A comparison of the time course of action and laryngeal mask airway insertion conditions with different doses of mivacurium for day-case urologic surgery in children: a prospective cohort study.

Objective: To investigate the time course of action of different doses of mivacurium and determine the appropriate dose for laryngeal mask airway (LMA) insertion for day-case urologic surgery in children. Methods: A total of 105 patients who enrolled in this study between March 2021 and December 2021 were randomised into 3 groups: Group A (mivacurium 0.15 mg/kg, n = 35), Group B (mivacurium 0.20 mg/kg, n = 35) and Group C (mivacurium 0.25 mg/kg, n = 35). The different doses of mivacurium were injected before LMA insertion. The primary outcomes included the grading of conditions for the LMA insertion-18 score, onset time, recovery index and the duration that mivacurium was effective. Secondary outcomes included pulse oxygen saturation, mean blood pressure, heart rate and the incidence of adverse events. Results: The score of the conditions for LMA insertion in Group A was significantly lower than in Groups C and B (p < 0.005). There was a significant difference in the onset time between Groups B and A (p < 0.005). There was no significant difference in the overall incidence of adverse reactions between these groups (p > 0.05). Conclusion: Anaesthesia with 0.2 mg/kg of mivacurium can effectively shorten the onset time and facilitate insertion of the LMA in children undergoing day-case urologic surgery.

Insights into the spectrofluorometric determination of the neuromuscular blocker mivacurium chloride.

Fluorescence spectroscopy is gaining interest in the analysis and quantitative determination of different drugs. This study was carried out to investigate the fluorometric properties of the short-acting muscle relaxant mivacurium in its pure form, injection, and human plasma. It is nondepolarizing skeletal muscle relaxant for intravenous (IV) administration. Mivacurium shows a strong native fluorescence in methanol at 317 nm after excitation at 230 nm (Method I). The critical parameters that may influence the fluorescence of this drug were carefully studied. A linear response between concentration and fluorescence was constructed over the concentration range: 20.0 to 400.0 ng/mL with determination coefficient (r2) equal to 0.9998. Additionally, the correlation coefficient of the linear relationship (r) was found to be 0.9999 with a slope = 2.196 and intercept = -16.61. Limits of quantitation and detection were calculated mathematically to be 17.45 and 5.75 ng/mL respectively. Further estimation of mivacurium in spiked human plasma was performed by construction of specific calibration curve and the obtained correlation coefficient was 0.9948. Moreover, the ability to determine mivacurium in the presence of commonly co-administered drugs were investigated including propofol and thiopental. Method II includes the determination of MVC in the presence of propofol utilizing the first derivative synchronous fluorescence spectroscopy. The results of method II indicated acceptable percentage recoveries from 98.88 to 100.75 %. Statistical evaluation of the results revealed satisfactory accuracy and precision.

Comparison of 3 Rates for the Continuous Infusion of Mivacurium During Ambulatory Vitreoretinal Surgery Under General Anesthesia: A Prospective, Randomized, Controlled Clinical Trial.

Purpose: Mivacurium, the shortest-acting benzylisoquinoline nondepolarizing neuromuscular blocker used in clinical practice, is suitable for short-term ambulatory operations under general anesthesia. We investigated the neuromuscular blockade effect of different maintenance doses of mivacurium during ambulatory vitreoretinal surgery under general anesthesia and tried to determine the appropriate maintenance dose. Patients and Methods: Ninety-nine patients undergoing general anesthesia for elective ambulatory vitreoretinal surgery were randomly divided into three groups using the random number table method. Patients received three maintenance doses of mivacurium during surgery as follows: 3 µg/(kg·min) in group M1 (n = 33), 6 µg/(kg·min) in group M2 (n = 33), and 9 µg/(kg·min) in group M3 (n = 33). The primary outcome was the time from mivacurium withdrawal to a train-of-four stimulation ratio (TOFr) ≥ 0.9, and the secondary outcomes were the time from mivacurium withdrawal to TOFr ≥ 0.7, extubation time, incidence of TOFr < 0.9 after surgery and neuromuscular block effect. Results: The time from mivacurium withdrawal to TOFr ≥ 0.9 and to TOFr ≥ 0.7 was significantly longer in group M3 than in groups M1 and M2 (25.6±7.2 min vs 16.4±5.9 min and 18.6±5.3 min, P < 0.001; 22.1±6.3 min vs 13.6 ± 5.8 min and 15.5 ± 4.8 min; P < 0.001, respectively). There was a significant difference in the extubation time, the incidence of TOFr < 0.9 during extubation and upon leaving the operating room between group M3 and group M1 (all P < 0.05), but there was no such significant difference between group M2 and group M1 (all P > 0.05). The intraoperative depth of neuromuscular blockade in the three groups was significantly different, with 69.7% shallow block in group M1, 75.8% moderate block in group M2 and 63.6% deep block in group M3 (P < 0.001). One patient in group M1 experienced slight body movement during the operation. Conclusion: An intraoperative continuous infusion of 6 µg/(kg·min) mivacurium can not only achieve good postoperative recovery but also provide a satisfactory neuromuscular blockade effect during surgery, and this maintenance dose is suitable for neuromuscular blockade during ambulatory vitreoretinal surgery.

Application of Mivacurium in Fast-Track Anesthesia for Transthoracic Device Closure of Ventricular Septal Defects in Children.

INTRODUCTION: The objective of this study was to investigate the effect of mivacurium in the application of fast-track anesthesia for transthoracic device closure of ventricular septal defects (VSDs) in children. METHODS: The data of 108 children who underwent transthoracic device closure of VSDs from December 2018 to June 2020 were recorded and analyzed. All children were divided into group M (mivacurium group, n=55) and group C (cisatracurium group, n=53) according to the different muscle relaxant drug used. RESULTS: No statistically significant differences in general preoperative data, intraoperative hemodynamic changes, or the incidence of adverse reactions were noted between the two groups (P>0.05). However, the intubation condition rating of children in group M was better than that in group C. The onset time, duration of clinical action and recovery index of the muscle relaxant, postoperative mechanical ventilation duration, and length of intensive care unit stay in group M were significantly lower than those in group C (P<0.05). CONCLUSION: It is safe and feasible to use mivacurium as a muscle relaxant in children undergoing fast-track cardiac anesthesia during transthoracic device closure of VSDs.

Application of Mivacurium in Fast-Track Anesthesia for Transthoracic Device Closure of Ventricular Septal Defects in Children

Abstract Introduction: The objective of this study was to investigate the effect of mivacurium in the application of fast-track anesthesia for transthoracic device closure of ventricular septal defects (VSDs) in children. Methods: The data of 108 children who underwent transthoracic device closure of VSDs from December 2018 to June 2020 were recorded and analyzed. All children were divided into group M (mivacurium group, n=55) and group C (cisatracurium group, n=53) according to the different muscle relaxant drug used. Results: No statistically significant differences in general preoperative data, intraoperative hemodynamic changes, or the incidence of adverse reactions were noted between the two groups (P>0.05). However, the intubation condition rating of children in group M was better than that in group C. The onset time, duration of clinical action and recovery index of the muscle relaxant, postoperative mechanical ventilation duration, and length of intensive care unit stay in group M were significantly lower than those in group C (P<0.05). Conclusion: It is safe and feasible to use mivacurium as a muscle relaxant in children undergoing fast-track cardiac anesthesia during transthoracic device closure of VSDs.

[Maximum dose of continuous infusion of mivacurium for thyroid surgery under total intravenous anesthesia: a sequential trial of monitoring neurological function in 30 patients].

OBJECTIVE: To investigate the maximum dose of continuous mivacurium infusion for intraoperative neuromonitoring (IONM) and observe the adverse reactions during thyroid surgery under total intravenous anesthesia (TIVA). METHODS: Thirty patients undergoing IONM during thyroid surgery received continuous infusion of mivacurium at the initial rate of 14.97 µg · kg-1 · min-1. The infusion rate was adjusted in the next patient based on the response of the previous patient in IONM. The depth of anesthesia was maintained with propofol and remifentanil during the surgery. The EC50 and 95%CI of mivacurium were calculated with Brownlee's up- and-down sequential method. During the operation, body movement and skin flushing of patient was monitored, and the mean arterial pressure (MAP) and heart rate (HP) were recorded immediately (T0) and at 5 min (T1) after injection of muscle relaxant for anesthesia induction, immediately (T2) and at 10 min (T3) and 20 min (T4) after initiation of intraoperative infusion of the muscle relaxant. RESULTS: The EC50 for continuous infusion of mivacurium without affecting IONM was 18.9 µg · kg-1 · min-1(95%CI: 17.3-20.5 µg · kg-1 · min-1) during thyroid surgery under TIVA. One patient (3.3%) developed transient facial skin redness after induction. Intubation difficulties or body motions occurred in none of the patients during the surgery. Pair-wise comparison showed no significant variations in MAP or HR of the patients at the 5 time points (P>0.05). CONCLUSIONS: In patients undergoing thyroid surgery under TIVA, the EC50 for continuous infusion of mivacurium is 18.9 µg · kg-1 · min-1 (95%CI: 17.3-20.5 µg · kg-1 · min-1), which does not affect IONM or causes serious adverse reactions during the operation.

Timing of blood sampling for butyrylcholinesterase phenotyping in patients with prolonged neuromuscular block after mivacurium or suxamethonium.

INTRODUCTION: Variants of butyrylcholinesterase are frequently associated with prolonged response to suxamethonium or mivacurium. Butyrylcholinesterase (BChE) can be characterized by phenotyping and determination of genotype. Inappropriate timing of blood sampling might interfere with phenotyping methods. However, guidelines regarding delay between exposure to anaesthesia and testing are not clearly defined. In this study, the BChE activity and phenotype in an early (T1) and late (T2) phase were compared and the phenotype/genotype correlation was assessed. METHODS: Patients with a prolonged paralysis after mivacurium or suxamethonium were selected after ethical committee approval and written consent. BChE activity was based on butyrylthiocholine hydrolysis rate and phenotyping on differential inhibition of BChE activity with dibucaine and fluoride. DNA sequencing allowed genotypic characterization. RESULTS: We included the results of 20 patients with prolonged neuromuscular block (NMB) induced by mivacurium or suxamethonium. In these patients, BChE activity was different at T1 and T2 (2120 [1506-2733] U L-1 and 4055 [2810-5301] U L-1 , respectively; P = 0.0014; values are mean [95% CI]). When phenotyping was possible, phenotyping at T1 and T2 yielded identical results. Phenotyping failed to identify one new variant (p.Tyr146Cys) and the K variant in 14 of 16 patients. CONCLUSION: Anaesthesia interfered with BChE activity, but not with phenotyping. Phenotyping can be performed on blood drawn during or immediately after recovery of mivacurium or suxamethonium to screen for clinically relevant variants of BChE. However, accurate diagnosis of BChE deficiency needs further confirmation by determination of genotype.

Maximum dose of continuous infusion of mivacurium for thyroid surgery under total intravenous anesthesia: a sequential trial of monitoring neurological function in 30 patients / 南方医科大学学报

OBJECTIVE@#To investigate the maximum dose of continuous mivacurium infusion for intraoperative neuromonitoring (IONM) and observe the adverse reactions during thyroid surgery under total intravenous anesthesia (TIVA).@*METHODS@#Thirty patients undergoing IONM during thyroid surgery received continuous infusion of mivacurium at the initial rate of 14.97 μg · kg@*RESULTS@#The EC@*CONCLUSIONS@#In patients undergoing thyroid surgery under TIVA, the EC

Comparison of efficacy of mivacurium versus cisatracurium in patients undergoing painless fiberoptic bronchoscopy / 中华麻醉学杂志

Objective:To compare the efficacy of mivacurium versus cisatracurium in patients undergoing painless fiberoptic bronchoscopy.Methods:A total of 100 patients of both sexes, aged 18-64 yr, of American Society of Anesthesiology physical status I or Ⅱ, scheduled for elective fiberoptic bronchoscopy were divided into 2 groups ( n=50 each) using a random number table method: mivacurium group (M group) and cisatracurium group (C group). Mivacurium 0.15 mg/kg was injected intravenously in group M, and cisatracurium 0.1 mg/kg was injected intravenously in group C. The onset time of neuromuscular block (ThD95), the duration of neuromuscular block (TOFR25), recovery index (RI), recovery time of autonomous respiration, extubation time and time of discharge from postanesthesia care unit (PACU) were recorded.The occurrence of intraoperative and postoperative adverse reactions and complications were recorded.The mean arterial pressure (MAP), heart rate (HR) and SpO 2 at restlessness at 10 min after entering the operating room (T 1), at loss of consciousness (T 2), when laryngeal mask airway was inserted (T 3), at the end of surgery (T 4), when laryngel mask airway was removed (T 5), and when the patients left the operating room (T 6). Results:Compared with group C, TOFR25, RI, recovery time of autonomous respiration, extubation time and time of discharge from PACU were significantly shortened, the total incidence of adverse reactions was decreased ( P<0.05), and no significant change was found in ThD95 in group M ( P>0.05). There was no significant difference in MAP, HR and SpO 2 at each time point between the 2 groups ( P>0.05). Conclusion:Mivacurium provides better efficacy than cisatracurium when used for painless fiberoptic bronchoscopy.

Effects of Cisatracurium, Rocuronium, and Mivacurium on Intraocular Pressure During Induction of General Anesthesia in Ophthalmic Surgery.

OBJECTIVE: Maintaining intraocular pressure (IOP) is important in preventing ocular complications in patients undergoing ophthalmic surgery for general anesthesia. The effects of non-depolarizing neuromuscular blockers on IOP remain unclear. The present study compared the effects of cisatracurium, rocuronium, and mivacurium on IOP during induction of general anesthesia in vitreous retinal surgery. MATERIALS AND METHODS: In this prospective randomized double-blinded study, 133 patients undergoing vitreous retinal surgery were randomized into one of the three groups: Group cisatracurium (n=45), Group rocuronium (n=44), or Group mivacurium (n=44). Each drug (cisatracurium 0.1 mg kg-1 in Group cisatracurium, rocuronium 0.6 mg kg-1 in Group rocuronium, and mivacurium 0.2 mg kg-1 in Group mivacurium) was administered during induction of anesthesia. IOP and hemodynamic parameters were measured at 1 min before anesthesia induction (T0). Bispectral index (BIS) was maintained between 45 and 55 after propofol administration (T1). Train-of-four stimulation (TOF) was below 0 after muscle relaxant administration (T2) and after laryngeal mask implantation (T3). RESULTS: Both ipsi-operative and control-operative IOP at T1, T2, and T3 significantly decreased from the baseline values (T0) in all three groups (P<0.05). The IOP changes between T1 and T2 among three groups were similar (P>0.05). The values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) at T1 and T2 significantly decreased in all three groups compared to T0 (P<0.05). CONCLUSION: Bilateral IOP significantly decreased from the baseline values in all three groups during the induction phase. Cisatracurium, rocuronium, and mivacurium did not induce significant changes in bilateral IOP.

Mivacurium induce mast cell activation and pseudo-allergic reactions via MAS-related G protein coupled receptor-X2.

BACKGROUND: Mivacurium is a non-depolarizing muscle relaxant and widely used as a short-acting anesthetic. Pseudo-allergic reactions to mivacurium occur when it is administered during perioperative anesthesia. These reactions may present a serious threat to the patient's life, particularly in children. METHODS: MAS-related G protein coupled receptor-related pseudo-allergic reactions that were induced by mivacurium were investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. RESULTS: Mivacurium caused pseudo-allergic reactions in wild-type mice by inducing mast cells to release histamine. However, it did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, MrgprB2-knockout mice displayed no inflammatory response to mivacurium. Mivacurium induced LAD2 cell degranulation in a dose-dependent manner. Mivacurium stimulated intracellular calcium ion (Ca2+) influx in MRGPRX2-HEK293 cells but not in NC-HEK293 cells. However, mivacurium induced the release of only low levels of mediators in LAD2 cells transfected with MRGPRX2-targeted small interfering (si)RNA. Notably, cytokine release was not observed in LAD2 cells even when stimulated with high concentrations of mivacurium. CONCLUSION: Mivacurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. However, mivacurium did not induce the release of other cytokines. Therefore, the targeting of MRGPRX2 can potentially block mivacurium-induced adverse drug effects, particularly pseudo-allergic reactions.

[Sequential method for determining the maximum dose of mivacurium continuously infused for intraoperative neuromonitoring in thyroid surgery].

OBJECTIVE: To determine the maximum dose of continuously infused mivacurium for intraoperative neuromonitoring and observe its adverse effects in thyroid surgery. METHODS: Twenty-eight patients undergoing thyroid surgery with intraoperative neuromonitoring received continuous infusion of mivacurium at the initial rate of 5.43 µg?kg-1?min-1, and the infusion rate for the next patient was adjusted based on the response of the previous patient according to the results of neurological monitoring. The depth of anesthesia was maintained with sevoflurane and remifentanil during the surgery. The LD50 and 95% CI of mivacurium were calculated using Brownlee's up-and-down sequential method. RESULTS: The LD50 of continuously infused mivacurium was 8.94 µg?kg-1?min-1 (95% CI: 8.89- 8.99 µg?kg-1?min-1) during thyroid surgery, which did not affect neurological function monitoring. Transient chest skin redness occurred after induction in 9 patients (32.1%). None of the patients experienced intubation difficulties or showed intraoperative body motions during the surgery. CONCLUSIONS: In patients undergoing thyroid surgery under anesthesia maintained by inhalation and intravenous infusion, the LD50 of mivacurium was 8.94 µg?kg-1?min-1 (95% CI: 8.89-8.99 µg?kg-1?min-1) for continuous infusion, which does not cause serious adverse effects during the operation.

Sequential method for determining the maximum dose of mivacurium continuously infused for intraoperative neuromonitoring in thyroid surgery / 南方医科大学学报

OBJECTIVE@#To determine the maximum dose of continuously infused mivacurium for intraoperative neuromonitoring and observe its adverse effects in thyroid surgery.@*METHODS@#Twenty-eight patients undergoing thyroid surgery with intraoperative neuromonitoring received continuous infusion of mivacurium at the initial rate of 5.43 μg?kg?min, and the infusion rate for the next patient was adjusted based on the response of the previous patient according to the results of neurological monitoring. The depth of anesthesia was maintained with sevoflurane and remifentanil during the surgery. The LD50 and 95% of mivacurium were calculated using Brownlee's up-and-down sequential method.@*RESULTS@#The LD50 of continuously infused mivacurium was 8.94 μg?kg?min (95% : 8.89- 8.99 μg?kg?min) during thyroid surgery, which did not affect neurological function monitoring. Transient chest skin redness occurred after induction in 9 patients (32.1%). None of the patients experienced intubation difficulties or showed intraoperative body motions during the surgery.@*CONCLUSIONS@#In patients undergoing thyroid surgery under anesthesia maintained by inhalation and intravenous infusion, the LD50 of mivacurium was 8.94 μg?kg?min (95% : 8.89-8.99 μg?kg?min) for continuous infusion, which does not cause serious adverse effects during the operation.

Effects of different doses of mivacurium chloride on muscle relaxation time- course and hemodynamics in children with different ages / 中国医师进修杂志

Objective To observe the effect of different doses of mivacurium chloride on muscle relaxation time-course and hemodynamics in children with different ages. Methods One hundred children of selective inguinal hernia repair under general anesthesia with endotracheal intubation from January 2016 to January 2017 were enrolled, and the age was 0.5 to 6.0 years. The children were divided into low age group (0.5 to 3.0 years) and high age group (3.1 to 6.0 years) according to the age, then the children were divided into low dose group (mivacurium chloride 0.20 mg/kg) and high dose group (mivacurium chloride 0.25 mg/kg) according to the doses of mivacurium chloride. Therefore, the children were divided into low age low dose group, low age high dose group, high age low dose group and high age high dose group with 25 cases each. The mean arterial pressure (MAP) and heart rates before anesthesia (T0) and 1 min (T1), 3 min (T2), 5 min (T3), 10 min (T4) after intravenous injection of mivacurium chloride were recorded. The times of first intravenous injection of mivacurium chloride to neuromuscular block 75% (ThD75), 90% (ThD90) and maximum (ThDmax) were recorded. The recovery index (RI) was recorded. The times of last intravenous injection of mivacurium chloride to onset of muscle convulsions (Th) and muscle convulsions recovery 10% (ThR10), 25% (ThR25), 75% (ThR75), 90% (ThR90) were recorded. The times of ratio of the fourth muscle twitch to the first muscle twitch (TOFR) recovery 75% (TOFR75) and 90% (TOFR90) were recorded. Results There were no statistical difference in MAP and heart rate among 4 groups (P＞0.05). The ThD75, ThD90 and ThDmax in low age low dose group were (126 ± 40), (163 ± 59) and (192 ± 49) s, those in low age high dose group were (73 ± 15), (115 ± 41) and (142 ± 37) s, those in high age low dose group were (149 ± 38), (193 ± 44) and (221 ± 47)s, and those in high age high dose group were (105 ± 32), (138 ± 35) and (167 ± 44)s. The ThD75, ThD90 and ThDmax in low age high dose group were significantly shorter than those in low age low dose group, those in high age high dose group were significantly shorter than those in high age low dose group, those in high age low dose group were significantly longer than those in low age low dose group, those in high age high dose group were significantly longer than those in low age high dose group, and there were statistical differences (P＜0.05). There were no statistical differences in Th, ThR10, ThR25, ThD75, ThD90, RI, TOFR75 and TOFR90 among low age low dose group and low age high dose group, high age low dose group and high age high dose group (P＞0.05). Conclusions In the children of 0.5 to 3.0 years, the effect of mivacurium chloride is significantly faster than that in the children of aged 3.1 to 6.0 years. Compared with 0.20 mg/kg of mivacurium chloride, 0.25 mg/kg of mivacurium chloride has less time to display muscle relaxation effect. The recovery time is not affected by age and induction dose. Mivacurium chloride has no significant effect on hemodynamics.

Muscle Relaxants as a Risk Factor for Vis-à-tergo During Penetrating Keratoplasty: A Prospective Interventional Study.

INTRODUCTION: This study aimed to investigate the influence of three muscle relaxants on intraocular pressure (IOP), ocular pulse amplitude (OPA), and vis-à-tergo (VAT) in patients undergoing penetrating keratoplasty (PKP) under general anesthesia. METHODS: Ninety-five patients undergoing PKP were included in this prospective single-center interventional study. IOP and OPA were measured with a dynamic contour tonometer before and 5 min after onset of general anesthesia. Mivacurium (n = 30), atracurium (n = 35), and rocuronium (n = 30) were administered as nondepolarizing muscle relaxants. VAT was assessed 15 min after surgery had begun. RESULTS: When mivacurium was used, IOP decreased by 2.2 mmHg [standard deviation (SD) ±2.2 mmHg; p < 0.001]. Atracurium decreased the IOP by an average of 5.8 mmHg (SD ±1.8 mmHg; p < 0.001) and rocuronium caused an IOP reduction of 7.2 mmHg (SD ±2 mmHg; p < 0.001). The relative IOP decrease was 12% with mivacurium, 29% with atracurium, and 37% with rocuronium (p < 0.001). OPA decreased by 0.6 mmHg with mivacurium (SD ±0.6 mmHg; 26%; p < 0.001), 1.3 mmHg with atracurium (SD ±1.3 mmHg; 40%; p < 0.001), and 1.2 mmHg with rocuronium (SD ±0.7 mmHg; 42%; p < 0.001). The relative OPA decrease was 26% with mivacurium, 40% with atracurium, and 42% with rocuronium (p < 0.001). VAT occurred in 36% of cases. Mivacurium was used in 77% of these cases, atracurium in 26%, and rocuronium in 6.6% (p < 0.001). CONCLUSIONS: Mivacurium is associated with a higher risk of VAT during PKP. Therefore, atracurium or rocuronium may minimize complications in ocular surgery with large incisions.

The efficacy and safety of mivacurium in pediatric patients.

BACKGROUND: Mivacurium is the shortest acting nondepolarizing muscle relaxant currently available; however, the effect of different dosages and injection times of intravenous mivacurium administration in children of different ages has rarely been reported. This study was aimed to evaluate the muscle relaxant effects and safety of different mivacurium dosages administered over different injection times in pediatric patients. METHODS: Six hundred forty cases of pediatric patients, aged 2 m-14 years, ASA I or II, were divided into four groups (Groups A, B, C, D) according to the age class (2-12 m, 13-35 m, 3-6 years and 7-14 years) respectively, also each group were divided into four subgroups by induction dose (0.15, 0.2 mg/kg in 2-12 m age class; 0.2, 0.25 mg/kg in other three age classes), and mivacurium injection time (20 s, 40 s), totally 16 subgroups. Neuromuscular transmission was monitored with supramaximal train-of-four stimulation of the ulnar nerve. Radial artery blood (1 ml) was sampled to quantify plasma histamine concentrations before and 1, 4, and 7 min after mivacurium injection (P0, P1, P2 and P3). RESULTS: Five hundred sixty-two cases completed the study. There were no demographic differences within the four groups. The onset time of 0.2 mg/kg groups in 2-12 m aged patients were shorter than those of 0.15 mg/kg groups (189 ± 64 s vs. 220 ± 73 s, 181 ± 60 s vs. 213 ± 71 s, P <0.05), and the recovery times were no statistical differences. The T1 25% recovery time of 0.2 mg/kg in 3-6 years aged patients was shorter than that of 0.25 mg/kg group (693 ± 188 s vs. 800 ± 206 s, P <0.05). The onset and recovery times of mivacurium were not different in 13-35 m and 7-14 years aged patients. The plasma concentrations of histamine at P0, P1, P2 and P3 were not different within four groups. CONCLUSIONS: The induction dose and injection time of mivacurium had mostly insignificant effects on onset and recovery times. The main exception to this was that in 2-12 m aged patients, increasing the dose of mivacurium from 0.15 to 0.2 mg/kg accelerated the onset time by about 30 s. Mivacurium produced no significant release of histamine in any age group at the doses studied. TRIAL REGISTRATION: ClinicalTrials.gov Identifier- NCT02117401 , July 14, 2014. (Retrospectively registered).

Effect of antagonism of neostigmine on residual neuromuscular blockade from mivacurium chloride in the elderly patients / 临床麻醉学杂志

Objective To investigate the effect of Neostigmine on Mivacurium Chloride in postoperative recovery of elderly patients with anesthesia.Methods A total of 46 patients (32 males,14 females,aged 60-73 years,ASA grade Ⅰ or Ⅱ) who underwent laparoscopic surgery for gastrointestinal tumor under general anesthesia,were randomly divided into two groups.Patients in the studying group (group A,n=22) were given a dosage of eostigmine 20 ug/kg after the end of surgery,and patients in control group (group B,n=24) were given 0.9% saline solution.Monitored the contract reaction of adductor pollicis through train-of-four ratio (TOFR) by stimulating ulnar nerve.Record condition of recovery from neuromuscular blocked,untoward effect after operation,the activity of the plasmacholinesterase at the time of induction of anaesthesia and extubation.Results The sex,age,height,weight,BMI,operation time,fluid volume,temperature,the activity of the plasmacholinesterase,recovery score and sedation score had no significant difference.Activity decline of the plasmacholinesterase is obviously related with infusion liquid volume,was statistically significant(P<0.05),group A is lower than group B obviously at the recovery of TOFR to 25%,to 70%,70% to 90%,onset time and recovery index time,was statistically significant (P<0.05),the difference of TOFR of the two groups was statistically significant at the time of 5 min、10 min、30 min after extubation (P<0.05).The difference of the incidence of TOFR<0.7 of the two groups at the time of 5 min,10 min,30 min after extubation and the difference of the incidence of TOFR<0.9 of the two groups at the time of 10 min,30 min after extubation were statistically significant (P<0.05).Conclusion There is obvious significance for neostigmine to resume muscle force in mivacurium chloride postoperative recovery in the elderly.

Butyrylcholinesterase deficiency.

Butyrylcholinesterase (EC 3.1.1.8; BChE) is a sister enzyme of acetylcholinesterase. Though BChE lacks obvious physiological functions, it is of toxicological and pharmacological importance in detoxifying or catabolising ester-containing drugs. Furthermore, individuals deficient in BChE appear asymptomatic, apart from a heightened sensitivity to the muscle relaxants suxamethonium and mivacurium, two BChE substrates used as myorelaxant. Although many acquired conditions may affect BChE activity, BChE deficiency is mainly due to mutations in the BCHE gene (OMIM 177400). Currently, more than 70 natural mutations have been documented in human BCHE. They have an adverse effect on BChE activity by affecting the catalytic functioning or the protein expression. However, the atypical variant (rs1799807) is the most frequently involved in prolonged apnea.

Understanding the non-catalytic behavior of human butyrylcholinesterase silent variants: Comparison of wild-type enzyme, catalytically active Ala328Cys mutant, and silent Ala328Asp variant.

Conformational dynamics of wild-type human butyrylcholinesterase (BChE), two mutants of residue Ala328, the catalytically active Ala328Cys, and the catalytically inactive (silent) Ala328Asp, and their interactions with butyrylcholine were studied. The aim was to understand the molecular mechanisms by which point mutations may lead to silent BChE variant or alter catalytic activity. Importance of BChE natural variants is due to medical consequences, i.e. prolonged apnea, following administration of the myorelaxant esters, succinylcholine and mivacurium. Comparison of molecular dynamics (MD) simulations for the three model systems showed that: 1) the active mutant Ala328Cys mutant has some changes in configuration of catalytic residues, which do not prevent binding of butyrylcholine to the active site; 2) in the naturally-occurring silent variant Ala328Asp, the Asp328 carboxylate may either form a salt bridge with Lys339 or a H-bond with His438. In the first case, the Ω-loop swings off the gorge, disrupting the π-cation binding site and the catalytic triad. In the second case, binding of cationic substrates in the catalytic center is also impaired. MD simulations carried out in 0.15 M NaCl, close to physiological ionic strength conditions, favored the second situation. It was seen that Asp328 forms a H-bond with the catalytic triad His438, which in turn disrupts the catalytic machinery. Therefore, we concluded that the Ala328Asp variant is not catalytically active because of that dramatic event. Computational results, consistent with in vitro biochemical data and clinical observations, validate our MD approach.

Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency.

BACKGROUND: Patients with butyrylcholinesterase (BChE) deficiency can experience prolonged paralysis after receiving suxamethonium or mivacurium. We hypothesized that patients suspected of BChE deficiency had a higher risk of being awakened while paralysed and having respiratory complications if neuromuscular monitoring was not applied before awakening. METHODS: We retrospectively included patients referred to the Danish Cholinesterase Research Unit between 2004 and 2012 on suspicion of BChE deficiency. We collected data on genotype, BChE activity, neuromuscular blocking agents administered, neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation <90%, assisted ventilation, reintubation of the trachea, and pulmonary aspiration. Patients were classified as prematurely awakened if anaesthesia had been terminated while the patient was still paralysed. RESULTS: We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored and monitored patients, respectively (P<0.001, Fisher's exact test). In 11 of the monitored patients, the results of neuromuscular monitoring were interpreted as equipment failure or were disregarded. Respiratory complications occurred in 19 (25%) and five (10%) of the unmonitored and monitored patients, respectively (P=0.06). CONCLUSIONS: Patients with BChE deficiency are at higher risk of being awakened while paralysed if neuromuscular monitoring is not applied or used; neuromuscular monitoring is recommended whenever a neuromuscular blocking agent is administered.