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*

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. 

Human ; Female ; Middle Aged (a Person 45-64 Years Of Age) ; Adult (a Person 19-44 Years Of Age) ; Cesarean Section ; Nalbuphine ; Fentanyl ; Meta-analysis

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

BACKGROUND: The addition of fentanyl or epinephrine to bupivacaine enhances the quality of intraoperative spinal anesthesia during cesarean section. This study aimed to evaluate the beneficial effects of adding fentanyl or epinephrine to bupivacaine in spinal anesthesia solutions used for patients undergoing cesarean section. METHODS: This retrospective study included 391 patients who underwent cesarean section under spinal anesthesia between March 2009 and February 2014. Parturients were categorized into group N (no addition; n = 103), group E (addition of epinephrine; n = 196), and group F (addition of fentanyl; n = 92). Perioperative hemodynamic changes, complications, sensory recovery times, Apgar scores, and cord blood pH were analyzed. RESULTS: Nausea and vomiting occurred more frequently in group E than in the other two groups (P < 0.001 and P = 0.027, respectively). The mean sensory recovery times to T10 level showed statistically significant intergroup differences (P < 0.001). Group F showed the highest 1-min and 5-min Apgar scores, with statistically significant differences amongst the three groups (P = 0.007 and P < 0.001, respectively). However, the blood gas analysis variables of the cord blood did not show significant differences. CONCLUSIONS: Addition of fentanyl to bupivacaine was related to a longer sensory recovery time than did the addition of nothing or epinephrine. Moreover, it had been associated with beneficial effects such as a reduction in complications following spinal anesthesia.
Anesthesia, Spinal* ; Blood Gas Analysis ; Bupivacaine* ; Cesarean Section* ; Epinephrine ; Female ; Fentanyl* ; Fetal Blood ; Hemodynamics ; Humans ; Hydrogen-Ion Concentration ; Nausea ; Pregnancy ; Retrospective Studies ; Vomiting

BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naive patients with moderate-to-severe cancer pain. METHODS: This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 microg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean +/- SD, 5.10 +/- 2.48 vs. 2.48 +/- 1.56; p < 0.001). TDF dose (27.8 microg/hr vs. 24.8 microg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted.
Administration, Cutaneous ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid/*administration & dosage/adverse effects ; Female ; Fentanyl/*administration & dosage/adverse effects ; Humans ; Intention to Treat Analysis ; Male ; Middle Aged ; Neoplasms/*complications ; Pain/diagnosis/*drug therapy/etiology ; Pain Measurement ; Prospective Studies ; Republic of Korea ; Severity of Illness Index ; Tertiary Care Centers ; Time Factors ; Transdermal Patch ; Treatment Outcome

PURPOSE: Opioid-based intravenous patient-controlled analgesia (IV PCA) is popular method of postoperative pain control, but many patients suffer from IV PCA-related postoperative nausea and vomiting (PONV). In this retrospective observational study, we have determined independent predictors of IV PCA-related PONV and predictive values of the Apfel's simplified risk score in pursuance of identifying high-risk patients. MATERIALS AND METHODS: We analyzed 7000 patients who received IV PCA with background infusion after elective surgery. Patients who maintained IV PCA for a postoperative period of 48 hr (completion group, n=6128) were compared with those who have discontinued IV PCA within 48 hr of surgery due to intractable PONV (cessation group, n=872). Patients, anesthetics, and surgical factors known for predicting PONV were evaluated by logistic regression analysis to identify independent predictors of IV PCA related intractable PONV. RESULTS: In a stepwise multivariate analysis, weight, background infusion dose of fentanyl, addition of ketolorac to PCA, duration of anesthesia, general anesthesia, head and neck surgery, and Apfel's simplified risk score were revealed as independent risk factors for intractable PONV followed by the cessation of IV PCA. In addition, Apfel's simplified risk score, which demonstrated the highest odds ratio among the predictors, was strongly correlated with the cessation rate of IV PCA. CONCLUSION: Multimodal prophylactic antiemetic strategies and dose reduction of opioids may be considered as strategies for the prevention of PONV with the use of IV PCA, especially in patients with high Apfel's simplified risk scores.
Adult ; Analgesia, Patient-Controlled/*adverse effects ; Anesthetics, Intravenous/administration & dosage/adverse effects/therapeutic use ; Antiemetics/administration & dosage/therapeutic use ; Female ; Fentanyl/administration & dosage/adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Postoperative Nausea and Vomiting/*drug therapy ; Retrospective Studies ; Risk Assessment/methods ; Risk Factors

BACKGROUNDOpioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown. The µ-opioid receptor (MOR) has an important role in mediating the actions of morphine and other analgesic agents. This study is aimed at exploring the changes of MOR in the periaqueductal gray (PAG) in rats when morphine is substituted for equianalgesic fentanyl.

METHODSForty rats were randomly assigned to five treatment groups: 7 days normal saline group (N group), 7 days fentanyl group (F group), 7 days morphine group (M group), 7 days morphine and 7 days fentanyl-switching group (MF group), and 14 days morphine group (MM group). Rats repeatedly received subcutaneous injections of morphine sulfate (10 mg/kg) or equianalgesic fentanyl sulfate (0.1 mg/kg) twice daily. Rats' antinociceptive response to thermal pain was evaluated by the tail flick latency assay. MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.

RESULTSThis study showed that after morphine was substituted with fentanyl on day 8, the tail flick latency (TFL) increased from (3.9 ± 0.4) seconds to (11.4 ± 0.4) seconds. The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group (P < 0.05) but more than that in MM group (P < 0.05).

CONCLUSIONSEquianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance, which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.

Analgesics, Opioid ; pharmacology ; Animals ; Drug Tolerance ; Fentanyl ; pharmacology ; Male ; Morphine ; pharmacology ; Periaqueductal Gray ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptors, Opioid, mu ; analysis ; genetics

OBJECTIVETo investigate the effect of dexmedetomidine on oxygenation function in adult patients with balanced anesthesia by propofol-fentanyl under one-lung ventilation (OLV).

METHODSTwenty-two patients undergoing thoracic operation were randomly divided into the study group and control group, both receiving propofol and fentanyl balanced anesthesia. In the study group, additional infusion of dexmedetomidine (0.3 µg/kg loading dose, 0.3 µg·kg(-1)·h(-1) maintenance dose) was administered, and the patients in the control group received only normal saline. Arterial blood samples were obtained at 4 time points from each patient during anesthesia for blood gas analysis.

RESULTSIn the study group, the pH values remained stable, the oxygenation index tended to decline progressively, but the incidence of hypoxemia was low; in the control group, the pH value and oxygenation index both declined progressively with a higher incidence of hypoxemia.

CONCLUSIONDexmedetomidine can better maintain the oxygenation function of OLV patients in balanced anesthesia by propofol and fentanyl, and its mechanism may be related to the decreased dose of propofol used.

Adult ; Balanced Anesthesia ; Blood Gas Analysis ; Dexmedetomidine ; pharmacology ; Female ; Fentanyl ; Humans ; Male ; Middle Aged ; One-Lung Ventilation ; Propofol

BACKGROUNDMu opioid receptor plays an important role in many physiological functions. Fentanyl is a widely used opioid receptor agonist for analgesia. This study was conducted to test the role of mu-opioid receptor on insulin release by determining whether fentanyl affected insulin release from freshly isolated rat pancreatic islets and if small interfering RNAs (siRNA) targeting mu-opioid receptor in the islets could knock down mu-opioid receptor expression.

METHODSIslets were isolated from ripe SD rats' pancreas by common bile duct intraductal collagenase V digestion and purified by discontinuous Ficoll density gradient centrifugation. The siRNA knock-down of mu-opioid receptor mRNA and protein in islet cells was analyzed by semi-quantitative real time-PCR and Western blotting. After siRNA-transfection for 48 hours, the islets were co-cultured with fentanyl as follows: 0 ng/ml, 3 ng/ml and 30 ng/ml for 48 hours. Then glucose-evoked insulin release was performed. As a control, the insulin release was also analyzed in islets without siRNA-trasfection after being co-cultured with fentanyl for 48 hours.

RESULTSAfter 48 hours of transfections, specific siRNA targeting of mu-opioid receptors produced significant reduction of mu-opioid receptor mRNA and protein (P < 0.01). Fentanyl significantly inhibited glucose-evoked insulin release in islets in a concentration dependent manner (P < 0.01). But after siRNA-transfection for 48 hours, the inhibition on glucose-evoked insulin release was reversed (P < 0.01).

CONCLUSIONSRNA interference specifically reduces mu-opioid receptor mRNA and protein expression, leading to reversal of the fentanyl-induced inhibition on glucose-evoked insulin release of rat islets. The activation of opioid receptor induced by fentanyl functions to inhibit insulin release. The use of RNAi presents a promising tool for future research in diabetic mechanisms and a novel therapy for diabetes.

Analgesics, Opioid ; pharmacology ; Animals ; Cell Survival ; drug effects ; Cells, Cultured ; Fentanyl ; pharmacology ; Glucose ; pharmacology ; Insulin ; secretion ; Islets of Langerhans ; drug effects ; secretion ; Male ; RNA Interference ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu ; antagonists & inhibitors ; genetics ; physiology

PURPOSE: Cervical epidural analgesia is used for pain control in head and neck or upper arm. But it is not commonly used for the purpose of pure regional anesthesia for upper arm surgery. Therefore, we investigated the usefulness of cervical epidural anesthesia (CEA) as a method of regional anesthesia for arteriovenous bridge graft (AVBG) for hemodialysis at upper arm and evaluated the effects of CEA on hemodynamics and respiration. METHODS: One hundred-fifty chronic renal failure patients scheduled for AVBG were randomly assigned. In the sitting position, an epidural catheter was inserted at C6-7 or C7-T1 and 15 ml of 0.375% ropivacaine with fentanyl 20microg was injected. Analgesic level, blood pressure and heart rate were measured at 5-minute intervals after injection of the drug. Arterial blood sampling was taken for aBGA before and twenty minutes after CEA. RESULTS: Average anesthetic dermatomalsensory levels were C3.4+/-1.2~T5.7+/-2.8. During surgery, hypotension was noted in 49% of patients. It was treated with ephedrine or phenylephrine i.v. Baseline PaCO2 changed from 42.4+/-2.9 mmHg to 44.6+/-3.6 mmHg. CONCLUSION: The above results suggest that CEA is suitable for AVBG at upper arm as a regional anesthesia.
Amides ; Analgesia, Epidural ; Anesthesia, Conduction ; Anesthesia, Epidural ; Arm ; Arteriovenous Shunt, Surgical ; Blood Gas Analysis ; Blood Pressure ; Catheters ; Ephedrine ; Fentanyl ; Head ; Heart Rate ; Hemodynamics ; Humans ; Hypotension ; Kidney Failure, Chronic ; Neck ; Phenylephrine ; Renal Dialysis ; Transplants