Korean J Anesthesiol 2009 Jul; 57(1): 13-9 □ Clinical Research Article □ DOI: 10.4097/kjae.2009.57.1.13 Comparison of intubating conditions and hemodynamic responses to tracheal intubation with different effect-site concentrations of remifentanil without muscle relaxants during target-controlled infusion of propofol Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea Seok Jai Kim, Kyung Yeon Yoo, Byoung Yun Park, Woong Mo Kim, and Cheol Won Jeong Background: We compared the effects of different remifentanil effect-site concentrations on intubating conditions, and cardiovascular and bispectral index score (BIS) responses to intubation at a fixed effect-site concentration of propofol without muscle relaxants. Methods: Sixty-four patients were randomly assigned to one of three groups: remifentanil 2 (group R2, n = 22), 4 (group R4, n = 21), or 6 ng/ml (group R6, n = 21). Anesthesia was induced using target-controlled infusion of propofol 5 μg/ml and each concentration of remifentanil. Laryngoscopy and intubation was attempted at 2.5 min following induction. Intubating conditions were assessed as excellent, good or poor using a standard scoring system. Mean arterial pressure (MAP), heart rate (HR), and BIS values were assessed. Results: Excellent or good intubating conditions were obtained in 91% of group R4 and 95% of R6, both of which are higher compared with 32% of R2 (P ＜ 0.01). MAP and HR decreased significantly after induction in all groups. After intubation, they recovered to baseline value in group R2 and R4 but were significantly less than baseline values in R6. BIS response to intubation was attenuated in group R4 and R6 but not R2. Hypotension was more frequent in group R6 than R2. Conclusions: Remifentanil target concentrations of 4 or 6 ng/ml combined with 5 μg/ml propofol provided good or excellent conditions for tracheal intubation and prevented cardiovascular and BIS response during induction without muscle relaxants. However, the use of 6 ng/ml dose was associated with frequent occurrence of hypotension and bradycardia requiring treatment. (Korean J Anesthesiol 2009; 57 13∼9) Key Words: Intubating conditions, Propofol, Remifentanil, Target controlled infusion. ade and anaphylactic shock [1]. Several studies have suggested INTRODUCTION that the use of propofol and adjuvants such as short-acting opioids, sympatholytics, midazolam, and local anesthetic agents Muscle relaxants are generally used to facilitate laryngoscopy may provide adequate conditions for laryngoscopy and tracheal and endotracheal intubation during induction of general ane- intubation without the need for neuromuscular blocking agents sthesia. In some situations, the use of muscle relaxants is un- [2,3]. desirable or contraindicated because they may have adverse ef- Remifentanil is a selective μ-opioid receptor agonist with a fects such as delayed paralysis, residual neuromuscular block- rapid onset, short duration, and a short blood/effect-site equili- bration half-time [4]. Stevens et al [5] have shown that propo- Received: March 24, 2009. fol 2 mg/kg and remifentanil 3 μg/kg co-administration pro- Accepted: May 14, 2009. vided adequate intubation conditions in healthy patients without Corresponding author: Kyung Yeon Yoo, M.D., Ph.D., Department of Anesthesiology and Pain Medicine, Chonnam National University Medical neuromuscular relaxants. Laryngoscopy and tracheal intubation School, 8, Hak-1dong, Dong-gu, Gwangju 501-757, Korea. Tel: 82-62- may cause cardiovascular changes, which can have adverse ef- 220-6893, Fax: 82-62-232-6294, E-mail: [email protected] fects [6,7], and arousal responses on the electroencephalogram Copyright ⓒ Korean Society of Anesthesiologists, 2009 during induction of anaesthesia [8]. Remifentanil has been re- ｃｃ This is an open-access article distributed under the terms of the Creative ported to attenuate these responses when combined with Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. propofol. The use of a target-controlled infusion (TCI) using a 13 Vol. 57, No. 1, July 2009 Korean J Anesthesiol computer-driven infusion device has been demonstrated to be After preoxygenation for 3 min, anesthesia was induced with Ⓡ more effective in controlling drug concentrations and in main- propofol (Fresofol 2%, Fresenius Kabi, Austria) of 5 μg/ml Ⓡ taining cardiovascular stability as compared with traditional using a TCI system (Orchestra Base Primea , Fresenius Vial, weight-adjusted infusions [9]. Because of its unique pharmaco- France). At the same time, remifentanil was started using the kinetic and pharmacodynamic profile, remifentanil is ideally same TCI system as in propofol. Propofol was administered 5 suited for continuous IV infusion [4]. However, the optimal ef- μg/ml at the effect site concentration in Marsh model [10] fect-site concentration of remifentanil required for intubation and remifentanil 2, 4, or 6 ng/ml in Minto model [11]. The without muscle relaxants while maintaining stable hemodynamic target and effect-site concentrations in each group had reached stability has not been determined using a steady effect-site within 90 s after start of TCI system, and then these concen- concentration of propofol. We therefore conducted this pro- trations were maintained for 60 s before intubation. spective, randomized, double-blind study to compare the differ- When the patients became unconscious, patients’ lungs were ent effect site concentrations of remifentanil on intubating con- ventilated manually with 100% oxygen through an anesthesia ditions, and hemodynamic and bispectral index (BIS) responses face mask connected to a semiclosed anesthesia circuit. Two to induction and endotracheal intubation without muscle relax- and half min following induction of anesthesia, laryngoscopy ants in patients receiving a propofol anesthesia. and endotracheal intubation was performed by an experienced anesthesiologist using a Macintosh 3 laryngoscope blade and a MATERIALS AND METHODS 7.0 or 8.0 mm endotracheal tube followed by slow inflation of the tracheal cuff between 25−30 mmHg with cuff pressure Ⓡ After approval from the Institutional Review Board of the gauge (VBM Cuff Pressure Gauge , VBM Medizintechnik University Hospital, informed written consent was obtained GmbH, Germany). After intubation, anesthesia was maintained from 69 American Society of Anesthesiologist physical status I with propofol 2−3 ug/ml, remifentanil 2−3 ng/ml. Intubating or II patients, aged 25−60 yrs. Patients with known car- conditions were evaluated by using a scoring system. Ease of diovascular, pulmonary, or renal disease, drug or alcohol abus- ventilation, jaw relaxation, ease of laryngoscopy, opening of ers, obesity greater than body mass index 30 kg/m2, and pa- vocal cords, degree of coughing and patient movement were tients with predicted difficult intubation (Mallampati classi- used to score overall intubating conditions as excellent (all cri- fication of airway anatomy higher than II) were excluded. teria scored as 1), good (mask ventilation scored as 1 and the All patients were premedicated with midazolam 0.1 mg/kg other criteria as 1 or 2) or poor (one of the criteria scored as orally 60 min before the induction of anesthesia. Before arrival 3) (Table 1) [12]. Patients who developed muscle rigidity and in the operating room, an IV catheter was placed to allow the thus could not be ventilated with face mask were given ro- administration of fluids and medications. Additionally, a 20- curonium 0.6 mg/kg IV to facilitate endotracheal intubation. gauge catheter was inserted into a radial artery connected to a These cases were excluded from data analysis. pressure transducer to measure blood pressure and to collect Mean arterial blood pressure (MAP), heart rate (HR), and blood samples. Monitoring consisted of invasive arterial blood BIS values were recorded by an independent investigator be- pressure, electrocardiogram, pulse oximetry, capnometry and fore induction of anesthesia (baseline), just before laryngoscopy BIS. A standard BIS electrode montage (BIS Sensor-Aspect and intubation, and at 1 min intervals up to 5 min thereafter. Medical Systems, Inc., Natick, MA, USA) was applied to the BIS values were recorded as the maximum value displayed forehead before induction of anesthesia, and BIS was measured within each minute. These values were confirmed by down- Ⓡ continuously throughout the study using an Aspect A-2000 BIS loading data from the electronic memory of the monitor at the Ⓡ monitor (BIS XP, software version 3.31; Aspect Medical end of surgery. Arousal response (defined by an increase in Systems, Natick, MA, USA). HR was determined from electro- BIS to intubation) was determined by calculating the difference cardiogram traces. Patients were randomized to one of three of highest BIS value observed after intubation (for 5 min after groups, each to receive one of the following effect site con- intubation) and BIS value measured just before starting laryn- centrations of remifentanil in a double-blind manner; 2 ng/ml goscopy. Hypotension was defined as MAP ＜ 55 mm Hg, (R2 group, n = 22), 4 ng/ml (R4 group, n = 21), and 6 ng/ml and intravenous ephedrine 8 mg was administered for hypo- (R6 group, n = 21). tension of more than 60 s. Bradycardia was defined as HR ＜ 14 Kim et al：Intubating conditions and remifentanil Table 1. Scoring Criteria at Tracheal Intubation Table 2. Demographic Data R2 (n = 22) R4 (n = 21) R6 (n = 21) R2 (n = 22) R4 (n = 21) R6 (n = 21) Mask ventilation Sex (M/F) 12 / 10 8 / 13 12 / 9 1. Easy 19 (86.4%) 19 (90.6%) 20 (95.3%) Age (yr) 44 ± 13 47 ± 9 41 ± 13 2. Difficult 3 (13.6%) 2 (9.4%) 1 (4.7%) BMI (kg/m2) 23.6 ± 2.8 22.9 ± 2.4 22.9 ± 3.0 3. Impossible 0 (0%) 0 (0%) 0 (0%) Height (cm) 162 ± 9 163 ± 6164 ± 6 Jaw relaxation Values are means ± SD or number of patients. BMI: body mass 1. Complete 19 (86.4%) 19 (90.6%) 21 (100%) index, R2: remifentanil 2 ng/ml, R4: remifentanil 4 ng/ml, R6: re- 2.