Header bg
  • Users Online: 79
  • Print this page
  • Email this page
Header bg


 
 
Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 93-97

Cisatracurium versus atracurium for abdominal surgeries regarding condition of intubation and hemodynamic effect: A randomized double-blind study


Department of Anaesthesiology and Critical Care Medicine, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

Date of Submission20-Nov-2020
Date of Decision23-Jan-2021
Date of Acceptance05-Feb-2021
Date of Web Publication16-Apr-2021

Correspondence Address:
Dr. Mohammad Faseehullah Alam
Flat No. 37, Draupadi Apartment, Behind JD Women's College, Shashtrinagar, Patna - 800 023, Bihar
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjoa.bjoa_246_20

Rights and Permissions
  Abstract 


Background: Neuromuscular-blocking drugs block neuromuscular transmission, causing paralysis of the affected skeletal muscles. In clinical use, neuromuscular block is used adjunctively to anesthesia to produce paralysis, first to paralyze the vocal cords, and permit intubation of the trachea, and second to optimize the surgical field by inhibiting spontaneous ventilation, and causing relaxation of skeletal muscles. Patients and Methods: This was a prospective, randomized study registered in Clinical Trials Registry of India (CTRI/2019/04/018580). We included 100 patients divided into two groups of 50 each. Group A received atracurium (0.5 mg/kg), whereas Group B received cisatracurium (0.15 mg/kg). Efficacy of both the drugs was compared in terms of onset of action, duration of action, duration of recovery, hemodynamic conditions during and after intubation, and signs of histamine release in both the drugs. Results: Mean duration of 25% recovery from the reversal in the atracurium group was 32.4 ± 1.90 min which was significantly less as compared to 49.46 ± 1.86 min of cisatracurium group (P < 0.001). The mean duration of recovery from the reversal in cisatracurium group was 2.18 ± 0.82 min which was significantly more as compared to 1.8 ± 0.75 min of atracurium group (P = 0.02). Conclusion: Cisatracurium in a dose of 0.15 mg/kg had a faster onset and duration of action than atracurium 0.5 mg/kg. At this dose, cisatracurium provides optimal intubating condition, rapid neuromuscular blocking with longer duration of action, stable hemodynamic status, no signs of histamine release clinically, and without any residual muscle paralysis compared to atracurium.

Keywords: Atracurium, cisatracurium, intubation, neuromuscular transmission


How to cite this article:
Ranjan R, Alam MF, Avinash R. Cisatracurium versus atracurium for abdominal surgeries regarding condition of intubation and hemodynamic effect: A randomized double-blind study. Bali J Anaesthesiol 2021;5:93-7

How to cite this URL:
Ranjan R, Alam MF, Avinash R. Cisatracurium versus atracurium for abdominal surgeries regarding condition of intubation and hemodynamic effect: A randomized double-blind study. Bali J Anaesthesiol [serial online] 2021 [cited 2021 Jun 23];5:93-7. Available from: https://www.bjoaonline.com/text.asp?2021/5/2/93/313894




  Introduction Top


Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles.[1] This is accomplished by acting presynaptically through the inhibition of acetylcholine synthesis. In clinical use, the neuromuscular block is used adjunctively to anesthesia to produce paralysis and permit intubation of the trachea and to optimize the surgical field by inhibiting spontaneous ventilation and causing relaxation of skeletal muscles.

Cisatracurium besylate is an intermediate-acting, nondepolarizing neuromuscular blocking drug (NMBD). Cisatracurium has a benzylisoquinoline structure and is the 1R cis-1'R cis isomer of atracurium. It also provides skeletal muscle relaxation to facilitate mechanical ventilation in an intensive care unit setting.[2],[3]

The neuromuscular blocking potency of cisatracurium is roughly three times that of atracurium.[4] The clinically beneficial duration of action and spontaneous recovery rate from equipotent doses of the two drugs are similar. Cisatracurium is a stereoisomer of atracurium with approximately 3–4 times greater than that of atracurium.[5],[6]

Despite the higher potency, cisatracurium is associated with more stable hemodynamics than atracurium and does not cause histamine release even at doses of up to 0.4 mg/kg.[7],[8],[9] Hence, this study was conducted to compare the atracurium and cisatracurium concerning neuromuscular blockade and recovery characteristics.


  Patients and Methods Top


This study was conducted after obtaining ethical approval from the Institutional Ethical Committee (IEC/848/ACAD dated 25.07.2017) for 2 years (January 2018 to December 2019). The trial was registered with Clinical Trial Registry India before patient enrollment per registration number CTRI/2019/04/018580. The study was conducted at Indira Gandhi Institute of Medical Sciences, Patna, India. Written informed consent was obtained from all the patients before enrolling them for the study. One hundred patients who underwent elective diagnostic and surgical procedures for abdominal surgeries under general anesthesia, who were willing to participate and fulfill the inclusion criteria were enrolled in this double-blind, randomized, controlled study.

Patients of either sex, with American Society of Anesthesiology (ASA) I and II, aged between 18 and 50 years and scheduled to undergo abdominal surgeries of an anticipated duration of at least 90 min. Patients with systemic diseases (diabetes mellitus, hypertension, and epilepsy), on medication known to interact with NMBDs, and known allergy to atracurium and cisatracurium were excluded from the study.

Using computer-generated random numbers, patients were allocated to one of two groups. Group A received atracurium with an initial dose of 0.5 mg/kg, a maintenance dose of 0.1 mg/kg, whereas Group C received cisatracurium with an initial dose of 0.2 mg/kg maintenance dose of 0.03 mg/kg.

Standard ASA monitoring was employed in the operating room. All the patients were premedicated with injection butorphanol 1 mg and 0.03 mg/kg midazolam. After preoxygenation with 100% oxygen, general anesthesia was induced with 2 mg/kg propofol. Neuromuscular monitoring was carried out after obtaining the control values by supramaximal stimulus (50 mA, 2 Hz) at every 15s to stimulate the ulnar nerve through surface electrodes. From the injection of neuromuscular blocking agent (NMBA), the patient's blood pressure and pulse rate were monitored each minute for the next 10 min and then every 10 min throughout the surgery.

The onset time was determined as the interval from the end of muscle relaxant injection until “Train of Four (TOF) score 0.” Endotracheal intubation was done using the proper size tube. Anesthesia was maintained with a mixture of 50% N2O in O2, isoflurane (0.8%–1%), boluses of the muscle relaxant (with the maintenance dose of either atracurium 0.1 mg/kg or cisatracurium 0.03 mg/kg) was given at TOF score 2. Patients were monitored for any signs of histamine release clinically by observing skin changes graded as flush (if redness lasted >120 s), erythema, or wheals, and presence of any hemodynamic changes or bronchospasm. Intraoperatively, the patient was on volume-controlled ventilation and maintained normocapnia.

Duration from the last dose of NMBA to 25% recovery of TOF was recorded. When TOF recovery was 25% from the last dose at the end of the surgery, the reversal was achieved by administering 0.05 mg/kg neostigmine and 8 μg/kg glycopyrrolate mixture. The patient was then shifted to the recovery room for postoperative monitoring.

Data were recorded in Microsoft Excel and analyzed using the Statistical Package for the Social Sciences (SPSS Inc.; Version 19.0., Chicago, IL, USA). Quantitative data were expressed as mean ± SD, whereas qualitative data were expressed as numbers and percentages (%). Student's t-test was used to test the significance of difference for the quantitative variables (heart rate [HR], BP) that follow a normal distribution, and Chi-square was used to test the significance of difference for qualitative variables. P < 0.05 was considered statistically significant.


  Results Top


A hundred patients were enrolled in this study [Figure 1], and the demographic characteristics were comparable for age, weight, sex, and ASA status [Table 1]. Group A's mean onset of action was 188.30 ± 11.59 as compared to 183.20 ± 18.00 s in Group C (P > 0.05), as shown in [Table 2]. Group C's mean duration of action was 70.14 ± 1.87 min, compared to Group A's 44.90 ± 2.45 min (P < 0.001).
Figure 1: CONSORT flow diagram

Click here to view
Table 1: Demographic characteristics of patients receiving atracurium and cisatracurium

Click here to view
Table 2: Comparison of atracurium and cisatracurium in terms of onset time

Click here to view


The mean duration of 25% recovery from a reversal in Group A was 32.4 ± 1.90 min which was significantly <49.46 ± 1.86 min of Group C (P < 0.001). The mean duration of recovery from reversal in Group C was 2.18 ± 0.82 min, compared to 1.8 ± 0.75 min in Group A (P = 0.02), as shown in [Table 3].
Table 3: Duration of action, 25% recovery, and recovery from reversal

Click here to view


The baseline values of the hemodynamics were comparable in both groups and remained so before intubation. After intubation, the rise in mean HR and mean arterial blood pressure (MABP) was found to be higher in Group A [Figure 2] and [Figure 3].
Figure 2: Mean heart rate

Click here to view
Figure 3: Mean arterial blood pressure

Click here to view


No signs of histamine release were noted in Group C, as compared to two cases in Group A [Table 4]. When compared according to the Copenhagen Consensus Scoring System [Table 5], we found that at the studied dose, cisatracurium gave optimal intubating conditions compared to atracurium.
Table 4: Adverse reaction comparison

Click here to view
Table 5: Intubating condition of cisatracurium and atracurium according to Copenhagen consensus scoring system

Click here to view



  Discussion Top


While selecting neuromuscular agents for tracheal intubation or skeletal muscle relaxation, an anesthesiologists' main aim is to select an agent with a fast onset of action, optimal intubating conditions, better hemodynamic stability, and good spontaneous reversal. In the present study, we have compared atracurium (0.5 mg/kg) and cisatracurium (0.15 mg/kg) in terms of onset time, duration of action, duration of 25% recovery, and duration of recovery from reversal. Hemodynamic parameters such as HR and mean arterial blood pressure and histamine release profiles were also being compared. Similar findings were observed in the previous studies.[8],[10],[11]

It has been reported earlier that the atracurium's 2 × ED95 dose has a faster onset of action as compared to cisatracurium's 4 × ED95 dose. Presumably, cisatracurium has greater potency than atracurium resulting in fewer molecules being administered even with the higher doses.[12] We found that the atracurium group's mean onset of action was insignificantly slower than the cisatracurium group (P = 0.075). El-Kasaby et al.[8] reported similar results in his study while comparing three groups of cisatracurium in different doses (2 × ED95, 4 × ED95, 6 × ED95 dose) with atracurium (2 × ED95 dose). They observed that higher doses of cisatracurium (4 × ED95 and 6 × ED95) provide a significantly faster onset of action. Bluestein et al.[13] also compared three different doses of cisatracurium (2 × ED95, 3 × ED95, 4 × ED95 dose) with atracurium (2 × ED95) and had similar results regarding the onset of action.

In our study, the mean duration of action in the cisatracurium group was 70.14 ± 1.87 min which was more and statistically significant (P = 0.001) compared to 44.9 ± 2.45 min in the atracurium group. Another study observed that increasing the cisatracurium dose (from 0.1 to 0.15 and 0.2 mg/kg) increases the mean time of clinically effective duration (45–55 and 61 min, respectively).[13]

Recovery of neuromuscular function occurs as the plasma concentration declines, and a greater part of this decrease occurs primarily because of distribution. Recovery comes to rely more on drug elimination than distribution (i.e., 25%–75% or greater).[2] In the present study, the mean duration of 25% recovery from reversal in the atracurium group was 32.4 ± 1.90 min which was significantly < 49.46 ± 1.86 min in the cisatracurium group (P < 0.001). Carroll et al.[11] observed the time from drug administration to 25% recovery with cisatracurium 0.15 mg/kg (51–59 min) was longer compared with both cisatracurium 0.1 mg/kg (45–48 min) and atracurium 0.5 mg/kg (47–48 min); however, the difference was insignificant. Shyamlal et al.[14] also found the mean 25% recovery in atracurium was 32.11 ± 3.2 min, and the mean 25% recovery in cisatracurium was 51.61 ± 2.5 (P < 0.05). They also found the time of recovery from a reversal in atracurium and cisatracurium was 2.1 ± 0.3 and 2.5 ± 0.2, respectively. Bergeron et al.[15] compared three different doses of cisatracurium 0.05 mg/kg, 0.15 mg/kg, and 0.3 mg/kg, and reported that the onset was not significantly different in adults, but the recovery time increased.

Lien et al.[16] and Basta et al.[2] concluded that the maximal MABP and HR changes of patients receiving cisatracurium were small and similar to those observed in patients receiving two times the ED95 of atracurium. Yazdanian et al.[17] reported comparable hemodynamic effects in atracurium and cisatracurium but found that cost-benefit was observed with atracurium.[17] Even with the higher doses of cisatracurium (8 × ED95), there was no histamine-release sign because of its stereospecific property.[18]

None of our participants had episodes of hypotension, bronchospasm, tachycardia, or urticaria. A study reported that atracurium releases histamine when doses of 0.5 mg/kg or more are injected rapidly. When plasma histamine levels increase to over 1000 pg/ml, a transient decrease in blood pressure, together with facial erythema, may be noted. The histamine-release can be prevented by slower injection from 30 to 60 s.[2]

Hosking et al.[19] stated that by using H1 and H2 receptor blockers before administering a large dose of atracurium, the histamine release's hemodynamic manifestations can be effectively prevented. Hughes and Chapple[20] stated that despite a 10–20 times increase in the plasma histamine levels, atracurium is not vagolytic and does not block the innervation by autonomic ganglia. Kumar et al.[21] reported that atracurium is not associated with urticaria formation in conventional doses, although significant hemodynamic changes may occur.


  Conclusion Top


Cisatracurium in a dose of 0.15 mg/kg had a faster onset and duration of action than atracurium 0.5 mg/kg. At this dose, cisatracurium provides optimal intubating condition, rapid neuromuscular blocking with longer duration of action, stable hemodynamic status, no signs of histamine release clinically, and without any residual muscle paralysis compared to atracurium.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ryalino C, Labobar OA, Wiryana M, Sinardja IK, Senapathi TG, Pradhana AP. Anaphylactic shock due to atracurium in a patient underwent general anesthesia. Open Access Maced J Med Sci 2020;8:60-2.  Back to cited text no. 1
    
2.
Basta SJ, Ali HH, Savarese JJ, Sunder N, Gionfriddo M, Cloutier G, et al. Clinical pharmacology of atracurium besylate (BW 33A): A new non-depolarizing muscle relaxant. Anesth Analg 1982;61:723-9.  Back to cited text no. 2
    
3.
Alhazzani W, Alshahrani M, Jaeschke R, Forel JM, Papazian L, Sevransky J, et al. Neuromuscular blocking agents in acute respiratory distress syndrome: A systematic review and meta-analysis of randomized controlled trials. Crit Care 2013;17:R43.  Back to cited text no. 3
    
4.
Wastila WB, Maehr RB, Turner GL, Hill DA, Savarese JJ. Comparative pharmacology of cisatracurium (51W89), atracurium, and five isomers in cats. Anesthesiology 1996;85:169-77.  Back to cited text no. 4
    
5.
Matthew RB, Cynthia AL, Steve Q, Abou-Donia MM, Abalos A, Eppich L, et al. The clinical neuromuscular pharmacology of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology 1995;82:1139-45.  Back to cited text no. 5
    
6.
Lepage JY, Malinovsky JM, Malinge M, Lechevalier T, Dupuch C, Cozian A, 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.  Back to cited text no. 6
    
7.
Cynthia AL, Matthew RB, Amy A, Larissa E, Steve Q, Martha M, et al. The cardiovascular effects and histamine releasing properties of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology 1995;82:1131-8.  Back to cited text no. 7
    
8.
El-Kasaby AM, Atef HM, Helmy AM, El-Nasr MA. Cisatracurium in different doses versus atracurium during general anesthesia for abdominal surgery. Saudi J Anaesth 2010;4:152-7.  Back to cited text no. 8
    
9.
Jirasiritham S, Tantivitayatan K, Jirasiritham S. A comparison of the efficacy of cisatracurium and atracurium in kidney transplantation operation. J Med Assoc Thai 2004;87:73-9.  Back to cited text no. 9
    
10.
Kaur H, Attri JP, Chatrath C, Kaur H, Kaur J. Recovery profile of atracurium versus cisatracurium. J Clin Diagn Res 2018;12:UC09-12.  Back to cited text no. 10
    
11.
Carroll MT, Mirakhur RK, Lowry D, Glover P, Kerr CJ. A comparison of the neuromuscular blocking effects and reversibility of cisatracurium and atracurium. Anaesthesia 1998;53:744-8.  Back to cited text no. 11
    
12.
Hunter JM. New neuromuscular blocking drugs. N Engl J Med 1995;332:1691-9.  Back to cited text no. 12
    
13.
Bluestein LS, Stinson LW Jr, Lennon RL, Quessy SN, Wilson RM. Evaluation of cisatracurium, a new neuromuscular blocking agent, for tracheal intubation. Can J Anaesth 1996;43:925-31.  Back to cited text no. 13
    
14.
Shyamlal T, Mridul P, Minnu P, Shalu P. Comparison of cis-atracurium with atracurium for balanced general anaesthesia: A randomized double blinded controlled study. MedPulse Int J Anesthesiol 2018;8:108-12.  Back to cited text no. 14
    
15.
Bergeron L, Bevan DR, Berrill A, Kahwaji R, Varin F. Concentration-effect relationship of cisatracurium at three different dose levels in the anesthetized patient. Anesthesiology 2001;95:314-23.  Back to cited text no. 15
    
16.
Lien CA, Belmont MR, Abalos A, Eppich L, Quessy S, Abou-Donia MM, et al. The cardiovascular effects and histamine-releasing properties of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology 1995;82:1131-8.  Back to cited text no. 16
    
17.
Yazdanian F, Ghandi I, Toutounchi Z. Comparison of hemodynamic effects of atracurium and cisatracurium in patients undergoing coronary artery bypass grafting. J Iran Soc Anaesthesiol Intensive Care 2008;61:56-66.  Back to cited text no. 17
    
18.
ShangGuan W, Lian Q, Li J, Gao F. Clinical pharmacology of cisatracurium during nitrous oxide-propofol anesthesia in children. J Clin Anesth 2008;20:411-4.  Back to cited text no. 18
    
19.
Hosking MP, Lennon RL, Gronert GA. Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high-dose atracurium for rapid sequence endotracheal intubation. Anesth Analg 1988;67:1089-92.  Back to cited text no. 19
    
20.
Hughes R, Chapple DJ. The pharmacology of atracurium: A new competitive neuromuscular blocking agent. Br J Anaesth 1981;53:31-44.  Back to cited text no. 20
    
21.
Kumar A, Jain AK, Gupta S. Frequency of occurrence of urticaria after the administration of atracurium. Int J Res Dermatol 2016;2:118-21.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Patients and Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed316    
    Printed18    
    Emailed0    
    PDF Downloaded38    
    Comments [Add]    

Recommend this journal