Long-term postoperative opioid use in orthopaedic patients.

BACKGROUND: The prevalence of long-term opioid use after orthopaedic surgery varies from 1.4% to 24% and has mostly been studied with prescription data, making it difficult to estimate the size and impact of the problem. This study aims to assess the prevalence and predictors of long-term postoperative opioid use in a high volume and tertiary orthopaedic centre by using online patient reported measures. METHODS: This Dutch prospective cohort study was conducted among adult patients who underwent any type of orthopaedic surgery from June to August 2021. Six months after surgery patients were invited to complete an online survey on current opioid use and patients' willingness to taper opioids. The demographics, clinical factors and preoperative opioid use were extracted from the patient file. RESULTS: In total, 607 patients (mean age 61.2 years, 63.4% female) completed the survey. Seventy-six patients (12.5%) used opioids 6 months after surgery of which 20 (3.3%) did not use opioids before surgery. The median (Q1-Q3) postoperative daily dose after 6 months was 29.9 mg (10.0-76.1) morphine equivalents. Most of them (88.2%) wanted to taper opioids. Affected body region (OR's: 6.84-12.75) and pre-operative opioid use (OR = 35.33) were significant predictors of long-term opioid use. CONCLUSION: The prevalence of long-term postoperative opioid use was 12.5%; one in thirty patients became a new long-term opioid user. Pre-operative opioid use and affected body region were predictive for long-term opioid use. These findings, together with the observation that long-term opioid users want to taper opioids, emphasize the relevance of prevention, recognition and tapering support in the perioperative setting. LEVEL OF EVIDENCE: Level II. SIGNIFICANCE: Short-term opioid use can unintentionally progress to long-term opioid use. The prevalence of long-term opioid use after orthopaedic surgery varies widely and is mostly prescription-based, making it difficult to estimate the magnitude of the problem. This study assessed long-term postoperative opioid use in a full breadth orthopaedic population using patient reported measures, making conclusions much more robust. The prevalence of long-term postoperative opioid use in this study was 12.5%.

Pharmacokinetics of 400 mg Locally Infiltrated Ropivacaine After Total Knee Arthroplasty Without Perioperative Tourniquet Use.

BACKGROUND AND OBJECTIVES: Local infiltration analgesia (LIA) with ropivacaine for total knee arthroplasty (TKA) is increasingly used. Despite the high doses of ropivacaine, LIA is considered safe, and this perception is sustained by pharmacokinetic data demonstrating that maximum concentrations of ropivacaine stay well below the toxic threshold in plasma. These pharmacokinetic studies all involve TKA procedures with the use of a tourniquet. Recently, performing TKA without the use of a tourniquet is gaining popularity, but no pharmacokinetic data exist when LIA is administered for TKA without the use of a tourniquet. The purpose of this study was to describe the pharmacokinetic profile of a single-shot ropivacaine (200 mL 0.2%) and 0.75 mg epinephrine (1000 µg/mL) when used for LIA in patients for TKA without a tourniquet. METHODS: In this prospective cohort study, 20 patients treated with LIA for TKA without a tourniquet were studied. Plasma samples were taken at 20, 40, 60, 90, 120, 240, 360, 480, 600, 720, and 1440 minutes after local anesthetic infiltration, in which total and unbound ropivacaine concentrations were determined. RESULTS: Results are given as median (interquartile range [IQR]). Median peak ropivacaine concentration was 1.16 µg/mL (IQR, 0.46); median peak unbound ropivacaine concentration was 0.05 µg/mL (IQR, 0.02). The corresponding times to reach the maximum concentration for total and unbound ropivacaine were 360 (IQR, 240) and 360 (IQR, 360) minutes, respectively. CONCLUSIONS: Although great interindividual variability in ropivacaine concentration was found, both total and unbound maximum serum concentrations remained below the assumed systemic toxic thresholds in all samples. CLINICAL TRIAL REGISTRATION: This study was registered at Netherlands Trial Registry (http://www.trialregister.nl), trial ID NTR6306.

Effect of local anesthetic concentration, dose and volume on the duration of single-injection ultrasound-guided axillary brachial plexus block with mepivacaine: a randomized controlled trial.

BACKGROUND: In what way volume, concentration and dose affect block duration is controversial. The purpose of the present study is to investigate the effect of dose, volume and concentration of mepivacaine on the duration of sensory and motor blockade in ultrasound-guided single shot axillary brachial plexus blockade. METHODS: In this parallel group randomized trial conducted in the Sint Maartenskliniek Nijmegen, 45 adult patients undergoing minor orthopaedic forearm, wrist or hand surgery were randomized to 3 groups. Group A: 20 mL mepivacaine 1.5 %, Group B: 30 mL mepivacaine 1 % and Group C: 30 mL mepivacaine 1.5 %. Randomization was computer-generated, with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and observers were blinded to group allocation. PRIMARY OUTCOME MEASURE: duration of sensory block. RESULTS: Forty-five patients were randomized, four patients were excluded and replaced, and 15 patients in each group were included in the analysis. Mean (95 % CI) sensory and motor block duration was 256 (230-282) and 254 (226-282) minutes in Group A, 226 (209-243) and 220 (200-240) minutes in Group B and 270 (249-291) and 264 (244-284) minutes in Group C. Duration of sensory and motor block duration differed significantly between groups (p = 0.012 and p = 0.016 respectively). Post-hoc analysis showed a significantly reduced sensory and motor block duration in Group B when compared to Group C of 44 min. No local anesthetic systemic toxicity was reported. CONCLUSIONS: When using mepivacaine for axillary brachial plexus block, a higher dose and concentration was associated with a longer duration of sensory and motor blockade, but not a higher volume. TRIAL REGISTRATION: The Netherlands National Trial Register NTR3648 . Registered October 3, 2012.

The effects of adding epinephrine to ropivacaine for popliteal nerve block on the duration of postoperative analgesia: a randomized controlled trial.

BACKGROUND: Duration of peripheral nerve blocks depends on multiple factors. Both technique and type of local anesthetic used, either with or without adjuncts, may result in different duration times of the block. The purpose of the present study was to compare the duration of postoperative analgesia of 30 mL ropivacaine 0.75 % with or without epinephrine for popliteal sciatic nerve block. METHODS: Thirty-eight patients were included to receive ultrasound guided continuous popliteal nerve block with ropivacaine 0.75 % either without (ROPI) or with epinephrine 5 µg/mL (ROPI-EPI) for ankle fusion, subtalar fusion, or a combination of both. The primary outcome parameter was the duration of postoperative analgesia as reflected by the time to first request for postoperative analgesia (TTFR) through the popliteal nerve catheter. Secondary outcome measures included the onset of sensory and motor block and NRS score for pain at rest and during movement. RESULTS: Thirty patients, 15 in each group, were studied. Eight patients were withdrawn because of specific withdrawal criteria described in the protocol and replaced according to their group allocation. Median [interquartile range] TTFR was 463 [300-1197] min and 830 [397-1128] min for the ROPI vs ROPI-EPI group respectively. Hodges Lehman median difference between groups was 71 min (95 % CI -415 - 473 min). There was no difference in any clinical outcome measure between the groups. CONCLUSION: The results of this study did not show any significant increase in the duration of postoperative analgesia by adding epinephrine to ropivacaine for popliteal nerve block. This may be due to the intrinsic vasoconstrictive properties of ropivacaine. The absence of a significant difference can also be the result of a type II error caused by a large variation in the individual TTFR. TRIAL REGISTRATION: Trial register.nl identifier: NTR3330 , keyword TTFR.

Cell-type-specific downregulation of heme oxygenase-1 by lipopolysaccharide via Bach1 in primary human mononuclear cells.

Heme oxygenase (HO)-1 is the inducible isoform of the heme-degrading enzyme HO, which is upregulated by multiple stress stimuli. HO-1 has major immunomodulatory and anti-inflammatory effects via its cell-type-specific functions in mononuclear cells. Contradictory findings have been reported on HO-1 regulation by the Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS) in these cells. Therefore, we reinvestigated the effects of LPS on HO-1 gene expression in human and murine mononuclear cells in vitro and in vivo. Remarkably, LPS downregulated HO-1 in primary human peripheral blood mononuclear cells (PBMCs), CD14(+) monocytes, macrophages, dendritic cells, and granulocytes, but upregulated this enzyme in primary murine macrophages and human monocytic leukemia cell lines. Furthermore, experiments with human CD14(+) monocytes revealed that activation of other TLRs including TLR1, -2, -5, -6, -8, and -9 decreased HO-1 mRNA expression. LPS-dependent downregulation of HO-1 was specific, because expression of cyclooxygenase-2, NADP(H)-quinone oxidoreductase-1, and peroxiredoxin-1 was increased under the same experimental conditions. Notably, LPS upregulated expression of Bach1, a critical transcriptional repressor of HO-1. Moreover, knockdown of this nuclear factor enhanced basal and LPS-dependent HO-1 expression in mononuclear cells. Finally, downregulation of HO-1 in response to LPS was confirmed in PBMCs from human individuals subjected to experimental endotoxemia. In conclusion, LPS downregulates HO-1 expression in primary human mononuclear cells via a Bach1-mediated pathway. As LPS-dependent HO-1 regulation is cell-type- and species-specific, experimental findings in cell lines and animal models need careful interpretation.