|Year : 2022 | Volume
| Issue : 4 | Page : 259-267
Comparison of rapid intubating conditions between rocuronium and cisatracurium: a randomized double-blind study
Rohini Bhat Pai, Anisha Deulkar, Deependra Kambli, Bhagyashri Kanekar, Pragati Volvoikar, Hemant Parsekar, Shaila Kamat
Department of Anaesthesiology, Goa Medical College, Bambolim, Goa, India
|Date of Submission||03-Jan-2022|
|Date of Decision||11-Apr-2022|
|Date of Acceptance||10-Jul-2022|
|Date of Web Publication||29-Dec-2022|
MD, DNB Rohini Bhat Pai
Department of Anaesthesiology, Goa Medical College, Bambolim 403202, Goa
Source of Support: None, Conflict of Interest: None
Background and aims Cisatracurium has many advantages over other nondepolarizing muscle relaxants; however, for rapid intubation, rocuronium is the preferred drug in lieu of succinylcholine. The aim of this study was to compare the onset time and intubating conditions at 90 s using 0.3 mg/kg cisatracurium (6× ED95) versus 1.2 mg/kg rocuronium (4× ED95).
Material and methods The study was conducted at a tertiary care hospital as a randomized double-blind prospective study after obtaining the ethical committee clearance. A total of 60 patients were randomly assigned to receive 1.2 mg/kg rocuronium (4× ED95) or 0.3 mg/kg cisatracurium (6× ED95) after premedication with fentanyl-midazolam and induction with propofol-sevoflurane. Laryngoscopy and intubation were done at 90 s. Primary outcomes assessed were laryngoscopy and intubation conditions and onset times. The Student t test was used to compare prospective, repeated measures. χ2 test was used to test the significance of difference for qualitative variables.
Results The onset of action of the muscle relaxant was predicted by measuring train-of-four ratio and was found to be significantly longer in the cisatracurium group (149.50±25.064 s) than in the rocuronium group (101±s) (P<0.05). Although the intubating conditions were better in the rocuronium group, cisatracurium also provided good to excellent intubation conditions at 90 s.
Conclusion Cisatracurium can be used to intubate the trachea at 90 s at a dose of 0.3 mg/kg in patients premedicated with fentanyl-midazolam and induced with propofol-sevoflurane, while maintaining hemodynamic stability, without increasing the incidence of adverse effects.
Keywords: cisatracurium, rapid intubation, rocuronium
|How to cite this article:|
Bhat Pai R, Deulkar A, Kambli D, Kanekar B, Volvoikar P, Parsekar H, Kamat S. Comparison of rapid intubating conditions between rocuronium and cisatracurium: a randomized double-blind study. Res Opin Anesth Intensive Care 2022;9:259-67
|How to cite this URL:|
Bhat Pai R, Deulkar A, Kambli D, Kanekar B, Volvoikar P, Parsekar H, Kamat S. Comparison of rapid intubating conditions between rocuronium and cisatracurium: a randomized double-blind study. Res Opin Anesth Intensive Care [serial online] 2022 [cited 2023 Mar 26];9:259-67. Available from: http://www.roaic.eg.net/text.asp?2022/9/4/259/365786
| Introduction|| |
Muscle relaxants are essential components in the armamentarium of anesthesiologists. Rocuronium at a dose higher than 0.6 mg/kg is the preferred muscle relaxant in lieu of succinylcholine in cases with a high risk of aspiration . Although the excellent rapid intubating conditions with rocuronium cannot be disputed, having an alternative muscle relaxant for rapid intubation may be necessary in certain situations wherein using succinylcholine and rocuronium may have undesirable outcomes or are contraindicated. Increased dose of rocuronium is known to hasten the onset of action . We hypothesized that by increasing the dose of cisatracurium to 0.3 mg/kg (6× ED95), we might be able to intubate the trachea at 90 s, thus demonstrating its noninferiority compared with the ‘gold standard’ rocuronium for rapid sequence induction and intubation (RSII).
Our primary aim of conducting the study was to compare the onset of action and intubating conditions at 90 s between 1.2 mg/kg rocuronium (4× ED95) and 0.3 mg/kg cisatracurium (6× ED95).
| Materials and methods|| |
This study was conducted in a tertiary hospital for a period of 6 months. After obtaining ethical committee clearance from the Hospital’s ethical committee, 60 patients with American Society of Anesthesiologists I and II aged between 18 and 60 years, scheduled for elective surgery under general anesthesia were recruited for the study.
Based on the article by Lee et al. , comparison of cisatracurium and rocuronium was done with the key parameter of onset time, with 95% confidence interval and 95% power of the study, considering a SD of 52 s with a mean difference of 35 s between the two groups. The sample size calculated was 24 using the following formula:
Where Zα= 1.96, Zβ=1.28, σ= 52, and μ1-μ2 =35.
To compensate for any excluded cases, we selected a sample size of 30 cases per group; refer Consort Chart in [Figure 1].
The exclusion criteria were a history of smoking, bronchial asthma, and chronic obstructive pulmonary disease; respiratory tract infection during the past 6 weeks; difficult intubation; pregnant patients; patients with BMI more than 30 kg/m2; patient refusal; patients with impaired kidney or liver functions; and hypertensive patients on beta-blockers.
After obtaining informed consent from the patients, randomization was done using a table of random numbers, and the patients were randomly allocated to one of the two groups: group R (n=30) received rocuronium 1.2 mg/kg (4× ED95), and group C (n=30) receive cisatracurium 0.3 mg/kg (6× ED95). Randomization and allotment to the two groups was done by an anesthesiologist who did not participate in other aspects of the study. The two experienced anesthesiologists who were allotted to intubate the patients and/or noted down the findings were blinded to the drug.
Standard monitoring, which included noninvasive blood pressure, ECG, and pulse oximetry, was applied and assessed continuously. Before the induction of anesthesia, surface electrodes were placed over the ulnar nerve at the wrist after careful cleansing of the skin to measure the train-of-four (TOF) ratio. The negative electrode was placed near the wrist and the positive electrode proximally, with a distance of 3–5 cm between the center of the electrodes. The transducer of the TOF-Watch SX was placed in the Hand Adapter. The fingers were immobilized using an elastic band and adhesive while the transducer was firmly fixed to the thumb. The blood pressure cuff was never attached to the monitored limb. After ascertaining loss of consciousness, neuromuscular transmission was monitored by recording the evoked twitch tension of the adductor pollicis muscle in response to supramaximal TOF stimuli with a square wave stimulus set at a current of 50 mA and duration of 0.2 ms at intervals of 15 s after automatic calibration. The upper limb that was used for monitoring TOF was wrapped from hand till the elbow to avoid hypothermia.
For premedication, intravenous midazolam 1.5–2 mg and intravenous fentanyl 2 µg/kg were given 5 min before induction. Patients were induced with intravenous propofol 2 mg/kg, 2% sevoflurane in 8 l of O2, followed by one of the nondepolarizing muscle relaxant, cisatracurium 0.3 mg/kg or rocuronium 1.2 mg/kg, given over 10 s.
Laryngoscopy was performed by one of the two allotted anesthesiologists at 90 s after the muscle relaxant, and the trachea was intubated only if the jaw and vocal cords were completely relaxed. The intubation conditions were recorded according to the score by Cooper et al.  ([Table 1]).
Intubation conditions  were classified as follows: excellent score: 8–9, good score: 6–7, fair score: 3–5, and poor score: 0–2.
TOF ratio was monitored until it was 0. After intubation, anesthesia was maintained with oxygen in nitrous oxide and 2.0 vol% sevoflurane (inspired).
The onset time was defined as the time interval from the end of neuromuscular blocking agent administration to the maximal suppression of T1%, that is, TOF=0.
Measurements of the heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the mean arterial pressure (MAP) were made just before induction, immediately before tracheal intubation, and at 1 and 5 min after tracheal intubation. Vasopressor ephedrine/phenylephrine was administered if the SBP decreased below 90 mmHg or MAP decreased below 60 mmHg. Any adverse effects suggestive of histamine release such as hypotension, tachycardia, erythema, and bronchospasm were noted. Statistical analysis was performed using IBM SPSS software (IBM, SPSS software, India), version 22. Data were expressed as mean±SD or as absolute values. The Student t test was used to compare prospective, repeated measures (age, weight, mean blood pressure, heart rate, and onset time) paired within groups and unpaired between groups. χ2 test was used to test the significance of difference for qualitative variables. The level of significance was set at probability value (P<0.05).
| Results|| |
There were no statistically significant differences in the demographic variables between the groups ([Table 2]). All of the patients could be successfully intubated at the first attempt. The intubating conditions were excellent in all of the patients in the rocuronium group, whereas in the cisatracurium group, 86.66% (26 patients) had excellent intubating conditions and 13.33% (four patients) had good intubating conditions ([Figure 2]). This difference was statistically significant (P<0.05). The onset time of the cisatracurium group was significantly longer as compared with the rocuronium group ([Figure 3]).
|Figure 2 Comparison of intubating conditions between the two groups: the intubation conditions as recorded according to the Cooper et al. score±SD were better in the rocuronium group as compared with the cisatracurium group. This difference was statistically significant (P<0.05).|
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|Figure 3 Comparison of onset time between the two groups: the difference between the two groups, was found to be statistically significant (P<0.05). The onset±SD was significantly longer in the cisatracurium group compared to rocuronium group.|
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There were no statistically significant differences in the heart rates at any time between the two groups (P<0.05) ([Table 3] and [Figure 4]). The heart rate decreased from the baseline after administration of induction agents in both the groups and increased from the baseline after intubation in both groups.
The SBP ([Table 3] and [Figure 5] and [Figure 6]), DBP ([Table 3] and [Figure 4]), and MAP ([Table 3] and [Figure 7]) before induction, after induction, as well as before and after intubation were assessed, and there was no statistically significant difference between the two groups (P<0.05). There was a decrease in SBP (>20% of baseline but above 90 mmHg), as well as DBP and MAP values (>20% of baseline but above 60 mmHg) after induction and increase in the SBP, DBP, and MAP after intubation in both groups. However, none of the patients needed any intervention for the decrease or increase in blood pressure.
There was no incidence of adverse effects attributable to histamine release such as hypotension, tachycardia, erythema, and bronchospasm in either of the groups ([Table 4]).
| Discussion|| |
RSII involves intubating the trachea rapidly while preventing aspiration. The main aim of the technique being reduction in the time interval between loss of protective airway reflexes and tracheal intubation with a cuffed endotracheal tube. Although the onset time of cisatracurium was significantly longer than rocuronium, excellent to good intubating conditions could be obtained at 90 s using 6× ED95 dose of cisatracurium in patients premedicated with fentanyl-midazolam and induced with propofol-sevoflurane without any notable adverse effects.
Depending on the volume and pH of the fluid entering the bronchial tree, the consequences of aspiration vary from subclinical pneumonitis to progressive respiratory failure . Indications for rapid sequence intubation include altered mental status, gastrointestinal disorders, incompetent lower esophageal sphincter, pregnancy, and metabolic disturbances . Succinylcholine is the traditionally used neuromuscular blocking agent in RSII, which has a rapid onset and offset of action, but it is associated with many adverse effects, some of which can be life-threatening .
With the use of propofol and rapidly acting opioid drugs like alfentanil and remifentanil, it might be tempting to attempt intubation without the use of neuromuscular blocking agents, but it is important to note that inadequate intubating conditions can lead to airway trauma, intubation failure, and difficulty of ventilation ,.
Rocuronium 1.2 mg/kg provides intubation conditions similar to succinylcholine during rapid sequence intubation . The absolute contraindication to rocuronium is allergy; however, caution must be exerted in people with myasthenia gravis or myasthenic syndrome, hepatic disease, and neuromuscular disease, as the duration of action may be profoundly increased . In patients with previous history of anaphylaxis to rocuronium and vecuronium, best options are avoiding the use of muscle relaxants or using cisatracurium because these patients have shown the lowest cross-reactivity to cisatracurium .
Cisatracurium offers many advantages like Hofmann elimination, which accounts for 80% of the clearance and cardiovascular stability, which makes it a good choice in patients with renal or hepatic function impairment and in the elderly . Cisatracurium being about four or five times as potent as atracurium, about five times less laudanosine is produced and accumulation of this metabolite is not thought to be of any consequence in clinical practice . As per literature, there was no evidence of histamine release with the use of cisatracurium up to 5× ED95 .
However, despite these advantages, the onset effect of cisatracurium was too slow to provide good conditions for intubation in less than 2 min, even after a dose, which is twice the ED95 .
The speed of onset of neuromuscular blockade is inversely proportional to the potency of nondepolarizing neuromuscular blockers. As rocuronium has a molar potency (ED95) of 0.54 μM/kg, which is about 9% that of cisatracurium, rapid onset effect of rocuronium (at the adductor pollicis) is expected . Increasing the dose of rocuronium from 0.6 mg/kg (twice the ED95) to 1.2 mg/kg (four times the ED95) shortened the onset time of complete neuromuscular blockade from 89±33 s (mean±SD) to 55±14 s .
Administering a higher dose of cisatracurium should thus hasten the onset of action as a large dose will lead to binding to a large number of nicotinic acetylcholine receptors .
Rocuronium at 4ED95 is 1.2 mg/kg and an equivalent dose of cisatracurium is 0.2 mg/kg (4ED95). In a study by Mandal , the patients receiving 0.2 mg/kg could be intubated at 90 s and those receiving 0.25 mg/kg could be intubated at 75 s. Another study had concluded that cisatracurium at 0.3 mg/kg (6ED95) provided excellent intubating conditions at 2±1.2 min . Yet another study had compared 0.3 mg/kg (modified dose) versus 0.4 mg/kg (high dose) cisatracurium and concluded that both the doses had the same effect in providing appropriate conditions for rapid sequence intubation after 90 s . They recommended using 0.3 mg/kg cisatracurium for RSII. Thus, the results in the aforementioned studies varied regarding the ideal time of excellent intubation conditions with the different doses of cisatracurium. In the current study, intubating conditions were unsurprisingly excellent in all of the patients in the rocuronium group, whereas in the cisatracurium group, 86.66% (26 patients) had excellent intubating conditions and 13.33% (four patients) had good intubating conditions. We did not have any difficulty in intubating any of the patients in either of the groups. However, the onset time of cisatracurium was significantly longer than rocuronium ([Table 4]).
Ideal intubation conditions for a rapid sequence scenario required the vocal cords to be fully relaxed for intubation in 90 s. In case of coughing or bucking, the consequences can be extremely hazardous in a full-stomach patient. There is no evidence that there is an increased incidence of aspiration or desaturation as long as tracheal intubation is accomplished within 90 s ; therefore, we reasoned that attempting intubation at 90 s by using the higher dose of 0.3 mg/kg (6ED95) cisatracurium would improve our chances of successfully intubating the patients.
The greater muscle blood flow per gram of muscle at the diaphragm or larynx results in delivery of a higher peak plasma concentration of drug to the central muscle in the brief period before rapid redistribution due to which the onset of blockade occurs 1–2 min earlier in the larynx than at the adductor pollicis .
Similarly, in the study by Lee et al. , the onset times after rocuronium (0.9 mg/kg) and cisatracurium (0.15 mg/kg) were 102±49 and 197±53 s, respectively. They used a smaller dose of 0.15 mg/kg of cisatracurium, supplementing a remifentanil-propofol combination and found that it provided excellent or good endotracheal intubating conditions at 90 s in 96% of patients, a rate similar to those achieved by rocuronium 0.9 mg/kg (100%). Although the difference in the onset time of both the drugs was significant, there was no case in either of the groups wherein intubation could not be achieved in 90 s. They concluded that maximal suppression of T1 in TOF was not a good indicator for intubation. We attempted intubation using clinical assessment-guided tracheal intubation, after ensuring complete relaxation of the jaw and vocal cords.
Propofol was compared with thiopental for RSII in combination with rocuronium 0.6 mg/kg, and the propofol group was found to have superior intubating conditions . This could be attributed to the ability of propofol to suppress the pharyngeal and laryngeal reflexes more effectively than any other induction drug . The effects of both cisatracurium and rocuronium-induced neuromuscular block are significantly enhanced during sevoflurane compared with propofol total intravenous anesthesia . We used propofol-sevoflurane to improve the intubating conditions provided by both the muscle relaxants.
The use of fentanyl (2 µg/kg) before thiopentone, propofol or etomidate, and succinylcholine has shown to result in more stable conditions for RSII than without the use of fentanyl . As the peak effect of intravenous fentanyl is 5 min , we timed the fentanyl premedication to coincide with the intubation. Hemodynamic responses to laryngoscopy and tracheal intubation were significantly attenuated if tracheal intubation was done following complete paralysis of laryngeal muscles .
In our study, the heart rates between the two groups were not statistically different at any recorded time. Although there was a decrease in SBP, DBP, and MAP postinduction, this fall could be attributed to induction agents and the decrease was not significant enough to warrant treatment with vasopressors. This is similar to another study, which showed that changes in heart rate and MAP pressure 5–20 min later were not statistically significant with the administration of 4 ED95 and 6 ED95 doses of cisatracurium .
Among the anesthetic agents, opioids, followed by nondepolarizing muscle relaxants are most commonly implicated in anaphylactic reactions . No signs of histamine release, which include tachycardia, hypotension, bronchospasm, and flushing, were noted in either of the groups ([Table 4]). Similarly, El-Kasaby et al.  concluded that none of the patients in the cisatracurium group including the ones receiving 4× ED95 and 6× ED95 showed any signs of histamine release.
Although earlier studies had found cisatracurium to be devoid of histamine release in doses up to 5× ED95 , later anaphylactoid /anaphylactic ,,,, reactions to the drug have been reported. We did not encounter any signs suggestive of histamine release during the course of this study; however, it would be prudent to exercise caution.
The study has a few limitations, as the patients enrolled in the study were elective cases. The onset of action and intubating conditions using the higher dose of cisatracurium will have to be studied in emergency full-stomach patients and the duration of action and residual muscle relaxation using the higher dose of muscle relaxants in patients with liver and kidney diseases will have to be studied.
| Conclusion|| |
Excellent to good intubating conditions with hemodynamic stability can be obtained at 90 s using 6× ED95 dose of cisatracurium in elective patients premedicated with fentanyl-midazolam and induced with propofol-sevoflurane.
The authors thank Dr M.S. Kulkarni, Associate Professor, Statistics and Demography, Department of PSM, Goa Medical College, for his valuable guidance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4]