Analysis of cardiohemodynamic and electrophysiological effects of morphine along with its toxicokinetic profile using the halothane-anesthetized dogs.

Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through IKr inhibition in vivo, but its potential to develop torsade de pointes will be small.

Effect of Preadministration of Nalmefene on Sufentanil-Induced Cough During Induction of General Anesthesia in Patients Undergoing Breast Surgery: A Double-Blind Randomized Controlled Trial.

Purpose: This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery. Patients and Methods: A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 µg·kg-1 (Group LN), and high-dose nalmefene 0.25 µg·kg-1 (Group HN). Sufentanil 0.5 µg·kg-1 was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery. Results: Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; P < 0.001), but no significant difference was observed between the two groups (P=0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181-0.735, P=0.008) in Group LN and by 75.9% (95% CI=0.432-0.898, P=0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C (P < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups. Conclusion: Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity.

Effect of Oxycodone-Based Multimodal Analgesia on Visceral Pain After Major Laparoscopic Gastrointestinal Surgery: A Randomised, Double-Blind, Controlled Trial.

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).

Assessing the Impact of Morphine on Adverse Outcomes in ACS Patients Treated with P2Y12 Inhibitors: Insights from Multiple Real-World Evidence.

Purpose: Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators. Patients and Methods: Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis. Results: Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42-5.28, false discovery rate adjusted-P =3.55*10-209). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI. Conclusion: The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.

TET1-Lipid Nanoparticle Encapsulating Morphine for Specific Targeting of Peripheral Nerve for Pain Alleviation.

Background: Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side effects. Restricting opioids to peripheral opioid receptors could reduce those effects while maintaining analgesia. Methods: To achieve this goal, we developed Tet1-LNP (morphine), a neural-targeting lipid nanoparticle encapsulating morphine that could specifically activate the peripheral opioid receptor in the dorsal root ganglion (DRG) and significantly reduce the side effects caused by the activation of opioid receptors in the brain. Tet1-LNP (morphine) were successfully prepared using the thin-film hydration method. In vitro, Tet1-LNP (morphine) uptake was assessed in differentiated neuron-like PC-12 cells and dorsal root ganglion (DRG) primary cells. The uptake of Tet1-LNP (morphine) in the DRGs and the brain was assessed in vivo. Von Frey filament and Hargreaves tests were used to assess the antinociception of Tet1-LNP (morphine) in the chronic constriction injury (CCI) neuropathic pain model. Morphine concentration in blood and brain were evaluated using ELISA. Results: Tet1-LNP (morphine) had an average size of 131 nm. Tet1-LNP (morphine) showed high cellular uptake and targeted DRG in vitro. CCI mice treated with Tet1-LNP (morphine) experienced prolonged analgesia for nearly 32 h compared with 3 h with free morphine (p < 0.0001). Notably, the brain morphine concentration in the Tet1-LNP (morphine) group was eight-fold lower than that in the morphine group (p < 0.0001). Conclusion: Our study presents a targeted lipid nanoparticle system for peripheral neural delivery of morphine. We anticipate Tet1-LNP (morphine) will offer a safe formulation for chronic neuropathic pain treatment, and promise further development for clinical applications.

Cannabis Co-Use Among Black Individuals with Chronic Pain Who Use Opioids: Associations with Other Substance Use and Pain Related Outcomes.

Background Black individuals with chronic musculoskeletal (MSK) pain tend to experience worse pain and opioid use-related outcomes, including other substance co-use, compared with non-Hispanic White individuals. Co-using cannabis with opioids could instigate a cascade of pain-related vulnerabilities and poor outcomes. Here, we test associations between cannabis/opioid co-use and pain-related outcomes among Black individuals with chronic MSK pain. Methods Black adults with chronic MSK pain who use opioids (N=401; 51.62% female, Mage=35.90, SD=11.03) completed online measures of pain intensity/interference, emotional distress, opioid dependence, and risky use of other substances. Results Compared with opioid use alone, opioid and cannabis co-use was associated with elevated anxiety and depression symptoms, opioid dependence, and risky substance use, but not pain. Conclusions Black individuals with chronic MSK pain who co-use opioids and cannabis warrant targeted interventions that address their needs. Tailored interventions could help address disparities in pain-related outcomes and opioid morbidity and mortality rates.

Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects.

The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) µM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.

Perioperative analgesic effects of the erector spinae plane block with bupivacaine or bupivacaine-dexmedetomidine in dogs undergoing hemilaminectomy: A randomized controlled trial.

Objective: To compare the perioperative opioid requirements among dogs receiving an erector spinae plane (ESP) block with bupivacaine, with or without dexmedetomidine, and a control group. Animals and procedure: Thirty client-owned, healthy adult dogs undergoing hemilaminectomy were included in this randomized, prospective, blinded clinical study. Dogs were randomly assigned to 1 of 3 treatment groups: Group B, ESP block with bupivacaine; Group BD, ESP block with bupivacaine and dexmedetomidine; and Group C, control. Rescue intra- and postoperative analgesia consisted of fentanyl and methadone, respectively. Postoperative pain was evaluated using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF). Results: In Group BD, 0/10 dogs required intraoperative fentanyl, compared to 9/10 in Group C (P < 0.001), whereas 1/10 required postoperative methadone, compared to 9/10 in Group B (P = 0.003) and 10/10 in Group C (P < 0.001). The total amount of intraoperative fentanyl (µg/kg) was 0 (0 to 4) in Group B and 0 (0 to 0) in BD, compared to 6 (0 to 8) in C (P = 0.004 and P < 0.001, respectively). Postoperative methadone (mg/kg) required during the first 12 h was 0.5 (0 to 1.4) in Group B (P = 0.003) and 0 (0 to 0) in BD (P < 0.001), compared to C (P = 0.003 and P < 0.001, respectively). Conclusion: An ESP block with bupivacaine, with or without dexmedetomidine, was associated with a reduction in perioperative opioid consumption and provided effective acute pain control.

Effets analgésiques périopératoires du bloc des érecteurs du rachis avec de la bupivacaïne ou de la bupivacaïne-dexmédétomidine chez les chiens subissant une hémilaminectomie: un essai contrôlé randomisé. Objectif: Comparer les besoins périopératoires en opioïdes chez les chiens recevant un bloc des érecteurs de la colonne vertébrale (ESP) avec de la bupivacaïne, avec ou sans dexmédétomidine, et un groupe témoin. Animaux et procédure: Trente chiens adultes en bonne santé appartenant à des clients subissant une hémilaminectomie ont été inclus dans cette étude clinique randomisée, prospective et en aveugle. Les chiens ont été répartis au hasard dans 1 des 3 groupes de traitement: groupe B, bloc ESP avec bupivacaïne; groupe BD, bloc ESP avec bupivacaïne et dexmédétomidine; et groupe C, témoin. L'analgésie de secours peropératoire et postopératoire consistait respectivement en fentanyl et en méthadone. La douleur postopératoire a été évaluée à l'aide du formulaire abrégé de l'échelle de mesure de la douleur de Glasgow (CMPS-SF). Résultats: Dans le groupe BD, 0/10 chiens ont eu besoin de fentanyl peropératoire, contre 9/10 dans le groupe C (P < 0,001), tandis que 1/10 ont eu besoin de méthadone postopératoire, contre 9/10 dans le groupe B (P = 0,003) et 10/10 dans le groupe C (P < 0,001). La quantité totale de fentanyl peropératoire (µg/kg) était de 0 (0 à 4) dans le groupe B et de 0 (0 à 0) dans le groupe BD, contre 6 (0 à 8) dans le groupe C (P = 0,004 et P < 0,001, respectivement). La méthadone postopératoire (mg/kg) nécessaire au cours des 12 premières heures était de 0,5 (0 à 1,4) dans le groupe B (P = 0,003) et de 0 (0 à 0) dans le groupe BD (P < 0,001), par rapport au groupe C (P = 0,003). et P < 0,001, respectivement). Conclusion: Un bloc ESP avec de la bupivacaïne, avec ou sans dexmédétomidine, a été associé à une réduction de la consommation peropératoire d'opioïdes et a permis un contrôle efficace de la douleur aiguë.(Traduit par Dr Serge Messier).

Prescription Opioids and Brain Structure in Community-Dwelling Older Adults.

OBJECTIVE: To evaluate the associations between prescription opioid exposures in community-dwelling older adults and gray and white matter structure by magnetic resonance imaging. METHODS: Secondary analysis was conducted of a prospective, longitudinal population-based cohort study employing cross-sectional imaging of older adult (≥65 years) enrollees between November 1, 2004, and December 31, 2017. Gray matter outcomes included cortical thickness in 41 structures and subcortical volumes in 6 structures. White matter outcomes included fractional anisotropy in 40 tracts and global white matter hyperintensity volumes. The primary exposure was prescription opioid availability expressed as the per-year rate of opioid days preceding magnetic resonance imaging, with a secondary exposure of per-year total morphine milligram equivalents (MME). Multivariable models assessed associations between opioid exposures and brain structures. RESULTS: The study included 2185 participants; median (interquartile range) age was 80 (75 to 85) years, 47% were women, and 1246 (57%) received opioids. No significant associations were found between opioids and gray matter. Increased opioid days and MME were associated with decreased white matter fractional anisotropy in 15 (38%) and 16 (40%) regions, respectively, including the corpus callosum, posterior thalamic radiation, and anterior limb of the internal capsule, among others. Opioid days and MME were also associated with greater white matter hyperintensity volume (1.02 [95% CI, 1.002 to 1.036; P=.029] and 1.01 [1.001 to 1.024; P=.032] increase in the geometric mean, respectively). CONCLUSION: The duration and dose of prescription opioids were associated with decreased white matter integrity but not with gray matter structure. Future studies with longitudinal imaging and clinical correlation are warranted to further evaluate these relationships.

Intrathecal Morphine for Cardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Cardiac surgeries often result in significant postoperative pain, leading to considerable use of opioids for pain management. However, excessive opioid use can lead to undesirable side effects and chronic opioid use. This systematic review and meta-analysis aimed to evaluate whether preoperative intrathecal morphine could reduce postoperative opioid consumption in patients undergoing cardiac surgery requiring sternotomy. We conducted a systematic search of Cochrane, EMBASE, and MEDLINE databases from inception to May 2022 for randomized controlled trials that evaluated the use of intrathecal morphine in patients undergoing cardiac surgery. Studies that evaluated intrathecal administration of other opioids or combinations of medications were excluded. The primary outcome was postoperative morphine consumption at 24 h. Secondary outcomes included time to extubation and hospital length of stay. The final analysis included ten randomized controlled trials, with a total of 402 patients. The results showed that postoperative morphine consumption at 24 h was significantly lower in the intervention group (standardized mean difference -1.43 [-2.12, -0.74], 95% CI, P < 0.0001). There were no significant differences in time to extubation and hospital length of stay. Our meta-analysis concluded that preoperative intrathecal morphine is associated with lower postoperative morphine consumption at 24 h following cardiac surgeries, without prolonging the time to extubation. The use of preoperative intrathecal morphine can be considered part of a multimodal analgesic and opioid-sparing strategy in patients undergoing cardiac surgery.

Low-Dose Alfentanil Inhibits Sufentanil-Induced Cough During Anesthesia Induction: A Prospective, Randomized, Double-Blind Study.

Background: Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the protective effect of alfentanil, afentanyl derivative with short onset time and short duration, in reducing sufentanil-induced cough. Patients and methods: Eighty patients that scheduled for thyroid surgery under general anesthesia were randomly divided into the alfentanil group and normal saline group, with 40 cases per group. Patients in the alfentanil group received intravenous administration of 2 µg/kg alfentanil prior to sufentanil injection during general anesthesia induction, while the same dose of normal saline was administered in the normal saline group. The outcomes measures included the incidence and severity of cough and common side effects of opioids following the administration of sufentanil during the induction of general anesthesia, intraoperative hemodynamics parameters and major adverse events during anesthesia recovery period. Results: The incidence of cough within one minute after the injection of sufentanil during anesthesia induction was 40% in the normal saline group, and the pretreatment of alfentanil significantly reduced the incidence of sufentanil-induced cough to 5% (p < 0.05). Correspondingly, the patients in the alfentanil group had decreased severity of sufentanil-induced cough compared with the normal saline group (p < 0.05). No significant differences in the incidences of common side effects of opioids (dizziness, nausea and vomiting, chest tightness and respiratory depression) within one minute after sufentanil injection were found (p > 0.05). Furthermore, there were no significant differences between the two groups in intraoperative hemodynamic parameters, extubation time, or the incidences of emergence agitation, respiratory depression, delayed recovery from anesthesia and postoperative nausea and vomiting during Postanesthesia Care Unit stay (p > 0.05). Conclusion: Pretreatment with low-dose alfentanil (2 µg/kg) effectively and safely reduced both the incidence and severity of sufentanil-induced cough during anesthesia induction. Clinical Trial Registration Number: Chinese Clinical Trial Registry (identifier: ChiCTR2300069286).

Erector spinae plane block as a rescue therapy in following cholecystectomy: a historical cohort study.

OBJECTIVE: The aim of this study is to evaluate the effect of erector spinae plane block (ESPB) as a rescue therapy in the recovery room. MATERIALS AND METHODS: This single-center historical cohort study included patients who received either ESPB or intravenous meperidine for pain management in the recovery room. Patients' numeric rating scale (NRS) scores and opoid consumptions were evaluated. RESULTS: One hundred and eight patients were included in the statistical analysis. Sixty-two (57%) patients received ESPB postoperatively (pESPB) and 46 (43%) patients were managed with IV meperidine boluses only (IV). The cumulative meperidine doses administered were 0 (0-40) and 30 (10-80) mg for the pESPB and IV groups, respectively (p < 0.001). NRS scores of group pESPB were significantly lower than those of Group IV on T30 and T60. CONCLUSION: ESPB reduces the frequency of opioid administration and the amount of opioids administered in the early post-operative period. When post-operative rescue therapy is required, it should be considered before opioids.

OBJETIVO: Evaluar el efecto del bloqueo del plano erector espinal (ESPB) como terapia de rescate en la sala de recuperación. MÉTODO: Este estudio de cohortes histórico de un solo centro incluyó a pacientes que recibieron ESPB o meperidina intravenosa para el tratamiento del dolor en la sala de recuperación. Se evaluaron las puntuaciones de la escala de calificación numérica (NRS) de los pacientes y los consumos de opiáceos. RESULTADOS: En el análisis estadístico se incluyeron 108 pacientes. Recibieron ESPB 62 (57%) pacientes y los otros 46 (43%) fueron manejados solo con bolos de meperidina intravenosa. Las dosis acumuladas de meperidina administradas fueron 0 (0-40) y 30 (10-80) mg para los grupos de ESPB y de meperidina sola, respectivamente (p < 0.001). Las puntuaciones de dolor del grupo ESPB fueron significativamente más bajas que las del grupo de meperidina sola en T30 y T60. CONCLUSIONES: El ESPB reduce la frecuencia de administración de opiáceos y la cantidad de estos administrada en el posoperatorio temprano. Cuando se requiera terapia de rescate posoperatoria, se debe considerar antes que los opiáceos.

Balanced opioid-free anesthesia with lidocaine and esketamine versus balanced anesthesia with sufentanil for gynecological endoscopic surgery: a randomized controlled trial.

In this randomized controlled trial, 74 patients scheduled for gynecological laparoscopic surgery (American Society of Anesthesiologists grade I/II) were enrolled and randomly divided into two study groups: (i) Group C (control), received sufentanil (0.3 µg/kg) and saline, followed by sufentanil (0.1 µg/kg∙h) and saline; and (ii) Group F (OFA), received esketamine (0.15 mg/kg) and lidocaine (2 mg/kg), followed by esketamine (0.1 mg/kg∙h) and lidocaine (1.5 mg/kg∙h). The primary outcome was the 48-h time-weighted average (TWA) of postoperative pain scores. Secondary outcomes included time to extubation, adverse effects, and postoperative sedation score, pain scores at different time points, analgesic consumption at 48 h, and gastrointestinal functional recovery. The 48-h TWAs of pain scores were 1.32 (0.78) (95% CI 1.06-1.58) and 1.09 (0.70) (95% CI 0.87-1.33) for Groups F and C, respectively. The estimated difference between Groups F and C was - 0.23 (95% CI - 0.58 - 0.12; P = 0.195). No differences were found in any of the secondary outcomes and no severe adverse effects were observed in either group. Balanced OFA with lidocaine and esketamine achieved similar effects to balanced anesthesia with sufentanil in patients undergoing elective gynecological laparoscopic surgery, without severe adverse effects.Clinical Trial Registration: ChiCTR2300067951, www.chictr.org.cn 01 February, 2023.

Informing evidence-based medicine for opioid use disorder using pharmacoeconomic studies.

INTRODUCTION: The health and economic consequences of inadequately treated opioid use disorder (OUD) are substantial. Healthcare systems in the United States (US) and other countries are facing a growing healthcare crisis due to opioids. Although effective medications for OUD exist, relying solely on clinical information is insufficient for addressing the opioid crisis. AREAS COVERED: In this review, the role of pharmacoeconomic studies in informing evidence-based medication treatment for OUD is discussed, with a particular emphasis on the US healthcare system, where the economic burden is significantly higher than the global average. The scope/objective of pharmacoeconomics as a distinct scientific research program is briefly defined, followed by a discussion of existing evidence informed by data from systematic reviews, in addition to a convenience sample of recently published pharmacoeconomic studies and protocols. The review also explores the need for methodological advancements in the field. EXPERT OPINION: Despite the potential of pharmacoeconomic research in shaping evidence-based medicine for OUD, significant challenges limiting its real-world application remain. How to address these challenges are explored, including how to combine cost-effectiveness and budget impact analyses to address the needs of the healthcare system as a whole and specific stakeholders interested in adopting new OUD treatment strategies.

Ultrasound-guided suprainguinal fascia iliaca block to position the patient for neuraxial anaesthesia in acetabular surgery - a randomized controlled pilot study.

INTRODUCTION: Neuraxial anaesthesia is a common choice for most hip and lower limb operations. Pain associated with positioning is often a deterrent, and the vast literature suggests different regional blocks and opioids for these patients. Patients with acetabular fractures may experience increased pain, and thus are more difficult to position for the neuraxial block. We conducted a randomized controlled pilot study to assess and compare the analgesic efficacy of ultrasound-guided suprainguinal fascia iliaca block (SFICB) versus systemic fentanyl to facilitate positioning for combined spinal epidural (CSE) anaesthesia in patients undergoing acetabular fracture surgery. MATERIAL AND METHODS: Twenty patients referred for surgical repair of acetabular fractures were randomly assigned to receive either ultrasound-guided SFICB (group B) or intravenous fentanyl (group F). Changes in visual analogue scale (VAS) scores in supine and sitting position, improvement in sitting angle (SA), positioning quality, rescue analgesic requirement, total opioid consumption, comfort VAS scores, and complications were noted to compare both groups. RESULTS: The post-intervention VAS score in the sitting position was significantly lower in group B than in group F (5.9 ± 2.1 vs. 3.5 ± 1.5, P = 0.01). Group B also had more significant improvement in SA (27.5° (20.75-36.5°), in comparison to group F (10 (5-18.75), P = 0.006). The positioning quality was better in group B, with 70% of patients achieving an optimal position compared to only 10% in group F ( P = 0.02). CONCLUSIONS: Ultrasound-guided SFICB, as compared to systemic fentanyl, provided better analgesia and helped to achieve a better and more comfortable position to perform the neuraxial block.

Ultrasound guided quadratus lumborum block versus interlaminar epidural block for analgesia in pediatric abdominal surgery: a randomized controlled trial.

BACKGROUND: Although the efficacy and safety of epidural block (EB) are fairly high, complications such as inadvertent dural puncture may limit its use. Ultrasound-guided quadratus lumborum block (QLB) is a relatively new regional technique that provides perioperative somatic and visceral analgesia for pediatric patients. This trial compared the quality of pain relief in pediatric patients undergoing abdominal surgery who received either QLB or EB. METHODS: Patients were randomly allocated into two equal groups: Group E(n = 29): received EB; Group QL(n = 29): received QLB. Both groups were injected with 0.25% bupivacaine (0.5 ml/kg). Assessment of total analgesia consumption was the primary outcome measure, whereas the secondary outcome measures were assessment of postoperative analgesic effect by Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and time of first analgesic request. RESULTS: Our study showed that the mean total fentanyl consumption was comparable between both groups(38.67 ± 5.02 and 36.47 ± 5.13 µg in the E and QL groups, respectively, P = 0.246). Only five patients did not require rescue analgesia (3 in the E group,2 in the QL group, P = 0.378). The mean duration of analgesia showed no significant difference between the two groups (9.9 ± 1.58 and 11.02 ± 1.74 h in the E and QL groups, respectively, P = 0.212). Evaluation of CHEOPS score values immediately in PACU and for the initial 24 h following operation showed no significant difference between the two study groups(P > 0.05). CONCLUSION: QLB can achieve analgesic effects comparable to those of EB as a crucial part of multimodal analgesia in children undergoing abdominal surgeries. CLINICAL TRIAL REGISTRATION NUMBER: PACTR202203906027106.

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).