Development and internal validation of a clinical risk tool to predict chronic postsurgical pain in adults: a prospective multicentre cohort study.

ABSTRACT: Chronic postsurgical pain (CPSP) is a highly prevalent condition. To improve CPSP management, we aimed to develop and internally validate generalizable point-of-care risk tools for preoperative and postoperative prediction of CPSP 3 months after surgery. A multicentre, prospective, cohort study in adult patients undergoing elective surgery was conducted between May 2021 and May 2023. Prediction models were developed for the primary outcome according to the International Association for the Study of Pain criteria and a secondary threshold-based CPSP outcome. Models were developed with multivariable logistic regression and backward stepwise selection. Internal validation was conducted using bootstrap resampling, and optimism was corrected by shrinkage of predictor weights. Model performance was assessed by discrimination and calibration. Clinical utility was assessed by decision curve analysis. The final cohort included 960 patients, 16.3% experienced CPSP according to the primary outcome and 33.6% according to the secondary outcome. The primary CPSP model included age and presence of other preoperative pain. Predictors in the threshold-based models associated with an increased risk of CPSP included younger age, female sex, preoperative pain in the surgical area, other preoperative pain, orthopedic surgery, minimally invasive surgery, expected surgery duration, and acute postsurgical pain intensity. Optimism-corrected area-under-the-receiver-operating curves for preoperative and postoperative threshold-based models were 0.748 and 0.747, respectively. These models demonstrated good calibration and clinical utility. The primary CPSP model demonstrated fair predictive performance including 2 significant predictors. Derivation of a generalizable risk tool with point-of-care predictors was possible for the threshold-based CPSP models but requires independent validation.

Prognostic clinical prediction models for acute post-surgical pain in adults: a systematic review.

BACKGROUND: Acute post-surgical pain is managed inadequately in many patients undergoing surgery. Several prognostic risk prediction models have been developed to identify patients at high risk of developing moderate to severe acute post-surgical pain. The aim of this systematic review was to describe and evaluate the methodological conduct of these prediction models. METHODS: We searched MEDLINE, EMBASE and CINAHL for studies of prognostic risk prediction models for acute post-surgical pain using predetermined criteria. Prediction model performance was evaluated according to discrimination and calibration. Adherence to TRIPOD guidelines was assessed. Risk of bias and applicability was independently assessed by two reviewers using the prediction model risk of bias assessment tool. RESULTS: We included 14 studies reporting on 17 prediction models. The most common predictors identified in final prediction models included age; surgery type; sex or gender; anxiety or fear of surgery; pre-operative pain intensity; pre-operative analgesic use; pain catastrophising; and expected surgical incision size. Discrimination, measured by the area under receiver operating characteristic curves or c-statistic, ranged from 0.61 to 0.83. Calibration was only reported for seven models. The median (IQR [range]) overall adherence rate to TRIPOD items was 62 (53-66 [47-72])%. All prediction models were at high risk of bias. CONCLUSIONS: Effective prediction models could support the prevention and treatment of acute post-surgical pain; however, existing models are at high risk of bias which may affect their reliability to inform practice. Consideration should be given to the goals, timing of intended use and desired outcomes of a prediction model before development.

The effect of intraoperative methadone on postoperative opioid requirements in children undergoing orchiopexy: A randomized clinical trial.

BACKGROUND: Children undergoing outpatient surgery are at risk of inadequate postoperative pain control. Methadone has a long duration of action and an intraoperative dose may provide stable analgesia throughout the postoperative period. Intraoperative methadone has been shown to improve pain control in adolescents but its use for postoperative pain in pediatric patients undergoing outpatient surgery has not been studied before. Therefore, we conducted a double-blind randomized placebo-controlled trial to investigate the effects of a single dose of intraoperative methadone in children aged less than 5 years undergoing orchiopexy for undescended testis. METHODS: A total of 68 children were randomized to receive either methadone (0.1 mg/kg) or isotonic saline following induction of anesthesia. Exclusion criteria included preterm birth, previous scrotal surgery, and parents' inability to consent. Primary outcomes were opioid requirements (first primary outcome) and pain intensity in the post-anesthesia care unit. Secondary outcomes included episodes of desaturation and time until readiness to discharge from the post-anesthesia care unit, sleep on the first postoperative night, pain intensity, and opioid requirements at home until the evening on the first postoperative day. Follow-up was 4 days. RESULTS: Sixty children completed the study (age, mean ± SD, 26.2 ± 13.9 months), 29 children received methadone, and 31 children received placebo. Eighteen children required opioids in the post-anesthesia care unit, five children in the methadone group (proportion = 0.17, 95% confidence interval (CI): 0.07, 0.36) compared to thirteen patients in the placebo group (0.42, 95% CI: 0.26, 0.60) (mean difference = -0.24 and 95% CI: -0.03, -0.47) (p = 0.037). Five children in the methadone group (0.17, 95% CI: 0.03, 0.31) versus ten in the placebo group (0.32, 95% CI: 0.16, 0.49) had a face, legs, activity, cry, consolability score of ≥5 in the post-anesthesia care unit (mean difference = -0.15, 95% CI: -0.36, 0.06) (p = .179). More children in the placebo group woke up due to pain the first night following surgery (seven children vs. one child). The methadone group had a longer stay in the post-anesthesia care unit. There were no differences between the two groups regarding the other secondary outcomes. CONCLUSION: A single dose of intraoperative methadone reduces short-term postoperative opioid requirements in children after orchiopexy for nondescended testes but prolongs the duration of their stay in the post-anesthesia care unit.

Duration of peripheral nerve blocks in opioid-tolerant individuals: A study protocol.

BACKGROUND: Peripheral nerve blocks effectively alleviate postoperative pain. Animal studies and human research suggest that opioid tolerance may reduce the effectiveness of local analgesics. The reduced effectiveness has been observed in opioid-tolerant humans and animals undergoing spinal and infiltration anaesthesia with both lidocaine and bupivacaine. However, the impact on peripheral nerve blocks in humans has not been evaluated. This study aims to assess the onset time and duration of a radial nerve block in opioid-tolerant individuals compared to opioid-naive individuals. We hypothesise that peripheral nerve blocks may be less effective in producing sensory and motor blockades in opioid-tolerant individuals compared to their opioid-naive counterparts. METHODS: Twenty opioid-tolerant individuals will be matched by sex and age with opioid-naïve counterparts. Participants will receive an ultrasound-guided radial nerve block. The primary outcome is the difference in the duration of sensory nerve blockade between the two groups. The secondary outcomes include the onset time of sensory blockade, onset time of motor blockade, and difference in duration of motor nerve blockade. CONCLUSION: This study will compare the effectiveness of a peripheral nerve block between opioid-tolerant and opioid-naïve individuals. Any found differences could support a specific postoperative protocol for opioid-tolerant individuals regarding the use of peripheral nerve blocks.

Opioids and personalized analgesia in the perioperative setting: A protocol for five systematic reviews.

BACKGROUND: Treatment with opioids is a mainstay in perioperative pain management. While the leading treatment paradigm has been procedure-specific pain management, efforts regarding personalized pain treatment are increasing. The OPI•AID project aims to develop personalized algorithms for perioperative pain management, taking demographic, surgical, and anaesthesiologic factors into account. We will undertake five parallel reviews to illuminate current evidence on different aspects of individual responses to perioperative opioid treatment. METHODS: Inclusion of adult populations in English-written studies. Review-specific searches are developed for the following databases: CENTRAL, MEDLINE, Embase, clinicaltrials.gov, and clinicaltrial.eu. Two authors will independently screen citations, extract data, and assess the risks of bias in each review (QUIPS, PROBAST and RoB2, as relevant). CONCLUSION: These reviews will evaluate various aspects of perioperative opioid treatment, including individualized treatment strategies, selection of specific opioids, and individual patient responses. These will guide future development of a personalized perioperative opioid treatment algorithm (OPI•AID) that will be validated and tested clinically against standard of care.

Effects of popliteal plexus block after total knee arthroplasty: a randomized clinical trial.

BACKGROUND AND OBJECTIVES: Motor-sparing peripheral nerve blocks enhance multimodal opioid-sparing strategies after total knee arthroplasty. We hypothesized that adding a popliteal plexus block to a femoral triangle block could reduce 24-hour opioid consumption after total knee arthroplasty, compared with standalone femoral triangle block or adductor canal block. METHODS: This patient- and assessor-blinded, randomized controlled trial allocated 165 patients into three equally sized parallel groups, receiving either 1) popliteal plexus block+femoral triangle block, 2) femoral triangle block, or 3) adductor canal block. Intravenous oxycodone was administered via patient-controlled analgesia pumps. The primary outcome was 24-hour postoperative opioid consumption. Secondary outcomes were preoperative maximum voluntary isometric contraction and manual muscle tests of knee and ankle movement assessed before and after the nerve block procedure together with postoperative pain scores, mobilization, and 12-hour opioid consumption. RESULTS: 24-hour postoperative intravenous oxycodone consumption varied significantly between groups (p<0.01), with medians (IQR) of 6 mg (2-12) in the popliteal plexus block+femoral triangle block group, 10 mg (8-16) in the femoral triangle block group, and 12 mg (6-18) in the adductor canal block group. Median consumption in the popliteal plexus block+femoral triangle block group was reduced by -4 mg (95% CI -7.4 to -1.0, p<0.01) and -6 mg (95% CI -8.3 to -1.3, p=0.01) compared with groups of femoral triangle block and adductor canal block, respectively. No differences were found in pain scores, mobilization, or changes in preoperative muscle strength. Post hoc analysis revealed successful 24-hour opioid-free postoperative care among 12 patients with popliteal plexus block+femoral triangle block, as compared with two with femoral triangle block and six with adductor canal block. CONCLUSION: Adding a popliteal plexus block to a femoral triangle block resulted in a statistically significant reduction of 24-hour postoperative opioid consumption after total knee arthroplasty. However, no differences were found in pain scores. Popliteal plexus block did not impair the lower leg muscles.

Low-dose ketamine as an adjunct to morphine: A randomized controlled trial among patients with and without current opioid use.

BACKGROUND: Pain is a common complaint among patients presenting to the emergency department (ED), yet pain treatment is frequently suboptimal. The aim of this study was to determine the effectiveness of low-dose ketamine (LDK) as an adjunct to morphine versus morphine alone for treatment of acute pain among ED patients with and without current opioid use. METHODS: Adult patients presenting with acute pain of ≥5 on a numeric rating scale (0-10) who were deemed by their treating ED physician to require intravenous opioids were randomized to receive either 0.1 mg/kg ketamine (treatment group) or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain was measured at baseline (T0) and 10, 20, 30, 45, 60, and 120 min after randomization. The primary outcome was pain reduction from T0 to T10. Secondary outcomes included pain intensity over 120 min, need of rescue opioids, side effects, and patient and provider satisfaction. RESULTS: A total of 116 patients were included from May 2022 to August 2023. Median (IQR) age was 51 (36.5-67) years; 58% were male and 36% had current opioid use. Pain reduction from T0 to T10 was greater in the LDK group (4 [IQR 3-6]) compared to the placebo group (1 [IQR 0-2]; p = 0.001). Pain intensity was lower in the LDK group at T10, T20, and T30, compared to the placebo group. There was a higher risk of nausea, vomiting, and dissociation in the LDK group during the first 10 min. CONCLUSIONS: LDK may be effective as an adjunct analgesic to morphine for short-term pain relief in treatment of acute pain in the ED for both patients with and without current opioid use.

Respiratory Depression Following Intraoperative Methadone: A Retrospective Cohort Study.

BACKGROUND: Methadone is used as a perioperative analgesic in the management of postoperative pain. Despite positive outcomes from randomized trials favoring methadone, concerns about its safety persist, particularly regarding respiratory depression (RD) and excessive sedation. In this study, we compared the incidence of naloxone administration between patients administered intraoperative methadone and those administered intraoperative morphine as a measure of severe RD. Time spent at the postanesthesia care unit (PACU) was used as a proxy variable for excessive sedation. METHODS: This was a retrospective cohort study including all patients aged ≥18 years who underwent surgery between March 2019 and March 2023 at Aarhus University Hospital, Denmark. We assessed the association between intraoperative administration of either methadone or morphine and postoperative naloxone administration within the first 24 hours using logistic regression (primary outcome). An analogous linear regression model was used for the secondary outcome of time spent in the PACU after surgery. Patients were weighted using propensity scores to adjust for potential confounding variables. RESULTS: A total of 14,522 patients were included in the analysis. Among the 2437 patients who received intraoperative methadone, 15 (0.62%) patients received naloxone within the first 24 hours after surgery compared to 68 of 12,0885 (0.56%) who received intraoperative morphine. No statistical difference was observed in the odds of naloxone administration between patients administered methadone or morphine (adjusted odds ratio 95% confidence interval [CI], 1.21 [0.40-2.02]). Patients who were administered intraoperative methadone had a mean PACU length of stay (LOS) of 334 minutes (standard deviation [SD], 382) compared to 195 minutes (SD, 228) for those administered intraoperative morphine. The adjusted PACU LOS of patients administered intraoperative methadone was 26% longer compared to those administered intraoperative morphine (adjusted ratio of the geometric means 95% CI, 1.26 [1.22-1.31]). CONCLUSIONS: The incidence of naloxone administration to treat severe RD was low. No difference was observed in the odds of naloxone administration to treat severe RD between patients administered intraoperative methadone or intraoperative morphine. Intraoperative methadone was associated with longer stays at the PACU; however, this result should be interpreted with care. Our findings suggest that intraoperative methadone has a safety profile comparable to that of morphine with regard to severe RD.

Cryoneurolysis versus radiofrequency ablation outcome on pain experience in chronic low back pain (COPE): a single-blinded randomised controlled trial.

OBJECTIVE: A comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and quality of life, with 1-year follow-up. DESIGN: Single-centre, single-blinded placebo-controlled randomised controlled trial. SETTING: Single-centre study. PARTICIPANTS: Inclusion from March 2020 to September 2022: consenting adults over 18 years of age, LBP>3 months, average Numeric Rating Scale LBP≥4 average last 14 days and a positive response to a diagnostic medial branch block (>50% pain reduction after 60 min). INTERVENTIONS: 120 patients were block randomised 1:1:1 to cryoneurolysis, RF or placebo of the medial branch nerves. Physical therapy was added after 4 weeks for all groups. MAIN OUTCOME MEASURES: Primary outcome was PGIC 4 weeks after the intervention. Secondary outcomes included pain intensity (Numeric Rating Scale, NRS), quality of life (Short Form 36, EQ-5D-5L), disability (Oswestry Disability Index), depression (Major Depression Inventory) and catastrophising (Pain Catastrophising Scale). Outcomes were measured at 4 weeks, 3, 6 and 12 months. RESULTS: There was no statistically significant difference in PGIC at 4 weeks between cryoneurolysis and placebo (risk ratio (RR) 2; 95% CI 0.75 to 5.33, p=0.17) and RF and placebo (RR 1.6; 95% CI 0.57 to 4.49, p=0.37), except PGIC for cryoneurolysis at 6-month follow-up (RR 5.1; 95% CI 1.20 to 22.03, p=0.03). No statistically significant differences were found in secondary follow-up endpoints. CONCLUSIONS: Denervation of the medial branch nerve by either cryoneurolysis or RF compared with placebo did not demonstrate significant improvement in PGIC, pain intensity, function and quality of life in patients with facetogenic chronic LBP at short-term or long-term follow-up. TRIAL REGISTRATION NUMBER: NCT04786145.

Intraoperative clonidine in endometriosis and spine surgery: A protocol for two randomised, blinded, placebo-controlled trials.

BACKGROUND: A high proportion of patients who undergo surgery continue to suffer from moderate to severe pain in the early postoperative period despite advances in pain management strategies. Previous studies suggest that clonidine, an alpha2 adrenergic agonist, administered during the perioperative period could reduce acute postoperative pain intensity and opioid consumption. However, these studies have several limitations related to study design and sample size and hence, further studies are needed. AIM: To investigate the effect of a single intravenous (IV) dose of intraoperative clonidine on postoperative opioid consumption, pain intensity, nausea, vomiting and sedation after endometriosis and spine surgery. METHODS: Two separate randomised, blinded, placebo-controlled trials are planned. Patients scheduled for endometriosis (CLONIPAIN) will be randomised to receive either 150 µg intraoperative IV clonidine or placebo (isotonic saline). Patients undergoing spine surgery (CLONISPINE) will receive 3 µg/kg intraoperative IV clonidine or placebo. We aim to include 120 patients in each trial to achieve power of 90% at an alpha level of 0.05. OUTCOMES: The primary outcome is opioid consumption within the first three postoperative hours. Secondary outcomes include pain intensity at rest and during coughing, nausea, vomiting and sedation within the first two postoperative hours and opioid consumption within the first six postoperative hours. Time to discharge from the PACU will be registered. CONCLUSION: This study is expected to provide valuable information on the efficacy of intraoperative clonidine in acute postoperative pain management in patients undergoing endometriosis and spine surgery.

As-needed opioid dosing for emergency patients with a daily use of opioids.

BACKGROUND: Patients with a daily use of opioids have a higher risk of insufficient pain treatment during hospitalization than other patients. This study aimed to examine whether as-needed opioid doses (PRN) were adequately adjusted when patients were admitted to the emergency department (ED) with pain. METHODS: Patients, with a daily use of opioids, who received PRN opioid within the first 3 h after admission at the ED at Aarhus University Hospital, Denmark, were prospectively included from February 2021 to June 2021. The primary outcome was the proportion of patients receiving an inadequate initial dose of PRN opioid, here defined as <15% of daily dose of opioids (DDO) based on sparse evidence, but aligning with the prevailing clinical practice. Secondary outcomes included risk of an inadequate PRN dose in relation to DDO (patients were dichotomized into two groups (DDO <60 or ≥60 mg/day). RESULTS: Among 252 patients admitted to the ED with a daily use of opioids, 149 were admitted with pain and 82 received a PRN opioid dose within 3 h. Twenty-seven out of 82 (33%) patients received a PRN dose of <15% of DDO (95% CI: 23.7-43). When dichotomised; 10 out of 50 (20%) patients with a DDO <60 mg/day (95% CI: 10.0-33.7) versus 17 out of 32 (53.1%) patients with a DDO ≥60 mg/day (95% CI: 34.7-70.9) received an inadequate PRN dose (relative risk, RR: 2.65 [95% CI: 1.4-5.1]). CONCLUSIONS: Patients with daily use of opioids presenting in the ED with acute pain had a high risk of inadequate PRN opioid dose, especially if the DDO was high. Awareness about and education focusing on sufficient PRN doses for patients with a daily use of opioids is (still) called for.

Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial.

Background: Laparoscopic hysterectomy is often carried out as day-stay surgery. Minimising postoperative pain is therefore of utmost importance to ensure timely discharge from hospital. Methadone has several desirable pharmacological features, including a long elimination half-life. Therefore, a single intraoperative dose could provide long-lasting pain relief. Methods: Patients scheduled to undergo laparoscopic hysterectomy were randomly allocated to receive methadone (0.2 mg kg-1) or morphine (0.2 mg kg-1) intraoperatively, 60 min before tracheal extubation. Primary outcomes were opioid consumption (oral morphine equivalents in milligrams) at 6 and 24 h. Secondary outcomes included pain intensity at rest and during coughing, patient satisfaction, postoperative nausea and vomiting, and adverse events up to 72 h after completion of surgery. Results: The postoperative median opioid consumption was reduced in the methadone group compared with the morphine group at 6 h (35.5 [0-61] mg vs 48 [31-74.5] mg; P=0.01) and 24 h (42 [10-67] mg vs 54.5 [31-83] mg; P=0.03). On arrival at the PACU, pain at rest was significantly lower in patients receiving methadone (numeric rating scale: 3 [2-5] vs 5 [3-6]), whereas pain scores at rest and coughing were not significantly different throughout the rest of the observation period. No differences in other secondary outcomes were found. Conclusions: In this randomised, blinded, controlled trial, opioid consumption was reduced during the first 24 postoperative hours in patients receiving methadone without causing an increase in adverse events. The difference observed might be considered as small and of limited clinical relevance. Clinical trial registration: NCT03908060; EudraCT no. 2018-004351-20.

An individualised tapering protocol reduces opioid use 1 year after spine surgery: A randomised controlled trial of patients with preoperative opioid use.

BACKGROUND: Persistent opioid use following surgery is common especially in patients with preoperative opioid use. This study aims to determine the long-term effect of an individualised opioid tapering plan versus standard of care in patients with a preoperative opioid use undergoing spine surgery at Aarhus University Hospital, Denmark. METHODS: This is the 1-year follow-up of a prospective, single-centre, randomised trial of 110 patients who underwent elective spine surgery for degenerative disease. The intervention was an individualised tapering plan at discharge and telephone counselling 1 week after discharge, compared to standard of care. Postoperative outcomes after 1 year include opioid use, reasons for opioid use and pain intensity. RESULTS: The overall response rate to the 1-year follow-up questionnaire was 94% (intervention group 52/55 patients and control group 51/55 patients). Forty-two patients (proportion = 0.81, 95% CI 0.67-0.89) in the intervention group compared to 31 (0.61, 95% CI 0.47-0.73; p = .026) patients in the control group succeeded in tapering to zero 1 year after discharge (p = .026). One patient (0.02, 95% CI 0.01-0.13) in the intervention group compared to seven patients (0.14, 95% CI 0.07-0.26) in the control group were unable to taper to their preoperative dose 1 year after discharge (p = .025). Back/neck and radicular pain intensity was similar between study groups. CONCLUSION: These results suggest that an individualised tapering plan at discharge combined with telephone counselling 1 week after discharge can reduce opioid use 1 year after spine surgery.

Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA): A consortium initiative for perioperative research.

Evidence in perioperative care is insufficient. There is an urgent need for large perioperative research programmes, including pragmatic randomised trials, testing daily clinical treatments and unanswered question, thereby providing solid evidence for effects of interventions given to a large and growing number of patients undergoing surgery and anaesthesia. This may be achieved through large collaborations. Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA) is a novel collaborative research network founded to pursue evidence-based answers to major clinical questions in perioperative medicine. The aims of CEPRA are to (1) improve clinical treatment and outcomes and optimise the use of resources for patients undergoing anaesthesia and perioperative care, and (2) disseminate results and inform caretakers, patients and relatives, and policymakers of evidence-based treatments in anaesthesia and perioperative medicine. CEPRA is inclusive in its concept. We aim to extend our collaboration with all relevant clinical collaborators and patient associations and representatives. Although initiated in Denmark, CEPRA seeks to develop an international network infrastructure, for example, with other Nordic countries. The work of CEPRA will follow the highest methodological standards. The organisation aims to structure and optimise any element of the research collaboration to reduce economic costs and harness benefits from well-functioning research infrastructure. This includes successive continuation of trials, harmonisation of outcomes, and alignment of data management systems. This paper presents the initiation and visions of the CEPRA network. CEPRA aims to be inclusive, patient-focused, methodologically sound, and to optimise all aspects of research logistics. This will translate into faster research conduct, reliable results, and accelerated clinical implementation of results, thereby benefiting millions of patients whilst being cost and labour-saving.

Subanaesthetic single-dose ketamine as an adjunct to opioid analgesics for acute pain management in the emergency department: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of a subanaesthetic single-dose ketamine (SDK) as an adjunct to opioids for acute pain in emergency department (ED) settings. DESIGN: Systematic review and meta-analysis. METHODS: A systematic search was performed in MEDLINE, Embase, Scopus and Web of Science through March 2022. Randomised controlled trials (RCTs) that investigated SDK as an adjunct to opioids in adult patients for any painful condition in ED settings were selected. Two reviewers screened studies, extracted data and assessed study quality. Data were pooled using random-effects models. The primary outcome was mean pain intensity score measured at baseline, >0-15 min, >15-30 min, >30-45 min, 60 min, 90 min and 120 min. Secondary outcomes included need for rescue analgesia, adverse events and patient satisfaction. Results were reported as mean differences (MDs) and risk ratios. Statistical heterogeneity was calculated using the I 2 statistic. RESULTS: Eight RCTs were included (n=903). Studies were judged to be at moderate to high risk of bias. Mean pain intensity scores were significantly lower 60 min after study drug administration favouring adjuvant SDK (MD -0.76; 95% CI -1.19 to -0.33), compared with opioids alone. There was no evidence of differences in mean pain intensity scores at any other time point. Patients who received adjuvant SDK were less likely to require rescue analgesia, no more likely to experience serious side effects and had higher satisfaction scores, compared with opioids alone. CONCLUSIONS: Available evidence suggests adjuvant SDK can have an effect on lowering pain intensity scores. Although reduction of pain scores was not clinically significant, the combination of reduced pain intensity and reduced opioid requirements suggest the results could be clinically important and support the potential utility of SDK as an adjunct to opioids to treat acute pain in adult ED patients. However, current evidence is limited and higher quality RCTs are needed. PROSPERO REGISTRATION NUMBER: CRD42021276708.

Post-operative opioid dosing relative to preoperative long-acting opioid dose.

INTRODUCTION: Acute post-operative pain treatment continues to pose a primary therapeutic challenge for clinicians, particularly in opioid-tolerant patients. The purpose of this study was to examine whether patients with a high total daily intake of long-acting opioids received the recommended PRN opioid doses in the first 24 hours after surgery. METHODS: This was a retrospective cohort study using a comprehensive hospital database at the Aarhus University Hospital, Denmark. Patients who received both slow-release long-acting and PRN opioids within the first 24 hours after inpatient surgery were included. Patients were defined as having a high intake if they received slow-release opioids ≥ 60 mg morphine equivalents (MME). RESULTS: In total, 199 patients (14%) received a 24-hour dose of slow-release long-acting opioids ≥ 60 MME and 1,247 patients (86%) received less-than 60 MME. The median age was 64 years (interquartile range: 49-74 years); 54% were female. Patients in the ≥ 60 MME group were less likely to receive the recommended first PRN dose (at least 10% of total 24-hour dose) within the first 24 hours after surgery (79 patients; proportion = 0.40, 95% confidence interval (CI): 0.33-0.47 versus 129 patients; proportion = 0.10, 95% CI: 0.09-0.12, p less-than 0.001). CONCLUSIONS: Our results suggest that patients with a high intake of long-acting opioids may be more likely to receive PRN opioid doses that are not sufficiently adjusted to their total intake during the first 24 hours after inpatient surgery than patients with a lower intake of long-acting opiods. FUNDING: none. TRIAL REGISTRATION: The study was approved by the AUH Ethical Committee and by the Danish Data Protection Agency (ID 1-16-02-341-21).

Making sense of phantom limb pain.

Phantom limb pain (PLP) impacts the majority of individuals who undergo limb amputation. The PLP experience is highly heterogenous in its quality, intensity, frequency and severity. This heterogeneity, combined with the low prevalence of amputation in the general population, has made it difficult to accumulate reliable data on PLP. Consequently, we lack consensus on PLP mechanisms, as well as effective treatment options. However, the wealth of new PLP research, over the past decade, provides a unique opportunity to re-evaluate some of the core assumptions underlying what we know about PLP and the rationale behind PLP treatments. The goal of this review is to help generate consensus in the field on how best to research PLP, from phenomenology to treatment. We highlight conceptual and methodological challenges in studying PLP, which have hindered progress on the topic and spawned disagreement in the field, and offer potential solutions to overcome these challenges. Our hope is that a constructive evaluation of the foundational knowledge underlying PLP research practices will enable more informed decisions when testing the efficacy of existing interventions and will guide the development of the next generation of PLP treatments.

Comparison of Spinal Cord Stimulation Outcomes Between Preoperative Opioid Users and Nonusers: A Cohort Study of 467 Patients.

OBJECTIVES: Spinal cord stimulation (SCS) is a surgical treatment modality reserved for a subset of patients with neuropathic pain in which conventional pharmacologic treatment has proven insufficient. Previous studies have suggested a possible negative relationship between opioid use at referral and subsequent success of SCS therapy. The aim of this cohort study was to investigate whether preoperative opioid use was associated with inferior SCS outcomes. MATERIALS AND METHODS: Data were obtained from the Danish Neurizon Neuromodulation Database and comprised preoperative registrations of analgesic use, postoperative Patients' Global Impression of Change (PGIC) ratings, pre- and postoperative pain intensity scores (Numeric Rating Scale), and detailed surgical data. Patients were dichotomized according to preoperative opioid use (users vs nonusers) with subsequent assessment of the latest PGIC rating, reduction in pain intensity, and current treatment status (implanted/explanted). In addition, daily preoperative opioid dosages were quantified in oral morphine equivalents (OME) and correlated to the treatment outcomes. RESULTS: A total of 467 patients were included; 296 consumed opioids before SCS implantation (median 80 OME/d). Preoperative opioid use was not associated with the latest PGIC rating, reduction in pain intensity (30% or 50%), or risk of undergoing explantation (median follow-up = 3.0 years). Likewise, preoperative median OME per day of opioid users was not correlated with any of the defined outcomes. CONCLUSIONS: Preoperative opioid usage did not predict the outcome of SCS therapy in a large cohort of patients permanently implanted with an SCS system. The results do not support withholding otherwise well-indicated SCS therapy in patients with chronic neuropathic pain conditions based merely on preoperative opioid usage.