Matching study design to prescribing intention: The prevalent new-user design for studying abuse-deterrent formulations of opioids.

PURPOSE: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. METHODS: In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. RESULTS: We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. CONCLUSIONS: Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.

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.

FEASIBILITY AND EFFECTIVENESS OF GENERAL ANESTHESIA WITH OPIOIDS VERSUS OPIOID-FREE ANESTHESIA PLUS TRANSVERSUS ABDOMINIS PLANE BLOCK ON POSTOPERATIVE OUTCOMES AFTER MINI GASTRIC BYPASS SURGERY.

Opioid-free anesthesia (OFA) is increasingly used at present in surgical practice by many hospitals as a new and very promising anesthesiologic regimen. This study aimed to compare the efficacy of standard general anesthesia with opioids with so-called opioid-free anesthesia on postoperative outcomes of patients who underwent gastric bypass surgery. This randomized, single-blind clinical study enrolled 103 patients scheduled for elective gastric bypass surgery. They were assigned randomly to receive either general anesthesia without opioids plus transversus abdominis plane (TAP) block (Group 1: 53 patients) or general anesthesia with opioids (Group 2: 50 patients). 21.4% (22/103) males and 78.6% (81/103) females were operated. The average age of patients was 40.9 and the average BMI - 48.4. Patients from both groups (patients who received general anesthesia + TAP and patients who received general anesthesia with opioids) were assessed for postoperative pain at rest using a 0-to-10 visual analog pain scale (0 = no pain, 5 = moderate pain, and 10 = the most severe pain possible). In group 1 - 34% (18/53) of patients did not receive any medication against pain and 66% (35/53) received Dexalgin Inject 25mg/ml 2 ml. There was no need in opioids. In group 2 - 10% (5/50) of patients did not receive any medication against pain, 38% (19/50) received Dexalgin Inject 25mg/ml 2 ml and 52% (26/50) received Dexalgin Inject 25mg/ml 2 ml + Promedol 20mg/ml 1ml. Type of anesthesia is a significant predictor of postoperative outcomes, such as pain intensity, extubation time, intensive care stay, and hospital length of stay in patients undergoing gastric bypass surgery. Patients, who received (OFA) plus (TAP) block had better pain control than those who received general anesthesia with opioids. No opioids were used in group 1. In addition, the duration of hospital stay in group 1 was shorter, and the average cost for postoperative hospital stay was 2.39 times lower than in group 2. OFA can be used as a reliable and effective anesthesiologic technique in patients scheduled for bariatric 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.

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).

Impact of neonatal pain and opiate administration in animal models: A meta-analysis concerning pain threshold.

BACKGROUND AND AIM: Neonatal intensive care treatment, including frequently performed painful procedures and administration of analgesic drugs, can have different effects on the neurodevelopment. This systematic review and meta-analysis aimed to investigate the influence of pain, opiate administration, and pre-emptive opiate administration on pain threshold in animal studies in rodents, which had a brain development corresponding to preterm and term infants. METHODS: A systematic literature search of electronic data bases including CENTRAL (OVID), CINAHL (EBSCO), Embase.com, Medline (OVID), Web of Science, and PsycInfo (OVID) was conducted. A total of 42 studies examining the effect of pain (n = 38), opiate administration (n = 9), and opiate administration prior to a painful event (n = 5) in rodents were included in this analysis. RESULTS: The results revealed that pain (g = 0.42, 95%CI 0.16-0.67, p = 0.001) increased pain threshold leading to hypoalgesia. Pre-emptive opiate administration had the opposite effect, lowering pain threshold, when compared to pain without prior treatment (g = -1.79, 95%CI -2.71-0.86, p = 0.0001). Differences were found in the meta regression for type of stimulus (thermal: g = 0.66, 95%CI 0.26-1.07, p = 0.001; vs. mechanical: g = 0.13, 95%CI -0.98-1.25, p = 0.81) and gestational age (b = -1.85, SE = 0.82, p = 0.027). In addition, meta regression indicated an association between higher pain thresholds and the amount of cumulative pain events (b = 0.06, SE = 0.03, p = 0.05) as well as severity of pain events (b = 0.94, SE = 0.28, p = 0.001). CONCLUSION: Neonatal exposure to pain results in higher pain thresholds. However, caution is warranted in extrapolating these findings directly to premature infants. Further research is warranted to validate similar effects in clinical contexts and inform evidence-based practices in neonatal care.

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).

Conversion ratios: Why is it so challenging to construct opioid conversion tables?

Standardizing opioid management is challenging due to the absence of a ceiling dose, the unknown ideal therapeutic plasma level, and the lack of an clear relationship between dose and therapeutic response. Opioid rotation or conversion, which is switching from one opioid, route of administration, or both, to another, to improve therapeutic response and reduce toxicities, occurs in 20-40 percent of patients treated with opioids. Opioid conversion is often needed when there are adverse effects, toxicities, or inability to tolerate a certain opioid formulation. A majority of patients benefit from opioid conversion, leading to improved analgesia and less adverse effects. There are different published ways of converting opioids in the literature. This review of 20 years of literature is centered on opioid conversions and aims to discuss the complexity of converting opioids. We discuss study designs, outcomes and measures, pain phenotypes, patient characteristics, comparisons of equivalent doses between opioids, reconciling conversion ratios between opioids, routes, directional differences, half-lives and metabolites, interindividual variability, and comparison to package insert information. Palliative care specialists have not yet come to a consensus on the ideal opioid equianalgesic table; however, we discuss a recently updated table, based on retrospective evidence, that may serve as a gold standard for practical use in the palliative care population. More robust, well-designed studies are needed to validate and guide future opioid conversion data.

Ultrasound-guided subcostal approach of transversus abdominis plane block compared with wound infiltration for postoperative analgesia following laparoscopic cholecystectomy: A systematic review and meta-analysis.

BACKGROUND: Despite laparoscopic cholecystectomy (LC) is a commonly performed operation under ambulatory setting, significant postoperative pain is still a major concern. The ultrasound-guided subcostal approach of transversus abdominis plane (sTAP) blocks and wound infiltration (WI) are both widely practiced techniques to reduce postoperative pain in patients undergoing LC. Although these methods have been shown to relieve postoperative pain effectively, the relative analgesic efficacy between ultrasound-guided sTAP blocks and WI is not well known. METHODS: We searched PubMed, EMBASE, and CENTRAL to identify all randomized controlled trials (RCTs) comparing ultrasound-guided sTAP block versus WI for postoperative pain control in adult patients undergone LC. The search was performed until May 2023. Primary outcome was defined as 24-hour cumulative opioid consumption. Secondary outcomes were postoperative pain scores and the incidence of postoperative nausea and vomiting (PONV). RESULTS: Finally, 6 RCTs were included, and data from 314 participants were retrieved. Postoperative 24-hour opioid consumption was significantly lower in ultrasound-guided sTAP group than in the WI group with a mean difference of -6.67 (95% confidence interval: -9.39 to - 3.95). The ultrasound-guided sTAP group also showed significantly lower pain scores. Incidence of PONV did not significantly differ between the 2 groups. CONCLUSIONS: We conclude that there is low to moderate evidence to advocate that ultrasound-guided sTAP block has better analgesic effects than WI in patients undergoing LC. Further trials are needed with robust methodology and clearly defined outcomes.

Opioid use and disposal at 2 weeks post-surgery: Brief communication regarding excess opioids and disposal habits.

OBJECTIVE: To measure the number of unused prescription opioids and disposal habits of patients following orthopedic shoulder surgery. DESIGN: A prospective observational study. SETTING: Academic orthopedic sports medicine department. PATIENTS: Sixty-seven patients undergoing shoulder surgery. INTERVENTIONS: Nine-question opioid use questionnaire. MAIN OUTCOME MEASURES: Responses to an opioid use questionnaire were collected at 2 weeks post-surgery. Outcomes of interest included the amount of initial opioid prescription used and the disposal of excess opioids. RESULTS: Sixty-seven patients completed the opioid use questionnaire. Forty-six (68.7 percent) patients reported having excess opioids at 2 weeks. Of the 46 patients with excess opioids, 57 percent disposed of the excess, and 43 percent planned to keep their opioids. CONCLUSION: Two-thirds of the patients reported having excess opioids, highlighting the issue of an overabundance of unused prescription opioids in America. Utilization of opioid-free pain management strategies and drug disposal kits should be explored to reduce the number of unused and improperly disposed opioids.

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.

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.

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.

High-dose naloxone formulations are not as essential as we thought.

Naloxone is an effective FDA-approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public and can be administered through intramuscular (IM), intravenous (IV), and intranasal spray (IN) routes. Our literature review investigates the adequacy of two doses of standard IM or IN naloxone in reversing fentanyl overdoses compared to newer high-dose naloxone formulations. Moreover, our initiative incorporates the experiences of people who use drugs, enabling a more practical and contextually-grounded analysis. The evidence indicates that the vast majority of fentanyl overdoses can be successfully reversed using two standard IM or IN dosages. Exceptions include cases of carfentanil overdose, which necessitates ≥ 3 doses for reversal. Multiple studies documented the risk of precipitated withdrawal using ≥ 2 doses of naloxone, notably including the possibility of recurring overdose symptoms after resuscitation, contingent upon the half-life of the specific opioid involved. We recommend distributing multiple doses of standard IM or IN naloxone to bystanders and educating individuals on the adequacy of two doses in reversing fentanyl overdoses. Individuals should continue administration until the recipient is revived, ensuring appropriate intervals between each dose along with rescue breaths, and calling emergency medical services if the individual is unresponsive after two doses. We do not recommend high-dose naloxone formulations as a substitute for four doses of IM or IN naloxone due to the higher cost, risk of precipitated withdrawal, and limited evidence compared to standard doses. Future research must take into consideration lived and living experience, scientific evidence, conflicts of interest, and the bodily autonomy of people who use drugs.

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.

Assessing modalities used to alleviate postoperative pain in children receiving dental treatment under general anaesthesia: a systematic review.

Postoperative pain is generally a novel experience among paediatric patients. Topical anaesthetics, distraction procedures, and buffering of anaesthetic solutions have been used in reducing the postoperative pain. In this review, the authors assessed various modalities used to alleviate postoperative pain in children's dental treatment under general anaesthesia. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol were strictly adhered to in this systematic review. Specific keywords including postoperative pain, general anaesthesia, children, and dental extraction were used in the search for relevant randomized control trial studies in Web of Science, Scopus and PubMed, and included articles published until June 2021. From a total of 191 abstracts, 21 were reviewed. From the six studies with the usage of non-steroidal anti-inflammatory drugs (NSAIDs) alone or in combination with paracetamol, four observed that the preoperative use of NSAIDs alone or in combination was better than paracetamol alone, one discovered preoperative intravenous paracetamol was better than postoperative intravenous paracetamol, and the remaining study found no difference among various groups. Of two studies comparing the usage of non-steroidal anti-inflammatory drugs with opioid analgesics, one stated intravenous fentanyl in combination was better, while the other study found no difference among groups. The results obtained in this review can be utilized by physicians to control postoperative pain in children undergoing dental treatment under general anaesthesia.

Shaping and shifting schemas on supervised injectable opioid treatment: findings from a cross-sectional qualitative study in two German treatment facilities.

BACKGROUND: Supervised injectable opioid treatment (SIOT) is a promising alternative for people living with opioid use disorder (OUD) who have not sufficiently benefitted from oral opioid substitution treatment. Yet, SIOT utilization remains limited in Germany. We propose that this is due to beliefs, or schemas, on SIOT among people living with OUD. Drawing from medical sociology and social psychology, this study explores the emergence and evolution of such schemas on SIOT. METHODS: We conducted semi-structured interviews with 34 individuals currently in or eligible for SIOT in two German outpatient treatment facilities and paralleled an inductive qualitative content analysis with the exploration of individual cases. RESULTS: The analysis revealed that peer-to-peer interaction and individuals' practical experiences in therapy are crucial in constructing and changing idiosyncratic and shared schemas of SIOT. When facing ambiguous information, cognitive strategies like subtyping served to mitigate uncertainty. CONCLUSION: This research has important practical implications for integrating experiential knowledge into clinical care and improve information sharing among people living with OUD. A nuanced understanding of the complex network of informal advice-seeking and -giving among people living with OUD is indispensable to adequately expand treatment modalities of proven effectiveness.