We sought to determine minimum alveolar anesthetic concentrations for skin incision (MAC) and for tracheal extubation (MACEX) for sevoflurane and its associated awakening time and respiratory complications during emergence from sevoflurane anesthesia in children.We studied 40 (20 in each group) unpremedicated pediatric patients ranging in age from 2 to 8 yr. For MACEX determination, anesthetic induction, tracheal intubation, and maintenance of anesthesia were performed with sevoflurane and N2 O in oxygen. However, N2 O administration was discontinued at the end of surgery. The ratio of the predetermined end-tidal to inspiratory concentration was maintained at 0.95-1.00 for at least 15 min. The trachea was gently extubated, and smooth tracheal extubation was defined by the absence of gross purposeful muscular movements. In addition, the respiratory complications and awakening time were investigated during emergence from anesthesia for each patient. For MAC determination, anesthesia induction and tracheal intubation were performed with 5% sevoflurane in oxygen. After the predetermined endtidal sevoflurane concentration had been established and maintained for at least 15 min, skin incision was attempted. Patients' responses to skin incision were described as "no movement" or "movements." The MAC or MACEX for sevoflurane was 2.22% +/- 0.13% (mean +/- SD) or 1.70% +/- 0.12%, and the 95% effective dose (ED95) for smooth extubation was 1.87% (95% confidence limits 1.75%-2.62%), respectively, in children. During emergence from anesthesia, none of patients held their breath or experienced laryngospasm in the current study. One patient in a subgroup at 1.5% coughed before tracheal extubation. All 10 patients with smooth tracheal extubation had hemoglobin oxygen saturation levels of >or=to98% in this study. Awakening time was 9.7 +/- 3.7 min in the subgroup that received 1.75% sevoflurane. In conclusion, the MACEX and ED95 values of sevoflurane were 1.64% and 1.87%, respectively, in children. The MACEX to MAC ratio for sevoflurane was 0.8 in children within the same age range and mean age. Implications: Because tracheal extubation of anesthetized patients may be advantageous in certain clinical situations, we performed this study. The ratio minimum alveolar anesthetic concentrations for skin incision and for tracheal extubation for sevoflurane was 0.8 in children within the same age range and mean age. No patient in the current study had laryngospasm.
(Anesth Analg 1998;87:1263-7)
Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
This study was presented in part at the 72th Clinical and Scientific Congress of the International Anesthesia Research Society, Orlando, FL, March 1998.
Accepted for publication September 3, 1998.
Address correspondence and reprint requests to Dr. Inomata, Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki 305, Japan.
Tracheal extubation of anesthetized patients may be advantageous in certain clinical situations. In children, tracheal extubation during deep anesthesia often can result in hemoglobin oxygen desaturation [1,2] but is also associated with fewer airwayrelated complications than awake extubation . The pharmacologic properties of sevoflurane [3-9] should provide a smooth tracheal extubation, rapid emergence from anesthesia, and, perhaps, fewer airwayrelated complications. However, no previous studies have quantified the depth of sevoflurane anesthesia, expressed by the end-tidal (ET) concentrations, required to perform smooth tracheal extubation in children. Moreover, these characteristics of sevoflurane vary in intensity with age [5,10,11]. Therefore, we attempted to determine the minimum alveolar anesthetic concentrations for skin incision (MAC) and for tracheal extubation (MACEX) of sevoflurane and to assess airway complications during emergence from anesthesia in children.
We studied 40 (20 in each group) pediatric patients, ASA physical status I, ranging in age from 2 to 8 yr, scheduled for general anesthesia for elective plastic surgery. The study protocol was approved by our clinical investigation committee, and informed consent was obtained from the parent or guardian of each patient. Preoperative examination disclosed no airway malformation or any sign of upper respiratory infection in any patient. No premedication was used.
All patients were fasted for a minimum of 8 h before the induction of anesthesia. Venous access was obtained for infusion of dextrose 2% in lactated Ringer's solution at a rate of 6 mL[center dot]kg[center dot]h-1 before arrival in the operating room. A precordial stethoscope was used to monitor heart and breath sounds. The patients were monitored with an electrocardiogram, a pulse oximeter, and indirect blood pressure monitor. Breath-by-breath inspired/ET sevoflurane and carbon dioxide concentrations were measured with a precalibrated gas monitor (AS/3[trade mark sign]; Datex, Helsinki, Finland). Inspired and ET gases for measurements were sampled from an angle piece placed at the proximal end of the tracheal tube after tracheal intubation and sampled from the cannula placed within the face mask attached to the patient's face after tracheal extubation, respectively, at a sampling flow rate of 90 mL/min. Accuracy of end-tidal measurements was maximized by confirming the return of the ETCO2 trace to zero and the good (square) wave formation with a plateau.
General anesthesia was induced via a mask using sevoflurane and nitrous oxide in oxygen (fraction of inspired oxygen [FIO2] 0.33), and the trachea was then intubated orally under 5% sevoflurane and nitrous oxide in oxygen without lidocaine topical spray or any neuromuscular relaxants. After the airway was secured, a nasogastric tube was advanced into the stomach.
We maintained anesthesia using 2%-2.5% sevoflurane and nitrous oxide in oxygen (FIO2 0.33) without neuromuscular relaxants during the surgery. The lungs were mechanically ventilated using a volumecycled ventilator. Nitrous oxide was discontinued at the end of surgery. The stomach contents were then suctioned via the indwelling nasogastric tube, and the gastric tube was removed from each patient with continuous suction to clear the pharyngeal and oral contents.
When the ET sevoflurane concentration reached a predetermined value, the ratio of the ET to inspiratory anesthetic concentration was maintained at 0.95-1.00 for at least 15 min to establish equilibration among cerebral, arterial blood, and alveolar gas tensions before tracheal extubation was attempted. At the time of tracheal extubation, no residual nitrous oxide >3% was detected in the ET sample. The trachea was extubated gently, and the volatile anesthetic was immediately discontinued. The reservoir bag was then emptied to eliminate the residual volatile anesthetic from the breathing circuit. The patient was subsequently given oxygen 6 L/min via a face mask. A smooth tracheal extubation was defined as one accomplished without gross purposeful muscular movement within 1 min. Coughing was considered purposeful movement. Absence of any purposeful movement was determined by an anesthesiologist who was blinded to the ET sevoflurane concentration during tracheal extubation. Additionally, patients who held their breath or experienced laryngospasm immediately after tracheal extubation were regarded as not having been extubated smoothly.
Patients were observed for respiratory complications, such as breath-holding and laryngospasm, and arterial oxygen desaturation during emergence from anesthesia until awakening. The adequacy of the airway was assessed by SpO2 levels >97%, auscultation, observation of the patient's chest wall movement, and the ETCO2 waveform with the sampling cannula placed within the face mask.
Dixon's up-down method  with 0.25% as a step size (1.25%, 1.50%, 1.75%, and 2.00%) was used. A single measurement was obtained per patient. In each patient, the times from discontinuation of the anesthetic (and tracheal extubation) until each patient moved spontaneously (moving time) and leaving the operating room (awakening time) were recorded. The patients were kept in the operating room until they achieved a postanesthetic recovery (PAR) score of 9-10. To determine the PAR score, we evaluated the following signs: activity, respiration, circulation, consciousness, and color. A rating of 0, 1, or 2 was given for each sign, and a score of 10 indicated a patient in the best possible condition. The PAR score was assessed by the anesthesiologist who was blinded to the ET sevoflurane concentration during tracheal extubation. No narcotics, benzodiazepines, or local anesthetics were administered during the study period.
General anesthesia was induced via a mask using sevoflurane in oxygen, and the trachea was then intubated orally without lidocaine topical spray or neuromuscular relaxants. ET sevoflurane concentration was determined according to a modification of Dixon's up-down method  with 0.25% as a step size and held constant for at least 15 min before the skin incision. Patients' responses to skin incision were described as "no movement" or "movement." No movement was defined as the absence of gross purposeful muscular movement during the first minute after skin incision. Twisting or jerking of the head was considered purposeful movement, but twitching or grimacing was not. Coughing, rigidity, swallowing, and chewing were not considered purposeful movement. Absence of any gross purposeful muscular movement was determined by an anesthesiologist who was blinded to the concentration of tested. In this study, the same anesthesiologist extubated the endotracheal tube. A single measurement was obtained per patient. Patients who moved during the skin incision were immediately given 4%-5% sevoflurane.
Patient demographics (age, weight, height), duration of tracheal intubation, moving time, and awakening time are expressed as mean +/- SD (Table 1). We analyzed values for MAC or MACEX obtained by calculating the midpoint concentration of all independent pairs of patients involving a cross-over (i.e., not smooth to smooth extubation). MAC or MACEX was defined as the average of the cross-over midpoints in each pair. In addition, the standard deviation of MAC or MACEX was the standard deviation of the crossover midpoints in each group . We also analyzed the probability in both 50% (ED50: MACEX) and 95% (ED95) of smooth tracheal extubation versus ET sevoflurane concentrations, and 95% confidence limits by using a probit test (SAS proprietary software[trade mark sign]; SAS Institute Inc., Cary, NC). The maximal likelihood estimators of the model variables were performed using a logistic regression test (SAS[trade mark sign]) that furnished the best-fitting sigmoid curve.
MACEX was 1.70% +/- 0.12% for sevoflurane (Figure 1). The dose-response curve constructed on the basis of a probit test of data in this patient population (Figure 2) revealed that the ED50 (MACEX) of ET sevoflurane concentration was 1.64% (1.52%-1.78%). The ED95 of ET sevoflurane concentration was 1.87% (1.75%-2.62%). Maximal likelihood estimators of the logistic regression model variables in this group showed a P value of 0.0115 and goodness of fit chi squared of 0.97. Bucking was observed in one patient in the subgroup that received 1.5% sevoflurane before tracheal extubation. One of two patients showed airway obstruction and required manual support in the subgroup that received 2.0% sevoflurane: he did not move within 1 min after tracheal extubation. All patients whose tracheal extubation was not smooth coughed. During emergence from anesthesia after extubation, none of the patients held their breath or experienced laryngospasm. All ten patients with smooth tracheal extubation had a SpO2 level of >or=to98% in the study period. In subgroups that received 1.75% sevoflurane (n = 9) as approximately 1 MACEX, the moving time and the awakening time were 5.7 +/- 3.5 and 9.7 +/- 3.7 min, respectively.
The MAC was 2.22% +/- 0.13% for sevoflurane (Figure 3). The MACEX to MAC ratio of sevoflurane was 0.8 in the patients within the same age range and mean age.
The MACEX for sevoflurane was 1.64%. Based on our MAC value (2.22%) for sevoflurane in patients of this age range, the MACEX to MAC ratio was 0.8 for sevoflurane. Our results indicate that, in 95% of pediatric patients, smooth tracheal extubation may be accomplished at 1.87% ET sevoflurane. The MACEX to MAC ratio for isoflurane and desflurane in children is approximately 0.9-0.95 [14,15]. The fact that the MACEX for sevoflurane was approximately 20% smaller than the MAC agrees with previous data from Neelakanta and Miller  and Cranfield and Bromley , who showed that the MACEX values for isoflurane and desflurane in children 4-9 yr old were approximately 5%-10% lower than the respective MAC values. We previously reported that the MAC values for endotracheal intubation (MACEI) of sevoflurane was 2.69  and 2.83%  and that the MACEI to MAC ratio was 1.3-1.4 in children. As for the difference between the ratios of MAC for intubation and extubation, sensitivity to mechanical stimuli (tracheal tube) in the mucosa of the larynx and trachea may decrease the time course of the administration of anesthesia. After comparing individual MAC values determined before and after surgery, Petersen-Felix et al.  reported that the MAC of isoflurane for electrical tetanic stimulation decreases by almost 20%. However, the calculation using values of sevoflurane MACEI (2.69)  and MACEX (1.64) revealed that the MAC for tracheal tube decreases by 40%. Another possibility is that low-threshold mechanoreceptors show rapid adaptation to a given stimulus in general. Receptors in the larynx and trachea may be activated by a change in pressure on them, but stimuli caused by an endotracheal tube may be easily tolerated. In addition, the characteristics of tetanic stimulation and stimuli by an endotracheal tube are different, and the receptors activated are also different.
Upper airway reflexes are of prime importance to anesthesia. Their activation during anesthesia can lead to apnea and laryngospasm, which besides being a minor inconvenience, can be life-threatening. Therefore, adequate suppression of airway reflexes is necessary for safe anesthesia, but their rapid return in the postoperative period is essential to protect the lungs from aspiration. Although laryngospasms were observed in 2 of 19 patients who received isoflurane  and 2 of 25 patients who received desflurane , none of the 20 patients who received sevoflurane experienced laryngospasm in the current study. There is no statistical difference among the three anesthetic groups. However, the result may be notable because none of sevoflurane group experienced laryngospasm as a life-threatening complication. In subgroups at 1.75% sevoflurane (n = 9), approximately 1 MACEX, the awakening time was 9.7 +/- 3.7 min. The use of sevoflurane was associated with a similar rapid awakening after tracheal extubation under deep anesthesia compared with desflurane . This rapid awakening was reflected in older pediatric patients' ability to follow commands earlier and/or a lesser requirement for manual support of the airway.
A potential source of error could have resulted from the use of nitrous oxide during the surgery. There was a significant but small ET concentration of nitrous oxide at the time of extubation, but the value was always <3%. This residual nitrous oxide is unlikely to have changed the MACEX value for sevoflurane by more than 0.05%.
In conclusion, the MACEX and ED95 valued for sevoflurane in children were 1.64% and 1.87%, respectively. The MACEX to MAC ratio for sevoflurane was 0.8 in children within the same age range and mean age.
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