Administration Of Mivacurium Research Articles

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.

Spontaneous Ventilation Combined with Double-Lumen Tube Intubation during Thoracic Surgery: A New Anesthesiologic Method Based on 141 Cases over Three Years.

Non-intubated thoracic surgery has not achieved widespread acceptance despite its potential to improve postoperative outcomes. To ensure airway safety, our institute has developed a technique combining spontaneous ventilation with double-lumen tube intubation (SVI). This study aimed to verify the feasibility and limitations of this SVI technique. For the SVI method, anesthesia induction involves fentanyl and propofol target-controlled infusion, with mivacurium administration. Bispectral index monitoring was used to ensure the optimal depth of anesthesia. Short-term muscle relaxation facilitated double-lumen tube intubation and early surgical steps. Chest opening preceded local infiltration, followed by a vagal nerve blockade to prevent the cough reflex and a paravertebral blockade for pain relief. Subsequently, the muscle relaxant was ceased. The patient underwent spontaneous breathing without coughing during surgical manipulation. Between 10 March 2020 and 28 October 2022, 141 SVI surgeries were performed. Spontaneous respiration with positive end-expiratory pressure was sufficient in 65.96% (93/141) of cases, whereas 31.21% (44/141) required pressure support ventilation. Only 2.84% (4/141) of cases reversed to conventional anesthetic management, owing to technical or surgical difficulties. Results of the 141 cases: The mean maximal carbon dioxide pressure was 59.01 (34.4-92.9) mmHg, and the mean lowest oxygen saturation was 93.96% (81-100%). The mean one-lung, mechanical and spontaneous one-lung ventilation time was 74.88 (20-140), 17.55 (0-115) and 57.73 (0-130) min, respectively. Spontaneous ventilation with double-lumen tube intubation is safe and feasible for thoracic surgery. The mechanical one-lung ventilation time was reduced by 76.5%, and the rate of anesthetic conversion to relaxation was low (2.8%).

Prolonged Recovery of Neuromuscular Transmission during General Anaesthesia after Mivacurium Administration - Case Report

Mivacurium is the shortest-acting non-depolarizing relaxant, used for brief procedures, such as those performed in the ambulatory setting. The recommended intubating dose of 0.2 mg/kg usually provides a clinically effective neuromuscular block for approximately 15 to 20 minutes and spontaneous recovery is 95% complete within about 25 to 30 minutes.

Prolonged Recovery of Neuromuscular Transmission during General Anaesthesia after Mivacurium Administration - Case Report

Mivacurium is the shortest-acting non-depolarizing relaxant, used for brief procedures, such as those performed in the ambulatory setting. The recommended intubating dose of 0.2 mg/kg usually provides a clinically effective neuromuscular block for approximately 15 to 20 minutes and spontaneous recovery is 95% complete within about 25 to 30 minutes.

A Companion Diagnostic for Personalizing Mivacurium at the Point-of-Care

Mivacurium chloride is envisioned as the “gold-adjunct” in anesthesia and emergency medicine. People across the world are administered mivacurium in emergency situations as clinicians prefer it among the frequently used neuromuscular blockers thanks to its rapid action and short duration. Mivacurium is promptly degraded and deactivated by plasma cholinesterase enzyme (PChE), however during emergency situations, some individuals were found to be unable to metabolize mivacurium shortly after its injection, resulting in prolonged paralysis and potentially lethal respiratory apnea. The most clinically significant cause of this residual paralysis and apnea is the reduced cholinesterase ability to effectively hydrolyze mivacurium. Hitherto, monitoring of mivacurium enzymatic degradation has been remaining a long-standing challenge for analytical chemists as well as anesthesiologists. Firstly, it undergoes rapid hydrolysis by the PChE-enzyme 8 min post-injection, therefore, frequent sampling all through the first minutes after mivacurium administration is mandatory. Secondly, its isolation from biological specimens is extremely difficult due to its chemical properties which involves both hydrophilic and lipophilic characteristics. These challenges impede the development of a universal protocol to be established for screening of PChE-activity towards mivacurium and which clearly identifies patients susceptible to prolonged paralysis. In this study, we designed a point-of-care (PoC) potentiometric sensor that can perform tracking of mivacurium enzymatic degradation kinetics with high accuracy and rapidly. Real serum samples were utilized for in vitro estimation of the rate of mivacurium metabolism, where values of 227 μmol l−1 and 62 μM min−1 were obtained for the characteristic parameters of the enzymatic reaction, Km and Vmax, respectively. Correlation of the results obtained using the proposed approach and earlier LC-MS/MS study is shown.

Neostigmine‐induced weakness: what are the facts?

Neostigmine‐induced weakness: what are the facts?

The efficacy and safety of mivacurium in pediatric patients

BackgroundMivacurium 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.MethodsSix 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).ResultsFive 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.ConclusionsThe 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 registrationClinicalTrials.gov Identifier-NCT02117401, July 14, 2014. (Retrospectively registered)

Human butyrylcholinesterase polymorphism: Molecular modeling.

Prolonged apnoea following injection of ester-containing myoralaxants was first described in 1953. Because a large part of administered succinylcholine is shortly hydrolyzed by plasma butyrylcholinesterase (BChE) under normal conditions, prolonged apnoea was attributed to deficiency in BChE. It was found that BChE deficiency was due to genetic variations. Human BChE gene shows a large polyallelism. About 75 natural mutations of the BCHE gene have been documented so far [1]. Most of them cause alteration in BChE activity through point mutation effect on catalytic activity. Frame shifts and stop codons may also affect expression, or cause truncations in the sequence. Recently, two novel BChE "silent" variants, Val204Asp [2] and Ala34Val [3], causing prolonged neuromuscular block after administration of mivacurium, were discovered. Mutations were genetically and kinetically characterized. The aim of the current study was to understand how these mutations determine "silent" phenotype. Molecular dynamics studies were carried out with NAMD 2.9 software at the Lomonosov supercomputer. Charmm 36 force field was used, periodical boundary conditions, 1 atm pressure, 298 K. 100 ns molecular dynamics runs were performed for the wild-type BChE and its mutants Val204Asp and Ala34Val. Unlike wild-type BChE, which retained its operative catalytic triad through the whole MD simulation, the catalytic triad of mutants was disrupted, making chemical step impossible. Val204Asp mutation leads to reorganization of hydrogen bonding network around the catalytic triad, which in turn increases the distance between catalytic residue main chains. Mutation Ala34Val, located on the protein surface, leads to increased fluctuations in the Ω-loop and subsequent disruption of the gorge structure, including disruption of the catalytic triad and formation of new hydrogen bonds involving catalytic center residues. Comparative study of the "silent" Ala328Asp mutant and the catalytically active mutant Ala328Cys shows that MD approach can discriminate between the differential effects of point mutations at a same position.

Awareness during emergence from anaesthesia: significance of neuromuscular monitoring in patients with butyrylcholinesterase deficiency

Butyrylcholinesterase deficiency can result in prolonged paralysis after administration of succinylcholine or mivacurium. We conducted an interview study to assess whether patients with butyrylcholinesterase deficiency were more likely to have experienced awareness during emergence from anaesthesia if neuromuscular monitoring had not been applied. Patients referred during 2004-2012 were included. Data on the use of neuromuscular monitoring were available from a previous study. Interviews, conducted by telephone, included questions about awareness and screening for post-traumatic stress disorder. Reports of panic, hopelessness, suffocation, or a feeling of being dead or dying resulted in the experience being classified further as distressful. Patients were categorized as aware or unaware by investigators blinded to use of neuromuscular monitoring. Ninety-five patients were eligible to be interviewed. Of the 70 patients interviewed, 35 (50%) were aware while paralysed during emergence. Of these, 28 (80%) were not monitored with a nerve stimulator when awakened, compared with 17 (49%) of the 35 unaware patients (P=0.012, Fisher's exact test). Thirty (86%) aware patients reported distress compared with seven (20%) unaware patients (P<0.001). The aware patients scored higher in screening for post-traumatic stress disorder (P=0.006, Mann-Whitney U-test). Butyrylcholinesterase deficiency is a major risk factor for distressing awareness during emergence. Lack of neuromuscular monitoring increases the risk significantly. Neuromuscular monitoring should be applied even when using short-acting neuromuscular blocking agents.

Characterization of a novel butyrylcholinesterase point mutation (p.Ala34Val), “silent” with mivacurium

Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivarcurium) in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of mivacurium leading to the discovery of a novel BCHE variant (c.185C>T, p.Ala34Val). Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation remote from the active center determines the “silent” phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine, and values of dibucaine and fluoride numbers fit with a heterozygous enzyme of type atypical/silent. Kinetic analysis with succinyldithiocholine (SCdTC) as the substrate showed that Ala34Val BChE was inactive against this substrate. However, with BTC, the mutant enzyme was active, displaying an unexpected activation by excess substrate. Competitive inhibition of BTC by mivacurium gave a Ki=1.35mM consistent with the lack of activity with the related substrate SCdTC, and with the clinical data. Molecular dynamic simulations revealed the mechanism by which mutation Ala34Val determines the silent phenotype: a chain of intramolecular events leads to disruption of the catalytic triad, so that His438 no longer interacts with Ser198, but instead forms hydrogen bonds either with residues Glu197 and Trp82, or peripheral site residue Tyr332. However, at high BTC concentration, initial binding of substrate to the peripheral site triggers restoration of a functional catalytic triad, and activity with BTC.

Metoclopramida e ondansetrona alteram o bloqueio neuromuscular induzido por mivacúrio? – um estudo randomizado

Background: We aimed to investigate the effects of metoclopramide and ondansetrone on mivacurium neuromuscular blockade. Methods: Seventy five, ASA I-II patients, aged 18-65 and scheduled for elective surgery requiring tracheal intubation were included in the study. The patients received metoclopramide 10 mg, ondansetrone 4 mg or normal saline 5 mL; group M, group O, group NS (n = 25), respectively. Before anesthesia study drugs were administered in a volume of 5 mL. The level of plasma cholinesterase were obtained before and 5 minutes after the administration of study drugs and5 minutes after the administration of mivacurium. Onset time, T25, T75, T25-75, T90 levelswere compared with each other and differences between each patients were investigated. After recording T90, the study was terminated and surgery was started. Results: Onset time was significantly shorter in group M, than the other two groups. Onset time in group O was significantly shorter than in group NS. In Group M T25, T75, T90 and recovery indices were significantly greater than in Group NS (p < 0.001). In Group O T25, T75 were greater than Group NS (p < 0.01 and p < 0.05, respectively). In Group M T75, T90 and emergence indices were significantly higher than Group O (p < 0.001, p < 0.01, p < 0.001, respectively). In Groups M and O, plasma cholinesterase levels decreased significantly (p < 0.001) after administration of study drugs and mivacurium. Plasma cholinesterase also was reduced in Group NS 5 minutes after the administration of mivacurium (p < 0.001). Conclusion: Ondansetrone is believed to be more reliable agent than metoclopramide when used with mivacurium.

Do metoclopramide and ondansetrone alter mivacurium-induced neuromuscular blockade? – a randomised trial

BackgroundWe aimed to investigate the effects of metoclopramide and ondansetrone on mivacurium neuromuscular blockade. MethodsSeventy five, ASA I-II patients, aged 18-65 and scheduled for elective surgery requiring tracheal intubation were included in the study. The patients received metoclopramide 10mg, ondansetrone 4mg or normal saline 5mL; group M, group O, group NS (n=25), respectively. Before anesthesia study drugs were administered in a volume of 5mL. The level of plasma cholinesterase were obtained before and 5minutes after the administration of study drugs and 5minutes after the administration of mivacurium. Onset time, T25, T75, T25-75, T90 levels were compared with each other and differences between each patients were investigated. After recording T90, the study was terminated and surgery was started. ResultsOnset time was significantly shorter in group M, than the other two groups. Onset time in group O was significantly shorter than in group NS. In Group M T25, T75, T90 and recovery indices were significantly greater than in Group NS (p<0.001). In Group O T25, T75 were greater than Group NS (p<0.01 and p<0.05, respectively). In Group M T75, T90 and emergence indices were significantly higher than Group O (p<0.001, p<0.01, p<0.001, respectively). In Groups M and O, plasma cholinesterase levels decreased significantly (p<0.001) after administration of study drugs and mivacurium. Plasma cholinesterase also was reduced in Group NS 5minutes after the administration of mivacurium (p<0.001). ConclusionOndansetrone is believed to be more reliable agent than metoclopramide when used with mivacurium.

Comparison of heart rate variability response in children undergoing elective endotracheal intubation with and without neuromuscular blockade: a randomized controlled trial

The routine use of neuromuscular blocking drugs (NMBD) for endotracheal intubation in children is the subject of much controversy. The analysis of heart rate variability (HRV) can reveal information about the functional state of the autonomic nervous system (ANS). The purpose of this study was to determine if HRV elucidates differences in the sympathovagal balance of children undergoing elective endo-tracheal intubation with and without neuromuscular blockade (NMB). In this prospective study, 38 children (2-6 years) scheduled for adenotonsillectomy were randomized into two groups to receive fentanyl 2 μg·kg(-1) and propofol 4 mg·kg(-1) , with either mivacurium 0.25 mg·kg(-1) (NMB group) or saline solution (NoNMB group) for anesthesia induction. The same experienced, blinded anesthesiologist performed endotracheal intubation. Heart rate variability, RR intervals, ECG as well as an electroencephalogram were recorded with HRV and BIS XP monitors, respectively. Heart rate variability was analyzed in the frequency domain. There was no significant difference in HRV changes immediately after mivacurium administration compared with an administration of saline. The groups were comparable for the bispectral index value (NMB 35 [33-41] vs NoNMB 34 [32-42]) during endotracheal intubation. Changes in both the low-frequency power and the low-/high-frequency ratio immediately after endotracheal intubation compared with the unstimulated state before laryngoscopy were significantly higher without NMB (P = 0.015 and P = 0.006, respectively), whereas there was no significant difference with respect to the high-frequency power. The stress response during endotracheal intubation in pediatric patients represented by the frequency domain analysis of HRV was found to be higher without NMB. When mivacurium was added to a propofol-fentanyl induction regimen, the ANS alterations during endotracheal intubation decreased significantly.

İKİ YAŞINDAKİ BİR ÇOCUKTA KONJENİTAL PSÖDOKOLİNESTERAZ ENZİM EKSİKLİĞİNE BAĞLI UZAMIŞ APNE

Mivacurium nondepolarizing neuromusculer blocking agent hydrolyzed by plasmacholinesterase, especially used for endotracheal intubation for short time surgeries. In this article a case of prolonged apnea after mivacurium administration pseudocholinesterase deficiency (serum level of pseudocholinesterase was 1658 IU/L, normal: 4000-11.000 IU/L) was reported

Clinical evaluation of a simultaneous closed-loop anaesthesia control system for depth of anaesthesia and neuromuscular blockade*

We developed a closed-loop system to control the depth of anaesthesia and neuromuscular blockade using the bispectral index and the electromyogram simultaneously and evaluated the clinical performance of this combined system for general anaesthesia. Twenty-two adult patients were included in this study. Anaesthesia was induced by a continuous infusion of remifentanil at 0.4 μg.kg(-1) .min(-1) (induction dose) and then 0.25 μg.kg(-1) .min(-1) (maintenance dose) and propofol at 2 mg.kg(-1) 3 min later. The combined automatic control was started 2 min after tracheal intubation. The depth of anaesthesia was recorded using bispectral index monitoring using a target value of 40. The target value of neuromuscular blockade, using mivacurium, was a T1/T1(0) twitch height of 10%. The precision of the system was calculated using internationally defined performance parameters. Twenty patients were included in the data analysis. The mean (SD) duration of simultaneous control was 129 (69) min. No human intervention was necessary during the computer-controlled administration of propofol and mivacurium. All patients assessed the quality of anaesthesia as 'good' to 'very good'; there were no episodes of awareness. The mean (SD) median performance error, median absolute performance error and wobble for the control of depth of anaesthesia and for neuromuscular blockade were -0.31 (1.78), 6.76 (3.45), 6.32 (2.93) and -0.38 (1.68), 3.75 (4.83), 3.63 (4.69), respectively. The simultaneous closed-loop system using propofol and mivacurium was able to maintain the target values with a high level of precision in a clinical setting.

Sertraline-induced pseudocholinesterase enzyme deficiency

A 47-year-old Turkish male was scheduled for laparoscopic cholecystectomy under general anesthesia. The patient had 2 operations 28 and 19 years ago under general anesthesia. It was learned that the patient was administered succinylcholine during both of these previous operations and that he did not have a history of prolonged recovery or postoperative apnea. The patient had been using sertraline for 3 years before the operation. Pseudocholinesterase is a drug-metabolizing enzyme responsible for hydrolysis of the muscle-relaxant drugs mivacurium and succinylcholine. Deficiency of this enzyme from any cause can lead to prolonged apnea and paralysis following administration of mivacurium and succinylcholine. The diagnosis of pseudocholinesterase enzyme deficiency can be made after careful clinic supervision and peripheral nerve stimulator monitoring. A decrease in the activity of pseudocholinesterase enzyme and a decline in the block effect over time will help verify the diagnosis. Our patient’s plasma cholinesterase was found to have low activity. Instead of pharmacological interventions that may further complicate the situation in such cases, the preferred course of action should be to wait until the block effect declines with the help of sedation and mechanical ventilation. In our case, the prolonged block deteriorated in the course of time before any complications developed.

The effects of mivacurium‐induced neuromuscular block on Bispectral Index and Cerebral State Index in children under propofol anesthesia – a prospective randomized clinical trial

In adults anesthetized with propofol, muscle relaxants may decrease the Bispectral Index (BIS). The aim of this prospective randomized trial was to detect the influence of a muscle relaxant bolus on the BIS and the Cerebral State Index (CSI) in children under propofol anesthesia. Forty pediatric patients, age 6.6 +/- 3.3 years, weight 24 +/- 9 kg, scheduled for surgical procedures requiring general anesthesia were enrolled. Two minutes after i.v. injection of 0.3 mcg.kg(-1) of sufentanil, general anesthesia was induced by an initial bolus of 3 mg.kg(-1) of propofol, followed by a continuous infusion titrated to achieve a stable BIS value of 50 +/- 5. Patients received either mivacurium 0.25 mg.kg(-1) (Group Miva) or NaCl 0.9% 0.12 ml.kg(-1) (Group Control). Mean BIS and CSI values per minute were compared between (Miva vs. Control) and within groups (Baseline vs 5 min. after study drug administration). The observed changes in BIS and CSI values before and after administration of study drugs revealed no differences between the study groups. Mean baseline BIS and CSI values were lower than 5 min after study drug administration. There were no intergroup differences with respect to BIS and CSI values at any time point. These data suggest that in pediatric patients anesthetized with propofol, administration of mivacurium has no impact on BIS and CSI values.

Pseudocholinesterase enzyme deficiency: a case series and review of the literature

IntroductionPseudocholinesterase (butyrylcholinesterase) is a drug metabolizing enzyme responsible for hydrolysis of the muscle relaxant drugs succinylcholine and mivacurium. Deficiency from any cause can lead to prolonged apnoea and paralysis following administration of succinylcholine and mivacurium.Case presentationWithin the last two years we have had four patients who have had prolonged apnea following the administration of mivacurium. It was understood that one was congenital and the other three due to various reasons had enzyme-deficiencies. In all four of the patients, the prolonged blocks deteriorated.ConclusionProlonged blocks may be encountered due to mivacurium use. The diagnosis of pseudocholinesterase enzyme deficiency can be given after a careful clinic supervision and peripheral nerve stimulator monitoring. A decrease in the activity of pseudocholinesterase enzyme and improvement in neuromuscular function will help verifying our diagnosis. Instead of pharmacological applications that may further complicate the situation, what should be done in such patients is to wait until the block-effect goes down by the help of sedation and mechanical ventilation.

Is your patient sleeping?

Is your patient sleeping?

The Involvement of Histaminic and Muscarinic Receptors in the Bronchoconstriction Induced by Myorelaxant Administration in Sensitized Rabbits

Muscle relaxants cause bronchospasm via histamine release and/or by acting on the muscarinic receptors; we sought to characterize the respective importance of these pathways in the presence of bronchial hyperreactivity. Ovalbumin-sensitized rabbits were randomly assigned to several protocol groups: Group C comprised untreated animals; in the other three groups, either H1 and H2 histaminic receptor blockade was performed, leaving the M1, M2, and M3 muscarinic receptors functional (Group M123), or combining this treatment with M3 muscarinic receptor blockade (Group M12), or with vagotomy (Group M3). Respiratory system impedance was measured over a 90-s period, during which succinylcholine, mivacurium or atracurium was administered. To monitor the changes in lung mechanics, respiratory system impedance was averaged in a 2-s time window and fitted by a model featuring airway resistance and inertance and tissue damping and elastance. The peak increases in airway resistance in Group C were greatest with succinylcholine (79 +/- 17[SE]%) and mivacurium administration (75% +/- 12%), whereas they were lower after attracurium (40% +/- 11%). These changes were markedly attenuated by both histamine and muscarinic receptor blockade with the largest reduction in Group M3 for succinylcholine (14% +/- 5.2%), and in Group M123 for mivacurium (5.1% +/- 9.1%) and attracurium (7.8% +/- 4.0%). Although the bronchospasm developing in the allergic airways after muscle relaxants is mediated primarily by the histaminic pathway, the interactions of succinylcholine on the M1, M2, and M3 receptors, those of atracurium on the M1 and M2 receptors, and those of mivacurium on the M3 receptors may also play a role.