Minimal important difference in opioid consumption based on adverse event reduction—A study protocol

Background

The patient-relevant minimal important difference for opioid consumption remains undetermined, despite its frequent use as primary outcome in trials on postoperative pain management. A minimal important difference is necessary to evaluate whether significant trial results are clinically relevant. Further, it can be used as effect size to ensure that trials are powered to find clinically relevant effects. By exploring the dose–response relationship between postoperative opioid consumption and opioid-related adverse effects, we aim to approximate the minimal important difference in opioid consumption anchored to opioid-related adverse effects.

Methods

This is a post-hoc analysis of aggregated data from two clinical trials (PANSAID NCT02571361 and DEX2TKA NCT03506789) and one observational cohort study (Pain Map NCT02340052) on pain management after total hip and knee arthroplasty. The primary outcome is the Hodges–Lehmann median difference in opioid consumption between patients with no opioid-related adverse effects and patients experiencing the mildest degree of one or more opioid-related adverse effects (i.e., mild nausea, sedation and/or dizziness or vomiting). Secondary outcomes include the Hodges–Lehmann median difference in opioid consumption that corresponds to one point on a cumulated opioid-related adverse event 0–10 scale. Further, we will explore the proportion of patients that experience opioid-related adverse effects for consecutive opioid dose intervals of 2 mg iv morphine equivalents. Quantile regression will be used to assess any significant interactions with patient baseline characteristics.

Conclusions

This study will hopefully bring us one step closer to determining relevant opioid reductions and thereby improve our understanding of intervention effects and planning of future trials.     

Retrospective evaluation of inpatient celecoxib use after total hip and knee arthroplasty at a Veterans Affairs Medical Center

A retrospective cohort study (1.5 years) was performed to investigate the efficacy of celecoxib vs non-celecoxib use in patient who underwent total knee arthroplasty (TKA) and total hip arthroplasty (THA). Study time frame encompassed a pre and post period of a local policy decision opening access to short-term celecoxib use after TKA/THA. Primary end point was the amount of opioid use during their inpatient stay postprocedure. The TKA (n = 81) and THA (n = 60) groups were analyzed independently. Both celecoxib groups used significantly less opioids during their inpatient stay vs noncelecoxib groups, given in oral morphine milligram equivalents (TKA: 203 vs 337 mg, P = .002; THA: 214 vs 336 mg, P = .005). Other secondary outcome measures showed that the celecoxib groups also reported reduction in pain scores, total as needed (PRN) opioid doses, PRN opioid doses per day, average dose of PRN opioids, total PRN opioids, use of intravenous opioids, and rehabilitation facility admissions (in the TKA group only). Linear regression analysis showed a statistically significant inverse relationship between opioid consumption and age. Short-term celecoxib use after TKA/THA may lead to a reduction in overall opioid use and improved pain scores; however, further studies will be required to validate the results of this study.     

Preemptive Analgesia With Oxycodone Is Associated With More Pain Following Total Joint Arthroplasty

BackgroundPreemptive multimodal analgesia (PMA) is a commonly used technique to control pain following total joint arthroplasty. PMA protocols use multiple analgesics immediately preoperatively to prevent central sensitization and amplification of pain during surgery. While benefits of some individual components of a PMA protocol have been established, there are little data to support inclusion or exclusion of opioids in this context.MethodsThis is a retrospective cohort study of 550 patients undergoing elective, primary total joint arthroplasty at a single institution using a standardized preoperative perioperative protocol. Two hundred seventy-five patients received oxycodone in addition to a standard multimodal preoperative analgesia regimen just before surgery and were compared to a matched cohort of 275 patients who received the standard regimen alone. Outcome measures included inpatient visual analog scale pain scores, inpatient opioid consumption, length of stay, and ambulation distance with physical therapy.ResultsPatients who received opioids in preoperative holding reported significantly greater visual analog scale pain scores on postoperative day 1 (3.7 vs 3.1; P = .01), when compared to those who did not. These patients also walked shorter distances on postoperative day 0 (59.5’ vs 125.7’; P < .001) and consumed greater morphine equivalents per hospital day over the course of their hospital stay (52.2 vs 37.2 mg; P < .001). These differences remained significant when stratified by procedure, total knee arthroplasty or total hip arthroplasty. Differences in pain and function between groups were more pronounced in patients undergoing total hip arthroplasty than those undergoing total knee arthroplasty.ConclusionTotal joint patients who were given preemptive opioids immediately before surgery experienced more pain, consumed more postoperative opioids, and exhibited impaired early function as compared to those who were not given preemptive opioids. Orthopedic surgeons should reconsider routine use of preemptive opioids in this context.     

Prospective analysis of a novel long-acting oral opioid analgesic regimen for pain control after total hip and knee arthroplasty

Parenteral opioid use after total knee (TKA) and hip (THA) arthroplasty often results in substantial functional interference and side effects. This prospective study compared use of traditional intravenous patient-controlled analgesia (IV PCA) with a novel oral regimen after TKA and THA. Sixty-two patients received IV PCA and 62 received scheduled long-acting and, as needed, short-acting oral opioids postoperatively. Surveys and chart audits documented functional interference, pain scores, opioid-related side effects, and opioid consumption. Patients who received the oral regimen had significantly less opioid consumption (P < .05) and experienced less functional interference (P < .05) than the IV PCA group. Both groups had similar pain scores and incidence of opioid side effects. This study demonstrates some significant advantages of an oral analgesic regimen compared with IV PCA after TKA and THA.     

Prolonged Opioid Use After Primary Total Knee and Total Hip Arthroplasty: Prospective Evaluation of Risk Factors and Psychological Profile for Depression,Pain Catastrophizing,and Aberrant Drug-Related Behavior

BackgroundForty percent of patients continue to use opioids at 3 months after joint arthroplasty. We sought to identify clinical and psychological risk factors associated with prolonged opioid use.MethodsIn this prospective study, psychological profile data were collected preoperatively. Prolonged use was defined as dispensation of an opioid after 90 days. Logistic regressions were used for univariate and multivariate modeling and to create receiver operating characteristic curves. A backward stepwise regression analysis was used to select significant factors in the multivariable model.ResultsThe study included 258 patients (163 total knee arthroplasty, 95 total hip arthroplasty). 29.84% of patients were on preoperative opioids and 14% (37 of 258) of patients had prolonged use of opioids. In the univariate analysis, age <65, associated back pain, chronic pain syndrome or fibromyalgia, prior opioid use, drug potency of more than 10 morphine equivalent, and total score on Opioid Risk Tool of more than 7 were associated with prolong use. In the multivariate analysis, age <65, associated back pain, chronic pain, and preoperative use of opioids were significant risk factors for prolonged use (combined area under the curve = 0.83). Preoperative opioid use had the highest area under the curve = 0.72 (P = .0005). Psychological profile tests did not predict prolonged opioid use.ConclusionPreoperative opioid use was the strongest predictor of postoperative prolonged opioid use. Younger age, associated backpain, and chronic pain syndrome were the other identified risk factors. Screening tools to detect aberrant drug-related behavior may be more helpful than those for depression or pain catastrophizing.     

What Happens to Unused Opioids After Total Joint Arthroplasty? An Evaluation of Unused Postoperative Opioid Disposal Practices

BackgroundThis study evaluates the fate of unused opioids after total hip arthroplasty (THA) and total knee arthroplasty (TKA) at our facility.MethodsMedication disposal after primary elective THA and TKA was classified as appropriate (in accordance with United States Food and Drug Administration guidelines) or inappropriate for all patients undergoing these procedures during the second half of the fiscal year 2015.ResultsIn total, 199 THAs and 144 TKAs met inclusion criteria. Total pills prescribed were 55,635. Approximately 8925 (16%) of pills were unused. About 39.9% of patients disposed of unused opioids appropriately, while 60.1% of patients reported still having (18.5%), not knowing where they were (8.2%), or other (33.4%). There was no significant association with the type of opioid prescribed.ConclusionA large volume of unused opioids were improperly disposed of after total joint arthroplasty.     

A Prospective Evaluation of 2 Different Pain Management Protocols for Total Hip Arthroplasty

Pain management after total hip arthroplasty has improved dramatically in the past decade. However, most protocols use opioid medications for pain control. In the current study, 100 patients were prospectively selected to receive a traditional narcotic-based patient-controlled analgesia protocol or a nonnarcotic oral protocol for pain management after primary total hip arthroplasty. Therapy programs were similar for both groups. Postoperatively, patients were followed daily for opioid use, medication adverse effects, pain control, and overall satisfaction. The nonnarcotic oral group showed lower mean pain scores during the first 24 hours after surgery. The satisfaction rate was high in both groups. Both protocols provided adequate pain control after total hip arthroplasty; the nonnarcotic pain management protocol resulted in significantly decreased opioid consumption and fewer adverse effects.     

Opioid use prior to total hip arthroplasty leads to worse clinical outcomes

Purpose

The purpose of this study was to compare the clinical outcomes of patients undergoing total hip arthroplasty (THA) who had been using narcotic medications prior to surgery to those who had not used them.

Methods

Fifty-four patients (62 hips) who had required opioid analgesia for hip pain in the three months prior to THA were compared to a matched group of opioid-naïve patients. Narcotic consumption was converted to a standardized morphine equivalent dose and compared between both groups of patients during their hospital stay, after six weeks, and at final follow-up. Other outcome measures included clinical outcome scores and the proportion of patients remaining on narcotic pain medication at final follow-up.

Results

The narcotic group required significantly higher total daily opioid doses as inpatients had a longer hospital stay and a higher proportion of patients who remained on opioids at six weeks and at final follow-up. Of the patients who were taking opioids pre-operatively, 81 % were able to wean off opioids at final follow-up. At a mean post-operative follow-up of 58 months (range, 24–258 months), Harris hip scores were lower in the narcotic group, with a mean of 84 compared to 91 points in the matching group. However, in both cohorts, there were significant improvements in Harris hip scores compared to pre-operative outcomes.

Conclusions

Patients who use narcotics prior to total hip arthroplasty may be more likely to suffer from opioid-induced hyperalgesia after surgery and have worse clinical outcomes. When possible, efforts should be made to use other modes of analgesia or wean patients from their use prior to total hip arthroplasty.     

Patients With Major Depressive Disorder Experience Increased Perception of Pain and Opioid Consumption Following Total Joint Arthroplasty

Background

Pain in the immediate postoperative period following total joint arthroplasty is influenced by various patient factors, including major depressive disorder (MDD). Therefore, this study aimed to compare the patient perception of pain and opioid consumption between patients with and without MDD who received either a total knee arthroplasty (TKA) or total hip arthroplasty (THA). Specifically, we compared (1) pain intensity, (2) lengths of stay, (3) opioid consumption, and (4) patient perception of pain control.

Subacute pain and function after fast-track hip and knee arthroplasty

In a well-defined fast-track setup for total hip and knee arthroplasty, with a multimodal analgesic regimen consisting of intra-operative local anaesthetic infiltration and oral celecoxib, gabapentin and paracetamol for 6 days postoperatively, we conducted a prospective, consecutive, observational study. The purpose was to describe the prevalence and intensity of subacute postoperative pain and opioid related side effects, use of analgesics and functional ability 1–10 and 30 days postoperatively. Fast-track total hip and knee arthroplasty with early discharge (< 3 days) resulted in acceptable levels of pain and postoperative nausea and vomiting with concomitant low use of opioids in > 95% of patients after discharge before day 10 after total hip arthroplasty. However, after total knee arthroplasty 52% patients reported moderate pain (VAS 30–59 mm), and 16% severe pain (VAS ≥ 60 mm) when walking 1 month after surgery with a concomitant increase in the use of strong opioids. These results emphasise the need for improvement in analgesia after discharge following total knee arthroplasty, to facilitate rehabilitation.     

Risk for Prolonged Opioid Use Following Total Knee Arthroplasty in Veterans

Background

Patients undergoing total knee arthroplasty (TKA) may be at risk for prolonged postsurgical opioid use due to a high prevalence of persistent postsurgical pain (20%) and high rates of presurgical opioid use.

A systematic review of pain outcomes reported by randomised trials of hip and knee arthroplasty

It is difficult to pool results from randomised clinical trials that report different outcomes. We want to develop a core set of pain-related outcomes after total hip or knee arthroplasty, the first stage of which is to systematically review published outcomes. We searched PubMed, Embase and CENTRAL for relevant trials to January 2020. We identified 165 outcomes from 565 trials with 50,668 participants, which we categorised into six domains: pain; analgesic consumption; quality of care; adverse events; mobility; and patient-reported outcome measures. The outcome in each domain reported by most trials was: visual analogue score for pain, 401 (71%); morphine consumption, 212 (38%); length of hospital stay, 166 (29%); nausea or vomiting, 425 (75%); range of motion, 173 (31%); and patient satisfaction score, 181 (32%). A primary outcome was reported in 281 (50%) trials: 101 (18%) trials reported consumption of rescue analgesics and 95 (17%) trials reported pain. We plan to publish a consensus on outcomes that should be reported in postoperative pain trials after hip or knee arthroplasty.