Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy (EBBT) has been shown to provide palliative therapy. It is the insertion of a radioactive material near the mass to reduce tumor size, thereby improving airway obstruction. This is the first case of EBBT done in our institution during the COVID-19 pandemic. A 53-year-old male, 60 kg, ASA Physical Status 2 for hypertension, smoker, malignancy, and previous pulmonary tuberculosis patient, presented with a cough and dyspnea. An endobronchial mass almost obstructing the right mainstem bronchus was seen on a computed tomography (CT) scan. He was diagnosed with squamous cell carcinoma of the lung and underwent radiotherapy and erlotinib chemotherapy. On repeat CT scan, there was no noted decrease in the size of the mass. EBBT was suggested, and a multi-disciplinary team was formed for the planned procedure. Pulmonology, radiation oncology, and anesthesiology teams were identified, and thorough planning was done prior to the actual procedure. Three fractions of EBBT were done under sedation using midazolam, fentanyl, and dexmedetomidine infusion. Lidocaine spray and transtracheal block were also performed as adjuncts prior to sedation. The procedure went as planned, and points for improvement were discussed for subsequent fractions. Due to persistent cough and discomfort from the catheter, additional ipratropium nebulization for minimization of secretions, and oral dextromethorphan for cough suppression were incorporated. After each fraction, the patient was monitored post-procedure for any side effects both from the radiotherapy and anesthetic technique. Qualitative reduction in mass size was noted in subsequent fractions. The patient was able to complete 3 fractions and was advised to follow-up after a month. EBBT is an emerging palliative and treatment modality for lung cancer, especially for intraluminal masses. Anesthetic considerations will depend on each case’s characteristics such as airway anatomy, patient comfort and capacity, and procedural requirements. Conscious sedation with topical anesthesia is an adequate and appropriate anesthetic option, especially in cases where severe airway obstruction may compromise ventilation if airway reflexes are blunted. A multidisciplinary approach with different services and stakeholders is important for the proper planning, execution, and management of such patients.
Lung Neoplasms ; Conscious Sedation ; Dexmedetomidine ; Midazolam ; Fentanyl ; Lidocaine ; Dextromethorphan

In recent years, the types and quantities of fentanyl analogs have increased rapidly. It has become a hotspot in the illicit drug control field of how to quickly identify novel fentanyl analogs and to shorten the blank regulatory period. At present, the identification methods of fentanyl analogs that have been developed mostly rely on reference materials to target fentanyl analogs or their metabolites with known chemical structures, but these methods face challenges when analyzing new compounds with unknown structures. In recent years, emerging machine learning technology can quickly and automatically extract valuable features from massive data, which provides inspiration for the non-targeted screening of fentanyl analogs. For example, the wide application of instruments like Raman spectroscopy, nuclear magnetic resonance spectroscopy, high resolution mass spectrometry, and other instruments can maximize the mining of the characteristic data related to fentanyl analogs in samples. Combining this data with an appropriate machine learning model, researchers may create a variety of high-performance non-targeted fentanyl identification methods. This paper reviews the recent research on the application of machine learning assisted non-targeted screening strategy for the identification of fentanyl analogs, and looks forward to the future development trend in this field.
Fentanyl ; Substance Abuse Detection/methods* ; Mass Spectrometry/methods* ; Illicit Drugs/analysis*

Fentanyl is a fully synthetic opioid with analgesic and anesthetic properties. It has become a primary driver of the deadliest opioid crisis in the United States and elsewhere, consequently imposing devastating social, economic, and health burdens worldwide. However, the neural mechanisms that underlie the behavioral effects of fentanyl and its analogs are largely unknown, and approaches to prevent fentanyl abuse and fentanyl-related overdose deaths are scarce. This review presents the abuse potential and unique pharmacology of fentanyl and elucidates its potential mechanisms of action, including neural circuit dysfunction and neuroinflammation. We discuss recent progress in the development of pharmacological interventions, anti-fentanyl vaccines, anti-fentanyl/heroin conjugate vaccines, and monoclonal antibodies to attenuate fentanyl-seeking and prevent fentanyl-induced respiratory depression. However, translational studies and clinical trials are still lacking. Considering the present opioid crisis, the development of effective pharmacological and immunological strategies to prevent fentanyl abuse and overdose are urgently needed.
Humans ; Fentanyl/therapeutic use* ; Opioid-Related Disorders/drug therapy* ; Drug Overdose/prevention & control* ; Analgesics, Opioid/adverse effects* ; Vaccines/therapeutic use* ; Brain

Background: Inadequately treated postoperative pain can contribute significantly to morbidity in women undergoing cesarean section.  Recent studies showed that nalbuphine and fentanyl has promising result as neuraxial adjuvants in terms of postoperative analgesia and with lower incidents of adverse effect when use in cesarean section. 

Objective: To determine the effectiveness of postoperative analgesia with intrathecal nalbuphine versus intrathecal fentanyl as neuraxial adjuvants in cesarean section. 

Methods:  A meta-analysis following the PRISMA guidelines was performed.  Articles were searched through the Cochrane Library, PubMed.Gov and Pubmed Central, Google Scholar, HERDIN, WPRIM and ProQuest Guideline Central using different search strategies such as keywords and MeSH term.  Cochrane version 2 risk-of-bias tool for randomized trials (RoB 2) was used to assess for quality.  Quantitative data were pooled and analyzed using Review Manager 5.4. 

Results: A total of four trials, involving 425 full term pregnant women were analyzed. The pooled mean difference showed significantly longer duration of postoperative analgesia (MD=21.12 minutes, 95%CI=11.13,31.11, I2=73%), pooled risk ratio showed lesser risk for pruritus (RR=0.09, 95%CI=0.02,0.50, I2 = 0%) and postoperative nausea and vomiting (RR=0.38, 95%CI= 0.19,0.78, I2 = 11%) who received intrathecal nalbuphine compared to intrathecal fentanyl. 

Conclusions: The results of this meta-analysis demonstrates that the use of intrathecal nalbuphine appears to have a better outcome in increasing the duration of postoperative analgesia and with lesser incidence of PONV and pruritus than fentanyl.  However, due to the presence of heterogeneity it warrants that the results should be treated with caution especially with the possibility of publication bias. 

Recommendations: Better literature search through inclusion of high-quality studies from relevant databases and strict adherence on the uniformity of the dosage and methods used are very crucial to achieve the target clinical outcomes and minimize the publication bias. 

Fentanyl as a synthetic opioid works by binding to the mu-opioid receptor (MOR) in brain areas to generate analgesia, sedation and reward related behaviors. As we know, cerebellum is not only involved in sensory perception, motor coordination, motor learning and precise control of autonomous movement, but also important for the mood regulation, cognition, learning and memory. Previous studies have shown that functional MORs are widely distributed in the cerebellum, and the role of MOR activation in cerebellum has not been reported. The aim of the present study was to investigate the effects of fentanyl on air-puff stimulus-evoked field potential response in the cerebellar molecular layer using in vivo electrophysiology in mice. The results showed that perfusion of 5 μmol/L fentanyl on the cerebellar surface significantly inhibited the amplitude, half width and area under the curve (AUC) of sensory stimulation-evoked inhibitory response P1 in the molecular layer. The half-inhibitory concentration (IC
Animals ; Cerebellum ; Evoked Potentials ; Fentanyl/pharmacology* ; Interneurons ; Mice ; Physical Stimulation

To investigate the role of metabotropic glutamate receptor 5 (mGluR5) in laterocapcular division of the central nucleus of amygdala (CeLC) in fentanyl-induced hyperalgesia in rats. 
 Methods: A total of 12 Sprague-Dawley male rats (60-100 g) were randomly divided into a normal group 1 (n=6) and an opioid-induced hyperalgesia (OIH) group 1 (n=6). The OIH group 1 was injected with fentanyl through the lower neck skin to build OIH model, and the normal group 1 was given the same volume of saline. After 6.5 h, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested to verify the success of the induction of OIH. Then rats were sacrificed and the right CeLC tissue were taken for detection of the mGluR5 by Western blotting. Forty SD male rats were randomly divided into 4 groups (n=10 each): an OIH+DMSO, an OIH+MTEP (3.0 μg), an OIH+MTEP (7.5 μg) and an OIH+MTEP (15.0 μg) group. MTEP was a selective antagonist of mGluR5. Catheterization in the right CeLC was first performed. After one-week recovery, OIH was induced. Then 0.5 μL DMSO, MTEP 3.0 μg, MTEP 7.5 μg and MTEP 15.0 μg were administrated through the CeLC catheter accordingly. PWMT and PWTL were tested at pre-OIH, 6 h after OIH and post-drug. Then the expression levels of mGluR5 of CeLC tissue were analyzed by Western blotting. Another 8 SD male rats were randomly divided into a normal group 2 and an OIH group 2 (n=4 each). The rats were induced OIH by injecting of fentanyl while rats in the normal group 2 were injected with same volume of saline. The miniature excitatory postsynaptic currents (mEPSCs) of the 2 groups' neurons in the right CeLC region were recorded by whole cell voltage-clamp before and after the administration of MTEP in brain slice.
 Results: Compared with the normal group 1, the PWTL and PWMT were significantly decreased and the expression of mGluR5 was apparently increased in the OIH group 1 (P<0.05). The PWMT and PWTL were significantly decreased in each group and indicated success of OIH model (P<0.05). The expression of mGluR5 in the CeLC was increased. MTEP reversed these changes in a dose-dependent way (P<0.05). Compared with the normal group 2, the amplitude and frequency of mEPSCs in the OIH group 2 were significantly increased (P<0.05) and they were reversed by MTEP (P<0.05). 
 Conclusion: mGluR5 in the CeLC may be involved in the maintenance of OIH. Inhibition of the activity of mGluR5 in the CeLC may alleviate the symptoms of fentanyl-induced hyperalgesia.
Animals ; Central Amygdaloid Nucleus ; Fentanyl ; Hyperalgesia ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5

BACKGROUND: To evaluate the efficacy and safety of fentanyl for sedation therapy in mechanically ventilated children. METHODS: This was a double-blind, randomized controlled trial of mechanically ventilated patients between 2 months and 18 years of age. Patients were randomly divided into two groups; the control group with midazolam alone, and the combination group with both fentanyl and midazolam. The sedation level was evaluated using the Comfort Behavior Scale (CBS), and the infusion rates were adjusted according to the difference between the measured and the target CBS score. RESULTS: Forty-four patients were recruited and randomly allocated, with 22 patients in both groups. The time ratio of cumulative hours with a difference in CBS score (measured CBS–target CBS) of ≥ 4 points (i.e., under-sedation) was lower in the combination group (median, 0.06; interquartile range [IQR], 0–0.2) than in the control group (median, 0.15; IQR, 0.04–0.29) (P < 0.001). The time ratio of cumulative hours with a difference in CBS score of ≥ 8 points (serious under-sedation) was also lower in the combination group (P < 0.001). The cumulative amount of midazolam used in the control group (0.11 mg/kg/hr; 0.07–0.14 mg/kg/hr) was greater than in the combination group (0.07 mg/kg/hr; 0.06–0.11 mg/kg/hr) (P < 0.001). Two cases of hypotension in each group were detected but coma and ileus, the major known adverse reactions to fentanyl, did not occur. CONCLUSION: Fentanyl combined with midazolam is safe and more effective than midazolam alone for sedation therapy in mechanically ventilated children. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02172014
Child* ; Coma ; Fentanyl* ; Humans ; Hypotension ; Ileus ; Midazolam* ; Respiration, Artificial*

Objective To provide the reference for the identification of unknown fentanyl analogues by studying the characteristic ions and main fragmentation pathways of fentanyl analogues in the modes of collision induced dissociation （CID） and electron ionization （EI）. Methods Nine fentanyl analogues （2, 2'-difluorofentanyl, acetyl fentanyl, fentanyl, butyl fentanyl, valeryl fentanyl, acryloyl fentanyl, furan fentanyl, 4-fluorine isobutyl fentanyl, carfentanyl） were selected and analyzed with ultra-high performance liquid chromatography-quadrupole time-of-flight-mass spectrometry （UHPLC-QTOF-MS） and gas chromatography-mass spectrometry （GC-MS）. The mass spectrum obtained was analyzed. The CID and EI fragmentation routes of fentanyl analogues were speculated. Results The CID and EI fragmentation pathways were highly similar. In the CID mode, characteristic ions were formed by the carbon-nitrogen bond cleavage between the piperidine ring and the N-phenyl-amide moiety, within the piperidine ring, and between the phenethyl and piperidine ring. While in the EI mode, dissociation of the piperidine ring, as well as cleavage between the piperidine ring and the phenethyl were the main fragmentation pathways. Conclusion This study summarizes the main fragmentation pathways and characteristic ions of fentanyl analogues in the CID and EI modes, which is useful for forensic laboratories to identify and structural analyze fentanyl type new psychoactive substance in practical work.
Chemistry Techniques, Analytical/methods* ; Chromatography, High Pressure Liquid ; Fentanyl/analysis* ; Gas Chromatography-Mass Spectrometry ; Humans ; Mass Spectrometry

Objective To establish an ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） rapid determination method for simultaneous analysis of 20 fentanyl-related substances in blood. Methods With fentanyl-D₅ as an internal standard, the blood was extracted by liquid-liquid extraction （LLE）, then separated with an ACQUITY UPLC HSS T₃ chromatographic column, and finally 20 fentanyl-related substances were simultaneously analyzed with multiple reaction monitoring （MRM） mode. Results The limits of detection （LOD） of all compounds were 0.02-0.03 ng/mL, and the limits of quantitation （LOQ） were 0.05-0.2 ng/mL. Within the mass concentration range of 0.05-40 ng/mL, 20 fentanyl-related substances had a good linear relationship, and correlation coefficients were larger than 0.99. The accuracy of the method was 87.69%-114.68% and the extraction recovery rate was 85.35%-101.80%, and no significant matrix effect was observed. The established method was successfully applied to the detection of sufentanil in rat blood after sufentanil was injected. Sufentanil could still be detected in blood of rats 10 h after sufentanil injection. Conclusion The established method has the advantages of simple pretreatment, high sensitivity and good selectivity, and can be used for the determination of fentanyl-related substances in forensic toxicology analysis.
Animals ; Chromatography, High Pressure Liquid ; Fentanyl/blood* ; Forensic Toxicology ; Rats ; Reproducibility of Results ; Sufentanil/blood* ; Tandem Mass Spectrometry

STUDY DESIGN: A retrospective study. PURPOSE: The first research on the erector spinae plane (ESP) block was published in 2016. To our knowledge, no cohort studies or randomized controlled trials of the ESP block were performed in 2016 and 2017. OVERVIEW OF LITERATURE: This study retrospectively investigated the efficacy of the ESP block in pain management after lumbar spinal surgery. METHODS: Patients who underwent lumbar spinal surgery in 2017 were enrolled in the study. Those who underwent secondary surgery with local anesthesia other than the ESP block were excluded. The primary outcome was the Numerical Rating Scale (NRS) pain score at various time points until the morning of postoperative day 2. The secondary outcomes were the amount of intravenous fentanyl administered during the first 24 hours following the surgery and the number of patients with complaints of complications such as nausea and vomiting until the morning of postoperative day 2. RESULTS: The data of 41 patients undergoing lumbar spinal surgery were retrospectively analyzed. Of these, 23 received only general anesthesia (G group), whereas the other 18 patients received the ESP block in addition to general anesthesia (E group). The NRS pain scores and the amount of fentanyl administered were lower in the G group than in the E group at all measured time points (all data were less than p<0.05). There was no significant difference in the incidence of complications between the two groups (p=0.11). CONCLUSIONS: The ESP block provides effective postoperative analgesic effect for 24 hours in patients undergoing lumbar spinal surgery.
Anesthesia, General ; Anesthesia, Local ; Cohort Studies ; Fentanyl ; Humans ; Incidence ; Nausea ; Pain Management ; Retrospective Studies ; Spinal Nerves ; Vomiting