Determining the Maximum Tolerable Concentration of Ropivacaine to Maintain Sensation of the Nerve Root in Percutaneous Endoscopic Transforaminal Lumbar Discectomy: Can Epidural Anaesthesia Achieve Pain-Tactile Separation Block to Avoid Nerve Injury?

Introduction: Nerve injury is a serious complication of percutaneous endoscopic transforaminal lumbar discectomy due to nerve root contact. The maximum tolerable concentration (MTC) of ropivacaine concentration for epidural anaesthesia, is defined as the concentration that minimises pain while preserving the sensation of the nerve roots. This distinct advantage allows the patient to provide feedback to the surgeon when the nerve roots are contacted. Methods: We used a biased-coin design to determine the MTC, which was estimated by the 10% effective concentration (EC10), ie, the concentration at which 10% of patients lost sensation in the nerve roots. The determinant for positive response was lack of sensory feedback upon contact with the nerve root, and the feedback from occurrence of sensations in the innervation area upon contact with the nerve root was defined as a negative response. Primary outcome was the response from contact nerve root. Secondary outcomes were the type and number of statements of negative response and each patient's pain score during surgery. Results: Fifty-four patients were included in this study. The EC10 was 0.434% (95% CI: 0.410%, 0.440%) using isotonic regression in comparison with 0.431% (95% CI: 0.399%, 0.444%) using probit regression. Three type statements of negative response were reported including "tactile sensation", radiculalgia, and numbness. Conclusion: The MTC of ropivacaine used for epidural anaesthesia was 0.434% to avoid nerve injury in percutaneous endoscopic transforaminal lumbar discectomy.

Switchable synthesis of natural-product-like lawsones and indenopyrazoles through regioselective ring-expansion of indantrione.

Lawsones and indenopyrazoles are the prevalent structural motifs and building blocks in pharmaceuticals and bioactive molecules, but their synthesis has always remained challenging as no comprehensive protocol has been outlined to date. Herein, a metal-free, ring-expansion reaction of indantrione with diazomethanes, generated in situ from the N-tosylhydrazones, has been developed for the synthesis of lawsone and indenopyrazole derivatives in acetonitrile and alcohol solvents, respectively. It provides these valuable lawsone and pyrazole skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials. DFT calculations were used to explore the mechanism in different solutions. The synthetic application example also showed the prospects of this method for the preparation of valuable compounds.

Synthesis of 2-Aminofurans and 2-Aminothiophenes through Elemental Sulfur-Promoted Switchable Redox Condensation Reaction of Enaminones with Methylene Nitriles.

Herein, we report an elemental sulfur-promoted switchable redox condensation reaction that can selectively prepare 2-aminofurans and 2-aminothiophenes from the corresponding enaminones and methylene nitriles, respectively. Mechanistic studies demonstrated that the enaminones, as dual nucleophiles, reacted with nitrile acetate to produce 2-aminofurans via 3,5-annulation under promotion by elemental sulfur. These reactions used readily available starting materials, transition metal-free, eco-friendly procedures, gram-scale syntheses, and wide functional group tolerance. The methodology may be useful for the construction of 2-aminofuran and 2-aminothiophene derivatives with potential biological activity.

Oxidative [2 + 1 + 1 + 1] Annulation of Aldehydes and Methylene Nitriles: Synthesis of Diastereoselective Polysubstituted Cyclopentenes.

Herein, we report a green cascade approach to prepare a variety of diastereoselective polysubstituted cyclopentene derivatives through metal-free oxidative [2 + 1 + 1 + 1] annulation of aldehydes and methylene nitriles. Mechanistic studies demonstrated that the reaction underwent a four-step cascade reaction including air oxidation and Michael addition to obtain the final product. This reaction features readily available starting materials, transition metal-free, eco-friendly operations, gram-scale syntheses, and wide functional group tolerance. The methodology may be useful for the construction of polysubstituted cyano-cyclopentene heterocycles with potential biological activity.

Palladium-Catalyzed [2+3] Cycloaddition/Cross-Coupling Reaction: Z/E and Diastereoselective Synthesis of Dendralene-Functionalized Dihydrofurans.

Herein, we describe a Pd-catalyzed [2+3] cycloaddition/cross-coupling reaction of allenyl acetates for the Z/E selective and diastereoselective synthesis of dendralene-functionalized dihydrofurans. Remarkably, mechanistic studies show the formation of an epoxide from a carbonyl bond via cycloaddition, which is practically and mechanistically significant for the construction of other bioactive heterocyclic epoxides. This research also revealed the utility and potential of allenic esters as C2 synthons and 1,2-biselectrophiles in cycloaddition reactions.

Determining the Minimum Effective Concentration of Ropivacaine in Epidural Anesthesia for Tolerable Pain in Transforaminal Percutaneous Endoscopic Lumbar Discectomy to Avoid Nerve Injury: A Double-Blind Study Using a Biased-Coin Design.

PURPOSE: Epidural anesthesia (EA) is the main anesthesia method for transforaminal percutaneous endoscopic lumbar discectomy (PELD). Reducing the concentration of ropivacaine can help preserve tactile sensation, allowing patients to provide timely feedback to the surgeons when a nerve root is contacted to avoid nerve injury. Therefore, a 90% effective concentration (EC90) that allows for mild pain [visual analog scale (VAS) score ≤3] while maximizing tactile sensation must be identified. METHODS: The concentration of ropivacaine for EA was varied for consecutive patients in this study using a two-stage biased-coin design (BCD) according to the response of the previous patient; the concentration used for the first patient was 0.2%. When the previous patient had a negative response (VAS score >3), the concentration used for the next one was increased by 0.015%. When the previous patient had a positive response (VAS score ≤3), the concentration used for the next one had an 89% probability of remaining the same and an 11% probability of being reduced by 0.015%. The EC90 of ropivacaine was estimated using isotonic regression, and the 95% confidence interval (CI) was estimated using the bootstrapping method in R. RESULTS: A total of 58 patients were included in the study. The calculated EC90 was 0.294% [95% CI (0.271%, 0.303%)]. Among 13 patients who reported unintended nerve root contact during the operation, none were found to have irreversible nerve injury after the operation. CONCLUSION: To preserve maximum tactile sensation, the EC90 of ropivacaine was 0.294% for patients with allowed mild pain. This concentration could allow for timely feedback when the nerve root is contacted, to avoid nerve injury.

Effect Analysis of Epidural Anesthesia with 0.4% Ropivacaine in Transforaminal Endoscopic Surgery.

Background: Epidural anesthesia used in percutaneous endoscopic lumber discectomy (PELD) has the risk of complete neurotactile block. Patients cannot timely respond to the operator when the nerve is touched by mistake, so the potential risk of nerve injury cannot be avoided. According to pharmacodynamics, with the decrease of local anesthetic concentration, the nerve tactile gradually recovered; however, the analgesic effect also gradually weakened. Therefore, it is necessary to explore an appropriate concentration of local anesthetics that can keep the patients' nerve touch without pain. By comparing the advantages and disadvantages of 0.4% ropivacaine epidural anesthesia, local anesthesia and intravenous anesthesia on intraoperative circulation fluctuation, the incidence of salvage analgesia and the incidence of nerve non-touch, the feasibility of using low concentration epidural anesthesia in PELD to obtain enough analgesia and avoid the risk of nerve injury was confirmed. Methods: 153 cases of intervertebral foramen surgery from October 2017 to January 2020 were selected and divided into local anesthesia group (LA group), 0.4% ropivacaine epidural anesthesia group (EA group), and intravenous anesthesia group (IVA group) according to different anesthesia methods. The changes of blood pressure and heart rate, the incidence of rescue analgesia and nerve root non-touch were compared among the three groups. Results: The difference of map peak value among the three groups was statistically significant (P < 0.001); pairwise comparison showed that the map peak value of the LA group was higher than that of the EA group (P < 0.001) and IVA group (P < 0.001), but there was no statistical significance between the EA group and IVA group. The difference of HR peak value among the three groups was statistically significant; pairwise comparison showed that the HR peak value of the LA group was higher than that of the EA group (P < 0.001) and IVA group (P < 0.001), but there was no statistical significance between the EA group and IVA group. There was significant difference in the incidence of intraoperative hypertension among the three groups (P < 0.05); pairwise comparison showed that the incidence of intraoperative hypertension in the EA group was lower than that in the LA group (P < 0.05), while there was no significant difference between the IVA group, EA group, and LA group. There was significant difference in the incidence of rescue analgesia among the three groups (P < 0.01); pairwise comparison showed that the incidence of rescue analgesia in the EA group was lower than that in the LA group (P < 0.05) and IVA group (P < 0.05), but there was no significant difference between the LA group and IVA group. Due to the different analgesic mechanisms of the three anesthesia methods, local anesthesia and intravenous anesthesia do not cause the loss of nerve tactile, while the incidence of nerve tactile in 0.4% ropivacaine epidural anesthesia is only 2.4%, which is still satisfactory. Conclusion: Epidural anesthesia with 0.4% ropivacaine is a better anesthesia method for PELD. It not only has a low incidence of non-tactile nerve, but also has perfect analgesia and more stable intraoperative circulation.

Effect of ADRA2A gene polymorphisms on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women with cesarean section.

It is well known that differences in drug reactions among individuals are widespread, and therefore the study of genetic polymorphisms of drug targets has become a research hotspot. Dexmedetomidine is clinically effective by acting on α2 adrenergic receptor and the impact of the adrenoceptor α2A gene (ADRA2A) polymorphisms on the anesthetic and analgesic effects of dexmedetomidine is related to the clinical application of dexmedetomidine. The present study aimed to analyze the effects of the rs1800035, rs201376588 and rs775887911 locus single-nucleotide polymorphisms of the ADRA2A on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women. A total of 434 Chinese women undergoing cesarean section were enrolled in this study. A 3-ml fasting venous blood sample was collected from all subjects for genomic DNA extraction and genotype detection. The pre-anesthetic and post-anesthetic pain threshold (PTh), pain tolerance threshold (PTTh), mean arterial pressure, heart rate, blood oxygen saturation, cortisol (Cor) content, blood glucose (Glu) content, opioid usage, patient-controlled analgesia pressing times, surgical satisfaction and postoperative adverse reactions were recorded. The visual analogue scale (VAS) and Ramsay sedation score were evaluated. PTh and PTTh in the wild-type women were higher than those in the women with mutations (P<0.05). The postoperative VAS scores of wild-type women were lower than those of mutants (P<0.05). The Ramsay sedation scores of wild-type patients at 12 h after the operation were significantly higher than in those with mutations (P<0.05). The levels of Cor and Glu in women with mutations were significantly higher than those of wild-type women at 12, 24 and 48 h after surgery (P<0.05). The satisfaction with surgery of wild-type patients was higher than that of patients with mutations (P<0.05). Gene mutations of rs1800035, rs201376588 and rs775887911 loci in the ADRA2A gene reduced the anesthetic and analgesic effect during and after cesarean section in Chinese Han women. Postoperative analgesia of mothers with mutations may require higher doses of analgesics.

The Efficacy and Safety of Transcutaneous Acupoint Interferential Current Stimulation for Cancer Pain Patients With Opioid-Induced Constipation: A Prospective Randomized Controlled Study.

INTRODUCTION: Opioid-induced constipation (OIC) is a principal complication secondary to analgesic therapy for cancer pain patients who suffer moderate to severe pain. In this study, we observe the efficacy and safety of transcutaneous acupoint interferential current (IFC) stimulation in those patients with OIC. METHODS: A total of 198 patients were randomly allocated to the IFC group and control group in a 1:1 ratio. Finally, 98 patients in the IFC group received 14 sessions administered over 2 weeks, whereas 100 patients in the control group took lactulose orally during the same period. Observation items were documented at management stage and at follow-up stage according to Cleveland Constipation Scales (CCS), pain Numeric Rating Scales (NRS) and Patient Assessment of Constipation Quality of Life (PAC-QoL). RESULTS: The total curative effects of the IFC group and the control group were indistinguishable (76.5% vs 70.0%, P = .299). Regarding CCS and PAC-QoL scores, no significant difference was observed between the 2 groups during the management time and at the follow-up stage of week 3 ( P > .05, respectively), but groups were distinguished at the follow-up stage of week 4 ( P < .001 and P = .031, respectively). The pain NRS decreased significantly at management stage week 2 and follow-up stage week 3 and week 4 ( P = .013, P = .041, P = .011, respectively). CONCLUSIONS: Transcutaneous acupoint IFC therapy over acupoints of Tianshu (ST25) and Zhongwan (RN12) may improve constipation and quality of life in cancer patients receiving opiates; further studies are worthwhile.