Korean J Anesthesiol Search

CLOSE


Kim, Sung, and Yang: Factors that affect the onset of action of non-depolarizing neuromuscular blocking agents

Abstract

Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractility, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics such as onset time and duration of neuromuscular blockade should be considered along with factors that affect the effects of the NMBDs. In this review, we discuss the factors that affect the onset time of NMBDs.

Introduction

Neuromuscular blockade in anesthetic management refers to the phenomenon in which non-depolarizing neuromuscular blocking drugs (NMBDs) block the binding of neurotransmitters to a subunit of the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction of the motor neurons of skeletal muscle. Such a neuromuscular blockade plays an important role in the safe management and maintenance of patient airways, surgical field improvement, and respiratory management [1]. The ideal NMBD should have a rapid onset and short duration of action, no cardiovascular side effects, no accumulation in the body, no active metabolites, organ-dependent drug metabolism and elimination, and an available and adequate antagonist [2].
The onset of NMBD action depends on the degree of twitch depression after administration [3]. Although succinylcholine has long been used in clinical trials, it has gradually been removed from clinical practice, except in emergencies, because of its adverse effects [4]. Several studies have been conducted to develop new NMBDs with an onset of action similar to that of succinylcholine [2,5].

The Clinical Importance of Rapid Onset of NMBD

The purpose of rapid-sequence induction of anesthesia and intensive care is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient [6]. Laryngoscope manipulation and airway management must proceed with ease; if a stable depth of anesthesia and neuromuscular blockade is not maintained during induction of anesthesia, the time required for airway management is prolonged and excessive pressure may be applied to ensure adequate ventilation. The excess inhaled air causes expansion of the stomach, which can then lead to regurgitation and aspiration of stomach content into the lung. This in turn results in increased morbidity and mortality, with pulmonary complications such as airway obstruction, atelectasis, pneumonia, and hypoxia that cause damage to the major organs, such as the heart and brain [7]. Rapid-sequence induction of anesthesia is also indispensable for emergency surgery and obstetric anesthesia, for which preoperative fasting is unlikely.
Succinylcholine has played an important role in clinical practice as a neuromuscular blocker with a rapid onset of action for the past 80 years. However, the use of succinylcholine results in myalgia; elevated gastric, intracranial, and intraocular pressure; as well as hyperkalemia, myoglobinemia, myoglobinuria, and malignant hyperthermia. Thus, there has been a continued search for new NMBDs that have a rapid onset of action but without adverse effects [4].
To obtain a rapid onset of action, the dosage of NMBDs can be increased, which also increases the duration of action. However, with the use of the new selective antagonist sugammadex and monitoring of neuromuscular function, neuromuscular block induced by aminosteroid NMBDs can be reversed safely [8,9].

Factors that Affect Onset Time

Onset time and potency

There is an inverse relationship between the onset time and potency of NMBDs, and changes in the degree of binding of NMBDs to nAChR can also alter their onset time [10,11]. Thus, administering a large amount of an NMBD may accelerate the onset of action, making it comparable to succinylcholine [12,13]. NMBDs should bind to 70–90% or more of nAChRs to block neuromuscular function at the neuromuscular junction. If the drug potency is low, administering a large dose can lead to binding to nAChRs among a large number of molecules, which then also leads to a rapid onset of action [14].
In a comparison of potency and onset time, the order of decreasing potency was as follows: rocuronium > atracurium > vecuronium > cisatracurium > pancuronium [15,16]. If potency is high, the onset time is delayed and recovery is slow, because removal of the NMBD by buffered diffusion at the neuromuscular junction is slow [16].

Rate of NMBDs reaching the effect site

If blood flow to the muscle is considerable, the onset of action will be rapid, but if it is decreased, onset will be delayed. Compared to laryngeal muscle and the adductor pollicis, the onset time for laryngeal muscles is faster because of the shorter distance and greater blood flow from the heart [17]. In addition, the onset time for the orbicularis oculi is faster than that for the adductor pollicis, which is one of the muscles more suitable for monitoring neuromuscular function during tracheal intubation [18].

Administration rate

Factors associated with the route of drug administration can speed up the onset of action. Oral administration of sufficient fluid (1,500 ml) 2 h before surgery can prevent dehydration and thus prolong the onset of action [19]. In terms of intravenous administration, the onset is accelerated if the drug is injected into a central blood vessel, particularly the pulmonary artery, rather than a peripheral blood vessel [20]. In addition, the site of administration should be elevated above the heart or a catheter with a large inner diameter should be used to rapidly achieve a high target concentration of NMBD [21].

Onset time by dose control

Mass administration method

The dose of NMBDs administered is based on the amount of ED95 that can suppress twitch height by 95%. The dose required for intubation is 2–3 times the ED95 amount [22,23]. As the dose increases, depression of the twitch response is accelerated [22,24].

Mixed administration method

The purposes of this method are to reduce side effects, speed up the onset of action, and shorten the duration of action. For example, combined administration of mivacurium and rocuronium may result in reduced side effects and enhanced neuromuscular blocking effects [25]. However, it is not the preferred approach, because new NMBDs with a more rapid onset of action and short duration of action, as well as available selective antagonists, are available.

Precurarization (priming principle)

According to the margin of safety theory, more than 75–80% of nAChR should be combined with a neuromuscular blocking agent to cause muscle paralysis. Thus, 10% of the dose should be administered initially to bind with some nAChR [26,27,28]. The precurarization regimen varies depending on the type of NMBD used, the administration interval, the initial dose, and the total dose [29,30]. However, in the case of sensitive patients, visual disturbances, difficulty swallowing, lung aspiration, respiratory weakness, and complete paralysis (albeit rare) may occur before the onset of action [31,32].

Timing methods

Timing approaches can also be used to promote the onset time, but this is not preferred in clinical practice because of the possibility of creating discomfort during induction of anesthesia [33].

Combining drugs to increase cardiac output

Cardiotonic drugs increase the circulating blood volume by accelerating cardiac output and blood pressure.
  • i. Ephedrine: Ephedrine increases cardiac output, which causes the neuromuscular blocker to reach the effect site quickly, leading to a rapid onset of action in proportion to its dose [34].

  • ii. Esmolol: This selective beta blocker has negative inotropic and chronotropic effects. Combining this drug with NMBDs may delay the onset of action [35].

Type of muscle

Skeletal muscles are classified as type I (slow twitch, high oxidative) or type II (fast twitch, low oxidative) depending on their histology. Neonates and infants have more type II muscles than type I muscles and are more sensitive to NMBDs, showing a faster onset of action than adults [36,37].

Metabolism and Elimination of NMBDs

The metabolism and elimination of NMBDs play an important role in maintaining adequate blood levels for the appropriate onset time. Time-course changes in plasma concentration after the administration of neuromuscular blockers differ according to characteristics of each NMBD. Increased the concentration and/or reached the maximum concentration at the effect site is dependent on the time course of the muscle relaxant in the plasma, the blood flow to the muscle, and the volume of interstitial space in the muscle because NMBDs are water soluble and pharmacologically active in the extracellular space. Reductions in blood levels are affected by redistribution, excretion, and metabolism and vary for each NMBD [36].

Metabolism

Metabolites of the ideal neuromuscular blocker should not have neuromuscular blocking effects per se but may differ depending on the nature of the NMBD. Only about 1% of rocuronium is metabolized, but most NMBDs are broken down extensively so that their action of duration is shortened [12,37]. Mivacurium is hydrolyzed rapidly by plasma cholinesterase, whereas atracurium and cisatracurium are metabolized by Hofmann elimination and ester hydrolysis. If NMBDs are eliminated rapidly because of their fast metabolism, administering large doses of NMBDs can accelerate the onset time [12,38,39].

Clearance

NMBDs with rapid plasma clearance are associated with a rapid onset of action. If the metabolism and redistribution of the drug progresses rapidly, its concentration in the blood will decline rapidly to the point of balance between the plasma concentration and the effect site fraction. Thus, higher doses of NMBDs will be required because the concentration of NMBDs at the effect site is reduced rapidly [40]. Atracurium and vecuronium, which have an intermediate duration of action, decrease their concentration in the blood more rapidly than do other NMBDs. However, their maximum effect occurs more rapidly than their concentration in the blood decreases, there is less of an effect on onset timing [11]. The mechanism of action of mivacurium and succinylcholine can be explained by this. For example, the onset of succinylcholine is delayed in patients with atypical plasma cholinesterase [11,40].

Buffered Diffusion to the Effect Site

Buffered diffusion refers to the process by which NMBDs spread to the neuromuscular junction from the blood. Factors that may affect buffered diffusion include the nerve–muscle contact area, the degree of muscle membrane folding, quantal content, the distribution of the contact area and the transverse width of individual nerve–muscle contacts, the type of muscle, and temperature [41,42].
The onset of action at the neuromuscular junction depends on the degree of lipophilicity, binding to proteins, the rate at which the drug reaches the neuromuscular junction, the potency of the drug, its metabolism, and its excretion [43]. NMBDs reach their maximum plasma concentration immediately after intravenous administration; however, the maximal blocking effect may be delayed for most NMBDs. This delayed response is due to the efficacy fraction of the drug (its effect in proportion to its concentration), which is influenced by separation of the neuromuscular junction from the plasma or central compartment. Reaching the efficient fraction from the central fraction in the plasma is affected by the rate constant (Keo); the higher the Keo value, the faster the onset of action. Keo of rapacuronium is 2.4 times that of rocuronium and 3.4 times that of vecuronium in the adductor pollicis; it is 2.4 times that of rocuronium and 3.5 times that of vecuronium in the laryngeal adductors [41,42].

Affinity of the nAChR Subunit

An increase in the number of free molecules of NMBD that bind to the nAChR subunit at the neuromuscular synaptic cleft accelerates the onset of action. This affinity depends on the structure of the nAChR subunit [44,45]. The nAChR to which NMBDs bind consists of five subunits, i.e., α2βδɛ in the adult type and α2βδγ in the fetal type. The strength of binding of the two alpha subunits to acetylcholine (ACh) or NMBDs also differs about 100-fold between the two alpha subunits because the different affinities of the gamma and epsilon subunits [46,47]. In nerve damage caused by burns and immobilization, the nAChR is composed of five α7 subunits and is resistant to NMBDs, because there are five sites to which the NMBD can bind [44,45]. In this way, changes in the nAChR type among various neuromuscular diseases or conditions, such as burns, immobilization, or myasthenia gravis, with increased or decreased numbers of nAChRs also change the onset time of NMBDs [48].

Drugs That Affect ACh Production and Release at the Neuromuscular Junction

The amount of ACh at the neuromuscular junction and drugs that move to the nerve endings to enhance release or to increase or decrease the synthesis of ACh by reabsorbing the choline degraded after release also affect the onset of action. Corticosteroids are used commonly in clinical practice. Corticosteroids have a direct mechanism of action on motor nerve axons, increasing ACh synthesis and spontaneous as well as stimulated release of ACh, thereby improving muscle performance but also preventing neuromuscular block. The recovery of neuromuscular block was accelerated when 8 mg dexamethasone was administered 2–3 h before surgery [49]. Long-term exposure to both corticosteroids and NMBDs decreases nAChR at the neuromuscular junction and increases resistance to NMBDs. There is a slight difference between aminosteroids and benzylisoquinolinium types of NMBDs in response to long-term corticosteroid administration [50,51]. Long-term (> 4 weeks) administration of prednisolone in patients with chronic inflammatory bowel disease slowed the onset of action of rocuronium by 35% and reduced its duration of action by 25–30%, whereas there were no differences in the onset time of atracurium, although its duration of action was reduced by 20% [50,51,52].

Drugs That Inhibit Plasma Cholinesterase

Plasma cholinesterase is an enzyme that degrades ACh, which is released from the synaptic cleft of the neuromuscular junction. The enzyme may be defective because of congenital or acquired conditions. If plasma cholinesterase activity is abnormal, the metabolism of drugs such as mivacurium and succinylcholine is affected. There is no effect on ACh synthesis at the neuromuscular junction, but its degradation is slow, and the concentration of ACh is increased, so neuromuscular blockade may be altered [53,54]. Drugs that are metabolized by plasma cholinesterase, such as ester-type local anesthetics (e.g., procaine) and steroid-type induction agents (e.g., propanidid), substantially reduce the amount of available plasma cholinesterase and thus affect the activity of NMBDs [44,54]. This can potentiate the onset time of mivacurium.
NMBDs also inhibit plasma and erythrocyte cholinesterases. These inhibitory actions are partly competitive, partly noncompetitive, and reversible, decreasing as the concentration of ACh increases [55]. This cholinesterase inhibitory effect is not related to the expression of NMBDs, except that mivacurium is degraded by plasma cholinesterase. Thus, in cases in which plasma cholinesterase levels may be affected, dose control and monitoring of neuromuscular function are required [56,57].

Presynaptic Receptors Responsible for the Release of ACh at the Neuromuscular Junction

Several types of receptors are found at neuromuscular presynaptic sites. Some of these receptors interact to control the release of ACh during rest or stimulation [58,59]. For example, muscarinic ACh receptors (AChRs), neuronal nicotinic cholinergic receptors, and purinergic receptors interact in the presynaptic neuronal region. Muscarinic AChRs primarily affect muscle tension in smooth muscle, but they also have modulating effects at the neuromuscular junction of striated muscle. Although some types of muscarinic receptors have stabilizing or structural functions in nerve endings, M1 and M2 receptors, respectively, facilitate and inhibit ACh release. When M1 receptors are blocked by specific antagonists, the evoked release of ACh and spontaneous miniature endplate potential (mEPP) frequency are reduced, but the evoked release of ACh is increased when M2 receptors rather than M1 receptors are blocked [60]. Atropine acts as a nonspecific muscarinic blocker to modulate ACh release by inhibiting both M1 and M2 receptors, which decreases the spontaneous mEPP frequency and increases the evoked release of ACh [59,61]. In addition, presynaptic purinergic A1 and A2A receptors also modulate the spontaneous and evoked release of ACh. During spontaneous or evoked release of ACh from the presynaptic terminal, the concentration of the endogenous purinergic agonist adenosine is increased at the neuromuscular junction, controlling ACh release through a feedback mechanism [62].

Factors that Affect Muscle Contractility

Muscle weakness, nerve conduction, and muscle contractility also affect neuromuscular blockade [63].

Local anesthetics

Local anesthetics may reduce muscle contractility by blocking nerve conduction and impairing the sensitivity of nAChR [11]. Intravenous lidocaine accelerates the action of rocuronium as well as facilitates intubation [64,65].

Antibiotics

Antibiotics such as aminoglycoside antibiotics and tetracycline, polymyxin B, and lincomycin may enhance the action of NMBDs or may have a neuromuscular blocking effect [63]. These antibiotics lead to a leftward shift in the dose–response curve and a rapid onset time of NMBDs [66,67].

Magnesium and calcium

Magnesium reduces muscle contraction in proportion to its concentration in the blood and accelerates the effects of NMBDs [68,69]. In contrast, calcium increases ACh release while maintaining action potential at the neuromuscular junction [70].

Anticonvulsants

Short-term exposure to anticonvulsants such as phenytoin increases susceptibility to NMBDs, but resistance develops with long-term exposure [71].

Intravenous anesthetics

Intravenous anesthetics have no direct interaction with neuromuscular blockers, but etomidate (which has fewer cardiovascular effects) and ketamine (which acts on GABA receptors) may have indirect effects [72,73]. A single bolus dose of intravenous anesthetic (e.g., propofol) can decrease blood pressure and cardiac output, delaying the onset of action of NMBDs, but it also decreases muscle tone, which can accelerate the onset of action [74].

Inhalation anesthetics

Inhalation anesthetics improve the action of NMBDs by inhibiting muscle contraction, but there are few differences between anesthetics, because they do not saturate the body sufficiently during induction of anesthesia [63,75].

Phosphodiesterase inhibitors

Phosphodiesterase inhibitors inhibit the action of NMBDs. Theophylline-related drugs (such as caffeine and aminophylline), nonselective phosphodiesterase inhibitors, and phosphodiesterase III inhibitors (such as milrinone) increase the contractility of cardiac muscle and skeletal muscle in patients with heart failure. This antagonizes the effects of NMBDs, resulting in delayed onset time and shortening of the duration of action [76,77].

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)

Statins decrease the risk of cardiovascular disease by decreasing low-density lipoprotein cholesterol (LDL-C) levels. However, statins increase muscle creatine kinase (CK) with muscle toxicity. With long-term administration, the onset time of NMBDs is delayed and the duration of action is reduced [78,79].

Toxins

Botulinum and tetanus toxins block the release of ACh at the nerve terminal of the neuromuscular junction, resulting in muscle weakness or paralysis [45,80,81]. This may promote the onset of action of NMBDs.

Antiemetics

5-Hydroxytryptamine (5-HT3) receptor antagonists, which assemble pseudosymmetrically in pentameric structures with muscle nAChR, potentiate the blocking effects of neuromascular transmission in proportion to their dose [82,83]. 5-HT3 receptor antagonists are more potent with the fetal-type gamma subunit than with the adult-type epsilon subunit. The interaction of 5-HT3 receptor antagonists with NMBDs in adult nAChR is proportional to the antiemetic potency (hydrodolasetron >> granisetron > dolasetron > ondansetron) [84]. Metoclopramide inhibits the secretion of acetylcholine at the neuromuscular junction and potentiates the effects of NMBDs [85].

Site and Methods for Monitoring of Neuromuscular Function

Mechanomyography is the gold standard for monitoring neuromuscular function, but electromyography, acceleromyography, kinemyography, and phonomyography are also used in clinical practice; acceleromyography in particular is easy to use [86]. Acceleromyography may differ in dose and response from the time of maximal onset of action to the time of complete neuromuscular blockade (the absence of any twitch response). Thus, to minimize the effect, 50 s of tetanic stimulation is recommended for calibration [22]. The method can involve double-burst stimulation along with single twitch and train-of-four (TOF) stimulation. TOF stimulation can be analyzed faster than a single twitch [87,88]. Depending on the location of the muscle used to monitor neuromuscular function, muscle blood flow may differ, affecting the onset time. For example, the diaphragm and laryngeal muscle are more resistant to the NMBDs than the adductor pollicis. However, the onset of block in the diaphragm is earlier than at the adductor pollicis muscle [89,90].

Individual Variability

Individual differences in terms of age, sex, smoking, living environment, race, circadian variation, nutrition, obesity, and body temperature can affect the onset time of neuromuscular blockers. If there is resistance to NMBDs, the onset of action will be delayed, whereas sensitivity to NMBDs will shorten the onset of action [11].

Age and sex

The onset time of NMBDs is faster in young adults than in the elderly and in women than in men. In the elderly, the onset of action is delayed in proportion to aging from over 60 years to over 80 years of age [90,91,92].

Smoking

Cessation of smoking for 10 h before the administration of anesthesia delays the onset time and decreases the maintenance dose of NMBDs compared to what is seen in smokers or nonsmokers [93].

Geographic location

Individuals differ in their response to NMBDs depending on altitude. For example, people who live in high-altitude areas such as Tibet experience a slower onset than people who live in lower plains regions [94]. That is, regional differences affect the mechanism of action and dose of NMBDs required.

Body temperature

Hypothermia increases susceptibility to NMBDs, enhancing the duration of action and delaying the onset of action [16,95]. When an individual's core temperature decreases, the adductor pollicis does not affect the twitch height, even if the muscles are warmed regionally, because the influence of the core temperature is greater than that of the local muscle temperature. When the core temperature is reduced by 2.5℃, neuromuscular blockade can be enhanced by 45–50%. Thus, the core temperature should be maintained at 35℃, and the temperature at the peripheral site should be maintained at 32℃ or higher [95,96,97].

Nutrition

In obese individuals, administration of NMBDs based on actual body weight results in a rapid onset of action and a long duration of action; thus, the dose is determined on the basis of ideal body weight rather than actual body weight [98,99]. In patients with poor nutritional status, depressed plasma protein levels, decreased muscle mass, and reduced water content in the muscles may delay the onset of action of NMBDs and shorten the duration of action but not the recovery time [99].

Circadian variation

When rocuronium (0.6 mg/kg) was administered based on lean body mass, the mean duration of action was 50 min at 08:00–11:00 and 29 min at 14:00–17:00. If these variations are fully determined, it will be possible to accelerate onset time while prolonging the duration of action [100].

Coexisting Disease

Diseases that cause changes in the nAChR subunit

Depending on the comorbid disease, up- and downregulation of the nAChR subunit may result in faster or slower expression of NMBDs [48]. A disease that results in a decreased number of nAChRs, such as myasthenia gravis, shows an accelerated onset time. In cases of neuronal injury, burns, or immobilization, the number of neuronal nAChRs consisting of five α7 subunits is upregulated; these receptors are resistant to NMBDs. These changes in nAChRs reach a peak 2–3 weeks after the injury and then gradually return to normal [45,48]. In particular, in burn patients, the expression of action is delayed regardless of the plasma cholinesterase activity, postburn days, or size of the injury. This is because of a decreased affinity of nAChR, which is presumed to be due to the upregulation of nAChR, but the delayed recovery is presumably due to decreased activity of AChesterase [30,48].

Electrolyte and acid–base balance

In the case of electrolyte imbalances, such as hypocalcemia, hypokalemia, hypermagnesemia, and respiratory acidosis, the action of aminosteroid-type NMBDs may be enhanced, whereas the effects of the benzylisoquinolinium derivative cisatracurium are unclear, given that it is prone to Hoffman degradation and ester hydrolysis [101].

Hemodilution

To reduce the amount of blood transfused before surgery, dilution of the blood according to a patient's condition may lead to a decrease in plasma protein concentrations, a change in the concentration of electrolytes such as potassium and calcium, a change in the volume of distribution, and a change in Keo. In a previous study, acute isovolemic hemodilution accelerated the onset time and prolonged the duration of action of NMBDs [102].

Sepsis

Although there is no difference in the onset of action of NMBDs in sepsis, recovery may be delayed because ACh-esterase activity is reduced at the neuromuscular junction, the acid–base balance is disturbed, and hemodynamic impairments are present [103].

Liver and kidney function

Liver disease prolongs the duration of action of rocuronium but has less of an effect on its onset of action. In patients with impaired renal function, there is no effect on the onset time, and the duration of action is prolonged [104,105].

Pregnancy

Physiological and pathological changes occur during pregnancy, leading to pharmacological changes [106]. However, there were no differences in the onset times of non-depolarizing neuromuscular blocking agents in a comparison of women who were not pregnant and women immediately after giving birth [107].

Cardiac disease

Myocardial infarction and cardiac failure are associated with decreased cardiovascular function and delayed onset of action. Patients with congenital heart disease (e.g., ventricular septal defect, atrial septal defect) often have a left-to-right or right-to-left shunt that affects the onset of action as a result of pharmacokinetic and pharmacodynamic changes of NMBDs [108].

Conclusions

NMBDs with a rapid onset of action are expected to be introduced in the next few years, and NMBDs with a lower potency will continue to be developed, even if the ED95 of the new drugs is similar to or greater than that of rocuronium. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia as well as the patient's condition. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics, such as the onset time and duration of neuromuscular blockade, should be considered.

References

1. Bevan DR. Fifty years of muscle relaxants. Acta Anaesthesiol Scand Suppl 1995; 106: 2-6. PMID: 8533539.
crossref pmid
2. Moore EW, Hunter JM. The new neuromuscular blocking agents: do they offer any advantages? Br J Anaesth 2001; 87: 912-925. PMID: 11878696.
crossref pmid pdf
3. Bevan DR. Neuromuscular blocking drugs: onset and intubation. J Clin Anesth 1997; 9(6 Suppl): 36S-39S. PMID: 9278854.
crossref pmid
4. Mahajan R. Is suxamethonium now obsolete? Curr Anaesth Crit Care 1996; 7: 289-294.
crossref
5. Tuba Z, Maho S, Vizi ES. Synthesis and structure-activity relationships of neuromuscular blocking agents. Curr Med Chem 2002; 9: 1507-1536. PMID: 12171561.
crossref pmid
6. Kwok H, Prekker M, Grabinsky A, Carlbom D, Rea TD. Use of rapid sequence intubation predicts improved survival among patients intubated after out-of-hospital cardiac arrest. Resuscitation 2013; 84: 1353-1358. PMID: 23665389.
crossref pmid
7. Sparr HJ. Choice of the muscle relaxant for rapid-sequence induction. Eur J Anaesthesiol Suppl 2001; 23: 71-76. PMID: 11766251.
crossref pmid
8. Fuchs-Buder T, Meistelman C, Raft J. Sugammadex: clinical development and practical use. Korean J Anesthesiol 2013; 65: 495-500. PMID: 24427454.
crossref pmid pmc
9. Keating GM. Sugammadex: a review of neuromuscular blockade reversal. Drugs 2016; 76: 1041-1052. PMID: 27324403.
crossref pmid pdf
10. Kopman AF. Pancuronium, gallamine, and d-tubocurarine compared: is speed of onset inversely related to drug potency? Anesthesiology 1989; 70: 915-920. PMID: 2729631.
crossref pmid
11. Feldman S, Karalliedde L. Drug interactions with neuromuscular blockers. Drug Safety 1996; 15: 261-273. PMID: 8905251.
crossref pmid
12. Lien CA. Development and potential clinical impairment of ultra-short-acting neuromuscular blocking agents. Br J Anaesth 2011; 107(1 Suppl): i60-i71. PMID: 22156271.
crossref pmid pdf
13. Bowman WC, Rodger IW, Houston J, Marshall RJ, McIndewar I. Structure:action relationships among some desacetoxy analogues of pancuronium and vecuronium in the anesthetized cat. Anesthesiology 1988; 69: 57-62. PMID: 2898902.
crossref pmid
14. Bhatt SB, Amann A, Nigrovic V. Onset-potency relationship of nondepolarizing muscle relaxants: a reexamination using simulations. Can J Physiol Pharmacol 2007; 85: 774-782. PMID: 17901887.
crossref pmid
15. Kopman AF, Klewicka MM, Neuman GG. Molar potency is not predictive of the speed of onset of atracurium. Anesth Analg 1999; 89: 1046-1049. PMID: 10512288.
crossref pmid
16. Min JC, Bekavac I, Glavinovic MI, Donati F, Bevan DR. Iontophoretic study of speed of action of various muscle relaxants. Anesthesiology 1992; 77: 351-356. PMID: 1353667.
crossref pmid
17. Pansard JL, Chauvin M, Lebrault C, Gauneau P, Duvaldestin P. Effect of an intubating dose of succinylcholine and atracurium on the diaphragm and the adductor pollicis muscle in humans. Anesthesiology 1987; 67: 326-330. PMID: 3631606.
crossref pmid
18. Kim KS, Chon SU. Assessment of facial nerve and ulnar nerve stimulation methods to determine the optimal time for tracheal intubation. Korean J Anesthesiol 1993; 26: 512-519.
crossref
19. Ishigaki S, Kanaya A, Ogura T. Effect of preoperative oral rehydration on onset time and recovery time of rocuronium. Masui 2015; 64: 123-126. PMID: 26121801.
pmid
20. Iwasaki H, Igarashi M, Kawana S, Namiki A. Accelerated onset of vecuronium neuromuscular block with pulmonary arterial administration. Can J Anaesth 1994; 41: 1178-1180. PMID: 7867112.
crossref pmid
21. Nitahara K, Sugi Y, Shigematsu K, Kusumoto G, Abe S, Higa K. Effect of bolus injection of 20 ml saline with arm elevation on the onset time of vecuronium administered via a peripheral vein: a randomised controlled trial. Anaesthesia 2013; 68: 904-907. PMID: 23789813.
crossref pmid
22. Viby-Mogensen J, Engbaek J, Eriksson LI, Gramstad L, Jensen E, Jensen FS, et al. Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents. Acta Anaesthesiol Scand 1996; 40: 59-74. PMID: 8904261.
crossref pmid
23. Mazurek AJ, Rae B, Hann S, Kim JI, Castro B, Coté CJ. Rocuronium versus succinylcholine: are they equally effective during rapid-sequence induction of anesthesia? Anesth Analg 1998; 87: 1259-1262. PMID: 9842809.
pmid
24. Magorian T, Flannery KB, Miller RD. Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients. Anesthesiology 1993; 79: 913-918. PMID: 7902034.
crossref pmid
25. Kim SY, Cho MH. Neuromuscular and cardiovascular advantages of combinations of mivacurium and rocuronium over either drug alone. Anaesthesia 1996; 51: 929-931. PMID: 8984866.
crossref pmid
26. Willcockson IU, Hong A, Whisenant RP, Edwards JB, Wang H, Sarkar HK, et al. Orientation of d-tubocurarine in the muscle nicotinic acetylcholine receptor-binding site. J Biol Chem 2002; 277: 42249-42258. PMID: 12196523.
crossref pmid
27. Waud DR, Waud BE. In vitro measurement of margin of safety of neuromuscular transmission. Am J Physiol 1975; 229: 1632-1634. PMID: 1211496.
crossref pmid
28. Waud BE, Waud DR. The margin of safety of neuromuscular transmission in the muscle of the diaphragm. Anesthesiology 1972; 37: 417-422. PMID: 5074723.
crossref pmid
29. Kopman AF, Khan NA, Neuman GG. Precurarization and priming: a theoretical analysis of safety and timing. Anesth Analg 2001; 93: 1253-1256. PMID: 11682407.
crossref pmid
30. Han TH, Martyn JA. Onset and effectiveness of rocuronium for rapid onset of paralysis in patients with major burns: priming or large bolus. Br J Anaesth 2009; 102: 55-60. PMID: 19029093.
crossref pmid pdf
31. Jones RM. The priming principle: how does it work and should we be using it? Br J Anaesth 1989; 63: 1-3. PMID: 2527525.
crossref pmid pdf
32. Musich J, Walts LF. Pulmonary aspiration after a priming dose of vecuronium. Anesthesiology 1986; 64: 517-519. PMID: 2870668.
crossref pmid
33. Sieber TJ, Zbinden AM, Curatolo M, Shorten GD. Tracheal intubation with rocuronium using the “timing principle”. Anesth Analg 1998; 86: 1137-1140. PMID: 9585312.
crossref pmid
34. Kim KS, Cheong MA, Jeon JW, Lee JH, Shim JC. The dose effect of ephedrine on the onset time of vecuronium. Anesth Analg 2003; 96: 1042-1046. PMID: 12651656.
crossref pmid
35. Lee JH, Kim Y, Lee KH, Rim SK, Lee JY, Lee C. The effects of nicardipine or esmolol on the onset time of rocuronium and intubation conditions during rapid sequence induction: a randomized double-blind trial. J Anesth 2015; 29: 403-408. PMID: 25374138.
crossref pmid
36. Nigrovic V, Banoub M. Onset of the nondepolarizing neuromuscular block in humans: quantitative aspects. Anesth Analg 1993; 76: 85-91. PMID: 8418747.
crossref pmid
37. Proost JH, Eriksson LI, Mirakhur RK, Roest G, Wierda JM. Urinary, biliary and faecal excretion of rocuronium in humans. Br J Anaesth 2000; 85: 717-723. PMID: 11094587.
crossref pmid pdf
38. Fisher DM, Canfell PC, Fahey MR, Rosen JI, Rupp SM, Sheiner LB, et al. Elimination of atracurium in humans: contribution of Hofmann elimination and ester hydrolysis versus organ-based elimination. Anesthesiology 1986; 65: 6-12. PMID: 3755306.
crossref pmid
39. Hughes R, Chapple DJ. The pharmacology of atracurium: a new competitive neuromuscular blocking agent. Br J Anaesth 1981; 53: 31-44. PMID: 6161627.
crossref pmid pdf
40. Szenohradszky J, Fisher DM, Segredo V, Caldwell JE, Bragg P, Sharma ML, et al. Pharmacokinetics of rocuronium bromide (ORG 9426) in patients with normal renal function or patients undergoing cadaver renal transplantation. Anesthesiology 1992; 77: 899-904. PMID: 1443743.
crossref pmid
41. Sheiner LB, Stanski DR, Vozeh S, Miller RD, Ham J. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther 1979; 25: 358-371. PMID: 761446.
crossref pmid
42. Wright PM, Brown R, Lau M, Fisher DM. A pharmacodynamic explanation for the rapid onset/offset of rapacuronium bromide. Anesthesiology 1999; 90: 16-23. PMID: 9915308.
crossref pmid
43. Gyermek L. Development of ultra short-acting muscle relaxant agents: history, research strategies, and challenges. Med Res Rev 2005; 25: 610-654. PMID: 16086361.
crossref pmid
44. Shear TD, Martyn JA. Physiology and biology of neuromuscular transmission in health and disease. J Crit Care 2009; 24: 5-10. PMID: 19272533.
crossref pmid
45. Lee S, Yang HS, Sasakawa T, Khan MA, Khatri A, Kaneki M, et al. Immobilization with atrophy induces de novo expression of neuronal nicotinic α7 acetylcholine receptors in muscle contributing to neurotransmission. Anesthesiology 2014; 120: 76-85. PMID: 24126263.
crossref pmid pmc
46. Pedersen SE, Cohen JB. d-Tubocurarine binding sites are located at alpha-gamma and alpha-delta subunit interfaces of the nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A 1990; 87: 2785-2789. PMID: 2320589.
crossref pmid pmc
47. Foldes F. Rapid tracheal intubation with non-depolarizing neuromuscular blocking drugs: the priming principle. Br J Anaesth 1984; 56: 663.
crossref pdf
48. Martyn JA, White DA, Gronert GA, Jaffe RS, Ward JM. Up-and-down regulation of skeletal muscle acetylcholine receptors. Effects on neuromuscular blockers. Anesthesiology 1992; 76: 822-843. PMID: 1575351.
crossref pmid
49. Soltész S, Fraisl P, Noé KG, Hinkelbein J, Mellinghoff H, Mencke T. Dexamethasone decreases the duration of rocuronium-induced neuromuscular block: a randomised controlled study. Eur J Anaesthesiol 2014; 31: 417-422. PMID: 24136379.
crossref pmid
50. Soltész S, Mencke T, Mey C, Röhrig S, Diefenbach C, Molter GP. Influence of a continuous prednisolone medication on the time course of neuromuscular block of atracurium in patients with chronic inflammatory bowel disease. Br J Anaesth 2008; 100: 798-802. PMID: 18400809.
crossref pmid pdf
51. Chen D, Yang MR, Huang LN, Qiu YW, Li ST. Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression. Genet Mol Res 2014; 13: 5892-5900. PMID: 25117347.
crossref pmid
52. Soltész S, Mencke T, Stunz M, Diefenbach C, Ziegeler S, Molter GP. Attenuation of a rocuronium-induced neuromuscular block in patients receiving prednisolone. Acta Anaesthesiol Scand 2009; 53: 443-448. PMID: 19317861.
crossref pmid
53. Gätke MR, Bundgaard JR, Viby-Mogensen J. Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia. Pharmacogenet Genomics 2007; 17: 995-999. PMID: 18075469.
crossref pmid
54. Davis L, Britten JJ, Morgan M. Cholinesterase. Its significance in anaesthetic practice. Anaesthesia 1997; 52: 244-260. PMID: 9124666.
crossref pmid
55. Kato M, Hashimoto Y, Horinouchi T, Ando T, Ito J, Yamanaka H. Inhibition of human plasma cholinesterase and erythrocyte acetylcholinesterase by nondepolarizing neuromuscular blocking agents. J Anesth 2000; 14: 30-34. PMID: 14564607.
crossref pmid
56. Kim S, Shim JC, Kim DW. Interactions between mivacurium and pancuronium. Br J Anaesth 1997; 79: 19-23. PMID: 9301383.
crossref pmid pdf
57. Rautoma P, Erkola O, Meretoja OA. Potency and hourly maintenance requirement of combinations of mivacurium and pancuronium in adults. Can J Anaesth 1998; 45: 212-216. PMID: 9579257.
crossref pmid
58. Slutsky I, Parnas H, Parnas I. Presynaptic effects of muscarine on ACh release at the frog neuromuscular junction. J Physiol 1999; 514: 769-782. PMID: 9882749.
crossref pmid pmc
59. Tomàs J, Santafé MM, Garcia N, Lanuza MA, Tomàs M, Besalduch N, et al. Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse. J Neurosci Res 2014; 92: 543-554. PMID: 24464361.
crossref pmid
60. Bornia EC, Correia-de-Sá P, Alves-Do-Prado W. Presynaptic facilitatory adenosine A2A receptors mediate fade induced by neuromuscular relaxants that exhibit anticholinesterase activity. Clin Exp Pharmacol Physiol 2011; 38: 164-169. PMID: 21208254.
crossref pmid
61. Santafé MM, Lanuza MA, Garcia N, Tomàs J. Muscarinic autoreceptors modulate transmitter release through protein kinase C and protein kinase A in the rat motor nerve terminal. Eur J Neurosci 2006; 23: 2048-2056. PMID: 16630052.
crossref pmid
62. Correia-de-Sá P, Sebastião AM, Ribeiro JA. Inhibitory and excitatory effects of adenosine receptor agonists on evoked transmitter release from phrenic nerve ending of the rat. Br J Pharmacol 1991; 103: 1614-1620. PMID: 1679362.
crossref pmid pmc
63. Feldman S, Karalliedde L. Drug interactions with neuromuscular blockers. Drug Saf 1996; 15: 261-273. PMID: 8905251.
crossref pmid
64. Lee YK, Choi WJ, Kang WC, Leem JG, Yang HS. The effects of lidocaine on pain due to rocuronium. Korean J Anesthesiol 2004; 46: 145-150.
crossref
65. Kim TY, Seong KW, Yang JS. Effect of additional lidocaine on the onset time of vecuronium. Korean J Anesthesiol 1999; 37: 763-768.
crossref
66. Pittinger C, Adamson R. Antibiotic blockade of neuromuscular function. Annu Rev Pharmacol 1972; 12: 169-184. PMID: 4261048.
crossref pmid
67. Lee C, Katz RL. Neuromuscular pharmacology. A clinical update and commentary. Br J Anaesth 1980; 52: 173-188. PMID: 6244842.
crossref pmid pdf
68. Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, Do SH. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth 2017; 36: 102-106. PMID: 28183544.
crossref pmid
69. Berdai MA, Labib S, Harandou M. Prolonged neuromuscular block in a preeclamptic patient induced by magnesium sulfate. Pan Afr Med J 2016; 25: 5.
crossref
70. Katz B, Miledi R. The effect of calcium on acetylcholine release from motor nerve terminals. Proc R Soc Lond B Biol Sci 1965; 161: 496-503. PMID: 14278410.
crossref pmid
71. Kim JU, Lee YK, Lee YM, Yang HO, Han SM, Yang HS. The effect of phenytoin on rocuronium-induced neuromuscular block in the rat phrenic nerve-hemidiaphragm preparation. J Neurosurg Anesthesiol 2005; 17: 149-152. PMID: 16037736.
crossref pmid
72. Stollings JL, Diedrich DA, Oyen LJ, Brown DR. Rapid-sequence intubation: a review of the process and considerations when choosing medications. Ann Pharmacother 2014; 48: 62-76. PMID: 24259635.
crossref pmid
73. Gill RS, Scott RP. Etomidate shortens the onset time of neuromuscular block. Br J Anaesth 1992; 69: 444-446. PMID: 1467072.
crossref pmid pdf
74. Stäuble CG, Stäuble RB, Schaller SJ, Unterbuchner C, Fink H, Blobner M. Effects of single-shot and steady-state propofol anaesthesia on rocuronium dose-response relationship: a randomised trial. Acta Anaesthesiol Scand 2015; 59: 902-911. PMID: 25962311.
crossref pmid
75. Lowry DW, Mirakhur RK, McCarthy GJ, Carroll MT, McCourt KC. Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and intravenous anesthesia. Anesth Analg 1998; 87: 936-940. PMID: 9768798.
crossref pmid
76. Saitoh Y. Drugs to facilitate recovery of neuromuscular blockade and muscle strength. J Anesth 2005; 19: 302-308. PMID: 16261467.
crossref pmid
77. Yang HS, Jung HS, Park SH, Lee JS, Park TS, Seo BT. Effects of aminophylline on the dose-response curve of atracurium on rat hemidiaphragm preparation. Korean J Anesthesiol 1999; 36: 1046-1050.

78. Magni P, Macchi C, Morlotti B, Sirtori CR, Ruscica M. Risk identification and possible countermeasures for muscle adverse effects during statin therapy. Eur J Intern Med 2015; 26: 82-88. PMID: 25640999.
crossref pmid
79. Ren H, Lv H. Neuromuscular effects of rocuronium bromide in patients in statin therapy for at least three months. Basic Clin Pharmacol Toxicol 2016; 119: 582-587. PMID: 27234897.
crossref pmid
80. Humeau Y, Doussau F, Grant NJ, Poulain B. How botulinum and tetanus neurotoxins block neurotransmitter release. Biochimie 2000; 82: 427-446. PMID: 10865130.
crossref pmid
81. Turton K, Chaddock JA, Acharya KR. Botulinum and tetanus neurotoxins: structure, function and therapeutic utility. Trends Biochem Sci 2002; 27: 552-558. PMID: 12417130.
crossref pmid
82. Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 1991; 254: 432-437. PMID: 1718042.
crossref pmid
83. Karlin A, Akabas MH. Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins. Neuron 1995; 15: 1231-1244. PMID: 8845149.
crossref pmid
84. Paul M, Callahan R, Au J, Kindler CH, Yost CS. Antiemetics of the 5-hydroxytryptamine 3A antagonist class inhibit muscle nicotinic acetylcholine receptors. Anesth Analg 2005; 101: 715-721. PMID: 16115980.
crossref pmid
85. Tercan M, Efe EM, Turker G, Kaya FN, Yavascaoglu B, Ozarda Y, et al. Do metoclopramide and ondansetrone alter mivacurium-induced neuromuscular blockade? - a randomised trial. Braz J Anesthesiol 2014; 64: 35-39. PMID: 24565386.
crossref pmid
86. Viby-Mogensen J. Clinical assessment of neuromuscular transmission. Br J Anaesth 1982; 54: 209-223. PMID: 6277354.
crossref pmid pdf
87. Loughnan T, Loughnan AJ. Overview of the introduction of neuromuscular monitoring to clinical anaesthesia. Anaesth Intensive Care 2013; 41(Suppl 1): 19-24. PMID: 23808558.
crossref pmid
88. Kelly D, Brull SJ. Monitoring of neuromuscular function in the clinical setting. Yale J Biol Med 1993; 66: 473-489. PMID: 7825349.
pmid pmc
89. Plaud B, Debaene B, Donati F. The corrugator supercilii, not the orbicularis oculi, reflects rocuronium neuromuscular blockade at the laryngeal adductor muscles. Anesthesiology 2001; 95: 96-101. PMID: 11465590.
crossref pmid
90. Cantineau JP, Porte F, d'Honneur G, Duvaldestin P. Neuromuscular effects of rocuronium on the diaphragm and adductor pollicis muscles in anesthetized patients. Anesthesiology 1994; 81: 585-590. PMID: 8092503.
crossref pmid
91. Yang HS, Goudsouzian NG, Cheng M, Martyn JA. The influence of the age of the rat on the neuromuscular response to mivacurium in vitro. Paediatr Anaesth 1996; 6: 367-372. PMID: 8880816.
crossref pmid
92. Adamus M, Hrabalek L, Wanek T, Gabrhelik T, Zapletalova J. Influence of age and gender on the pharmacodynamic parameters of rocuronium during total intravenous anesthesia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011; 155: 347-353. PMID: 22336647.
crossref pmid
93. Rodrigo C. The effects of cigarette smoking on anesthesia. Anesth Prog 2000; 47: 143-150. PMID: 11432181.
pmid pmc
94. Dahaba AA, Perelman SI, Moskowitz DM, Bennett HL, Shander A, Xiao Z, et al. Geographic regional differences in rocuronium bromide dose-response relation and time course of action: an overlooked factor in determining recommended dosage. Anesthesiology 2006; 104: 950-953. PMID: 16645446.
crossref pmid
95. Eriksson LI, Viby-Mogensen J, Lennmarken C. The effect of peripheral hypothermia on a vecuronium-induced neuromuscular block. Acta Anaesthesiol Scand 1991; 35: 387-392. PMID: 1679593.
crossref pmid
96. Heier T, Caldwell JE, Sessler DI, Kitts JB, Miller RD. The relationship between adductor pollicis twitch tension and core, skin, and muscle temperature during nitrous oxide-isoflurane anesthesia in humans. Anesthesiology 1989; 71: 381-384. PMID: 2774265.
crossref pmid
97. Heier T, Caldwell JE, Eriksson LI, Sessler DI, Miller RD. The effect of hypothermia on adductor pollicis twitch tension during continuous infusion of vecuronium in isoflurane-anesthetized humans. Anesth Analg 1994; 78: 312-317. PMID: 7906109.
crossref pmid
98. Casati A, Putzu M. Anesthesia in the obese patient: pharmacokinetic considerations. J Clin Anesth 2005; 17: 134-145. PMID: 15809132.
crossref pmid
99. Sinha S, Jain AK, Bhattacharya A. Effect of nutritional status on vecuronium induced neuromuscular blockade. Anaesth Intensive Care 1998; 26: 392-395. PMID: 9743854.
crossref pmid
100. Cheeseman JF, Merry AF, Pawley MD, de Souza RL, Warman GR. The effect of time of day on the duration of neuromuscular blockade elicited by rocuronium. Anaesthesia 2007; 62: 1114-1120. PMID: 17924891.
crossref pmid
101. Aziz L, Ono K, Ohta Y, Morita K, Hirakawa M. The effect of CO2-induced acid-base changes on the potencies of muscle relaxants and antagonism of neuromuscular block by neostigmine in rat in vitro. Anesth Analg 1994; 78: 322-327. PMID: 8311285.
crossref pmid
102. Xue FS, Liao X, Liu JH, Zhang YM, An G, Luo LK. Influence of acute normovolaemic haemodilution on the dose-response and time-course of action of atracurium. Acta Anaesthesiol Scand 2000; 44: 163-169. PMID: 10695909.
crossref pmid
103. Wu J, Jin T, Wang H, Li ST. Sepsis strengthens antagonistic actions of neostigmine on rocuronium in a rat model of cecal ligation and puncture. Chin Med J (Engl) 2016; 129: 1477-1482. PMID: 27270546.
crossref pmid pmc
104. Magorian T, Wood P, Caldwell J, Fisher D, Segredo V, Szenohradszky J, et al. The pharmacokinetics and neuromuscular effects of rocuronium bromide in patients with liver disease. Anesth Analg 1995; 80: 754-759. PMID: 7893030.
crossref pmid
105. Craig RG, Hunter JM. Neuromuscular blocking drugs and their antagonists in patients with organ disease. Anaesthesia 2009; 64(Suppl 1): 55-65. PMID: 19222432.
crossref pmid
106. Guay J, Grenier Y, Varin F. Clinical pharmacokinetics of neuromuscular relaxants in pregnancy. Clin Pharmacokinet 1998; 34: 483PMID: 9646009.
crossref pmid
107. Gin T, Chan MT, Chan KL, Yuen PM. Prolonged neuromuscular block after rocuronium in postpartum patients. Anesth Analg 2002; 94: 686-689. PMID: 11867398.
crossref pmid
108. Wu Z, Wang S, Peng X, Lu C, Ye X, Wu B. Altered cisatracurium pharmacokinetics and pharmacodynamics in patients with congenital heart defects. Drug Metab Dispos 2016; 44: 75-82. PMID: 26470914.
crossref pmid


ABOUT
ARTICLE CATEGORY

Browse all articles >

BROWSE ARTICLES
AUTHOR INFORMATION
Editorial Office
101-3503, Lotte Castle President, 109 Mapo-daero, Mapo-gu, Seoul 04146, Korea
Tel: +82-2-792-5128    Fax: +82-2-792-4089    E-mail: journal@anesthesia.or.kr                

Copyright © 2024 by Korean Society of Anesthesiologists.

Developed in M2PI

Close layer
prev next