Thoracotomy Patients Under General Anesthesia: A Comparison on Intra-Operative Anesthetic and Analgesic Requirements, When Combined with Either Epidural Analgesia or Continuous Unilateral Paravertebral Analgesia.

BACKGROUND AND OBJECTIVE: Regional analgesia is effective for post-thoracotomy pain. The primary objective of the study is to compare the intraoperative requirement of isoflurane and fentanyl between general anaesthesia (GA) with epidural analgesia and GA with paravertebral analgesia. METHODS AND MATERIAL: A prospective observational comparative study was conducted on 56 patients undergoing open thoracotomy procedures. The patients were divided into two groups of 28 by assigning the study participants alternatively to each group: Group GAE - received thoracic epidural catheterization with GA, and Group GAP - received ultrasound guided thoracic paravertebral catheterization on the operative side with GA. Intraoperative requirement of isoflurane, fentanyl, postoperative analgesia, stress response, need of rescue analgesics and adverse effects were observed and analysed. RESULTS: 25 patients in each group were included in the data analysis. The intraoperative requirement of isoflurane (32.28 ± 1.88 vs 48.31 ± 4.34 ml; p < 0.0001) and fentanyl (128.87 ± 25.12 vs 157 ± 30.92 µg; p = 0.0009) were significantly less in the GAE group than in the GAP group. VAS scores and need of rescue analgesics and blood glucose levels were not statistically significant during the postoperative period (p > 0.05). The incidence of adverse effects was comparable except for hypotension and urinary retention which were significantly higher in the GAE group. CONCLUSION: GA with epidural analgesia resulted in significant reduction in the intraoperative consumption of isoflurane and fentanyl in comparison to GA with paravertebral analgesia. However, both the techniques were equally effective in the postoperative period.

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).

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.

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.

Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.

Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

Erector spinae plane block in dogs undergoing hemilaminectomy: A prospective randomized clinical trial.

OBJECTIVE: To compare the perioperative cumulative opioid consumption and the incidence of cardiovascular complications in dogs undergoing hemilaminectomy in which either an erector spinae plane (ESP) block or systemic opioids were administered. STUDY DESIGN: Prospective randomized clinical trial. ANIMALS: A total of 60 client-owned dogs. METHODS: Dogs were randomized to one of three groups: an ESP block (group ESP), a constant rate infusion of fentanyl (group FNT, positive control) or a single dose of methadone as premedication (group MTD, negative control). Intraoperative nociceptive response was treated with fentanyl [1 µg kg-1, intravenously (IV)] boli. Before closure of the surgical site, morphine (0.1 mg kg-1) was applied to the dura mater. The cumulative dose of opioids was recorded and compared between groups. The incidence of intraoperative bradycardia and/or hypotension and the time to extubation were compared between groups. The short form of the Glasgow Composite Pain Scale (SF-GCPS) was used to score nociception before anaesthetic induction and 1, 2, 6, 12,18 and 24 hours postoperatively. Methadone 0.2 mg kg-1 was administered IV if the SF-GCPS score was ≥ 5. RESULTS: Group MTD required more intraoperative rescue analgesia than groups ESP (p = 0.008) and FNT (p = 0.001). The total cumulative intraoperative dose of fentanyl was higher in groups FNT (p < 0.0001) and MTD (p = 0.002) than in group ESP. The incidence of cardiovascular complications was similar between groups. Extubation time was longer in group MTD (p = 0.03). Postoperatively, the time to first rescue analgesia was longer in group ESP than in group MTD (p = 0.03). The cumulative postoperative opioid consumption and pain scores were similar between groups. CONCLUSIONS AND CLINICAL RELEVANCE: The ESP block resulted in a reduced intraoperative opioid consumption compared with the control positive and negative groups.

Effectiveness of opioid switching for dyspnea and its predictors in cancer patients: a single-center retrospective observational study.

BACKGROUND: Morphine is the most used opioid for dyspnea, but other opioids such as oxycodone and fentanyl are increasingly used, and opioid switching to these is sometimes undertaken. No studies have verified the effectiveness of opioid switching for relief of dyspnea. We retrospectively investigated the effectiveness of opioid switching for dyspnea and its predictors. METHODS: All patients with opioid switching for dyspnea during hospitalization at Komaki City Hospital from January 2019 to August 2022 were included. Opioid switching was defined as a change to another opioid, and the assessment period for evaluating the effectiveness and adverse events of opioid switching was set as 1 week. Patients with Numeric Rating Scale or Japanese version of the Support Team Assessment Schedule reduction for dyspnea of at least 1, or with clear improvement based on medical records, were considered valid. Mitigating factors for dyspnea were identified using logistic regression analysis. RESULTS: Of the 976 patients with opioid switching, 57 patients had opioid switching for relief of dyspnea. Of these, opioid switching was effective in 21 patients (36.8%). In a multivariate analysis, older patients (odds ratio: 5.52, 95% CI: 1.50-20.20, P < 0.01), short prognosis for post-opioid switching (odds ratio: 0.20, 95% CI: 0.04-0.87, P = 0.03) and cachexia (odds ratio: 0.12, 95% CI: 0.02-0.64, P < 0.01) were significantly associated with opioid switching effects for dyspnea. There were no serious adverse events after opioid switching. CONCLUSION: This study indicates that opioid switching for dyspnea may have some effect. Furthermore, opioid switching for dyspnea may be more effective in older patients and less effective in terminally ill patients or in those with cachexia.

Subcutaneous vs intravenous fentanyl for labor pain management: a multicenter randomized controlled trial.

BACKGROUND: Labor pain is the most intense pain a woman will experience during her lifetime. Epidural anesthesia is recommended as the most effective method for pain relief, but it has several limitations. Fentanyl has high analgesic potency with short-acting duration, but the large-scale trials that assessed the effectiveness and safety of it for labor pain management are still limited. OBJECTIVE: This study aimed to compare the effectiveness and harm and maternal satisfaction of subcutaneous vs intravenous fentanyl for labor pain management. STUDY DESIGN: We conducted a multicenter, open-label randomized controlled trial. A total of 226 women were randomized to receive intravenous or subcutaneous fentanyl for labor pain management. Pain scores were evaluated before and after fentanyl administration at 5, 30, and 60 minutes and then every 60 minutes until delivery. The data were analyzed based on the intention-to-treat principle. RESULTS: Both intravenous and subcutaneous fentanyl significantly decreased labor pain from baseline to delivery (overall mean change, -1.39; 95% confidence interval, -1.62 to -1.17; and -0.89; 95% confidence interval, -1.24 to -0.05, respectively). The reduction in the pain score between the 2 groups was not different (overall mean difference, -0.35; 95% confidence interval, -0.76 to 0.05). Maternal satisfaction was high for both intravenous and subcutaneous fentanyl (89.4% and 93.8%, respectively). There was no difference in the maternal satisfaction rate between the 2 groups (relative risk, 0.95; 95% confidence interval, 0.88-1.03). No serious maternal and neonatal adverse effects were observed. CONCLUSION: Both intravenously and subcutaneously administered fentanyl were safe and significantly reduced pain from baseline to delivery among low-risk pregnancies. Maternal satisfaction with the childbirth experience was high regardless of the route of administration of fentanyl. No serious adverse effects of fentanyl were observed in either the mothers or the neonates.

Not Carfentanil-A Case of Unexpected Xylazine Detection.

Historically, xylazine has been utilized in veterinary medicine for decades as an anesthetic and analgesic sedative to facilitate safe handling, diagnostic testing, and surgical procedures in large animals. Currently, xylazine is an emerging threat to human health. It has been detected in the illicit drug supply chain, often as an adulterant. It has been more commonly added to illicit substances, most notably fentanyl, by drugmakers to enhance drug effect. End users are often unaware of its presence. This is alarming given the large number of xylazine-involved overdose deaths while laboratory detections are deficient and reversal agents are absent. Herein, we present the first documented case of xylazine identified via gas chromatography-tandem mass spectrometry at University of California Davis Health despite a peculiarly mild clinical presentation. We hope to increase awareness of this potentially fatal adulterant that is often missed in evaluation and engender further opportunities to study this ongoing issue.

A Comparison of Three Anesthetic Drug Combinations for Use in Inducing Surgical Anesthesia in Female Guinea Pigs (Cavia porcellus).

Guinea pigs are often used in translational research, but providing them with safe and effective anesthesia is a challenge. Common methods like inhalant anesthesia and injectable ketamine/xylazine induce surgical anesthesia but can negatively affect cardiovascular, respiratory, and thermoregulatory systems and complicate the interpretation of research outcomes. Several alternative anesthetic regimens have been investigated, but none have consistently achieved a surgical plane of anesthesia. Therefore, identifying an anesthetic regimen that achieves a stable state of the surgical plane of anesthesia while preserving cardiorespiratory function would be a valuable contribution. To address this issue, we compared the efficacy of 3 anesthetic combinations in female Dunkin-Hartley guinea pigs: 1) alfaxalone, dexmedetomidine, and fentanyl (ADF); 2) alfaxalone, midazolam, and fentanyl (AMF); and 3) alfaxalone, midazolam, fentanyl, and isoflurane (AMFIso). We monitored anesthetic depth, heart rate, oxygenation, respiratory rate, respiratory effort, blood pressure, and body temperature every 15 min from injection to recovery. We also recorded the time to loss of righting reflex, duration of anesthesia, and time to achieve a surgical plane. The results showed no statistically significant differences in induction and recovery times among the groups. In the AMFIso group, 100% of the animals achieved a surgical plane of anesthesia, whereas only 10% of the animals in the AMF group reached that level. None of the animals in ADF group reached a surgical plane of anesthesia. Respiratory rate was significantly lower in the AMFIso as compared with the ADF group (P < 0.001) but was not different between the AMF and ADF groups. Temperature was significantly lower in the AMFIso group as compared with both the ADF and AMF groups (P < 0.001). In conclusion, both combinations of solely injectable anesthetics assessed in this study can be used for short, nonpainful procedures without significant cardiorespiratory depression. However, for mildly to moderately painful surgical procedures, the addition of an inhalant anesthetic like isoflurane is necessary for female guinea pigs.

Effectiveness of intrathecal dexmedetomidine vs fentanyl as additives to hyperbaric bupivacaine for postoperative analgesia in women undergoing cesarean section: a systematic review protocol.

OBJECTIVE: The aim of this review is to compare the effectiveness of intrathecal dexmedetomidine vs fentanyl as additives to hyperbaric bupivacaine in providing postoperative analgesia in patients undergoing cesarean section. INTRODUCTION: Pain following cesarean section remains a challenge, with limited treatment options due to potential undesirable parturient and neonatal side effects. Intrathecal dexmedetomidine has emerged as a favorable alternative to opioid additives to hyperbaric bupivacaine in prolonging postoperative analgesia, but its effectiveness requires further investigation. INCLUSION CRITERIA: The review will evaluate studies of patients who underwent cesarean section under spinal anesthesia where dexmedetomidine and fentanyl were compared as intrathecal additives to hyperbaric bupivacaine for postoperative analgesia. This review will consider randomized controlled trials, non-randomized controlled trials, and prospective cohort studies for inclusion. No limits regarding publication date or language will be applied. METHODS: A preliminary search of PubMed and Cochrane Central Register of Controlled Trials has been conducted to identify relevant index terms and keywords, which will be applied in a second search across PubMed, Cochrane CENTRAL, Scopus, and Embase. Google Scholar, National Library of Medicine (Clinicaltrials.gov), and the World Health Organization International Clinical Trial Registry Platform will be searched to identify unpublished literature. Full-text studies will be subjected to an assessment of methodological quality, and data extraction will be performed independently by 2 reviewers. The results will be presented in both tabular and narrative format and, where possible, pooled into a meta-analysis. A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings will be created to grade the certainty of evidence of the reported outcomes. REVIEW REGISTRATION: PROSPERO CRD42022364815.

Perceptions of fentanyl among African Americans who misuse opioids: implications for risk reduction.

BACKGROUND: Fentanyl is a powerful synthetic opioid that is 50 times more powerful than heroin and has become ubiquitous in the illicit drug supply in the USA. Studies show that among people who use drugs, fentanyl is sometimes viewed as a desirable substance due to its high potency and low cost, while others have an unfavorable perception because of its association with overdose. Unfortunately, studies on the perceptions of fentanyl are relatively rare and existing studies tend to rely on samples with little African American representation. The objective of this study, therefore, was to identify and describe perceptions of fentanyl among African Americans who misuse opioids, while capturing their motivations for seeking out or avoiding fentanyl. METHODS: In-depth interviews (n = 30) were conducted with a sample of African American adults who misuse opioids in Southwest Florida between August 2021 and February 2022. Audiotapes of interviews were transcribed, coded, and thematically analyzed. RESULTS: Analyses revealed the presence of three subtypes of fentanyl-related perceptions: (1) fentanyl as an avoided adulterant, (2) fentanyl as a tolerated adulterant, and (3) fentanyl as a drug of choice. CONCLUSIONS: These findings show that African Americans' perceptions of fentanyl are not monolithic and suggest the distribution of fentanyl test strips and naloxone may be an effective risk reduction strategy. Given that most studies on fentanyl rely on quantitative data from drug seizures and death certificates, this study uniquely contributes to the literature by capturing the voices of African Americans who use drugs.

Put It in the Air? Nebulized Opioids in the Emergency Department.

The emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last several years, investigations into the use of medications via the nebulization route have greatly increased, with varying degrees of efficacy identified. This route has multiple theoretical advantages. Medications affecting bronchopulmonary function or secretions can be administered directly to the site of action, possibly utilizing a lower dose and hence minimizing side effects. It is also possible to have a faster onset of action compared with other routes, given the enhanced surface area for absorption. One group of medications that has been explored via this route of administration, and is frequently administered in EDs across the nation, is opioids, most notably fentanyl, hydromorphone, and morphine. However multiple questions exist regarding the implementation of these therapies via this route, including efficacy, dosing, and the functional aspects of medication administration that are more complex than that of more traditional routes. The intent of this review is to explore the supporting literature behind the use of nebulized opioids, most specifically fentanyl, hydromorphone, and morphine, in the ED for the treatment of acute pain presentations and provide the most up-to-date guidance for practitioners.

Continuous fentanyl administration and spontaneous withdrawal decreases home cage wheel running in rats with and without hindpaw inflammation.

Fentanyl is a potent analgesic with a rapid onset and short half-life that make it a useful treatment for pain and a lethal drug of abuse. The present study used voluntary home cage wheel running to assess the effect of hindpaw inflammation, fentanyl administration, and spontaneous fentanyl withdrawal. Fentanyl (0.32 or 1.0 mg/kg/day) or placebo osmotic pumps were implanted subcutaneously and rats received an intraplantar injection of Complete Freund's Adjuvant (CFA) or saline. Rats with hindpaw inflammation caused by CFA administration were less active than rats injected with saline into the hindpaw. The antinociceptive effect of 0.32 mg/kg/day of fentanyl was evident as a recovery of wheel running in these rats. Administration of 1 mg/kg/day of fentanyl almost completely inhibited wheel running during the first day in rats with and without hindpaw inflammation. Wheel running increased each subsequent day until the pumps were surgically removed after day 3. Withdrawal from 0.32 or 1 mg/kg/day of fentanyl caused a decrease in wheel running that lasted 2 days in rats without hindpaw inflammation. In contrast, withdrawal was only evident following termination of 1 mg/kg/day of fentanyl in rats with hindpaw inflammation. This decrease in running seemed to persist beyond the 3 days of assessment. These data demonstrate that fentanyl can either depress or restore activity depending on the dose and pain condition. Moreover, termination of 3 days of continuous fentanyl administration resulted in a dose and time dependent decrease in wheel running consistent with opioid withdrawal.

The motives and methods of methamphetamine and 'heroin' co-use in West Virginia.

BACKGROUND: Opioid and methamphetamine co-use is increasing across the USA with overdoses involving these drugs also rising. West Virginia (WV) has led the US in opioid overdose death rates since at least 2013 and rising co-use of methamphetamine with opioids has played a greater role in deaths over the last 5 years. METHODS: This study used rapid ethnography to examine methods and motivations behind opioids and methamphetamine co-use from the viewpoint of their consumers. Participants (n = 30) were people who injected heroin/fentanyl also using methamphetamine who participated in semi-structured interviews. RESULTS: We found multiple methods of co-using opioids and methamphetamine, whether alternately or simultaneously and in varying order. Most prioritized opioids, with motives for using methamphetamine forming three thematic categories: 'intrinsic use', encompassing both inherent pleasure of combined use greater than using both drugs separately or for self-medication of particular conditions; 'opioid assisting use' in which methamphetamine helped people manage their existing heroin/fentanyl use; and 'reluctant or indifferent use' for social participation, reflecting methamphetamine's low cost and easy availability. CONCLUSIONS: Methamphetamine serves multiple functions among people using opioids in WV. Beliefs persist that methamphetamine can play a role in preventing and reversing opioid overdose, including some arguments for sequential use being protective of overdose. 'Reluctant' uptake attests to methamphetamine's social use and the influence of supply. The impact on overdose risk of the many varied co-use patterns needs further investigation.

Efficacy of reconstituted intravenous fentanyl to sublingual solution versus oral morphine syrup for breakthrough pain among patients with chronic gynecologic cancer pain: A randomized, double-blind, placebo-controlled trial.

Rapid-acting fentanyl formulations are superior to oral morphine (OM) syrup in controlling breakthrough pain among patients with cancer, but they are expensive and unavailable in many countries. OBJECTIVE: To evaluate the efficacy of reconstituted intravenous fentanyl to sublingual solution (IFS) in relieving breakthrough pain as compared with OM. METHODS: In this randomized, double-blind, double-dummy, placebo-controlled trial, patients with gynecologic cancer aged ≥18 years experiencing chronic cancer pain with breakthrough pain were enrolled. Patients were randomly allocated (1:1) to receive either 50 µg IFS or 5 mg OM. Pain intensity level was assessed at 5, 15, 30, 45, 60, and 120 min after treatment. The primary outcome was the reduction in pain intensity at 15 min in the intention-to-treat population (ClinicalTrials.gov, NCT05037539). RESULTS: Between June 15, 2021 and December 30, 2021, 40 participants were equally and randomly assigned to receive IFS or OM. The primary outcome was significantly higher in the IFS group (4.25 vs. 1.05, p < 0.0001). The secondary outcomes also showed higher reduction in pain intensity at 5 min in the IFS group. Subsequent breakthrough pain did not differ between the two groups. However, the reduction in pain was lower in the IFS group at 45, 60, and 120 min, where pain was classified as mild. No severe adverse effects were observed in both groups. Burning sensation without noticeable lesion was found in 20% of the IFS group. CONCLUSION: IFS can reduce early breakthrough pain. IFS may be considered for breakthrough pain when rapid-acting fentanyl formulations are unavailable.

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress.

There is comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD), perhaps because PTSD-like stressful experiences early in life alter the hypothalamic-pituitary-adrenal stress axis to increase the risk for OUD. The present study determined if the glucocorticoid receptor antagonist PT150 reduces the escalation of fentanyl intake in rats exposed to a "two-hit" model of early-life stress (isolation rearing and acute stress). Male and female rats were raised during adolescence in either isolated or social housing and then were given either a single acute stress (restraint and cold-water swim) or control treatment in young adulthood. Rats were then treated daily with PT150 (50 mg/kg, oral) or placebo and were tested for acquisition of fentanyl self-administration in 1-hr sessions, followed by escalation across 6-hr sessions. Regardless of PT150 treatment or sex, acquisition of fentanyl self-administration in 1-hr sessions was greater in isolate-housed rats compared to social-housed rats; the acute stress manipulation did not have an effect on self-administration even though it transiently increased plasma corticosterone levels. During the 6-hr sessions, escalation of fentanyl was observed across all treatment groups; however, there was a significant PT150 Treatment × Sex interaction. While males self-administered more than females overall, PT150 decreased intake in males and increased intake in females, thus negating the sex difference. Although PT150 may serve as an effective treatment for reducing the risk of OUD following early-life stress in males, further work is needed to determine the mechanism underlying the differential effects of PT150 in males and females. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Intraoperative Neuromonitoring for Spinal Surgery in a Pregnant Patient: Case Report and Literature Review.

We report the strategy of anesthesia and intraoperative neurophysiological monitoring (IONM) in a 29-year-old, 22 weeks pregnant patient posted for surgery for aggressive vertebral body hemangioma. We used propofol and fentanyl-based anesthesia for IONM. Motor-evoked potentials (MEP) and somatosensory-evoked potentials (SSEP) were used to monitor the neural tracts during surgery. Fetal heart rate monitoring was done preoperatively and postoperatively. Train of 8, 75 µs duration pulse, 250-500 Hz stimulus was used for MEP and 30 mA, 200-400 µs, 3-5 Hz was used for SSEP. No new motor or somatosensory deficits appeared. Our findings suggest that IONM can be safely done in pregnant women.

Nebulized fentanyl for respiratory symptoms in patients with COVID-19 (ventanyl trial).

ABSTRACT: Patients with coronavirus disease (COVID-19) commonly experience distressing and challenging respiratory symptoms. Interventions such as oxygen therapy, oral opiates, and traditional nebulizers like ipratropium bromide and salbutamol are variable in their efficacy, and therapy responses in patients are difficult to predict. The purpose of this study is to investigate the efficacy of nebulized fentanyl citrate on dyspnea, cough, and throat pain in patients with COVID-19 and evaluate the safety with any potential adverse events.In COVID-19, about 59% of patients will exhibit cough, 35% generalized body ache and sore throat, and 31% dyspnea. Some methods such as nebulized lidocaine, magnesium sulfate, and systemic opioids have been used to manage the respiratory symptoms. It has been previously shown that fentanyl nebulizer has beneficial effect in improving shortness of breath in patients with chronic obstructive pulmonary disease. The proposed theory behind that was that fentanyl decreased the rate of spontaneous respiratory rate, diminished the brain stem chemoreceptor response to hypoxia and hypercarbia, in addition to exhibiting a modulating effect on the brain stem. Therefore, we hypothesize that nebulized fentanyl has superior effect in improving shortness of breath and relieving cough compared to normal saline, in addition to its advantageous throat pain relief, while exhibiting fewer side effects in patients with COVID 19 infection. Therefore, this phase-III, randomized, comparative, parallel assignment, single-blinded clinical trial aims at assessing the efficacy and safety of nebulized fentanyl to suppress cough, improve breathlessness, and relieve throat pain in patients with COVID-19.

Fentanyl transdermal patches: Extraction and evaluation of a novel disposal method using NarcX®.

Currently, there is no known commercially available product for disposing of used fentanyl transdermal patches. To eliminate the potential for harm and abuse, a proper disposal method is needed-one that neutralizes the dangerous amount of residual fentanyl that remains after therapeutic use of the fentanyl patch. The patent-pending liquid solution of activated carbon, known as NarcX® , was investigated as a potential fentanyl adsorbing agent. In order to determine the amount of fentanyl remaining after a patch is treated with NarcX® , here, we utilized hexanes to first dissolve the patch adhesive and then followed with liquid-liquid extraction with methanol to recover the fentanyl. Using liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS), the extracts obtained with this method yielded between 85% and 117% recovery of fentanyl from new and unused patches. Further optimization of this method allowed for a quantitative evaluation of NarcX® -treated fentanyl patches. 100 µg/h Apotex brand fentanyl patches were exposed to NarcX® for 1, 24, 48, and 72 h. NarcX® was shown to adsorb fentanyl from the patches with varying degrees of success, demonstrating an average of 66.98 ± 0.75% fentanyl adsorption after 72 h. These findings suggest that more work is needed to successfully neutralize the fentanyl patches in their entirety using NarcX® ; however, this work does demonstrate proof of concept.