Are Muscle Relaxants Needed for Nasal Intubation in Propofol and Remifentanil Anesthesia?



Are Muscle Relaxants Needed for Nasal Intubation in Propofol and Remifentanil Anesthesia?




Journal of Oral and Maxillofacial Surgery, 2014-11-01, Volume 72, Issue 11, Pages 2134-2139, Copyright © 2014 American Association of Oral and Maxillofacial Surgeons


Purpose

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).

Results

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.

Conclusion

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.

Table 1
Evaluation of Intubation Conditions
Variable Assessed Clinically Acceptable Not Clinically Acceptable
Excellent Good Poor
Laryngoscopy easy fair difficult
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 §

Intubation conditions—excellent, all qualities are excellent; good, all qualities are excellent or good; poor, presence of a single quality rated as poor.

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.

One to 2 weak contractions or movement for shorter than 5 seconds.

§ More than 2 contractions or movement for longer than 5 seconds.

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:







2





(




Z


α



+



Z


β




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2



S



D


2




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Δ


2





=




2





(



1.64


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0.84



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0.34



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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.


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Are Muscle Relaxants Needed for Nasal Intubation in Propofol and Remifentanil Anesthesia? Masatoshi Ide DDS , Katsuhisa Sunada DDS, PhD and Naohiko Katsuyama DDS, PhD Journal of Oral and Maxillofacial Surgery, 2014-11-01, Volume 72, Issue 11, Pages 2134-2139, Copyright © 2014 American Association of Oral and Maxillofacial Surgeons Purpose 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). Results 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. Conclusion 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. Table 1 Evaluation of Intubation Conditions ∗ Variable Assessed Clinically Acceptable Not Clinically Acceptable Excellent Good Poor Laryngoscopy † easy fair difficult 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 § ∗ Intubation conditions—excellent, all qualities are excellent; good, all qualities are excellent or good; poor, presence of a single quality rated as poor. † 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. ‡ One to 2 weak contractions or movement for shorter than 5 seconds. § More than 2 contractions or movement for longer than 5 seconds. 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: 2(Zα+Zβ)2SD2/Δ2=2(1.64+0.84)2SD2/0.342 2 ( Z α + Z β ) 2 S D 2 / Δ 2 = 2 ( 1.64 + 0.84 ) 2 S D 2 / 0.34 2 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. Results Fifty-three consecutive patients were recruited ( Fig 1 ), whereas 44 were included in the study (S group, n = 22; R group, n = 22). Patients in the S group were older, although the difference was not important ( Table 2 ). Artificial respiration was uncomplicated for all patients, with no chest wall rigidity observed. The R group included 1 patient who required an extended time to pass the tube through the nasal cavity, with the remifentanil administration time exceeding 10 minutes. The S group included 1 patient who received sevoflurane because the patient's eyes opened during passage through the nasal cavity; 1 patient received a 50-μg bolus of remifentanil for similar reasons; and 1 patient whose vocal cords were closed from a difficult laryngoscopy was intubated after R administration because of an advanced age (83 years). The S and R groups each included 1 patient with Cormack grade 4, and the state of the vocal cords could not be assessed. Thus, assessment of the state of the vocal cords was possible for 21 patients in the S and R groups. Statistically processing these data showed no difference in the difficulty of laryngoscopy and intubation conditions, but show a meaningful difference between the S and R groups in the state of the vocal cords and response to intubation or cuff filling ( Table 3 ). Salivary amylase levels after intubation in the R group were significantly lower than the levels before intubation ( P = .022; Fig 2 ). No patient complained of throat pain or hoarseness. Figure 1 Recruitment and enrollment of study participants. Table 2 Patient and Anesthetic Characteristics S (n = 22) R (n = 22) P Value Men/women 11/11 8/14 .272 Age (yr) 45.2 ± 16.8 35.6 ± 16.0 .052 Height (cm) 163.7 ± 9.6 162.4 ± 9.9 .665 Weight (kg) 60.7 ± 14.9 56.6 ± 11.9 .319 ASA physical status 1/2 16/6 17/5 1.000 Supplemental boluses of propofol (mg/kg) 0.80 ± 0.45 0.88 ± 0.49 .574 Note: Data are presented as number or mean ± standard deviation. Abbreviations: ASA, American Society of Anesthesiologists; R, remifentanil, propofol, and rocuronium; S, remifentanil and propofol. Table 3 Intubation Conditions and Number of Intubation Trials for Remifentanil and Propofol Versus Remifentanil, Propofol, and Rocuronium S R P Value Laryngoscopy ∗ easy 12 13 fair 8 8 difficult 2 1 .829 Position of vocal cords † abducted 12 21 intermediate or moving 8 0 closed 1 0 .003 Reaction to insertion of tracheal tube and cuff inflation none 14 22 slight 5 0 vigorous or sustained 3 0 .008 Intubation conditions excellent 12 13 good 7 8 poor 3 1 .575 Abbreviations: R, remifentanil, propofol, and rocuronium; S, remifentanil and propofol. ∗ 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. † Each of 2 groups included 1 patient in whom the vocal cords could not be assessed. Therefore, the numbers of recorded vocal cords positions are 21 in each group. Figure 2 Salivary amylase levels for the R and S groups before and after intubation. * P = .022. R, remifentanil, propofol, and rocuronium; S, remifentanil and propofol. Discussion When nasal intubation was performed after R and S administration, an important difference was noted in the state of the vocal cords and the response to intubation or cuff filling. However, intubation conditions were not different. The S group included 1 patient in whom R was administered because of glottal closure, and the need for R may have been underestimated in the ITT analysis. Therefore, this case was removed from the S group and included in the R group analysis and assessed as an easy laryngoscopy, an abducted vocal cord position, and no reaction to insertion of the tracheal tube and cuff inflation based on status after R administration, but there still was no significant difference observed in intubation conditions ( P = .508). As determined from these observations, the null hypothesis that the presence of a muscle relaxant has no meaningful difference in intubation conditions for nasal intubation performed during remifentanil and propofol anesthesia cannot be rejected. However, intubation is a procedure that is directly linked to life support, and all problems should be avoided. Closure of the vocal cords must be recognized as a serious problem, because it can make intubation impossible. If intubation conditions are compared, a discussion of individual cases is more important than statistical tests, and the ordinary significant difference test at which a 5% (or 1%) error is observed may or may not be suitable in determinations involving life support. One possible reason for the trivial difference observed in intubation conditions between the S and R groups could be a feature of this method of assessment in which intubation conditions are excellent only if all assessment items are rated as excellent. With nasal intubation, the tracheal tube can contact the upper wall of the trachea when passing through the vocal cords, which makes intubation difficult, and laryngoscopy is often performed with more force than in oral intubation. As a result, the resistance to the laryngoscope blade also may have been overestimated in the R group, which made a difference less likely to occur between the S and R groups. Salivary amylase secretions increase in response to sympathetic stimuli; therefore, it is an indicator of stress load and is reportedly also elevated by tracheal intubation. Therefore, this study used salivary amylase level as an indicator to study the impact of the presence of a muscle relaxant on intubation-related stress. The results showed that R caused salivary amylase levels after intubation to decrease meaningfully compared with levels before intubation and decreased intubation-related stress. No patient complained of throat pain or hoarseness, but it is undeniably possible that intubation in the S group involved greater force from around the vocal cords. The S group also included 8 patients who showed a response to intubation or cuff filling. These patients required highly concentrated inhaled sevoflurane or a bolus administration of remifentanil to control the coughing reflex. A severe coughing reflex after intubation can damage the vocal cords and dislodge the tracheal tube. Although intubation was possible, these patients needed to be administered a muscle relaxant. This leads the authors to believe that although the null hypothesis cannot be denied, a muscle relaxant should be administered at once if a patient is suspected to pose intubation difficulties or if resistance is perceived during the intubation procedure. The first limitation of this study was the possibility that the dosage of remifentanil or propofol was not adequate. If laryngoscopy is performed with only remifentanil and propofol and without administering a muscle relaxant, then the 90% effective concentration required to suppress body movement is reportedly remifentanil 10 ng/mL and propofol 2 μg/mL, and the 95% effective concentration for nasal intubation is reportedly remifentanil 7.43 ng/mL and propofol 5 μg/mL. Using the pharmacokinetics and pharmacodynamics simulation model of Minto et al and the pharmacokinetics simulation model of Marsh et al to study the protocol, the results showed that the effect site concentration at intubation was approximately 9 ng/mL for remifentanil and approximately 3.0 μg/mL for propofol. When the dosage of remifentanil is increased, there is an increased frequency of the appearance of chest wall rigidity, so it seems that increasing the propofol dosage could suppress the response to intubation or cuff filling. A second problem could be the fact that patients in the S group were older. Sensitivity to remifentanil increases with age, so the S group may have been in a stronger analgesic state than the R group. This means that the muscle response to stimuli might have been suppressed in the S group. In summary, with nasal intubation performed after a 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, there is little need for muscle relaxants. References 1. Tramèr M.R., Fuchs-Buder T.: Omitting antagonism of neuromuscular block: Effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review. Br J Anaesth 1999; 82: pp. 379. 2. Løvstad R.Z., Thagaard K.S., Berner N.S., et. al.: . Acta Anaesthesiol Scand 2001; 45: pp. 495. 3. Grant S., Noble S., Woods A., et. al.: Assessment of intubating conditions in adults after induction with propofol and varying doses of remifentanil. Br J Anaesth 1998; 81: pp. 540. 4. Stevens J.B., Wheatley L.: Tracheal intubation in ambulatory surgery patients: Using remifentanil and propofol without muscle relaxants. Anesth Analg 1998; 86: pp. 45. 5. Alexander R., Olufolabi A.J., Booth J., et. al.: Dosing study of remifentanil and propofol for tracheal intubation without the use of muscle relaxants. Anaesthesia 1999; 54: pp. 1037. 6. Erhan E., Ugur G., Alper I., et. al.: Tracheal intubation without muscle relaxants: Remifentanil or alfentanil in combination with propofol. Eur J Anaesthesiol 2003; 20: pp. 37. 7. Erhan E., Ugur G., Gunusen I., et. al.: Propofol—Not thiopental or etomidate—With remifentanil provides adequate intubating conditions in the absence of neuromuscular blockade. Can J Anaesth 2003; 50: pp. 108. 8. Troy A.M., Huthinson R.C., Easy W.R., et. al.: Tracheal intubating conditions using propofol and remifentanil target-controlled infusions. Anaesthesia 2002; 57: pp. 1204. 9. Leone M., Rousseau S., Avidan M., et. al.: Target concentrations of remifentanil with propofol to blunt coughing during intubation, cuff inflation, and tracheal suctioning. Br J Anaesth 2004; 93: pp. 660. 10. Kwak H.J., Min S.K., Kim D.H., et. al.: Effect-site concentration of remifentanil for nasotracheal versus orotracheal intubation during target-controlled infusion of propofol. J Int Med Res 2011; 39: pp. 1816. 11. Baum B.J.: Principles of salivary secretion. Ann N Y Acad Sci 1993; 694: pp. 17. 12. Fuchs-Buder T., Claudius C., Skovgaard L.T., et. al.: 8th International Neuromuscular Meeting: Good clinical research practice in pharmacodynamics studies of neuromuscular blocking agents II: The Stockholm revision. Acta Anaesthesiol Scand 2007; 51: pp. 789. 13. Schlaich N., Mertzlufft F., Soltész S., et. al.: Remifentanil and propofol without muscle relaxants or with different doses of rocuronium for tracheal intubation in outpatient anaesthesia. Acta Anaesthesiol Scand 2000; 44: pp. 720. 14. Nater U.M., La Marca R., Florin L., et. al.: Stress-induced changes in human salivary alpha-amylase activity—Associations with adrenergic activity. Psychoneuroendocrinology 2006; 31: pp. 49. 15. Kern S.E., Xie G., White J.L., et. al.: A response surface analysis of propofol-remifentanil pharmacodynamic interaction in volunteers. Anesthesiology 2004; 100: pp. 1373. 16. Minto C.F., Schnider T.W., Egan T.D., et. al.: Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 1997; 86: pp. 10. 17. Marsh B., White M., Morton N., et. al.: Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: pp. 41.

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