search for


 

Current use of neuromuscular blocking agents and antagonists in Korea: a 2018 survey
Anesth Pain Med 2019;14(4):441-8
Published online October 31, 2019
© 2019 Korean Society of Neuroscience in Anesthesiology and Critical Care.

Jin Sun Kim1 , Jung Woo Han1 , Jae Ho Lee1 , Jae Moon Choi2 , Ha Jung Kim2 , Tae-Yun Sung3 , Yong Beom Kim4 , Yong Seop Shin5 , and Hong Seuk Yang6
Department of Anesthesiology and Pain Medicine, 1Gangneung Asan Medical Center, University of Ulsan College of Medicine, Gangneung, 2Asan Medical Center, University of Ulsan College of Medicine, Seoul, 3Konyang University Hopsital, Konyang University College of Medicine, Daejeon, 4Gil Medical Center, Gachon University College of Medicine, Incheon, 5Chungnam National University Hospital, Chungnam National University College of Medicine, 6Daejeon Sun General Hospital, Daejeon, Korea
Correspondence to: Hong Seuk Yang, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, Daejeon Sun General Hospital, 29 Mokjung-ro, Jung-gu, Daejeon 34811, Korea Tel: 82-42-220-8921 Fax: 82-42-220-8933 E-mail: hsyang@amc.seoul.kr
ORCID https://orcid.org/0000-0003-2023-8705
Received November 19, 2018; Revised May 14, 2019; Accepted May 14, 2019.
cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

Background:

Neuromuscular blocking agents (NMBAs) and neuromuscular monitoring in anesthetic management are integral for endotracheal intubation, better visualization of the surgical field, and prevention of residual neuromuscular blockade and pulmonary complications. Sugammadex is a drug that reduces risk of residual neuromuscular blockade, with more rapid recovery compared to anticholinesterase. The purpose of this study was to investigate current usage status of NMBAs and antagonist with neuromuscular monitoring, among anesthesiologists in Korea.

Methods:

Anesthesiologists working in Korea were invited to participate in an online survey via email January 2–February 28, 2018. The questionnaire consisted of 45 items, including preferred NMBAs, antagonists, neuromuscular monitoring, and complications related to the use sugammadex. A total of 174 responses were analyzed.

Results:

Rocuronium was a commonly used NMBA for endotracheal intubation (98%) of hospitals, and maintenance of anesthesia (83.3%) in of hospitals. Sugammadex, pyridostigmine, and neostigmine were used in 89.1%, 87.9%, and 45.4% of hospitals. Neuromuscular monitoring was employed in 79.3% of hospitals; however only 39.7% of hospitals used neuromuscular monitoring before antagonist administration. Usual dosage range of sugammadex was 2.1–4 mg/kg in 35.1% of hospitals, within 2 mg/kg in 34.5% of hospitals, and 1 vial regardless of body weight in 22.4% of hospitals. Sugammadexrelated complications were encountered by 14.9% of respondents.

Conclusions:

This survey indicates several minor problems associated with the use of antagonists and neuromuscular monitoring. However, most anesthesiologists appear to have appropriate information regarding the usage of NMBAs and sugammadex.

Key Words : Neostigmine; Neuromuscular blocking agents; Neuromuscular monitoring; Pyridostigmine bromide; Sugammadex.
INTRODUCTION

During anesthetic management, neuromuscular blocking agents (NMBAs) can enhance ease of endotracheal intubation, field of view, and operating conditions while reducing the dose of inhalation or intravenous anesthetic agents and are also essential for respiratory management for intraoperative controlled mechanical ventilation [1,2]. Furthermore, neuromuscular monitoring and antagonist administration are important for preventing complications of residual neuromuscular blockade, such as dyspnea, hypoxia, atelectasis, and pneumonia [3]. Particularly, neuromuscular monitoring provides important information for neuromuscular dose adjustment, neuromuscular action for endotracheal intubation, timing of antagonist administration postoperatively, and determination of its dose. The use of antagonists during recovery for patients who received NMBAs restores spontaneous breathing and prevents residual neuromuscular blockade and recurarization by adequately recovering muscle strength (train-of-four ratio [TOFr] > 0.9) [4,5].

Sugammadex is an antagonist of the aminosteroid nondepolarizing neuromuscular blockers vecuronium and rocuronium; compared to anticholinesterases, it is an effective drug that promotes and quick recovery while lowering the risk of residual neuromuscular blockade [6]. In Korea, it has been introduced in 2013. Thus, it was considered possible that there might have been changes in the use of NMBAs and antagonists in clinical practice.

We hereby report a survey of the selection of NMBAs for endotracheal intubation and anesthesia maintenance, the usage of neuromuscular monitoring and choice of antagonists well as anesthesiologists’ update concepts in Korea.

MATERIALS AND METHODS

An anonymous questionnaire was administered to anesthesia specialists and residents in clinical practice who are registered members of the Korean Society of Anesthesiologists (KSA) and who live in Korea. The survey was sent via email for the anesthesiologists to complete the online survey themselves; 174 responses that were delivered via the web link (https://goo.gl/forms/cNLvOyoftVJjWfKS2) within two months from January 2 to February 28, 2018 were analyzed.

Participants were instructed to give either a single response or three responses in order of preference, depending on the type of question; the assessment was made based on the popular responses. In some instances, the total number of responses could exceed 174, due to duplicate responses, so the sum of responses was computed with the sum of duplicate responses and presented as percentage of total number. The survey consisted of 45 items, including demographic information such as length of career at the hospital, features of the hospital, and area of residence, as well as information about application of NMBAs and neuromuscular monitoring devices, preference for NMBA antagonists, current use of sugammadex, and its complications.

RESULTS

Table 1 shows the details of anesthesiologists who participated in the survey.

Demographic Data

QuestionResult
Position
  Resident trainees38 (21.8)
  Board-certified anesthesiologists136 (78.2)
Affiliation
  University hospital135 (77.6)
  Nonteaching hospital39 (22.4)
Years of working in anesthesiology department
  < 546 (26.4)
  5–1045 (25.9)
  11–2049 (28.2)
  > 2034 (19.5)
Size of hospital
  < 50 beds7 (4.0)
  50–100 beds10 (5.8)
  > 100 beds157 (90.2)
Number of daily average general anesthesiawhich is performed by respondent
  < 583 (47.7)
  5–1069 (39.7)
  10–2018 (10.3)
  > 204 (2.3)
Number of daily average general anesthesiawhich is performed in respondent’s hospital
  < 525 (14.4)
  5–1013 (7.5)
  10–208 (4.6)
  21–5067 (38.5)
  51–10034 (19.5)
  100–20011 (6.3)
  > 20016 (9.2)
The practice location of respondents
  Seoul70 (40.2)
  Gyeonggi-do32 (18.4)
  Busan14 (8.0)
  Incheon10 (5.7)
  Daejeon, Gangwon-do8 (4.6) each
  Daegu, Gwangju7 (4.0) each
  Ulsan1 (0.6)
  Chungcheong-do, Jeolla-do6 (3.4) each
  Gyungsang-do5 (2.9)
  Jeju-do0 (0)

Values are presented as number (%).



Rocuronium was the most popular agent for endotracheal intubation and intraoperative maintenance of neuromuscular blockade (Table 2). Regarding neuromuscular reversal agents available at each hospital, sugammadex was the most common (89.1%), followed by pyridostigmine (87.9%). When asked to choose three neuromuscular block reversal agents in the order of frequent use, 142 out of 174 (80.2%; 177 cases including duplicate responses) chose anticholinesterases (pyridostigmine, n = 96 [54.2%], neostigmine n = 46 [26.0%]) as the most preferred agent, while 35 (19.8%) chose sugammadex as their primary choice. On the other hand, 101 out of 160 (63.1%) chose sugammadex as the second-most preferred antagonist, while 39 (24.4%) chose pyridostigmine and 20 (12.5%) chose neostigmine. The most popular combination of anticholinergics used with anticholinesterases was pyridostigmine + glycopyrrolate, followed by neostigmine + glycopyrrolate and neostigmine + atropine. The reasons for not using antagonists were “because NMBAs are not used at all” (30.5%), “because patient seemed adequately recovered or an adequate amount of time has passed” (26.4%), and “complete recovery was confirmed using monitoring devices such as TOF” (13.8%); 22.4% of participants stated that they always used neuromuscular block reversal agents.

Availability and Usage Status of Neuromuscular Blocking and Reversal Agents

QuestionResult
Choose NMBAs that are mainly used for endotracheal intubation (multiple selection is possible)
  Succinylcholine17 (9.8)
  Rocuronium167 (96.0)
  Vecuronium14 (8.0)
  Atracurium2 (1.1)
  Cisatracurium44 (25.3)
Choose NMBA that is mainly used for maintenance of anesthesia
  Succinylcholine0 (0)
  Rocuronium145 (83.3)
  Vecuronium15 (8.6)
  Atracurium1 (0.6)
  Cisatracurium13 (7.5)
Choosereversal agents of neuromuscular blockade that were prepared in your hospital (multiple selection is possible)
  Neostigmine79 (45.4)
  Pyridostigmine153 (87.9)
  Edrophonium0 (0)
  Sugammadex155 (89.1)
If you do not use the reversal agents during recovery from anesthesia, why is that?
  Because of not use of any NMBAs at all53 (30.5)
  Because sufficient time has passed since the administration of the NMBA23 (13.2)
  Because the symptoms of the patient are fully recovered23 (13.2)
  Since complete recovery was confirmed using neuromuscular monitoring device such as TOF24 (13.8)
  I always use the reversal agent39 (22.4)
  Others12 (6.9)

Values are presented as number (%). NMBA: neuromuscular blocking agent, TOF: train-of-four.



Approximately 93.1% of the participants stated that they were aware of the cost of sugammadex. Regarding the use of sugammadex, it was used for all patients of general anesthesia by 9.8% of the respondents, only used for recommended indications by 40.2%, occasionally or rarely used by 36.2%, and never used by 9.2%. The reasons for the restrictions in clinical usage included regulations such as diagnosis-related group (50.0%), price (31.1%), and limited indications (10.9%). Regarding the degree of restriction of sugammadex usage, 89.1% of the participants stated that they “use it without restrictions” or “use only for a small minority of patients,” suggesting that the majority of them are using it in clinical practice. Regarding the dosage of sugammadex, 22.4% said that they administer one vial (200 mg), regardless of the patient’s weight or condition (Table 3).

Availability and Usage Status of Sugammadex

QuestionResult
Do you know the amount of money you need to use sugammadex?
  Yes162 (93.1)
  No12 (6.9)
How often do you use sugammadex as an antagonist of neuromuscular blockade?
  In all patients17 (9.8)
  Use only in recommended indications70 (40.2)
  I use it occasionally53 (30.5)
  It is rarely used10 (5.7)
  I do not use it at all16 (9.2)
  Others8 (4.6)
Do you have limited use of sugammadex, select a reason
  Due to (expensive) price54 (31.1)
  Due to regulations such as DRG, car insurance87 (50.0)
  Due to restricted indication19 (10.9)
  Due to sugammadex-related side effects2 (1.1)
  Others12 (6.9)
If you have restrictions on using sugammadex, select a level of restriction
  None restriction29 (16.7)
  There are some limitations, but they are freely usable82 (47.1)
  Partially restricted29 (16.7)
  Used only in very few patients who have indications15 (8.6)
  Completely restricted12 (6.9)
  Others7 (4.0)
If sugammadex is administered to antagonize the neuromuscular blockade, select a routine dosage
  ≤ 2 mg/kg60 (34.5)
  2.1–3.9 mg/kg42 (24.1)
  4 mg/kg19 (10.9)
  8 mg/kg1 (0.6)
  16 mg/kg0 (0)
  One vial regardless the body weight39 (22.4)
  Others13 (7.5)
Have you experienced any complications due to sugammadex?
  Yes26 (14.9)
  No148 (85.1)

Values are presented as number (%). DRG: diagnosis-related group.



A total of 79.3% of the participants said that their hospital was equipped with devices for monitoring neuromuscular function. Approximately 39.7% said that the monitoring device was used prior to administering antagonists, while 60.3% said that it was not. When determining the timing of antagonist administration, most participants used TOF stimulation results, while 1.2% said that they administer antagonists once surgery is concluded, regardless of the results of neuromuscular monitoring (Table 4).

Application Status of Neuromuscular Function Monitoring Device

QuestionResult
Does your hospital have monitoring device of neuromuscular function?
  Yes138 (79.3)
  No36 (20.7)
Do you measure neuromuscular function recovery before administration of reversal agents?
  Yes69 (39.7)
  No105 (60.3)
How often do you monitor neuromuscular function in your patients receiving NMBAs?
  In all patients15 (8.6)
  In 75% of patients19 (10.9)
  In 50% of patients10 (5.7)
  In 25% of patients56 (32.2)
  Only in patients with abnormal neuromuscular function (e.g., myasthenia gravis)27 (15.5)
  Only for a limited number of studies9 (5.2)
  Never33 (19.0)
  Others5 (2.9)
If the neuromuscular monitoring is performed during surgery, select when to administer the reversal agents to reversal of the neuromuscular blockade
  Posttetanic count ≤ 50 (0)
  Posttetanic count 6–100 (0)
  TOF count 17 (4.0)
  TOF count 236 (20.7)
  TOF count 330 (17.2)
  TOF count 439 (22.4)
  TOF ratio ≤ 0.57 (4.0)
  TOF ratio ≥ 0.519 (10.9)
  TOF ratio ≥ 0.99 (5.2)
  Others27 (15.5)

Values are presented as number (%). NMBA: neuromuscular blocking agent, TOF: train-of-four.



Approximately 14.9% encountered adverse reactions after sugammadex administration. Types of adverse reactions included decreased systolic blood pressure below 80 mmHg, anaphylaxis, and increased intra-tracheal pressure (e.g., due to bronchospasm) requiring endotracheal intubation and mechanical ventilation, and reduced oxygen saturation: other adverse reactions included bradycardia, cardiac arrest, reduced vigor, perspiration, postoperative delirium, and headache. If hypoxia or dyspnea occurred after sugammadex administration, the most common causes were thought to be insufficient dose of antagonist, residual effect of narcotic analgesics, residual effects of anesthetics, residual effects of NMBA and recurarization. Countermeasures included oxygen administration, additional administration of sugammadex, endotracheal intubation, placement of ventilator, administration of opioid antagonist and application of continuous positive pressure ventilation, administration of vasopressors, and treatment equivalent to cardiopulmonary resuscitation.

DISCUSSION

Anesthetic management has undergone substantial changes with the introduction of novel pharmacologic agents such as NMBAs. The present survey aimed to investigate changes of anesthesiologists’ perceptions and current use of NMBAs and antagonists, and the application of neuromuscular monitoring since the introduction of sugammadex; a total of 174 participants completed the survey. A considerable percentage of anesthesia specialists who participated in the survey (over 40%) worked in large hospitals in Seoul and Gyeonggi regions, and in other large cities, which was borne out by the proportion of their responses [7]. A total of 136 out of 4,521 anesthesia specialists (3,946 excluding those on leave; 3.4%) and 38 out of 815 anesthesiology residents nationwide participated in the survey, so the present survey has an established significance.

An ideal NMBA is a non-depolarizing agent with fast onset and short duration of action that enables fast recovery with low or non-organ dependence, and no other toxicity effects, must not be accumulated in the body, have no side effects such as cardiac arrhythmia or histamine release, and be easy to reverse [8,9]. There is currently no such NMBA available, and among NMBAs that are currently used in clinical practice, rocuronium and cisatracurium would be the closest to an ideal NMBA among aminosteroids and benzylisoquinoliniums, respectively. Particularly, rocuronium has gained preference before the introduction sugammadex that enables fast and predictable recovery [10]. In the present survey, only a handful of anesthesiologists (9.8%) chose succinylcholine as the NMBA for endotracheal intubation, while 96.0% chose rocuronium. This contrasts to the results of a 2010 survey of Korean anesthesiologists, in which 73.1% chose succinylcholine for endotracheal intubation [11]. This trend seems to be attributable to the fact that anesthesiologists prefer agents with a fast onset and easy reversal of rocuronium and vecuronium, such as sugammadex.

Among anticholinesterases, edrophonium cannot be used due to its unavailability in Korea, while neostigmine and pyridostigmine are available for use. The less frequent use of neostigmine compared to pyridostigmine seems to be attributable to a past trend. Compared to pyridostigmine, neostigmine has a faster onset but shorter duration, has a five-fold higher potency, and greater muscarinic action, although there are no differences in recovery with neuromuscular blockade [12,13]. Hence, if an anticholinesterase must be used, neostigmine, which is high potency and has a fast onset of action, is preferentially recommended [13,14]. Although there has been a report suggesting that anticholinesterase administration increases upper respiratory collapsibility and risk of postoperative atelectasis after reversal of neuromuscular blockade, subsequent studies concluded that using an appropriate dose of anticholinesterase under neuromuscular monitoring was helpful in preventing postoperative respiratory complications related to NMBAs [15]. If an additional administration is needed because the initial dose of anticholinesterase did not induce complete reversal, the authors recommend that they must be used with caution, and sugammadex is recommended [6,16]. With the introduction of sugammadex, the formation of rocuroniumsugammadex complex has enabled predictable and prompt reversal of neuromuscular blockade regardless of the depth of blockade, which has not been possible with other NMBAantagonist combinations, and as a result, catch phrases such as “So Long, Sux!” and “So Long, Neostigmine!” were introduced [4]. Currently, determining the accurate dose and timing of sugammadex with neuromuscular monitoring, and, if an emergency reoperation is needed for patients who were administered sugammadex, determining the accurate dose and timing of rocuronium has become more important as opposed to selecting an anticholinesterase [17,18]. In addition, if neuromuscular blockade is required for reoperation but cannot be achieved with rocuronium and sugammadex, benzylisoquinoliniums (e.g., cisatracurium) or succinylcholine could probably be used [6,19,20]. If cisatracurium is used, rocuronium that did not bind to sugammadex and nicotinic acetylcholine receptors that did not bind neuromuscular blockers could induce priming effects, thereby causing an earlier onset of action for cisatracurium [21].

Anticholinergics used with anticholinesterases include atropine and glycopyrrolate. In clinical practice, glycopyrrolate is generally preferred to atropine despite its lower antimuscarinic effects, which was reflected in the present survey. Takkunen et al. [22] reported that the combination of neostigmine and glycopyrrolate has less effects on the central nervous system with greater protective effects against oral secretions, such as saliva, and promotes cardiac stability due to a low risk of bradycardia and junctional arrhythmias compared to the combination of neostigmine and atropine during the reversal of neuromuscular blockade by pancuronium, but there is no difference in the incidence of postoperative nausea and vomiting [13,23].

In rare cases, antagonists are not used during recovery after the use of NMBAs. In the present survey, only 22.4% of the respondents said that they always use an antagonist, and the rates of routine use of antagonists in Europe and United States are only 18% and 34%, respectively [14]. However, it is impossible to qualitatively and quantitatively examine the residual effects of NMBAs without using antagonists, thereby increasing the risk of residual neuromuscular blockade or recurarization [24]. Therefore, a neuromuscular monitoring device should be used for all patients who are administered NMBAs, and the use of antagonists (and if used, the type and dose of the agent) should be decided with reference to the monitoring results [24,25].

The most important factors for addressing the problems after neuromuscular blockade, such as residual neuromuscular block, recurarization, and consequent pulmonary complications, are monitoring of neuromuscular functions and administration of appropriate antagonists [26]. In the present survey, 79.3% reported that a neuromuscular monitoring device was available for clinical application at their hospital, which was similar to the rates reported in a 2010 Korean survey (available in operating room [OR]: 83.3%, available in hospital: 79.5%) [11]. Methods such as TOF are used at a frequency of 22.7% in the United States and 70.2% in Europe, and the percentage of hospitals equipped with a neuromuscular monitoring device in an OR is 71.4% in the United States and 44.5% in Europe [14]. Furthermore, the percentage of participants who do not use neuromuscular monitoring at all was 9.4% in the United States and 19.3% in Europe [14]. In Korea, the clinical application of sugammadex seems to have been influenced by insurance coverage, financial burden due to costly drug price, diagnosis-related group (DRG), and indications designated by the Ministry of Food and Drug Safety. Furthermore, only 25.3% said that they apply neuromuscular monitoring for more than 50% of all surgical patients. These results indicate that there have been no changes in the clinical application of NMBAs over the last decade, calling for the KSA and Korean Neuromuscular Research Society (KNRS) to develop, promote, and provide education with relevant guidelines.

Regarding the determination of the timing of antagonist administration, none of the participants chose tetanic stimulation and post-tetanic counts (PTC); most participants reported using TOF to determine the timing of reversal administration for performing neuromuscular monitoring. More than 90% of the participants used TOF, and they reported administering antagonists after T2 or higher was detectable. However, some anesthesiologists administered antagonists after surgery was completed, regardless of the results of neuromuscular monitoring. Regarding the dose of sugammadex, most participants reported using one vial or less, presumably due to the high cost of the agent. Although many studies recommend administering 2.0 mg/kg of sugammadex when T2 is detectable, the dosage may be adjusted based on the PTC or TOF ratio. The authors suspect that if sugammadex is administered after T2 is detected, administering 1 vial of sugammadex without neuromuscular monitoring, based only on body weight, may lead to an unnecessary excessive dose, but anesthesiologists should take precaution as insufficient dosage in obese patients may induce residual neuromuscular blockade or re-blockade [27].

Regarding adverse reactions with sugammadex administration, we only listed the type of reactions because duplicate responses could alter the actual frequency. The causes of adverse reactions included residual effects of NBMAs, recurarization, insufficient dose of sugammadex, and hypersensitivity, but some participants mentioned the residual effects of the main anesthetic and opioid. Countermeasures included oxygen administration, additional sugammadex administration, pressor agents, endotracheal intubation and ventilation, and CPR, and anesthesiologists seem to have performed appropriate therapeutic interventions according to the severity of the adverse reactions. However, residual neuromuscular blockade and recurarization may occur after sugammadex administration, and insufficient dosage, hypersensitivity, and anticoagulation can also occur. Moreover, we must think about measures to address problems regarding interactions between sugammadex and drugs that may affect its binding affinity, as well as patients’ condition and other abnormalities [27]. To resolve or prevent these problems, an accurate understanding of the timing and dosage of sugammadex is needed in addition to neuromuscular monitoring [28]. Residual neuromuscular block after sugammadex administration occurs as a result of non-routine use of neuromuscular monitoring, low usage of monitoring results, lack of standard for neuromuscular monitoring, lack of accurate data about prevalence and mortality of adverse reactions, and high costs. Furthermore, although hypersensitivity cannot be predicted, most cases occur within five minutes of administration, so changes in the patient’s state immediately after administration should be carefully observed. In general, bradycardia can occur proportionally to the dose, so treatment using appropriate drugs in addition to accurate neuromuscular monitoring and dosage are crucial [29].

One limitation of this study is the possibility of bias, as the sample size was 174, which is less than 5% of the total number of registered anesthesiology specialists and residents currently working in Korea (as of 2018). Despite the small sample size and the fact that some participants work at the same hospital and thus their responses may be redundant, the study population varied in terms of job position, length of career, type of hospital, and region of work, so the findings would be helpful in understanding the current use of NMBAs, neuromuscular monitoring, and antagonists. Second, in the survey about the adverse reactions of sugammadex, the questionnaire was designed such that online submission was only possible after choosing a response even if some items were redundant or were not applicable. In such cases, we only listed the type and excluded them from analysis to eliminate the possibility of delivering wrong information, but this should be addressed in subsequent surveys.

In conclusion, based on the results of this survey, neuromuscular monitoring should be coupled with the use of NMBAs and antagonists, which are important agents for anesthetic management. Nevertheless, it seems that most anesthesiologists have the correct information about the use of neuromuscular monitoring and timing and dosage of antagonists, though there are practical difficulties for clinical application. Therefore, the KSA and the KNRS should implement and continually promote and educate anesthesiologists about guidelines for the use of neuromuscular monitoring devices according to the use of NMBAs and antagonists.

SUPPLEMENTARY MATERIALS

Supplementary data containing Korean version of this article is available at https://doi.org/10.17085/apm.2019.14.4.441.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

References
  1. Madsen MV, Staehr-Rye AK, Claudius C, and Gätke MR. Is deep neuromuscular blockade beneficial in laparoscopic surgery?Yes, probably. Acta Anaesthesiol Scand 2016;60:710-6.
    Pubmed CrossRef
  2. Meakin GH. Role of muscle relaxants in pediatric anesthesia. Curr Opin Anaesthesiol 2007;20:227-31.
    Pubmed CrossRef
  3. Dubois PE, and Mulier JP. A review of the interest of sugammadex for deep neuromuscular blockade management in Belgium. Acta Anaesthesiol Belg 2013;64:49-60.
    Pubmed
  4. Lee C, and Katz RL. Clinical implications of new neuromuscular concepts and agents:so long, neostigmine!So long, sux!. J Crit Care 2009;24:43-9.
    Pubmed CrossRef
  5. Naguib M, Brull SJ, and Arkes HR. Reasoning of an anomaly:residual block after sugammadex. Anesth Analg 2013;117:297-300.
    Pubmed CrossRef
  6. Yang LP, and Keam SJ. Sugammadex:a review of its use in anaesthetic practice. Drugs 2009;69:919-42.
    Pubmed CrossRef
  7. Cho CK, Kim DK, and Park HJ. Current supply and future workforce projections of anesthesiologists for safe anesthetic care of the Korean population. Anesth Pain Med 2016;11:85-90.
    CrossRef
  8. Haerter F, and Eikermann M. Reversing neuromuscular blockade:inhibitors of the acetylcholinesterase versus the encapsulating agents sugammadex and calabadion. Expert Opin Pharmacother 2016;17:819-33.
    Pubmed CrossRef
  9. de Boer HD. Neuromuscular transmission:new concepts and agents. J Crit Care 2009;24:36-42.
    Pubmed CrossRef
  10. Meistelman C, and Donati F. Do we really need sugammadex as an antagonist of muscle relaxants in anesthesia?. Curr Opin Anaesthesiol 2016;29:462-7.
    Pubmed CrossRef
  11. Seo HJ, Lee YK, Lee SS, Kim KS, and Yang HS. A survey of postoperative residual neuromuscular block and neuromuscular monitoring. Anesth Pain Med 2010;5:70-4.
  12. Mirakhur RK, Lavery TD, Briggs LP, and Clarke RS. Effects of neostigmine and pyridostigmine on serum cholinesterase activity. Can Anaesth Soc J 1982;29:55-8.
    Pubmed CrossRef
  13. Donati F, McCarroll SM, Antzaka C, McCready D, and Bevan DR. Dose-response curves for edrophonium, neostigmine, and pyridostigmine after pancuronium and d-tubocurarine. Anesthesiology 1987;66:471-6.
    Pubmed CrossRef
  14. Naguib M, Kopman AF, Lien CA, Hunter JM, Lopez A, and Brull SJ. A survey of current management of neuromuscular block in the United States and Europe. Anesth Analg 2010;111:110-9.
    Pubmed CrossRef
  15. McLean DJ, Diaz-Gil D, Farhan HN, Ladha KS, Kurth T, and Eiker-mann M. Dose-dependent association between intermediateacting neuromuscular-blocking agents and postoperative respiratory complications. Anesthesiology 2015;122:1201-13.
    Pubmed CrossRef
  16. Bartkowski RR. Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium. Anesth Analg 1987;66:594-8.
    Pubmed CrossRef
  17. Eleveld DJ, Kuizenga K, Proost JH, and Wierda JM. A temporary decrease in twitch response during reversal of rocuroniuminduced muscle relaxation with a small dose of sugammadex. Anesth Analg 2007;104:582-4.
    Pubmed CrossRef
  18. Kaufhold N, Schaller SJ, Stäuble CG, Baumüller E, Ulm K, and Blob-ner M et al. Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20). Br J Anaesth 2016;116:233-40.
    Pubmed CrossRef
  19. Lee HJ, Kim KS, Kim TY, Lee JH, and Jeong M. The use of 3 sugammadex out of 5 reversal of during recovery of rocuronium-induced neuromuscular blockade in a patient with post-tonsillectomy hemorrhage:a case report. Korean J Anesthesiol 2014;67:43-7.
    Pubmed KoreaMed CrossRef
  20. Cammu G, de Kam PJ, De Graeve K, van den Heuvel M, Suy K, and Morias K et al. Repeat dosing of rocuronium 1.2 mg kg-1 after reversal of neuromuscular block by sugammadex 4.0 mg kg-1 in anaesthetized healthy volunteers:a modelling-based pilot study. Br J Anaesth 2010;105:487-92.
    Pubmed CrossRef
  21. Paton WD, and Waud DR. The margin of safety of neuromuscular transmission. J Physiol 1967;191:59-90.
    Pubmed KoreaMed CrossRef
  22. Takkunen O, Salmenperä M, and Heinonen J. Atropine vs glycopyrrolate during reversal of pancuronium block in patients anaesthetized with halothane. Acta Anaesthesiol Scand 1984;28:377-80.
    Pubmed CrossRef
  23. Mirakhur RK, Briggs LP, Clarke RS, Dundee JW, and Johnston HM. Comparison of atropine and glycopyrrolate in a mixture with pyridostigmine for the antagonism of neuromuscular block. Br J Anaesth 1981;53:1315-20.
    Pubmed CrossRef
  24. Ortega R, Brull SJ, Prielipp R, Gutierrez A, De La Cruz R, and Conley CM. Monitoring neuromuscular function. N Engl J Med 2018;378:6.
    Pubmed CrossRef
  25. Kotake Y, Ochiai R, Suzuki T, Ogawa S, Takagi S, and Ozaki M et al. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesth Analg 2013;117:345-51.
    Pubmed CrossRef
  26. Duţu M, Ivaşcu R, Tudorache O, Morlova D, Stanca A, and Negoiţă S et al. Neuromuscular monitoring:an update. Rom J Anaesth Intensive Care 2018;25:55-60.
  27. Cammu G. Sugammadex:appropriate use in the context of budgetary constraints. Curr Anesthesiol Rep 2018;8:178-85.
    Pubmed KoreaMed CrossRef
  28. Iwasaki H, Renew JR, Kunisawa T, and Brull SJ. Preparing for the unexpected:special considerations and complications after sugammadex administration. BMC Anesthesiol 2017;17:140.
    Pubmed KoreaMed CrossRef
  29. Hunter JM, and Naguib M. Sugammadex-induced bradycardia and asystole:how great is the risk?. Br J Anaesth 2018;121:8-12.
    Pubmed CrossRef


October 2019, 14 (4)