The authors hypothesized that a muscle relaxant would have no meaningful difference in intubation conditions during nasal intubation under remifentanil and propofol anesthesia.
Materials and Methods
This parallel-group, double-blinded, randomized controlled trial included 44 patients who received saline (S group; n = 22) or rocuronium (R group; n = 22). In addition to remifentanil 0.5 μg/kg per minute and propofol 5 mg/kg per hour, propofol 0.5 mg/kg was administered until loss of consciousness. Nasal intubation was performed 10 minutes after administration of R or S 0.6 mg/kg. Significant differences in intubation conditions and salivary amylase levels before and after intubation were tested ( P < .05).
Vocal cord status ( P = .003) and response to intubation or cuff filling ( P = .008) were significantly different, but intubation conditions were not. Salivary amylase level was significantly lower with R administration ( P = .022). No patient complained of postoperative throat pain and hoarseness.
Muscle relaxants during nasal intubation performed after bolus administration of propofol 0.9 mg/kg in addition to 10 minutes of remifentanil 0.5 μg/kg per minute plus propofol 5 mg/kg per hour are unnecessary.
Tracheal intubation is the most invasive procedure during anesthesia. Hence, an inhalation anesthetic or intravenous anesthetic alone fails to adequately block the stimuli that accompany intubation. Invasive actions around the glottis produce laryngeal spasms and body movement in response to nociceptive stimuli. Therefore, a muscle relaxant is ordinarily used as an adjunct to ensure smooth intubations. However, muscle relaxants can cause arousal delay, malignant hyperthermia, awareness under anesthesia, and anaphylaxis and delay the rapid return of spontaneous ventilations, and anticholinesterase antagonists can cause postoperative nausea and vomiting. From an economic standpoint, it is desirable to avoid muscle relaxants and antagonists, which are costly.
Remifentanil has a strong analgesic effect and shuts down the input from nociceptive stimuli to the central nervous system. Therefore, many reports have noted that introducing anesthesia with remifentanil suppresses the response around the glottis to nociceptive stimuli and produces adequate intubation conditions without a muscle relaxant. However, these studies considered oral intubation and almost no research has been performed on nasal intubation. Nasal intubation is a more invasive procedure than oral intubation, because the tracheal tube passes through the nasal cavity. Thus, it is not clear whether a muscle relaxant is necessary during nasal intubation with remifentanil administration.
The present study used intubation scores and salivary amylase levels (ie, increase in sympathetic stimuli ) as indicators to study the need for muscle relaxants during nasal intubation performed with remifentanil and propofol. Thus, the null hypothesis was that the presence of a muscle relaxant would have no meaningful difference in intubation conditions for nasal intubations performed with remifentanil and propofol anesthesia.
Materials and Methods
The present study was conducted in accordance with Declaration of Helsinki and the Japanese ethical guidelines for clinical studies. The study protocol was approved by the ethics review board of The Nippon Dental University School of Life Dentistry (Tokyo, Japan; approval number NDU-T2011-22) and the ethics review board of Fuji City General Hospital (Shizuoka, Japan; approval number 59). It was conducted after clinical trial registration as certified by the International Committee of Medical Journal Editors (trial identification number UMIN000009385).
The study design was a parallel-group, double-blinded, randomized controlled trial of the standard of care. The content of the study was described in writing and verbally to oral and maxillofacial surgical patients scheduled for airway management by nasal intubation at Fuji City General Hospital. The subjects were patients who gave consent to be included in the study. Patients with a body mass index of at least 25 kg/m 2 , those with suspected intubation difficulties (Mallampati score, >3; mouth opening, <3.5 cm; and patients with cervical spine disease), and those with an American Society of Anesthesiologists (ASA) physical status 3 and 4 were excluded.
A computer-generated number table was used to randomly distribute patients into 2 groups (block size = 4) for rocuronium 10 mg/mL (R; Eslax MSD, Inc, Tokyo, Japan) or saline (S). Random allocation concealment was performed by the envelope method. No premedication was administered. After being brought into the operating room, patients were fitted with monitors for noninvasive blood pressure measurement, electrocardiography, and transcutaneous oxygen saturation. A salivary amylase monitor (Nipro, Inc, Osaka, Japan) was used to measure salivary amylase levels before intubation. With 100% O 2 administered from a face mask, a syringe pump (TE-332S, Terumo, Tokyo, Japan) was used to begin administering remifentanil 0.5 μg/kg per minute (Janssen Pharmaceutical, Inc, Tokyo, Japan) and propofol 5 mg/kg per hour (1% Diprivan Injection Kit AstraZeneca, Tokyo, Japan) from an intravenous line established in the forearm. If there was no loss of consciousness, then propofol 0.5 mg/kg was repeatedly administered until there was no longer a response to verbal prompting. After loss of consciousness, R 0.6 mg/kg or the equivalent amount of S was administered, and artificial respiration with 100% O 2 was performed. The inside of the nose was cleaned with benzalkonium chloride using a cotton swab, with 0.1% adrenaline for hemostasis and 8% lidocaine for surface anesthesia. Ten minutes after the start of administration, nasal intubation was performed using a nasal RAE tube (Mallinckrodt, Covidien, Dublin, Ireland) with an inner diameter of 6.5 mm for men or 6.0 mm for women and a size 3 Macintosh laryngoscope. Magill forceps were used as necessary. In all cases, the intubation operation was performed by a single dental anesthesia specialist. The spraying of a surface anesthetic was not performed. Immediately after intubation, positive pressure was applied inside the airway and the cuff was filled with air until there was no sound of leakage. Next, salivary amylase levels after intubation were measured. Anesthesia was maintained using remifentanil, propofol, and R or S. At the same time as the end of surgery, sugammadex 4 mg/kg (Bridion, MSD, Inc) was administered to the R group and an equivalent amount of saline was administered to the S group. The preparation of muscle relaxants and antagonists was performed by the oral and maxillofacial surgeon (OMS), and the attending anesthetist was unaware of whether R or S was being administered.
For intubation conditions, the “good practice guideline for pharmacodynamics studies of neuromuscular blocking agents II” method of Fuchs-Buder et al was used ( Table 1 ). Namely the difficulty of the laryngoscopy (easy, fair, difficult), state of the vocal cords (abducted, intermediate or moving, closed), and response to intubation or cuff filling (none, slight, vigorous or sustained) were assessed using 3 grades (excellent, good, or poor), and the results determined whether overall intubation conditions were excellent, good, or poor. Excellent means that all assessment items were rated as excellent, good means that all assessment items were rated as excellent or good, and poor means that any item was rated as poor. The salivary amylase levels before and after intubation also were measured. Intubation conditions were assessed by the attending anesthetist and salivary amylase levels were assessed by the OMS.
|Variable Assessed||Clinically Acceptable||Not Clinically Acceptable|
|Position of vocal cords||abducted||intermediate /moving||closed|
|Reaction to insertion of tracheal tube and cuff inflation (diaphragmatic movement or coughing)||none||slight ‡||vigorous /sustained §|
† Laryngoscopy—easy, jaw relaxed, no resistance to blade insertion; fair, jaw not fully relaxed, slight resistance to blade insertion; difficult, poor jaw relaxation, active resistance to laryngoscopy.
For statistical analysis, unpaired t tests were used to compare body weight, age, and additional propofol administration. Because outliers were noted, the Wilcoxon test was used for salivary amylase levels. The χ 2 test, Yates χ 2 test, and Fisher exact test were used to compare the difficulty of the laryngoscopy, state of the vocal cords, response to intubation or cuff filling, intubation conditions, ASA status, and gender. All tests were set to a significance level of 5%, and the statistical software used was KyPlot (KyensLab, Tokyo, Japan) for Windows 7. An intention-to-treat (ITT) analysis was performed.
The required sample size was calculated by the following method. Comparing the oral intubation conditions between the presence and absence of R 0.6 mg/kg for remifentanil 0.5 μg/kg per minute and propofol 2 mg/kg reportedly yielded good or excellent intubation conditions in 100% of cases in the R group, but produced similar conditions in only 66% of the non-R group. Therefore, with the null hypothesis that the presence of a muscle relaxant has no meaningful difference in intubation conditions and the alternative hypothesis that administering a muscle relaxant improves intubation conditions, the required sample size was determined:
This equation yielded a value of 18 patients in each group, even assuming the standard deviation (SD) to be 40%, where the α error is equal to 0.05 (1-sided) and the β error is equal to 0.2.