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Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0–24 h and 24–48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

PURPOSE: Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. METHODS: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. RESULTS: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. CONCLUSION: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052085).

Oxycodone is widely used for pain management and acts via binding to mu- and kappa opioid receptors. It was shown that extended oxycodone usage can result from the demyelination and degeneration of neurons through the stress response, which triggers apoptotic signaling pathways. The striatum and cerebellum are recognized as significant contributors to addiction; however, there is no report on the effect of oxycodone on the cerebellum and striatum and motor coordination. We treated rats daily with oxycodone at 15 mg/kg doses for thirty days. Motor performance and electromyography activity were then evaluated. Stereological methods were performed to assess the number of neurons in the cerebellum and striatum as well as immunohistochemistry for microgliosis and astrogliosis. Furthermore, the Sholl analysis method was utilized to evaluate the cellular structure of both microglia and astrocytes. Results of the rotarod test for motor coordination show no significant (P < 0.05) difference between the oxycodone subjects and those in the control group. In addition, open-field assessments indicated that the application of oxycodone did not alter the amount of distance covered (as an indicator of locomotion) or time spent in the central area (as an indicator of anxiety) (P < 0.001). The electromyography (EMG) test result showed that oxycodone caused a delay in the reaction of the muscular nerves (P < 0.001). Data and results from our experiment revealed that administering oxycodone did not affect astrogliosis and the number of neurons in the cerebellum and striatum (P < 0.05). In contrast, it altered neuromuscular function. In addition, oxycodone administration activated microglia in the cerebellum and striatum. In conclusion, we encourage more research on the adverse effects of oxycodone on the brain. [ABSTRACT FROM AUTHOR]

A single-blind, randomized controlled trial comparing oxycodone and fentanyl for patient-controlled intravenous analgesia (PCIA) after laparoscopic hysteromyomectomy found comparable pain relief between the two groups. The study included 60 participants, with NRS scores for pain at rest and when moving showing no significant differences between oxycodone and fentanyl groups at various time points postoperatively. Self-rating depression scale scores were also similar between the groups at 48 h. However, patients' satisfaction with PCIA was higher in the oxycodone group, with 73.3% reporting being very satisfied compared to 36.7% in the fentanyl group. Additionally, the oxycodone group had fewer incidences of headaches within 48 h postoperatively compared to the fentanyl group. These findings suggest that oxycodone may offer comparable pain relief, higher patient satisfaction, and fewer headaches for patients undergoing laparoscopic hysteromyomectomy compared to fentanyl, making it a suitable option for postoperative pain management in this population. Clinical trial registration number The study was registered with CHICTR.org, ChiCTR2100051924. [ABSTRACT FROM AUTHOR]

Myocardial injury and cardiovascular dysfunction are the most common complications of sepsis, and effective therapeutic candidate is still lacking. This study aims to investigate the protective effect of oxycodone in myocardial injury of lipopolysaccharide‐induced sepsis and its related signalling pathways. Wild‐type and nuclear factor erythroid 2‐related factor 2 (Nrf2)‐knockout mice, as well as H9c2 cardiomyocytes cultures treated with lipopolysaccharide (LPS) were used as models of septic myocardial injury. H9c2 cardiomyocytes culture showed that oxycodone protected cells from pyroptosis induced by LPS. Mice model confirmed that oxycodone pretreatment significantly attenuated myocardial pathological damage and improved cardiac function demonstrated by increased ejection fraction (EF) and fractional shortening (FS), as well as decreased cardiac troponin I (cTnI) and creatine kinase isoenzymes MB (CK‐MB). Oxycodone also reduced the levels of inflammatory factors and oxidative stress damage induced by LPS, which involves pyroptosis‐related proteins including: Nod‐like receptor protein 3 (NLRP3), Caspase 1, Apoptosis‐associated speck‐like protein contain a CARD (ASC), and Gasdermin D (GSDMD). These changes were mediated by Nrf2 and heme oxygenase‐1 (HO‐1) because Nrf2‐knockout mice or Nrf2 knockdown in H9c2 cells significantly reversed the beneficial effect of oxycodone on oxidative stress, inflammatory responses and NLRP3‐mediated pyroptosis. Our findings yielded that oxycodone therapy reduces LPS‐induced myocardial injury by suppressing NLRP3‐mediated pyroptosis via the Nrf2/HO‐1 signalling pathway in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Background: Central pain, characterized by neuropathic pain, can manifest due to injury to the superior spinothalamic tract. The brainstem includes sensory and motor pathways as well as nuclei of the cranial nerves, and therefore cancer metastasis in the region requires early intervention. Although stereotactic radiosurgery (SRS) is commonly employed for the treatment of brain metastasis, it poses risks of late complications like radiation necrosis (RN). RN exacerbates the progression of brain lesions within the irradiated area, and in the brainstem, it can damage multiple nerves, including the superior spinothalamic tract. Central neuropathic pain is often intractable and empirically managed with a combination of conventional drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. However, their efficacy is often limited, leading to a decline in performance status (PS) and quality of life (QOL). Case presentation: We present the case of a 53-year-old man diagnosed with stage IV lung cancer, referred to our palliative care team for managing severe central pain resulting from SRS-related RN in the pons. Despite administration of opioids, including oxycodone and hydromorphone, and adjuvant analgesics, the patient continued to require frequent use of immediate-release opioids. The addition of methadone alone proved successful in achieving optimal pain control. Conclusions: Provided that RN in the brainstem can lead to intractable neuropathic pain, it is advisable to avoid SRS for brainstem metastasis when possible. Add-on methadone should be considered as a viable pain management medication for patients experiencing unresolved central pain. [ABSTRACT FROM AUTHOR]

In the United States, illicit fentanyl is often trafficked as blue tablets mimicking the legitimate M‐30 oxycodone tablet produced by Mallinckrodt. The analysis of dyes extracted from seized fentanyl tablets could provide a useful tool for law enforcement to establish linkages between cases and could prove useful for attributing a seizure to a given trafficking organization. Fentanyl tablet seizures associated with a particular drug trafficking organization (DTO), either through investigative or intelligence information, were used as the sample set for this study. The blue dye from the tablets was isolated by solid phase extraction and then qualitatively and quantitatively analyzed via ultraviolet‐visible spectroscopy. This research revealed that the illicit tableting facilities use a different dye than several known pharmaceutical companies. The concentration of dye in individual tablets within a seizure proved to be very minimal, and the small sample size made it difficult to draw linkages from case to case. Analysis of the dyes could not effectively differentiate between the drug trafficking organizations in the tested population due to each DTO using the same dye; however, it is important to note that the dye found was consistent between illicit tablets. [ABSTRACT FROM AUTHOR]

Background: Cancer pain significantly impacts individuals' quality of life, with opioids being employed as the primary means for pain relief. Nevertheless, concerns persist regarding the adverse reactions and effectiveness of opioids such as morphine. Hydromorphone, recognized as a potent opioid, is a viable alternative for managing cancer-related pain. The goal of this systematic review and meta-analysis was to determine the effectiveness and safety characteristics of hydromorphone in comparison to other opioids, as well as different methods of administering this medication within the scope of cancer pain treatment. Methods: The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched on December 25th, 2023. Following the PRISMA guidelines, a systematic investigation of databases was carried out, and suitable studies were chosen according to predetermined criteria (PICO framework). The meta-analyses were performed using a random-effects model. Results: This review included 18 RCTs with 2271 patients who compared hydromorphone with morphine, oxycodone, or fentanyl, as well as other types of hydromorphone. Hydromorphone demonstrated efficacy similar to that of morphine and oxycodone in reducing cancer pain intensity, decreasing additional analgesic consumption, and improving quality of life. However, morphine showed slight superiority over hydromorphone in reducing breakthrough pain. Adverse events were comparable between hydromorphone and morphine or oxycodone. Patient-controlled and clinician-controlled hydromorphone administration routes yielded similar outcomes. Conclusions: The outcomes of this study substantiate the efficacy of hydromorphone in the management of cancer-related pain, demonstrating similar levels of effectiveness and safety as morphine and oxycodone. These findings are consistent with prior comprehensive analyses, suggesting that hydromorphone is a feasible choice for alleviating cancer-associated pain. Additional investigations are warranted to determine its efficacy in distinct patient cohorts and for different modes of administration. Trial registration: Prospero registration ID: CRD42024517513. Link: https://www.crd.york.ac.uk/PROSPERO/#recordDetails. [ABSTRACT FROM AUTHOR]