ABSTRACT
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.
Subject(s)
Drug Design , Isoquinolines , Neuromuscular Blocking Agents , Neuromuscular Blocking Agents/pharmacology , Neuromuscular Blocking Agents/chemical synthesis , Neuromuscular Blocking Agents/chemistry , Structure-Activity Relationship , Animals , Isoquinolines/chemistry , Isoquinolines/pharmacology , Isoquinolines/chemical synthesis , Rabbits , Receptors, Nicotinic/metabolism , Molecular Docking Simulation , Molecular Structure , Dose-Response Relationship, Drug , Mivacurium , Atracurium/analogs & derivatives , Atracurium/pharmacology , Atracurium/chemical synthesis , Atracurium/chemistryABSTRACT
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.
Subject(s)
Anesthesia, General , Arm , Eyelids , Mivacurium , Neuromuscular Blockade , Humans , Anesthesia, General/methods , Middle Aged , Male , Adult , Female , Neuromuscular Blockade/methods , Aged , Eyelids/drug effects , Adolescent , Isoquinolines/pharmacology , Young Adult , Neuromuscular Nondepolarizing AgentsABSTRACT
BACKGROUND: The neuromuscular blocking agent mivacurium can be used during anesthesia to facilitate tracheal intubation. Data on onset time, duration of action, and effect on intubating conditions in patients 80 years and older are however limited. We hypothesized that onset time and duration of action of mivacurium would be longer in elderly patients than in younger adults. METHODS: This prospective observational study included 35 elderly (≥80 years) and 35 younger (18-40 years) patients. Induction of anesthesia comprised fentanyl 1-3 µg kg-1 and propofol 1.5-2.5 mg kg-1 and propofol and remifentanil for maintenance. Acceleromyography was used for monitoring neuromuscular blockade. The primary outcome was onset time defined as time from injection of mivacurium 0.2 mg kg-1 to a train-of-four (TOF) count of zero. Other outcomes included duration of action (time to TOF ratio ≥0.9), intubating conditions using the Fuchs-Buder scale and the intubating difficulty scale (IDS), and occurrence of hoarseness and sore throat postoperatively. RESULTS: No difference was found in onset time comparing elderly with younger patients; 219 s (SD 45) versus 203 s (SD 74) (difference: 16 s (95% CI: -45 to 14), p = .30). Duration of action was significantly longer in elderly patients compared with younger patients; 52 min (SD 17) versus 30 min (SD 8) (difference: 22 min [95% CI: 15 to 28], p < .001). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 31/35 (89%) versus 26/35 (74%) (p = .12) or IDS score (p = .13). A larger proportion of younger patients reported sore throat 24 h postoperatively; 34% versus 0%, p = .0002. No difference was found in hoarseness. CONCLUSION: No difference in onset time of mivacurium 0.2 mg kg-1 was found comparing elderly and younger patients. However, elderly patients had significantly longer duration of action. No difference was found in intubating conditions.
Subject(s)
Intubation, Intratracheal , Mivacurium , Humans , Adult , Male , Female , Intubation, Intratracheal/methods , Prospective Studies , Aged, 80 and over , Young Adult , Adolescent , Isoquinolines/administration & dosage , Age Factors , Hoarseness/etiology , Aged , Neuromuscular Nondepolarizing Agents/administration & dosage , Time Factors , Pharyngitis/etiology , Neuromuscular Blockade/methodsABSTRACT
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.
Subject(s)
Antiemetics , Postoperative Nausea and Vomiting , Alfentanil , Ambulatory Surgical Procedures , Anesthesia, General/adverse effects , Antiemetics/therapeutic use , Benzodiazepines , Dexamethasone/therapeutic use , Droperidol/therapeutic use , Female , Humans , Mivacurium , Postoperative Nausea and Vomiting/drug therapy , Postoperative Nausea and Vomiting/epidemiology , Postoperative Nausea and Vomiting/prevention & control , TropisetronABSTRACT
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 â . 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.
Subject(s)
Anesthetics , Neuromuscular Nondepolarizing Agents , Adolescent , Adult , Aged , Atracurium/analogs & derivatives , Female , Humans , Isoquinolines/pharmacology , Lasers , Male , Microsurgery , Middle Aged , Mivacurium , Neuromuscular Nondepolarizing Agents/adverse effects , Young AdultABSTRACT
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.
Subject(s)
Butyrylcholinesterase/genetics , Mutation/genetics , Succinylcholine/adverse effects , Adult , Aged, 80 and over , Female , Humans , Kinetics , Middle Aged , Mivacurium/adverse effects , PhenotypeABSTRACT
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.
Subject(s)
Neuromuscular Blockade , Succinylcholine , Apnea , Butyrylcholinesterase/genetics , Humans , MivacuriumABSTRACT
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.
Subject(s)
Cholinesterase Inhibitors/pharmacology , Mivacurium/pharmacology , Neuromuscular Blockade , Edrophonium/pharmacology , Humans , Neostigmine/pharmacology , Randomized Controlled Trials as Topic , Time FactorsABSTRACT
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.
Subject(s)
Anesthesia , Apnea/physiopathology , Butyrylcholinesterase/deficiency , Metabolism, Inborn Errors/physiopathology , Humans , Mivacurium/pharmacology , Neuromuscular Blockade , Neuromuscular Monitoring , Succinylcholine/pharmacologyABSTRACT
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.
Subject(s)
Drug-Related Side Effects and Adverse Reactions/immunology , Mast Cells/drug effects , Mivacurium/adverse effects , Mivacurium/immunology , Receptors, G-Protein-Coupled/immunology , Anaphylaxis/immunology , Animals , Calcium/immunology , Cell Degranulation/immunology , Cell Line , Cytokines/immunology , HEK293 Cells , Histamine/immunology , Humans , Male , Mast Cells/immunology , Mice , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
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).
Subject(s)
Isoquinolines/adverse effects , Isoquinolines/pharmacology , Muscle Relaxation/drug effects , Adolescent , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Histamine/analogs & derivatives , Histamine/blood , Humans , Infant , Isoquinolines/administration & dosage , Male , Mivacurium , Neuromuscular Monitoring , Neuromuscular Nondepolarizing Agents/administration & dosage , Neuromuscular Nondepolarizing Agents/adverse effects , Neuromuscular Nondepolarizing Agents/pharmacologyABSTRACT
INTRODUCTION: Mutations in the butyrylcholinesterase enzyme (BChE) can result in prolonged duration of action of the neuromuscular blocking agents, succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low BChE activity can cause extensively prolonged apnoea during general anaesthesia when these drugs are used. The aim of this study was to describe novel mutations in the butyrylcholinesterase gene (BCHE) in patients who have experienced prolonged duration of action of mivacurium or succinylcholine. METHODS: The Danish Cholinesterase Research Unit registers patients with prolonged duration of action to succinylcholine and mivacurium. Patients were studied if they had equivocal phenotypes on the basis of BChE activity, biochemical inhibitor reactions and with pedigree if possible. Complete nucleotide sequencing was performed to describe the genotype and pedigree was used to separate the alleles. Multiple sequence alignment of BChE was performed for comparison with other species. RESULTS: Genotyping indicated seven novel mutations in the BCHE (I373T, G467S, W518R, L184S, V421A, M462I and R577H). CONCLUSION: We have found seven new variants of the BCHE, which seem to reduce the activity of BChE in patients undergoing anaesthesia involving succinylcholine or mivacurium.
Subject(s)
Butyrylcholinesterase/genetics , Isoquinolines/pharmacology , Mutation/genetics , Neuromuscular Depolarizing Agents/pharmacology , Neuromuscular Nondepolarizing Agents/pharmacology , Succinylcholine/pharmacology , Female , Genotype , Humans , Male , Mivacurium , PedigreeABSTRACT
PURPOSE: Juvenile scoliosis (JS), among different types of spinal deformity, remains still a challenge for orthopedic surgeons. Elongation, derotation and flexion (EDF) casting technique is a custom-made thoracolumbar cast based on a three-dimensional correction concept. The primary objective of the present study was to measure changes on plain radiographs of patients with JS treated with EDF plaster technique. The second aim was to evaluate the effectiveness of the EDF plaster technique realized under general anesthesia (GA) and neuromuscular blocking drugs, i.e. curare, on the radiological curve correction. METHODS: A retrospective comparative case series study was performed in which were included forty-four skeletally immature patients. Three patient groups were selected. Group 1: EDF cast applied with patients awaken and no anesthesia; Group 2: EDF cast applied under GA without neuromuscular blocking drugs; Group 3: EDF cast applied under GA with neuromuscular blocking drugs. All the patients were treated with two serial EDF casts by 2 months and a half each. All measurements were taken from the radiographic exams. Cobb's angle; RVAD and Nash and Moe grade of rotation were assessed before and after applying the cast. Thirty-four (77.3 %) patients were followed up at least 24 months after removal of last EDF cast. RESULTS: Eighteen patients (3 males, 15 females) were included in Group 1, 12 (2 males, 10 females) in Group 2 and 14 (5 males, 9 females) in Group 3. Serial EDF casting was more effective at initial curve reduction and in preventing curve progression when applied under GA with neuromuscular blocking drugs, i.e. curare. RVAD and Nash and Moe score improved significantly in all groups of patients treated according to principles of EDF technique. During follow-up period, six patients required surgery in Group 1 (6/18; 33.3 %), 3 patients required surgery in Group 2 (3/12; 25 %) and 2 patients underwent surgery in Group 3 (2/14; 15 %). CONCLUSIONS: Preliminary results show EDF casting is effective in controlling the curve in both frontal (Cobb's angle) and transverse plane (rib vertebral angle and apical vertebral rotation degree).
Subject(s)
Anesthesia, General , Casts, Surgical , Isoquinolines/therapeutic use , Neuromuscular Blocking Agents/therapeutic use , Scoliosis/therapy , Adolescent , Braces , Disease Progression , Female , Follow-Up Studies , Humans , Male , Mivacurium , Radiography , Retrospective Studies , Scoliosis/diagnostic imaging , Young AdultABSTRACT
BACKGROUND: The routine use of neuromuscular blocking agents reduces the occurrence of unacceptable surgical conditions. In some surgeries, such as retroperitoneal laparoscopies, deep neuromuscular block (NMB) may further improve surgical conditions compared with moderate NMB. In this study, the effect of deep NMB on surgical conditions was assessed. METHODS: Twenty-four patients undergoing elective laparoscopic surgery for prostatectomy or nephrectomy were randomized to receive moderate NMB (train-of-four 1-2) using the combination of atracurium/mivacurium, or deep NMB (post-tetanic count 1-2) using high-dose rocuronium. After surgery, NMB was antagonized with neostigmine (moderate NMB), or sugammadex (deep NMB). During all surgeries, one surgeon scored the quality of surgical conditions using a five-point surgical rating scale (SRS) ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Video images were obtained and 12 anaesthetists rated a random selection of images. RESULTS: Mean (standard deviation) SRS was 4.0 (0.4) during moderate and 4.7 (0.4) during deep NMB (P<0.001). Moderate block resulted in 18% of scores at the low end of the scale (Scores 1-3); deep block resulted in 99% of scores at the high end of the scale (Scores 4 and 5). Cardiorespiratory conditions were similar during and after surgery in both groups. Between anaesthetists and surgeon, there was poor agreement between scores of individual images (average κ statistic 0.05). CONCLUSIONS: Application of the five-point SRS showed that deep NMB results in an improved quality of surgical conditions compared with moderate block in retroperitoneal laparoscopies, without compromise to the patients' peri- and postoperative cardiorespiratory conditions. Trial registration The study was registered at clinicaltrials.gov under number NCT01361149.
Subject(s)
Laparoscopy , Neuromuscular Blockade , Neuromuscular Blocking Agents , Adult , Aged , Androstanols/administration & dosage , Androstanols/antagonists & inhibitors , Anesthesia, Intravenous , Anesthetics, Intravenous , Consciousness Monitors , Data Interpretation, Statistical , Electric Stimulation , Electromyography , Endpoint Determination , Hemodynamics , Humans , Isoquinolines/administration & dosage , Isoquinolines/antagonists & inhibitors , Middle Aged , Mivacurium , Monitoring, Intraoperative , Muscle Contraction/physiology , Neuromuscular Blocking Agents/antagonists & inhibitors , Neuromuscular Nondepolarizing Agents/administration & dosage , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Propofol , Rocuronium , Sample Size , Sufentanil , Sugammadex , Video Recording , gamma-CyclodextrinsABSTRACT
Mutations in the butyrylcholinesterase gene can lead to a prolonged effect of the neuromuscular blocking agents, succinylcholine and mivacurium. If the anaesthesiologist is not aware of this condition, it may result in insufficient respiration after tracheal extubation. However, this can be avoided with the use of objective neuromuscular monitoring if used adequately. Three case reports of prolonged effect of succinylcholine or mivacurium were presented to illustrate the importance of neuromuscular monitoring during anaesthesia. In the first case, continuous intraoperative neuromuscular monitoring allowed a prolonged neuromuscular blockade to be discovered prior to tracheal extubation of the patient. The patient was extubated after successful reversal of the neuromuscular blockade. On the contrary, neuromuscular monitoring was not used during anaesthesia in the second patient; hence, the prolonged effect of the neuromuscular blocking agent was not discovered until after extubation. In the third patient, the lack of response to nerve stimulation was interpreted as a technical failure and the prolonged effect of succinylcholine was discovered when general anaesthesia was terminated. Both patients had insufficient respiration. They were therefore re-sedated, transferred to the intensive care unit and the tracheas were extubated after full recovery from neuromuscular blockade. We recommend the use of monitoring every time these agents are used, even with short-acting drugs like succinylcholine and mivacurium.
Subject(s)
Butyrylcholinesterase/deficiency , Isoquinolines/adverse effects , Metabolism, Inborn Errors/diagnosis , Neuromuscular Blockade , Neuromuscular Depolarizing Agents/adverse effects , Neuromuscular Monitoring , Neuromuscular Nondepolarizing Agents/adverse effects , Succinylcholine/adverse effects , Accelerometry/methods , Aged , Antidotes/therapeutic use , Apnea , Appendicitis , Butyrylcholinesterase/genetics , Butyrylcholinesterase/metabolism , Butyrylcholinesterase/physiology , Cholecystectomy, Laparoscopic , DNA Mutational Analysis , Female , Femoral Neck Fractures/surgery , Genotype , Humans , Hypnotics and Sedatives/therapeutic use , Isoquinolines/pharmacokinetics , Isoquinolines/pharmacology , Laparoscopy , Metabolism, Inborn Errors/genetics , Metabolism, Inborn Errors/metabolism , Middle Aged , Mivacurium , Neostigmine/therapeutic use , Neuromuscular Depolarizing Agents/pharmacokinetics , Neuromuscular Depolarizing Agents/pharmacology , Neuromuscular Nondepolarizing Agents/pharmacokinetics , Neuromuscular Nondepolarizing Agents/pharmacology , Respiration, Artificial , Respiratory Paralysis/chemically induced , Respiratory Paralysis/prevention & control , Respiratory Paralysis/therapy , Succinylcholine/pharmacokinetics , Succinylcholine/pharmacology , Time Factors , Young AdultABSTRACT
We systematically reviewed factors associated with intubation conditions in randomised controlled trials of mivacurium, using random-effects meta-regression analysis. We included 29 studies of 1050 healthy participants. Four factors explained 72.9% of the variation in the probability of excellent intubation conditions: mivacurium dose, 24.4%; opioid use, 29.9%; time to intubation and age together, 18.6%. The odds ratio (95% CI) for excellent intubation was 3.14 (1.65-5.73) for doubling the mivacurium dose, 5.99 (2.14-15.18) for adding opioids to the intubation sequence, and 6.55 (6.01-7.74) for increasing the delay between mivacurium injection and airway insertion from 1 to 2 min in subjects aged 25 years and 2.17 (2.01-2.69) for subjects aged 70 years, p < 0.001 for all. We conclude that good conditions for tracheal intubation are more likely by delaying laryngoscopy after injecting a higher dose of mivacurium with an opioid, particularly in older people.
Subject(s)
Intubation, Intratracheal/methods , Isoquinolines/administration & dosage , Neuromuscular Nondepolarizing Agents/administration & dosage , Female , Humans , Male , Mivacurium , Randomized Controlled Trials as Topic , Regression AnalysisABSTRACT
OBJECTIVE: To determine the effects of pretreatment with either promethazine or dexamethasone on mivacurium-induced histamine release in children. METHODS: Eighty ASA I-II children (4-10 years of age) scheduled for tonsillectomy and/or adenoidectomy were randomly divided into 4 groups (n = 20 per group) designated as either the rocuronium, mivacurium, dexamethasone (DXM), or promethazine group. Children in the DXM and promethazine groups were treated separately with intramuscular DXM 0.2 mg·kg(-1) or promethazine 0.5 mg·kg(-1) injections 60 min before operation. Radial artery blood samples were collected to quantify plasma histamine concentrations 1 min before and 1, 3, and 5 min after administration of the relaxant. Mean arterial pressure (MAP), heart rate (HR), and skin flushing were recorded at the same time. RESULTS: No significant decreases in plasma histamine concentrations were observed between groups; however, more stable MAP and HR and less skin flushing were observed in DXM group participants compared with individuals in the mivacurium group (P < 0.05). By contrast, children in the promethazine group had significantly decreased plasma histamine concentrations and stable MAP and HR (without a significant increase in HR) compared with patients in mivacurium group. In addition, skin flushing was significantly decreased compared with that observed in the rocuronium group (P < 0.05). CONCLUSIONS: Pretreatment with promethazine significantly decreased mivacurium-induced histamine release in children and provided stable hemodynamics during administration of anesthesia.
Subject(s)
Anti-Allergic Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Dexamethasone/therapeutic use , Histamine H1 Antagonists/therapeutic use , Histamine Release/drug effects , Isoquinolines/adverse effects , Neuromuscular Nondepolarizing Agents/adverse effects , Promethazine/therapeutic use , Adenoidectomy , Adolescent , Androstanols/adverse effects , Blood Pressure/drug effects , Child , Child, Preschool , Female , Galvanic Skin Response/drug effects , Heart Rate/drug effects , Histamine/blood , Humans , Male , Mivacurium , Preoperative Care , Rocuronium , TonsillectomyABSTRACT
OBJECTIVE: To explore the effects of pri ming rocuronium on neuromuscular blockade produced by mivacurium. METHODS: Ethical approval was granted by the medical ethics committee of our hospital with a reference number of C-2013-018-01. A total of 120 ASA physical status I and II patients undergoing selective otorhinolaryngologic surgery under general anesthesia signed the form of informed consent. And they were randomly divided by a random number table into 4 groups. After a standardized imidazole-propofol-fentanyl induction, they received a saline placebo injection (GroupI) and a pri ming dose of rocuronium 0.06 mg/kg (GroupII) , rocuronium 0.075 mg/kg (Group III) and rocuronium 0.1 mg/kg (Group IV). An intubating dose of mivacurium 0.15 mg/kg was offered 3 minutes later. Anesthesia was maintained with propofol and remifentanyl continuous infusion. Neuromuscular block was monitored with train of four (TOF) stimulation. The onset time, reappearance of T1 (DUR TOFc 1), times of T1 25% and 75% recovery, recovery index and times of TOF25%, 75% and 90% recovery were recorded. RESULTS: The onset time of mivacurium was significantly shorter and the times of T1 25% and 75% recovery were significantly longer in groups of II, III and IV than those in groupI. No significant difference existed in recovery index among 4 groups. The onset time of mivacurium became progressively shorter with the growing pri ming dose of rocurium among three experiment groups. And it was not statistically significant. CONCLUSIONS: Pri ming rocuronium decreases the onset and intubating times of mivacurium without effect on recovery index. No significant difference exists in drug effect among 3 experiment groups.
Subject(s)
Isoquinolines/pharmacokinetics , Neuromuscular Nondepolarizing Agents/pharmacokinetics , Androstanols , Anesthesia, General , Fentanyl , Humans , Mivacurium , Propofol , RocuroniumABSTRACT
Pseudocholinesterase or butyrylcholinesterase (BChE) inactivates the relaxant drugs mivacurium and suxamethonium. A deficiency in plasma activity of this enzyme may result in prolonged muscular paralysis and subsequently the need for an extended duration of mechanical ventilation. We report the case of a 65-year-old patient who was diagnosed with butyrylcholinesterase deficiency for the first time during elective surgery. Neuromuscular monitoring constitutes a central diagnostic asset in ensuring patient safety.