Muscle relaxants are used during surgery to ensure good skeletal muscle relaxation. Griffth and Johnson [1] used d-tubocurarine in 1942 followed by Cullen [2], in general anesthesia to facilitate tracheal intubation. Succinyl choline introduced by Therleff [3] and Foldes4 in 1952 revolutionized anesthetic practice by providing intense neuro muscular blockade of very rapid onset and ultra-short acting duration favoring ease of endotracheal intubation. The synthetic and semi synthetic neuromuscular blocking agents like gallamine, di-methyl tubocurarine and alcuronium were introduced. Baird and Reid [5] used synthetic aminosteroid Pancuronium with its lack of hypotensive action and mild stimulation of heart rate and blood pressure. 

Atracurium, Vecuronium. Pipcuronium, Doxacurium, Mivacurium, Rocuronium and Rapacuronium were added to the armamentarium [6]. The properties of the ideal neuromuscular blocking agents include its rapid onset of action, short duration of action, rapid recovery, non-cumulative without any histamine release or cardiovascular side effects, high potency, reversible by cholinesterase inhibitors and pharmacologically inactive metabolites [7].       

Rocuronium is the first none depolarizing muscle relaxant followed by Rapacuronium considered to be an acceptable substitute for succinyl choline in facilitating rapid intubation of trachea due to its rapid onset of action  [8]. Rocuronium also has similar rapid onset but with prolonged duration of action facilitating ease of tracheal intubation and this favored condition was used as a comparison in our study.

Aim and Objectives of the Study

The main aim of our study was to evaluate and compare the onset time, intubation conditions and duration of action of various doses of Rocuronium. The secondary objective includes the haemodynamics monitoring and noted if there was any complication with the study drug.

A study entitled “A Prospective randomized study to compare the onset time, intubation condition and duration of various doses of Rocuronium in adult patients undergoing endotracheal intubation” was done in PSG Institute of Medical Sciences and Research, Coimbatore, after obtaining Institutional Human ethics committee clearance from the institution and informed written consent from all the patients who participated in the study. It is a prospective randomized control study and the sample size was calculated using 95% confidence interval and power of the study being 80%. The sample size was 30 in each group with allocation ratio being 1:1:1.

This is a randomized, prospective single blind study where the person assessing the response (observer) was blinded to the group the patient belonged to and the person administering the drug was aware of the dosage of the drug he is administering. 60 adult patients of age group between 20 – 60 years belonging to ASA 1 and 2 of either sex posted for laparoscopic surgery were included in the study.

60 patients were divided into three groups of 20 each and randomly allocated to one of the three below mentioned groups: Group I received 0.6mg/kg Rocuronium, Group II received 0.75mg/kg Rocuronium and Group III received 0.9mg/kg Rocuronium.

Inclusion Criteria

• ASA Grade 1 and 2

• Age ranging from 20 to 60 years

• Patients undergoing Laparoscopic surgery

• Duration of surgery of at least one hour duration

Exclusion Criteria

• Patient denial

• Cardiovascular, renal, hepatic diseases

• Neuromuscular disorders

• Pregnancy

• Difficult airway

Routine preoperative assessment done and informed written consent was obtained. All patients were premedicated orally with Tablet Pantoprazole 40 mg and Alprazolam 0.25 mg the previous night and 2 hours before surgery. Patients were assigned individually to one among the three groups Group I, Group II or Group III by computer generated random table number. In the preoperative room, an 18G intravenous cannula was inserted and an infusion of Plasmalyte solution started. On arrival in the operation theatre, pre induction monitors like ECG, NIBP and SpO2 were connected and monitoring of these parameters started after noting the baseline values. 

Preoxygenation was done with 100% Oxygen for 3 minutes and premedicated with Glycopyrolate 0.004mg/kg, analgesia supplemented with Fentanyl 2µg/kg and induced with Thiopentone sodium 5mg/kg. Titrated with incremental dose of thipentone sodium if needed till the abolition of eyelash reflex. Baseline single twitch and train of four (TOF) were assessed using neuromuscular stimulator. One of the three doses of Rocuronium was given intravenously in less than 10 seconds into a fast running Plasmalyte solution. 

The onset time was defined as the time between the end of the injection and disappearance of all four twitches in TOF (visual and palpation) and duration of action as the time between end of the injection of Rocuronium and recovery of the first twitch of TOF. Laryngoscopy was done at 60 seconds post Rocuronium injection in all the three groups and intubation attempted. Train of four was assessed every 12 seconds and duration of action assessed. Anesthesia was maintained with O2: N2O (2:3), sevoflurane to achieve a MAC value of 1.2 and maintenance dose of Rocuronium given depending upon the duration of surgery. The following parameters were noted in our study

• Time of giving Rocuronium

• Dose of Rocuronium

• Time at which intubation was done

• Time at which all four twitches of TOF disappeared

• Time at which the first twitch of TOF recovered

The ease of laryngoscopy during intubation conditions, the position and movement of the vocal cords and the degree of coughing were evaluated using Krieg et al. intubation assessment scoring system [9]. Intubation assessment scoring: 

• Total Score: 9

• Excellent: 8–9

• Good: 6–7                     

• Fair: 3–5                       

• Poor: 0–2

The haemodynamic parameters were monitored. Hypotension (Systolic BP <90mmHg and Diastolic BP ˂50 mm Hg was treated with intravenous fluids±vasopressors – Injection Ephedrine or Mephentremine 6 mg IV bolus SOS. Bradycardia (Heart rate <50/min) was treated with injection Glycopyrrolate 0.02mg / kg IV bolus SOS. 

Data were statistically analyzed with the Mann Whitney test and Kruskal Wallis test and p-value less than 0.05 were considered as significant. Baseline characteristics were presented as mean±S.D.

Table 1: Intubation Condition Scoring

Table 2: Demographic Data Between the Three Groups

Table 3: Intubation Scores at 60 Seconds Among all 3 Groups

Table 4: Relationship Between the Dosage, Onset Time and Duration Among Three Groups

Table 5: Haemodynamic Parameters Among the Study Groups

Suxamethonium is being used for rapid tracheal intubation because of its rapid onset of action. Though it has its own side effects, its contraindicated in situations like burns, and hyperkalemia. Atracurium and Vecuronium although have less side effects the onset is slow and cannot be used for rapid tracheal intubation and its dose should be increased for their use. Rocuronium an intermediate duration of action nondepolarising muscle relaxant is shown to have a rapid onset of action due to its low potency [10].

In one of the clinical studies with Rocuronium, Wierda et al. [11] found that intubating conditions were excellent at 1 minute with a dose of 0.5mg/kg. In our study also we found that, using equipotent doses, the mean time to 75% block was 68 seconds for Rocuronium compared to 155 seconds for vecuronium.

De Mey et al. [12-13] evaluated the influence of two different doses (1.5 x ED 90 and 3 x ED 90) of Rocuronium on the 3 different phases of onset of block. This study confirmed the three phases of onset and concluded that an increase of the bolus dose results in a significantly faster decrease of T1 height, especially during the second phase.

Cooper et al. [14] found that the time to complete block decreased from about 1 minute with a dose of 0.6mg/kg, to approximately 45 seconds with a dose of 0.9mg/kg. In another study by De Mey et al. intubation conditions were determined in 60 patients, either 45 or 60 seconds after administration of 0.6, 0.75 or 0.9 mg/kg Rocuronium. In general intubation conditions were excellent or good and in only 3 patients obtained poor conditions at 45 seconds.

Crul et al. [15] investigated the intubation conditions of Rocuronium under Propofol/Alfentanyl anesthesia and concluded that the increasing the dose of Rocuronium from 0.6 to 0.9 mg/kg improves the conditions for rapid sequence intubation significantly. In a study by Cooper et al., time to complete block decreased from about 1 minute with a dose of 0.6mg/kg to approximately 45 seconds with a dose of 0.9mg/kg. However, clinical duration and recovery index were significantly longer than the higher dose.

In our study, in Group I intubation conditions were excellent in 16 patients and good in 4 patients. In Group II it was excellent in 19 and good in 1 patient. In Group III all 20 patients had excellent intubation conditions. There was not much difference for the overall score between the various three groups.

The onset time is the time between the end of injection of Rocuronium and disappearance of all 4 twitches of TOF and duration of action as the time between end of injection and recovery of the first twitch of TOF16. All 60 patients in our study showed intubation condition at 60 seconds with excellent / good intubation scores. 55 patients have excellent score and good in 5 patients out of which 4 were in Group I – 0.6mg/kg.

The onset time was shown to reduce significantly with increasing the dosage from 0.6mg/kg to 0.75mg/kg and from 0.75mg/kg to 0.9mg/kg (p<0.002) in Mann Whitney test and p<0.009 in Kruskal Wallis test. Onset time when compared to Group I, Group II was shorter and in Group III it was much shorter than the other groups. 3 way Kruskal Wallis test gives significant p<0.009 for onset time related to dosage. That is increase in the dosage reduces the onset time much significantly. By applying Mann Whitney test p<0.002 was obtained when comparing onset times for doses 0.6mg/kg and 0.75mg/kg, 0.75mg/kg and 0.9mg/kg and 0.6mg/kg and 0.9mg/kg.

These data as with other studies support the view that suitable clinical intubation conditions can present with only partial depression of the twitch response of the thumb probably because muscular relaxation of the laryngeal muscles has shown to occur faster [17-18]. Hence in our study the intubation was possible within 60 seconds which is just before the onset time of the drug. 

There was no statistical significance among heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure in haemodynamic parameters and no complications were noted in our study groups.

3 way Kruskal Wallis test gives significance p<0.009 by increasing the dosage from 0.6mg/kg to 0.9mg/kg. Duration is significantly prolonged by increasing the dose. Regarding duration of action there is significant increase in duration by increasing the dose 0.6mg/kg and 0.9mg/kg, 0.75mg/kg and 0.9mg/kg and 0.6mg/kg and 0.9mg/kg. p<0.002 was obtained by Mann Whitney test.

Our study as compared with other similar studies showed that increasing the dose from 0.6mg/kg to 0.9mg/kg the duration nearly doubles as evidenced by Mann Whitney test and Kruskal Wallis test [19].

Increasing the dosage from 0.6mg/kg to 0.75mg/kg and to 0.9mg/kg reduces the onset time, prolongs the clinical duration and gives excellent intubation conditions at 60 seconds.

1. Griffith, Harold R. and G. Enid Johnson. "The use of curare in general anaesthesia." Anesthesiology, vol. 3, no. 7, 1942, pp. 418–420.

2. Cullen, S.C. "Curare; its rational use as an adjunct to anaesthesia." Surgery, vol. 20, no. 8, 1946, p. 200.

3. Therleff, S. "Succinyl choline iodide: studies on its pharmacological properties and clinical use." Acta Physiologica Scandinavica Supplementum, vol. 27, no. 99, 1952, pp. 1–36.

4. Foldes, F.F. et al. Borrego-Hinojosa. "Succinyl choline, a new approach to muscular relaxation in anaesthesiology." The New England Journal of Medicine, vol. 247, no. 16, 1952, pp. 596–600.

5. Baird, W.L. and A.M. Reid. "Neuromuscular blocking properties of a new steroidal compound, Pancuronium bromide."British Journal of Anaesthesia, vol. 39, no. 10, 1967, pp. 775–780.

6. Bowman, W.C. "Neuromuscular block." British Journal of Pharmacology, vol. 147, no. S1, 2006, pp. S277–S286.

7. Wierda, J.M.K.H. et al. "Comparison of the time course of action and endotracheal intubating conditions of vecuronium bromide, rocuronium bromide and mivacurium chloride." Anaesthesia, vol. 50, no. 5, 1995, pp. 393–396.

8. Puhringer, F.K. et al. "Evaluation of the endotracheal intubating conditions of rocuronium (Org 9426) and succinyl choline in outpatient surgery." Anesthesia & Analgesia, vol. 75, no. 1, 1992, pp. 37–40.

9. Gaszynski, Tomasz. et al. "A comparison of performance of endotracheal intubation using the Levitan FPS optical stylet or Lary flex videolaryngoscope in morbidly obese patients." The Scientific World Journal, vol. 2014, 2014, pp. 1–9, http:/ /dx.doi.org/10.1155/2014/207591.

10. Meistelman, C. et al. "Rocuronium: neuromuscular blockade at the adductor muscles of the larynx and abductor pollicis in humans." Canadian Journal of Anaesthesia, vol. 39, no. 7, 1992, pp. 665–669.

11. Wierda, K.M.K.H. et al. "Clinical observation on the neuromuscular blocking action of Org 9426, a new steroidal non-depolarizing agent." British Journal of Anaesthesia, vol. 64, no. 4, 1990, pp. 521–523.

12. De Mey, J.C. et al. "The influence of dose of the profile of onset of the neuromuscular blockade after a bolus dose of rocuronium." British Journal of Anaesthesia, vol. 71, no. 1, 1995, p. A258.

13. De Mey, J.C. et al. "Evaluation of the onset and intubation condition of rocuronium bromide." European Journal of Anaesthesiology, vol. 11, no. 9, 1994, pp. 37–40.

14. Cooper, R.A. et al. "Neuromuscular effects of rocuronium bromide (Org 9426) during fentanyl and halothane anaesthesia." Anaesthesia, vol. 48, no. 2, 1993, pp. 103–105.

15. Crul, J.F. et al. "Rocuronium with alfentanyl and propofol allows intubation within 45 seconds." European Journal of Anaesthesiology, vol. 12, no. 11, 1995, pp. 111–112.

16. Abouleish, E. et al. "Rocuronium for caesarean section." British Journal of Anaesthesia, vol. 73, no. 3, 1994, pp. 336–341.

17. Bunburaphong, P. et al. "Intubating conditions after three different doses of rocuronium in the elderly." Journal of the Medical Association of Thailand, vol. 84, no. Suppl 3, 2001, pp. S244–S250.

18. Sudha, P. and B. Manju. "Comparison of the effect of two different doses of rocuronium on intubating condition." International Surgery Journal, vol. 3, no. 3, 2016, pp. 582–585.

19. Raizada, Neena. et al. "Comparison of different doses of Rocuronium for endotracheal intubation." International Journal of Contemporary Medical Research, vol. 5, no. 2, 2018, pp. B13–B17.