Effect-site concentration of remifentanil for laryngeal mask airway insertion during target-controlled infusion of propofol

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1 doi: /j x Effect-site concentration of remifentanil for laryngeal mask airway insertion during target-controlled infusion of propofol M. K. Kim, 1 J. W. Lee, 2 D. J. Jang, 3 O. Y. Shin 4 and S. B. Nam 2 1 Clinical Assistant Professor, 4 Professor, Department of Anaesthesiology and Pain Medicine, College of Medicine, Kyung Hee University, Seoul, Korea 2 Assistant Professor, 3 Fellow, Department of Anaesthesiology and Pain Medicine, and Anaesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea Summary The purpose of this study was to determine the effect-site concentration of remifentanil that would provide optimal conditions for successful laryngeal mask airway insertion during a target-controlled infusion (TCI) of propofol at 3.5 lg.ml )1 without the use of neuromuscular blockade. Five minutes after propofol infusion, remifentanil was infused at a dose determined by a modified Dixon s up-and-down method. Five minutes after remifentanil infusion, the laryngeal mask was inserted. The effect-site concentration of remifentanil for successful laryngeal mask insertion in 50% of adults (EC 50 ) was 3.04 (SD 0.49) ng.ml )1 during a TCI of 3.5 lg.ml )1 propofol without neuromuscular blockade. From the probit analysis, the EC 50 and EC 95 of remifentanil were 2.84 ng.ml )1 (95% CI ng.ml )1 ) and 3.79 ng.ml )1 (95% CI ng.ml )1 ), respectively.... Correspondence to: Dr Sang Beom Nam sbnam@yuhs.ac Accepted: 30 July 2008 Propofol has been widely used for laryngeal mask airway insertion because it provides greater inhibitory effect on pharyngeal and laryngeal reactivity than does thiopental [1, 2]. However, induction with propofol alone requires a high bolus dose ( mg.kg )1 ) or target plasma concentration (7 9 lg.ml )1 ), which may result in cardiovascular and or respiratory depression [3 6]. There have been some reports that propofol at 2.5 mg.kg )1 as the sole agent does not provide adequate anaesthesia for laryngeal mask airway insertion in unpremedicated patients [7 9]. The addition of opioids as adjuvant agents during induction reduces the amount of propofol required to insert the laryngeal mask airway, provides better insertion conditions, and attenuates haemodynamic instability [10 12]. In particular, remifentanil has been shown to be ideal for the attenuation of brief but strong noxious stimuli, such as tracheal intubation or laryngeal mask airway insertion, because it provides intense analgesia with a rapid onset and ultrashort duration of action [12, 13]. However, little is known about the optimal effect-site concentration of remifentanil required for the successful insertion of the laryngeal mask airway during a targetcontrolled infusion (TCI) of propofol. This study was designed to determine the optimal effect-site concentration of remifentanil for facilitation of laryngeal mask airway insertion in patients receiving a TCI of propofol set at an effect-site concentration of 3.5 lg.ml )1. Methods After obtaining the approval of our institutional ethics committee and written informed consent, we enrolled ASA physical status I-II patients who were years old and scheduled for general anaesthesia for minor elective surgery. Adults with a potentially difficult airway (cervical spine disease, Mallampati classification III or IV, or a mouth opening of < 2.5 cm), reactive airway disease or signs of upper respiratory infection, a history of cardiac, pulmonary, or renal disease, or taking analgesic medication were excluded from the study. We also excluded patients who had a risk of gastric aspiration upon anaesthesia induction or a body mass index > 30 kg.m ) Journal compilation Ó 2009 The Association of Anaesthetists of Great Britain and Ireland

2 M. K. Kim et al. Æ Remifentanil and laryngeal mask insertion Upon arrival in the pre-anaesthetic preparing room, a 20G venous cannula was sited and 10 ml.kg )1 lactated Ringer s solution was infused. Subsequently, fluid was infused at a rate of 100 ml.h )1. The infusion port for propofol and remifentanil was connected as close as possible to the intravenous catheter to minimise dead space. Glycopyrrolate mg.kg )1 was administered intravenously min before anaesthesia induction. No other opioid or sedative premedication was given. Once in the operating theatre, standard monitoring included electrocardiogram, oxyhaemoglobin saturation, noninvasive arterial blood pressure, and end-tidal CO 2 concentration. The depth of anaesthesia was monitored using the bispectral index (BIS) monitor (A-2000 TM, Version 3.4; Aspect Medical System Inc., Newton, MA, USA). All patients were pre-oxygenated using 100% oxygen with a normal tidal volume for 3 min. After the administration of 40 mg intravenous lidocaine with venous occlusion for 2 min, anaesthesia was induced with propofol at an effect-site concentration of 3.5 lg.ml )1 using a TCI device (Orchestra Ò ; Fresenius- Vial, Brezins, France). We used the Schnider pharmacokinetic model for propofol, in which the plasma-effect-site equilibration rate constant (k e0 ) is 0.46 min )1 [3, 14 16]. If necessary, ventilation was assisted manually to maintain a concentration of endtidal CO kpa. Five minutes after start of propofol TCI, remifentanil was administered through a TCI device (Orchestra Ò ; Fresenius-Vial, Brezins, France) at the predetermined effect-site concentration. We used the Minto pharmacokinetic model (k e0 = 0.60 min )1 ) for remifentanil [17]. Five minutes following remifentanil administration, an experienced anaesthetist inserted the laryngeal mask airway in all patients of the study according to the manufacturers recommendations [18]. The anaesthetist who performed or evaluated the conditions of insertion was unaware of the dose of remifentanil used. The effect-site concentration of remifentanil used for each patient was determined by the response of the previously tested patient using a modified up-and-down sequential allocation technique [19 21]. The first patient received an effect-site concentration of remifentanil of 5 ng.ml )1. The response of each patient determined the effect-site concentration of remifentanil of the next patient. If the insertion of the laryngeal mask airway was a success, then the target effect-site concentration was decreased by a step of 1 ng.ml )1. If insertion was a failure, the target effect-site concentration was increased by the same dose. According to the modified up-and-down method [20], the first stage consisted of an up-and-down sequence of steps of 1 ng.ml )1 until three changes of response type were observed. After the first three such negative-positive up-and-down crossovers, the step change of dose was reduced to 0.5 ng.ml )1. Patient movement at the time of laryngeal mask airway insertion or within 1 min of insertion was classified as a failure of insertion ( movement defined as coughing, straining, bucking, laryngospasm or gross purposeful movement). Also, significant resistance to mouth opening (Muzi score > 2; 1 = fully relaxed, 2 = mild resistance, 3 = resistance but could be opened, and 4 = resistance requiring further doses of propofol [9, 22]) was defined as a failure of insertion. If laryngeal mask airway insertion failed, further doses of propofol or remifentanil were given according to each patient s needs, and insertion was reattempted. The patient s heart rate and non-invasive blood pressure were recorded immediately before (baseline) and at 1, 3, and 5 min after propofol and remifentanil administration. These variables were also recorded 1 min after laryngeal mask airway insertion. Hypotension was defined as a mean arterial pressure of < 60 mmhg or a decrease of > 30% from the baseline value that persisted for more than 1 min and was treated by an incremental boluses of intravenous ephedrine (4 6 mg). A heart rate of < 40 beats.min )1 or a decrease of > 30% from the baseline value lasting more than 1 min was defined as bradycardia and treated with 0.5 mg of intravenous atropine. All patients were interviewed in the postoperative anaesthetic care unit to assess memory recall. Statistical analysis was performed using the Statistical Package for Social Sciences software (SPSS 12.0 for windows; SPSS Inc, IL, USA) and SigmaStat (SIGMASTAT 3.1; Systat Software, Inc., CA, USA). The effect-site concentration of remifentanil required for successful laryngeal mask airway insertion in 50% of adults (EC 50 ) was determined by calculating the mean of the midpoint concentration of all independent pairs of patients who manifested a crossover from a negative response to a positive one (i.e. failure to success of laryngeal mask airway insertion) [19 21]. EC 50 and EC 95 with 95% confidence intervals (CI) were determined by a probit analysis. Haemodynamic data were analysed with repeated measures of ANOVA. A p value < 0.05 was considered statistically significant. Results Twenty patients were enrolled in this study. Figure 1 shows individual concentration-responses according to the up-and-down sequence. From the modified Dixon s up-and-down method, the EC 50 of remifentanil for laryngeal mask airway insertion during a TCI of 3.5 lg.ml )1 propofol was 3.04 (SD 0.49) ng.ml )1. From Journal compilation Ó 2009 The Association of Anaesthetists of Great Britain and Ireland 137

3 M. K. Kim et al. Æ Remifentanil and laryngeal mask insertion Anaesthesia, 2009, 64, pages Table 1 Changes in arterial blood pressure and heart rate. Values are mean (SD). HR MAP (beats.min )1 ) p value (mmhg) p value Figure 1 Patient responses to laryngeal mask airway insertion. Arrows indicate the midpoint of the effect-site concentration of all independent pairs of patients involving crossover from a negative response to a positive response (i.e. failure to success of laryngeal mask airway insertion). The effect-site concentration of remifentanil for successful laryngeal mask airway insertion in 50% of patients was 3.04 (SD 0.49) ng.ml )1. Baseline 86.2 (16.7) 94.3 (12.0) After propofol infusion 1 min 89.4 (12.9) (13.3) min 84.0 (13.8) (12.5) min 81.4 (13.6) (9.3) After remifentanil infusion 1 min 78.6 (12.7) (10.4) min 70.6 (11.0) (11.4) < min 66.7 (9.4) < (9.5) < After LMA insertion 1 min 64.0 (11.2) < (9.0) < HR, heart rate; MAP, mean arterial blood pressure; baseline, immediately before propofol infusion. probit analysis, the EC 50 and EC 95 were 2.84 ng.ml )1 (95% CI ng.ml )1 ) and 3.79 ng.ml )1 (95% CI ng.ml )1 ), respectively (Fig. 2). The EC 50 value obtained with a probit analysis did not differ significantly from the EC 50 value calculated from the up-and-down method. Haemodynamic data of the patients are shown in Table 1. Mean arterial blood pressure after remifentanil infusion and after laryngeal mask airway insertion were significantly decreased compared with baseline values. However, there were no patients with clinically significant hypotension or bradycardia requiring treatment. No patients demonstrated memory recall during the induction or anaesthetic period. Discussion Figure 2 The effect-site concentration and response curve from the probit analysis. The effect-site concentrations at which there were 50% and 95% probabilities of successful laryngeal mask airway insertion were 2.84 and 3.79 ng.ml )1, respectively. Using the modified Dixon s up-and-down method, this study demonstrated that the required effect-site concentration of remifentanil at which successful laryngeal mask airway insertion is possible in 50% of adults was 3.04 (SD 0.49) ng.ml )1 during a TCI of 3.5 lg.ml )1 propofol. Various adjuncts such as lidocaine [23], midazolam [24], and opioids [10 12] have been used with propofol at induction to facilitate laryngeal mask airway insertion. Of these agents, remifentanil (a selective l-opioid receptor agonist with rapid onset and ultrashort duration of action) prevents sympathetic responses induced by short and intense stimuli. There have been a few studies reporting that a bolus dose of remifentanil facilitates laryngeal mask airway insertion. Lee et al. reported that a bolus dose of 0.25 lg.kg )1 remifentanil, when administered after 2.5 mg.kg )1 propofol, facilitated laryngeal mask airway insertion [12]. Also, a bolus dose of 0.3 lg.kg )1 remifentanil followed by the induction of anaesthesia with a propofol target-controlled infusion, improved the conditions of laryngeal mask airway insertion [25]. In this study, we used TCI as the method of continuous infusion because it results in fewer overdose-linked adverse effects and provides greater cardiovascular stability as compared with traditional weight-adjusted infusions [26]. Also, TCI targets the effect-site concentration rather than the plasma concentration because it more accurately reproduces the desired time course of drug effect [27 29]. 138 Journal compilation Ó 2009 The Association of Anaesthetists of Great Britain and Ireland

4 M. K. Kim et al. Æ Remifentanil and laryngeal mask insertion During this study we did not measure actual plasma concentrations of propofol and remifentanil. The plasmasite and effect-site concentrations were predicted only via pharmacokinetic parameters and the plasma effect-site equilibration rate constant (k e0 ), respectively. The variable sets of Schnider et al. [14, 28] selected for propofol and Minto et al. [17] selected for remifentanil have been shown to be adequately accurate in predicting plasma and effect-site concentrations. Previous studies have used target concentrations of propofol for laryngeal mask airway insertion considerably different from that in our study. For example, Higuchi et al. [4] reported that the required target effect-site concentration of propofol for laryngeal mask airway insertion is 8.72 lg.ml )1, while Kodaka et al. [15, 16] reported 3.25 lg.ml )1. These differences may be due to differences in study design, such as using either the effect-site concentration or plasma concentration of propofol, using sedative premedication, or different definitions for successful laryngeal mask airway insertion. As compared with these previous studies, we tried to maintain a relatively low target effect-site concentration of propofol in order to minimise haemodynamic instability [27, 28]. Taylor et al. [3] reported that patients lose consciousness at a blood concentration of propofol at 9 lg.ml )1, but the concentration at the effect-site is only around 3.5 lg.ml )1 because of the lag time of equilibration between the blood and the effect-site. The k e0 values and time to peak effect that we selected for propofol and remifentanil were 0.46 and 0.60 min )1 and 1.7 and min, respectively [17, 28]. In some studies, the steady-state infusion for propofol was maintained for 15 min before administering verbal command or other drugs to ensure equilibration between the blood- and effect-site concentration [4, 30]. However, this protocol cannot be applied to busy clinical settings, and haemodynamic instability may be inevitable. In conclusion, the effect-site concentration of remifentanil for successful laryngeal mask airway insertion in 50% of adults was 3.04 (SD 0.49) ng.ml )1 during induction using a TCI of 3.5 lg.ml )1 propofol without a neuromuscular blocking agent. From the probit analysis, the EC 50 and EC 95 of remifentanil were 2.84 ng.ml )1 (95% CI ng.ml )1 ) and 3.79 ng.ml )1 (95% CI ng.ml )1 ), respectively. References 1 Brown GW, Patel N, Ellis FR. Comparison of propofol and thiopentone for laryngeal mask insertion. Anaesthesia 1991; 46: McKeating K, Bali IM, Dundee JW. The effects of thiopentone and propofol on upper airway integrity. Anaesthesia 1988; 43: Taylor IN, Kenny GN. Requirements for target-controlled infusion of propofol to insert the laryngeal mask airway. Anaesthesia 1998; 53: Higuchi H, Adachi Y, Arimura S, Nitahara K, Satoh T. Oral clonidine premedication reduces the EC 50 of propofol concentration for laryngeal mask airway insertion in male patients. Acta Anaesthesiologica Scandinavica 2002; 46: Richebé P, Rivalan B, Baudouin L, et al. Comparison of the anaesthetic requirement with target-controlled infusion of propofol to insert the laryngeal tube vs. the laryngeal mask. European Journal of Anaesthesiology 2005; 22: Hickey S, Cameron AE, Asbury AJ. Cardiovascular response to insertion of Brain s laryngeal mask. Anaesthesia 1990; 45: Brain AI. The laryngeal mask a new concept in airway management. British Journal of Anaesthesia 1983; 55: Scanlon P, Carey M, Power M, Kirby F. Patient response to laryngeal mask insertion after induction of anaesthesia with propofol or thiopentone. Canadian Journal of Anaesthesia 1993; 40: Burlacu CL, Gaskin P, Fernandes A, Carey M, Briggs L. A comparison of the insertion characteristics of the laryngeal tube and the laryngeal mask airway: a study of the ED50 propofol requirements. Anaesthesia 2006; 61: Kazama T, Ikeda K, Morita K. Reduction by fentanyl of the Cp 50 values of propofol and hemodynamic responses to various noxious stimuli. Anesthesiology 1997; 87: Iselin-Chaves IA, Flaishon R, Sebel PS, et al. The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the Bispectral Index. Anesthesia and Analgesia 1998; 87: Lee MP, Kua JS, Chiu WK. The use of remifentanil to facilitate the insertion of the laryngeal mask airway. Anesthesia and Analgesia 2001; 93: Hall AP, Thompson JP, Leslie NA, Fox AJ, Kumar N, Rowbotham DJ. Comparison of different doses of remifentanil on the cardiovascular response to laryngoscopy and tracheal intubation. British Journal of Anaesthesia 2000; 84: Schnider TW, Minto CF, Shafer SL, et al. The influence of age on propofol pharmacodynamics. Anesthesiology 1999; 90: Kodaka M, Okamoto Y, Koyama K, Miyao H. Predicted values of propofol EC 50 and sevoflurane concentration for insertion of laryngeal mask Classic TM and ProSeal TM. British Journal of Anaesthesia 2004; 92: Kodaka M, Handa F, Kawasaki J, Miyao H. Cp50 of propofol for laryngeal mask airway insertion using predicted concentrations with and without nitrous oxide. Anaesthesia 2002; 57: Minto CF, Schnider TW, Egan TD, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 1997; 86: Brimacombe J, Berry A. Insertion of the laryngeal mask airway a prospective study of four techniques. Anaesthesia and Intensive Care 1993; 21: Journal compilation Ó 2009 The Association of Anaesthetists of Great Britain and Ireland 139

5 M. K. Kim et al. Æ Remifentanil and laryngeal mask insertion Anaesthesia, 2009, 64, pages Dixon WJ. Staircase bioassay: the up-and-down method. Neuroscience and Biobehavioral Reviews 1991; 15: Choi SC. Interval estimation of the LD50 based on an up-and-down experiment. Biometrics 1990; 46: Jung H, Choi SC. Sequential method of estimating the LD50 using a modified up-and-down rule. Journal of Biopharmaceutical Statistics 1994; 4: Muzi M, Robinson BJ, Ebert TJ, O Brien TJ. Induction of anesthesia and tracheal intubation with sevoflurane in adults. Anesthesiology 1996; 85: Stoneham MD, Bree SE, Sneyd JR. Facilitation of laryngeal mask insertion. Effects of lignocaine given intravenously before induction with propofol. Anaesthesia 1995; 50: Godsiff L, Magee L, Park GR. Propofol versus propofol with midazolam for laryngeal mask insertion. European Journal of Anaesthesiology 1995; 12: Grewal K, Samsoon G. Facilitation of laryngeal mask airway insertion: effects of remifentanil administered before induction with target-controlled propofol infusion. Anaesthesia 2001; 56: De Castro V, Godet G, Mencia G, Raux M, Coriat P. Target-controlled infusion for remifentanil in vascular patients improves hemodynamics and decreases remifentanil requirement. Anesthesia and Analgesia 2003; 96: Shafer SL, Gregg KM. Algorithms to rapidly achieve and maintain stable drug concentrations at the site of drug effect with a computer-controlled infusion pump. Journal of Pharmacokinetics and Biopharmaceutics 1992; 20: Schnider TW, Minto CF, Gambus PL, et al. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology 1998; 88: Struys MM, De Smet T, Versichelen LF, Van De Velde S, Van den Broecke R, Mortier EP. Comparison of closed-loop controlled administration of propofol using Bispectral Index as the controlled variable versus standard practice controlled administration. Anesthesiology 2001; 95: Albertin A, Casati A, Federica L, et al. The effect-site concentration of remifentanil blunting cardiovascular responses to tracheal intubation and skin incision during bispectral index-guided propofol anesthesia. Anesthesia and Analgesia 2005; 101: Journal compilation Ó 2009 The Association of Anaesthetists of Great Britain and Ireland