Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects. METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23. RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05). CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

Tracing Opioids Across the US: A High-Resolution Pharmaceutical Distribution Dataset.

In the field of pharmaceutical supply chains, there is a lack of comprehensive historical data, representing a significant barrier to advancing research. To address this gap, we introduce a high-resolution dataset comprising drug packages distributed to approximately 300,000 pharmacies, hospitals, and practitioners across the US. We reconstruct 375 million distribution paths from ARCOS, a DEA-maintained database comprising half a billion shipping records between 2006 and 2014. While ARCOS tracks dyadic shipments, it does not provide information on the complete journey of single packages from manufacturers to final destinations. Our algorithm is able to reconstruct complete distribution paths from these dyadic records. The reconstructed dataset, with its high temporal and spatial resolution, offers an unprecedented view of US pharmaceutical distribution and is a valuable resource for investigating supply and distribution networks.

Nalbuphine in Pediatric Emergence Agitation Following Cochlear Implantation: A Randomized Trial.

Background: To investigate the effects of nalbuphine on emergency agitation (EA), which affects up to 80% of the children following otolaryngology procedures, in children undergoing cochlear implantation. Methods: A prospective double-blinded randomized controlled clinical trial was conducted between November 2020 and October 2022. Eligible children, aged 6 months to 3 years old, were randomly assigned to either 0.1 mg/kg, 0.15 mg/kg, 0.2 mg/kg nalbuphine or 0.9% saline groups. EA was defined by the Pediatric Anesthesia Emergence Delirium (PAED) score ≥10. Extubation time, post-anesthesia care unit (PACU) length of stay, severe EA (PAED ≥ 15), peak PAED score, the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale, Ramsay sedation score, and adverse events were also recorded. Results: A total of 104 children were enrolled, with 26 children in each group. Nalbuphine significantly reduced the EA occurrence from 73.1% in the saline group to 38.5%, 30.8%, and 26.9% in the 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg nalbuphine groups, respectively (P < 0.001), without affecting the extubation time and PACU length of stay. More children (34.6%) in the 0.9% saline group experienced severe EA. Higher dose nalbuphine (0.15 mg/kg, 0.2 mg/kg) showed lower peak PAED score, better analgesia and sedation effect compared with 0.1 mg/kg nalbuphine and saline groups. However, 0.2mg/kg nalbuphine caused undesired over-sedation in two (7.7%) children. No other adverse events were reported. Conclusion: Young children undergoing cochlear implantation surgery were at a high risk of EA and postoperative pain, while 0.2 mg/kg nalbuphine might be an ideal candidate for EA and pain prevention when used under close monitoring. Trial Registration: ChiCTR2000040407.

Use of Medications for Opioid Use Disorder and Child Welfare Outcomes.

This cohort study investigates whether use of medications for opioid use disorder in pregnancy is associated with higher rates of infants discharge home with their mothers after birth.

Analgesic treatment for refractory cancer pain caused by gastric cancer bone metastasis: A case report and literature review.

RATIONALE: Patients with bone metastasis-associated cancer pain often experience a complex mix of pain types. Consequently, the use of multimodal combination therapy is essential. While monitoring for common adverse reactions in pain treatment, it is also crucial to be vigilant for the rare but serious serotonin syndrome. PATIENT CONCERNS: A 53-year-old female with metastatic gastric cancer was hospitalized due to severe, uncontrolled thoracic and cervical pain. During the titration of her cancer pain medication, she developed serotonin syndrome. DIAGNOSES: He was diagnosed with refractory cancer pain and serotonin syndrome. INTERVENTIONS: The complete process of cancer pain medication in a patient with gastric cancer and bone metastasis was analyzed, with a primary focus on the selection of analgesic medications, adjustment of opioid dosages, and prevention and treatment of medication-associated adverse reactions. OUTCOMES: The patient's cancer pain was well controlled, with the prompt management of adverse reactions. Furthermore, by adjusting the medication regimen, intolerable adverse reactions were prevented. LESSONS: In clinical settings, personalized analgesic regimens must be developed for patients with cancer pain to enhance patient compliance with medication, prevent the occurrence of severe adverse reactions, and improve the overall quality of life of patients with cancer. Healthcare professionals should pay increased attention to ADRs associated with opioid medications, whereas pharmacists should assist them in promptly identifying ADRs.

Anterior quadratus lumborum block provided superior pain control and reduced opioid consumption in kidney transplantation: A randomized controlled trial.

BACKGROUND: The research aimed to assess the effectiveness of inside-out anterior quadratus lumborum (QL3) block and local wound infiltration in managing postoperative pain and total morphine dosage following kidney transplantation. METHODS: In this prospective, randomized, double-blind study; 46 end-stage renal disease patients undergoing kidney transplantation were randomly allocated into 2 groups: a QL group (n = 23) receiving 20 mL of 0.25% bupivacaine using the ultrasound-assisted inside-out technique before wound closure, while the local wound infiltration (LA) group (n = 23) receiving the same dose around the surgical wound and drain at the time of skin closure. The primary outcome measure was the numerical pain rating scale, with secondary outcomes including amount of morphine consumption at various postoperative time points (2nd, 4th, 6th, 12th, 18th and 24th hours). RESULTS: Patients in the QL group had significantly lower numerical rating scale scores at the 2nd and 4th hours, both at rest and during movement (P < .05). Although pain scores at rest and during movement at later time points were lower in the QL group compared to the LA group, these differences were not statistically significant. Cumulative morphine consumption at postoperative 4th, 6th, 12th, 18th and 24th hours was significantly lower in the QL group (P < .05). No patients experienced complications from the QL3 block. CONCLUSION: Ultrasound-assisted inside-out QL3 block significantly reduced postoperative pain levels at the 2nd and 4th hours, both at rest and during movement, and led to a reduction in cumulative morphine consumption from the 4th hour postoperatively, and persisting throughout the 24-hour period.

Preliminary investigation of potential links between pigmentation variants and opioid analgesic effectiveness in horses during cerebrospinal fluid centesis.

BACKGROUND: The pleiotropic effects of the melanocortin system show promise in overcoming limitations associated with large variations in opioid analgesic effectiveness observed in equine practice. Of particular interest is variation in the melanocortin-1-receptor (MC1R) gene, which dictates pigment type expression through its epistatic interaction with the agouti signalling protein (ASIP) gene. MC1R has previously been implicated in opioid efficacy in other species; however, this relationship is yet to be explored in horses. In this study, analgesic effectiveness was scored (1-3) based on noted response to dura penetration during the performance of cerebrospinal fluid centisis after sedation and tested for association with known genetic regions responsible for pigmentation variation in horses. RESULTS: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P<0.05) in association with opioid analgesic effectiveness. This included the location of the known e MC1R variant resulting in the chestnut coat colour. CONCLUSIONS: The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. The application of an easily identifiable phenotype indicating variable sensitivity presents a promising opportunity for accessible precision medicine in the use of analgesics and warrants further investigation.

Insulated by opioids.

Opioids trigger myelin insulation of reward circuit axons in a feedforward loop of addiction.

What Should the US Learn From New York's and Portugal's Approaches to the Opioid Crisis?

Between 1999 and 2020, more than 564 000 people in the United States died from opioid overdose. Domestically, the opioid epidemic tends to be approached not as a public health problem but as a law enforcement or judicial problem. Some US localities, however, are trying interventions modeled after international approaches that decriminalize opioid dependence. This article describes Portuguese approaches to persons with opioid use disorder.

How Should the Use of Opioids Be Regulated to Motivate Better Clinical Practice?

This article describes historical and political reasons for-and devastating consequences of-US opioid prescribing policy since the 1990s, which has restricted opioid prescribing for pain less than for treating opioid use disorder (OUD) treatment. This article considers merits and drawbacks of a new diagnostic category and proposes a regulatory and clinical framework for prescribing long-term opioid therapy for pain and for prescribing opioids to treat OUD.

How Should Risks and Benefits of Short-Acting Opioids Be Evaluated in the Care of Inpatients With OUD?

Severe opioid withdrawal, risk of patient-initiated discharge, and some inpatients' use of unregulated substances prompt clinical and ethical questions considered in this commentary on a case. Short-acting opioids can be used to manage inpatients' pain and opioid use disorder (OUD) withdrawal symptoms. Including evidence-based interventions-such as naloxone kits, substance use equipment, and supervised consumption-in some inpatients' care plans may make those patients safer and reduce their risk of death. These and other strategies align with clinicians' ethical duties to minimize harms and maximize benefits for inpatients with OUD.

How Should Harm Reduction Strategies Differ for Adolescents and Adults?

Overall rates of opioid use are low in adolescents; however, recent increases in mortality from overdose in adolescents have outpaced increases in the general population. This article highlights the importance of expanding evidence-based treatment for adolescent opioid use, especially medication, while also addressing key ethical considerations of harm reduction practices and how application of such practices with adolescents may differ from adults. Concepts related to adolescent populations are discussed, including autonomy, confidentiality, and brain development. Application of harm reduction practices should be age appropriate, express respect for patients' autonomy, include social support, and be accompanied by broader aims to minimize adolescent initiation, escalation, and overall harm caused by opioid use.

Opioid Epidemic Grief and Characterological Harm Reduction.

This article considers what it might mean to do the moral work of grieving during an opioid epidemic. Becoming callous, bitter, or resentful are harms we can suffer to our characters when grieving losses, especially at epidemic scale. This article suggests how appreciating beauty can play roles in grieving that could help mitigate these harms.

Opioid-Obviating Analgesia for Adolescent Multilevel Spinal Fusion Surgery: A Problem-Based Learning Discussion.

A female teenager with a history of polysubstance use, including a recent overdose, is scheduled for multilevel posterior spinal fusion surgery due to idiopathic scoliosis and has asked to avoid the use of opioids in the context of her upcoming surgery. This problem-based learning discussion (PBLD) focuses on the examination of the care of a spinal fusion patient that allowed for the successful provision of opioid-obviating care.

Descriptive molecular pharmacology of the δ opioid receptor (DOR): A computational study with structural approach.

This work focuses on the δ receptor (DOR), a G protein-coupled receptor (GPCR) belonging to the opioid receptor group. DOR is expressed in numerous tissues, particularly within the nervous system. Our study explores computationally the receptor's interactions with various ligands, including opiates and opioid peptides. It elucidates how these interactions influence the δ receptor response, relevant in a wide range of health and pathological processes. Thus, our investigation aims to explore the significance of DOR as an incoming drug target for pain relief and neurodegenerative diseases and as a source for novel opioid non-narcotic analgesic alternatives. We analyze the receptor's structural properties and interactions using Molecular Dynamics (MD) simulations and Gaussian-accelerated MD across different functional states. To thoroughly assess the primary differences in the structural and conformational ensembles across our different simulated systems, we initiated our study with 1 µs of conventional Molecular Dynamics. The strategy was chosen to encompass the full activation cycle of GPCRs, as activation processes typically occur within this microsecond range. Following the cMD, we extended our study with an additional 100 ns of Gaussian accelerated Molecular Dynamics (GaMD) to enhance the sampling of conformational states. This simulation approach allowed us to capture a comprehensive range of dynamic interactions and conformational changes that are crucial for GPCR activation as influenced by different ligands. Our study includes comparing agonist and antagonist complexes to uncover the collective patterns of their functional states, regarding activation, blocking, and inactivation of DOR, starting from experimental data. In addition, we also explored interactions between agonist and antagonist molecules from opiate and opioid classifications to establish robust structure-activity relationships. These interactions have been systematically quantified using a Quantitative Structure-Activity Relationships (QSAR) model. This research significantly contributes to our understanding of this significant pharmacological target, which is emerging as an attractive subject for drug development.