|Year : 2012 | Volume
| Issue : 1 | Page : 62-68
Comparison of intubating conditions following administration of low-dose rocuronium or succinylcholine in adults: A randomized double blind study
Ramkumar Venkateswaran, Souvik Chaudhuri, KM Deepak
Department of Anaesthesiology, Kasturba Medical College, Manipal, India
|Date of Web Publication||14-Nov-2012|
Bilva Kunja, Ground Floor, House No.01, Eshwarnagar, Manipal, Karnataka - 576 104
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Though rocuronium has a rapid onset of neuromuscular blockade like succinylcholine without the latter's adverse effects, its use is limited due to its prolonged action.
Aim: Aim was to evaluate whether reducing the intubating dose of rocuronium shortens its duration of action, yet provides clinically acceptable intubating conditions.
Settings and Design: tt was a prospective, randomized, and double blind trial.
Materials and Methods: 100 American Society of Anaesthesiologists Physical Status (ASAPS) I or II patients aged between 18-65 years scheduled for elective surgery were randomly allotted one of the four rocuronium groups (rocuronium dose of 0.3 mg/kg intubated at 60 s or at 90 s, rocuronium 0.6 mg/kg intubated at 60 s or at 90 s) orsuccinylcholine group (succinylcholine 1.0 mg/kg intubated at 60 s) and intubating conditions were assessed with: Ease of laryngoscopy, vocal cord position, and reaction to insertion of tracheal tube and cuff inflation.
Statistical Analysis: Statistical tests used were analysis of variance (ANOVA), Chi-Square test, Repeated measures of ANOVA and Mann-Whitney U test.
Results: Rocuronium in dosage of 0.3 mg/kg gaveclinically acceptable intubating conditions in 35% and 60% subjects at 60 s or 90 s, respectively, whereas in dosage of 0.6 mg/kg, intubating conditions were acceptable in 80% and 100% subjects intubated at 60 s and 90 s.
Conclusion: Rocuronium in dose of 0.3 mg/kg does not give clinically acceptable intubating conditions at 60 or 90 s but has shorter duration of action. Rocuronium in dose of 0.6 mg/kg gives clinically acceptable intubating conditions at 60 or 90 s, comparable to succinylcholine 1 mg/kg.
Keywords: Intubating conditions, rocuronium, succinylcholine
|How to cite this article:|
Venkateswaran R, Chaudhuri S, Deepak K M. Comparison of intubating conditions following administration of low-dose rocuronium or succinylcholine in adults: A randomized double blind study. Anesth Essays Res 2012;6:62-8
|How to cite this URL:|
Venkateswaran R, Chaudhuri S, Deepak K M. Comparison of intubating conditions following administration of low-dose rocuronium or succinylcholine in adults: A randomized double blind study. Anesth Essays Res [serial online] 2012 [cited 2022 Aug 16];6:62-8. Available from: https://www.aeronline.org/text.asp?2012/6/1/62/103377
| Introduction|| |
Rocuronium is a newer nondepolarizing muscle relaxant that is used for rapid sequence induction (RSI) when succinylcholine is contraindicated. Rocuronium has an onset of action comparable to succinylcholine when used in doses > 0.9 mg/kg. ,,,,,, It has the shortest onset time of all the nondepolarizing neuromuscular blocking agents currenly available. , Rocuronium has little or no adverse cardiovascular effects, nor does it cause histamine release. For these reasons, it may be preferred over succinylcholine in compromized patients in whom haemodynamic or other changes are to be minimized. Doses of rocuronium usually used for RSI (1 mg/kg) allow rapid paralysis (30 to 60 s) but the duration of action is prolonged (upto 1 h), making it unsuitable in difficult airway scenarios in the unavailability of sugammadex. Even if available, the benefit of having sugammadex reversing a large dose of rocuronium will come at a cost which will be substantial. For an average 75 kg patient reversal of profound blockade with 4 mg/kg sugammadex requires two 2 mL vials (ͳ119.28).  Also the foreseeable problem of a patient who has recently received sugammadex, who needs a surgery for re-exploration for instance has not been addressed. 
In theory, use of low doses of neuromuscular blocking agents shortens the time for recovery from neuromuscular block and reduces the requirement for anticholinesterase drugs. The ED95 dose of rocuronium is 0.3 mg/kg.  But low doses may also compromise the intubating condition. The aim of the study was to compare intubating conditions, onset of neuromuscular blockade and its clinical duration following two doses of rocuronium (0.3 or 0.6 mg/kg) or succinylcholine (1.0 mg/kg) administered in adult patients undergoing elective surgery requiring endotracheal intubation at 60 s and 90 s following administration of rocuronium 0.3 and 0.6 mg/kg and at 60 s following administration of succinylcholine 1.0 mg/kg. Duration of action, hemodynamic response and incidence of postoperative sore throat were also noted.
| Materials and Methods|| |
A total of 100 patients were enrolled in the study. Patients of either gender aged between 18 to 65 years belonging to ASA-PS I or II scheduled for elective surgery expected to last about 45 min, requiring endotracheal intubation under general anesthesia were included in the study.
Following were the exclusion criteria:
Clearance for performing the study was obtained from the Department Ethical Committee. Written and informed consent was taken from the patients who were willing to volunteer for the study. All patients received tablet diazepam 0.1 mg/kg body weight to a maximum of 10 mg as premedication on the evening before surgery and 3 h before induction of anesthesia on the day of surgery. Tablet ranitidine 150 mg and metoclopramide 10 mg was given at midnight on the day before surgery and 3 h before surgery.
- Potential or manifest airway problems.
- Modified Mallampati class 3 or 4.
- Presence of neuromuscular disease.
- Need for rapid sequence induction.
- Upper limb surgery.
- Aminoglycoside antibiotic administration in the previous 24 h.
- History of allergy to drugs used
Patients were randomly allocated to one of five groups using a computer-generated randomization table.
Group R3/60: Patients received intravenous rocuronium 0.3 mg/kg body weight, intubated at 60 s.
Group R3/90: Patients received intravenous rocuronium 0.3 mg/kg body weight, intubated at 90 s.
Group R6/60: Patients received intravenous rocuronium 0.6 mg/kg body weight, intubated at 60 s.
Group R6/90: Patients received intravenous rocuronium 0.6 mg/kg body weight, intubated at 90 s.
Group S/60: Patients received intravenous succinylcholine 1.0 mg/kg body weight, intubated at 60 s.
Observer one conducted the preoperative evaluation of the patient and prepared the drugs for administration. He/she monitored neuromuscular transmission during the first 10min following administration of the neuromuscular blocking agent and noted the time of onset of neuromuscular blockade (marked by a train-of-four count of 0) and duration of neuromuscular blockade (from abolition of all four twitches onTOF till return of first twitch on TOF sequence). The incidence of sore throat at 24 h following the surgery was also evaluated by bserver one.
Observer two, who was blinded to the study drug and the neuromuscular monitoring, performed laryngoscopy and endotracheal intubation and graded the intubating conditions.
Basic preinduction monitoring was established using a five electrode electrocardiogram (ECG), pulse oximetry, and noninvasive blood pressure (NIBP). Neuromuscular monitoring, end-tidal carbon dioxide (ETCO2) and anesthetic agent monitoring was established following induction of anesthesia. Surface electrodes of a peripheral nerve stimulator were placed over the ulnar nerve at the wrist on the hand with the intravenous access. The NIBP cuff was applied over the otherarm.
Patients were preoxygenated for 3min with 100% oxygen at a flow rate of 5 L/min using a circle absorber system. Intravenous fentanyl 2 μg/kg was given to all patients at the start of preoxygenation. Anesthesia was induced with intravenous propofol 2 mg/kg with the dose being titrated until the loss of response to verbal commands. The ability to "mask ventilate" was confirmed before administration of a bolus dose of a muscle relaxant (rocuronium or succinylcholine corresponding to the study group). Anesthesia was maintained with 100% oxygenand 2% isoflurane by mask ventilation using a respiratory rate of 10-12 breaths/min and tidal volume of 8-10 mL/kg body weight.
Heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, and pulse oximetric saturation were recorded for the first 3 min after intubation. Neuromuscular monitoring was done using a peripheral nerve stimulator to stimulate the ulnar nerve at the wrist using surface electrodes placed along the course of the nerve. The hand was stabilized such that only the thumb was allowed to move while the other fingers were immobilized using a tape.
A screen was used to cordon the area where neuromuscular transmission was being monitored. To avoid observer bias, the consultant anesthesiologist who performed the tracheal intubation (Observer two) was blinded to the muscle relaxant used or the response to the train-of-four stimulus at the time of intubation. Using the peripheral nerve stimulator, supramaximal square wave impulses of 0.2 ms duration were delivered in aTOF sequence at 2 Hz for 2 s. Visual and tactile evaluation of the baseline evoked mechanical response of adductor pollicis muscle was then noted. A repeat TOF stimulation was used once every 12 s to follow the time course and depth of neuromuscular blockade.
Laryngoscopy was performed by the consultant anesthesiologist 60 or 90 s after administration of the neuromuscular blocker as dictated by the group to which the patient was assigned. The duration of laryngoscopy and intubation was restricted to 30 s. If diaphragmatic or limb movement occurred at the time of endotracheal intubation, then this was recorded and propofol administered as a rescue drug in a dose of 1 mg/kg body weight.
Assessment of intubating conditions
Intubating conditions were assessed clinically by Observer two according to the following three criteria:
- Laryngoscopy 
Easy - Jaw relaxed, no resistance to blade insertion.
Fair - Jaw not fully relaxed, slight resistance to blade insertion.
Difficult - Poor jaw relaxation, active resistance of the patient to laryngoscopy.
- Vocal cord position
- Reaction to insertion of tracheal tube and cuff inflation (diaphragmatic movement or coughing)
Slight (1 or 2 weak contractions/movement lasting <5 s) Vigorous/sustained (>2 contractions and or diaphragmatic movement for >5 s)
Overall intubating conditions were then classified as excellent, good or poor accordingly:
All three parameters were taken into consideration for scoring overall intubating conditions. Thus, the final score was considered "poor" if any of the parameters was rated poor. It was "good" if one or more items were rated good and none were rated poor. It was "excellent" only if all items were judged excellent [Table 1].
Following intubation, correct tracheal location was confirmed by the presence of bilaterally equal breath sounds and appearance of a square wave on the capnograph. Postintubation, anesthesia was maintained with nitrous oxide in oxygen (2:1) and isoflurane (1%), till the completion of the study period that was till the return of first twitch on TOF as evaluated visually. The intracuff pressure of the endotracheal tube was kept below 25 cm H2O throughout surgery by checking every 15 min with a cuff pressure monitor.
Onset time and duration of neuromuscular blockade
The onset time (T1) from the time of administration of muscle relaxant to the complete abolition of all four twitches on train-of-four (TOF) stimulation was noted. The assessment of neuromuscular blockade was done by the appearance of first twitch in the TOF response in the rocuronium groups (nondepolarizingblockers). In the case of succinylcholine group, the return of all twitches with the lowest amplitude (depolarizing blocker) was regarded as time T2. A repeat TOF stimulation was used once every 12 s to follow the time course of neuromuscular blockade
If the TOF count did not become 0 even 10 m after administration of the muscle relaxant, monitoring with the peripheral nerve stimulator was stopped and the above fact was documented.
Hemodynamic variables such as heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure were recorded just prior to intubation and every minute for the first 3min following intubation.
The incidence of sore throat was assessed by Observer one at 24 h after surgery using the following criteria. Sore throat was graded as follows: 
0 = no sore throat.
1 = mild sore throat (pain only on deglutition).
2 = moderate sore throat (pain present constantlyand also increasing with deglutition).
3 = severe sore throat (pain interfering with eating and requiring analgesic medication).
The statistical tests used were: Analysis of variance (ANOVA), Chi- Square test and Mann-Whitney U-Test. For all tests in the study, P<0.05 was considered significant.
| Results|| |
Patients in all the five groups were comparable with respect to age, weight, and ASA physical status [Table 2] and [Table 3].
Intubating criteria as assessed by ease of laryngoscopy, vocal cord position, reaction to intubation were as under [Table 4], [Table 5] and [Table 6]. There was a significant difference among the five groups with regard to the number of patients having clinically acceptable intubating conditions with a P value of < 0.0001 [Table 7] and [Table 8].
|Table 8: Intubating conditions clinically acceptable versus clinically not acceptable|
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In one patient in R3/60 group, laryngoscopy was difficult with active resistance to blade insertion, vocal cord position was thus not assessed in this patient [Table 5].
To determine the onset and duration of neuromuscular blockade of low dose rocuronium, groups R3/60 and R3/90 were combined into a single group, rocuronium 0.3 group. Similarly the groups R6/60 and R6/90 were combined into a single group, rocuronium 0.6 group. Group S/60 was named the Succinylcholine group. The onset of neuromuscular blocade was fastest in Succinylcholine group, followed by the rocuronium 0.6 group and then the rocuronium 0.3 group. The median time of onset of neuromuscular blockade (T1) in rocuronium 0.3 group was 5.08 min. It was 2.60 minutes and 1.08 min respectively in the rocuronium 0.6 and Succinylcholine groups. The onset time was noted to be statistically significant between the three groups (P<0.0001) using Mann-Whitney test- Kruskal Wallis [Table 9].
The assessment of duration of neuromuscular blockade was done by the appearance of first twitch in the TOF response in the rocuronium groups (nondepolarizing blockers). In the case of the succinylcholine group, the return of all twitches with the lowest amplitude (depolarizing blocker) was regarded as time T2. There was also a statistically significant difference in the duration of neuromuscular blockade among the three groups: Rocuronium 0.3 group, Rocuronium 0.6, and Succinylcholine group (P<0.0001) using Mann-Whitney test-Kruskal Wallis [Table 10].
The longest duration of blockade was in the Rocuronium 0.6 group (48 min) and the shortest duration was in the Succinylcholine group (7 min). Reducing the dose of rocuronium resulted in reduction in duration of neuromuscular blockade that was 18.5 min in the Rocuronium 0.3 group.
[Table 11] shows the incidence of sore throat in patients in the different groups. While two patients had mild sore throat in the R3/60 group, all the other groups had only one patient each with mild sore throat. Using the Pearson Chi-square test, no significant difference was found between the various groups with regard to incidence of sore throat (P value = 0.935).
Sore throat was not assessed in the patient who had active resistance to laryngoscopy in R3/60 group as patient was intubated after administering additional drugs, after including the patient as clinically unacceptable intubating condition.
Heart rate and blood pressure changes
Heart rate, systolic blood pressure, and diastolic blood pressure were also recorded at the time of intubation and for the first 3 min thereafter. The changes in hemodynamic are represented graphically in [Figure 1], [Figure 2] and [Figure 3]. These parameters showed a trend that was comparable in the five groups.
|Figure 1: Change of heart rate at different time intervals among all groups|
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|Figure 2: Change of systolic blood pressure at different time intervals among all groups|
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|Figure 3: Changes in diastolic blood pressure at different time intervals among all groups|
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| Discussion|| |
The purpose of the study was to know if low-dose rocuronium reduced its duration of action, yet gave acceptable intubating condition, permitting its use in cases where short apnoea time is desirable. To evaluate overall intubating conditions, we used three parameters, ease of laryngoscopy, vocal cord position at laryngoscopy and reaction to tracheal intubation and cuff inflation. Though there have been previous studies on low dose rocuronium and intubating conditions, those studies had been done in different clinical scenarios using varying induction agents and opioids.
In our study on low-dose rocuronium, we chose agents that are most commonly used in most institutions for induction of general anesthesia, that is fentanyl, propofol, and isoflurane, and maintenance with nitrous oxide, oxygen, and isoflurane. We also studied exactly which factor out of the three parameters actually lead to overall intubating condition being clinically unacceptable in the different groups. In our study, only 35% patients in R3/60 group and 60% patients in R3/90 group had clinically acceptable intubating conditions. However, the percentage of clinically acceptable intubating condition were 80% and 100%, respectively, in the R6/60 and R6/90 groups. The factor that contributed to intubating condition being not acceptable clinically was the reaction to intubation. This is an important finding because most of the patients in R3/60 or R3/90 groups had easy or fair laryngoscopy and had vocal cords in either abducted or intermediate position through which an endotracheal tube could be passed without any vocal cord trauma. But it was the reaction to intubation that made the overall intubating condition clinically unacceptable. We had the recorded heart rate, systolic blood pressure, and diastolic blood pressure at the time of intubation and for the first 3 min thereafter to know the effect of reaction to intubation in the different groups. Repeated measures of ANOVA was used to analyze these parameters that showed comparable trends in the five groups.
Also the incidence of sore throat post operatively was minimal in both the R3/60 and R3/90 groups. That implies that in an anticipated difficult airway scenario where succinylcholine is contraindicated, the placement of the endotracheal tube can be successfully done even with low-dose Rocuronium without having postoperative sore throat even though the overall intubating condition will be graded as clinically unacceptable, due to the reaction to intubation.
The intubating conditions in the low-dose rocuronium groups in our study were in contrast to those of Tullock et al.,  where patients had good to excellent intubating scores in 100% patients intubated with rocuronium 350 μg/kg at 150 s following anesthetic induction with alfentanil and propofol. Our results were also different from the results of a study done by Barclay et al.,  with low-dose Rocuronium. In their study, 18/20 (90%) who were intubated using Rocuronium 0.3 mg/kg following induction of anesthesia with alfentanil and propofol had optimal intubating conditions when assessed at 2 min.
Intubating conditions in the R3/90 group in our study were in contrary to the results of a study done by Siddik-Sayyid et al. where they found excellent intubating conditions in 90% patients, comparable to 1.5 mg/kg of succinylcholine, when anesthesia was induced with remifentanil 2 μg/kg, propofol 2 mg/kg, and lidocaine 1.5 mg/kg and intubation performed 90 s after rocuronium 0.3 mg/kg.  Only 25% patients in R3/90 group in our study had excellent intubating conditions, which is strikingly different.
The intubating conditions in the 0.3 mg/kg rocuronium groups were also in contrast to the study done by Schlaich et al. where intubating conditions were assessed 3 min after induction of anesthesia with remifentanil 0.5 μg/ kg/ min, propofol 2 mg/kg and 0.3 mg/ kg rocuronium and showed good or excellent intubating conditions in 30 out of 30 patients. Clinical onset time was 249 s and clinical duration was 16 min. Intubating conditions were also good or excellent in all 30 patients following rocuronium 0.6 mg/kg. The clinical onset time was 136 s and the clinical duration was 38 min. However, the onset time and duration with 0.3 mg/kg rocuronium and 0.6 mg/kg rocuronium was comparable to that in our study. The median onset times in Rocuronium 0.3 group and 0.6 group were 305 s and 156 s, respectively, in our study, and the duration was 18.5 and 48 min, respectively.
Eikermann et al.'s study on 120 children aged between 2-7 years to define the optimal rocuronium dose that provides a 95% probability of acceptable intubating conditions during inhalational induction with sevoflurane  after administrating rocuronium in doses 0.1, 0.15, 0.22, 0.3, or 0.6 mg/kg or placebo concluded that during inhalation induction with 8% sevoflurane in 60% nitrous oxide and 40% oxygen, rocuronium 0.29 mg/ kg (ED 95 ) optimizes intubating conditions for surgery of short duration.
However, in our study, 0.3 mg/kg Rocuronium did not optimize intubating conditions when used in adults with 2% isoflurane, nitrous and oxygen along with fentanyl and propofol.
Sermin et al. Studied intubation conditions at 90 s following two different low doses of rocuronium (0.15 mg/kg or 0.3 mg/kg) during remifentanil and propofol anesthesia  in children aged 3-12 years and concluded that 95.5% had a clinically acceptable intubating condition in the 0.3 mg/ kg group, which was in glaring contrast to that of ours, even though the study group was adults in our study.
De Miranda et al. in their comparative study between one and two effective doses (ED95) of Rocuronium for tracheal intubation in adult patients concluded that both doses of Rocuronium, 0.3 mg/kg and 0.6 mg/kg provided clinically satisfactory parameters of tracheal intubation in elective procedures  that was again absolutely different to that of our study. Thus, even though previous studies done by different authors concluded that Rocuronium 0.3 mg/kg can be used to provide clinically acceptable intubating conditions, our findings were completely different from those studies. The strikingly different findings could be because of the different induction agents and opioids used in the previous studies, which may lead us to conclude that the same Rocuronium 0.3 mg/kg can give different intubating conditions, depending on the induction methods.
The results of our study were similar to the one done by Kirkegaard-Nielsen et al. In their study, after premedication with midazolam, and induction with fentanyl and propofol, 11 out of 20 patients had unacceptable intubating conditions when intubation was done at 60 s.
Lam A compared intubating conditions, and the onset and offset times of Rocuronium bromide and succinylcholine.  He concluded that Rocuronium at a dose of 0.6 mg/kg (when used with propofol and fentanyl for induction) provides intubating conditions comparable to succinylcholine 1.0 mg/kg at 60 s, which was a similar finding as that of our study. The actual onset and offset times, however, were significantly longer with rocuronium. The author concluded that Rocuronium is suitable for surgical procedures greater than 30 min eliminating the need for an additional relaxant to succinylcholine.
In our study, the median onset time of neuromuscular blockade in R 0.3 group was 5.08 min, which was much more than in the study done by Meistelman et al.,  In their study, the onset time at adductor pollicis using 0.3 mg/kg rocuronium was 3.0 ± 0.3 min.
In our study, there was no difference in the incidence of sore throat in the various groups 24 h into the postoperative period. There was no sore throat even in the clinically unacceptable intubating condition patients probably because most of those patients had vocal cords in either abducted or intermediate position, through which the endotracheal tube could be passed without trauma. These findings were also similar to that of Mencke et al. on the incidence of postoperative sore throat and hoarseness comparing Rocuronium 0.6 mg/kg and succinylcholine 1.0 mg/kg. 
| Conclusion|| |
Following anesthetic induction with fentanyl, propofol, and isoflurane in oxygen.
- Rocuronium in a dose of 0.3 mg/kg does not give clinically acceptable intubating conditions at 60 or 90 s.
- Rocuronium in a dose of 0.6 mg/kg gives clinically acceptable intubating conditions at 60 or 90 s that are comparable to intubation at 60 s following succinylcholine 1 mg/kg.
- Reducing the dose of rocuronium to 0.3 mg/kg shortens the duration of action but at the expense of providing clinically unacceptable intubating conditions, the reaction to insertion of the tracheal tube and cuff inflation being the factor responsible for the unacceptable intubating condition.
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[Table 7], [Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 8], [Table 9], [Table 10], [Table 11]
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