Anesth Analg 2007;105:57-61
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000266447.23037.e4
PEDIATRIC ANESTHESIOLOGY
Remifentanil Halves the EC50 of Propofol for Successful Insertion of the Laryngeal Mask Airway and Laryngeal Tube in Pediatric Patients
Hye-Jin Park, MD*,
Jeong-Rim Lee, MD ,
Chong Sung Kim, MD,
Seong Deok Kim, MD, and
Hee-Soo Kim, MD
From the *Department of Anesthesiology, College of Medicine, Eulji University, and Department of Anesthesiology, Seoul National University College of Medicine, Seoul, Korea.
Address correspondence and reprint requests to Hee-Soo Kim, MD, No. 28 Yongondong, Jongnogu, Seoul, 110-744, Korea. Address e-mail to dami0605{at}snu.ac.kr.
Abstract
BACKGROUND: Propofol and remifentanil are the drugs of choice for insertion of the supraglottic airway without muscle relaxants for short duration surgery. In this study, we compared propofol concentrations required for insertion of laryngeal mask way (LMA) or laryngeal tube (LT) with and without remifentanil.
METHODS: We included children scheduled for surgeries lasting <2 h, and assigned them to four groups in a randomized, double-blind manner: LMA with propofol + saline (LMA-P), LT with propofol + saline (LT-P), LMA with propofol + 7.5 ng/mL remifentanil (LMA-PR), LT with propofol +7.5 ng/mL remifentanil (LT-PR). Anesthesia was conducted by target-controlled infusion in determined target effect site concentration of propofol and remifentanil with the STELPUMP program. The EC50 of propofol for airway device placement was determined using Dixon's up-and-down method. The concentration of propofol for consecutive patients in each group was determined by the response of the previous patient, using increments or decrements of 0.2 µg/mL.
RESULTS: In patients receiving remifentanil, propofol EC50 for insertion of a LMA was 2.57 ± 0.22 µg/mL and that of LT was 2.59 ± 0.20 µg/mL (n.s.). In patients receiving saline, the corresponding values were 5.45 ± 0.21 µg/mL and 5.58 ± 0.23 µg/mL (n.s.). Conditions were excellent in 64% (9 of 14) and 79% (11 of 14) of patients receiving remifentanil, but in patients receiving saline, the values were 18% (2 of 11) for the LMA and 40.0% (4 of 10) for the LT.
CONCLUSIONS: Remifentanil 7.5 ng/mL reduced the propofol concentration required for airway insertion by half, and improved conditions for insertion. Propofol concentrations for insertion of the LMA and LT were similar.
As day surgery in pediatric patients becomes more popular, supraglottic airways are being increasingly used. The laryngeal tube (LT), a recently introduced device, is similar to the laryngeal mask way (LMA), used to secure a patent airway during anesthesia (1). It consists of an airway tube with a small cuff attached at the tip (the distal cuff) and a larger central balloon cuff (the proximal cuff) (2). The upper airway contact sites are different in the LT and LMA, but the devices share the same indication for spontaneous breathing or controlled ventilation during anesthesia.
Propofol is one of the most useful induction drugs for insertion of supraglottic airways, because of its superior relaxation of the jaw (3,4) and suppression of airway reflexes (5), although adjuvants may be needed in many cases. Opioids are suitable, and are often used with propofol for this purpose (6). Remifentanil is an ultrashort-acting potent opioid metabolized by nonspecific plasma and tissue esterase. Combined with propofol, it is ideal for improving conditions for insertion of supraglottic airways in minor surgery (7).
The aims of this study were to determine the clinically required concentration of propofol for LMA and LT insertion, and to examine to what extent remifentanil reduces the dose of propofol and improves conditions for insertion of these devices.
METHODS
After IRB approval and written informed consent from parents or guardians, we studied 98 children between 2 and 12-yr-old, ASA status I or II, undergoing elective minor urologic, orthopedic or plastic surgery, in whom the use of the LMA or LT was indicated. Patients with abnormal airway, gastroesophageal reflux, reactive airway disease, or a history of a respiratory tract infection in the preceding 6 wk were excluded. The children were randomized into four groups: LMA with propofol + saline (LMA-P), LT with propofol + saline (LT-P), LMA with propofol + remifentanil (LMA-PR), LT with propofol + remifentanil (LT-PR).
All patients were unpremedicated and had been fasted for at least 6 h and hydrated with Ringer's lactated solution according to body weight and fasting duration. Electrocardiogram, heart rate, Spo2 and noninvasive arterial blood pressure were monitored at 1 min intervals in the operating room. Atropine 0.02 mg/kg for preventing bradycardia and 1 mg/kg of 1% lidocaine for reducing injection pain were given before IV anesthetics. Propofol and remifentanil were administered by target-controlled infusion via a syringe pump (Pilot Anesthesia 2, Fresenius vial, France) driven by STELPUMP (Ver.1.07). Marsh et al.'s (8) pharmacokinetic model for propofol and Minto et al.'s (9) for remifentanil were used. After loss of consciousness, mask ventilation was maintained with 100% oxygen. The propofol infusion was started with coadministration of saline or remifentanil at target-controlled infusion 7.5 ng/mL (10). Preliminary studies suggested an initial target effect site concentration of propofol of 5.0 µg/mL in the propofol + saline groups and 3 µg/mL in the propofol + remifentanil groups.
After equilibration of plasma and effect site propofol concentrations, the airway devices were inserted by a single anesthesiologist, without the use of muscle relaxants, using the same method for both airway devices. The cuffs were evacuated completely. The anesthesiologist inserted the airway device with the tip pressed against the hard palate, and slid it smoothly along the palate through the midline of the mouth until resistance was felt, while the operator's free hand held the patient's mouth open. The finger was not introduced into the mouth. The patient's response to the insertion was classified by the same blinded investigator as "excellent," "good," or "fail." (11); Excellent was defined as lack of movement of the body or limbs within 1 min of insertion, with no cough or gagging, and good jaw relaxation. Good was defined as minor movement, such as finger movement within 1 min of insertion and good jaw relaxation; but one or two coughs or gags was permitted. Fail was defined as major movement of the body or limbs within 1 min of insertion of the device or >2 coughs or gags, or mouth opening resistance (12). The incidence of laryngospasm, upper airway trauma, bradycardia, and hypotension were recorded. Laryngospasm was defined as the presence of stridor, the absence of a capnograph wave, or any other evidence of upper airway obstruction during assisted or controlled manual ventilation. Upper airway trauma was defined by the presence of bloodstains on the device after removal, or if the patient complained of sore throat. Bradycardia and hypotension were defined as the decrease of >20% of the preoperative value within 1 min after insertion of the LMA or LT.
The EC50 of propofol for airway device placement was determined by a modification of Dixon's up-and-down method (13). If the patient response was good or excellent, the next target concentration of propofol was decreased by a step of 0.2 µg/mL. If patient response was "fail," the target concentration was increased by 0.2 µg/mL. The process was repeated until the sixth cross-over point (fail/excellent or good) was obtained. The midpoint was defined as the mean cross-over concentration. The EC50 was defined as the mean cross-over midpoint in each group. Patients were interviewed in the recovery room to assess memory recall if the patients were old enough to answer the question. Statistical analyses were performed using ANOVA and the  2 test. Probit analysis was used for calculating confidence interval and plotting the dose-response curve. Values are expressed as mean ± sd or number of patients. P < 0.05 was considered to be statistically significant.
RESULTS
There were no significant differences inpatient characteristics among the groups (LMA-P, n = 25, 7.6 ± 3.1-yr-old; LT-P, n = 23, 8.0 ± 4.1-yr-old; LMA-PR, n = 25, 7.8 ± 2.3-yr-old; LT-PR, n = 25, 7.7 ± 3.1-yr-old). There were no cases of airway trauma, recall, or significant hypotension or bradycardia. Without remifentanil, the EC50 of propofol for LMA insertion was 5.45 ± 0.21 µg/mL [95% confidence interval 5.23–5.82] and 5.58 ± 0.23 µg/mL [5.41–5.81] for the LT (Fig. 1). With 7.5 ng/mL of remifentanil, the EC50 of propofol for LMA insertion was 2.57 ± 0.22 µg/mL [2.00–2.97] and 2.59 ± 0.20 µg/mL [2.02–2.81] for the LT (Fig. 2). There were no differences between the propofol EC50 required for insertion of the classic LMA and the LT.
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Figure 1. Consecutive target propofol concentrations in LMA and LT insertion without remifentanil for EC50 determination. The arrow represents the mean propofol concentration when crossing from a failure to a success for insertion. The average of these concentrations is EC50. EC50 for the LMA was 5.45 ± 0.21 µg/mL and 5.58 ± 0.23 µg/mL for the LT. LMA: laryngeal mask airway; LT: laryngeal tube.
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Figure 2. Consecutive target propofol concentration in LMA and LT with adding remifentanil 7.5 ng/mL for EC50 determination. The arrow represents the mean propofol concentration when crossing from a failure to a success for insertion. The average of these concentrations is EC50. EC50 for LMA was 2.57 ± 0.22 µg/mL and 2.59 ± 0.20 µg/mL for the LT. LMA: laryngeal mask airway; LT: laryngeal tube.
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Conditions for insertion in successful cases are shown in Table 1. In the LMA groups, conditions were excellent in 18.2% (2 of 11) of patients in the propofol-saline group and 64.3% (9/14) of patients in the propofol-remifentanil group (P = 0.05). In the LT groups, the figures were 40.0% (4 of 10) and 78.6% (11 of 14) (P = 0.04).
For airway device insertion, the requirement for propofol was reduced in the groups in which remifentanil was added compared to those receiving propofol alone by 47.2% in the LMA group and 46.4% in the LT group (P < 0.01). Insertion conditions were also improved (P < 0.05) (Fig. 3).
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Figure 3. Dose-response curves plotted from probit analysis of individual propofol concentration and respective reactions to supraglottic airway insertion. LMA: laryngeal mask airway; LT: laryngeal tube, LMA-P: the LMA group with propofol + saline; LT-P: the LT group with propofol + saline; LMA-PR: the LMA group with propofol + remifentanil; LT-PR: the LT group with propofol + remifentanil.
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DISCUSSION
This study is the first to determine the EC50 for propofol required for insertion of the classic LMA and LT, with or without remifentanil 7.5 ng/mL, in children. The direct contact site in the upper airway of the LMA and LT differ, but their predicted propofol EC50s do not differ. The addition of remifentanil 7.5 ng/mL halved the propofol EC50 for both devices and also improved insertion conditions.
The major factors that may hinder insertion are inadequate jaw relaxation and stimulation of the airway reflexes. Opioids suppressed the reflexes (7), improved jaw relaxation (14,15), and effectively reduced propofol requirements in this study. Fentanyl pretreatment (1 µg/kg) reduces the propofol requirement for LMA insertion (from 3.4 ± 0.3 to 1.4 ± 0.3 mg/kg) (16) and remifentanil significantly improves conditions for LMA insertion during propofol induction (7). Grewal and Samsoon (17) reported that the addition of remifentanil not only provided a better quality of airway patency with less coughing and gagging, but also facilitated airway manipulation and LMA insertion.
Richebe et al. (18) found that the LMA required a larger propofol concentration than the LT. However, they used different insertion methods for the two devices, whereas in our study the same method was used for both; the finger was not introduced into the mouth. Probably for this reason we found similar propofol requirements in the two groups. Burlacu et al. (19) reported similar propofol concentrations for insertion of the two devices, although the potent inhibitory effect of coadministered alfentanil on the upper airway reflexes may have masked any differences in airway stimulation effects. This agrees with our finding that the reduction in propofol requirements was similar for the two devices.
Day surgeries are an increasing trend and the use of LMAs or LTs is also increasing. Propofol is also a suitable IV anesthetic for short surgeries when used with remifentanil. The results of this study assist pediatric anesthesiologists in determining appropriate doses of propofol and remifentanil for short day surgeries. Whether LMAs or LTs are used in pediatric patients, remifentanil will improve insertion conditions and reduce the propofol concentration. In this study, we administered atropine to prevent hypotension or bradycardia because patients frequently present with hypotension or bradycardia when propofol and remifentanil are used together. In our study, no patient had profound hypotension or bradycardia when atropine was administered. Therefore, the administration of appropriate amounts of atropine, propofol, and remifentanil is useful for short surgeries as IV anesthetics in children. There was also no difference in arterial blood pressure and heart rate between the propofol-saline groups and the propofol-remifentanil groups after insertion of airway devices. The might be because the propofol concentration in the propofol-saline group was higher than that in the propofol-remifentanil group (nearly double the concentration) and atropine was administered before anesthetic induction.
In conclusion, we found that the propofol concentration required for insertion of the LMA and LT in children is similar, and that the coadministration of remifentanil 7.5 ng/mL halved propofol requirements and improved insertion conditions.
Footnotes
Accepted for publication March 12, 2007.
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