- Development of an UPLC-MS/MS method for the analysis of 16 synthetic opioids in segmented hair, and evaluation of the polydrug history in fentanyl analogue users. [Journal Article]Forensic Sci Int 2019; 307:110137FS
- Seizures of synthetic opioids have increased since 2012, with a 45 % increase in synthetic opioid related deaths between 2016 and 2017 in US. Recently, concerns have arisen around these substances and their illicit use also in several European countries. Our aim was to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of …
Seizures of synthetic opioids have increased since 2012, with a 45 % increase in synthetic opioid related deaths between 2016 and 2017 in US. Recently, concerns have arisen around these substances and their illicit use also in several European countries. Our aim was to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of 16 synthetic opioids in segmented hair, including fentanyl, norfentanyl, acetylfentanyl, U-47700, AH-7921, acrylfentanyl, crotonylfentanyl, butyrylfentanyl, methoxacetylfentanyl, U-49900, valeryfentanyl, 4-fluoro-iso-butyrylfentanyl, ocfentanyl, furanylfentanyl, tetrahydrofuranylfentanyl, and alfetanyl. Sample preparation involved washing the hair in dichloromethane, water and methanol, and extraction in methanol, followed by solid phase extraction clean-up. This method was validated for linearity, limit of quantification (LLOQ), precision and bias, selectivity, stability, matrix effects, extraction efficiency of the clean up procedure, and carryover. LLOQs ranged from 0.15-1pg/mg, and the calibration ranged from the LLOQ up to 500pg/mg. Intra and inter-day precision were evaluated at low and high concentrations, with spiked QCs, during 8 days and the results were satisfactory with RSD<15 % for all the compounds except for norfentanyl (22 %) and alfentanyl (19 %). Two external certified QCs containing fentanyl at 11 and 105pg/mg were also analysed within each batch and the RSD and bias were lower than 16 % and 10 %, respectively. Matrix effects compensated by internal standard fentanyl-d5 (MEIS), were between 77-115 % (RSD<10 %) and extraction efficiency of the clean-up procedure was between 66-93 % (RSD<21 %). Processed sample stability and carryover were acceptable for all of the compounds. The method was applied to 17 authentic hair samples (body or head hair) from US fentanyl analogue users. When head hair was available, the hair strands were analysed in 1cm/segment. Concentrations ranges were as follows: fentanyl (n=16) 2->ULOQ (500) pg/mg, norfentanyl (n=14) 1-38pg/mg, acetylfentanyl (n=7) 0.6->ULOQ (250) pg/mg, furanylfentanyl (n=5) 2-123pg/mg, tetrahydrofuranylfentanyl (n=1) 0.5-63pg/mg and valerylfentanyl (n=1) 2.1->ULOQ (50) pg/mg, along the hair strands. To our knowledge, this is the first time where concentrations of tetrahydrofuranylfentanyl, and valerylfentanyl in hair are reported. The same samples were also analysed for the determination of other drugs of abuse using our routine method (also in 1cm/segment for head hair when available). The results demonstrated poly-drug use in these fentanyl-analogue users population (mean drugs: n=5): amphetamine and/or methamphetamine (n=10), buprenorphine (n=5), cocaine (n=8), methadone (n=8), 6-MAM (n=17), meperidine (n=1), oxycodone (n=11), tramadol (n=3). Evaluation of the concentrations of these drugs, together with the fentanyl analogues is discussed in the present paper. Two authentic samples from two Belgian post-mortem cases, were also analysed showing fentanyl use and in one case polydrug use. The results demonstrated multi-analyte quantitative methods, including fentanyl analogues, are becoming useful in forensic laboratories involved in hair analysis, and in particular when polydrug use is suspected.
- The efficacy of transversus abdominis plane block for post-operative analgesia after the cesarean section performed under general anesthesia. [Journal Article]North Clin Istanb 2019; 6(4):368-373NC
- CONCLUSIONS: The USG-TAP block with 0.25% bupivacaine 60 ml (30 ml on each side) significantly reduced post-operative pain in patients undergoing the cesarean section. We think that TAP block is a comfortable and feasible method which reduces post-operative analgesia need and does not lead any serious complications.
- Pharmacological Approach for the Prevention of Postoperative Shivering: A Systematic Review of Prospective Randomized Controlled Trials [Journal Article]Asian J Anesthesiol 2019; 57(3):66-84AJ
- Shivering is a common postoperative complication that occurs after both general and regional anesthesia even in the cases when hypothermia during surgery has been averted. Patients describe it as a highly unpleasant experience, while clinicians are concerned due to its adverse effects such as increased oxygen consumption. In this article, we present a summary of the pathophysiological mechanisms …
Shivering is a common postoperative complication that occurs after both general and regional anesthesia even in the cases when hypothermia during surgery has been averted. Patients describe it as a highly unpleasant experience, while clinicians are concerned due to its adverse effects such as increased oxygen consumption. In this article, we present a summary of the pathophysiological mechanisms involved in postoperative shivering (POS), risk factors, and inadvertent effects. The major objective of this article was to review the existing literature on the effi ciency of various drug interventions as a prophylactic measure against POS. Since α2-adrenergic, opioid, anticholinergic, and serotonergic pathways are thought to play a role in the pathogenesis of POS, a wide variety of drugs has been investigated in this regard. Although the methodological diversity of the study designs and regimens does not support drawing defi nite conclusions, there is evidence indicating a benefi cial effect of dexmedetomidine, ketamine, tramadol, meperidine, dexamethasone, nefopam, granisetron, and ondansetron in the prevention of POS. The purpose of this review is to provide a thorough insight on various drug options and to serve as an aid for clinicians for careful analysis of the advantages and disadvantages of each regimen to decide which regimen will be ideally suited for the medical profi le of each patient.
- Dynamic changes in prescription opioids from 2006 to 2017 in Texas. [Journal Article]PeerJ 2019; 7:e8108P
- CONCLUSIONS: Collectively, these findings indicate that continued vigilance is needed in Texas to appropriately treat pain and an OUD while minimizing the potential for prescription opioid diversion and misuse. Texas may lead the US in a return to pre-opioid epidemic prescription levels.
- Extrapolation of Drug Clearance in Children ≤ 2 Years of Age from Empirical Models Using Data from Children (> 2 Years) and Adults. [Journal Article]Drugs R D 2019DR
- CONCLUSIONS: The study indicated that simple empirical models can provide more accurate results than complex empirical models.
- Comparison of Single-Dose Infraclavicular Brachial Plexus Block and Continuous Infraclavicular Brachial Plexus Block Applications in the Treatment of Finger Amputations. [Journal Article]J Hand Microsurg 2019; 11(3):134-139JH
- Introduction The aim of this study is to evaluate the replantation success of single-dose infraclavicular brachial plexus block and continuous infraclavicular brachial plexus block (CIBPB) applied with bupivacaine and prilocaine in patients with finger amputation. Materials and Methods This prospective randomized nonblinded study was conducted between January 2012 and September 2017, and 47 patie…
Introduction The aim of this study is to evaluate the replantation success of single-dose infraclavicular brachial plexus block and continuous infraclavicular brachial plexus block (CIBPB) applied with bupivacaine and prilocaine in patients with finger amputation. Materials and Methods This prospective randomized nonblinded study was conducted between January 2012 and September 2017, and 47 patients, all male, were included. Patients were randomly separated into two groups as 23 patients CIBPB applied group (group A) and 24 patients single-dose infraclavicular block applied group (group B). In group B, after the effect of block is ceased, intravenous patient-controlled (PC) opioid analgesia and, where necessary, 1 mg/kg meperidine and 75 mg diclofenac sodium intramuscularly were alternately administered at 4 to 6 hours intervals. The average ages were 30.7 ± 10.06 and 29 ± 9.08, respectively. Replantations were applied as being two venous anastomoses to one artery, where possible. Hourly skin temperatures of fingers of the hands in which both surgeries applied and no surgery applied in both the groups were measured for 3 days with an infrared thermometer. Also, Numerical Rating Scale (NRS) evaluations in both the groups were performed in 3-hour intervals for 3 days. Results Replantations were successful in 22 patients in whom CIBPB was applied (95.6%) and in 19 patients in whom single block was applied (79.16%). Regarding the finger temperatures, no significant difference was detected between both the groups for 3 days following the operation. No significant difference was found between the length of hospital stays (4.73 ± 2.21-4.71 ± 1.53) and duration of operations (2.90 ± 0.73-2.83 ± 0.58). There was no significant difference between the temperature values of both the groups. NRS scores of group A were statistically significantly lower than those of group B. Conclusion In this prospective randomized study performed by using bupivacaine and prilocaine on 24 patients, the success rate of finger replantations with CIBPB was found to be higher. CIBPB is a very beneficial method that should be taken in consideration in hand injuries with anastomosis and high risk of vasospasm. Further studies with more number of cases would help reduce the question marks related with the success of this method.
- Prescriber Education Interventions to Optimize Opioid Prescribing in Acute Care: A Systematic Review. [Journal Article]Pain Physician 2019; 22(6):E551-E562PP
- CONCLUSIONS: Overall study quality was fair to poor. Significant heterogeneity in settings, patient groups, methodologies, and outcomes prevented pooled quantitative analysis. No studies examined all available opioid agents or formulations.These findings support prescriber education as an effective strategy to reduce opioid use and optimize prescribing in acute settings. Further research, particularly high quality randomized studies, describing the impact of education on all available opioid formulations and total MME is required. Reviewing the existing literature has offered useful models that can be implemented to improve care with opioid prescribing in acute settings.
- Creation of a score to predict risk of high conscious sedation requirements in patients undergoing endoscopy. [Journal Article]Gastrointest Endosc 2019GE
- CONCLUSIONS: The HCSR risk score, based on 5 key patient and procedure characteristics, can function as a useful tool for physicians when discussing sedation options with patients before endoscopy.
- Opioids and frequency counts in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database: a quantitative view of the epidemic. [Journal Article]Drug Healthc Patient Saf 2019; 11:65-70DH
- CONCLUSIONS: The FAERS database represents an important source for detection and reporting of adverse drug events (ADEs), in particular the opioids and related drugs. It remains a challenge to estimate the true incidence of ADEs for this class of drugs in the general population.
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- The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review. [Review]Br J Anaesth 2020; 124(1):44-62BJ
- Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthr…
Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthrenes. Symptoms of serotonin toxicity are attributable to an effect on monoaminergic transmission caused by an increased synaptic concentration of serotonin. The serotonin transporter (SERT) maintains low serotonin concentrations and is important for the reuptake of the neurotransmitter into the presynaptic nerve terminals. Some opioids inhibit the reuptake of serotonin by inhibiting SERT, thus increasing the plasma and synaptic cleft serotonin concentrations that activate the serotonin receptors. Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity. Tramadol also has a direct serotonin-releasing action. Fentanyl produces an efflux of serotonin, and binds to 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptors, whilst methadone, meperidine, and more weakly tapentadol, bind to 5-HT2A but not 5-HT1A receptors. The perioperative period is a time where opioids and other serotonergic drugs are frequently administered in rapid succession, sometimes to patients with other serotonergic drugs in their system. This makes the perioperative period a relatively risky time for serotonin toxicity to occur. The intraoperative recognition of serotonin toxicity is challenging as it can mimic other serious syndromes, such as malignant hyperthermia, sepsis, thyroid storm, and neuroleptic malignant syndrome. Anaesthetists must maintain a heightened awareness of its possible occurrence and a readiness to engage in early treatment to avoid poor outcomes.