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Rapid induction of anesthesia with high concentrations of halothane or sevoflurane in children
Original Contributions Rapid Induction of Anesthesia With High Concentrations of Halothane or Sevoflurane in Children Yasuhiro Morimoto, MD,* James F. Mayhew, MD,† S. Lynn Knox, MD,‡ Mark H. Zornow, MD§ Department of Anesthesiology, University of Texas Medical Branch at Galveston, Galveston, TX
*Research Fellow †Professor of Anesthesiology ‡ Assistant Professor of Anesthesiology §Phillips Professor of Anesthesiology Address correspondence to Dr. Zorrow at the Department of Anesthesiology, The University of Texas Medical Branch, Galveston, Texas 77555-0591. E-mail: mzornow@utmb. edu Received for publication September 23, 1999; revised manuscript accepted for publication February 8, 2000.
Study Objective: To compare the characteristics of the rapid induction of anesthesia in pediatric patients with high concentrations of sevoflurane or halothane, and to determine the ability of anesthesiologists to correctly identify the anesthetic drug when administered in this fashion. Design: Randomized, prospective, open-label study. Setting: Academic university hospital Patients: 78 ASA physical status I and II healthy children scheduled for brief surgical procedures with general anesthesia and medicated with midazolam. Interventions: Assessments were made by 5 pediatric anesthesiologists and 18 anesthesiology residents. Sevoflurane or halothane was randomly selected for anesthetic induction. The anesthetic circuit was primed with the drug (8% sevoflurane or 4% halothane) in 50% nitrous oxide and oxygen. The anesthesiologists were blinded as to the anesthetics being administered. After completion of anesthetic induction, the anesthesiologists were asked to identify the anesthetic and to assess the quality and speed of induction. Measurement and Main Results: The pediatric anesthesiologists correctly identified the anesthetic in 55 of 78 assessments (70.5%). This figure is statistically better than what could be achieved by random guessing (p ⬍ 0.001). The residents correctly identified the anesthetic in only 46 of 78 assessments (60.0%). Statistically, this figure is no better than what could be achieved by random guessing (p ⫽ 0.06). Speed of induction was subjectively felt to be faster with sevoflurane than halothane but there were no differences in actual induction time (sevoflurane group, 3.7 ⫾ 2.7 min; halothane group, 3.7 ⫾ 2.6 min). There were no differences in the quality of induction or the incidence of airway complications. The perceived incidence of tachycardia was significantly higher with sevoflurane than halothane(sevoflurane group, 74%; halothane group 20%). Conclusion: The induction of anesthesia with high concentrations of either halothane or sevoflurane can be safely accomplished. Pediatric anesthesiologists can differentiate between halothane and sevoflurane when either drug is given in high initial concentrations. The presence of tachycardia may have served as the primary clue in determining which drug was being used. © 2000 by Elsevier Science Inc. Key words: Anesthesia, pediatric; halothane, induction; sevoflurane.
Journal of Clinical Anesthesia 12:184 –188, 2000 © 2000 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
0952-8180/00/$–see front matter
Rapid induction of anesthesia: Morimoto et al.
Introduction Sevoflurane is a nonpungent volatile anesthetic with a low blood gas solubility that should allow for the rapid induction of anesthesia. These characteristics may make sevoflurane the preferred drug for inhalation inductions in pediatric patients. In some studies, it has been shown that sevoflurane produces faster anesthetic induction and emergence times than halothane, as well as a lower incidence of airway complications.1–5 Some of these studies also describe better hemodynamic stability4 or fewer dysrhythmias4,5 with sevoflurane compared to halothane. However, in other studies, no difference 6 or only minimal differences7 were found between the two drugs. In a recent study6 in which gradual incremental increases in the inspiratory concentrations were used, it was found that anesthesiologists could not reliably identify whether sevoflurane and halothane was being used for the induction of anesthesia in pediatric patients. Studies have suggested that inhalation of 8% sevoflurane, the maximum concentration delivered by calibrated vaporizers, results in a significantly faster anesthesia induction than incremental sevoflurane, with no serious complications.8,9 Meretoja et al.5 reported that induction time was shorter using 7% sevoflurane in 66% nitrous oxide (N2O) than using 3% halothane in 66% halothane. In this study, we induced anesthesia by having the children breathe from an anesthesia circuit primed with approximately 4 times the minimum alveolar concentration (MAC) of either sevoflurane (8%) or halothane (4 %),10,11 and then compared the induction characteristics of the two drugs. We also sought to determine whether pediatric anesthesiologists could correctly identify the administered drug when used in this fashion. Thus, the study sought to better characterize the suitability of using high concentrations of these drugs for induction, and to determine whether pediatric anesthesiologists could correctly identify the administered drug when given in this manner.
Materials and Methods After the study protocol was approved by the University of Texas Medical Branch institutional review board, anesthesiologists from a university teaching hospital were prospectively studied. The study population was composed of five pediatric anesthesiologists supervising 18 anesthesiology residents caring for ASA physical status I and II children who were scheduled for brief otolaryngologic surgery. All anesthesiologists had experience with the use of sevoflurane. The children (n ⫽ 78, aged 7 mo to 9 yr) were premedicated with midazolam (0.5 mg/kg orally) approximately 30 minutes before the start of anesthesia. Standard monitoring was used. Anesthesia was induced by letting the children breathe a mixture of 8% sevoflurane or 4% halothane in 50% N2O and oxygen from a face mask attached to the circle system of the anesthesia machine. One MAC was considered to be 2.0% for sevoflurane and 1% for halothane.10,11 The anesthesia circuit was primed with the selected anesthetics
in the above concentration before application of face mask. The desired concentrations of anesthetic drugs were verified using a Datex Ultima (Datex Medical Instrumentation, Inc., Helsinki, Finland) gas monitor. Surgery started as soon as the patients lost consciousness. The times for each patient’s entry into the operating room (OR), start of anesthetic induction, and start of surgery were recorded. Loss of consciousness was defined as start of surgery (insertion of ear speculum for myringotomies, which represented over 73% of the study cases) or start of laryngoscopy in the remaining cases for which tracheal intubation was indicated. These times were selected because they represented clearly defined endpoints that closely approximated loss of consciousness as assessed by eyelid reflexes. Vaporizers for both anesthetics were mounted on the anesthesia machine. The vaporizer of the anesthesia delivery system was hidden from the view of the anesthesiologists by a sheet of cardboard taped to the front of the anesthesia machine. A person who did not participate in rating the target variables of the study selected either the sevoflurane or the halothane vaporizer in a randomized fashion. To avoid recognition of the volatile anesthetic by smell, the face masks of the study participants were treated with a drop of artificial strawberry flavor. After completion of the anesthetic induction, the anesthesiologists who administered the anesthetic were asked to identify the drug used in their particular case. Further, the pediatric anesthesiologists were asked to rate the speed and quality of anesthetic induction. A visual analog scale (VAS), with a minimum score of 0 and a maximum score of 100, was used for quantification. The incidence of coughing, breath holding, tachycardia, laryngospasm, and need for succinylcholine during the induction of anesthesia were recorded at the same time.The ability of the anesthesiologists to correctly identify the drug was tested using a procedure based on the normal distribution (the Z test). The anesthesiologists’ assessments concerning which drug was administered were also tested using the chi-square analysis. The chi-square analysis also was used for comparing the incidence of cough, breath holding, tachycardia, laryngospasm, and need for succinylcholine. VAS scores were compared using the Mann-Whitney U-test. The twosample t-test was used for comparing the ages and weights of the patients. P-values ⬍ 0.05 were considered statistically significant. Descriptive statistics are expressed as means ⫾ SD whenever appropriate.
Results Of the 78 patients studied, 43 children received sevoflurane and 35 children received halothane. 57 patients (73%) received bilateral myringotomies with tube placement and the remaining patients also underwent brief otolaryngologic surgery. The children in the two groups were well-matched with regard to age (sevoflurane group 44 ⫾ 29 mo; halothane group 40 ⫾ 29 mo; p ⫽ 0.57), sex (sevoflurane group 21 females /22 males; halothane group 17 females /18 males; p ⫽ 0.88 ), and weight (sevoflurane group 17 ⫾ 7 kg; halothane group 17 ⫾7 kg; J. Clin. Anesth., vol. 12, May 2000
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Figure 1. A. Frequency of correct and incorrect answers. B. Frequency of identifying sevoflurane or halothane in each of two groups. The anesthesiologist’s judgments from the column; the drugs actually administered from the rows.
p ⫽ 0.96). The time intervals from entering the operating room until the start of induction (sevoflurane group 1.4 ⫾ 1.2 min; halothane group 1.2 ⫾ 1.1 min; p ⫽ 0.67) and from the start of induction to the start of surgery (sevoflurane group, 3.7 ⫾ 2.7 min; halothane, group 3.7 ⫾ 2.6 min; p ⫽ 0.96) were not significantly different between the two groups. The pediatric anesthesiologists correctly identified the anesthetic in 55 of 78 assessments (70.5%, Figure 1A). This figure is statistically better than what could be achieved by random guessing (p ⬍ 0.001). By chi-square analysis, the pediatric anesthesiologists gave the reply that sevoflurane was used significantly more often in the sevoflurane group (and vice versa for halothane; p ⬍ 0.001; Figure 1B). The residents correctly identified the anesthetic in only 46 of 78 assessments (60.0%). Statistically, this figure is no better than what could be achieved by random guessing (p ⫽ 0.06). By chi-square analysis, the residents did not give the reply that sevoflurane was used significantly more often in the sevoflurane group (and vice versa for halothane; p ⫽ 0.12). The perceived speed of induction was significantly 186
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faster in sevoflurane group than in halothane group (p ⫽ 0.008; Figure 2), although there was no difference in actual time between the start of induction and start of surgery for the two drugs. There were no differences in the VAS for quality of induction (p ⫽ 0.94). The incidence of coughing (sevoflurane group, 12%; halothane group 14%; p ⫽ 0.73), breath holding (sevoflurane group, 12%; halothane group 18%; p ⫽ 0.42), laryngospasm (sevoflurane group, 7%; halothane group 6%; p ⫽ 0.82), and need for succinylcholine (sevoflurane group, 0%; halothane group, 0%) was not different between the two groups. However, the incidence of tachycardia (sevoflurane group, 74%; halothane group 20%; p ⬍ 0.001) as perceived by anesthesiologist was significantly greater in the sevoflurane group.
Discussion Numerous studies have attempted to identify the benefits of sevoflurane for induction of anesthesia in pediatric patients. Some of these studies1,4,5,12 found that sevoflurane permitted a faster anesthetic induction than halo-
Rapid induction of anesthesia: Morimoto et al.
Figure 2. Box plots of the median, 10th, 25th, 75th, and 90th percentiles for the visual analog scale scores for the speed and quality of induction of sevoflurane versus halothane anesthesia. The visual analog scale ranged from 0 (lowest quality or speed) to 100 (highest quality or speed). Speed of induction was significantly faster in the sevoflurane group than in the halothane group (p ⫽ 0.008). There were no differences in quality of induction (p ⫽ 0.94)(Mann-Whitney U-test).
thane. Some of these studies also describe better hemodynamic stability4 or fewer dysrhythmias4,5 with sevoflurane compared to halothane. However, some investigators have not found the induction characteristics of sevoflurane to be different from other volatile anesthetics. No significant differences in the time to loss of eyelid reflex in children were observed when comparing sevoflurane with halothane,2,3,7 nor was there a significant difference between the two drugs in emergence time after anesthesia.7 It has been reported that pediatric anesthesiologists could not reliably identify sevoflurane when it was given in a blinded, randomized fashion with gradual increases in inspiratory concentrations.6 In the same study, it was concluded that there were no significant differences in the perceived speed of induction between the two drugs. Considering the high cost of sevoflurane compared with halothane, evaluation of the differences between the two drugs and the advantages of sevoflurane under clinical conditions is relevant and important. In this study, we re-evaluated the differences between the two drugs by administering high initial concentrations (approximately 4 MAC) for anesthetic induction. Similar studies using this technique found a significantly faster induction of anesthesia with high initial concentrations than incremental increases in the inspired concentration, without serious complications.8,9 In this study, we used 8% sevoflurane, the maximum concentration delivered by calibrated vaporizers. MAC of sevoflurane in children has been reported to be both 2.03%10 and 2.5%.13 Inomata et. al.10 reported MAC of sevoflurane was 2.03% in pediatric patients, aged 1 to 9 years. As most patients in this study were in this age range, we estimated that 8% sevoflurane is equal to 4 MAC. MAC of halothane in children in a similar age range has been
reported to be between 0.87% and 0.97%.11 Based on these previous studies, we are confident that the 8% sevoflurane and 4% halothane used in this study are comparable doses of anesthetics. The perceived presence of tachycardia during the induction of sevoflurane was an interesting finding of this study. It may have been the primary clue used by the pediatric anesthesiologists in determining which drug was being administered. There are a number of reports of tachycardia during induction with sevoflurane. Lerman et al.13 reported that heart rate (HR) increased over 10% above awake values in children older than three years at 1 MAC of sevoflurane. Kawana et al. 4 compared hemodynamic changes induced by sevoflurane and halothane in pediatric patients. They found that HR increased at both 1 MAC and 2 MAC of sevoflurane but did not increase with 1 MAC of halothane. Incidence of tachycardia with sevoflurane was observed to be dose-dependent and higher than at the same MAC of halothane. Rapid induction with high concentrations of sevoflurane might increase the patients’ HR more than when sevoflurane is given in an incremental fashion. This theory may be the main reason that the anesthesiologists could differentiate between halothane and sevoflurane in this study. Another difference between the two drugs was the perceived speed of induction. As assessed by the pediatric anesthesiologists, induction was significantly faster with sevoflurane than halothane. However, the actual recorded time from start of induction to the start of surgery was not different between two groups (sevoflurane group, 3.7 ⫾ 2.7 min; halothane group, 3.7 ⫾ 2.6 min). Since the start of surgery coincided with achieving surgical anesthesia (no need to prep and drape for myringotomies), we consider the time from start of induction to the start of J. Clin. Anesth., vol. 12, May 2000
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surgery as actual anesthetic induction time. As expected, these times were faster by about one minute than those in our previous study, 6 in which there was a gradual increase in the inspired concentration (sevoflurane group, 4.7 ⫾ 2.1 min; halothane group, 4.6 ⫾ 2.1 min). When immediate high concentrations of volatile drugs are used for induction, respiratory complications caused by airway irritation may possibly be a problem. However, the incidence of airway complications in this study was similar to previous reports, and there were no serious complications that required succinylcholine during induction with either sevoflurane and halothane. Moreover, there was no difference in perceived quality of induction between the two drugs. Epstein et al.9 reported that there were no significant differences in induction complications between immediate high concentration and incremental increase of sevoflurane. Doi et. al. 15compared airway irritation caused by halothane, enflurane, isoflurane and sevoflurane. They reported that sevoflurane was the least irritant anesthetic, followed by halothane. These characteristics allowed the use of the high initial concentrations employed in this study. We conclude that the rapid induction of anesthesia with high concentrations of either halothane or sevoflurane can be safely accomplished, and that there are no differences in objective time for induction of anesthesia. High initial concentrations of these drugs reduce induction time by approximately 25% (i.e., from 4.7 min to 3.7 min in sevoflurane group) as compared to incremental increases. We found no differences between sevoflurane and halothane in the incidence of airway complications. The study further demonstrates that pediatric anesthesiologists can differentiate between halothane and sevoflurane when the drugs are given in high initial concentrations. The significant differences between the two drugs were found in the incidence of tachycardia and the perceived speed of induction. The tachycardia, which was frequently noted with the sevoflurane, may have served as the primary clue in determining which drug was being used.
References 1. Taivainen T, Tiainen P, Meretoja OA, Raiha L, Rosenberg PH: Comparison of the effects of sevoflurane and halothane on the
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quality of anaesthesia and serum glutathione transferase alpha and fluoride in paediatric patients. Br J Anaesth 1994;73:590 –5. Sarner JB, Levine M, Davis PJ, Lerman J, Cook DR, Motoyama EK: Clinical characteristics of sevoflurane in children. A comparison with halothane. Anesthesiology 1995;82:38 – 46. Piat V, Dubois M-C, Johanet S, Murat I: induction and recovery characteristics and hemodynamic responses to sevoflurane and halothane in children. Anesth Analg 1994; 79:840 – 4. Johannesson GP, Floren M, Lindahl SGE: Sevoflurane for ENTsurgery in children. A comparison with halothene. Acta Anaesthesiol Scand 1995;39:546 –50. Meretoja OA, Taivainen T, Raiha L, Korpela R, Wirtavuori K: Sevoflurane-nitrous oxide or halothane-nitrous oxide for paediatric bronchoscopy and gastroscopy. Br J Anaesth 1996;76:767–71. Bacher A, Burton AW, Uchida T, Zornow MH: Sevoflurane or halothane anesthesia: can we tell the difference? Anesth Analg 1997;85:1203– 6. Michalek-Sauberer A, Wildling E, Pusch F, Semsroth M: Sevoflurane anaesthesia in paediatric patients: better than halothane? Eur J Anaesthesiol 1998;15:280 – 6. Baum VC, Yemen TA, Baum LD: Immediate 8% sevoflurane induction in children: a comparison with incremental sevoflurane and incremental halothane. Anesth Analg 1997;85:313– 6. Epstein RH, Stein AL, Marr AT, Lessin JB: High concentration versus incremental induction of anesthesia with sevoflurane in children: a comparison of induction times, vital signs, and complications. J Clin Anesth 1998;10:41– 45. Inomata S, Watanabe S, Taguchi M, Okada M: End-tidal sevoflurane concentration for tracheal intubation and minimum alveolar concentration in pediatric patients. Anesthesiology 1994;80: 93– 6. Gregory GA, Eger EI 2d, Munson ES: The relationship between age and halothane requirement in man. Anesthesiology 1969;30: 488 –91. Lerman J, Davis PJ, Welborn LG, et al.: Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery. A comparison with halothane. Anesthesiology 1996;84:1332– 40. Lerman J, Sikich N, Kleinman S, Yentis S: The pharmacology of sevoflurane in infants and children. Anesthesiology 1994;80:814 – 24. Kawana S, Wachi J, Nakayama M, Namiki A: Comparison of haemodynamic changes induced by sevoflurane and halothane in paediatric patients. Can J Anaesth 1995;42:603–7. Doi M, Ikeda K: Airway irritation produced by volatile anaesthetics during brief inhalation: comparison of halothane, enflurane, isoflurane and sevoflurane. Can J Anaesth 1993;40:122– 6.
*Research Fellow †Professor of Anesthesiology ‡ Assistant Professor of Anesthesiology §Phillips Professor of Anesthesiology Address correspondence to Dr. Zorrow at the Department of Anesthesiology, The University of Texas Medical Branch, Galveston, Texas 77555-0591. E-mail: mzornow@utmb. edu Received for publication September 23, 1999; revised manuscript accepted for publication February 8, 2000.
Study Objective: To compare the characteristics of the rapid induction of anesthesia in pediatric patients with high concentrations of sevoflurane or halothane, and to determine the ability of anesthesiologists to correctly identify the anesthetic drug when administered in this fashion. Design: Randomized, prospective, open-label study. Setting: Academic university hospital Patients: 78 ASA physical status I and II healthy children scheduled for brief surgical procedures with general anesthesia and medicated with midazolam. Interventions: Assessments were made by 5 pediatric anesthesiologists and 18 anesthesiology residents. Sevoflurane or halothane was randomly selected for anesthetic induction. The anesthetic circuit was primed with the drug (8% sevoflurane or 4% halothane) in 50% nitrous oxide and oxygen. The anesthesiologists were blinded as to the anesthetics being administered. After completion of anesthetic induction, the anesthesiologists were asked to identify the anesthetic and to assess the quality and speed of induction. Measurement and Main Results: The pediatric anesthesiologists correctly identified the anesthetic in 55 of 78 assessments (70.5%). This figure is statistically better than what could be achieved by random guessing (p ⬍ 0.001). The residents correctly identified the anesthetic in only 46 of 78 assessments (60.0%). Statistically, this figure is no better than what could be achieved by random guessing (p ⫽ 0.06). Speed of induction was subjectively felt to be faster with sevoflurane than halothane but there were no differences in actual induction time (sevoflurane group, 3.7 ⫾ 2.7 min; halothane group, 3.7 ⫾ 2.6 min). There were no differences in the quality of induction or the incidence of airway complications. The perceived incidence of tachycardia was significantly higher with sevoflurane than halothane(sevoflurane group, 74%; halothane group 20%). Conclusion: The induction of anesthesia with high concentrations of either halothane or sevoflurane can be safely accomplished. Pediatric anesthesiologists can differentiate between halothane and sevoflurane when either drug is given in high initial concentrations. The presence of tachycardia may have served as the primary clue in determining which drug was being used. © 2000 by Elsevier Science Inc. Key words: Anesthesia, pediatric; halothane, induction; sevoflurane.
Journal of Clinical Anesthesia 12:184 –188, 2000 © 2000 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
0952-8180/00/$–see front matter
Rapid induction of anesthesia: Morimoto et al.
Introduction Sevoflurane is a nonpungent volatile anesthetic with a low blood gas solubility that should allow for the rapid induction of anesthesia. These characteristics may make sevoflurane the preferred drug for inhalation inductions in pediatric patients. In some studies, it has been shown that sevoflurane produces faster anesthetic induction and emergence times than halothane, as well as a lower incidence of airway complications.1–5 Some of these studies also describe better hemodynamic stability4 or fewer dysrhythmias4,5 with sevoflurane compared to halothane. However, in other studies, no difference 6 or only minimal differences7 were found between the two drugs. In a recent study6 in which gradual incremental increases in the inspiratory concentrations were used, it was found that anesthesiologists could not reliably identify whether sevoflurane and halothane was being used for the induction of anesthesia in pediatric patients. Studies have suggested that inhalation of 8% sevoflurane, the maximum concentration delivered by calibrated vaporizers, results in a significantly faster anesthesia induction than incremental sevoflurane, with no serious complications.8,9 Meretoja et al.5 reported that induction time was shorter using 7% sevoflurane in 66% nitrous oxide (N2O) than using 3% halothane in 66% halothane. In this study, we induced anesthesia by having the children breathe from an anesthesia circuit primed with approximately 4 times the minimum alveolar concentration (MAC) of either sevoflurane (8%) or halothane (4 %),10,11 and then compared the induction characteristics of the two drugs. We also sought to determine whether pediatric anesthesiologists could correctly identify the administered drug when used in this fashion. Thus, the study sought to better characterize the suitability of using high concentrations of these drugs for induction, and to determine whether pediatric anesthesiologists could correctly identify the administered drug when given in this manner.
Materials and Methods After the study protocol was approved by the University of Texas Medical Branch institutional review board, anesthesiologists from a university teaching hospital were prospectively studied. The study population was composed of five pediatric anesthesiologists supervising 18 anesthesiology residents caring for ASA physical status I and II children who were scheduled for brief otolaryngologic surgery. All anesthesiologists had experience with the use of sevoflurane. The children (n ⫽ 78, aged 7 mo to 9 yr) were premedicated with midazolam (0.5 mg/kg orally) approximately 30 minutes before the start of anesthesia. Standard monitoring was used. Anesthesia was induced by letting the children breathe a mixture of 8% sevoflurane or 4% halothane in 50% N2O and oxygen from a face mask attached to the circle system of the anesthesia machine. One MAC was considered to be 2.0% for sevoflurane and 1% for halothane.10,11 The anesthesia circuit was primed with the selected anesthetics
in the above concentration before application of face mask. The desired concentrations of anesthetic drugs were verified using a Datex Ultima (Datex Medical Instrumentation, Inc., Helsinki, Finland) gas monitor. Surgery started as soon as the patients lost consciousness. The times for each patient’s entry into the operating room (OR), start of anesthetic induction, and start of surgery were recorded. Loss of consciousness was defined as start of surgery (insertion of ear speculum for myringotomies, which represented over 73% of the study cases) or start of laryngoscopy in the remaining cases for which tracheal intubation was indicated. These times were selected because they represented clearly defined endpoints that closely approximated loss of consciousness as assessed by eyelid reflexes. Vaporizers for both anesthetics were mounted on the anesthesia machine. The vaporizer of the anesthesia delivery system was hidden from the view of the anesthesiologists by a sheet of cardboard taped to the front of the anesthesia machine. A person who did not participate in rating the target variables of the study selected either the sevoflurane or the halothane vaporizer in a randomized fashion. To avoid recognition of the volatile anesthetic by smell, the face masks of the study participants were treated with a drop of artificial strawberry flavor. After completion of the anesthetic induction, the anesthesiologists who administered the anesthetic were asked to identify the drug used in their particular case. Further, the pediatric anesthesiologists were asked to rate the speed and quality of anesthetic induction. A visual analog scale (VAS), with a minimum score of 0 and a maximum score of 100, was used for quantification. The incidence of coughing, breath holding, tachycardia, laryngospasm, and need for succinylcholine during the induction of anesthesia were recorded at the same time.The ability of the anesthesiologists to correctly identify the drug was tested using a procedure based on the normal distribution (the Z test). The anesthesiologists’ assessments concerning which drug was administered were also tested using the chi-square analysis. The chi-square analysis also was used for comparing the incidence of cough, breath holding, tachycardia, laryngospasm, and need for succinylcholine. VAS scores were compared using the Mann-Whitney U-test. The twosample t-test was used for comparing the ages and weights of the patients. P-values ⬍ 0.05 were considered statistically significant. Descriptive statistics are expressed as means ⫾ SD whenever appropriate.
Results Of the 78 patients studied, 43 children received sevoflurane and 35 children received halothane. 57 patients (73%) received bilateral myringotomies with tube placement and the remaining patients also underwent brief otolaryngologic surgery. The children in the two groups were well-matched with regard to age (sevoflurane group 44 ⫾ 29 mo; halothane group 40 ⫾ 29 mo; p ⫽ 0.57), sex (sevoflurane group 21 females /22 males; halothane group 17 females /18 males; p ⫽ 0.88 ), and weight (sevoflurane group 17 ⫾ 7 kg; halothane group 17 ⫾7 kg; J. Clin. Anesth., vol. 12, May 2000
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Figure 1. A. Frequency of correct and incorrect answers. B. Frequency of identifying sevoflurane or halothane in each of two groups. The anesthesiologist’s judgments from the column; the drugs actually administered from the rows.
p ⫽ 0.96). The time intervals from entering the operating room until the start of induction (sevoflurane group 1.4 ⫾ 1.2 min; halothane group 1.2 ⫾ 1.1 min; p ⫽ 0.67) and from the start of induction to the start of surgery (sevoflurane group, 3.7 ⫾ 2.7 min; halothane, group 3.7 ⫾ 2.6 min; p ⫽ 0.96) were not significantly different between the two groups. The pediatric anesthesiologists correctly identified the anesthetic in 55 of 78 assessments (70.5%, Figure 1A). This figure is statistically better than what could be achieved by random guessing (p ⬍ 0.001). By chi-square analysis, the pediatric anesthesiologists gave the reply that sevoflurane was used significantly more often in the sevoflurane group (and vice versa for halothane; p ⬍ 0.001; Figure 1B). The residents correctly identified the anesthetic in only 46 of 78 assessments (60.0%). Statistically, this figure is no better than what could be achieved by random guessing (p ⫽ 0.06). By chi-square analysis, the residents did not give the reply that sevoflurane was used significantly more often in the sevoflurane group (and vice versa for halothane; p ⫽ 0.12). The perceived speed of induction was significantly 186
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faster in sevoflurane group than in halothane group (p ⫽ 0.008; Figure 2), although there was no difference in actual time between the start of induction and start of surgery for the two drugs. There were no differences in the VAS for quality of induction (p ⫽ 0.94). The incidence of coughing (sevoflurane group, 12%; halothane group 14%; p ⫽ 0.73), breath holding (sevoflurane group, 12%; halothane group 18%; p ⫽ 0.42), laryngospasm (sevoflurane group, 7%; halothane group 6%; p ⫽ 0.82), and need for succinylcholine (sevoflurane group, 0%; halothane group, 0%) was not different between the two groups. However, the incidence of tachycardia (sevoflurane group, 74%; halothane group 20%; p ⬍ 0.001) as perceived by anesthesiologist was significantly greater in the sevoflurane group.
Discussion Numerous studies have attempted to identify the benefits of sevoflurane for induction of anesthesia in pediatric patients. Some of these studies1,4,5,12 found that sevoflurane permitted a faster anesthetic induction than halo-
Rapid induction of anesthesia: Morimoto et al.
Figure 2. Box plots of the median, 10th, 25th, 75th, and 90th percentiles for the visual analog scale scores for the speed and quality of induction of sevoflurane versus halothane anesthesia. The visual analog scale ranged from 0 (lowest quality or speed) to 100 (highest quality or speed). Speed of induction was significantly faster in the sevoflurane group than in the halothane group (p ⫽ 0.008). There were no differences in quality of induction (p ⫽ 0.94)(Mann-Whitney U-test).
thane. Some of these studies also describe better hemodynamic stability4 or fewer dysrhythmias4,5 with sevoflurane compared to halothane. However, some investigators have not found the induction characteristics of sevoflurane to be different from other volatile anesthetics. No significant differences in the time to loss of eyelid reflex in children were observed when comparing sevoflurane with halothane,2,3,7 nor was there a significant difference between the two drugs in emergence time after anesthesia.7 It has been reported that pediatric anesthesiologists could not reliably identify sevoflurane when it was given in a blinded, randomized fashion with gradual increases in inspiratory concentrations.6 In the same study, it was concluded that there were no significant differences in the perceived speed of induction between the two drugs. Considering the high cost of sevoflurane compared with halothane, evaluation of the differences between the two drugs and the advantages of sevoflurane under clinical conditions is relevant and important. In this study, we re-evaluated the differences between the two drugs by administering high initial concentrations (approximately 4 MAC) for anesthetic induction. Similar studies using this technique found a significantly faster induction of anesthesia with high initial concentrations than incremental increases in the inspired concentration, without serious complications.8,9 In this study, we used 8% sevoflurane, the maximum concentration delivered by calibrated vaporizers. MAC of sevoflurane in children has been reported to be both 2.03%10 and 2.5%.13 Inomata et. al.10 reported MAC of sevoflurane was 2.03% in pediatric patients, aged 1 to 9 years. As most patients in this study were in this age range, we estimated that 8% sevoflurane is equal to 4 MAC. MAC of halothane in children in a similar age range has been
reported to be between 0.87% and 0.97%.11 Based on these previous studies, we are confident that the 8% sevoflurane and 4% halothane used in this study are comparable doses of anesthetics. The perceived presence of tachycardia during the induction of sevoflurane was an interesting finding of this study. It may have been the primary clue used by the pediatric anesthesiologists in determining which drug was being administered. There are a number of reports of tachycardia during induction with sevoflurane. Lerman et al.13 reported that heart rate (HR) increased over 10% above awake values in children older than three years at 1 MAC of sevoflurane. Kawana et al. 4 compared hemodynamic changes induced by sevoflurane and halothane in pediatric patients. They found that HR increased at both 1 MAC and 2 MAC of sevoflurane but did not increase with 1 MAC of halothane. Incidence of tachycardia with sevoflurane was observed to be dose-dependent and higher than at the same MAC of halothane. Rapid induction with high concentrations of sevoflurane might increase the patients’ HR more than when sevoflurane is given in an incremental fashion. This theory may be the main reason that the anesthesiologists could differentiate between halothane and sevoflurane in this study. Another difference between the two drugs was the perceived speed of induction. As assessed by the pediatric anesthesiologists, induction was significantly faster with sevoflurane than halothane. However, the actual recorded time from start of induction to the start of surgery was not different between two groups (sevoflurane group, 3.7 ⫾ 2.7 min; halothane group, 3.7 ⫾ 2.6 min). Since the start of surgery coincided with achieving surgical anesthesia (no need to prep and drape for myringotomies), we consider the time from start of induction to the start of J. Clin. Anesth., vol. 12, May 2000
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surgery as actual anesthetic induction time. As expected, these times were faster by about one minute than those in our previous study, 6 in which there was a gradual increase in the inspired concentration (sevoflurane group, 4.7 ⫾ 2.1 min; halothane group, 4.6 ⫾ 2.1 min). When immediate high concentrations of volatile drugs are used for induction, respiratory complications caused by airway irritation may possibly be a problem. However, the incidence of airway complications in this study was similar to previous reports, and there were no serious complications that required succinylcholine during induction with either sevoflurane and halothane. Moreover, there was no difference in perceived quality of induction between the two drugs. Epstein et al.9 reported that there were no significant differences in induction complications between immediate high concentration and incremental increase of sevoflurane. Doi et. al. 15compared airway irritation caused by halothane, enflurane, isoflurane and sevoflurane. They reported that sevoflurane was the least irritant anesthetic, followed by halothane. These characteristics allowed the use of the high initial concentrations employed in this study. We conclude that the rapid induction of anesthesia with high concentrations of either halothane or sevoflurane can be safely accomplished, and that there are no differences in objective time for induction of anesthesia. High initial concentrations of these drugs reduce induction time by approximately 25% (i.e., from 4.7 min to 3.7 min in sevoflurane group) as compared to incremental increases. We found no differences between sevoflurane and halothane in the incidence of airway complications. The study further demonstrates that pediatric anesthesiologists can differentiate between halothane and sevoflurane when the drugs are given in high initial concentrations. The significant differences between the two drugs were found in the incidence of tachycardia and the perceived speed of induction. The tachycardia, which was frequently noted with the sevoflurane, may have served as the primary clue in determining which drug was being used.
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