Chloroprocaine 3% Gel as a Novel Ocular Topical Anesthetic: Results from a Multicenter, Randomized Clinical Trial in Patients Undergoing Cataract Surgery.

Purpose: To compare the efficacy and safety of a novel ophthalmic anesthetic, chloroprocaine 3% gel to tetracaine 0.5% eye drops in patients undergoing cataract surgery with phacoemulsification. Methods: This was a prospective, randomized, multicenter, active-controlled, masked-observer, parallel group competitive equivalence study. The study comprised 338 patients having routine cataract extraction by clear corneal phacoemulsification, randomized to receive 3 drops of chloroprocaine gel (n = 166) or tetracaine eye drops (n = 172) before surgery. The primary objective of the study was to assess the equivalence of chloroprocaine gel to tetracaine eye drops as proportion of patients with successful ocular surface anesthesia, without any supplementation just before intraocular lens implantation. Safety measurements were pain, irritation, burning, stinging, photophobia, and foreign body sensation, graded by the patient and objective ocular signs. Results: Equivalence was demonstrated, with a somewhat higher success rate of chloroprocaine gel: 152/166 (92.0%) chloroprocaine versus 153/172 (90.5%) tetracaine patients achieved ocular surface anesthesia with no supplementation. Difference in proportions was 1.5% confidence interval [95% CI: (-3.6 to 6.6)] and 90% CI fell within (-10 to 10). Mean onset of anesthesia was 1.35 ± 0.87 min for chloroprocaine and 1.57 ± 1.85 for tetracaine (P = 0.083). Mean duration of anesthesia was 21.57 ± 12.26 min for chloroprocaine and 22.04 ± 12.58 for tetracaine (P = 0.574). No treatment emergent adverse events related to chloroprocaine were reported and no relevant findings related to local tolerance or vital signs were observed in both arms. Conclusions: Results obtained from the present cataract study demonstrated that chloroprocaine 3% ophthalmic gel is safe and effective, representing a valid alternative in ocular topical anesthesia. Clinical Trial Registration number: NCT04685538.

Chloroprocaine antagonizes progression of breast cancer by regulating LINC00494/miR-3619-5p/MED19 axis.

Breast cancer, as the most prevalent female malignancy, leads the cancer-related death in women worldwide. Local anesthetic chloroprocaine exhibits antitumor potential, but its specific functions and underlying molecular mechanisms in breast cancer remain unclear. Here, we demonstrated chloroprocaine significantly inhibited proliferation, invasion and induced apoptosis of breast cancer cells in vitro. Tumor growth and pulmonary metastasis were also suppressed in BABL/c nude mice model with chloroprocaine treatment. LINC00494 was identified as one of the most downregulated long noncoding RNAs in chloroprocaine-treated breast cancer cells by high-throughput sequencing. Futhermore, high level of LINC00494 was positively associated with poor outcome of breast cancer patients. LINC00494 acted as a "miRNAs sponge" to compete with MED19 for the biding of miR-3619-5p, led to the upregulation of MED19. LINC00494/miR-3619-5p/MED19 axis participated in chloroprocaine-mediated inhibition of proliferation, invasion and promotion of apoptosis of breast cancer cells. Consequently, our finding suggested local anesthetic chloroprocaine attenuated breast cancer aggressiveness through LINC00494-mediated signaling pathway, which detailly revealed the clinical value of chloroprocaine during breast cancer treatment.

Efficacy and Safety of Oxybuprocaine Hydrochloride Gel in Alleviating Pain during Male Urethral Catheterization: A Single-Center Randomized Controlled Study.

Background: The purpose of this study was to determine whether oxybuprocaine hydrochloride gel could alleviate pain during male catheterization. Methods: Between September 2021 and March 2022, a randomized controlled trial was conducted at the Urology Department of Harbin Medical University Cancer Hospital (China). A total of 192 adult male patients requiring catheterization were enrolled and randomly assigned to one of two groups: 96 in the test group and 96 in the control group. The test group included patients who received oxybuprocaine hydrochloride gel as urethral lubricant, while patients in the control group received liquid paraffin. The preoperative and postoperative pain scores were compared using nonparametric tests. Results: At the baseline, there was no significant difference between the two groups. There was no significant difference in preoperative pain scores between the test group (mean ± SD = 20.04 ± 2.68 mm) and the control group (mean ± SD = 20.21 ± 3.23 mm) (p=0.694). Postoperative pain scores increased significantly in the test (mean ± SD = 31.98 ± 2.57 mm, p < 0.001) and control groups (mean ± SD = 38.96 ± 2.02 mm, p < 0.001) groups. Postoperative pain scores were significantly lower in the test group (mean ± SD = 31.98 ± 2.57 mm) than those in the control group (mean ± SD = 38.96 ± 2.02 mm (p < 0.001). Conclusions: The use of oxybuprocaine hydrochloride gel significantly reduced pain during male urethral catheterization. The study provides evidence for clinicians to use oxybuprocaine hydrochloride gel during male catheterization.

Influence of height on ED95 of intrathecal 2-chloroprocaine for knee arthroscopy: A prospective dose-response clinical trial.

BACKGROUND: Plain 2-chloroprocaine , a rapid acting amino-ester-type local anaesthetic, is used in short ambulatory procedures under spinal anaesthesia. The ED 95 of 2-chloroprocaine for lower limb surgery has not yet been defined. Moreover, patients' body height could influence the effects of the administered dose. OBJECTIVES: The aim of this study was to determine the ED 95 of plain 2-chloroprocaine based on the height of patients undergoing ambulatory knee arthroscopy under spinal anaesthesia using the continual reassessment statistical method (CRM). DESIGN: Prospective, dose-response, double blind, controlled, bi-center, clinical trial. SETTING: One university teaching hospital in Brussels and one general teaching hospital, Braine l'Alleud, Belgium. Université libre de Bruxelles. PATIENTS: ASA I-III (120 patients) scheduled for day-case knee arthroscopy under spinal anaesthesia. INTERVENTIONS: Patients were divided into three groups of 40, each comprising 10 cohorts of 4 patients, according to their respective heights (Group 1: 150-165 cm, Group 2: 166-180 cm, Group 3: 181-195 cm). Each patient enrolled into one of the 3 groups received an intrathecal dose of plain 2-chloroprocaine determined by the CRM. The starting doses for the first cohorts of four were 40 mg in group 1, 45 mg in group 2 and 50 mg in group 3. The doses for subsequent cohorts were determined by CRM of outcomes in all patients in the previous competed cohorts. Anaesthesia was considered successful when there was a lack of pinprick or cold sensation up to T12, the visual analogue scale score for tourniquet pain was < 2 and no pain during surgery. MAIN OUTCOMES: The primary outcome was the success or failure of the block. Side effects were also recorded. RESULTS: ED 95 of 2-chloroprocaine is 40 mg in group 1, 35 mg in group 2, 45 mg in group 3. Groups were different in terms of height and gender ( P  < 0.05) and similar in terms of body mass index and age ( P  > 0.05). CONCLUSION: The ED95 of intrathecal 2-chloroprocaine for patients undergoing ambulatory knee arthroscopy is between 35 and 45 mg. Height could be a factor involved in the calculation, and patient sex could partly explain the nonlinear relation between height and dose. TRIAL REGISTRY NUMBER: Clinicaltrials.gov NCT03882489.

Pharmacokinetics and Tolerability of Intraperitoneal Chloroprocaine After Fetal Extraction in Women Undergoing Cesarean Delivery.

BACKGROUND: Intraperitoneal chloroprocaine has been used during cesarean delivery to supplement suboptimal neuraxial anesthesia for decades. The short in vitro half-life of chloroprocaine (11-21 seconds) has been cited to support the safety of this approach. However, there are no data regarding the rate of absorption, representing patient drug exposure, through this route of administration. Accordingly, we designed a study to determine the in vivo half-life of intraperitoneal chloroprocaine and assess clinical tolerability. METHODS: We designed a single-center, prospective, cohort, multiple-dose escalation study of women 18 to 50 years of age undergoing cesarean delivery with spinal anesthesia. Chloroprocaine (40 mL) was administered after delivery of the newborn and before uterine closure. The first cohort (n = 5) received 1%, the second cohort (n = 5) received 2%, and the third cohort (n = 5) received 3% chloroprocaine solution. Maternal blood samples were obtained before administration and 1, 5, 10, 20, and 30 minutes after dosing. The primary objective was to define the pharmacokinetic profile of intraperitoneal chloroprocaine, including in vivo half-life. The secondary objective was to evaluate tolerability through determination of peak plasma concentration and prospective assessment for local anesthetic systemic toxicity. RESULTS: The peak plasma concentration occurred 5 minutes after intraperitoneal administration in all 3 cohorts: 64.8 ng/mL (6.5 µg/kg), 28.7 ng/mL (2.9 µg/kg), and 799.2 ng/mL (79.9 µg/kg) for 1%, 2%, and 3% chloroprocaine, respectively. The in vivo half-life of chloroprocaine after intraperitoneal administration was estimated to be 5.3 minutes (95% confidence interval, 4.0-6.6). We did not detect clinical signs of local anesthetic systemic toxicity in any of the 3 cohorts. CONCLUSIONS: The in vivo half-life of intraperitoneal chloroprocaine (5.3 minutes) is more than an order of magnitude greater than the in vitro half-life (11-21 seconds). However, maximum plasma concentrations of chloroprocaine (C max range, 0.05-79.9 µg/kg) were not associated with local anesthetic systemic toxicity and remain well below our predefined safe level of exposure (970 µg/kg) and levels associated with clinical symptoms (2.6-2.9 mg/kg). Therefore, our study suggests that intraperitoneal chloroprocaine, in a dosage ≤1200 mg, administered after fetal extraction, is well tolerated during cesarean delivery.

[Effect of dexamethasone combined with oxybuprocaine hydrochloride gel on prevention of postoperative sore throat after nasal endoscopy].

OBJECTIVE: To explore the effectiveness and feasibility of dexamethasone combined with oxybuprocaine hydrochloride gel on the prevention of postoperative sore throat after nasal endoscopy. METHODS: In the study, 60 patients with American Society of Anesthesiologist (ASA) physical statuses Ⅰ to Ⅱ, aged 18 to 72 years, scheduled for elective nasal endoscope surgery under general anesthesia requiring endotracheal intubation were randomly divided into dexamethasone combined with oxybuprocaine hydrochloride gel group (G group, n=30) and control group (C group, n=30). The patients in the G group received dexamethasone 0.1 mg/kg before induction and the oxybuprocaine gel was applied to the endotracheal catheter cuff and the front end within 15 cm. The patients in the C group received the same dose of saline and the saline was applied to the endotracheal catheter cuff and the front end within 15 cm. Then, all the patients in the two groups received the same induction and anesthesia maintainance. The operation time, anesthesia time, emergence time, extubation time and departure time were recorded. The intraoperative infusion volume, blood loss volume, propofol, remifentanil, rocuronium dosage were also recorded. The adverse reactions such as intraoperative hypotension, bradycardia and postoperative agitation were recorded. The postoperative sore throat score was recorded at the end of operation and 4 h, 8 h, 12 h, and 24 h after operation. RESULTS: Compared with the C group, the emergence time [(8.4±3.9) min vs. (10.8±4.7) min], extubation time [(8.8±3.7) min vs. (11.9±4.8) min], and departure time [(20.0±5.3) min vs. (23.0±5.8) min] were significantly shorter, and the propofol dosage [(11.8±1.8) mg/kg vs. (15.9±4.6) mg/kg], remifentanil dosage [(10.9±4.7) µg/kg vs. (14.1±3.6) µg/kg] were significantly less in the G group, and there was no difference of rocuronium dosage in the two groups. Compared with the C group the incidence of intraoperative hypotension [10%(3/30) vs. 30%(9/30)], bradycardia [16.7%(5/30) vs. 20%(6/30)] and postoperative agitation [6.7%(2/30) vs. 23.3%(7/30)] were significantly lower in the C group. The postoperative sore throat score at the end of operation, 4 h, 8 h, 12 h and 24 h after operation in the G group were significantly lower than in the C group respectively [0 (0, 1) vs. 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs. 1 (0.75, 1), 0 (0, 0) vs. 1 (0, 1)]. CONCLUSION: Dexamethasone combined with oxybuprocaine hydrochloride gel was effective and feasible on the prevention of postoperative sore throat after nasal endoscopy.

Intrathecal bupivacaine versus chloroprocaine for transvaginal cervical cerclage placement: a retrospective cohort study.

BACKGROUND: Bupivacaine is commonly used in spinal anesthesia for cervical cerclage placement, but its long duration of action can delay hospital discharge. Chloroprocaine has a short duration of action and has re-emerged as an agent for ambulatory neuraxial anesthesia. There are limited data comparing intrathecal bupivacaine and chloroprocaine when used for cerclage placement. This retrospective study compares the time to hospital discharge between these drugs when used in spinal anesthesia for cervical cerclage placement. METHODS: A retrospective analysis of patients who underwent transvaginal cerclage placement under neuraxial anesthesia with intrathecal hyperbaric bupivacaine or plain chloroprocaine between January 1, 2015 and October 31, 2020. The primary outcome was the time to hospital discharge. Secondary outcomes included the incidence of inadequate anesthesia, postoperative pain scores and postoperative neurologic symptoms. RESULTS: Three hundred and sixty patients were included in the final analysis (bupivacaine n=236, chloroprocaine n=124). The median (IQR) intrathecal dose was 7.5 (7.5, 9) mg and 45 (45, 50) mg in the bupivacaine and chloroprocaine groups respectively. The time (median [IQR]) from spinal anesthesia to hospital discharge was significantly shorter in the chloroprocaine group compared with the bupivacaine group (218 [180, 253] vs. 370 [309, 424] min, P<0.001). There were no significant differences between the groups for secondary outcomes and neither group had a patient report neurologic symptoms. CONCLUSION: When utilized in spinal anesthesia for transvaginal cervical cerclage placement, chloroprocaine may reduce the time to discharge while providing comparable anesthesia to that provided by bupivacaine.

ED 90 of Intrathecal Chloroprocaine With Fentanyl for Prophylactic Cervical Cerclage: A Sequential Allocation Biased-Coin Design.

BACKGROUND: Chloroprocaine is a short-acting local anesthetic that has been used for spinal anesthesia in outpatient surgery. There is limited experience with spinal chloroprocaine for prophylactic cervical cerclage placement. We sought to determine the effective dose of intrathecal chloroprocaine for 90% of patients (ED90) undergoing prophylactic cervical cerclage placement. We hypothesized that the ED90 of intrathecal chloroprocaine when combined with 10-ug fentanyl would be between 33 and 54 mg. METHODS: In this prospective 2-center double-blinded study, we enrolled women undergoing prophylactic cervical cerclage placement under combined spinal-epidural anesthesia. A predetermined dose of intrathecal 3% chloroprocaine with fentanyl 10 ug was administered. The initial dose was 45-mg intrathecal chloroprocaine. Subsequent dose adjustments were determined based on the response of the previous subject using an up-down sequential allocation with a biased-coin design. A dose was considered effective if at least a T12 block was achieved, and there was no requirement for epidural activation or intraoperative analgesic supplementation during the procedure. The primary outcome was the ED90 of intrathecal chloroprocaine with fentanyl 10 ug. Secondary outcomes included duration of surgery, anesthetic side effects, time to resolution of motor and sensory block, time to achieve recovery room discharge criteria, and patient satisfaction with anesthetic care. Isotonic regression was used to estimate the ED90. RESULTS: Forty-seven patients were enrolled into the study. Two patients were excluded (1 protocol violation and 1 failed block). In total, 45 patients completed the study. The estimated ED90 (95% confidence interval) for intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg (45.0-50.1 mg). The median (interquartile range [IQR]) duration of surgery was 15 (10-24) minutes. Resolution of the motor (Bromage 0) and sensory block took a median time of 60 (45-90) minutes and 90 (75-105) minutes, respectively. The median time to achieve recovery room discharge criteria was 150 (139-186) minutes. Satisfaction with anesthetic management was high in all patients. There were no reports of postdural puncture headache or transient neurological symptoms postoperatively. CONCLUSIONS: The ED90 of intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg. Intrathecal chloroprocaine was associated with rapid block recovery and high patient satisfaction, which makes it well suited for outpatient obstetric procedures.

ED90 of spinal 2-chloroprocaine 1% in ambulatory knee arthroscopy up to 45 min: a randomized biased-coin- up-and-down sequential allocation trial.

BACKGROUND: A short acting spinal anesthetic facilitates smooth flow since quick recovery of motor function will facilitate unassisted ambulation. The aim of this study was to estimate the effective dose (ED90) of intrathecal 2-chloroprocaine 1% in outpatient knee arthroscopy. METHODS: Two cohorts were included in two different hospitals. In cohort I, a randomized biased-coin up-and-down design with 40 patients was used to find the ED90. Four dose-levels of plain 2-chloroprocaine 1% were used: 25, 30, 35 and 40 mg. The identified primary outcome, the ED90, was validated in 50 patients in cohort II with an open label design. Secondary outcomes included time to complete recovery from motor and sensory block with spinal injection as time zero, peak sensory block level, urine retention and time until hospital discharge. RESULTS: Forty patients were included in the final analysis in cohort I. The ED90 was estimated at 27.8 mg, successful spinal anesthesia was obtained in 38 patients (95%). Fifty patients were included in the final analysis in cohort II, 49 patients had successful anesthesia with a fixed round dose of 28 mg. In this Cohort, peak sensory block was T10/T11 (range: (L4-T4)). The median time to full recovery of the motor block was 60 min (45-60) and 90 min (75-105) for the sensory block. The mean time to hospital discharge was 2.9 hours (0.7). CONCLUSION: The ED90 of 2-chloroprocaine 1% in knee arthroscopy was estimated to be 27.8 mg. In an external population, the ED90 resulted in successful anesthesia in 98% of the patients (95% CI 89% to 100%). TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL6769).

Continuous epidural chloroprocaine after abdominal surgery is associated with lower postoperative opioid exposure in NICU infants.

BACKGROUND: Epidural anesthesia in infants undergoing open abdominal surgery has the potential to reduce opioid consumption, lower pain scores, and expedite tracheal extubation. We evaluated associations between use of continuous epidural chloroprocaine and improved intra- and post-operative outcomes. METHODS: This matched retrospective cohort study first identified 24 patients who between April 2018 through December 2019 were treated with a caudal catheter and epidural chloroprocaine infusion for a laparotomy at postnatal age of 6 months or less. A matched comparator group of 24 patients was derived based on age and type of surgery. Exclusion criteria were the presence of a preoperative opioid infusion, comorbidities that would preclude appropriate pain assessment, or a recent surgical procedure. Primary outcomes included opioid consumption and pain scores; we secondarily analyzed intraoperative anesthetic requirements, other systemic analgesic use, vital signs, tracheal extubation time, and procedural times. RESULTS: Treatment with epidural anesthesia was associated with lower 5-day total postoperative opioid consumption (3.2 mg/kg vs. 19.7 mg/kg in the respective epidural vs. systemic groups, p = 0.001) and time to tracheal extubation (1.3 days vs. 3.2 days, p = 0.005). Any statistically significant differences in pain scores were not clinically meaningful. There were no differences in mean arterial pressure or intraoperative inhaled anesthetic doses. CONCLUSION: Continuous infusion of epidural chloroprocaine in infants following open abdominal surgery may limit exposure to systemic opioid medications while providing adequate postoperative analgesia and shortening time to tracheal extubation.

Investigation of the fluorescence of benoxinate for facile determination in pure form, eye drops and aqueous humor.

A new approach to determine the local anesthetic benoxinate spectrofluorimetrically was developed. It was found that benoxinate exhibits strong native fluorescence in ethanol at 371 nm after excitation at 297 nm. There was a linear response between the fluorescence intensity and the concentration of the studied drug over the range of 10.0-100.0 ng/ mL. The suggested spectrofluorimetric method was optimized and validated following the pharmacopoeial guidelines. The obtained results were fully discussed and statistically analyzed in relevance to a previous published spectroscopic method. The limit of quantification (LOQ) of the present method was 1.79 ng/mL. Inter-day and intra-day precision relative standard deviations were lower than 1.5%.Finally, the proposed methodology has been adopted for determination of benoxinate in aqueous humor with a mean percentage recovery 99.87 ± 1.66 as well as in the pharmaceutical eye drops with a mean percentage recovery 100.37 ± 1.32. The method is cost-effective and green as it depends in water and ethanol mainly.

Intrathecal 2-Chloroprocaine 3% Versus Hyperbaric Bupivacaine 0.75% for Cervical Cerclage: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Cervical cerclage is a short ambulatory procedure. For spinal anesthesia, local anesthetic agents with rapid postoperative resolution are desired. We hypothesized that in combination with fentanyl, intrathecal 2-chloroprocaine would produce earlier resolution of motor block, resulting in shorter time to meet recovery room discharge criteria than hyperbaric bupivacaine. METHODS: Women undergoing cervical cerclage with spinal anesthesia were randomized to receive intrathecal 2-chloroprocaine 3% 50 mg or hyperbaric bupivacaine 0.75% 9 mg, both with fentanyl 15 µg. Doses were empirically selected. The onset and resolution of sensory and motor blockade and time to achieve recovery room discharge criteria were monitored. On postoperative day 1, patients rated their satisfaction with the anesthetic and reported on transient neurologic symptoms (TNS), back pain, or headache. The primary outcome was time from spinal injection to motor block resolution. The main secondary outcomes included times from spinal injection to (i) T12 dermatomal level, (ii) sensory block resolution, and (iii) ability to ambulate and void. RESULTS: Forty-three women were enrolled and randomized to either the chloroprocaine (N = 23) or bupivacaine group (N = 20). The mean (standard deviation [SD]) duration of surgery was 35.3 (11.4) minutes. There was no difference between groups for time to motor block resolution-the median [interquartile range] time for the bupivacaine group (N = 17) was 112 [97-143] minutes versus 109 [88-148] minutes in the chloroprocaine group (N = 22), P = .66, but there was a significant difference in median time to sensory block resolution: 143 [116-162] minutes in the chloroprocaine group versus 198 [152-263] minutes in the bupivacaine group, P = .002. The recovery room discharge criteria, which at our institution include the ability to ambulate unassisted and void urine, were met 76 (95% CI, 33-145) minutes earlier in the chloroprocaine group, P < .0005. One complete block failure occurred with hyperbaric bupivacaine and 2 subjects in each group received treatment for intraoperative discomfort. No patients reported TNS. CONCLUSIONS: Intrathecal 2-chloropocaine 3% provided similarly effective surgical anesthesia for cerclage placement. Although no difference in time to motor block resolution between groups was observed, the time to sensory block resolution and time to meet recovery room discharge criteria were both significantly shorter among patients who received chloroprocaine than patients who received bupivacaine. Future studies are needed to identify and compare equipotent doses of chloroprocaine and bupivacaine to confirm the superiority of chloroprocaine for this ambulatory obstetric procedure.

Simultaneous estimation of recently FDA approved co-formulated ophthalmic solution benoxinate and fluorescein: Application to aqueous humor.

Nine simple, cost-effective, and sensitive spectrophotometric methods were developed to simultaneously assay benoxinate HCl and fluorescein sodium in their co-formulated eye drops without barring common excipients. A direct UV spectrophotometric method (method I) was developed for their FLU assay at 481 nm over the concentration range of 0.6-10.0 µg mL-1. Meanwhile, BEN was assayed over the concentration range of 1.0-25.0 µg mL-1 by different UV based methods, namely, conventional dual-wavelength method (DW) (method II), first derivative1D spectrophotometry (method III), second derivative2D spectrophotometry (method IV), ratio spectra difference spectrophotometry (method V), the first derivative of ratio spectra (method VI), ratio subtraction method (method VII), isosbestic point method (ISP) (method VIII) and absorption factor method (method IX). The performance of the proposed methods was assessed relying on the correlation coefficients, relative standard deviations, and limits of detection and quantitation. The variance ratio F-test and Student t-test showed no significant differences between the obtained results of the developed methods and those of reference methods. The proposed methods were also applied to determine studied drugs in commercial eye drops and aqueous humor.

Evaluation of neurotoxicity and long-term function and behavior following intrathecal 1 % 2-chloroprocaine in juvenile rats.

Spinally-administered local anesthetics provide effective perioperative anesthesia and/or analgesia for children of all ages. New preparations and drugs require preclinical safety testing in developmental models. We evaluated age-dependent efficacy and safety following 1 % preservative-free 2-chloroprocaine (2-CP) in juvenile Sprague-Dawley rats. Percutaneous lumbar intrathecal 2-CP was administered at postnatal day (P)7, 14 or 21. Mechanical withdrawal threshold pre- and post-injection evaluated the degree and duration of sensory block, compared to intrathecal saline and naive controls. Tissue analyses one- or seven-days following injection included histopathology of spinal cord, cauda equina and brain sections, and quantification of neuronal apoptosis and glial reactivity in lumbar spinal cord. Following intrathecal 2-CP or saline at P7, outcomes assessed between P30 and P72 included: spinal reflex sensitivity (hindlimb thermal latency, mechanical threshold); social approach (novel rat versus object); locomotor activity and anxiety (open field with brightly-lit center); exploratory behavior (rearings, holepoking); sensorimotor gating (acoustic startle, prepulse inhibition); and learning (Morris Water Maze). Maximum tolerated doses of intrathecal 2-CP varied with age (1.0 µL/g at P7, 0.75 µL/g at P14, 0.5 µL/g at P21) and produced motor and sensory block for 10-15 min. Tissue analyses found no significant differences across intrathecal 2-CP, saline or naïve groups. Adult behavioral measures showed expected sex-dependent differences, that did not differ between 2-CP and saline groups. Single maximum tolerated in vivo doses of intrathecal 2-CP produced reversible spinal anesthesia in juvenile rodents without detectable evidence of developmental neurotoxicity. Current results cannot be extrapolated to repeated dosing or prolonged infusion.

Effect of dexamethasone combined with oxybuprocaine hydrochloride gel on prevention of postoperative sore throat after nasal endoscopy / 北京大学学报(医学版)

OBJECTIVE@#To explore the effectiveness and feasibility of dexamethasone combined with oxybuprocaine hydrochloride gel on the prevention of postoperative sore throat after nasal endoscopy.@*METHODS@#In the study, 60 patients with American Society of Anesthesiologist (ASA) physical statuses Ⅰ to Ⅱ, aged 18 to 72 years, scheduled for elective nasal endoscope surgery under general anesthesia requiring endotracheal intubation were randomly divided into dexamethasone combined with oxybuprocaine hydrochloride gel group (G group, n=30) and control group (C group, n=30). The patients in the G group received dexamethasone 0.1 mg/kg before induction and the oxybuprocaine gel was applied to the endotracheal catheter cuff and the front end within 15 cm. The patients in the C group received the same dose of saline and the saline was applied to the endotracheal catheter cuff and the front end within 15 cm. Then, all the patients in the two groups received the same induction and anesthesia maintainance. The operation time, anesthesia time, emergence time, extubation time and departure time were recorded. The intraoperative infusion volume, blood loss volume, propofol, remifentanil, rocuronium dosage were also recorded. The adverse reactions such as intraoperative hypotension, bradycardia and postoperative agitation were recorded. The postoperative sore throat score was recorded at the end of operation and 4 h, 8 h, 12 h, and 24 h after operation.@*RESULTS@#Compared with the C group, the emergence time [(8.4±3.9) min vs. (10.8±4.7) min], extubation time [(8.8±3.7) min vs. (11.9±4.8) min], and departure time [(20.0±5.3) min vs. (23.0±5.8) min] were significantly shorter, and the propofol dosage [(11.8±1.8) mg/kg vs. (15.9±4.6) mg/kg], remifentanil dosage [(10.9±4.7) μg/kg vs. (14.1±3.6) μg/kg] were significantly less in the G group, and there was no difference of rocuronium dosage in the two groups. Compared with the C group the incidence of intraoperative hypotension [10%(3/30) vs. 30%(9/30)], bradycardia [16.7%(5/30) vs. 20%(6/30)] and postoperative agitation [6.7%(2/30) vs. 23.3%(7/30)] were significantly lower in the C group. The postoperative sore throat score at the end of operation, 4 h, 8 h, 12 h and 24 h after operation in the G group were significantly lower than in the C group respectively [0 (0, 1) vs. 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs. 1 (0.75, 1), 0 (0, 0) vs. 1 (0, 1)].@*CONCLUSION@#Dexamethasone combined with oxybuprocaine hydrochloride gel was effective and feasible on the prevention of postoperative sore throat after nasal endoscopy.

Evaluation of corneal anaesthesia after the application of topical 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine in normal horses.

OBJECTIVE: To compare the corneal anaesthetic effect of 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine on normal equine eyes. STUDY DESIGN: Prospective, blinded crossover study. ANIMALS: A group of 10 clinically healthy horses. METHODS: Corneal sensitivity was determined in each eye by measuring corneal touch threshold (CTT). The study had three phases. Each subject was randomly given one of the three treatments followed by a 72 hour washout period. Every horse received all treatments. Baseline CTT was recorded prior to anaesthetic instillation (T0) then CTT was measured 5 and 10 minutes after (T1 and T2, respectively), then 20 to 90 minutes (T3 to T10) at 10 minute intervals. CTT data were compared among treatments at each time point using the Friedman test p < 0.05. RESULTS: Median (range) baseline CTT was 51.3 (25.0-60.0) mm for bupivacaine, 50.0 (40.0-55.0) mm for oxybuprocaine and 55.0 (30.0-60.0) mm for lidocaine. All treatments caused a significant decrease in CTT at T1. The lowest CTT was observed at T3 with bupivacaine and oxybuprocaine treatments. Median CTTs at this time point were 18.7 (5.0-25.0) mm and 28.7 (25.0-40.0) mm, respectively. The lowest CTT with lidocaine treatment was 28.7 (20.0-50.0) mm at T6 (50 minutes). At T3, CTT was significantly lower with the bupivacaine treatment compared with oxybuprocaine and lidocaine treatments (p < 0.0074). There was no significant difference in CTT values between T1 and T6 for bupivacaine, between T1 and T7 for lidocaine, and between T1 and T8 for oxybuprocaine. Duration of the maximum effect was 45 minutes for the bupivacaine, 55 minutes for the lidocaine and 65 minutes for the oxybuprocaine treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a 0.5% injectable solution of bupivacaine or a 2% lidocaine had similar anaesthetic effect to the commonly used oxybuprocaine. Therefore, they might be used as alternatives for corneal anaesthesia.

A randomised, non-inferiority study of chloroprocaine 2% and ropivacaine 0.75% in ultrasound-guided axillary block.

Chloroprocaine is a short-acting local anaesthetic with a rapid onset of action and an anaesthesia duration up to 60 min. In this pivotal study success rates, onset and remission of motor and sensory block and safety of chloroprocaine 2% was compared to ropivacaine 0.75% for short-duration distal upper limb surgery with successful block rates as primary outcome. The study was designed as a prospective, randomised, multi-centre, active-controlled, double-blind, parallel-group, non-inferiority study, performed in 4 European hospitals with 211 patients scheduled for short duration distal upper limb surgery under axillary plexus block anaesthesia. Patients received either ultrasound guided axillary block with 20 ml chloroprocaine 2%, or with 20 ml ropivacaine 0.75%. Successful block was defined as block without any supplementation in the first 45 min calculated from the time of readiness for surgery. 90.8% patients achieved a successful block with chloroprocaine 2% and 92.9% patients with Ropivacaine 0.75%, thus non-inferiority was demonstrated (10% non inferiority margin; 95% CI - 0.097, 0.039; p = 0.02). Time to onset of block was not significantly different between the groups. Median time to motor and sensory block regression was significantly shorter as was time to home discharge (164 [155-170] min for chloroprocaine versus 380 [209-450] for the ropivacaine group, p < 0.001). For short-duration surgical procedures, the short-acting Chloroprocaine 2% may be used, with success rates non-inferior to ropivacaine and a favourable safety profile.Trial registration: The trial was registered at Clinicaltrials.gov with registration number NCT02385097 (March 11th, 2015) and European Clinical Trial Database with the EudraCT number 2014-002519-40 (July 7th, 2015, Austria-BASG).