Among the 11 patients who had poor intubating conditions, poor condition for laryngoscopy was the cause in three, and a vigorous or sustained reaction to insertion of the tracheal tube or cuff inflation was the cause in eight. A bolus dose of propofol 0.5 mg kg−1 was given to two patients who had a vigorous reaction to insertion of the tracheal tube.
SBP and HR decreased significantly 30 s after injection of propofol (P30) compared with the preinduction values (Base; SBP 15.2% and HR 11.0%, respectively, P < 0.001), but both were within acceptable ranges and no significant changes occurred thereafter until 3 min after tracheal intubation (INT3; Fig. 2). No patient needed ephedrine or atropine.
In the PACU, six patients (21.4%) reported a sore throat. No patient had hoarseness or recall of intraoperative events.
This study demonstrated that, after induction of anaesthesia with remifentanil 2 μg kg−1 and propofol 2 mg kg−1, the dose of rocuronium which provided a 50% probability of acceptable intubating conditions in a rapid sequence intubation was 0.20 mg kg−1 (95% CI 0.17 to 0.23 mg kg−1). In other words, after induction with remifentanil and propofol, acceptable intubating conditions could be obtained within 60 s using rocuronium 0.8 mg kg−1.
Rapid sequence intubation was performed traditionally using thiopental and succinylcholine. When used in a large dose of 0.9 to 1.2 mg kg−1, rocuronium could replace succinylcholine in rapid sequence intubation but a prolonged duration of action could be a problem. Sugammadex can reverse the block rapidly, but it is still expensive and is not yet available to every practitioner. As a hypnotic agent, propofol is known to result in more favourable airway conditions for tracheal intubation compared to thiopental; pharyngeal and laryngeal muscle tone during laryngoscopy were more depressed14 and vocal cords were more widely open15 after induction with propofol compared with an equipotent dose of thiopental.
Recent studies into the possibility of tracheal intubation without the use of muscle relaxants show that full relaxation is not mandatory for successful tracheal intubation.16 However, caution is needed because the intubating conditions are related to laryngeal morbidity.5,17 Postoperative hoarseness and vocal cord damage were more frequent in patients who had poor intubating conditions compared to those who had excellent conditions.17
The most commonly recommended doses for acceptable intubating conditions without a neuromuscular blocker4,18 are remifentanil 4 μg kg−1 or alfentanil 40 μg kg−1 in combination with propofol 2 to 2.5 mg kg−1. The doses of opioids used are higher than those used usually at the time of induction of anaesthesia using a muscle relaxant, and significant bradycardia or hypotension can be a problem when a high dose of opioid is used. Rapid sequence intubation with propofol 2 mg kg−1 and succinylcholine 1 mg kg−1 induced a significant 14% increase in MAP and a 25 to 30% increase in HR, whereas remifentanil 4 μg kg−1 instead of succinylcholine induced a significant 24 to 31% decrease in MAP.19 In contrast, the haemodynamic changes were not so severe and were within acceptable ranges in our patients. Remifentanil 2 μg kg−1 combined with propofol 2 mg kg−1 did not decrease HR or blood pressure significantly before intubation and also prevented increases in HR and blood pressure after intubation.
There have been other studies of intubating conditions with only a small dose of rocuronium. After inhalational induction with sevoflurane, 90% of children had acceptable intubating conditions within 2 min of injection of rocuronium 0.22 mg kg−1 and the twitch tension was 26% of baseline at that point.20 In adult patients, after induction with lidocaine 1.5 mg kg−1, remifentanil 2 μg kg−1 and propofol 2 mg kg−1, intubating conditions 90 s after injection of rocuronium 0.3 mg kg−1 were comparable to those 60 s after injection of succinylcholine 1.5 mg kg−1 and the mean train-of-four (TOF) ratio was 0.65 at the time of intubation in the rocuronium group.21 After rocuronium 0.25 mg kg−1, the onset time was 1.6 and 3.0 min at the laryngeal muscles and the adductor pollicis muscle respectively, and the maximum TOF ratios achieved were 0.37 and 0.69, respectively.22 By reducing the dose of rocuronium, the duration of action could be shortened, which makes reversal of neuromuscular block easier and reduces the risk of residual paralysis after recovery. After a single intubating dose of an intermediate duration non-depolarising neuromuscular blocker, it has been reported that up to 45% of patients have residual paralysis, defined as a TOF ratio below 0.9.23 At a TOF ratio below 0.9, there are increased risks of upper airway obstruction and pulmonary aspiration due to functional impairment of pharyngeal and upper oesophageal muscles.24
The differences between our study and previous investigations are that tracheal intubation was performed only 60 s after injection of rocuronium to simulate rapid sequence intubation and we tried to find the lowest dose of rocuronium needed in this situation. It would have been better if we had measured the degree of neuromuscular block, but we could infer from previous studies that the degree of neuromuscular block obtained would be variable according to the dose of rocuronium used but could be only partial at the time of intubation. We expected a decreased incidence of residual paralysis by reducing the dose of rocuronium during induction of anaesthesia. However, the use of a nerve stimulator for management of muscle relaxation is mandatory and reducing the dose of rocuronium does not justify not using the nerve stimulator. This is a limitation of our study.
This study has several additional limitations. First, we only obtained the ED50 of rocuronium for acceptable intubating condition, even though the values of ED90 or ED95 are of clinical interest. For this purpose, we also calculated ED95 using probit analysis (Fig. 3), but the ED95 could be incorrect and the CI is wide25 because up-and-down methods do not provide an accurate estimate at the upper part of the distribution.26 The intubating dose is classically expressed as 2 x ED95 or alternatively 4 x ED50. On the basis of our ED50 results, we recommend an intubating dose of rocuronium of 0.8 mg kg−1. This is lower than previous recommendations. However, further study is needed to obtain a more accurate ED95 value. The advantage of using the modified up-and-down method is, however, that we could reduce the number of patients to converge to an ED50 and to increase the precision of the final estimate.11
Second, we regarded both excellent and good intubating condition as a success according to the Guidelines For Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents and several related studies.1,13,20 However, it should be kept in mind that in some situations, such as trauma patients with severe head injury, excellent intubating conditions are preferable. Caution is also needed for interpretation of previous studies because some studies regarded only excellent conditions as optimal.27
Another limitation is that we evaluated recall and sore throat only in the PACU. It is known that patients who do not have recall or a sore throat in the PACU may complain of them later.28,29 It is known that only 35% of patients who had intraoperative awareness report it during their stay in the PACU.29 The incidence of postoperative sore throat varies between 14.4 and 50%.28,30,31 After rapid sequence intubation with propofol and succinylcholine, sore throat in the PACU was reported to be 22.9%.28 The incidence of sore throat in the PACU in this study was 21.4% and was similar to previous reports.
In conclusion, after induction of anaesthesia with remifentanil 2 μg kg−1 and propofol 2 mg kg−1, we recommend a dose of rocuronium of 0.8 mg kg−1 for rapid sequence intubation. Full relaxation is not mandatory for rapid sequence intubation when propofol and remifentanil are used together. Remifentanil-propofol-low dose rocuronium could be one of the alternative methods employed when rapid sequence intubation is needed.
Assistance with the study: none declared.
Financial support and sponsorship: none declared.
Conflicts of interest: none declared.
1. Kirkegaard-Nielsen H, Caldwell JE, Berry PD. Rapid tracheal intubation with rocuronium: a probability approach to determining dose. Anesthesiology
2. Stevens JB, Wheatley L. Tracheal intubation in ambulatory surgery patients: using remifentanil and propofol without muscle relaxants. Anesth Analg
3. Klemola UM, Mennander S, Saarnivaara L. Tracheal intubation without the use of muscle relaxants: remifentanil or alfentanil in combination with propofol. Acta Anaesthesiol Scand
4. Bouvet L, Stoian A, Rimmele T, et al Optimal remifentanil dosage for providing excellent intubating conditions when co-administered with a single standard dose of propofol. Anaesthesia
5. Bouvet L, Stoian A, Jacquot-Laperriere S, et al Laryngeal injuries and intubating conditions with or without muscular relaxation: an equivalence study. Can J Anaesth
6. Combes X, Andriamifidy L, Dufresne E, et al Comparison of two induction regimens using or not using muscle relaxant: impact on postoperative upper airway discomfort. Br J Anaesth
7. Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet
8. Murphy GS, Szokol JW, Marymont JH, et al Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg
9. Mertes PM, Tajima K, Regnier-Kimmoun MA, et al Perioperative anaphylaxis. Med Clin North Am
10. O’Hare R, McAtamney D, Mirakhur RK, et al Bolus dose remifentanil for control of haemodynamic response to tracheal intubation during rapid sequence induction of anaesthesia. Br J Anaesth
11. Jung H, Choi SC. Sequential method of estimating the LD50 using a modified up-and-down rule. J Biopharm Stat
12. Paul M, Fisher DM. Are estimates of MAC reliable? Anesthesiology
13. Fuchs-Buder T, Claudius C, Skovgaard LT, et al Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand
14. McKeating K, Bali IM, Dundee JW. The effects of thiopentone and propofol on upper airway integrity. Anaesthesia
15. Stevens JB, Vescovo MV, Harris KC, et al Tracheal intubation using alfentanil and no muscle relaxant: is the choice of hypnotic important? Anesth Analg
16. Woods AW, Allam S. Tracheal intubation without the use of neuromuscular blocking agents. Br J Anaesth
17. Mencke T, Echternach M, Kleinschmidt S, et al Laryngeal morbidity and quality of tracheal intubation: a randomized controlled trial. Anesthesiology
18. Scheller MS, Zornow MH, Saidman LJ. Tracheal intubation without the use of muscle relaxants: a technique using propofol and varying doses of alfentanil. Anesth Analg
19. Hanna SF, Ahmad F, Pappas AL, et al The effect of propofol/remifentanil rapid-induction technique without muscle relaxants on intraocular pressure. J Clin Anesth
20. Eikermann M, Renzing-Kohler K, Peters J. Probability of acceptable intubation conditions with low dose rocuronium during light sevoflurane anaesthesia in children. Acta Anaesthesiol Scand
21. Siddik-Sayyid SM, Taha SK, Kanazi GE, et al Excellent intubating conditions with remifentanil-propofol and either low-dose rocuronium or succinylcholine. Can J Anaesth
22. Meistelman C, Plaud B, Donati F. Rocuronium (ORG 9426) neuromuscular blockade at the adductor muscles of the larynx and adductor pollicis in humans. Can J Anaesth
23. Debaene B, Plaud B, Dilly MP, Donati F. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology
24. Sundman E, Witt H, Olsson R, et al The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology
25. Kim MK, Lee JW, Jang DJ, et al Effect-site concentration of remifentanil for laryngeal mask airway insertion during target-controlled infusion of propofol. Anaesthesia
26. Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a precis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology
27. Abou-Arab MH, Heier T, Caldwell JE. Dose of alfentanil needed to obtain optimal intubation conditions during rapid-sequence induction of anaesthesia with thiopentone and rocuronium. Br J Anaesth
28. Mencke T, Knoll H, Schreiber JU, et al Rocuronium is not associated with more vocal cord injuries than succinylcholine after rapid-sequence induction: a randomized, prospective, controlled trial. Anesth Analg
29. Ghoneim MM, Block RI, Haffarnan M, Mathews MJ. Awareness during anesthesia: risk factors, causes and sequelae – a review of reported cases in the literature. Anesth Analg
30. McHardy FE, Chung F. Postoperative sore throat: cause, prevention and treatment. Anaesthesia
© 2013 European Society of Anaesthesiology
31. Christensen AM, Willemoes-Larsen H, Lundby L, Jakobsen KB. Postoperative throat complaints after tracheal intubation. Br J Anaesth