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A comparison of sevoflurane with halothane in outpatient adenotomy in children with mild upper respiratory tract infections
ELSEVIER
A Comparison of Sevoflurane with Halothane in Outpatient Adenotomy in Children with Mild Upper Respiratory Tract Infections Armin Rieger, MD, DEAA,* Gerd Schriiter, Walter Philippi, MD,? Isabel HassJ Klaus Eyrich, MD, PhD§
MD,?
of Anesthesiology and Operative Intensive Care Medicine, Franklin Medical Center, Free University of Berlin, Berlin, Germany
Department
*Senior Registrar tRegistrar $House Officer SProfessor, Chairman Address reprint requests to Dr. Rieger at the Department of Anesthesiology and Operative Intensive Care Medicine, Benjamin Franklin Medical Center, Free University of Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. Received for publication October 21, 1994; revised manuscript accepted for publication May 8, 1995. This work was supported by Abbott Laboratories, Abbott Park, Illinois 600643500, USA.
Benjamin
Study Objective: To investigate the efficaq and safety of seuojlurane compared with halothane in pediatric outpatient ear-nose-throat (ENT) surgery during the induction, maintenance, emergence, and recovery of anesthesia. Design: Prospective, randomized, comparative, open-label study. Setting: ENTT operating room and postojzrative recovery room at a university medical ten to-. Patients: 41 ASA status I and II children between the ages of 2 to 10 years, with mild upper respiratoq tract infection (URI). Interventions: Induction and maintenance of anesthesia with either sevofurane or halothane for outpatient adenotomy, otomicroscopy, and myn’ngotomy. Measurements and Main Results: Induction (means + SEM) was significantly shorter in the sevoflurane group (2.6 + 0.2 minutes) than in the halothane group (3.2 + 0.2 minutes). There was no difference between the two groups with regard to complications that occurred during the induction and maintenance period. The time to emergence and recovery was signijcantly shorter with seuofZurane than with halothane (means + SEM; time to extubation 9.9 + 0.98 minutes vs. 13.4 + 1.06 minutes, time to eye opening 12.9 + 1.6 minutes vs. 24.5 f 1.8 minutes, command response time 20.7 * 2.5 minutes vs. 36.4 + 2.8 minutes). No difference in the incidence of complications during emergence and recovery was found. Evaluation of recovery as assessedby a modified Aldrete score showed that children who had received sevoflurane reached higher scores in the first 30 minutes following the discontinuation of the anesthetic. The Pain/Discomfort Scale demonstrated a difference in the sevoflurane group, with more children being agitated and restless. Conclusion: Sevoflurane provides a safe and rapid anesthetic induction with no dfferences in complications during the induction, maintenance, and emergence period. With sevoflurane, the time of emergence and recovery was significantly shorter. The characteristics of sevoflurane as evaluated in the present study make it a suitable anesthetic in pediatric outpatient surgery even in the presence of mild URI. Keywords: halothane;
Journal of Clinical Anesthesia 8:188-193, 1996 0 1996 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Airway infections, pediatric; anesthesia: induction, pediatrics; sevoflurane; surgery, outpatient.
recovery;
0952-8180/96/$15.00 SSDI 0952-8180(95)00227-8
Introduction Halothane continues to play a dominant role in pediatric anesthetic practice. Because of its nonirritating odor, halothane is far better tolerated for inhalational induction in children than isoflurane or the newer volatile anesthetic, desflurane, which frequently leads to breath holding or laryngospasm during induction.” Sevoflurane, which was first described in 1975, is a seven-fold fluorinated derivative of methyl isopropyl ether.’ It has a blood/gas-partition coefficient of 0.6g4 and seems to have the least irritating effect on the respiratory tract as compared with halothane, enflurane, and isoflurane.” These properties enhance a rapid increase in the alveolar anesthetic concentration during the induction period and a rapid decrease after discontinuation of the drug. Due to its exclusive fluorination, sevoflurane is less potent than chlorinated and brominated inhaled anesthetics.” The minimal alveolar concentration (MAC) of sevoflurane in children ages 1 to 12 years is 2.5 vol ‘%.7,x Children with hyperplastic adenoids often have coexisting mild upper respiratory tract infections (URIS). In the presence of mild URIS, use of a fastacting, nonirritating inhalational anesthetic might reduce complications. The aim of this study was to compare the speed and the quality of the induction and emergence of anesthesia with sevoflurane and halothane in this population with mild URI.
Materials
and Methods
The study was approved by the Ethics Committee of the Benjamin Franklin Medical Center of the Free University of Berlin. Written informed consent was obtained from the parents or guardians at least 24 hours prior to the onset of the study. Included in the study were 41 ASA physical status I and II children between the ages of 2 and 10 years. All children were scheduled for outpatient adenotomy, otomicroscopy, and myringotomy in our earnose-throat (ENT) outpatient clinic. All children had mild URIS with rhinorrhea (clear secretion) and partially obstructed nasal breathing. Children with fever (>38”C rectal) and bacterial infections, as assessed by purulent nasal secretions, were excluded from the study. The children were randomly assigned, via computer-generated list, to receive either halothane or sevoflurane 30 minutes prior to induction. Fifteen minutes prior to induction all children received a rectal premeditation consisting of midazolam 0.5 rng/kg and atropine 0.02 rng/kg. Induction of anesthesia was performed via a face mask and a stepwise illcrease in the inspired concentration of the inhaled anesthetic at every fifth breath. The concentration of halothane was increased in steps of 0.5 vol %, sevoflurane was increased in 1..5 vol %, steps. The fresh gas flow was 6 IJmin with 4 I,
nitrous oxide (N,O) in oxygen (0,). Following the loss of the lid reflex and transition to a regular breathing pattern, an intravenous cannula was placed in a cubital or forearm vein. Endotracheal intubation was then facilitated with succinylcholine 1.5 mg/kg. Anesthesia was maintained with a reduced fresh gas flow of 2 L N,O in 1 L 0, per minute and either sevoflurane or halothane, respectively. At the end of the operation, the inhaled anesthetic was abruptly discontinued. Tapering of anesthetic gases was not allowed. Monitoring included ECG (lead II), oscillometric blood pressure measurements (Dinamap 8100, Critikon, Tampa, FL) every minute during induction and evev 5 minutes during maintenance, inspired and expirational concentrations of anesthetic gases, end-tidal carbon dioxide partial pressure (P&O,; Capnomac Ultima lT”, Datex Instrumentarium, Helsinki, Finland), and arterial hemoglobin 0, saturation measured by pulse oximetry (Biox 3740, Ohmeda, Madison, WI). Normoventilation (P&O, 35 to 45 mmHg) was maintained by manually assisted bag ventilation. ,4 semi-closed circuit (Circle System 7a, Drager, Liibeck, Germany; Pediatric AIIesthesia Set with Latex Spiral Hoses, I.D. 10.5 mm, Rtisch, Kernen-Stuttgart, Germany) with a soda lime CO,absorber was used. Sevoflurane and halothane were administered outside the circle system via appropriately calibrated vaporizers (Vapor 19.1, Drager, I,iibeck, Germany). MAC-hours were obtained by multiplying the quotient of mean end-tidal anesthetic gas concentration by agedependent MAC with the time of application. The following times were measured: (1) induction time, defined as the time from the beginning of the anesthetic until the loss of the lid reflex and transition to a regular breathing pattern, (2) time to extubation (full recovery of ailway competence) after discontinuation of inhaled anesthetic, (3) emergence time, i.r., interval between discontinuation of inhaled anesthetic and eye opening or response to nonpainful stimuli, (4) command response time, i.r., time after discontinuation of the inhaled anesthetic until response to commands or purposeful movements, (5) tirne to sitting up without nausea and dizziness after anesthesia, (6) time to first use of analgesics after allesthesia, (7) time from discontinuation of inhaled anesthetic until discharge from the recovery room. The incidence of laryngospasrn, breath holding, excessive secretion, and excitation during induction and emergence was documented. Recovery was characterized and evaluated by a11 indepeuclent observer using a modified ,4ldrete score” and a Pain/Discomfort scale described by Hannallah it nl. I0 (A!)pmlix) Results are presented in the text as means & SEM. The Mann-Whitney U-Wilcoxon rank sum MI test and Fishers exact test for independent samples were used to identify significant intergroup differences for ordinal Lralues. Intergroup differences of parametric values were determined by Students t-test for independent samples. A pvahic> less than 0.05 WdS considered statistically sign& cant.
Original Contributions Table 1.
Demographic
Characteristics
of Both Patient Croups
Sevofluraue Group (n = 22)
Age (~1 Weight (kg) Height (cm) Duration of surgery
3.9 19.6 108.6 57.7
(min)
and Undesired
Halothane Group (n = 19)
f 1.8 rt: 6.4 3~13.1 k 5.4
Note: Data are means k SEM. No significant groups were noted.
Table 3. Complications during Induction
3.7 18.2 107.2 54.1 differences
f k f f
1.9 4.6 11.6 5.8
between
Side Effects
Sevofluraue Group (n = 22) Coughing Laryngospasm Breath holding Excessive secretion Excitation Bradycardia (>30% from baseline)
6 0 1 0 16 1
Halothane Group (n = 19) 4 0 0 1 16 4
Note: Data are numbers of patients.
Results The two groups were comparable with weight, height, and duration of surgery
mum end-tidal rane
during
concentrations
induction,
respect
to age,
(Table 1). Maxiof halothane and sevoflu-
as well
as minimum,
mean,
and
maximum end-tidal concentrations during maintenance are listed in Table 2. MAC-hours were similar in both groups (sevoflurane 1.16 ? 0.14; halothane 1.20 + 0.15). Induction time with sevoflurane was 2.6 & 0.2 minutes. Although there was only a 0.6 minute difference between the mean values in both groups, this was significantly shorter than with halothane (3.2 + 0.2 minutes). The rate of complications and side effects during induction was similar in both groups (Table 3). Four children in the halothane group and one child in the sevoflurane group had a more than 30% decrease in heart rate (HR) from baseline, but this difference was not statistically significant. Sevoflurane demonstrated a significant advantage in postanesthetic time parameters (Table 4). Again, during the emergence and recovery period there was no difference between both groups with regard to undesired events ( Table 5). Children in the sevoflurane group were able to sit upright without nausea and dizziness significantly sooner than
the halothane
group
children
(71.8
f 5.1 minutes
US.88.8 k 4.3 minutes). There was no difference application of analgesics after anesthesia
first
Table 2. Anesthetic Gas Concentrations Maintenance of Anesthesia End-tidal
Concentration
Sevoflnraue Group (n = 22) Induction Maximum Maintenance Minimum Maximum Mean
Induction
and
(vol %)
1.79 + 1.74
1.65 f 0.09 2.52 k 0.09 2.16 + 0.08
0.80 f 0.10 1.09 f 0.09 0.95 f 0.09
J, Clin. Anesth., vol. 8, May 1996
more
discomfort
than
those
group. During the remainder tion period, no difference groups.
children
in the
halothane
of the 120-minute observawas found between both
Discussion Induction of anesthesia by inhalation of anesthetic gases via a face mask is an acceptable option and, in many hospitals, a preferred technique in pediatric anesthesia.” Because of its nonpungent odor, halothane has been consid-
Table 4.
Time Course of the Postanesthetic
Halo&me Group (n = 19)
7.33 f 1.62
Note: Data are means ? SEM.
190
during
as to the (sevoflu-
rane: 52.3 f 17.9 minutes vs. halothane: 42.5 i 21.4 minutes). The tendency that children in the sevoflurane group were discharged sooner from the recovery room than children in the halothane group could not be statistically verified (sevoflurane: 78.0 + 3.3 VS. halothane: 87.2 * 3.5). Ten minutes after the end of the anesthetic, significantly more children in the sevoflurane group had reached an Aldrete score of 8 points or more. At 20, 30, 40, and 50 minutes after anesthesia, the percentage of children with an Aldrete score of 8 or more was not statistically different between groups (Figure I). Scores evaluated via the Pain/Discomfort scale during recovery showed significant differences at 20, 30, and 40 minutes after anesthesia (F@Lw 2), with higher scores in the sevoflurane group, indicating that these children experienced
Halothane Group (n = 19)
p-Value
9.9 f 0.98 12.9 f 1.6
13.4 + 1.06 24.5 + 1.8
20.7 f 2.5
36.4 iz 2.8
Sevoflurane Group (n = 22) Time to extubation (min) Eye opening (min) Responds to commands (min) Note: Data are means + SEM.
Period
Complications and Undesired Side Effects during Emergence and Recovery from Anesthesia
Table 5.
Sevofluraue Group (n = 22)
Halo&me Group (n = 19)
16 1 17 1
19 1 21 1
Coughing Laryngospasm Excitation Vomiting
Note: Data are numbers of patients.
ered superior to other currently available inhaled anesthetics. Sevoflurane, which has been available in Japan since 1990, will probably be available in near future in Europe and in the United States. It combines the advantages of low airway irritation with a blood gas coefficient close to N,O. This allows for rapid changes in alveolar anesthetic concentrations during induction, maintenance, and emergence of anesthesia. We evaluated the characteristics of sevoflurane in comparison to halothane in a population with mild URIS. Whereas Naito ef al.” did not find a significant difference between sevoflurane and halothane in induction times in children ages 1 to 7 years, we found a slight but statistically significant shorter induction time with sevoflurane in a similar population. This discrepancy could be explained by the fact that our increments of inspired sevoflurane concentration (1.5 vol %) were somewhat higher and probably more equianesthetic than the increments used by Naito et al. (0.5 to 1.0 vol % for halothane and sevoflurane), because the MAC value for sevoflurane is approximately threefold higher than the MAC value for halothane.7 The difference in the induction times between sevoflurane and halothane may be equalized by an
induction technique using higher inspired halothane concentrations. However, the standardized induction procedure of our protocol with restricted and equianesthetic increments of the volatile anesthetics makes the pharmacokinetic profile of both substances more comparable. Sevoflurane provided a rapid and smooth induction with no difference in complication rates between both study groups. Coughing during induction in approximately one-fourth of the children in both groups may suggest the presence of bronchial hyperreactivity due to URI.‘s Excitation was mild and quickly terminated in both groups. Sevoflurane preserved stable hemodynamic conditions during induction, which is in agreement with previous laboratory and clinical findings.‘4.” Only one child in the sevoflurane group and four children in the halothane group demonstrated a transient decrease in HR of more than 30% from preanesthetic baseline. The intraoperative course was uneventful and revealed no differences in hemodynamic parameters. MAC-hours were calculated to confirm that equianesthetic concentrations of inhaled anesthetics were administered in both groups. As the duration of surgery and MAC-hours were similar, the prerequisite was given to compare emergence and recovery between the sevoflurane and halothane groups. Although tapering of anesthetic gases at the end of surgery is certainly the appropriate technique in clinical practice, we abruptly discontinued volatile anesthetics to establish identical starting conditions for the evaluation of emergence and recovery. The more rapid decrease of alveolar anesthetic concentration of sevoflurane after discontinuation of administration allowed a significantly earlier extubation of children in the sevoflurane group. Differences in emergence (time until eye opening) and command response times were highly significant, with a clear advantage for sevoflurane. However, it must be kept
100 90 80 70 %
60 50 40 30 20 10 0
10
20
30 Minutes after anesthesia
40
50
Figure 1. Percentage of children scoring 8 or more points in the modified Aldrete scoring system at 10, 20, 30,40, and 50 minutes after anesthesia. Only at 10 minutes after anesthesia was there a significant difference between the sevoflurane and the halothane group (*p < 0.05).
J. Clin. Anesth., vol. 8, Mav 1996
191
Original
Contributions
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Minutes after Anaesthesia Figure 2. Scores and median-values in the Pain/Discomfort scale.“’ Differences were statistically different at 20, 30, and 40 minutes (*p < 0.05) after anesthesia. (Individual values: 0 Halothane (Halo), v Sevoflurane (Sevo); median values: --).
in mind that recovery of cognition and motor coordination, which defines the patient’s readiness to leave the recovery room, requires a longer period of time than recovery for response to command. Evaluation of coordination and cognitive function was not studied in our protocol. Children in the sevoflurane group were able to sit up without nausea and dizziness somewhat sooner than the halothane group children, but the time until discharge from the recovery room was not statistically different between the two groups. This is in contrast to the findings of Naito rt &,I2 who demonstrated a significantly earlier discharge from recovery room in the sevoflurane group. This is possibly due to the different type of surgery (laser therapy of port-wine stains of the face and neck region), which did not carry the risk of potential airway complications per se. As recovery scores do not correlate with postoperative hypoxemia in children, we regarded prolonged observation of airway patency after adenotomy mandator)‘.‘“.” Immediate recovery after sevoflurane administration was faster, as documented by a higher percentage of children with Aldrete scores of at least 8 in this group. However, Aldrete scores were similar in both groups from 20 minutes after anesthesia. In the sevoflurane group, there was a trend to more unruly recoveries characterized by agitation, movement, and crying. Scores assessed by the Pain/Discomfort Scale were higher after sevoflurane at 20, 30, and 40 minutes after discontinuation of administration and were due to crying, moving, and agitation. This supports the finding of Naito PL nl.,” who observed more children with restlessness and agitation after sevoflurane but could not verify a statistical difference. A high incidence of this so-called recovery delirium is also described
192
,J. Clin. Anesth., vol. 8, May 1996
after anesthesia with desflurane.” Earlier perception of pain after the more rapid elimination of the inhaled anesthetic may be an etiologic factor.‘” However, in our study, the time of the first application of analgesics, determined by the independent observer, was not different between groups. We presume that following sevoflurane anesthesia the earlier and rather immediate perception of the strange and unknown surroundings in the operating theater may contribute to the child’s confusion, restlessness, and agitation. However, further investigation is required to investigate this issue. As we awaited full recovery of airway competence before extubation, a high incidence of coughing occurred in both groups. The rate of vomiting was low in both groups. This is in keeping with previous findings by Morisaki rl nl.“’ In conclusion, we found that sevoflurane provided a rapid and smooth induction of anesthesia in children with mild URIS. With respect to complications and undesired side effects, there was no difference between halothane and sevoflurane during induction, maintenance, and Although agitation and restlessness were emergence. more frequent following sevoflurane than halothane, we consider it a suitable anesthetic for pediatric anesthesia, especially for outpatient surgery. It may be preferable to halothane as the time course of emergence and recovery is significantly faster with sevoflurane.
Acknowledgment We wish to thank Dr. Glenda Brurnmer and Dr. Christian Apenburg, staff anesthesiologists of our department, for her careful preparation of this manuscript and for his statistical review of the data.
S~uojlurane vs. ha&ham in outpatient admotomy zn children: Riegw rt (11. Appendix.
Characterization Modified
of Recovery’~‘” Aldrete
Pain/Discomfort
Score
Parameter Blood pressure >20% of preanesthetic level fl l-20% of preanesthetic level ~10% of preanesthetic level Crying not responding to TLC* responding to TLC not crying Moving thrashing restless none Agitation hysterical mild asleep or calm Verbal evaluation moderate pain mild pain asleep or no pain
Score
Parameter Activity able to move 4 extremities able to move ‘2 extremities able to move 0 extremities Respiration Breathes deeply and coughs dyspneic, shallow breathing apneic Blood pressure ~10% of preanesthetic level fl l-20% of preanesthetic lrvel >20% of preanesthetic level Consciousness fully a\vake al-ousable on calling not responding Rectal temperature hetlveen 35.6”C and 37.5”C between J5’C . > I 2 and 35.6”c’ 45°C: or >97.5’C
Scale
2 1 0 2 1 0 2 1 0 2 1 0 2 1 0
Score 2 0 2 1 0 2 1 0 2 1 0 2 1 0
*TLC: = tender loving care.
Il.
score. AnP\th
Berry FA (ed): An&h&c Management o/U(fjdt and Koutirw fklzntnc Patimt.\. New York: Churchill Livingstone, 1990:15-52. 12. Naito Y, Tamai S, Shingu K, Fujimori R, Mori K: Comparison between sevoflurane and halothane for pacdiatric ambulatory anaesthesia. BrJAnnrsth 1991;67:387-9. 13. Empey DW, Laitinen LA, Jacobs I~, Gold U’M, Nadel J& Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory infections. Am RPII Resp Di.s 1976;113:131-9. 14. Karama T, Ikeda K: The comparative cardiovascular effects of srvoflurane with halothane and isoflurane. ,JAne.sth 1989;2:63-8. 1.5. Frink EJ JI, Malan TP, Atlas M, Dominguey LM, DiNardo JA, Brown BR Jr: Clinical comparison of sevoflurane and isoflurane in healthy patients. An&h Analg 1992;74:241-5. 16. Soliman IE, Patel RI, Ehrenpreis MB, Hannallah RS: Recover) scores do not correlate with postoperative hypoxemia in children. Anrrth Annlg 1988;67:53-6. 17. DeSoto H, Pate1 RI, Soliman IE, Hannallah RS: Changes in oxygen saturation following general anesthesia in children with upper respiratory infection signs and symptoms undergoing otolaryngological procedures. An~sthrsiolo,~ 1988;68:27&9. 18. Davis F’J, Cohen IT, McGowan FX Jr, Latta K: Recovery characteristics of desfhu-dne versus halothane for maintenance of anesthesia in pediatric ambulatoq~ patients. Anrsthrsiolqq 1994;80: 29x-302.
10. Harmallah KS, Broadman LM, Behnan AB, Abramowitz MD, Epstein BS: (:ompal-ison of caudal and ihoinguinal/iliohypogdstric nr~-ve blocks tar contl-ol of I”‘st-“rchioI)exy pain in pediatric an,I)rll;itol\ \urgel-y. .~~~lhe~io/og?’ 1987;66:832-4.
19. Egcr EI 2d: New inhalrd anesthetics. Alzrs/hrriolo,q 1994;80:90622. 20. Morisdki H, Suzuki G, Miydzawd N, Kiichi Y, ,Misaki T, Slr/uki A: A cliniral trial of sevoflurane in children for herniorrhaphy. ,J AnPrfh 1988;2:94-7.
References 1, Taylor WI, LermanJ: Induction, maintenance and recovev characteristics of desflurane in infants and children. Cnn ,/ Ann&h 1992;39:&13. 2. Z~ass MS, Fisher DM, Welhorn LG, et al: Induction and maintenance characteristics of anesthesia with desfhlrdne and nitrous oxide in infants and childI-en. Annthesiolog) 1992;76:378-8. 3. Wallin RF, Regan BM, Napoli MD, Stern IJ: Sevoflurane: a new inhalational anesthetic agent. .4nmth Analg 1975;34:738-66. 4. Strum DP, Eger EL 2d: Partition coefficients for sevoflurane in human blood, saline, and olive oil. AmAth Anolg 1987;66:654-6. .i. Doi M, Ikeda K: Airway iI-ritation produced by volatile anaesthrtits during brief inhalation: comparison of halothane, enflurane, isoflurane and sevoflurane. Gn J Anarrth 1993;40:122-6. 6. Tat-g A(;, Yasuda N, Eger El 2d, ?t al: Halogenation and anesrhrtic I)otency. Anrtlh iinrclg 1989;68:599-602. i. 1.~man J, Sikich N, Klrinman S, Yentis S: The pharmacolog of sr\ofl~lranc in infants and children. 4nrrthrriolqgy 1994;80:81424. 8. Katoh T, Ikeda K: Minimum alveolar concentration rane in children. Hr./ Anmwh 1992;68:139-41. 9. Aldrcte JA, Kroulik D: A postanesthetic ANN/g 1970;49:924-54.
recovery
of
sevofl~~-
,J. <:lin. ilnesth., vol. 8, May 1996
193
A Comparison of Sevoflurane with Halothane in Outpatient Adenotomy in Children with Mild Upper Respiratory Tract Infections Armin Rieger, MD, DEAA,* Gerd Schriiter, Walter Philippi, MD,? Isabel HassJ Klaus Eyrich, MD, PhD§
MD,?
of Anesthesiology and Operative Intensive Care Medicine, Franklin Medical Center, Free University of Berlin, Berlin, Germany
Department
*Senior Registrar tRegistrar $House Officer SProfessor, Chairman Address reprint requests to Dr. Rieger at the Department of Anesthesiology and Operative Intensive Care Medicine, Benjamin Franklin Medical Center, Free University of Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. Received for publication October 21, 1994; revised manuscript accepted for publication May 8, 1995. This work was supported by Abbott Laboratories, Abbott Park, Illinois 600643500, USA.
Benjamin
Study Objective: To investigate the efficaq and safety of seuojlurane compared with halothane in pediatric outpatient ear-nose-throat (ENT) surgery during the induction, maintenance, emergence, and recovery of anesthesia. Design: Prospective, randomized, comparative, open-label study. Setting: ENTT operating room and postojzrative recovery room at a university medical ten to-. Patients: 41 ASA status I and II children between the ages of 2 to 10 years, with mild upper respiratoq tract infection (URI). Interventions: Induction and maintenance of anesthesia with either sevofurane or halothane for outpatient adenotomy, otomicroscopy, and myn’ngotomy. Measurements and Main Results: Induction (means + SEM) was significantly shorter in the sevoflurane group (2.6 + 0.2 minutes) than in the halothane group (3.2 + 0.2 minutes). There was no difference between the two groups with regard to complications that occurred during the induction and maintenance period. The time to emergence and recovery was signijcantly shorter with seuofZurane than with halothane (means + SEM; time to extubation 9.9 + 0.98 minutes vs. 13.4 + 1.06 minutes, time to eye opening 12.9 + 1.6 minutes vs. 24.5 f 1.8 minutes, command response time 20.7 * 2.5 minutes vs. 36.4 + 2.8 minutes). No difference in the incidence of complications during emergence and recovery was found. Evaluation of recovery as assessedby a modified Aldrete score showed that children who had received sevoflurane reached higher scores in the first 30 minutes following the discontinuation of the anesthetic. The Pain/Discomfort Scale demonstrated a difference in the sevoflurane group, with more children being agitated and restless. Conclusion: Sevoflurane provides a safe and rapid anesthetic induction with no dfferences in complications during the induction, maintenance, and emergence period. With sevoflurane, the time of emergence and recovery was significantly shorter. The characteristics of sevoflurane as evaluated in the present study make it a suitable anesthetic in pediatric outpatient surgery even in the presence of mild URI. Keywords: halothane;
Journal of Clinical Anesthesia 8:188-193, 1996 0 1996 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Airway infections, pediatric; anesthesia: induction, pediatrics; sevoflurane; surgery, outpatient.
recovery;
0952-8180/96/$15.00 SSDI 0952-8180(95)00227-8
Introduction Halothane continues to play a dominant role in pediatric anesthetic practice. Because of its nonirritating odor, halothane is far better tolerated for inhalational induction in children than isoflurane or the newer volatile anesthetic, desflurane, which frequently leads to breath holding or laryngospasm during induction.” Sevoflurane, which was first described in 1975, is a seven-fold fluorinated derivative of methyl isopropyl ether.’ It has a blood/gas-partition coefficient of 0.6g4 and seems to have the least irritating effect on the respiratory tract as compared with halothane, enflurane, and isoflurane.” These properties enhance a rapid increase in the alveolar anesthetic concentration during the induction period and a rapid decrease after discontinuation of the drug. Due to its exclusive fluorination, sevoflurane is less potent than chlorinated and brominated inhaled anesthetics.” The minimal alveolar concentration (MAC) of sevoflurane in children ages 1 to 12 years is 2.5 vol ‘%.7,x Children with hyperplastic adenoids often have coexisting mild upper respiratory tract infections (URIS). In the presence of mild URIS, use of a fastacting, nonirritating inhalational anesthetic might reduce complications. The aim of this study was to compare the speed and the quality of the induction and emergence of anesthesia with sevoflurane and halothane in this population with mild URI.
Materials
and Methods
The study was approved by the Ethics Committee of the Benjamin Franklin Medical Center of the Free University of Berlin. Written informed consent was obtained from the parents or guardians at least 24 hours prior to the onset of the study. Included in the study were 41 ASA physical status I and II children between the ages of 2 and 10 years. All children were scheduled for outpatient adenotomy, otomicroscopy, and myringotomy in our earnose-throat (ENT) outpatient clinic. All children had mild URIS with rhinorrhea (clear secretion) and partially obstructed nasal breathing. Children with fever (>38”C rectal) and bacterial infections, as assessed by purulent nasal secretions, were excluded from the study. The children were randomly assigned, via computer-generated list, to receive either halothane or sevoflurane 30 minutes prior to induction. Fifteen minutes prior to induction all children received a rectal premeditation consisting of midazolam 0.5 rng/kg and atropine 0.02 rng/kg. Induction of anesthesia was performed via a face mask and a stepwise illcrease in the inspired concentration of the inhaled anesthetic at every fifth breath. The concentration of halothane was increased in steps of 0.5 vol %, sevoflurane was increased in 1..5 vol %, steps. The fresh gas flow was 6 IJmin with 4 I,
nitrous oxide (N,O) in oxygen (0,). Following the loss of the lid reflex and transition to a regular breathing pattern, an intravenous cannula was placed in a cubital or forearm vein. Endotracheal intubation was then facilitated with succinylcholine 1.5 mg/kg. Anesthesia was maintained with a reduced fresh gas flow of 2 L N,O in 1 L 0, per minute and either sevoflurane or halothane, respectively. At the end of the operation, the inhaled anesthetic was abruptly discontinued. Tapering of anesthetic gases was not allowed. Monitoring included ECG (lead II), oscillometric blood pressure measurements (Dinamap 8100, Critikon, Tampa, FL) every minute during induction and evev 5 minutes during maintenance, inspired and expirational concentrations of anesthetic gases, end-tidal carbon dioxide partial pressure (P&O,; Capnomac Ultima lT”, Datex Instrumentarium, Helsinki, Finland), and arterial hemoglobin 0, saturation measured by pulse oximetry (Biox 3740, Ohmeda, Madison, WI). Normoventilation (P&O, 35 to 45 mmHg) was maintained by manually assisted bag ventilation. ,4 semi-closed circuit (Circle System 7a, Drager, Liibeck, Germany; Pediatric AIIesthesia Set with Latex Spiral Hoses, I.D. 10.5 mm, Rtisch, Kernen-Stuttgart, Germany) with a soda lime CO,absorber was used. Sevoflurane and halothane were administered outside the circle system via appropriately calibrated vaporizers (Vapor 19.1, Drager, I,iibeck, Germany). MAC-hours were obtained by multiplying the quotient of mean end-tidal anesthetic gas concentration by agedependent MAC with the time of application. The following times were measured: (1) induction time, defined as the time from the beginning of the anesthetic until the loss of the lid reflex and transition to a regular breathing pattern, (2) time to extubation (full recovery of ailway competence) after discontinuation of inhaled anesthetic, (3) emergence time, i.r., interval between discontinuation of inhaled anesthetic and eye opening or response to nonpainful stimuli, (4) command response time, i.r., time after discontinuation of the inhaled anesthetic until response to commands or purposeful movements, (5) tirne to sitting up without nausea and dizziness after anesthesia, (6) time to first use of analgesics after allesthesia, (7) time from discontinuation of inhaled anesthetic until discharge from the recovery room. The incidence of laryngospasrn, breath holding, excessive secretion, and excitation during induction and emergence was documented. Recovery was characterized and evaluated by a11 indepeuclent observer using a modified ,4ldrete score” and a Pain/Discomfort scale described by Hannallah it nl. I0 (A!)pmlix) Results are presented in the text as means & SEM. The Mann-Whitney U-Wilcoxon rank sum MI test and Fishers exact test for independent samples were used to identify significant intergroup differences for ordinal Lralues. Intergroup differences of parametric values were determined by Students t-test for independent samples. A pvahic> less than 0.05 WdS considered statistically sign& cant.
Original Contributions Table 1.
Demographic
Characteristics
of Both Patient Croups
Sevofluraue Group (n = 22)
Age (~1 Weight (kg) Height (cm) Duration of surgery
3.9 19.6 108.6 57.7
(min)
and Undesired
Halothane Group (n = 19)
f 1.8 rt: 6.4 3~13.1 k 5.4
Note: Data are means k SEM. No significant groups were noted.
Table 3. Complications during Induction
3.7 18.2 107.2 54.1 differences
f k f f
1.9 4.6 11.6 5.8
between
Side Effects
Sevofluraue Group (n = 22) Coughing Laryngospasm Breath holding Excessive secretion Excitation Bradycardia (>30% from baseline)
6 0 1 0 16 1
Halothane Group (n = 19) 4 0 0 1 16 4
Note: Data are numbers of patients.
Results The two groups were comparable with weight, height, and duration of surgery
mum end-tidal rane
during
concentrations
induction,
respect
to age,
(Table 1). Maxiof halothane and sevoflu-
as well
as minimum,
mean,
and
maximum end-tidal concentrations during maintenance are listed in Table 2. MAC-hours were similar in both groups (sevoflurane 1.16 ? 0.14; halothane 1.20 + 0.15). Induction time with sevoflurane was 2.6 & 0.2 minutes. Although there was only a 0.6 minute difference between the mean values in both groups, this was significantly shorter than with halothane (3.2 + 0.2 minutes). The rate of complications and side effects during induction was similar in both groups (Table 3). Four children in the halothane group and one child in the sevoflurane group had a more than 30% decrease in heart rate (HR) from baseline, but this difference was not statistically significant. Sevoflurane demonstrated a significant advantage in postanesthetic time parameters (Table 4). Again, during the emergence and recovery period there was no difference between both groups with regard to undesired events ( Table 5). Children in the sevoflurane group were able to sit upright without nausea and dizziness significantly sooner than
the halothane
group
children
(71.8
f 5.1 minutes
US.88.8 k 4.3 minutes). There was no difference application of analgesics after anesthesia
first
Table 2. Anesthetic Gas Concentrations Maintenance of Anesthesia End-tidal
Concentration
Sevoflnraue Group (n = 22) Induction Maximum Maintenance Minimum Maximum Mean
Induction
and
(vol %)
1.79 + 1.74
1.65 f 0.09 2.52 k 0.09 2.16 + 0.08
0.80 f 0.10 1.09 f 0.09 0.95 f 0.09
J, Clin. Anesth., vol. 8, May 1996
more
discomfort
than
those
group. During the remainder tion period, no difference groups.
children
in the
halothane
of the 120-minute observawas found between both
Discussion Induction of anesthesia by inhalation of anesthetic gases via a face mask is an acceptable option and, in many hospitals, a preferred technique in pediatric anesthesia.” Because of its nonpungent odor, halothane has been consid-
Table 4.
Time Course of the Postanesthetic
Halo&me Group (n = 19)
7.33 f 1.62
Note: Data are means ? SEM.
190
during
as to the (sevoflu-
rane: 52.3 f 17.9 minutes vs. halothane: 42.5 i 21.4 minutes). The tendency that children in the sevoflurane group were discharged sooner from the recovery room than children in the halothane group could not be statistically verified (sevoflurane: 78.0 + 3.3 VS. halothane: 87.2 * 3.5). Ten minutes after the end of the anesthetic, significantly more children in the sevoflurane group had reached an Aldrete score of 8 points or more. At 20, 30, 40, and 50 minutes after anesthesia, the percentage of children with an Aldrete score of 8 or more was not statistically different between groups (Figure I). Scores evaluated via the Pain/Discomfort scale during recovery showed significant differences at 20, 30, and 40 minutes after anesthesia (F@Lw 2), with higher scores in the sevoflurane group, indicating that these children experienced
Halothane Group (n = 19)
p-Value
9.9 f 0.98 12.9 f 1.6
13.4 + 1.06 24.5 + 1.8
20.7 f 2.5
36.4 iz 2.8
Sevoflurane Group (n = 22) Time to extubation (min) Eye opening (min) Responds to commands (min) Note: Data are means + SEM.
Period
Complications and Undesired Side Effects during Emergence and Recovery from Anesthesia
Table 5.
Sevofluraue Group (n = 22)
Halo&me Group (n = 19)
16 1 17 1
19 1 21 1
Coughing Laryngospasm Excitation Vomiting
Note: Data are numbers of patients.
ered superior to other currently available inhaled anesthetics. Sevoflurane, which has been available in Japan since 1990, will probably be available in near future in Europe and in the United States. It combines the advantages of low airway irritation with a blood gas coefficient close to N,O. This allows for rapid changes in alveolar anesthetic concentrations during induction, maintenance, and emergence of anesthesia. We evaluated the characteristics of sevoflurane in comparison to halothane in a population with mild URIS. Whereas Naito ef al.” did not find a significant difference between sevoflurane and halothane in induction times in children ages 1 to 7 years, we found a slight but statistically significant shorter induction time with sevoflurane in a similar population. This discrepancy could be explained by the fact that our increments of inspired sevoflurane concentration (1.5 vol %) were somewhat higher and probably more equianesthetic than the increments used by Naito et al. (0.5 to 1.0 vol % for halothane and sevoflurane), because the MAC value for sevoflurane is approximately threefold higher than the MAC value for halothane.7 The difference in the induction times between sevoflurane and halothane may be equalized by an
induction technique using higher inspired halothane concentrations. However, the standardized induction procedure of our protocol with restricted and equianesthetic increments of the volatile anesthetics makes the pharmacokinetic profile of both substances more comparable. Sevoflurane provided a rapid and smooth induction with no difference in complication rates between both study groups. Coughing during induction in approximately one-fourth of the children in both groups may suggest the presence of bronchial hyperreactivity due to URI.‘s Excitation was mild and quickly terminated in both groups. Sevoflurane preserved stable hemodynamic conditions during induction, which is in agreement with previous laboratory and clinical findings.‘4.” Only one child in the sevoflurane group and four children in the halothane group demonstrated a transient decrease in HR of more than 30% from preanesthetic baseline. The intraoperative course was uneventful and revealed no differences in hemodynamic parameters. MAC-hours were calculated to confirm that equianesthetic concentrations of inhaled anesthetics were administered in both groups. As the duration of surgery and MAC-hours were similar, the prerequisite was given to compare emergence and recovery between the sevoflurane and halothane groups. Although tapering of anesthetic gases at the end of surgery is certainly the appropriate technique in clinical practice, we abruptly discontinued volatile anesthetics to establish identical starting conditions for the evaluation of emergence and recovery. The more rapid decrease of alveolar anesthetic concentration of sevoflurane after discontinuation of administration allowed a significantly earlier extubation of children in the sevoflurane group. Differences in emergence (time until eye opening) and command response times were highly significant, with a clear advantage for sevoflurane. However, it must be kept
100 90 80 70 %
60 50 40 30 20 10 0
10
20
30 Minutes after anesthesia
40
50
Figure 1. Percentage of children scoring 8 or more points in the modified Aldrete scoring system at 10, 20, 30,40, and 50 minutes after anesthesia. Only at 10 minutes after anesthesia was there a significant difference between the sevoflurane and the halothane group (*p < 0.05).
J. Clin. Anesth., vol. 8, Mav 1996
191
Original
Contributions
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Minutes after Anaesthesia Figure 2. Scores and median-values in the Pain/Discomfort scale.“’ Differences were statistically different at 20, 30, and 40 minutes (*p < 0.05) after anesthesia. (Individual values: 0 Halothane (Halo), v Sevoflurane (Sevo); median values: --).
in mind that recovery of cognition and motor coordination, which defines the patient’s readiness to leave the recovery room, requires a longer period of time than recovery for response to command. Evaluation of coordination and cognitive function was not studied in our protocol. Children in the sevoflurane group were able to sit up without nausea and dizziness somewhat sooner than the halothane group children, but the time until discharge from the recovery room was not statistically different between the two groups. This is in contrast to the findings of Naito rt &,I2 who demonstrated a significantly earlier discharge from recovery room in the sevoflurane group. This is possibly due to the different type of surgery (laser therapy of port-wine stains of the face and neck region), which did not carry the risk of potential airway complications per se. As recovery scores do not correlate with postoperative hypoxemia in children, we regarded prolonged observation of airway patency after adenotomy mandator)‘.‘“.” Immediate recovery after sevoflurane administration was faster, as documented by a higher percentage of children with Aldrete scores of at least 8 in this group. However, Aldrete scores were similar in both groups from 20 minutes after anesthesia. In the sevoflurane group, there was a trend to more unruly recoveries characterized by agitation, movement, and crying. Scores assessed by the Pain/Discomfort Scale were higher after sevoflurane at 20, 30, and 40 minutes after discontinuation of administration and were due to crying, moving, and agitation. This supports the finding of Naito PL nl.,” who observed more children with restlessness and agitation after sevoflurane but could not verify a statistical difference. A high incidence of this so-called recovery delirium is also described
192
,J. Clin. Anesth., vol. 8, May 1996
after anesthesia with desflurane.” Earlier perception of pain after the more rapid elimination of the inhaled anesthetic may be an etiologic factor.‘” However, in our study, the time of the first application of analgesics, determined by the independent observer, was not different between groups. We presume that following sevoflurane anesthesia the earlier and rather immediate perception of the strange and unknown surroundings in the operating theater may contribute to the child’s confusion, restlessness, and agitation. However, further investigation is required to investigate this issue. As we awaited full recovery of airway competence before extubation, a high incidence of coughing occurred in both groups. The rate of vomiting was low in both groups. This is in keeping with previous findings by Morisaki rl nl.“’ In conclusion, we found that sevoflurane provided a rapid and smooth induction of anesthesia in children with mild URIS. With respect to complications and undesired side effects, there was no difference between halothane and sevoflurane during induction, maintenance, and Although agitation and restlessness were emergence. more frequent following sevoflurane than halothane, we consider it a suitable anesthetic for pediatric anesthesia, especially for outpatient surgery. It may be preferable to halothane as the time course of emergence and recovery is significantly faster with sevoflurane.
Acknowledgment We wish to thank Dr. Glenda Brurnmer and Dr. Christian Apenburg, staff anesthesiologists of our department, for her careful preparation of this manuscript and for his statistical review of the data.
S~uojlurane vs. ha&ham in outpatient admotomy zn children: Riegw rt (11. Appendix.
Characterization Modified
of Recovery’~‘” Aldrete
Pain/Discomfort
Score
Parameter Blood pressure >20% of preanesthetic level fl l-20% of preanesthetic level ~10% of preanesthetic level Crying not responding to TLC* responding to TLC not crying Moving thrashing restless none Agitation hysterical mild asleep or calm Verbal evaluation moderate pain mild pain asleep or no pain
Score
Parameter Activity able to move 4 extremities able to move ‘2 extremities able to move 0 extremities Respiration Breathes deeply and coughs dyspneic, shallow breathing apneic Blood pressure ~10% of preanesthetic level fl l-20% of preanesthetic lrvel >20% of preanesthetic level Consciousness fully a\vake al-ousable on calling not responding Rectal temperature hetlveen 35.6”C and 37.5”C between J5’C . > I 2 and 35.6”c’ 45°C: or >97.5’C
Scale
2 1 0 2 1 0 2 1 0 2 1 0 2 1 0
Score 2 0 2 1 0 2 1 0 2 1 0 2 1 0
*TLC: = tender loving care.
Il.
score. AnP\th
Berry FA (ed): An&h&c Management o/U(fjdt and Koutirw fklzntnc Patimt.\. New York: Churchill Livingstone, 1990:15-52. 12. Naito Y, Tamai S, Shingu K, Fujimori R, Mori K: Comparison between sevoflurane and halothane for pacdiatric ambulatory anaesthesia. BrJAnnrsth 1991;67:387-9. 13. Empey DW, Laitinen LA, Jacobs I~, Gold U’M, Nadel J& Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory infections. Am RPII Resp Di.s 1976;113:131-9. 14. Karama T, Ikeda K: The comparative cardiovascular effects of srvoflurane with halothane and isoflurane. ,JAne.sth 1989;2:63-8. 1.5. Frink EJ JI, Malan TP, Atlas M, Dominguey LM, DiNardo JA, Brown BR Jr: Clinical comparison of sevoflurane and isoflurane in healthy patients. An&h Analg 1992;74:241-5. 16. Soliman IE, Patel RI, Ehrenpreis MB, Hannallah RS: Recover) scores do not correlate with postoperative hypoxemia in children. Anrrth Annlg 1988;67:53-6. 17. DeSoto H, Pate1 RI, Soliman IE, Hannallah RS: Changes in oxygen saturation following general anesthesia in children with upper respiratory infection signs and symptoms undergoing otolaryngological procedures. An~sthrsiolo,~ 1988;68:27&9. 18. Davis F’J, Cohen IT, McGowan FX Jr, Latta K: Recovery characteristics of desfhu-dne versus halothane for maintenance of anesthesia in pediatric ambulatoq~ patients. Anrsthrsiolqq 1994;80: 29x-302.
10. Harmallah KS, Broadman LM, Behnan AB, Abramowitz MD, Epstein BS: (:ompal-ison of caudal and ihoinguinal/iliohypogdstric nr~-ve blocks tar contl-ol of I”‘st-“rchioI)exy pain in pediatric an,I)rll;itol\ \urgel-y. .~~~lhe~io/og?’ 1987;66:832-4.
19. Egcr EI 2d: New inhalrd anesthetics. Alzrs/hrriolo,q 1994;80:90622. 20. Morisdki H, Suzuki G, Miydzawd N, Kiichi Y, ,Misaki T, Slr/uki A: A cliniral trial of sevoflurane in children for herniorrhaphy. ,J AnPrfh 1988;2:94-7.
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recovery
of
sevofl~~-
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193