A Comparative Study of Atracurium and Cisatracurium in paediatric cleft Lip and Cleft palate surgeries

 

Dr Shruti Shrey, Dr. Amol Singam*

Department of Anaesthesiology, AVBRH, JNMC, Sawangi (M), Wardha-442001, Maharashtra.

 

ABSTRACT:

General anaesthesia with intubation with RAE tube is preferred in children undergoing cleft lip and palate surgeries. Neuromuscular blocking drugs (NMBDs), are given to infants and children to attain ideal intubating conditions by providing adequate muscle relaxation. In contrast to routinely used atracurium,cisatracurium is comparatively a newer drug with lesser histamine release. The study was designed with the aim to compare the efficacy of atracurium (2×ED₉₅) and cisatracurium (4×ED₉₅).90 patients, 6 months-5 years , ASA class I &II were randomly allocated to cisatracurium and atracurium group. After administration of induction agent, dose of neuromuscular blocking drug atracurium 0.5mg/kg or cisatracurium 0.2mg/kg was given to the patients. The intubating conditions were graded using ‘Cooper et al’ scoring system.Neuromuscular blockade was assesed using train of four ratio. Alongwith intubating conditions, onset and duration of action, hemodynamic effects, and signs of histamine release were measured in both the groups.In the atracurium group the mean score according to ‘Cooper et al’scale was 6.86±0.54,whereas in the cisatracurium group it was 8.12±0.64, the difference between the groups was statistically significant.Time of onset was found to be 2.7±0.12 minutes in the cisatracurium group and 3.28±0.64 minutes in the atracurium group.Duration of action was 64.6±6.18minutes in the cisatracurium group as compared to 35.4±4.64minutes in the atracurium group.Cisatracurium(0.2mg/kg) is more efficacious as compared to atracurium(0.5mg/kg)with respect to intubating conditions, it has a faster onset of action, good intraoperative hemodynamic parameters, longer duration of action with no side effects.

 

 

INTRODUCTION:

Cleft lip and palate is one of the commonest congenital deformities. Anaesthesia for primary cleft lip and palate surgery may be successfully provided in a wide range of environments from the well-equipped dedicated paediatric hospital to isolated resource poor clinics. General anaesthesia with intubation with RAE tube is preferred in pediatric age group undergoing cleft lip and palate surgeries.[1,2].Neuromuscular blocking drugs are given to infants and children to attain ideal intubating conditions by providing adequate muscle relaxation, to reduce the quantity of anaesthetic agent required and to facilitate controlled ventilation. [3]

 

 

Atracurium and Cisatracurium are intermediate acting nondepolarizing NMB. Cisatracurium is approximately four times as potent as atracurium.[4]. In contrast to atracurium, cisatracurium is devoid of chemically mediated histamine release [5,6]. Routinely atracurium is used for neuromuscular blockade in most pediatric surgeries. Cisatracurium is comparatively a newer drug with lesser histamine release. According to the literature published earlier comparison of the intubating conditions according to the ‘Cooper et al scale’[7] between 2 ED95 of atracurium and cisatracurium showed that atracurium provided better intubating conditions than cisatracurium. With regards to the onset of action, 2×ED₉₅ dose of atracurium had more rapid onset of action as compared to the equivalent dose of cisatracurium (2×ED₉₅) [8,9]. The study was designed with the aim to compare atracurium and cisatracurium with respect to intubating conditions, onset of action,duration of action, hemodynamic effects, and signs of histamine release.

 

MATERIALS AND METHODS:

The study was carried out in the department of Anaesthesiology AVBRH ,a unit of Jawaharlal Nehru Medical College Sawangi Wardha over a period of one year from march 2018 to march 2019. Institution ethics committee approval and written informed consent from patients' guardians were obtained. The preoperative anaesthetic evaluation was done using history, general and systemic examination and routine blood investigations. Patients of age less than 6 months and more than 5 years, weighing less than 5kgs,malnourished,ASA class III and above, those with significant airway anomalies, or suffering from acute respiratory illness were excluded from the study. Sample size calculation was performed using openepi.com keeping power at 80% and confidence intervals at 95%.The selected patients were randomly allocated into two groups of 45 each based on a computer generated random number table.

 

GROUP A: Atracurium with initial dose of 0.5 mg/kg(2*ED₉₅)

GROUP C: Cisatracurium with initial dose of 0.2 mg/kg (4*ED₉₅)

 

In the preoperating room, an intravenous access was achieved using 24G OR 22G cannula. Inj. Ringer Lactate infusion started at the rate of 10ml/kg. Inection midazolam 0.05mg/kg IV was given to prevent seperation anxiety of the child from the parents. On arrival in the operating room monitoring equipments were attached to the patient including three lead ECG, non-invasive blood pressure,pulse oximetry, capnography and temperature probe. The Datex relaxograph (Type-NMT-100-23-01, S/N: 37541)was used for neuromuscular monitoring. Patients were administered Inj. Glycopyrrolate 4μg/kg i.v.,Inj Ranitidine 10 mg i.v., Inj. Ondansetron 0.1mg/kg i.v. Patients were preoxygenated with 100% oxygen for 3 min and induced with 1mcg/kg fentanyl, 1.5-2mg/kg propofol. Anaesthesia was maintained with a mixture of 50% N₂O in O₂ and sevoflurane with assisted ventilation.After attaining a stable base line of vital hemodynamic parameters, the muscle relaxant was given to patients according to the previously mentioned initial doses for each group and injected intravenously within 5-10 s. Neuromuscular monitoring was carried out after obtaining the control values by supramaximal stimulus (70mA) from relaxograph (2 Hz/0.5s; pulse width 0.2 ms) every 15s to stimulate the ulnar nerve via surface electrodes. The onset time was determined as the interval from the end of muscle relaxant injection until the maximal suppression of T₁% after which, endotracheal intubation was attempted using proper size RAE tube. The condition of intubation was assessed and recorded according to ‘Cooper et al’ scoring system [7], which is shown in the following table:

 

Table 1: Cooper et al scoring system.

Score	Jaw relaxation	Vocal cord	Response to intubation
0	Poor	Closed	Severe coughing/bucking
1	Nominal	Closed	Mild cough
2	Moderate	Moving	Slight diaphragmatic movement
3	Good	Open	None

 

An intubation score of 8-9 was considered excellent, 6-7 good, 3-5 poor and 0-2 bad. Good to excellent intubation score were taken as clinically acceptable.

 

Anesthesia was maintained with a mixture of 50% N₂O in O₂, sevoflourane (1.8-2 MAC), boluses of the muscle relaxant (10% of the initial dose) with 25% recovery of response to T₁%.The duration of action of the muscle relaxant was defined as the time from the end of injection of the drug until 25% recovery of T₁%. Neuromuscular blockade after induction was monitored and recorded every 5 min by supramaximal train-of-four (TOF) stimuli. Patients were put on the Datex-Ohmeda^™ ventilator and normocapnia was maintained throughout. Patients were monitored for any signs of histamine release clinically through skin changes graded as flush, erythema, or wheals and presence of any hemodynamic changes or bronchospasm. Intra-operative hemodynamic changes were continuously monitored including: heart rate (HR), mean arterial blood pressure (MABP) every 15 min, oxygen saturation (SO₂), and end tidal CO₂.Body temperature maintained between 35 and 37°C by means of warmed IV fluids and warming blankets. At the end of operation reversal was achieved by administration of neostigmine 0.05 mg/kg and 8µg/kg glycopyrrolate mixture through slow IV injection. TOF-ratio >0.9 was considered adequate for safe extubation of the trachea.

 

RESULTS:

Demographically both the groups were comparable without any statistically significant difference (table 2).

 

Table 2: Demographic characteristics of the studied patients

	GROUP A	GROUP C	p value
AGE (years)	4.8±0.89	4.6±0.68	0.23
SEX
Male	56.24%	46.76 %	0.33
Female	42.76%	57.24 %	0.26

 

Both the groups were compared in terms of change in heart rate and mean arterial blood pressure post intubation with respect to baseline. It was found that there was significant increase in HR, MABP post intubation when compared to baseline in the atracurium group, whereas there was no significant change in HR, MABP in the cisatracurium group (Table 3, Table 4).

Table 3: Heart Rate (beats/min)

Group	Baseline	After injection of muscle relaxant	After attempt of intubation	P value
Atracurium	98.8±6.65	96.4±5.84	108.8±7.88	<0.0001 (S)
Cisatracurium	94.4±7.28	98.6±6.24	96.7±5.90	0.1034 (NS)

 

Table 4: Mean Arterial Blood Pressure (mmHg)

Group	Baseline	After injection of muscle relaxant	After attempt of intubation	p value
Atracurium	89.6±9.88	93.4±8.86	97.5±5.65	<0.0001 (S)
Cisatracurium	90.86±7.44	92.36±4.84	93.66±8.12	0.0916 (NS)

S: Statistically significant difference versus Baseline reading (P-value < 0.05)

 

Time of onset was found to be 2.7±0.12 minutes in the cisatracurium group which was lower as compared to 3.28±0.64 minutes in the atracurium group and the difference between the two groups was found to be statistically significant. Regarding the duration of action, cisatracurium group had a duration of action of 64.6±6.18minutes which was longer as compared to atracurium group in which the duration of action was 35.4±4.64minutes and the difference being statistically significant(table 5).

 

Table 5:Onset time and duration of action (minutes)

Group	Onset time(minutes)	Duration of action(minutes)
Atracurium	3.28±0.64	35.4±4.64
Cisatracurium	2.70±0.12	64.6±6.18

 

The intubating conditions were graded using ‘Cooper et al’ scoring system. In the atracurium group the mean score was 6.86±0.54, whereas in the cisatracurium group it was 8.12±0.64, the difference between the groups was statistically significant(table 6)

 

Table 6: ‘Cooper et al’ score

Group	Atracurium	Cisatracurium	p vlaue
Score	6.86±0.54	8.12±0.68	<0.0001 (S)

 

DISCUSSION:

In our study two non-depolarising muscle relaxants, Atracurium and Cisatracurim besylate were compared with respect to onset of action, duration of action, intubating conditions, hemodynamic parametres such as heart rate and mean arterial blood pressure. The two groups of the study were matched regarding patients’ age and sex and were demographically comparable.

 

In the present study onset of action was found to be 2.7±0.12 minutes in the cisatracurium group which was lower as compared to 3.28±0.64 minutes in the atracurium group and the difference between the two groups was found to be statistically significant. In a study conducted by El –kasaby et al similar results were obtained while comparing 3 groups of cisatracurium in different doses(2×ED95, 4×ED95, 6×ED95 dose) with 1 group of atracurium (2×ED95 dose). It was observed that with the higher doses of cisatracurium (4×ED95 and 6×ED95) onset of action was significantly faster than with atracurium [9]. Bluestein and colleagues also compared 3different doses of cisatracurium (2×ED95, 3×ED95, 4×ED95 dose) with 1 group of atracurium (2×ED95) and had similar results regarding mean time of onset of action [8]. M.T. Carroll et al, also had similar observations in their study [10]. Another study was conducted by Mellinghoff et al where 80 patients were randomized to receive either cisatracurium or atracurium and the time course of neuromuscular block was compared. The onset time was 3.1±1.0 minutes with cisatracurium and 2.3±1.1 minutes with atracurium (p=0.008). Mean onset of action in Cisatracurium besylate group was 3.75 minutes which was faster as compared to 4.79 minutes in Atracurium besylate in a study conducted by Rochana G Bakhshi et al which is consistent with our study [11].

 

In our study mean duration of action of 1st dose in Cisatracurium group was 64.6±6.18minutes with a dose of 0.2mg/kg which was more and statistically significant as compared to 35.4±4.64 in the atracurium group with dose of 0.5mg/kg. Similar results were obtained by El –kasaby et al where 65.5±10.5minutes was the mean duration of action in the cisatracurium group with the dose of 0.2mg/kg as compared to 44.4±4.13 minutes in the atracurium group [9]. C.E. Smith, compared duration of action of cisatracurium 0.1mg/kg and atracurium 0.5mg/kg and found no statistical significance[12]. Bluestein and colleagues observed that increasing the dose of cisatracurium (from 0.1 to 0.15 and 0.2 mg/kg) increases the mean time of duration of action (45 to 55 and 61 min, respectively) [8].

 

With respect to intubating conditions, which was compared using the ‘Cooper et al’ scoring system [7] we found that cisatracurium group was better as compared to atracurium group. In the study conducted by El –kasaby et al it was found that 6×ED95 dose of cisatracurium was statistically significant versus the atracurium dose with higher percentages of patients with excellent condition of intubation. 4×ED₉₅ and 6×ED₉₅ doses of cisatracurium were significantly better than 2×ED₉₅ dose of cisatracurium [9].

 

In the present study with the dose of cisatracurium (0.2mg/kg) there was no signs of histamine release while skin rashes were noted in 3 patients who received atracurium (0.5mg/kg).Similar results were obtained by El-kasaby et al. In their study it was found that with any doses of cisatracurium no signs of histamine release were noted, while with atracurium 2 cases developed signs of histamine release (1 case showed flush and the other case showed erythema) [9].

 

In our study it was found that there was significant increase in heart rate and mean arterial blood pressure post intubation as compared to baseline in the atracurium group as compared to ccisatracurium group. Our results are consistent with a similar study conducted by El-kasaby et al where there was a statistically significant increase in HR, MABP post intubation when compared to baseline and post injection of 2×ED₉₅ dose of atracurium [10]. In a study conducted by Yazdanian F et al hemodynamic effects were comparable in atracurium and cisatracurium patients but cost benefit was observed with atracurium [13].

 

CONCLUSION:

Our study concluded that cisatracurium is superior as compared to atracurium with respect to intubating conditions. Cisatracurium(0.2mg/kg) has a faster onset of action, good intraoperative hemodynamic parameters, longer duration of action with lesser side effects as compared to atracurium (0.5mg/kg).Like previous several studies, our study led to the conclusion that cisatracurium even with the higher dose is safe and more efficacious as compared to atracurium.

 

REFERENCES:

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2.      Sen J, Sen B. Airway management: A comparative study in cleft lip and palate repair surgery in children. Anesth Essays Res. 2014;8(1):36–40.

3.      Neuromuscular blocking drugs in infants and children George H Meakin, MD FRCA Continuing Education in Anaesthesia Critical Care & Pain, 2007;7(5):143-7.

4.      Ronald D. Miller’s Anaesthesia 8th ed.Millers Anaesthesia 7thed Churchill Livingston 2010 Pg.1129,1130, table 34-2

5.      Doenicke A, Soukup J, Hoerneck R, Moss J. The lack of histamine release with cisatracurium: a double-blind comparison with vecuronium. Anesth Analg 1997; 84: 623—8.

6.      Doenicke A, Czeslick E, Moss J, Hoernecke R. Onset time, endotracheal intubating conditions, and plasma histamine after cisatracurium and vecuronium administration. Anesth Analg 1998; 87: 434—8.

7.      Cooper R, Mirakhur RK, Clark RSJ, Boules Z. Comparison of intubating conditions after administration of Org 9426 (rocuronium) and suxamethonium. Br J Anaesth 1992; 69: 269-73.

8.      Bluestein LLS, Stinson LW, Lennon RL, Quessy SN, Wilson RM. Evaluation of cisatracurium, a new neuromuscular blocking agent, for tracheal intubation. Can J Anaesth 1996; 43: 925—31.

9.      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(3):152–157.

10.   .M. T. Carroll,1 R. K. Mirakhur,1 D. W. Lowry,1 K. C. McCourt1 and C. Kerr2, A comparision of the neuromuscular blocking effects and reversibility 0f cisatracurium and atracurium, Anesthesia 1998,53,744.

11.   Dr Rochana G Bakhshi, Dr Anisha Nagaria, Dr Shubha N Mohite, Dr Gurlyn Ahluwalia, Comparison of Neuromuscular Blockade and Recovery Characterstics of Cisatracurium Besylate versus Atracurium Besylate in Adult Surgical Patients. JMSCR 2016, 4( 12),14613-21.

12.   Smith CE, van Miert MM, Parker CJ, Hunter JMA comparison of the infusion pharmacokinetics and pharmacodynamics of cisatracurium, the 1R-cis 1'R-cis isomer of atracurium, with atracurium besylate in healthy patients. Anaesthesia. 1997 Sep;52(9):833-41.)

13.   Yazdanian f.,ghandi i.,toutounchi z., comparison of hemodynamic effects of atracurium and cisatracurium in patients undergoing coronary artery bypass grafting. Journal of iranian society anaesthesiology and intensive care 2008 , Volume 30 , Number 61; Page(s) 56- 66.

 

 

Accepted on 27.10.2019           © RJPT All right reserved

Research J. Pharm. and Tech 2020; 13(2):867-870.