Association of peri-operative prescription of non-steroidal anti-inflammatory drugs with continued prescription of opioids after total knee arthroplasty: a retrospective claims-based cohort study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre-clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri-operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90-180 days in previously opioid-naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid-naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri-operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri-operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736-patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri-operative NSAID prescription within 30 days was 1.32 (1.30-1.35), p < 0.001; and 1.12 (1.10-1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre-existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population-based cohort study suggests that peri-operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision-making for post-surgical pain management, risk-benefit discussions with patients and future research.

Network meta-analysis of the analgesic effectiveness of regional anaesthesia techniques for anterior cruciate ligament reconstruction.

Anterior cruciate ligament reconstruction can cause moderate to severe acute postoperative pain. Despite advances in our understanding of knee innervation, consensus regarding the most effective regional anaesthesia techniques for this surgical population is lacking. This network meta-analysis compared effectiveness of regional anaesthesia techniques used to provide analgesia for anterior cruciate ligament reconstruction. Randomised trials examining regional anaesthesia techniques for analgesia following anterior cruciate ligament reconstruction were sought. The primary outcome was opioid consumption during the first 24 h postoperatively. Secondary outcomes were: rest pain at 0, 6, 12 and 24 h; area under the curve of pain over 24 h; and opioid-related adverse effects and functional recovery. Network meta-analysis was conducted using a frequentist approach. A total of 57 trials (4069 patients) investigating femoral nerve block, sciatic nerve block, adductor canal block, local anaesthetic infiltration, graft-donor site infiltration and systemic analgesia alone (control) were included. For opioid consumption, all regional anaesthesia techniques were superior to systemic analgesia alone, but differences between regional techniques were not significant. Single-injection femoral nerve block combined with sciatic nerve block had the highest p value probability for reducing postoperative opioid consumption and area under the curve for pain severity over 24 h (78% and 90%, respectively). Continuous femoral nerve block had the highest probability (87%) of reducing opioid-related adverse effects, while local infiltration analgesia had the highest probability (88%) of optimising functional recovery. In contrast, systemic analgesia, local infiltration analgesia and adductor canal block were each poor performers across all analgesic outcomes. Regional anaesthesia techniques that target both the femoral and sciatic nerve distributions, namely a combination of single-injection nerve blocks, provide the most consistent analgesic benefits for anterior cruciate ligament reconstruction compared with all other techniques but will most likely impair postoperative function. Importantly, adductor canal block, local infiltration analgesia and systemic analgesia alone each perform poorly for acute pain management following anterior cruciate ligament reconstruction.

Incidence of persistent postoperative opioid use in patients undergoing ambulatory surgery: a retrospective cohort study.

The opioid crisis remains a major public health concern. In ambulatory surgery, persistent postoperative opioid use is poorly described and temporal trends are unknown. A population-based retrospective cohort study was undertaken in Ontario, Canada using routinely collected administrative data for adults undergoing ambulatory surgery between 1 January 2013 and 31 December 2017. The primary outcome was persistent postoperative opioid use, defined using best-practice methods. Multivariable generalised linear models were used to estimate the association of persistent postoperative opioid use with prognostic factors. Temporal trends in opioid use were examined using monthly time series, adjusting for patient-, surgical- and hospital-level variables. Of 340,013 patients, 44,224 (13.0%, 95%CI 12.9-13.1%) developed persistent postoperative opioid use after surgery. Following multivariable adjustment, the strongest predictors of persistent postoperative opioid use were pre-operative: utilisation of opioids (OR 9.51, 95%CI 8.69-10.39); opioid tolerance (OR 88.22, 95%CI 77.21-100.79); and utilisation of benzodiazepines (OR 13.75, 95%CI 12.89-14.86). The time series model demonstrated a small but significant trend towards decreasing persistent postoperative opioid use over time (adjusted percentage change per year -0.51%, 95%CI -0.83 to -0.19%, p = 0.003). More than 10% of patients who underwent ambulatory surgery experienced persistent postoperative opioid use; however, there was a temporal trend towards a reduction in persistent opioid use after surgery. Future studies are needed that focus on interventions which reduce persistent postoperative opioid use.

Analgesic benefits of the quadratus lumborum block in total hip arthroplasty: a systematic review and meta-analysis.

The quadratus lumborum block (QLB) is reported to reduce pain and improve function following total hip arthroplasty; however, randomised controlled trials evaluating the benefits of adding this block to general or spinal anaesthesia in this population are conflicting. We performed a systematic review seeking randomised controlled trials investigating QLB benefits for total hip arthroplasty, stratifying comparisons regarding the addition of QLB to either general or spinal anaesthesia. The primary outcome was 24-h area under the curve (AUC) pain score. Pain scores were interpreted in the context of a population-specific minimal clinically important difference of 1.86 cm on a 10-cm visual analogue scale, or an AUC pain score of 5.58 cm.h. Secondary outcomes included analgesic consumption, functional recovery and opioid-related side-effects. In all, 18 trials (1318 patients) were included. Adding QLB to general or spinal anaesthesia improved 24-h AUC rest pain scores by a mean difference (95%CI) of -3.56 cm.h (-6.70 to -0.42; p = 0.034) and - 4.19 cm.h (-7.20 to -1.18; p = 0.014), respectively. These improvements failed to reach the pre-determined minimal clinically important difference, as did the reduction in analgesic consumption. Quadratus lumborum block improved functional recovery for general, but not spinal, anaesthesia. Opioid-related side-effects were reduced with QLB regardless of anaesthetic modality. Low-to-moderate quality evidence suggests that the extent to which adding QLB to either general or spinal anaesthesia reduces postoperative pain and opioid consumption after total hip arthroplasty is statistically significant but may be clinically unimportant for most patients. However, adding QLB to general anaesthesia might enhance functional recovery. Taken together, our findings do not support the routine use of QLB as part of multimodal analgesic regimens for total hip arthroplasty.

Regional anaesthesia quality indicators for adult patients undergoing non-cardiac surgery: a systematic review.

Improvement in healthcare delivery depends on the ability to measure outcomes that can direct changes in the system. An overview of quality indicators within the field of regional anaesthesia is lacking. This systematic review aims to synthesise available quality indicators, as per the Donabedian framework, and provide a concise overview of evidence-based quality indicators within regional anaesthesia. A systematic literature search was conducted using the databases MEDLINE, Embase, CINAHL and Cochrane from 2003 to present, and a prespecified search of regional anaesthesia society websites and healthcare quality agencies. The quality indicators relevant to regional anaesthesia were subdivided into peri-operative structure, process and outcome indicators as per the Donabedian framework. The methodological quality of the indicators was determined as per the Oxford Centre for Evidence-Based Medicine's framework. Twenty manuscripts met our inclusion criteria and, in total, 68 unique quality indicators were identified. There were 4 (6%) structure, 12 (18%) process and 52 (76%) outcome indicators. Most of the indicators were related to the safety (57%) and effectiveness (19%) of regional anaesthesia and were general in nature (60%). In addition, most indicators (84%) were based on low levels of evidence. Our study is an important first step towards describing quality indicators for the provision of regional anaesthesia. Future research should focus on the development of structure and process quality indicators and improving the methodological quality and usability of these indicators.

Analgesic benefits and clinical role of the posterior suprascapular nerve block in shoulder surgery: a systematic review, meta-analysis and trial sequential analysis.

The posterior suprascapular nerve block has been proposed as an analgesic alternative for shoulder surgery based on the publication of several comparisons with interscalene block that failed to detect differences in analgesic outcomes. However, quantification of the absolute treatment effect of suprascapular nerve block on its own, in comparison with no block (control), to corroborate the aforementioned conclusions has been lacking. This study examines the absolute analgesic efficacy of suprascapular nerve block compared with control for shoulder surgery. We systematically sought electronic databases for studies comparing suprascapular nerve block with control. The primary outcomes included postoperative 24-h cumulative oral morphine consumption and the difference in area under the curve for 24-h pooled pain scores. Secondary outcomes included the incidence of opioid-related side-effects (postoperative nausea and vomiting) and patient satisfaction. Data were pooled using random-effects modelling. Ten studies (700 patients) were analysed; all studies examined landmark-guided posterior suprascapular nerve block performed in the suprascapular fossa. Suprascapular nerve block was statistically but not clinically superior to control for postoperative 24-h cumulative oral morphine consumption, with a weighted mean difference (99%CI) of 11.41 mg (-21.28 to -1.54; p = 0.003). Suprascapular nerve block was also statistically but not clinically superior to control for area under the curve of pain scores, with a mean difference of 1.01 cm.h. Nonetheless, suprascapular nerve block reduced the odds of postoperative nausea and vomiting and improved patient satisfaction. This review suggests that the landmark-guided posterior suprascapular nerve block does not provide clinically important analgesic benefits for shoulder surgery. Investigation of other interscalene block alternatives is warranted.

Local anaesthetic-induced myotoxicity in regional anaesthesia: a systematic review and empirical analysis.

Recent reports of local-anaesthetic (LA)-induced myotoxicity after peripheral nerve blocks have increased the interest in this less commonly known complication. Basic science evidence investigating LA-induced myotoxicity seems to demonstrate a pattern, but findings from human studies vary. This systematic review summarises the existing myotoxicity evidence and empirically examines its implications. Databases were searched for all in vitro animal and human studies evaluating LA-induced myotoxicity. Studies were stratified by design. Data sought included the model examined, LA used, injury mechanisms, nature of damage, and extent of recovery. For human studies, we also aimed to estimate prevalence and recovery rates. One hundred and fifteen studies, mainly animal and ophthalmic, were included. Myotoxicity risk factors included higher concentrations and prolonged exposure to LA, and use of bupivacaine. Injury mechanisms involved early and late aberrations to cytoplasmic calcium (Ca2+) homeostasis by the sarcoplasmic reticulum Ca2+ ATPase. Incidence in ophthalmic studies was 0.77% (392 of 50 618). Inflammatory changes within a few days after exposure marked the onset of myotoxicity, and myo-degeneration followed within the first week post-exposure. Time to recovery in human muscles ranged between 4 days to 1 yr. None/partial and complete recovery were observed in 61% and 38% of patients, respectively. Across all experimental models, skeletal muscles exposed to LA consistently display myotoxic effects. Evidence is robust in animal and ophthalmic studies, and displays a concerning signal with continuous adductor canal block use in human case reports. Exploring the clinical prevalence, severity, and risk-reducing strategies of myotoxicity should be prioritised.

The mid-point transverse process to pleura (MTP) block: a new end-point for thoracic paravertebral block.

Current descriptions of thoracic paravertebral block techniques require the needle tip to be anterior to the superior costotransverse ligament. We hypothesised that an injection point midway between the posterior border of the transverse process and the pleura would result in spread to the paravertebral space. We completed bilateral injections of 5 ml methylene blue 0.2% midway between the posterior border of the transverse process and the pleura at T2, T4, T6, T8 and T10 in three unembalmed cadavers. The presence of methylene blue dye at the nerve root in the paravertebral space, the corresponding intercostal nerve and sympathetic chain at the level of injection, and at additional levels, was examined. We identified the superior costotransverse ligament, pleural displacement and spread to the erector spinae plane. We describe two case reports using this technique in patients. Our cadaver results and clinical cases demonstrate that, with the exception of cadaver 1, an injection point midway between the posterior border of the transverse process and pleura consistently achieved spread of dye at least to the paravertebral space at the level of injection, and frequently to adjacent levels. This may be a plausible explanation for the landmark technique's inability to reliably achieve a multilevel block. We describe a new ultrasound-guided technique for a single level paravertebral block.

Impact of including regional anaesthesia in enhanced recovery protocols: a scoping review.

Regional anaesthesia (RA) is often included in enhanced recovery protocols (ERPs) as an important component of a bundle of interventions to improve outcomes after surgery. We sought to delineate whether the literature supports the use of RA in this setting with regard to commonly measured outcomes. We further sought to assess whether such improvements would translate into positive impacts on healthcare value as defined by the Institute for Healthcare Improvement Triple Aim. We conducted a scoping review to address our objectives. Studies of ERPs that included RA and reported at least one outcome of interest in comparison to a control group were included. MEDLINE, EMBASE, CENTRAL, CDSR, PROSPERO, and the NHS Economic Evaluation Database were searched up to May 2015. Two reviewers assessed studies and extracted data. Of 695 identified citations, 58 studies were included for analysis. The majority (53%) were in colorectal surgery. Positive impacts of RA on all outcomes were identified; however, value-based outcomes were rarely reported. Where value-based outcomes were reported, RA appears to have a positive impact on global measures of health and function and on economic outcomes. Existing literature supports a positive impact of RA on ERP outcomes, which may be reflected in improved healthcare value. In order to justify the value of RA in ERPs, a future focus on appropriate measures is needed to align research with widely accepted frameworks, such as the Triple Aim.

Pregabalin reduces postoperative opioid consumption and pain for 1 week after hospital discharge, but does not affect function at 6 weeks or 3 months after total hip arthroplasty.

BACKGROUND: This study examined whether a perioperative regimen of pregabalin added to celecoxib improved pain scores and functional outcomes postdischarge up to 3 months after total hip arthroplasty (primary outcome) and acute postoperative pain and adverse effects (secondary outcomes). METHODS: One hundred and eighty-four patients were enrolled in a randomized, double-blind, placebo-controlled study. Two hours before receiving a spinal anaesthetic and undergoing surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either pregabalin 150 mg p.o. or placebo p.o. After surgery, patients received pregabalin 75 mg or placebo twice daily in hospital and for 7 days after discharge. Patients also received celecoxib 200 mg every 12 h for 72 h and morphine i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, 6 weeks, and 3 months after surgery. RESULTS: There was no difference between groups in physical function or incidence and intensity of chronic pain 3 months after total hip arthroplasty. The pregabalin group used less morphine [mean (sd): 39.85 (28.1) mg] than the placebo group [54.01 (31.2) mg] in the first 24 h after surgery (P<0.01). Pain scores were significantly lower in the pregabalin group vs the placebo group on days 1-7 after hospital discharge, and the pregabalin group required less adjunctive opioid medication (Percocet) 1 week after hospital discharge (P<0.05). CONCLUSIONS: Perioperative administration of pregabalin did not improve pain or physical function at 6 weeks or 3 months after total hip arthroplasty. Perioperative administration of pregabalin decreased opioid consumption in hospital and reduced daily pain scores and adjunct opioid consumption for 1 week after discharge.

Perioperative gabapentin reduces 24 h opioid consumption and improves in-hospital rehabilitation but not post-discharge outcomes after total knee arthroplasty with peripheral nerve block.

BACKGROUND: This study was designed to determine whether a 4 day perioperative regimen of gabapentin added to celecoxib improves in-hospital rehabilitation and physical function on postoperative day 4 and 6 weeks and 3 months after total knee arthroplasty (TKA). METHODS: After Research Ethics Board approval and informed consent, 212 patients were enrolled in a randomized, double-blinded, placebo-controlled study. Two hours before surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either gabapentin 600 mg or placebo p.o. Two hours later, patients received femoral, sciatic nerve blocks, and spinal anaesthesia. After operation, patients received gabapentin 200 mg or placebo three times per day (TID) for 4 days. All patients also received celecoxib 200 mg q12 h for 72 h and i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, during hospitalization, on postoperative day 4 (POD4), and 6 weeks and 3 months after surgery. RESULTS: The gabapentin group used less morphine in the first 24 h after surgery [G=38.3 (29.5 mg), P=48.2 (29.4 mg)] (P<0.0125) and had increased knee range of motion compared with the placebo group in-hospital (P<0.05). There were no differences between groups in favour of the gabapentin group for pain or physical function on POD 4 [95% confidence interval (CI): pain: -1.4, 0.5; function: -6.3, 2.0], 6 weeks (95% CI: pain: 0.1, 1.9; function: -0.2, 6.5) or 3 months (95% CI: pain: -0.2, 1.7; function: -2.2, 4.3) after TKA. CONCLUSIONS: In the context of celecoxib, spinal anaesthesia, femoral and sciatic nerve blocks, a dose of gabapentin 600 mg before operation followed by 4 days of gabapentin 200 mg TID decreased postoperative analgesic requirements and improved knee range of motion after TKA. Gabapentin provided no improvement in pain or physical function on POD4 and 6 weeks or 3 months after surgery.

Effects of dexamethasone as a local anaesthetic adjuvant for brachial plexus block: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Brachial plexus nerve blocks (BPBs) have analgesic and opioid sparing benefits for upper extremity surgery. Single-injection techniques are limited by the pharmacological duration and therapeutic index of local anaesthetics (LAs). Continuous catheter techniques, while effective can present management challenges. Off-label use of perineural dexamethasone as an LA adjuvant has been utilized to prolong single-injection techniques. The objectives of this systematic review and meta-analysis are to assess the contemporary literature and quantify the effects of dexamethasone on BPB. METHODS: The authors searched for randomized, placebo-controlled trials that compared BPB performed with LA alone with that performed with LA and perineural dexamethasone. Meta-analysis was performed using a random effects model with subgroup analysis stratified by LA (long vs intermediate). The primary outcome was duration of sensory block or analgesia; the secondary outcomes were motor block duration, opioid consumption, and BPB complications. RESULTS: Nine trials (801 patients) were included with 393 patients receiving dexamethasone (4-10 mg). Dexamethasone prolonged the analgesic duration for long-acting LA from 730 to 1306 min [mean difference 576 min, 95% confidence interval (CI) 522-631] and for intermediate from 168 to 343 min (mean 175, 95% CI 73-277). Motor block was prolonged from 664 to 1102 min (mean 438, 95% CI 89-787). The most recent trial demonstrated equivalent prolongation with perineural or systemic administration of dexamethasone compared with placebo. CONCLUSIONS: Perineural administration of dexamethasone with LA prolongs BPB effects with no observed adverse events. The effects of systemic administration of dexamethasone on BPB must be investigated.