Comparing Neuromuscular Blockade Measurement Between Upper Arm (TOF Cuff®) and Eyelid (TOF Scan®) Using Mivacurium during General Anesthesia.

BACKGROUND Mivacurium is a non-depolarizing neuromuscular blocking agent. TOF-Cuff® is a device that monitors intraoperative neuromuscular blockade and blood pressure. TOF-Scan® measures muscle relaxation status of an anaesthetized patient. This study included 36 patients aged 18 to 75 years presenting for elective surgery, to compare neuromuscular blockade measured using the TOF-Cuff of the upper arm and the TOF-Scan of the facial corrugator supercilii muscle during general anesthesia and following administration of mivacurium. MATERIAL AND METHODS Train-of-four (TOF) values were obtained every 30 s before intubation and successively every 5 min until extubation. RESULTS The median onset time for TOF-Cuff was longer than for TOF-Scan (210 s vs 90 s, P<0.00001). Multiplying the time to relaxation (according to TOF-Scan) by 1 to 8, respectively, provided concordance with the TOF-Cuff result for the following cumulative percentages of patients: 5.5%, 38.9%, 58.3%, 77.8%, 83.3%, 86.1%, 88.9%, and 91.7%. Analogue values for time to recovery from the last dose were 11.1%, 63.9%, 83.3%, 86.1%, 86.1%, 88.9%, 88.9%, and 91.7%. The proportion of patients who still had TOFratio=0 in the assessment performed at min 15 did not differ significantly between these 2 methods (P=0.088). Both TOF-Scan and TOF-Cuff showed a false-negative result in patients with clinical symptoms of preterm recovery; the numerical difference favored TOF-Cuff (1.6% vs 2.1%) but without statistical significance (P=0.2235). CONCLUSIONS When measurement on the limb is not possible, TOF-Scan on the eyelid can be an alternative for TOF-Cuff on the upper arm, if the time to relaxation is multiplied by at least 8, which is enough for 90% of patients.

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

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.

Prevention of postoperative nausea and vomiting after gynaecological day surgery under remimazolam general anesthesia: a randomized double-blind controlled study.

PURPOSE: To observe the effect of different antiemetic drugs for the prevention of postoperative nausea and vomiting (PONV) after gynaecological day surgery under remimazolam general anesthesia. METHODS: One hundred ninety-two patients were selected for gynaecological day surgery and randomly divided into three groups: droperidol group (DD group), tropisetron group (DT group) and control group (DC group). Flurbiprofen axetil 50 mg and dexamethasone 5 mg were given intravenously before induction of anesthesia, and 2 min later droperidol 1 mg was given intravenously to the DD group, tropisetron 5 mg to the DT group and saline (5 ml) to the DC group. Induction of anesthesia: remimazolam 6 mg/kg/h was continuously infused until sleep, mivacurium 0.2 mg/kg and alfentanil 20ug/kg were slowly pushed, 3 min later intubation was performed to control breathing. Maintenance of anesthesia: 40ug/kg/h of alfentanil, 1 mg/kg/h of remimazolam continuous infusion. After awakening and extubation, the patient was transferred to the PACU. PONV were recorded in the PACU and an electronic questionnaire was pushed 24 h after surgery. RESULTS: The incidence of PONV within the PACU was significantly lower in the DD (14.5%)and DT(26.7%) groups than in the DC(50%) group (p < 0.01), there was no significantly difference between the DT and DD groups. There were no significant difference in the incidence of PONV in 24 h after surgery between the three groups(DD:DT:DC = 44.5%:45.1%:63.8%,p > 0.05). CONCLUSIONS: Droperidol or tropisetron combined with dexamethasone is superior to dexamethasone alone for the prevention of PONV in the PACU after remimazolam combined with alfentanil anesthesia, with no significant difference in the incidence of PONV in 24 h after surgery.

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.

[Comparison of the anesthetic effects of mivacurium and cisatracurium besylate in laser laryngeal microsurgery].

Objective: To compare the anesthetic effects of mivacurium and cisatracurium besylate in laser laryngeal microsurgery, and to provide clinical evidence and reference for further optimization of muscle relaxation application. Methods: From October 2021 to January 2022, fifty-six patients of Beijing Tongren Hospital, Capital Medical University, scheduled for laser laryngeal microsurgery with general anesthesia, were enrolled. These patients, aged 18-65 years old, 25 males and 31 females, were divided into two groups (n=28) by random number table method. Cisatracurium besylate group (group C): cisatracurium besylate was injected at 0.1 mg/kg. Normal saline was continuously infused during operation. Mivacurium group (group M):Mivacurium was injected at 0.25 mg/kg and continuously infused at 0.3 mg·kg-1·h-1 during operation.The intubation time, the extubation time, recovery index, Cooper's score, Cormack-Lehane grade, surgical condition grade, postoperative residual neuromuscular block and allergic related adverse events were compared between the two groups. Results: The intubation time and the extubation time of group M were (3.7±1.1) and (16.2±5.0) min, which were statistically significant shorter than those of group C (4.9±0.7) and (26.4±8.6) min (all P<0.05). The recovery indexes of the patients in group M and group C were (4.5±3.4) and (6.2±5.0) min. The Cooper's scores of the two groups were both 9(9, 9). The Cormack-Lehane grades of the two groups were all grade Ⅰ. The number of cases with good/excellent surgical condition grades in group M and group C were 5/23 and 0/28. There were no significant differences in recovery index, Cooper's score, Cormack-Lehane grades and surgical condition grades between the two groups (all P>0.05). The TOF ratio of group M in the post anesthesia care unit (PACU) was (95.7±2.6) %, which was significantly higher than (92.9±3.9) % of group C(P=0.015). There were no significant differences in MAP and HR between the two groups at different time points (all P>0.05). The incidence of skin flushing in group M and group C was 10.7% (3/28) and 0, and the difference was not statistically significant (P=0.074). There were no cases of severe hypotension, significantly elevated airway pressure or airway spasm in both groups. Conclusion: In laser laryngeal microsurgery, compared with cisatracurium besylate, mivacurium has shorter intubation time and extubation time, stable hemodynamics, no significant increase in allergic related adverse events. mivacurium is safe and effective.

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.

[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.

Characterization of four BCHE mutations associated with prolonged effect of suxamethonium.

Butyrylcholinesterase (BChE) deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in the BCHE gene. Here, we report the characterization of four BCHE mutations associated with prolonged effect of suxamethonium (amino acid numbering based on the matured enzyme): p.20delValPheGlyGlyThrValThr, p.Leu88His, p.Ile140del and p.Arg386Cys. Expression of recombinant BCHE mutants, kinetic analysis and molecular dynamics were undertaken to understand how these mutations induce BChE deficiency. Three of the mutations studied (p.20delValPheGlyGlyThrValThr, p.Ile140del and p.Arg386Cys) lead to a "silent" BChE phenotype. Recombinant BCHE expression studies for these mutants revealed BChE activity levels comparable to untransfected cells. Only the last one (hBChE-L88H) presented BChE activity in the transfected cell culture medium. This BChE mutant (p.Leu88His) is associated with a lower kcat value compare to the wild-type enzyme. Molecular dynamics simulations analyses suggest that a destabilization of a structure implicated in enzyme activity (Ω-loop) can explain the modification of the kinetic parameter of the mutated protein.

Pseudocholinesterase Deficiency Considerations: A Case Study.

Pseudocholinesterase deficiency, sometimes called butyrylcholinesterase deficiency, is a rare disorder in which the neuromuscular blocking drugs succinylcholine and mivacurium cannot be metabolized properly in the blood plasma. This disorder can either be acquired as a result of certain comorbidities or it can be inherited genetically. Anesthesia providers must understand the pathophysiology of pseudocholinesterase deficiency and be prepared to safely and effectively manage patients who show signs and symptoms consistent with the disorder after the use of the indicated neuromuscular blocking drugs. This article summarizes the pharmacologic and physiologic data relevant to understanding the basic pathophysiology associated with pseudocholinesterase deficiency and illustrates a case study of a young woman suspected of having the disorder after a prolonged delay in emergence from general anesthesia.

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.

Butyrylcholinesterase deficiency and its clinical importance in anaesthesia: a systematic review.

Butyrylcholinesterase deficiency prolongs the effects of the drugs it degrades; succinylcholine and mivacurium. Existing literature on butyrylcholinesterase deficiency is dominated by genetic and biochemical studies. We searched MEDLINE, Embase, Web of Science and Biosis to systematically review the causes and clinical consequences of butyrylcholinesterase deficiency. We considered outcomes clinically relevant if neuromuscular blockade, induced by succinylcholine or mivacurium, was assessed using clinical criteria or neuromuscular monitoring. We included 66 studies: 25 randomised controlled trials; 13 clinically controlled trials; 26 prospective observational studies; 1 retrospective study; and 1 qualitative study. Data heterogeneity precluded quantitative synthesis. Studies described genetic, physiological, acquired or pharmacologically induced causes of butyrylcholinesterase deficiency. The prolongation of neuromuscular blockade by butyrylcholinesterase deficiency was most pronounced with homozygosity of a genetic variant, but other more common factors included increasing age, pregnancy, severe liver disease, burn injuries and drug interactions.

Reversal of mivacurium-induced neuromuscular blockade with a cholinesterase inhibitor: A systematic review.

BACKGROUND: Mivacurium is a short-acting non-depolarizing muscle relaxant, which is hydrolyzed by butyrylcholinesterase. The neuromuscular block (NMB) can be antagonized with cholinesterase inhibitors (CHEI), but the short duration of action of mivacurium questions the need. This systematic review evaluated if the use of CHEIs (neostigmine, pyridostigmine or edrophonium) facilitates reversal of mivacurium-induced NMB. METHOD: Randomized controlled trials and crossover-studies comparing spontaneous recovery with CHEI reversal in patients with mivacurium-induced NMB, assessed with quantitative neuromuscular monitoring, were included. Mean time from injection of the CHEI or allowing of spontaneous recovery to an endpoint representing full recovery was used as outcome. First response to train-of-four nerve stimulation (T1 ) described the level of NMB for administration of the CHEI. Moderate NMB refers to T1  ≥ 5% and deeper NMB refers to T1  < 5%. Systematic critical appraisal was performed using the Scottish Intercollegiate Guidelines Network guidelines. Overall quality assessment was done using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Sixteen studies with data from 546 patients were included. Low quality of evidence was found that neostigmine and edrophonium administered at moderate NMB accelerated recovery with up to approximately 5.5-6.5 and 6.5-9.0 minutes, respectively. At deeper NMB only edrophonium accelerated recovery. The effect of neostigmine was not clarified at deeper mivacurium-induced NMB. No studies with reversal by pyridostigmine were identified. CONCLUSION: Low quality of evidence supports that neostigmine and edrophonium accelerate the recovery of mivacurium-induced NMB with 5-6.5 and 6-9.0 minutes respectively, when administered at moderate NMB. At deeper NMB only edrophonium accelerated the recovery.

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.

Regulation of developing myelin sheath elongation by oligodendrocyte calcium transients in vivo.

How action potentials regulate myelination by oligodendrocytes is uncertain. We show that neuronal activity raises [Ca2+]i in developing oligodendrocytes in vivo and that myelin sheath elongation is promoted by a high frequency of [Ca2+]i transients and prevented by [Ca2+]i buffering. Sheath elongation occurs ~1 h after [Ca2+]i elevation. Sheath shortening is associated with a low frequency of [Ca2+]i transients but with longer duration [Ca2+]i bursts. Thus, [Ca2+]i controls myelin sheath development.

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).