scholarly journals Low-frequency Neuromuscular Depression Is a Consequence of a Reduction in Nerve Terminal Ca2+ Currents at Mammalian Motor Nerve Endings

2013 ◽  
Vol 119 (2) ◽  
pp. 326-334
Author(s):  
Eugene M. Silinsky
Keyword(s):  
Nerve Terminal ◽  
Nerve Stimulation ◽  
Neurotransmitter Release ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Neuromuscular Block ◽  
Low Frequency ◽  
Neuromuscular Blocking ◽  
Train Of Four ◽  
Train Of Four Monitoring

Abstract Background: The decline in voluntary muscle contraction during low-frequency nerve stimulation is used clinically to assess the type and degree of neuromuscular block. The mechanism underlying this depression is unknown. Methods: Simultaneous electrophysiological measurements of neurotransmitter release and prejunctional Ca2+ currents were made at mouse neuromuscular junctions to evaluate the hypothesis that decreases in nerve terminal Ca2+ currents are responsible for low-frequency depression. Results: Under conditions generally used to measure Ca2+ currents at the neuromuscular junction, increasing the frequency of nerve stimulation briefly from 0.017 to 0.1–1 Hz caused a simultaneous reduction in the release of the neurotransmitter acetylcholine to 52.2 ± 4.4% of control and the Ca2+ current peak to 75.4 ± 2.0% of control (P < 0.001, n = 5 experiments for both measurements, mean ± SEM for all data). In conditions used for train-of-four monitoring (4 stimuli, 2 Hz), neurotransmitter release declined to 42.0 ± 1.0% of control and the Ca2+ current peak declined to 75.8 ± 3.3% of control between the first and fourth stimulus (P < 0.001, n = 7 experiments for both measurements). Depression in acetylcholine release during train-of-four protocols also occurred in the absence of neuromuscular-blocking drugs. Discussion: The results demonstrate that neuromuscular depression during train-of-four monitoring is due to a decline in nerve terminal Ca2+ currents, hence reducing the release of acetylcholine. As similar processes may come into play at higher stimulation frequencies, agents that antagonize the decline in Ca2+ currents could be used to treat conditions in which neuromuscular depression can be debilitating.

Residual Block after Mivacurium with or without Edrophonium Reversal in Adults and Children

1996 ◽  
Vol 84 (2) ◽  
pp. 362-367. ◽  
Author(s):  
David R. Bevan ◽  
Raymond Kahwaji ◽  
John M. Ansermino ◽  
Eleanor Reimer ◽  
Michael F. Smith ◽  
...  
Keyword(s):  
Ulnar Nerve ◽  
Neuromuscular Block ◽  
Saline Group ◽  
Neuromuscular Blocking ◽  
Postanesthesia Care Unit ◽  
Random Allocation ◽  
Train Of Four ◽  
Residual Neuromuscular Block ◽  
Residual Block ◽  
Stimulation Of

Background The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. Methods In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. Results Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P<0.01), TOF was >0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P<0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was <0.7 in four others), compared with TOF <0.7 in only one of the edrophonium group (P<0.05). Conclusions This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

A872 MOTOR NERVE TERMINAL EFFECTS OF HALOTHANE (HAL) POTENTIATE CURARE-(DTC) INDUCED NEUROMUSCULAR BLOCK

1990 ◽  
Vol 73 (3A) ◽  
pp. NA-NA ◽  
Author(s):  
M. D. Sokoll ◽  
B. Bhattacharyya ◽  
L. R. Davies ◽  
D. Q. Zwagerman
Keyword(s):  
Nerve Terminal ◽  
Motor Nerve ◽  
Neuromuscular Block ◽  
Motor Nerve Terminal

Response to Mivacurium in Patients Carrying the K Variant in the Butyrylcholinesterase Gene

2005 ◽  
Vol 102 (3) ◽  
pp. 503-508 ◽  
Author(s):  
Mona R. Gätke ◽  
Jørgen Viby-Mogensen ◽  
Doris Østergaard ◽  
Jens R. Bundgaard
Keyword(s):  
Nerve Stimulation ◽  
Dna Analysis ◽  
Neuromuscular Block ◽  
Nucleotide Sequencing ◽  
Wild Type ◽  
Duration Of Action ◽  
Prolonged Duration ◽  
Train Of Four ◽  
K Variant

Background Mivacurium is hydrolyzed by the butyrylcholinesterase enzyme, and patients with hereditary changes of the enzyme often have prolonged duration of action of mivacurium. In this study, the authors investigated the significance of the most commonly occurring variant, the Kalow (K) variant, established using DNA analysis, for the response to mivacurium. Methods A total of 58 patients carrying either the wild-type butyrylcholinesterase or different combinations of the atypical (A) variant and the K variant were included. Patients who were homozygous for the A variant were given 0.03 mg/kg mivacurium. All other patients received 0.2 mg/kg mivacurium. The neuromuscular block was measured using train-of-four nerve stimulation and mechanomyography. Genotyping was performed with complete nucleotide sequencing. Results Heterozygosity of the K variant prolonged the time to train-of-four 0.70 from 26.6 to 34.5 min (30%; not significant) as compared with the wild type. Heterozygosity of the K variant linked to the A variant prolonged the corresponding time from 32 to 42.7 min (33%; P = 0.03) as compared with patients who were heterozygous for solely an A allele. For eight patients who were homozygous for both the A and K variants, the time to 25% recovery was 78-89 min as compared with 44-57 min in patients who were homozygous for the A variant or had only one linked K variant. Conclusion The K variant prolongs the duration of action of mivacurium. The current results indicate that the effect is modest when the K variant occurs heterozygously with the wild type or the A variant but is marked in patients who are homozygous for both the A and K variants.

Pharyngeal Function and Breathing Pattern during Partial Neuromuscular Block in the Elderly

2014 ◽  
Vol 120 (2) ◽  
pp. 312-325 ◽  
Author(s):  
Anna I. Hårdemark Cedborg ◽  
Eva Sundman ◽  
Katarina Bodén ◽  
Hanne Witt Hedström ◽  
Richard Kuylenstierna ◽  
...  
Keyword(s):  
Neuromuscular Block ◽  
The Elderly ◽  
Pulmonary Complications ◽  
Neuromuscular Blocking ◽  
Residual Effects ◽  
Airway Protection ◽  
Healthy Elderly ◽  
Increased Risk ◽  
Train Of Four ◽  
Pharyngeal Function

Abstract Background: Intact pharyngeal function and coordination of breathing and swallowing are essential for airway protection and to avoid respiratory complications. Postoperative pulmonary complications caused by residual effects of neuromuscular-blocking agents occur more frequently in the elderly. Moreover, elderly have altered pharyngeal function which is associated with increased risk of aspiration. The purpose of this study was to evaluate effects of partial neuromuscular block on pharyngeal function, coordination of breathing and swallowing, and airway protection in individuals older than 65 yr. Methods: Pharyngeal function and coordination of breathing and swallowing were assessed by manometry and videoradiography in 17 volunteers, mean age 73.5 yr. After control recordings, rocuronium was administered to obtain steady-state train-of-four ratios of 0.70 and 0.80 followed by spontaneous recovery to greater than 0.90. Results: Pharyngeal dysfunction increased significantly at train-of-four ratios 0.70 and 0.80 to 67 and 71%, respectively, compared with 37% at control recordings, and swallowing showed a more severe degree of dysfunction during partial neuromuscular block. After recovery to train-of-four ratio of greater than 0.90, pharyngeal dysfunction was not significantly different from the control state. Resting pressure in the upper esophageal sphincter was lower at all levels of partial neuromuscular block compared with control recordings. The authors were unable to demonstrate impaired coordination of breathing and swallowing. Conclusion: Partial neuromuscular block in healthy elderly individuals causes an increased incidence of pharyngeal dysfunction from 37 to 71%, with impaired ability to protect the airway; however, the authors were unable to detect an effect of partial neuromuscular block on coordination of breathing and swallowing.

Distinct Pharmacologic Properties of Neuromuscular Blocking Agents on Human Neuronal Nicotinic Acetylcholine Receptors

2006 ◽  
Vol 105 (3) ◽  
pp. 521-533 ◽  
Author(s):  
Malin Jonsson ◽  
David Gurley ◽  
Michael Dabrowski ◽  
Olof Larsson ◽  
Edwin C. Johnson ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Messenger Rna ◽  
Motor Nerve ◽  
Neuromuscular Block ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agents ◽  
Xenopus Laevis Oocytes ◽  
Motor Nerve Ending ◽  
Nicotinic Acetylcholine ◽  
Blocking Agents

Background Nondepolarizing neuromuscular blocking agents (NMBAs) are extensively used in the practice of anesthesia and intensive care medicine. Their primary site of action is at the postsynaptic nicotinic acetylcholine receptor (nAChR) in the neuromuscular junction, but their action on neuronal nAChRs have not been fully evaluated. Furthermore, observed adverse effects of nondepolarizing NMBAs might originate from an interaction with neuronal nAChRs. The aim of this study was to examine the effect of clinically used nondepolarizing NMBAs on muscle and neuronal nAChR subtypes. Methods Xenopus laevis oocytes were injected with messenger RNA encoding for the subunits included in the human alpha1beta1epsilondelta, alpha3beta2, alpha3beta4, alpha4beta2, and alpha7 nAChR subtypes. The interactions between each of these nAChR subtypes and atracurium, cisatracurium, d-tubocurarine, mivacurium, pancuronium, rocuronium, and vecuronium were studied using an eight-channel two-electrode voltage clamp setup. Responses were measured as peak current and net charge. Results All nondepolarizing NMBAs inhibited both muscle and neuronal nAChRs. The neuronal nAChRs were reversibly and concentration-dependently inhibited in the low micromolar range. The mechanism (i.e., competitive vs. noncompetitive) of the block at the neuronal nAChRs was dependent both on subtype and the NMBA tested. The authors did not observe activation of the nAChR subtypes by any of the NMBAs tested. Conclusions The authors conclude that nondepolarizing NMBAs concentration-dependently inhibit human neuronal nAChRs. The inhibition of the presynaptic alpha3beta2 nAChR subtype expressed at the motor nerve ending provides a possible molecular explanation for the tetanic and train-of-four fade seen during a nondepolarizing neuromuscular block.

scholarly journals Optimal neuromuscular blocking effects of remifentanil during tracheal intubation under general anesthesia

2018 ◽  
Vol 46 (8) ◽  
pp. 3097-3103 ◽  
Author(s):  
So Young Kwon ◽  
Si Wook Chung ◽  
Jin Deok Joo
Keyword(s):  
General Anesthesia ◽  
Elective Surgery ◽  
Neuromuscular Block ◽  
Onset Time ◽  
Neuromuscular Blocking ◽  
Blocking Effects ◽  
Train Of Four ◽  
The Times ◽  
Time Required ◽  
Retrospective Comparative Study

Objective This study was performed to determine the effect of the remifentanil dose on the onset time of rocuronium with electromyography. Methods This retrospective comparative study included 75 patients undergoing general anesthesia for elective surgery. Patients received lidocaine (40 mg) and propofol (2 mg/kg) followed by rocuronium (0.6 mg/kg) with either saline infusion (Group S), remifentanil at 0.5 µg/kg/minute (Group R 0.5), or remifentanil at 1.0 µg/kg/minute (Group R 1.0). Neuromuscular block was monitored by train-of-four (TOF) electromyography, and the times taken to reach TOF 0 and TOF ratio (TOFR) 25% were recorded. Results The times taken to reach TOF 0 and TOFR 25% were significantly higher in Groups R 0.5 and R 1.0 than in Group S. The time taken to reach TOF 0 was 130.0 ± 6.4 s in Group S, 142.6 ± 6.0 s in Group R 0.5, and 183.0 ± 11.6 s in Group R 1.0. The time taken to reach TOFR 25% was also higher in Groups R 0.5 and R 1.0 than in Group S. Conclusions As the remifentanil dose increases, the intubation time required to reach TOF 0 also increases. Remifentanil has an effect on the onset of rocuronium.

scholarly journals Presynaptic Proteins as Markers of the Neurotoxic Activity of BmjeTX-I and BmjeTX-II Toxins fromBothrops marajoensis(Marajó Lancehead) Snake Venom

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Antonio Lisboa ◽  
Rodolfo Melaré ◽  
Junia R. B. Franco ◽  
Carolina V. Bis ◽  
Marta Gracia ◽  
...  
Keyword(s):  
Nerve Terminal ◽  
Neurotransmitter Release ◽  
Acetylcholine Receptors ◽  
Motor Nerve ◽  
Synaptic Proteins ◽  
Muscle Fibres ◽  
Motor Nerve Terminal ◽  
Transmission Electron ◽  
Skeletal Muscle Fibres

Neuromuscular preparations exposed toB. marajoensisvenom show increases in the frequency of miniature end-plate potentials and twitch tension facilitation followed by presynaptic neuromuscular paralysis, without evidences of muscle damage. Considering that presynaptic toxins interfere into the machinery involved in neurotransmitter release (synaptophysin, synaptobrevin, and SNAP25 proteins), the main objective of this communication is to analyze, by immunofluorescence and western blotting, the expression of the synaptic proteins, synaptophysin, synaptobrevin, and SNAP25 and by myography, light, and transmission electron microscopy the pathology of motor nerve terminals and skeletal muscle fibres of chick biventer cervicis preparations (CBC) exposedin vitroto BmjeTX-I and BmjeTX-II toxins fromB. marajoensisvenom. CBC incubated with toxins showed irreversible twitch tension blockade and unaffected KCl- and ACh-evoked contractures, and the positive colabelling of acetylcholine receptors confirmed that their action was primarily at the motor nerve terminal. Hypercontraction and loose myofilaments and synaptic vesicle depletion and motor nerve damage indicated that the toxins displayed both myotoxic and neurotoxic effect. The blockade resulted from interference on synaptophysin, synaptobrevin, and SNAP25 proteins leading to the conclusion that BmjeTX-I and BmjeTX-II affected neurotransmitter release machinery by preventing the docking of synaptic vesicles to the axolemma of the nerve terminal.

Neuromuscular blockade and reversal

2017 ◽  
Author(s):  
Jennifer M. Hunter ◽  
Thomas Fuchs-Buder
Keyword(s):  
Neuromuscular Block ◽  
Neuromuscular Disorders ◽  
Upper Airway ◽  
Blocking Agent ◽  
Rapid Onset ◽  
Neuromuscular Blocking ◽  
Onset Of Action ◽  
Disease States ◽  
Train Of Four ◽  
Residual Block

Over the past 70 years since the introduction of d-tubocurarine, the search for an ideal neuromuscular blocking agent has led to the development of the depolarizing drug, succinylcholine (suxamethonium), with its rapid onset of action and plasma metabolism, and a series of non-depolarizing agents of which there are two groups: benzylisoquinoliniums (e.g. atracurium, cisatracurium and mivacurium) and aminosteroidal agents (e.g. pancuronium, vecuronium and rocuronium). The need to monitor neuromuscular block perioperatively to ensure the appropriate dose of any neuromuscular blocking drug is given has led to the development of several nerve stimulation techniques. Particularly useful clinically are the train-of-four twitch response, double-burst stimulation, and the post-tetanic count. Their benefits and limitations are considered in this chapter. The most suitable equipment to monitor neuromuscular block and the appropriate anatomical sites for stimulation are discussed. To prevent residual block with its pathophysiological consequences such as upper airway and pharyngeal dysfunction and potential respiratory failure at the end of surgery, antagonizing agents are used. These are of two types: anticholinesterases such as neostigmine and edrophonium, and the γ‎-cyclodextrin, sugammadex. The pharmacodynamics and pharmacokinetics of neuromuscular blocking drugs and their antagonists are altered by the extremes of age, obesity, and several disease states including renal and hepatic failure, neuromuscular disorders, and critical illness. The altered response to all these drugs in these pathologies, which is related to their metabolism and excretion, is considered in detail, together with their other side-effects including the particular disadvantages to the use of succinylcholine.

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