Acta Anaesthesiol Scand 2014; 58: 815–819 Printed in Singapore. All rights reserved

© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd ACTA ANAESTHESIOLOGICA SCANDINAVICA

doi: 10.1111/aas.12338

The median effective dose of dexmedetomidine for laryngeal mask airway insertion with propofol 2.0 mg/kg H. J. Kwak1, S. K. Min2, J. Y. Yoo2, K. H. Park2 and J. Y. Kim2

1 Department of Anaesthesiology and Pain Medicine, Gil Medical Center, Gachon University, Incheon, Korea, 2Department of Anaesthesiology Pain Medicine, Ajou University School of Medicine, Suwon, Korea

Background: Dexmedetomidine can be used as a co-induction agent to facilitate laryngeal mask airway (LMA) insertion with minimal effect on respiratory function. The purpose of the study was to determine the median effective dose (ED50) of dexmedetomidine to facilitate LMA insertion during anaesthesia induction with propofol 2.0 mg/kg without neuromuscular blockade. Methods: Twenty-two patients, whose American Society of Anesthesiologists physical status was I or II with ages between 18 and 60 years undergoing minor orthopaedic or gynaecological surgery, were enrolled. After an injection of pre-determined bolus dose of dexmedetomidine over 2 min, anaesthesia was induced with propofol 2.0 mg/kg. The modified Dixon’s up-and-down method was used to determine the bolus dose of dexmedetomidine, starting from 0.5 μg/kg (step size; 0.1 μg/ kg). LMA insertion was conducted 90 s after the propofol injec-

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or successful laryngeal mask airway (LMA) insertion, a proper mouth opening and sufficient anaesthesia depth are required in order to reduce the reflexes of the upper airway and to avoid the unwanted events of gagging, coughing and laryngospasm. During LMA insertion, propofol is used as a prevalent induction agent because of its depressant effects on airway reflexes. However, propofol as a sole anaesthetic agent does not completely suppress undesirable airway responses, and the use of a higher than standard induction dose of propofol can provoke unintended cardiorespiratory depression.1–3 Potent short-acting opioids (e.g., fentanyl or remifentanil) have often been co-administered with propofol for LMA insertion to reduce the propofol requirement and haemodynamic changes.4–6 However, the incidence and duration of apnoea time may increase with these opioids.7–9 Dexmedetomidine is a highly selective α2 receptor agonist, which produces sedative, anxiolytic and

tion, and the response of patients was categorized as either ‘success’ or ‘failure.’ Results: Insertion of the LMA was unsuccessful in 12 of 22 patients. The ED50 (95% confidence interval) of dexmedetomidine for successful LMA insertion with propofol 2.0 mg/kg was 0.55 (0.44–0.66) μg/kg. Bradycardia occurred in four patients, and seven patients had an apneic episode. Conclusion: The single dose of dexmedetomidine for successful LMA insertion to be feasible in 50% of patients was 0.55 μg/kg during anaesthesia induction with propofol 2 mg/kg. Accepted for publication 11 April 2014 © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd

analgesic effects without causing clinically significant respiratory depression.10,11 Dexmedetomidine also reduces the propofol requirement for sedation and anaesthesia induction.12 Therefore, dexmedetomidine may be a useful co-induction agent to facilitate LMA insertion with minimal effects on respiratory function. A recent study showed that dexmedetomidine administration prior to propofol induction provided similar conditions for successful LMA insertion, as does fentanyl without respiratory depression.13 The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine required for successful LMA insertion during induction with propofol of 2 mg/kg in absence of neuromuscular blockade.

Methods This study was approved by the institutional review board (Ajou University Hospital, Suwon, Korea) and registered at ClinicalTrials.gov (NCT 01852539).

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Written informed consent for the study was obtained from each patient. Twenty-two patients, whose American Society of Anesthesiologists (ASA) physical status was I or II, and were of ages between 18 and 60 years, undergoing minor orthopaedic or gynaecological surgery under general anaesthesia, were enrolled in this study. Exclusion criteria were a suspected difficult airway, reactive airway disease, recent upper respiratory tract infection, gastrointestinal reflux and obesity (body mass index > 30 kg/ m2). No sedative pre-medication was given before surgery. Upon arrival in the operating room, all patients were monitored with pulse oximeter, electrocardiogram, non-invasive blood pressure and bispectral index (BIS) (BIS VISTA™ monitor, four electrode sensor; Aspect Medical Systems, Norwood, MA, USA). All patients were preoxygenated with 100% oxygen over 3 min. Each patient received a pre-determined single dose of dexmedetomidine over 2 min. The study syringe was prepared by an independent researcher who was not involved in anaesthesia induction. One minute later, anaesthesia was induced with 2.0 mg/kg of propofol. Lidocaine and neuromuscular blocking agents were not administered. Following loss of consciousness, the patient’s airway was maintained via facemask using 100% oxygen with gentle neck extension and jaw lifting. Spontaneous breathing was maintained, if possible, during the study period. If prolonged apnoea (> 30 s) developed, gentle manual ventilation was applied. Sixty seconds after completion of propofol administration, the insertion of LMA (LMA-Classic™, The Laryngeal Mask Co. Ltd., Nicosia, Cyprus) was conducted after confirming BIS scores less than 60. The LMA was inserted by one of two experienced anaesthesiologists who were unaware of the dose of dexmedetomidine, according to manufacturer’s recommendations. The LMA size chosen was #3 for women and #4 for men. Maintenance of anaesthesia was done with sevoflurane in oxygen and air. The dose of dexmedetomidine for each patient was determined by the response of the previously tested patients using the modified Dixon’s up-anddown method.14 The first patient was tested at 0.5 μg/kg dexmedetomidine (0.1 μg/kg as a step size). The response of the patients to the LMA insertion was categorized as either ‘success (no movement)’ or ‘failure (movement).’ Movement was defined as difficult mouth opening, gross purposeful muscular movement, coughing, gagging, or laryngospasm occurring before or after inflation of

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the LMA cuff. Laryngospasm was defined as the presence of stridor or other evidence of upper airway obstruction. No movement was depicted when the reactions mentioned earlier were absent. A single assessment was obtained from each patient whether the attempt was a success or failure, and the result of the first attempt was only used for analysis. Haemodynamic data and BIS were measured at baseline (T0), after dexmedetomidine administration (T1), immediately before (T2), and 1 min after LMA insertion (T3). Bradycardia was defined as a heart rate (HR) < 45 beats/min or a decrease of > 30% from the baseline value persisting more than 30 s and was treated with IV atropine 0.5 mg. The sample size was decided based on that of prior literature, which had demonstrated that at least six independent pairs with success/failure LMA insertion are required for reliable estimates of the ED50 of dexmedetomidine with the Dixon’s up-and-down method,14 and data from seven independent pairs of patients were collected for this study. The ED50 (95% confidence interval, CI) of dexmedetomidine for successful LMA insertion was calculated according to the formula of Dixon and Massey.14,15 SPSS 13.0 for Windows (SPSS, Inc., Chicago, IL, USA) was used for statistical analyses. Data are expressed as mean ± SD or number of patients. Haemodynamic changes were compared by repeated measures ANOVA. A P-value < 0.05 was considered significant.

Results A total of 22 patients were enrolled from July 2013 to August 2013 and completed the study. Patients’ characteristics are shown in Table 1. Insertion of the LMA was unsuccessful in 12 of 22 patients. Causes of unsuccessful condition of LMA insertion was difficulty in opening the mouth (four patients), gross purposeful movement (nine patients) and coughing/gagging (five patients). The sequences of successful and unsuccessful LMA insertion for each patient acquired by the up-and-down method are illustrated in Fig. 1. The ED50 (95% CI) of dexmedetomidine for successful insertion of LMA during propofol induction was 0.55 (0.44–0.66) μg/kg by Dixon’s method. Haemodynamic and BIS data of patients with successful LMA insertion are presented in Table 2. Mean arterial pressure (MAP), HR, SpO2 and BIS changed significantly (all P < 0.001). When compared with the baseline value (T0), a biphasic

Dexmedetomidine for LMA insertion Table 1 Patients’ characteristics. Variables

All (n = 22)

Success (n = 10)

Failure (n = 12)

Sex (M/F) Age (years) Weight (kg) Height (cm) ASA physical status (I/II) Cause of failure Difficult mouth opening Gross purposeful movement Coughing Laryngospasm

7/15 36.4 ± 10.5 60.5 ± 9.2 164.3 ± 9.5 19/3

4/6 39.7 ± 12.1 61.9 ± 9.4 166.3 ± 10.3 8/2

3/9 33.6 ± 8.4 59.3 ± 9.2 162.6 ± 8.9 11/1

— — — —

— — — —

4 9 5 0

Values are mean ± standard deviation or numbers. ASA, American Society of Anesthesiologists.

Fig. 1. The responses of 22 patients on laryngeal mask airway (LMA) insertion and the dose of dexmedetomidine. Arrows represent the midpoint doses of all independent pairs of patients involving a crossover (i.e. failure to success). The median effective dose (ED50) [95% confidence interval (CI)] of dexmedetomidine for successful LMA insertion were 0.55 (0.44–0.66) μg/kg.

change in MAP, i.e. a significant increase after dexmedetomidine administration (T1) followed by a decrease before LMA insertion (T2), was observed. HR transiently decreased at T1 when compared with T0. BIS did not change at T1 but significantly decreased at T2 when compared with T0. Bradycardia occurred in four patients and was treated with atropine. Seven patients had an apnoeic episode that was managed with positive pressure ventilation with 100% oxygen until spontaneous respiration was restored. No patients developed laryngospasm or desaturation to SpO2 < 90% throughout the study.

Discussion The ED50 (95% CI) of a single-dose dexmedetomidine for successful insertion of LMA during

anaesthesia induction with propofol 2.0 mg/kg was 0.55 (0.44–0.66) μg/kg by Dixon’s method. Propofol has been commonly used for LMA insertion because it has faster induction time and better patient satisfaction compared with inhalation anaesthetics such as sevoflurane or desflurane.16–18 However, when used alone, propofol has been reported to cause coughing in 22% of patients, gagging in 40% of patients and laryngospasm in 16% of patients.19,20 The co-administration of short-acting opioids, such as fentanyl and remifentanil, or neuromuscular blocking agents have been used. While these opioids were associated with increased incidence and duration of apnoea,7–9 a neuromuscular blockade did not improve the success rate for the LMA insertion.21 Dexmedetomidine is reported to have sedative, analgesic and anaesthetic-sparing effect through its action on the α2-adrenergic receptor.12 Continuous infusion of dexmedetomidine could conceivably cause delayed recovery from anaesthesia because of its sedative property,22 but Liu et al.23 demonstrated that a single dose of dexmedetomidine (0.25–1 μg/ kg) did not delay the recovery and rather improved the recovery profiles after brief procedures. Thus, in this study, a single dose of dexmedetomidine was chosen as an adjunct to propofol for LMA insertion. Dexmedetomidine has been shown to have minimal respiratory depression.10,11 At supramaximal plasma concentration, dexmedetomidine did not lead to prolonged apnoea causing desaturation, as was seen with relatively low plasma concentration of remifentanil.10 Uzümcügil et al.13 also reported that dexmedetomidine 1 μg/kg caused fewer apnoea incidence and shorter apnoea time than fentanyl 1 μg/kg during propofol induction. In this study, mean administered dose of dexmedetomidine

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H. J. Kwak et al. Table 2 Haemodynamic changes during anaesthesia induction in successful LMA insertion (n = 10). MAP (mmHg) HR (beats/min) SpO2 (%) BIS

T0

T1

T2

T3

94.6 ± 15.5 74.5 ± 11.6 99.2 ± 0.6 97.9 ± 0.3

101.8 ± 15.9* 53.3 ± 9.5* 100 ± 0.0* 97.3 ± 0.8

77.1 ± 14.0*† 66.0 ± 8.4† 100 ± 0.0* 39.6 ± 3.1*†

89.3 ± 13.9†‡ 67.2 ± 10.0† 100 ± 0.0* 44.4 ± 4.4*†

*P < 0.05 compared with T0, †P < 0.05 compared with T1, ‡P < 0.05 compared with T2. Values are means ± standard deviation. LMA, laryngeal mask airway; MAP, mean arterial blood pressure; HR, heart rate; SpO2, oxygen saturation; BIS, bispectral index; T0, baseline value; T1, after dexmedetomidine administration; T2, immediately before LMA insertion; T3, 1 min after LMA insertion.

was 0.49 μg/kg, and 7 of 22 patients experienced apnoeic episodes, but no patient had clinically significant desaturation. In a previous study, dexmedetomidine 1 μg/kg administered before propofol 1.5 mg/kg provided a success rate of 92% (24 of 26 patients) for the LMA insertion, which was comparable with fentanyl 1 μg/kg.13 However, dexmedetomidine 1 μg/kg was more frequently associated with episodes of bradycardia than that of 0.5 μg/kg during propofolremifentanil anaesthesia.23 In this study, 4 of 22 patients (18% of patients) experienced bradycardia, which was treated with atropine. Dexmedetomidine has a biphasic effect on blood pressure, a transient increase followed by a longer lasting decrease in arterial blood pressure.24 We also observed this biphasic response in MAP before LMA insertion. In addition, this study showed that haemodynamic responses to the LMA insertion were almost attenuated due to its bradycardiac and hypotensive effects of dexmedetomidine during anaesthesia induction. One of the limitations of this study is the presence of relatively young (mean age of 36 years) and healthy patients and its small scale. The effects of dexmedetomidine may be different in patients with old age, disease and medications. Our results should not be extrapolated to the elderly or diseased patients. Another is the lack of ED95 of dexmedetomidine. The ED95 was not estimated in this study. The up-and-down method was originally designed to determine the ED50. Because physicians are interested in the ED95 in most anaesthetic circumstances, ED95 is estimated with probit analysis or logistic regression with intercept at zero. However, because probit analysis is a technique to transform a 0–1 space into a −∞ to +∞ space, it has no pharmacological meaning. It is better to use a logistic regression with intercept at zero, but because most data points are concentrated around the

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median in this study, the procedure only gives a vague idea of the real curve. In addition, the power of this study was not designed to calculate ED95 with either probit or logistic regression. The aim of this study was to determine the ED50 of dexmedetomidine required for LMA insertion with propofol 2.0 mg/kg, which is commonly used during anaesthesia induction. However, because the subject of interest for many anaesthesiologists is what is the reduction of the induction dose of propofol with a fixed dose of dexmedetomidine, further study is needed to find out ED50 of propofol with dexmedetomidine 0.55 μg/kg based on this study result. In conclusion, the ED50 of a single-dose dexmedetomidine for successful LMA insertion is 0.55 μg/kg when propofol 2.0 mg/kg was used for anaesthesia induction. Conflict of interest: Authors declare no conflicts of interest.

References 1. Richebe’ P, Rivalan B, Baudouin L, Sesay M, Sztark F, Cros AM, Maurette P. Comparison of the anaesthetic requirement with target-controlled infusion of propofol to insert the laryngeal tube vs. the laryngeal mask. Eur J Anaesthesiol 2005; 22: 858–63. 2. Hickey S, Cameron AE, Asbury AJ. Cardiovascular response to insertion of Brain’s laryngeal mask. Anaesthesia 1990; 45: 629–33. 3. Kodaka M, Okamoto Y, Handa F, Kawasaki J, Miyao H. Relationship between fentanyl dose and predicted EC50 of propofol for laryngeal mask airway insertion. Br J Anesth 2004; 92: 238–41. 4. Park HJ, Lee JR, Kim CS, Kim SD, Kim HS. Remifentanil halves the EC50 of propofol for successful insertion of the laryngeal mask airway and laryngeal tube in pediatric patients. Anesth Analg 2007; 105: 57–61. 5. Lee MP, Kua JS, Chiu WK. The use of remifentanil to facilitate the insertion of the laryngeal mask airway. Anesth Analg 2001; 93: 359–62. 6. Goyagi T, Tanaka M, Nishikawa T. Fentanyl decreases propofol requirement for laryngeal mask airway insertion. Acta Anaesthesiol Scand 2003; 47: 771–4.

Dexmedetomidine for LMA insertion 7. Goh PK, Chiu CL, Wang CY, Chan YK, Loo PL. Randomized double-blind comparison of ketamine-propofol, fentanylpropofol and propofol-saline on hemodynamics and laryngeal mask airway insertion conditions. Anesth Intensive Care 2005; 33: 223–8. 8. Yazicioglu H, Muslu S, Yamak B, Erdemli O. Laryngeal mask airway insertion with remifentanill. Acta Anaesthesiol Belg 2005; 56: 171–6. 9. Grewal K, Samsoon G. Facilitation of laryngeal mask airway insertion: effects of remifentanil administered before induction with target-controlled propofol infusion. Anaesthesia 2001; 56: 897–901. 10. Hsu YW, Cortinez LI, Robertson KM, Keifer JC, Sum-Ping ST, Moretti EW, Young CC, Wright DR, Macleod DB, Somma J. Dexmedetomidine pharmacodynamics: part I, crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 2004; 101: 1066–76. 11. Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000; 90: 699– 705. 12. Dutta S, Karol MD, Cohen T, Jones RM, Mant T. Effect of dexmedetomidine on propofol requirements in healthy subjects. J Pharm Sci 2001; 90: 172–81. 13. Uzümcügil F, Canbay O, Celebi N, Karagoz AH, Ozgen S. Comparison of dexmedetomidine-propofol vs. fentanylpropofol for laryngeal mask insertion. Eur J Anaesthesiol 2008; 25: 675–80. 14. Dixon WJ. The up and down method for small samples. J Am Stat Assoc 1965; 60: 967–78. 15. Dixon WJ, Mood AM. A method for obtaining and analyzing sensitivity data. J Am Stat Assoc 1948; 43: 109–26. 16. Siddik-Sayyid SM, Aouad MT, Taha SK, Daaboul DG, Deeb PG, Massouh FM, Muallem MR, Baraka AS. A comparison of sevoflurane-propofol vs. sevoflurane or propofol for laryngeal mask airway insertion in adults. Anesth Analg 2005; 100: 1204–9.

17. Leong WM, Ong EL. Laryngeal mask airway can be inserted with inhaled desflurane induction. J Anesth 2005; 19: 112–7. 18. Suzuki KS, Oohata M, Mori N. Multiple-deep-breath inhalation induction with 5% sevoflurane and 67% nitrous oxide: comparison with intravenous injection of propofol. J Anesth 2002; 16: 97–101. 19. Cheam EW, Chui PT. Randomised double-blind comparison of fentanyl, mivacurium or placebo to facilitate laryngeal mask airway insertion. Anaesthesia 2000; 55: 323–6. 20. Sivalingam P, Kandasamy R, Madhavan G, Dhakshinamoorthi P. Conditions for laryngeal mask insertion. A comparison of propofol vs. sevoflurane with or without alfentanil. Anaesthesia 1999; 54: 271–6. 21. Hemmerling TM, Beaulieu P, Jacobi KE, Babin D, Schmidt J. Neuromuscular blockade does not change the incidence or severity of pharyngolaryngeal discomfort after LMA anesthesia. Can J Anaesth 2004; 51: 728–32. 22. Zeyneloglu P, Pirat A, Candan S, Kuyumcu S, Tekin I, Arslan G. Dexmedetomidine causes prolonged recovery when compared with midazolam/fentanyl combination in outpatient shock wave lithotripsy. Eur J Anaesthesiol 2008; 25: 961–7. 23. Liu C, Zhang Y, She S, Xu L, Ruan X. A randomised controlled trial of dexmedetomidine for suspension laryngoscopy. Anaesthesia 2013; 68: 60–6. 24. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology 1992; 77: 1134–42.

Address: Jong Yeop Kim Department of Anaesthesiology and Pain Medicine Ajou University School of Medicine San 5, Wonchon-dong, Yeongtong-gu 443-721 Suwon Korea e-mail: [email protected]

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Dexmedetomidine can be used as a co-induction agent to facilitate laryngeal mask airway (LMA) insertion with minimal effect on respiratory function. T...
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