Tramadol-paracetamol for postoperative pain after spine surgery - A randomized, double-blind, placebo-controlled study.

OBJECTIVES: Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative pain and pain outcome at 12 months after spine surgery in randomized, double-blind, placebo-controlled trial. METHODS: We randomized 120 patients undergoing spine surgery to receive, for add-on pain management, two tramadol-paracetamol 37.5 mg/325 mg (n = 61) or placebo tablets (n = 59) twice a day for 5 postoperative days. In the hospital, multimodal pain management consisted of dexketoprofen and oxycodone. After discharge, patients were prescribed ibuprofen 200 mg, maximum 1,200 mg/day. Pain, analgesic use, and satisfaction with pain medication were followed up with the Brief Pain Inventory questionnaire before surgery and at 1 and 52 weeks after surgery. The primary outcome was patients' satisfaction with pain medication 1 week after surgery. RESULTS: At 1 week after surgery, patients' satisfaction with pain medication was similarly high in the two groups, 75% [interquartile range, 30%] in the placebo group and 70% [40%] in the tramadol-paracetamol group (p = 0.949) on a scale: 0% = not satisfied, 100% = totally satisfied. At 1 week, ibuprofen dose was lower in the placebo group 200 mg [1,000] compared to the tramadol-paracetamol group, 800 mg [1,600] (p = 0.016). There was no difference in the need for rescue oxycodone. Patients in the tramadol-paracetamol group had more adverse events associated with analgesics during the first postoperative week (relative risk = 1.8, 95% confidence interval, 1.2-2.6). CONCLUSION: Add-on pain treatment with tramadol-paracetamol did not enhance patients' satisfaction with early pain management after back surgery.

Pharmacological prevention and treatment of opioid-induced constipation in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients. METHODS: A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed. RESULTS: Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I2 = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I2 = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I2 = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I2 = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates. CONCLUSIONS: Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.

Chronic Pain Management in a CYP2D6 Poor Metabolizer: A Case Report for Oxycodone.

The objective of this case report is to illustrate pharmacogenomics (PGx)-guided oxycodone treatment, given the conflicting data on the analgesic response from oxycodone in Cytochrome P450 (CYP)2D6 poor metabolizers (PMs). PGx-guided therapy can help improve treatment outcomes. This case report describes a 58-year-old patient who was prescribed oxycodone for chronic pain management. The patient presented with a history of inadequate pain control despite analgesic treatment with oxycodone (morphine milliequivalent [MME] = 22.5). Pharmacogenetic testing revealed that the patient was a CYP2D6 Poor Metabolizer (PM), which may shed light on the observed lack of analgesic response to oxycodone. The clinical pharmacist recommended switching to an alternative opioid not metabolized via the CYP2D6 pathway. The patient was subsequently switched to hydromorphone (MME = 16), resulting in improved pain control and fewer side effects. The newer hydromorphone dose accounted for a 30% MME dose reduction. The patient's initial average and worst pain score were 7 and 9 out of 10, respectively, per the numeric rating scale (NRS). Upon follow-up with the patient in two weeks, her average and worst pain scores improved to 3 and 3.5 out of 10, respectively, per the NRS. Further PGx testing results led to an overall positive outcome, such as her willingness to participate in physical therapy as a result of improved pain scores. This case highlights the importance of considering individual variability in drug metabolism when prescribing medications, particularly opioids such as oxycodone, to ensure optimal therapeutic outcomes and minimize the risk of adverse events in CYP2D6 PMs.

Analgesic effect of the ultrasound-guided thoracolumbar paravertebral block in patients undergoing robot-assisted laparoscopic nephrectomy: a randomized controlled trial.

BACKGROUND: Paravertebral block has similar effect as epidural anesthesia, and has good somatic and visceral analgesic effect. Paravertebral block is widely used in thoracic surgery, but rarely used in abdominal surgery. AIMS: This study aimed to evaluate the analgesic effect of thoracolumbar paravertebral block in patients undergoing robot-assisted laparoscopic nephrectomy. METHODS: One hundred patients undergoing elective robot-assisted laparoscopic nephrectomy were included in this study. Based on whether the thoracolumbar paravertebral block was performed, the patients were randomly divided into the thoracolumbar paravertebral block combined with general anesthesia group (TL-PVB group) and simple general anesthesia group (NO-PVB group). Oxycodone was administered for patient-controlled intravenous analgesia (PCIA). The primary outcomes included the amount of remifentanil used during surgery, the amount of oxycodone used in 24 and 48 h after surgery. Secondary outcomes included the changes of heart rate (HR) and mean arterial pressure (MAP), time for the first analgesia administration, visual analog score (VAS) of pain during rest and movement, and time of postoperative recovery. RESULTS: Compared to the NO-PVB group, the amount of remifentanil used during surgery in patients with TL-PVB group was significantly reduced (1.78 ± 0.37 mg vs. 3.09 ± 0.48 mg, p < 0.001), the amount of oxycodone used 24 h after surgery was significantly reduced (8.70 ± 1.70 mg vs. 13.79 ± 2.74 mg, p < 0.001), and the amount of oxycodone used 48 h after surgery was remarkably reduced (21.83 ± 4.28 mg vs. 27.27 ± 4.76 mg, p < 0.001). There were significant differences in the changes of HR and MAP between the two groups (p < 0.001). The first analgesic requirement time of TL-PVB group was significantly longer than that of NO-PVB group (468.56 ± 169.60 min vs. 113.48 ± 37.26 min, p < 0.001). The postoperative VAS during rest and movement of TL-PVB group were significantly lower than that of NO-PVB group (p < 0.01). Compared with NO-PVB group, patients in TL-PVB group needed shorter time to awaken from anesthesia, leave the operating room, anal exhaust, get out of bed, and had shorter length of postoperative hospital stay (p < 0.001). The incidence of postoperative adverse reactions were lower in the TL-PVB group than that in the NO-PVB group (p < 0.05). CONCLUSIONS: Ultrasound-guided thoracolumbar paravertebral block significantly reduces intraoperative and postoperative opioid consumption, and provides better analgesia in patients undergoing robot-assisted laparoscopic nephrectomy, which is a recommendable combined anesthesia technique. TRIAL REGISTRATION: ChiCTR2200061326, 21/06/2022.

Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.

OBJECTIVE: This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. METHODS: A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. RESULTS: A total of 40 276 tramadol, 141 023 hydrocodone, and 45 221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. CONCLUSION: Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.

Perceptions in orthopedic surgery on the use of cannabis in treating pain: a survey of patients with spine pain (POSIT Spine).

BACKGROUND: Back pain is the leading cause of disability worldwide. Despite guidelines discouraging opioids as first-line treatment, opioids remain the most prescribed drugs for back pain. There is renewed interest in exploring the potential medical applications of cannabis, and with the recent changes in national legislation there is a unique opportunity to investigate the analgesic properties of cannabis. METHODS: This was a multi-center survey-based study examining patient perceptions regarding cannabis for spine pain. We included patients presenting with back or neck pain to one of three Orthopedic clinics in Ontario. Our primary outcome was perceived effect of cannabis on back pain, while secondary outcomes were perceptions regarding potential applications and barriers to cannabis use. RESULTS: 259 patients participated in this study, 35.3% (90/255) stating they used cannabis medically. Average pain severity was 6.5/10 ± 0.3 (95% CI 6.2-6.8). Nearly three-quarters were prescribed opioids (73.6%, 148/201), with oxycodone/oxycontin (45.9% 68/148) being the most common, and almost half of (49.3%, 73/148) had used an opioid in the last week. Patients estimated cannabis could treat 54.3% ± 4.0 (95% CI 50.3-58.3%) of their spine pain and replace 46.2% ± 6. 6 (95% CI 39.6-52.8%) of their current analgesics. Age (ß = - 0.3, CI - 0.6-0.0), higher pain severity (ß = 0.4, CI 0.1-0.6) and previous cannabis use (ß = 14.7, CI 5.1-24.4) were associated with a higher perceived effect of cannabis. Patients thought cannabis would be beneficial to treat pain (129/146, 88.4%), and reduce (116/146, 79.5%) or eliminate opioids (102/146, 69.9%). Not considering using cannabis for medical purposes (65/150, 43.3%) was the number one reported barrier. CONCLUSIONS: Patients estimated medical cannabis could treat more than half of their spine pain, with one in three patients already using medical cannabis. 79% of patients also believe cannabis could reduce opioid usage. This data will help support more research into cannabis for musculoskeletal pain.

Private prescribing of controlled opioids in England, 2014-2021: a retrospective observational study.

BACKGROUND: Trends in NHS opioid prescribing have been well published, yet trends in private prescribing of opioids have not been widely established. AIM: To assess trends and geographical variation in controlled opioids prescribed by private prescribers in England. DESIGN AND SETTING: This was a retrospective observational study in English primary health care. METHOD: Data on Schedule 2 and 3 controlled opioids ('controlled opioids') were obtained from the NHS Business Services Authority (BSA) using Freedom of Information (FOI) requests between 1 January 2014 and 30 November 2021. Absolute counts and rates of the number of items dispensed per cumulative number of registered private prescribers were calculated and stratified over time, by opioid type, and geographical region. RESULTS: This study found that 128 341 items of controlled opioids were prescribed by private prescribers in England between January 2014 and November 2021, which decreased by 50% from 23 339 items (4.09 items/prescriber) in 2014 to 11 573 items (1.49 items/prescriber) in 2020. Methadone (36%, n = 46 660) was the most common controlled opioid prescribed privately, followed by morphine (18%, n = 22 543), buprenorphine (16%, n = 20 521), and oxycodone (12%, n = 15 319). Prescriptions were highest in London (74%, n = 94 438), followed by the South-East of England (7%, n = 9237). A proportion of items (n = 462; 0.36%) were prescribed by 'unidentified doctors' where the prescription is not readily attributable to an individual prescriber by the BSA. CONCLUSION: Controlled opioids prescribed by private prescribers in England decreased and were primarily prescribed in London. To ensure patient safety, the monitoring and surveillance of controlled opioids dispensed privately should continue and items linked to 'unidentified doctors' should be addressed further.

Comparison of the Effects of OPRM1 A118G Polymorphism Using Different Opioids: A Prospective Study.

CONTEXT: µ-opioid receptor gene (OPRM1) A118G polymorphism (rs1799971) causes loss of N-glycosylation sites at the extracellular domain of µ-opioid receptors. G-allele carriers show a limited response to morphine; however, studies investigating the impact of A118G polymorphism on the efficacy of opioids other than morphine are limited. OBJECTIVE: To compare the impact of A118G polymorphism on the efficacy of various opioids. METHODS: This prospective cohort study enrolled 222 in-patients administered one of the following opioid therapies for cancer pain as part of an opioid introduction or rotation strategy: tapentadol extended-release tablets, methadone tablets, hydromorphone controlled-release tablets, oxycodone controlled-release tablets, or transdermal fentanyl patches. The impact of A118G polymorphism on the difference in the Brief Pain Inventory-Short Form score on days three, seven, and 14 from baseline was compared among the groups. RESULTS: Overall, 81, 74, and 67 patients had the AA, AG, and GG genotypes, respectively, with an OPRM1 A118G G-allele variant frequency of 0.47. The reduction in the Brief Pain Inventory-Short Form score after opioid therapy initiation did not differ significantly among the patients with the three A118G genotypes treated with tapentadol (p = 0.84) or methadone (p = 0.97), whereas it was significantly smaller in G-allele carriers than that in AA homozygous patients treated with hydromorphone (p < 0.001), oxycodone (p = 0.031), or fentanyl (p < 0.001). CONCLUSION: Tapentadol and methadone may be more suitable than hydromorphone, oxycodone, and fentanyl for G-allele carriers due to their dual mechanism of action and low susceptibility to OPRM1 A118G polymorphism.

Reducing Pediatric Posttonsillectomy Opioid Prescribing: A Quality Improvement Initiative.

OBJECTIVE: Postoperative pain is the most common morbidity associated with tonsillectomy. Opioids are frequently used in multimodal posttonsillectomy analgesia regimens; however, concerns regarding respiratory depression, drug-drug interactions, and medication misuse necessitate responsible opioid stewardship among prescribing surgeons. It is unclear if intentionally reducing opioid prescription doses negatively affects the patient experience. METHODS: A quality improvement team reviewed all posttonsillectomy opioid prescriptions at a pediatric ambulatory surgery center between January and June 2021 (preintervention, 163 patients). Following this review, we performed an opioid education session for surgeons and studied opioid prescribing habits between July and December 2021 (Plan-Do-Study-Act [PDSA] 1, 152 patients). We then implemented a standardized prescription protocol of 7 doses of oxycodone per patient and again reviewed prescriptions between January and June 2022 (PDSA 2, 178 patients). The following measures were evaluated: initial number of opioid doses prescribed, need for refills, 7-day emergency department (ED) visits, and readmissions. RESULTS: Each intervention reduced the average number of initial oxycodone doses per patient (12.2 vs 9.2 vs 6.9 doses, P < .001). There were no changes in the rate of refill requests, 7-day ED visits, and readmissions, by descriptive or Statistical Process Control analyses. DISCUSSION: In 2 PDSA cycles, we achieved a 43% reduction in the number of doses of oxycodone prescribed following tonsillectomy. We did not observe any increased rates in balancing measures, which are surrogates for unintentional effects of PDSA changes, including refills, ED presentations, and readmission rates. IMPLICATIONS FOR PRACTICE: Directed provider education and standardized posttonsillectomy prescription protocols can safely decrease postoperative opioid prescribing. Further PDSA cycles are required to consider even fewer opioid prescription doses.

Randomized Trial on Expectations and Pain Control Advancement in Surgery: The REPAIR Study.

IMPORTANCE: Following standardized preoperative education and adoption of shared decision making positively affects postoperative narcotic practices. OBJECTIVES: The aim of this study was to assess the impact of patient-centered preoperative education and shared decision making on the quantities of postoperative narcotics prescribed and consumed after urogynecologic surgery. STUDY DESIGN: Women undergoing urogynecologic surgery were randomized to "standard" (standard preoperative education, standard narcotic quantities at discharge) or "patient-centered" (patient-informed preoperative education, choice of narcotic quantities at discharge) groups. At discharge, the "standard" group received 30 (major surgery) or 12 (minor surgery) pills of 5-mg oxycodone. The "patient-centered" group chose 0 to 30 (major surgery) or 0 to 12 (minor surgery) pills. Outcomes included postoperative narcotics consumed and unused. Other outcomes included patient satisfaction/preparedness, return to activity, and pain interference. An intention-to-treat analysis was performed. RESULTS: The study enrolled 174 women; 154 were randomized and completed the major outcomes of interest (78 in the standard group, 76 in the patient-centered group). Narcotic consumption did not differ between groups (standard group: median of 3.5 pills, interquartile range [IQR] of [0, 8.25]; patient centered: median of 2, IQR of [0, 9.75]; P = 0.627). The patient-centered group had fewer narcotics prescribed ( P < 0.001) and unused ( P < 0.001), and chose a median of 20 pills (IQR [10, 30]) after a major surgical procedure and 12 pills (IQR [6, 12]) after a minor surgical procedure, with fewer unused narcotics (median difference, 9 pills; 95% confidence interval, 5-13; P < 0.001). There were no differences between groups' return to function, pain interference, and preparedness or satisfaction ( P > 0.05). CONCLUSIONS: Patient-centered education did not decrease narcotic consumption. Shared decision making did decrease prescribed and unused narcotics. Shared decision making in narcotic prescribing is feasible and may improve postoperative prescribing practices.

Cancer-related breathlessness: opioids other than morphine - comprehensive literature review.

INTRODUCTION: Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using opioids other than morphine. METHODS: The author conducted a non-systematic literature review in the PubMed/Medline and Embase until 4 October 2022. Eligible studies have evaluated the efficacy of opioids other than morphine for cancer-related breathlessness. Studies focused on sedation, anaesthesia, paediatric patients, opioid toxicity or basic research were excluded. Reviews/meta-analyses and non-English language publications were also excluded. RESULTS: A total of 1556 records were identified, of which 23 studies including 469 patients who were treated with fentanyl (n=223), oxycodone (n=171) and hydromorphone (n=75) were considered eligible. Six phase II randomised clinical trials (RCTs), four observational studies and four case reports of fentanyl were found. For breathlessness on exertion, fentanyl yielded promising results, but no RCT showed significant superiority of fentanyl to placebo or morphine. For terminal breathlessness, three RCTs, five non-randomised or observational studies and one case report on oxycodone or hydromorphone were found. Although the results of the observational studies suggested that oxycodone and hydromorphone might be effective alternatives to morphine, the superiority over placebo or non-inferiority to morphine had not been demonstrated in the RCTs. CONCLUSION: As an alternative to morphine, the author recommends fentanyl for breathless crisis or breathlessness on exertion, and oxycodone or hydromorphone for terminal breathlessness in advanced cancer. Larger and well-designed studies based on firm research policies are needed to confirm this current knowledge.

Restrictive opioid prescribing after surgery for prolapse and incontinence: a randomized, noninferiority trial.

BACKGROUND: Opioids are routinely prescribed for postoperative pain control after gynecologic surgery with growing evidence showing that most prescribed opioids go unused. Restrictive opioid prescribing has been implemented in other surgical specialties to combat the risk for opioid misuse and diversion. The impact of this practice in the urogynecologic patient population is unknown. OBJECTIVE: This study aimed to determine if a restrictive opioid prescription protocol is noninferior to routine opioid prescribing in terms of patient satisfaction with pain control after minor and major surgeries for prolapse and incontinence. STUDY DESIGN: This was a single-center, randomized, noninferiority trial of opioid-naïve patients who underwent minor (eg, colporrhaphy or mid-urethral sling) or major (eg, vaginal or minimally invasive abdominal prolapse repair) urogynecologic surgery. Patients were excluded if they had contraindications to all multimodal analgesia and if they scored ≥30 on the Pain Catastrophizing Scale. Subjects were randomized on the day of surgery to the standard opioid prescription protocol (wherein patients routinely received an opioid prescription upon discharge [ie, 3-10 tablets of 5 mg oxycodone]) or to the restrictive protocol (no opioid prescription unless the patient requested one). All patients received multimodal pain medications. Participants and caregivers were not blinded. Subjects were asked to record their pain medication use and pain levels for 7 days. The primary outcome was satisfaction with pain control reported at the 6-week postoperative visit. We hypothesized that patient satisfaction with the restrictive protocol would be noninferior to those randomized to the standard protocol. The noninferiority margin was 15 percentage points. Pain level scores, opioid usage, opioid prescription refills, and healthcare use were secondary outcomes assessed for superiority. RESULTS: A total of 133 patients were randomized, and 127 (64 in the standard arm and 63 in the restrictive arm) completed the primary outcome evaluation and were included in the analysis. There were no statistically significant differences between the study groups, and this remained after adjusting for the surgery type. Major urogynecologic surgery was performed in 73.6% of the study population, and minor surgery was performed in 26.4% of the population. Same-day discharge occurred for 87.6% of all subjects. Patient satisfaction was 92.2% in the standard protocol arm and 92.1% in the restrictive protocol arm (difference, -0.1%; P=.004), which met the criterion for noninferiority. No opioid usage in the first 7 days after hospital discharge was reported by 48.4% of the patients in the standard protocol arm and by 70.8% in the restrictive protocol arm (P=.009). Opioid prescription refills occurred in 8.5% of patients with no difference between the study groups (9.4% in the standard arm vs 6.7% in the restrictive arm; P=.661). No difference was seen in the rate of telephone calls and urgent visits for pain control between the study arms. CONCLUSION: Among women who underwent minor and major surgery for prolapse and incontinence, patient satisfaction rates were noninferior after restrictive opioid prescribing when compared with routine opioid prescribing.

An ultrasound-guided serratus anterior plane block with continuous local anaesthetic infusion and epidural analgesia for rib fracture pain.

BACKGROUND: We compared analgesia with an ultrasound (US)-guided serratus anterior plane block (SAPB) to thoracic epidural analgesia (EA) with continuous local anaesthetic infusion in patients with unilateral multiple traumatic rib fractures. EA often carries contraindications in patients with multiple rib fractures (MRFs), whereby having alternative effective methods to treat rib fracture pain remains important to patient care. Thus, we hypothesised that both regional anaesthetic techniques would provide effective pain relief. METHODS: In this study, we included 59 patients with unilateral MRFs and a numerical rating scale (NRS) pain score ≥4 at rest or upon movement. Patients were randomised to receive a US-guided SAPB or continuous infusion EA with 2 mg/mL ropivacaine. Patients were given a patient-controlled analgesia (PCA) device with intravenous oxycodone boluses for rescue medication. The primary outcome was a change in the NRS score at rest and upon movement from baseline to Day 2 following the block. We also measured the forced expiratory volume in 1 s of expiration (FEV1) and FEV1% at the same time points when NRS was measured. The total consumption of oxycodone with PCA was measured at 24 and 48 h after the block. RESULTS: We detected a significant reduction (≥2) in NRS for both groups; however, EA associated with a greater reduction in NRS upon movement after block initiation. The mean reduction in NRS upon movement within 1 h was 3 (1.8, p < .01) in the SAPB group versus 4.7 (2.4, p < .01) in the EA group. We found no significant difference between groups in pain scores on Days 1 and 2 following the block. In the EA group, FEV1% increase in the first 12 h from baseline. Finally, PCA oxycodone consumption did not differ between groups. CONCLUSIONS: SAPB with continuous local anaesthetic infusion is an effective alternative to treat rib fracture pain when EA is contraindicated. We found that SABP significantly reduces pain in patients with unilateral MRFs, although EA achieves better analgesia over the first 12 h following the block.

Continuous lumbar erector spinae plane block as an alternative to epidural analgesia in pain treatment in patients undergoing hip replacement surgery - a prospective pilot study.

INTRODUCTION: Postoperative pain associated with hip replacement surgery can be severe, decreasing the patient's mobility and satisfaction with perioperative treatment. Regional techniques are commonly used as postoperative analgesia in hip surgery patients. MATERIAL AND METHODS: We performed a prospective pilot study on patients undergoing hip replacement surgery. We anesthetized each participant with spinal technique and allocated patients according to postoperative analgesia to the continuous epidural group and the continuous lumbar erector spinae plane block (ESPB) group. We measured postope-rative oxycodone consumption with patient-controlled analgesia (PCA) demands. At several points, we evaluated the patients' pain at rest and during activity on the visual analog scale (VAS, 0-10), their quadriceps femoris' muscle strength on the Lovett scale (0-5), and their ability to sit, stand upright, and walk on the Timed Up and Go test. Moreover, we assessed the patients' recovery through the Quality of Recovery 40 (QoR-40) questionnaire on the first postoperative day. RESULTS: We found lower oxycodone consumption via PCA in the epidural than in the ESPB group (9.1 (mean) mg (5.2-13.0) (confidence interval) vs. 15.5 mg (9.8-21.3), P = 0.049). Patients in the ESPB group had more demands with PCA than participants in the epidural group (10.5 (median) (6-16) (interquartile range) vs. 25 (16-51), P = 0.016). We did not find differences between the groups in the other outcomes or in terms of postoperative complications. CONCLUSIONS: The results suggest that the continuous lumbar ESPB group is equivalent to epidural analgesia as a pain treatment technique in patients undergoing hip replacement surgery.

Opioid Analgesia Compared with Non-Opioid Analgesia After Operative Treatment for Pediatric Supracondylar Humeral Fractures: Results from a Prospective Multicenter Trial.

BACKGROUND: Minimal pain and opioid use after operative treatment for pediatric supracondylar humeral fractures have been previously described; however, opioid-prescribing practices in the United States remain variable. We hypothesized that children without an opioid prescription would report similar postoperative pain compared with children prescribed opioids following closed reduction and percutaneous pinning (CRPP) of supracondylar humeral fractures. METHODS: Children who were 3 to 12 years of age and were undergoing CRPP for a closed supracondylar humeral fracture were prospectively enrolled in a multicenter, comparative study. Following a standardized dosing protocol, oxycodone, ibuprofen, and acetaminophen were prescribed at 2 hospitals (opioid cohort), and 2 other hospitals prescribed ibuprofen and acetaminophen alone (non-opioid cohort). The children's medication use and the daily pain that they experienced (scored on the Wong-Baker FACES Scale) were recorded at postoperative days 1 to 7, 10, 14, and 21, using validated text-message protocols. Based on an a priori power analysis, at least 64 evaluable subjects were recruited per cohort. RESULTS: A total of 157 patients were evaluated (81 [52%] in the opioid cohort and 76 [48%] in the non-opioid cohort). The median age at the time of the surgical procedure was 6.2 years, and 50% of the subjects were male. The mean postoperative pain scores were low overall (<4 of 10), and there were no significant differences in pain ratings between cohorts at any time point. No patient demographic or injury characteristics were correlated with increased pain or medication use. Notably, of the 81 patients in the opioid cohort, 28 (35%) took no oxycodone and 40 (49%) took 1 to 3 total doses across the postoperative period. Patients rarely took opioids after postoperative day 2. A single patient in the non-opioid cohort (1 [1%] of 76) received a rescue prescription of opioids after presenting to the emergency department with postoperative cast discomfort. CONCLUSIONS: Non-opioid analgesia following CRPP for pediatric supracondylar humeral fractures was equally effective as opioid analgesia. When oxycodone was prescribed, 84% of children took 0 to 3 total doses, and opioid use fell precipitously after postoperative day 2. To improve opioid stewardship, providers and institutions can consider discontinuing the routine prescription of opioids following this procedure. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Effect of oxycodone combined with ultrasound-guided thoracic paravertebral nerve block on postoperative analgesia in patients with lung cancer undergoing thoracoscopic surgery: protocol for a randomised controlled study.

INTRODUCTION: Postoperative pain is a main component influencing the recovery of patients with lung cancer. The combination of patient-controlled intravenous analgesia (PCIA) and paravertebral nerve block for postoperative analgesia in patients undergoing thoracoscopic lobectomy for lung cancer can achieve a satisfactory analgesic effect and promote early rehabilitation of patients. The objective is to investigate the optimal dose of oxycodone for PCIA combined with paravertebral nerve block, to achieve effective multimodal analgesia management in patients undergoing thoracoscopic lung cancer lobectomy. METHODS AND ANALYSIS: This prospective, double-blind, single-centre, parallel-group, superiority study from 7 April 2023 to 31 December 2024 will include 160 participants scheduled for thoracoscopic lobectomy for lung cancer. Participants will be randomly assigned to four groups in a 1:1:1:1 ratio: OCA group (oxycodone: 0.5 mg/kg), OCB group (oxycodone: 1.0 mg/kg), OCC group (oxycodone: 1.5 mg/kg) and one sufentanil group (sufentanil: 2 µg/kg). Flurbiprofen 50 mg and ondansetron 16 mg are added to each group. All the drugs are diluted with 0.9% saline in a 100 mL volume, with a background infusion rate of 2 mL/hour, a bolus dose of 0.5 mL and a lockout interval of 15 min. The primary outcome is pain scores at rest and dynamic at 24 hours after surgery using a Numeric Rating Scale (NRS). Dynamic NRS scores are defined as NRS when coughing. NRS scores will be assessed at 2, 4, 12, 24 and 48 hours postoperatively. The secondary outcomes include the following variables: (1) NRS score at rest and dynamic at 2, 4, 12 and 48 hours postoperatively; (2) total dose of sufentanil or oxycodone consumption in PCIA; (3) the times of patient-controlled analgesia; (4) Ramsay Sedation Score (RSS) at 2, 4, 12, 24 and 48 hours after the surgery; (5) extubation time; (6) serum C-reactive protein and interleukin six levels; (7) incidence of postoperative nausea and vomiting; (8) incidence of itching; (9) incidence of respiratory depression and (10) gastrointestinal recovery (exhaust time). ETHICS AND DISSEMINATION: The First Affiliated Hospital of Shandong First Medical University's Ethics Committee granted consent for this study (approval number: YXLL-KY-2022(116)). To enable widespread use of the data gathered, we plan to publish the trial's findings in an appropriate scientific journal after it is complete. TRIAL REGISTRATION NUMBER: NCT05742256.

Reported adverse events related to use of hepatitis C virus direct-acting antivirals with opioids: 2017-2021.

INTRODUCTION: Due to concerns over potential interactions between some hepatitis C direct-acting antivirals (DAAs) and opioids, we describe adverse event (AE) reports of concomitant use of opioids and DAAs. METHODS: AEs reported (July 28, 2017-December 31, 2021) with the administration of the DAAs glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir/voxilaprevir, and elbasvir/grazoprevir as suspect products were downloaded from the US Food and Drug Administration AE Reporting System Public Dashboard. The number of AE reports containing opioids (fentanyl, hydrocodone, oxycodone) as co-suspect products/concomitant products were counted and summarized by severity, reporting country and whether an outcome of death was reported. Overdose AEs were counted irrespective of opioid use, and changes over time were assessed. RESULTS: In total, 40 AEs were reported for DAAs and concomitant fentanyl use, 25 (62.5%) were in the USA, 35 (87.5%) were considered serious, and 14 (35.0%) resulted in death; and 626 were reported with concomitant oxycodone/hydrocodone use, 596 (95.2%) were in the USA, 296 (47.3%) were considered serious, and 28 (4.5%) resulted in death. There were 196 overdose AEs (32 [16%] deaths) declining from 2018 (N = 56) to 2021 (N = 29). CONCLUSIONS: Treating people with hepatitis C virus (HCV) infection who use drugs is key to achieving HCV elimination. Low numbers of DAA AE reports with opioids may provide reassurance to prioritize HCV treatment in this population. These data contribute to evidence supporting the continued scale-up of DAA treatment among people who use drugs to achieve HCV elimination goals.

Neonatal Outcomes after Medications for Opioid Use Disorder during Pregnancy in a State Women's Prison Facility, 2016-2019.

OBJECTIVE: Although medications for opioid use disorder improve both maternal and neonatal outcomes, little is known about opioid-exposed infants born during episodes of incarceration. The study sought to examine birth outcomes for infants born with opioid exposure during perinatal incarceration. METHODS: Participants were identified from clinic rosters in a Southeastern women's prison (2016-2019). Included infants born to pregnant people with opioid use disorder incarcerated in the study facility at the time of delivery. We abstracted hospital length of stay, neonatal opioid withdrawal syndrome (NOWS) severity, and discharge plan from hospital records and report descriptive statistics, analysis of variance F tests, and chi-square tests to compare outcomes by opioid exposure type. RESULTS: There were 125 infants born after exposure to methadone (n = 34), buprenorphine (n = 15), oxycodone (n = 22), or no opioid medication (n = 54) during prenatal incarceration. Most infants exposed to methadone or buprenorphine had difficulty with eating, sleeping, or consoling (97% and 80%), and 59% and 47% were treated with medication for NOWS, respectively. The majority with prenatal opioid exposure required intervention for NOWS symptoms after their birthing parent was discharged to the prison. The average hospital length of stay was different for infants with no opioid, methadone, buprenorphine, and oxycodone exposure during incarceration (4, 15, 12, and 9 days, respectively, P < 0.001). CONCLUSIONS: Neonatal hospitalization experiences of infants with perinatal opioid exposures during maternal incarceration mirror those of similarly exposed infants born outside the context of incarceration, except for hospital length of stay. Consideration of avoiding separation of the parent-infant dyad may be needed to improve outcomes for these infants.

The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement.

Despite the thousands of lives lost during the ongoing opioid crisis, a scarcity of new and effective clinical treatments for opioid use disorder (OUD) remains. To address this unmet need, some researchers have turned to dissociative and psychedelic drugs to treat multiple psychiatric conditions. In particular, low doses of ketamine have been shown to attenuate opioid withdrawal and drug use in clinical and preclinical studies. However, ketamine has misuse liability and dissociative side effects that may limit its widespread application as a treatment for OUD. More recently, (2R,6R)-hydroxynorketamine (HNK), a ketamine metabolite that lacks misuse potential, has gained attention for its effectiveness in depression and stress models. To uncover its role in OUD, we tested the time-dependent effects of (2R,6R)-HNK on oxycodone withdrawal and reinstatement of oxycodone conditioned place preference (CPP). In male and female oxycodone-dependent mice, we found that 24h pretreatment with (2R,6R)-HNK (10 or 30mg/kg, s.c.) reduced the frequency of withdrawal-like behaviors and global withdrawal scores during naloxone-precipitated withdrawal, whereas 1h pretreatment with (2R,6R)-HNK only reduced paw tremors and the sum of global withdrawal scores but not GWS Z-scores. In other experiments, both 1h and 24h pretreatment with (2R,6R)-HNK (30mg/kg, s.c.) blocked drug-induced reinstatement of oxycodone CPP. Finally, we found (2R,6R)-HNK (30mg/kg, sc) had no effect on locomotor activity and thigmotaxis. Together, these results indicate that acute (2R,6R)-HNK has efficacy in some preclinical models of OUD without producing locomotor or anxiety-like side effects.