Inhalation agents in pediatric anaesthesia an update Jerrold Lerman

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1 Inhalation agents in pediatric anaesthesia an update Jerrold Lerman Purpose of review To present the most recent publications on inhaled agents in children and their implications for clinical care. Recent findings The roles of clonidine, dexmedetomidine, ketamine and nalbuphine in the treatment of emergence delirium after sevoflurane and desflurane are discussed. Bispectral index monitoring has generated several curious findings in children. Halothane consistently produced higher Bispectral index readings than equi-minimum-alveolarconcentration multiples of ether anesthetics. Bispectral index readings increased as the sevoflurane concentration increased beyond 3%. Inhalation agents may cause two serious complications when administered to children with Duchenne s muscular dystrophy: hyperkalemia in younger children and myocardial depression in adolescents. Recovery after desflurane anesthesia is more rapid than with the other ether anesthetics in infants and children. Single-breath inductions are of interest in children >6 years for rapid anesthesia induction. Summary Sevoflurane and desflurane continue to challenge our abilities to anesthetize children safely and efficiently. Although transient emergence delirium after insoluble agents is a problem, several medications may be used to attenuate it. Inhaled agents must be used with caution in children with Duchenne s muscular dystrophy as hyperkalemia may occur in young males and myocardial depression in adolescents. Rapid recovery after desflurane and single-breath inductions with sevoflurane continue to fascinate clinicians. Keywords Bispectral index, Duchenne s muscular dystrophy, emergence delirium Curr Opin Anaesthesiol 20: ß 2007 Lippincott Williams & Wilkins. Women and Children s Hospital of Buffalo, SUNY, Strong Memorial Hospital, University of Rochester, Rochester, New York, and St. Christopher s Hospital for Children, Philadelphia, Pennsylvania, USA Correspondence to Jerrold Lerman, Clinical Professor of Anesthesia, Department of Anesthesia, Women and Children s Hospital of Buffalo, 219 Bryant Street, Buffalo, NY 14222, USA Tel: ; fax: ; jerrold.lerman@gmail.com Current Opinion in Anaesthesiology 2007, 20: Abbreviations BIS Bispectral index DMD Duchenne s muscular dystrophy EEG electroencephalographic MAC minimum alveolar concentration PAED scale Pediatric Anesthesia Emergence Delirium scale ß 2007 Lippincott Williams & Wilkins Introduction Despite the radical shift in clinical practice from halothane to sevoflurane in the 1990s and an apparent improvement in the safety and pharmacokinetics of inhaled anesthetics, there remain issues and concerns regarding the administration of inhaled anesthetics to infants and children. Most of the published research on inhaled anesthetics in infants and children in the past year fell neatly into four categories: (a) emergence delirium, (b) Bispectral index (BIS), (c) muscular dystrophy and (d) miscellaneous. In this paper we shall explore these publications and provide a perspective for their potential contributions to the care of infants and children in Emergence delirium Since the early 1960s, emergence delirium has been reported after the introduction of every new anesthetic. The introductions of sevoflurane and desflurane into clinical pediatric practice have been no exceptions. Although emergence delirium has become a topic discussed by numerous stakeholders including anesthesiologists, recovery-room nurses and parents, addressing the problem has proven to be difficult. First, rapid recovery from anesthesia without the provision of adequate analgesia has muddied the diagnosis of emergence delirium as an entity distinct from acute postoperative pain. Recognizing that the greatest incidence of emergence delirium occurs in prelingual children who are unable to articulate their complaints has compounded the difficulty in differentiating emergence delirium from pain. Two contributions however have addressed these difficulties. First, Cravero et al. [1] compared recovery after sevoflurane and halothane in children during MRI, to avoid the overlapping effects of pain on emergence delirium. They found that the incidence of emergence delirium after sevoflurane was substantively greater than that after halothane. Second, we validated a tool, the Pediatric Anesthesia Emergence Delirium (PAED) scale, to 221

2 222 Paediatric anaesthesia diagnose emergence delirium [2]. These two contributions have and should continue to help further define emergence delirium during emergence from anesthesia. The incidence of emergence delirium varies after the inhalation agents: sevofluranedesflurane>isoflurane halothane. In two studies, the authors hypothesized that switching from sevoflurane to either isoflurane or desflurane might attenuate the incidence of emergence delirium in children [3,4 ]. In the first study, Bortone et al. [3 ] compared the incidence of emergence delirium in preschool age children with regional blocks after inguinal surgery with sevoflurane or isoflurane. Using a self-styled scale to evaluate emergence delirium and a large cohort of children (n ¼ 128), they concluded that switching from sevoflurane to isoflurane for maintenance reduced the incidence of emergence delirium by 66%. The authors used a nonvalidated scale to evaluate emergence delirium which limits the universality of the results and precludes verification by other authors. In the second study, Mayer et al. [4 ] randomized children to receive either sevoflurane or desflurane for maintenance of anesthesia during tonsillectomy and adenoidectomy surgery and measured emergence delirium during recovery with the PAED scale. They determined that the incidence of emergence delirium after sevoflurane was twice that after desflurane. Although their sample size was small and pain may have been a confounding variable, this study is the first to establish credible evidence for the incidence of emergence delirium in the perioperative period using a reproducible scale. Although I believe that the emergence delirium is a class effect that occurs after most inhalational anesthetics with limited blood solubility, differences among these anesthetics must be examined using a valid tool that is sensitive and specific. Many drugs, including propofol, fentanyl, clonidine and dexmedetomidine, have been investigated to attenuate the incidence of emergence delirium. However, most of the studies that involved these drugs were flawed for the reasons cited above. a-2 Agonists have been administered prophylactically to prevent emergence delirium after inhalational anesthesia. In two studies of preschool-age children, 2 mg/kg clonidine attenuated the incidence of emergence delirium by 50% after sevoflurane or isoflurane anesthesia for minor surgery [5,6]. However, recovery was prolonged after clonidine in one of the studies as evidenced by a 50% increase in time to awakening, 25% greater stay in the post-anesthetic care unit and a 2-fold greater incidence of sleepiness after discharge [5 ]. In neither study was a validated scale used to evaluate emergence delirium. In a third study, Lankinen et al. [7 ] compared the effectiveness of intravenous clonidine 1.5 mg/kg, tropisetron 0.1 mg/kg (a serotonin-receptor antagonist) or placebo on the incidence of emergence delirium after sevoflurane anesthesia. The study cohort was preschool age children who had received several analgesics. Emergence delirium was evaluated using a nonvalidated scale. In this study, surprisingly, clonidine did not attenuate the incidence of emergence delirium compared with placebo. However, tropisetron did attenuate the incidence of emergence delirium, by approximately 50%! If this surprising finding can be reproduced with a validated scale to measure emergence delirium, particularly with other serotonin-receptor antagonists, then serotonin receptor antagonists may provide an unexpected solution to this most curious side effect of insoluble inhaled anesthetics. Dexmedetomidine has also been shown to be effective in attenuating the incidence of emergence delirium after sevoflurane anesthesia. In a cohort of 3 7-year-old children who were anesthetized with sevoflurane for tonsillectomy and adenoidectomy surgery, Guler et al. [8] demonstrated that a single dose of dexmedetomidine 0.5 mg/kg 5 min before the end of surgery significantly reduced the incidence of emergence delirium compared with placebo. Shukry et al. [9] studied continuous infusions of dexmedetomidine (0.2 mg/kg per min) during surgery and determined that the incidence of emergence delirium was attenuated by 66% compared with placebo. The results from these studies must be interpreted with caution as a validated scale for emergence delirium was not used and the surgeries were painful. Dexmedetomidine likely exerts its effects on emergence delirium through its analgesic and sedative properties. However, the use of dexmedetomidine also requires that it is prepared, solubilized and diluted for administration via a syringe pump. Furthermore, with an elimination halflife of 2 h in children, dexmedetomidine is not ideal for ambulatory surgery [10]. Finally, the acquisition cost for this medication likely exceeds that of alternatives with similar degrees of effectiveness. Dalens et al. [11 ] compared the efficacy of ketamine or nalbuphine to attenuate the incidence of emergence delirium after sevoflurane anesthesia for MRI in preschool-age children. Using a nonvalidated five-point scale, they found that as little as 0.25 mg/kg ketamine or 0.1 mg/kg nalbuphine attenuated the incidence of emergence delirium by 60 and 90% respectively, without prolonging emergence from anesthesia. The authors concluded that ketamine and nalbuphine may be effective in attenuating the incidence of emergence delirium after inhalational anesthesia. Bispectral index The BIS, which was developed for use in adults, is a monitor that assesses the depth of anesthesia.

3 Inhalation agents Lerman 223 Although not designed using an electroencephalographic (EEG) algorithm from children, this monitor has been used in infants without software modification. However, the utility of the BIS to provide a measure of the depth of anesthesia in children has been stalled by its inability to record an appropriate depth of anesthesia when used with halothane. With the shift of practice to sevoflurane, the relationship between the concentration of sevoflurane and BIS has come under even closer scrutiny. Kim et al. [12] examined the effect of the depth of sevoflurane anesthesia on the BIS in children. The study cohort was healthy children undergoing surgery without regional blocks. BIS was measured at concentrations of sevoflurane that were increased or decreased randomly in a stepwise manner. They found that the lowest BIS reading was recorded with 3% sevoflurane for all age groups and that the BIS actually increased as the sevoflurane concentrations increased to 4%. This is difficult to understand given that increasing concentrations of inhalational anesthetics should increase the depth of anesthesia and thus decrease the BIS reading. However, as the authors acknowledge, they did not control pain but rather waited for 15 min after surgical stimulation before they began to collect data and averaged their data over 5 min. Furthermore, the authors randomized the sequences of sevoflurane concentrations, either stepwise increases or decreases, but not the concentrations individually. Nonetheless, this attempt to remove bias by randomizing the sequences is laudable. The most curious finding in this study remains this paradoxical increase in the BIS reading as the concentration of sevoflurane increased from 3 to 4%. These findings more than suggest that the BIS algorithm is not ideally and thoroughly characterized for either halothane or the methyl isopropyl volatile anesthetic sevoflurane in children. Edwards et al. [13] determined the BIS values for halothane and sevoflurane in infants and children. They concluded that in children as in adults, the BIS values for equi-minimum-alveolar-concentration (MAC) halothane concentrations were significantly greater than those for sevoflurane by approximately 50%. In contrast, the difference between the two anesthetics in infants was attenuated. Differences in the BIS readings between anesthetics is likely explained by the different EEG responses to these inhaled anesthetics. Halothane produces a faster EEG pattern whereas sevoflurane and the other ether anesthetics produce a slower pattern. The concern is the greater BIS reading during halothane anesthesia and how to gauge an acceptable depth of anesthesia using the BIS. It may be that the threshold for awareness during halothane anesthesia exceeds the widely held value of 60. Unfortunately, the authors limited the dose of sevoflurane to a maximum concentration of 3%, thus preventing validation of the paradoxical observations of Kim et al. [12] Tirel et al. [14 ] compared the BIS during halothane and desflurane anesthesia in children and determined that the relationship between halothane and desflurane was similar to that reported by Edwards et al. [13] between halothane and sevoflurane. The BIS reading during halothane was consistently greater than during desflurane. Unfortunately, the authors did not randomize the concentration administered and therefore the effect of time is not accounted for in the results or the statistical analysis. The data support an age-dependent effect of BIS at 1 MAC, the younger the child, the greater the BIS for sevoflurane, desflurane and halothane. Why the BIS for 1 MAC halothane was consistently greater than that for sevoflurane and desflurane remains incompletely understood at this time. These three studies all support the notion that BIS increases with decreasing age, that the BIS at equi- MAC concentrations of halothane are consistently greater than those for the ether anesthetics and, in a most peculiar and paradoxical observation, that the BIS increases as the concentration of sevoflurane approaches 2 MAC (i.e. 4%). Further studies that are properly designed, randomized, controlled and blinded arerequiredtodefinitively establish and validate these purported notions in properly designed randomized, controlled and blinded studies. What is the role of the BIS and other monitors of brain function in children during inhalational anesthesia? It is my view that awareness, as best as it is discerned in children who have undergone surgery, is extraordinarily rare. Unfortunately, instances of awareness that have begun to appear in the literature have, for the most part, been the result of prematurely discontinuing completely or decreasing the concentration of insoluble anesthetics such as sevoflurane. Such maneuvers may be at the root cause of the recall in children. Enigmatically, not one instance of awareness has ever been reported after the MAC trials that were performed in adults and children in which the only anesthetic administered was the potent inhalational anesthetic at approximately 1 MAC. This leads me to ask: do we need to monitor for awareness or learn how to give a proper anesthetic with these new insoluble inhalation anesthetics? Duchenne s muscular dystrophy The relationship between dystrophinopathies and inhalational anesthetics has been unraveling slowly over the past two decades but confusion persists. We have begun to better understand the pathophysiology of Duchenne s muscular dystrophy (DMD) and how medications such as anesthetic agents, interact with this disease. Despite

4 224 Paediatric anaesthesia this understanding, two recent reports [15,16] of perioperative cardiac arrests in children with DMD prompted a thought-provoking editorial regarding the avoidance of inhalation agents in children with DMD [17 ] The two recent reports of cardiac arrests in male children were of two distinct etiologies. In the first, a 5-year-old without a history of DMD received a sevoflurane and isoflurane anesthetic that was followed by a hyperkalemic cardiac arrest in post-anesthetic care unit [15 ]. This was an otherwise healthy child who exhibited no clinical features of muscular dystrophy, any other myopathy or any other disorder that placed him at risk for hyperkalemia, although, at autopsy, the muscle pathology was diagnostic of DMD. Short of banning inhalational anesthetics from use in all male children globally, this arrest could not have been predicted. In the editorial, the authors suggest a careful history and physical exam for neuromuscular developmental problems should be undertaken in all instances, although I am unconvinced of their sensitivity and specificity to predict DMD. Nonetheless, whether the child could have been resuscitated from the hyperkalemia depended on how aggressively intravenous calcium was administered to restore normal cardiac rhythm as well as the effects of cardiopulmonary resuscitation and epinephrine to restore cardiac output and wash the potassium out of the heart muscle. How aggressively the authors implemented these strategies is difficult to discern from the report. We might also query at what age is the risk of hyperkalemia after succinylcholine substantive in children with DMD? Muscle breakdown is a feature of younger (male) children that all but ceases by adolescence. Indeed, at the Hospital for Sick Children in Toronto, Canada, we used succinylcholine for tracheal intubation in adolescents with DMD undergoing scoliosis surgery for many number of years without sequelae. These observations support the notion that DMD is a developmental muscle disorder of young children in whom skeletal-muscle degradation burns itself out by adolesence. In the second report, an adolescent with DMD and an ejection fraction of 25% transiently arrested after 4 h of desflurane anesthesia for scoliosis surgery [16]. The presumptive diagnosis in this report was desfluraneinduced myocardial depression that compounded a DMD-associated cardiomyopathy. It is well known that the probability that a cardiomyopathy is present in a child with DMD substantively increases throughout adolescence and into adulthood. Given the possibility of a cardiomyopathy, however, one should design an anesthetic regimen that does not further compromise myocardial contractility. In this case, the authors chose desflurane as the major anesthetic and found it well tolerated by the child for 4 h before the arrest occurred. According to the report, no evidence directly linked desflurane to the arrest, it was a matter of exclusion. However, the volume status of the heart at the time of the arrest was not reported and the concentrations of calcium/ magnesium were not presented. It is this author s opinion that the cause of this transient arrest remains undetermined and not firmly linked to desflurane. Should inhaled anesthetics be avoided in all children with DMD? [17 ]. Recognizing that there is a risk of hyperkalemia (even in the absence of succinylcholine) in young males and a risk of a cardiomyopathy and myocardial depression in adolescents and adults with DMD who receive inhalation agents, it would seem reasonable to consider other anesthetic agents for these children. Propofol, ketamine and dexmedetomidine are reasonable alternatives, although propofol is known to produce a graded dose-dependent decrease in myocardial contractility in children undergoing cardiac catheterization. Low doses of these inhalational anesthetics supplemented with a benzodiazepine, opioid and nitrous oxide would seem reasonable and satisfy the demands of sensory and motor-evoked potential monitoring systems. But in cases where no signs of DMD are present, are we to avoid inhalational anesthetics if the children are males? I think not. Finally, in the absence of any evidence linking children with DMD to malignant hyperthermia, there is no role for dantrolene in treating complications from DMD. Miscellaneous research In children whose airways were intubated, recovery after desflurane anesthesia has been compared with that after isoflurane and sevoflurane [18,19 ]. In both studies, the authors determined that the recovery after desflurane was more rapid than after isoflurane or sevoflurane. In the desflurane/isoflurane study in children [18 ], all recovery milestones were reached more readily after desflurane. However, discharge from hospital after desflurane was more rapid for children over 4 years of age, but not for those under 4 years. Interestingly, recovery after desflurane was independent of the duration of exposure whereas recovery after isoflurane increased with the duration of anesthesia. This is consistent with the concept of a context-sensitive half-life for inhaled agents in which the recovery after desflurane, the most insoluble inhalational anesthetic, was rapid and constant since it did not accumulate in tissues [18 ]. As reported in several studies previously, the incidence of airway reflex responses after tracheal extubation after both desflurane and isoflurane was exceedingly small. In the second study, the same investigators as in the previous study compared the recovery after desflurane and sevoflurane in ex-preterm infants [19 ]. They found that recovery was more rapid after desflurane than after

5 Inhalation agents Lerman 225 sevoflurane. They also verified the absence of airway reflex responses after tracheal extubation after desflurane anesthesia. In both of these studies [18,19 ], the authors maintained a constant end-tidal concentration of inhaled anesthetics until the conclusion of surgery, after which the anesthetic was discontinued. This has been the standard design for all studies that compared the emergence after inhalation agents but it fails to reflect the real-life clinical situation. The difference in recovery after maintaining equi-mac concentrations is determined by the blood/gas partition coefficients of the anesthetics. Consequently, it is no surprise that recovery after desflurane, the agent with the lowest blood solubility, 0.42, was more rapid than after isoflurane, 1.4, and sevoflurane, In the clinical real-life situation, however, the inspired concentration of the anesthetic is tapered as surgery concludes, which would attenuate the difference in the speed of recovery. I am quite certain that even in a study designed to reflect real life, recovery after desflurane would be more rapid than after the other anesthetics. Lejus et al. [20 ] compared the induction of anesthesia with sevoflurane during a vital-capacity breath or normal tidal volume in children over 5 years of age. Consistent with published data [21], they found that the time to loss of consciousness was more rapid with a vital-capacity breath than with normal tidal breathing. In previous studies, older children have complained of the odor of sevoflurane when questioned after their surgery. Nonetheless, that has not prevented successful single-breath inductions in these older children. I occasionally perform these singlebreath inductions in children over 6 years of age; however, the benefits are limited, as Lejus et al. concede [20 ]. Conclusion Inhalational anesthetics remain the cornerstone for anesthesia in children. Although the focus has shifted from halothane to sevoflurane as the induction agent for children, ether anesthetics continue to dominate the maintenance period. Together with the introduction of these new and insoluble inhalational anesthetics, interesting concerns including emergence delirium, interactions with myopathies, measures of depth of anesthesia (BIS) and others continue to challenge us. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 288). 1 Cravero J, Surgenor S, Whalen K. Emergence agitation in paediatric patients after sevoflurane anaesthesia and no surgery: a comparison with halothane. Paediatr Anaesth 2000; 10: Sikich N, Lerman J. Development and psychometric evaluation of the Pediatric Anesthesia Emergence Delirium scale. Anesthesiology 2004; 100: Bortone L, Ingelmo P, Grossi S, et al. Emergence agitation in preschool children; double-blind, randomized, controlled trial comparing sevoflurane and isoflurane anesthesia. Pediatr Anesth 2006; 16: Emergence delirium after sevoflurane induction and isoflurane for maintenance in children was less than after an anesthetic that was entirely sevoflurane. 4 Mayer J, Boldt J, Rohm KD, et al. Desflurane anesthesia after sevoflurane inhaled induction reduces severity of emergence agitation in children undergoing minor ear-nose-throat surgery compared with sevoflurane induction and maintenance. Anesth Analg 2006; 102: Emergence delirium after sevoflurane induction and desflurane for maintenance in children was evaluated using the PAED scale compared with sevoflurane alone. The former technique was associated with less emergence delirium and faster recovery. 5 Malviya S, Voepel-Lewis T, Ramamurthi RJ, et al. Clonidine for the prevention of emergence agitation in young children: efficacy and recovery profile. Pediatr Anesth 2006; 16: Clonidine reduced the incidence of emergence delirium after sevoflurane induction and isoflurane maintenance, but produced sleepier children in the recovery area. 6 Tesoro S, Mezzetti D, Marchesini L, Peduto VA. Clonidine treatment for agitation in children after sevoflurane anesthesia. Anesth Analg 2005; 101: Lankinen U, Avela R, Tarkkila P. The prevention of emergence agitation with tropisetron or clonidine after sevoflurane anesthesia in small children undergoing adenoidectomy. Anesth Analg 2006; 102: This study contained the curious observation that tropisetron but not clonidine attenuated the incidence of emergence delirium after sevoflurane anesthesia in children. 8 Guler G, Akin A, Tosun Z, et al. Single-dose dexmedetomidine reduces agitation and provides smooth extubation after pediatric adenostonsillectomy. Pediatr Anesth 2005; 15: Shukry M, Clyde MC, Kalarickal PL, Ramadhyani U. Does dexmedetomidine prevent emergence delirium in children after sevoflurane-based general anesthesia? Pediatr Anesth 2005; 15: Petroz G, Sikich N, van Dyk H, et al. A phase 1, two center study of the pharmacokinetics and pharmacodynamics of dexmedetomidine in children. Anesthesiology 2006; 105: Dalens B, Pinard AM, Letourneau D-R, et al. Prevention of emergence agitation after sevoflurane anesthesia for pediatric cerebral magnetic resonance imaging by small doses of ketamine or nalbuphine administered just before discontinuing anesthesia. Anesth Analg 2006; 102: Small doses of ketamine and nalbuphine at the end of sevoflurane anesthesia for MRI attenuates the incidence of emergence delirium compared with placebo. 12 Kim HS, Oh AY, Kim CS, et al. Correlation of bispectral index with end-tidal sevoflurane concentration and age in infants and children. Br J Anaesth 2005; 95: Edwards JJ, Soto RG, Bedford RF. Bispectral Index TM values are higher during halothane vs. sevoflurane anesthesia in children, but not in infants. Acta Anaesthesiol Scan 2005; 49: Tirel O, Wodey E, Harris R, et al. The impact of age on bispectral index values and EEG bispectrum during anaesthesia with desflurane and halothane in children. Br J Anaesth 2006; 96: Evidence is presented that the EEG algorithm in the BIS yields greater readings after halothane than desflurane. There is further evidence that the BIS increases substantively with decreasing age (at 1 MAC) for the two agents (r 2 ¼ ). 15 Girshin M, Mukherjee J, Clowney R, et al. The postoperative cardiovascular arrest of a 5-year-old male: an initial presentation of Duchenne s muscular dystrophy. Pediatr Anesth 2006; 16: During recovery from a sevoflurane/isoflurane anesthetic, this 5-year-old boy suffered a cardiac arrest which ultimately resulted in his death 7 days later. This child was discovered to have DMD. 16 Smelt WLH. Cardiac arrest during desflurane anesthesia in a child with Deuchenne s muscular dystrophy. Acta Anaesth Scand 2005; 49: Yemen TA, McClain C. Muscular dystrophy, anesthesia and the safety of inhalational agents revisited: again. Pediatr Anesth 2006; 16: This is a thought-provoking editorial that questions whether inhalational agents should be administered to all children (really, only males) who have not had histories and physical examinations completed specifically for DMD.

6 226 Paediatric anaesthesia 18 Nordmann GR, Read JA, Sale SM, et al. Emergence and recovery in children after desflurane and isoflurane anaesthesia: effect of anaesthetic duration. Br J Anaesth 2006; 96: In this study there was a very rapid and complete recovery after desflurane anesthesia in children compared with isoflurane. 19 Sale SM, Read JA, Stoddart PA, Wolf AR. Prospective comparison of sevoflurane and desflurane in formerly premature infants undergoing inguinal herniotomy. Br J Anaesth 2006; 96: The study showed a very rapid and complete recovery after desflurane anesthesia. 20 Lejus C, Bazin V, Fernandez M, et al. Inhalation induction using sevoflurane in children: the single-breath vital capacity technique compared to the tidal volume technique. Anaesthesia 2006; 61: Single-breath inductions with sevoflurane are tolerated and efficient for inducing anesthesia in children greater than 5 or 6 years of age. 21 Baum VC, Yemen TA, Baum LD. Immediate 8% sevoflurane induction in children: a comparison with incremental sevoflurane and incremental halothane. Anesth Analg 1997; 85: