials were planned to compare a new higher dose DXM (1 mg/kg) to the earlier used high-dose DXM (0.3 mg/kg). Study 1: predicted Low Pain TKA; study 2: predicted High Pain Responder (HPR) TKA; study 3: predicted HPR THA. Predicted HPR groups consist of either PCs with PCS-score of ≥ 21 and/or history of ongoing opioid-treatment of 30 mg/day of morphine or equivalents > 30 days. In total, 408 patients were planned for inclusion (160 Low Pain TKA, 88 HPR TKA, 160 HPR THA). PRIMARY OUTCOME: Pain upon ambulation in a 5-meter walk test 24 hours after surgery. Secondary outcomes include use of analgesics, rescue-opioids, antiemetics, cumulated pain, CRP, OR-SDS, QoR-15, quality of sleep, length of stay (LOS), reasons for hospitalization, readmission, morbidity, and mortality. Patients completed follow-up on day 90. Recruiting commenced February 2019 and is expected to finish in September 2020.