The Median Effective Dose (ED50) of cis-Atracurium for Laryngeal Mask Airway Insertion during General Anaesthesia for Patients Undergoing Urinary Surgery

DOI: https://doi.org/10.21203/rs.2.14853/v1

Abstract

Background In clinical practice, the laryngeal mask airway is an easy-to-use supraglottic airway device. However, the cis- atracurium dosage for laryngeal mask insertion is not standardised. We aimed to determine the optimal dose and hypnotic median effective dose of cis- atracurium using a sequential method for successful laryngeal mask insertion when inducting general anaesthesia. Method s : The cohort study protocol is registered at clinicaltrial.gov (NCT-03358680). Twenty-three patients undergoing elective urinary surgery were sequentially administered doses (mg·kg -1 ) of cis- atracurium as follows: 0.15, 0.1, 0.07, 0.05, 0.03, and 0.02. Systolic and diastolic blood pressure, heart rate, bispectral index, and train-of-four were continuously monitored. Successful laryngeal mask insertion occurred without resistance to mouth opening, resistance to insertion, coughing, swallowing, laryngospasm/airway obstruction, and head and body movement. The main outcome was the response to laryngeal mask airway insertion: ≥16 points and <16 points indicated “satisfactory” and “unsatisfactory” responses, respectively. The median effective dose was estimated using the mean of the seven crossovers from “satisfactory” and “unsatisfactory” responses. Result s : The median effective dose of cis- atracurium was 0.0265 mg·kg -1  (95% CI 0.0236-0.0298) using the sequential method. The heart rate was decreased in the 0.05 group compared to the 0.03 group at timepoints T7, T8, and T10. The systolic blood pressure was decreased in the 0.02 group compared to the 0.05 group at timepoints T2, T3, T4. The train-of-four value was significantly lower in the 0.05 group than in the 0.03 group at timepoint T3. Conclusion s : cis- a tracurium was a good option for muscle relaxation in urinary surgery.

Background

The laryngeal mask airway (LMA) is a supraglottic ventilation device that is more effective than mask airway in difficult airway management and has characteristics of a mask and endotracheal intubation [1]. LMA insertion has more advantages than endotracheal intubation; it has little influence on the patient's circulation during insertion, reduces the dosage of analgesics required to maintain anaesthesia during surgery, and is well-tolerated [2]. Therefore, the laryngeal mask is widely used in elective minor surgery, particularly in minor urinary surgery [3]. The use of muscle relaxants is necessary to improve the conditions of laryngeal mask insertion [4]. Without muscle relaxants, the pharyngeal tissues are not relaxed and appropriate laryngeal mask placement is difficult owing to resistance to mouth opening and biting [5]. Moreover, muscle relaxation is needed to avoid excessive airway reactivity of laryngeal mask insertion (e.g., laryngeal spasm, hypersalivation, coughing); to reduce laryngeal mask insertion-related complications (e.g., postoperative throat pain); and to reduce the incidence of airway complications such as hypoxia, ineffective ventilation, and sternal muscle stiffness that are induced by opioid analgesia reagents [6-8]. Analgesic and narcotic agents require higher dosages when used without muscle relaxants, which then inhibit the patient’s haemodynamics [9]. Smaller doses of neuromuscular blocking agents (NMBAs) may improve mandibular relaxation and shorten the time required for laryngeal mask placement, and thereby improve the laryngeal mask placement conditions [10].

cis-atracurium is a non-depolarizing NMBA and has been widely used adjunctively during anaesthesia to facilitate endotracheal intubation and provide a relatively longer duration of muscle relaxation [11]. It is spontaneously degraded at physiological pH via Hofmann elimination, which is an organ-independent degradative mechanism that yields laudanosine and plasma esterase-mediated hydrolysis [12]. Little or no risk is associated with the use of cis-atracurium in patients with renal disease; therefore, it is frequently used in general anaesthesia during urinary surgery. Furthermore, cis-atracurium also has unique advantages and is approximately three-fold more potent than atracurium as a muscle relaxant [13]; it has less propensity to induce histamine release, which causes subsequent cutaneous flushing, hypotension, and tachycardia complication [14], and it significantly reduces proinflammatory markers during surgery [15]. However, an overdose of cis-atracurium may increase the risk of aspiration, airway obstruction, and delayed recovery. The dosages of muscle relaxants used in trachea intubation vary greatly and range from 10 to 200 µg·kg-1 [16-19]. However, a reasonable dosage of cis-atracurium under LMA has not been reported.

This study aimed to determine the median effective dose (ED50) of cis-atracurium for laryngeal mask insertion in anesthetised adults using Dixon’s up-and-down method, and to determine the dose-response curves for laryngeal mask insertion in urinary surgery.

Methods

Patient Characteristics

This prospective observational study was approved by the university’s institutional review board (IRB no.: 2017-D136). All individuals participating in the trial provided written informed consent. The trial is also registered at http://ClinicalTrials.gov  (registry no.: NCT-03358680; date of registration: April 1, 2018). The methodology in this study followed the international guidelines for observational studies according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 2010 statement (Supplementary Table-1). We recruited twenty-three prospective consecutive patients who were scheduled for elective minor urological surgery with general anesthesia between May 1, 2018, and July 3, 2018, at Xuanwu Hospital(Beijing, China). All patients met the criteria for the American Society of Anesthesiologists (ASA) Physical Status I–Ⅲ; Body  Mass Index (BMI), 18.5-30; age, 20-60 years; predicted operation duration <180 min; and estimated blood loss <5 ml·kg-1 . The exclusion criteria were as follows: neuromuscular diseases; metabolic diseases; preoperative condition complicated with electrolyte disorders, serious hepatic insufficiency (i.e., liver transaminase level >40 U·L-1), or renal insufficiency (i.e., serum creatinine level >1.2 mg·dL-1); serious heart and lung disease; predicted difficult airway; use of preoperative medications that interact with nondepolarising NMBAs (e.g., aminoglycosides, polymyxin, steroids, phenytoin sodium, neuroleptics, carbamazepine); history of allergy to NMBAs; and history of alcoholism or drug abuse.

 

Anaesthesia Protocol

After the patient entered the operating room, lactate Ringer’s solution was infused at a rate of 5 ml·kg-1·h-1. After 3 min of oxygen supplied via the mask, intravenous sufentanil (dose, 0.25 μg·kg-1; injection time, 30 s) and etomidate (dose, 0.2 mg·kg-1; injection time, 30 s) were administered. The train-of-four (TOF) value was calibrated after the patient lost consciousness. After the eyelash reflex was lost, cis-atracurium was administered (injection time, 5 s). Three minutes after the cis-atracurium injection, and once the bispectral index (BIS) reached a value of 40-60, an experienced anaesthesiologist placed a flexible LMA (Teleflex Medical, Wayne, PA, USA; Athlone Co., Westmeath, Ireland) of the appropriate type (LMA ® Flexible criteria: 30-50 kg for No. 3; 50-70 kg for No. 4; and 70-100 kg for No. 5). The patients’ responses were jointly evaluated by another anaesthesiologist who was blinded to the cis-atracurium concentrations when the LMA was inserted. The tidal volume setting was 7 ml·kg-1, and the respiration ratio setting was 12 RR·min-1. If laryngeal mask insertion was unsuccessful, anaesthesia was deepened with further increments of cis-atracurium, or an inhalation agent, or both, until the laryngeal mask was tolerated; however, the patient was placed in the “unsatisfactory” group. Propofol combined with remifentanil was used to maintain the BIS at 40-60 throughout the duration of the operation. The range of blood pressure and heart rate (HR) fluctuation did not exceed the 20% baseline value. Body temperature was maintained at >36°C using a warm air blanket.

 

 Cis-Atracurium Administration and Evaluation of the LMA Placement Conditions

Laryngeal mask Placement Conditions. The insertion condition was evaluated only when the laryngeal mask was inserted the first time. Using the recognised six-point-three scale proposed by Sivalingam [20], which has been used successfully in previous research, the following were graded: resistance to mouth opening, resistance to insertion, coughing, swallowing, laryngospasm/airway obstruction(including Paw pressure more than 40mmHg after insertion immediately), and head and body movement. Each item was scored with 3 points, 2 points, and 1 point, based on the severity. A full score was 18 points. A score of ≥16 points was a “satisfactory” response, and a score of <16 points was an “unsatisfactory” response (Supplementary Table 1). If insertion was an “unsatisfactory” response, the cis-atracurium concentration was increased in the next patient. After approximately 60 s of successful laryngeal mask insertion, the position and ventilation condition of the laryngeal mask and whether the patient had a “satisfactory” or “unsatisfactory” response were recorded.

Administration of cis-Atracurium. The first patient enrolled in the study was exposed to an initial cis-atracurium concentration of 0.15 mg·kg-1. The step size of the concentration was calculated by common ratio 1.5, so the administered doses was 0.1=[0.15/(1.5)], 0.06667=[0.15/(1.5)2], 0.04444=[0.15/(1.5)3], 0.02962=[0.15/(1.5)4], and 0.01975= [0.15/(1.5)5]mg. Based on the clinical practical meaning, the actual administered doses were 0.15, 0.1, 0.07, 0.05, 0.03, and 0.02 in this study. Depending on the previous patient’s response to the laryngeal mask, using a modified Dixon’s up-and-down method, we adjust the subsequent dose in the remaining patients [21]. Beginning with the first case of unsatisfactory response, the number of observation units was counted. A “satisfactory-satisfactory” response occurred at seven exchange points. This marked the completion of the test (Figure 1). When self-contained respiration occurred during the operation, additional doses of cis-atracurium were re-administered to the patient.

 

Muscle Relaxation (TOF) Monitoring and General Parameter Monitoring

The patient's upper limb was extended and fixed. After degreasing the skin with alcohol, surface electrodes were placed on the side of the ulnar nerve of the wrist for TOF stimulation monitoring (TOF-Watch; Organon Ireland, Ltd., Swords, Dublin, Ireland). The sensor probe of the TOF monitor was placed between the thumb and forefinger with no resistance between them. When the patient lost consciousness, the calibration scale of T1 was 100, the stimulation current was 45-75 mA, the interval was 5 s, and the frequency was 2 Hz. Electrocardiography, blood pressure, HR, Pulse oxygen saturation(SpO2), and BIS of patients were routinely monitored. We set ten timepoints to record variations during the operation, as follows: at the administration of cis-atracurium (T1); at 3 min after the administration of cis-atracurium (i.e., at LMA insertion) (T2), 10 min after the administration of cis-atracurium (at the beginning of the operation) (T3), 20 min after the administration of cis-atracurium (T4), 30 min after the administration of cis-atracurium (T5), 40 min after the administration of cis-atracurium (T6), 50 min after the administration of cis-atracurium (T7), 60 min after the administration of cis-atracurium (T8), 70 min after the administration of cis-atracurium (T9), and 80 min after the administration of cis-atracurium (T10). The systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, SpO2, and BIS were recorded at each timepoint.  TOF and airway peak pressure (Paw peak pressure) were recorded at T1-T8, because after T8 the muscle relaxation recover in most case in 0.02 group, the participant cannot tolerance the laryngeal mask. Additional doses of cis-atracurium were re-administered to the patient after T8 timepoint. The TOF and airway peak pressure (Paw peak pressure) were effect by re-administer cis-atracurium, so didn`t include this TOF and airway peak pressure (Paw peak pressure) in T9 and T10 in statistical analysis. The Intraoperative haemodynamic changes and adverse reactions such as cough, respiratory depression, dizziness, nausea, and vomiting were also recorded.

 

Statistical Analysis
The ED50 of cis-atracurium was determined by calculating the midpoint concentration of the crossover point from the “satisfactory” or “unsatisfactory” responses. To facilitate the dose-response analysis, the laryngeal mask insertion conditions were recorded as dichotomous outcomes. A probit analysis linear regression plot of the log dose versus the percentage response was generated and interpolation (with 95% CIs) was used to determine the laryngeal mask condition. The average of the midpoints of all pairs was used to calculate the ED50 using Dixon’s up-and-down method. The number of responders at each dose was used to plot a sigmoid dose-response curve and a log-dose probit response relation. The other parameters were analysed using repeated measures ANOVA. The patient characteristics are presented as the mean (± SD) or the number (proportion). A P-value of <0.05 was considered to represent significant difference among outcomes. These data were analysed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). The sample size of 23 patients was based on α = 0.05 for the two-sided chi-square test to analyse trends in proportions and a logistic model of β = 0.1 to detect the insertion success rates. The sample size of this study also was based on the fact that a minimum of seven independent pairs of participants exhibiting a crossover point from a “satisfactory” response to an “unsatisfactory” response. In similar studies in the field of airway device insertion, the number of crossover points varied from six to eight, with six crossover points being the most common. For this study, seven crossovers were sufficient to determine the ED50 of cis-atracurium required to insert a laryngeal mask. A minimum of seven pairs of failure-success were required for the statistical analysis. The total score for the insertion conditions was calculated by addition. A score of ≥16 represented the optimal condition for LMA insertion.

Results

Patient Profile, Haemodynamics, TOF Value, and Ventilation Condition for Each Dosage

The three dosage groups were similar with respect to age, sex, weight, height, BMI, and ASA Physical Status (Table 1). No significant differences existed in the pH values and nasopharyngeal temperatures of all patients. The haemoglobin values, globulin fraction of plasma protein, and albumin fraction of plasma protein were similar among groups (Table 1). The preoperative Mallampati variable did not differ among groups. The operation duration, anaesthesia duration, and blood loss were non-significantly different among groups (Table 1). There was no statistical difference in the DBP among groups. The SBP was significantly decreased in the 0.02 group compared to the 0.05 group at T2, T3, and T4 (P = 0.0159, P = 0.0233, and P = 0.0428, respectively; Figure 2a and 2b). For each group, the HR did not significantly differ at most timepoints; however, the HR was significantly decreased at T7, T8, and T10 in the 0.05 group compared to the 0.03 group (P = 0.0482, P = 0.0460, and P = 0.0236, respectively). This finding indirectly reflected lower stress at these timepoints (Figure 2c).

The BIS value did not significantly differ among the three groups and was maintained at 40-60 during surgery (Figure 2d).

The TOF value at T3 was significantly lower in the 0.05 group than in the 0.03 group (P = 0.0326) (Figure 2e). The Paw pressure indicates airway protection and the supraglottic airway device placement condition. In this study, the airway peak pressure (i.e., mean Paw pressure) did not significantly differ between the 0.05 group and 0.03 group at any timepoint. However, it was significantly higher at T8 in the 0.02 group than in the 0.03 group (P = 0.0423; Figure 2F). There were no severe intraoperative haemodynamic changes and adverse reactions such as respiratory depression,  nausea, and vomiting happen in each group.

 

The ED50 and ED95 of cis-Atracurium

In these patients, the ED50 (95% CI) of cis-atracurium for laryngeal mask insertion, which was obtained using the up-and-down method, was 0.0265 mg·kg-1 (95% CI, 0.0236-0.0298). We found that the laryngeal mask, based on probit regression analysis, can be successfully inserted in 50% (95% CI) of anesthetised adults at a cis-atracurium concentration of 0.0265 mg·kg-1 (95% CI, 0.0236-0.0298). The log dosage probit response curves for cis-atracurium for the insertion of the laryngeal mask (probability unit vs. concentration) are provided in Figure 3a. We generated dose response curves and determined the effective doses of cis-atracurium required for the insertion of the laryngeal mask in adult patients (Figure 3b).

Discussion

In this study, we aimed to determine the optimal cis-atracurium dosage for LMA insertion in anesthetised adults using Dixon’s up-and-down method, and to determine the dose-response curves for LMA insertion in patients undergoing urinary surgery. We found that the ED50 of cis-atracurium for LMA insertion of the patients in this study was 0.0265 mg·kg-1. Based on our findings, we concluded that laryngeal mask insertion requires the same cis-atracurium dosage as tracheal intubation and is an important adjuvant to general anaesthesia. A previous study reported that the calculated ED50 value was 0.0262 mg·kg-1 (95% CI: 0.0258-0.0265) [22]. In another study, the ED50 (SD) and ED95 (SD) values of cis-atracurium were 0.021 (0.04) and 0.051 (0.013) mg·kg-1, respectively, for tracheal intubation under total intravenous anaesthesia [23]. Tracheal intubation is required when the neuromuscular response is abolished; laryngeal mask insertion requires the same condition. No consensus exists regarding the appropriate dose of muscle relaxants required for placing a laryngeal mask; the dose ranges from 1/10 dose to the full dose for normal tracheal intubation [18]. One study [18] also demonstrated that the dosage of muscle relaxants required for laryngeal mask placement was smaller than that of the muscle relaxants required for endotracheal intubation. This finding coincided with our results. The estimated ED50 for the total patient group was 35.11 μg·kg-1 [24]. The results of the effective dose in our study differed from the 48 μg·kg-1 that was estimated as the ED95 of cis-atracurium by Belmont et al. [25], and differed from the ED50 and ED95 of 30 μg·kg-1 and 53 μg·kg-1, respectively, reported by Lepage et al. [26].

 In our study, the SBP was significantly lower in the 0.02 group at T2 (i.e., anaesthesia induction time point), T3, and T4, and was indistinguishable from the SBP in the 0.03 and 0.05 groups. No significant difference in SBP was observed between the 0.05 and 0.03 groups. However, the propensity to maintain the SBP at a relatively stable level at the preoperative stage was same in the three groups.

Over 50% of the patients in the 0.02 group had an unsatisfactory first response to laryngeal mask insertion. Placement of a laryngeal mask requires adequate anaesthesia depth and mouth opening. Therefore, we were required to administer an additional dose of propofol and sufentanil to achieve satisfactory insertion. The combination of an appropriate dose of muscle relaxants can improve laryngeal mask placement without increasing the incidence of associated adverse reactions, while reducing the amount of propofol or sufentanil anesthetics and reducing their inhibitory effect on circulation [27]. Without the use of muscle relaxants, it is necessary to increase the depth of anaesthesia, which prolongs the time of a patient's recovery of consciousness.

Our results indicated that the HR was significantly decreased in the 0.05 group compared to the 0.03 group at T7, T8, and T10. This finding indirectly reflected lower stress in the 0.05 group than in the 0.03 and 0.02 groups. cis-Atracurium did not exert significant haemodynamic changes, even at different concentrations. However, the interaction among anaesthetic agents caused a statistically significant decline in some haemodynamic parameters at certain time points. This change was not a clinical effect and required no vasopressor agents. Using an appropriate NMBA did not affect the extubation time, but it did reduce the stress reaction [28]. cis-Atracurium did not cause harmful autonomic nervous system effects and resulted in reduced secretion of histamine. Some investigators have demonstrated no cardiovascular system variations, even with histamine secretion, when administering a double dose of ED95 to patients with coronary artery disease [29, 30]. The pharmacodynamics of NMBAs are affected by several factors such as inhalation agents, temperature [31, 32], magnesium, local anesthetics [33], antiepileptic drugs, age [34], weight [35], and plasma clearance and volume of distribution [36, 30]. Our study revealed no difference among the three groups in terms of the ASA Physical Status, age, weight, height, and sex. The patients’ body temperature in each group was maintained within the normal range. We avoided using inhalation anaesthesia throughout the operation.

Based on our findings, all three groups had recovered to the 100% TOF value by T6. The TOF value was significantly lower in the 0.05 group than in the 0.03 group. This finding indicated that the 0.05 group had more efficient muscle relaxation. At the earliest timepoint, the TOF value did not significantly differ between the 0.03 and 0.02 groups. The use of a relatively high dose of muscle relaxants will also prolong the extraction of the laryngeal mask due to the prolonged TOF recovery time. The administration of 200% of the ED95 values of cis-Atracurium, producing an onset duration of 5.2 min, and the duration of the time to 25% of T1 recovery at 45 min have been reported [37, 38]. Tulgar [39] demonstrated that the use of subclinical doses of muscle relaxants does not affect anaesthesia recovery time. In this study, the airway peak pressure (mean Paw pressure) insignificantly differed between the 0.05 group and the 0.03 group at each timepoint. However, the airway peak pressure at T8 was significantly higher in the 0.02 group than in the 0.03 group (P = 0.0423). Hemmerling [40] reported that a certain degree of muscle relaxation could prevent reduced sealing of the laryngeal mask due to the recovery of throat muscle strength.

 Our study was limited in that we did not analyse subgroups of these patients. We plan to determine the differences in the ED50 between younger and elderly patients in our future research, because reactions and pharmacokinetics differ between young and elderly patients. We will also analyse the differences based on sexes in the future. Our research provides information for anaesthesiologists that could help them improve general anaesthesia induction and LMA insertion in patients undergoing minor surgeries.

Conclusions

The ED50 of cis-atracurium for LMA insertion of the patients in this study was 0.0265 mg·kg-1. cis-atracurium was a good option for muscle relaxation in urinary surgery.

 

Abbreviations

LMA, laryngeal mask airway; NMBAs, neuromuscular blocking agents; ED50, the median effective dose;STROBE, Observational Studies in Epidemiology; IRB, institutional review board; ASA, American Society of Anesthesiologists; TOF, train-of-four; BIS, bispectral index; HR, heart rate;SpO2, Pulse oxygen saturation; SBP, the systolic blood pressure; DBP, diastolic blood pressure;BMI, Body  Mass Index

Declarations

Ethics approval and consent to participate

This prospective observational study was approved by the local ethics committee (Capital Medical University Institutional Review Board, China, December 8, 2017; IRB no.: 2017-D136). Written informed consent was obtained from all patients participating in the trial. The trial was registered with http://www.ClinicalTrials.gov (NCT-03358680; date of registration, April 1, 2018). Our methodology followed the international guidelines for observational studies.

 

Consent for publication

Not applicable.

 

Availability of data and material

The raw data of this study are available from the corresponding author on reasonable request.

 

Competing Interests

No external funding and no competing interests declared.

 

Funding statement

 The National Natural Science Foundation of China (No. 81401084); Beijing Municipal Administration of Hospital Ascent Plan (No. DFL20150802); Beijing 215 high level healthcare talent plan academic leader(No. 008-0027); Beijing Municipal commission of Health and Family Planning (No. PXM2017_026283_000002); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201706; No. 303-01-005-0137-11) in part funded this work in part.

 

Author Contributions

Name: Xiaohua Wang MD. PhD

Contribution: helped draft the manuscript.

Name: Ke Huang MD.

Contribution: helped prepare the cis-atracurium concentrations

Name: Dongxu Yao MD.

Contribution: helped place a flexible LMA of the appropriate type

Name: Jixiu Xue MD.

Contribution: helped evaluate the patients’ responses and was blinded to the cis-atracurium concentrations

Name: Tianlong Wang MD. PhD

Contribution: contributed to the design of the research and agreed to be accountable for all aspects of this work.

 

Acknowledgements:

This research was supported by the National Natural Science Foundation of China and the department of Urinary surgery at Xuanwu Hospital. The authors thank Jiangtao Wu, Hao Yan, and Tongwen Ou for performing the operation and assisting in manuscript preparation.

References

[1] Cattano D, Van Zundert TCRV, Wojtczak J. Laryngeal mask airway and the enigma of anatomical sizing. J Clin Monit Comput. 2019 Apr 24.

[2] Hohlrieder M, Brimacombe J, von Goedecke A, et al. Postoperative nausea, vomiting, airway morbidity, and analgesic requirements are lower for the ProSeal laryngeal mask airway than the tracheal tube in females undergoing breast and gynaecological surgery. Br J Anaesth. 2007 Oct;99(4):576-80.

[3] Erhan E, Ugur G, Anadolu O, et al. General anaesthesia or spinal anaesthesia for outpatient urological surgery. Eur J Anaesthesiol. 2003 Aug;20(8):647-52.

[4] Baker AR, Baker AB. Anaesthesia for endoscopic sinus surgery. Acta Anaesthesiol Scand. 2010 Aug;54(7):795-803.

[5] Hu LQ, Leavitt OS, Malwitz C, et al. Comparison of laryngeal mask airway insertion methods, including the external larynx lift with pre-inflated cuff, on postoperative pharyngolaryngeal complications: A randomized clinical trial. Eur J Anaesthesiol. 2017 Jul;34(7):448-455.

[6] Scanlon P, Carey M, Power M,et al. Patient response to laryngeal mask insertion after induction of anaesthesia with propofol or thiopentone. Can J Anaesth. 1993 Sep;40(9):816-8.

[7] Chandra S, Pryambodho P, Melati AC,et al. Comparison Between Lidocaine Inhalation and Intravenous Dexamethasone in Reducing Postoperative Sore Throat Frequency After Laryngeal Mask Insertion. Anesth Pain Med. 2018 Aug 25;8(5):e82131.

[8] Eichelsbacher C, Ilper H, Noppens R,et al. Rapid sequence induction and intubation in patients with risk of aspiration: Recommendations for action for practical management of anesthesia]. Anaesthesist. 2018 Aug;67(8):568-583.

[9] Michel J, Hofbeck M, Gerbig I, et al. Nurse-driven analgesia and sedation in pediatric patients with univentricular hearts requiring extracorporeal life support after first-stage palliation surgery: A pilot study. Paediatr Anaesth. 2017 Dec;27(12):1261-1270.

[10] Nasseri K. Effect of Low-dose Atracurium on Laryngeal Mask Airway Insertion Conditions: A Randomized Double-blind Clinical Trial. Adv Biomed Res, 2017, 6(1): 119.

[11] Ortiz JR, Percaz JA, Carrascosa F. [Cisatracurium]. Rev Esp Anestesiol Reanim. 1998 Jun-Jul;45(6):242-7.

[12] Fuchs-Buder T. New muscle relaxants. Update on mivacurium, rocuronium and cis-atracurium. Anaesthesist. 1997 Apr;46(4):350-9.

[13] Diefenbach C, Buzello W. New muscle relaxants. Anasthesiol Intensivmed Notfallmed Schmerzther. 1996 Feb;31(1):2-8. Review.

[14] Savarese JJ, Wastila WB. The future of the benzylisoquinolinium relaxants. Acta Anaesthesiol Scand Suppl 1995; 106:91-93.

[15]Konrad FM, Unertl KE, Schroeder TH. [Mastocytosis. A challenge in anaesthesiology]. Anaesthesist. 2009 Dec;58(12):1239-43.

[16]Kim KS, Chun YS, Chon SU, et al. Neuromuscular interaction between cisatracurium and mivacurium, atracurium, vecuronium or rocuronium administered in combination. Anaesthesia. 1998 Sep;53(9):872-8.

[17] Bergeron L, Bevan DR, Berrill A, et al. Concentration–effect relationship of cisatracurium at three different dose levels in the anesthetized patient. Anesthesiology. 2001; 95:314–23.

[18] Naguib M, Samarkandi AH, Ammar A ,et al. Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination. Anesthesiology. 1998 Nov;89(5):1116-24.

[19] Kim JH, Lee YC, Lee SI, et al. Effective doses of cisatracurium in the adult and the elderly. Korean J Anesthesiol. 2016 Oct;69(5):453-459.

[20] Sivalingham P, Kandasamy R, Madhaven G, et al. Conditions for laryngeal mask insertion: A comparison of propofol versus sevoflurane with or without alfentanil. Anaesthesia 1999; 54:271–6.

[21] Dixon WJ. Staircase bioassay: the up-and-down method. Neurosci Biobehav Rev. 1991 Spring;15(1):47-50.

[22] Naguib M, Samarkandi AH, Ammar A, et al. Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination. Anesthesiology. 1998 Nov;89(5):1116-24.

[23] Wulf H, Kahl M, Ledowski T. Augmentation of the neuromuscular blocking effects of cisatracurium during desflurane, sevoflurane, isoflurane or total i.v.anaesthesia. Br J Anaesth. 1998 Mar;80(3):308-12.

[24] Park WY, Choi JC, Yun HJ, et al. Optimal dose of combined rocuronium and cisatracurium during minor surgery: A randomized trial. Medicine (Baltimore). 2018 Mar;97(10):e9779. 

[25] Belmont MR, Lien CA, Quessy S, et al. The clinical neuromuscular pharmacology of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology 1995; 82: 1139-45.

[26] Lepage JY, Malinovsky JM, Malinge M, et al. Pharmacodynamic dose-response and safety study of cisatracurium (51W89) in adult surgical patients during N2O-O2-opioid anesthesia. Anesth Analg 1996; 83: 823-9.

[27] George L R, Sahajanandan R, Ninan S. Low-dose Succinylcholine to Facilitate Laryngeal Mask Airway Insertion: A Comparison of Two Doses. Anesth Essays Res, 2017, 11(4): 1051-1056.

[28] Smith SE, Hamblin SE, Dennis BM. Effect of Neuromuscular Blocking Agents on Sedation Requirements in Trauma Patients with an Open Abdomen. Pharmacotherapy. 2019 Mar;39(3):271-279.

[29] Naguib M, Lien CA, Meistelman C. Pharmacology of muscle relaxants and their antagonists. In: Miller’s Anesthesia. 8th ed. Edited by Miller RD: Philadelphia, Churchill Livingstone/Elsevier. 2015, pp 958-94.

[30] Kisor DF, Schmith VD. Clinical pharmacokinetics of cisatracurium besilate. Clin Pharmacokinet 1999; 36: 27-40.

[31] Sorooshian SS, Stafford MA, Eastwood NB, et al. Pharmacokinetics and pharmacodynamics of cisatracurium in young and elderly adult patients. Anesthesiology 1996; 84: 1083-91.

[32] Amin AM, Mohammad MY, Ibrahim MF. Comparative study of neuromuscular blocking and hemodynamic effects of rocuronium and cisatracurium under sevoflurane or total intravenous anesthesia. Middle East J Anaesthesiol. 2009 Feb;20(1):39-51.

[33] Kim YB, Sung TY, Yang HS. Factors that affect the onset of action ofnon-depolarizing neuromuscular blocking agents. Korean J Anesthesiol. 2017; 70:500–10.

[34] Ornstein E, Lien CA, Matteo RS, et al. Pharmacodynamics and pharmacokinetics of cisatracurium in geriatric surgical patients. Anesthesiology 1996; 84: 520-5.

[35] Leykin Y, Pellis T, Lucca M, et al. The pharmacodynamic effects of rocuronium when dosed according to real body weight or ideal body weight in morbidly obese patients. Anesth Analg 2004; 99:1086–9.

[36] Arain SR, Kern S, Ficke DJ, et al. Variability of duration of action of neuromuscular-blocking drugs in elderly patients. Acta Anaesthesiol Scand 2005; 49: 312-5.

[37] Belmont MR, Lien CA, Quessy S, et al. The clinical neuromuscular pharmacology of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology. 1995; 82:1139–45.

[38] Naguib M. Neuromuscular effects of rocuronium bromide and mivacurium chloride administered alone and in combination. Anesthesiology 1994; 81:388–95.

[39] Tulgar S, Boga I, Cakiroglu B, et al. Short-lasting pediatric laparoscopic surgery: Are muscle relaxants necessary? Endotracheal intubation vs. laryngeal mask airway. Journal of Pediatric Surgery, 2017, 52(11): 1705-1710.

[40] Hemmerling T M, Michaud G, Deschamps S, et al. 'Patients who sing need to be relaxed'--neuromuscular blockade as a solution for air-leaking during intermittent positive pressure ventilation using LMA. Can J Anaesth, 2005, 52(5): 549.

Tables

Table 1. Population Demographics and Intraoperative and Preoperative Data

Variable

0.05 µg·kg-1

0.03 µg·kg-1

0.02 µg·kg-1

Female sex

1 (25)

1 (10)

2 (33.3)

Age (years)

54.50 (14.08)

50.60 (12.65)

48.83 (13.23)

Weight (kg)

77.00 (12.36)

76.90(5.28)

75.67 (14.90)

Height (cm)

168.75 (7.14)

171.40(4.97)

169.00 (6.20)

BMI

26.90 (2.37)

26.21 (2.02)

26.32 (3.93)

Haemoglobin (g·dL -1)

137.5 (19.16)

140.30 (9.59)

138.67 (25.45)

Globin fraction of plasma protein (g·dL -1)

30.98 (4.89)

24.21 (3.45)

23.87 (5.61)

Albumin fraction of plasma protein (g·dL -1)

40.19 (4.24)

39.82 (3.67)

41.22 (6.23)

pH value

7.37 (0.04)

7.38 (0.03)

7.39 (0.03)

Nasopharyngeal temperature (°C)

36.33 (0.25)

36.34 (0.28)

36.38 (0.10)

Operation duration (min)

93 (42.42)

67.20 (41.58)

56.17 (90.27)

Anaesthesia duration (min)

122.25 (41.16)

104.20 (45.85)

99.33 (81.02)

Blood loss (ml)

141.03 (13.52)

139.01 (10.18)

138.89 (20.11)

Mallampati class

 

 

 

0 (0)

1 (10)

1 (16.67)

0 (0)

2 (20)

1 (16.67)

4 (100)

7 (70)

3 (50)

0 (0)

0 (0)

1 (16.67)

ASA score

 

 

 

2 (50)

2 (20)

1 (16.67)

2 (50)

8 (80)

5 (83.33)

ASA, American Society of Anesthesiologists; BMI, Body  Mass Index

The numerical values (e.g., Mallampati class, ASA score, sex) are expressed as the number (%) or number (proportion). All other values are expressed as the mean (SD).

*P < 0.05; **P < 0.01.