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PEDIATRIC ANESTHESIA

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

Jochen Mayer, MD^*, Joachim Boldt, MD^*, Kerstin D. Röhm, MD^*, Klaus Scheuermann, MD, and Stefan W. Suttner, MD^*

Department of *Anesthesia and Intensive Care Medicine and ENT Department, Klinikum Ludwigshafen, Ludwigshafen, Germany

Address correspondence and reprint requests to Jochen Mayer, Department of Anesthesia and Intensive Care Medicine, Klinikum Ludwigshafen, Bremserstr. 79, 67063 Ludwigshafen, Germany. Address e-mail to j-mayer{at}gmx.de.

	Abstract

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Emergence agitation may occur after general anesthesia with volatile anesthetics in children. We designed this study to examine the emergence behavior of children undergoing ear-nose-throat surgery after sevoflurane induction and desflurane maintenance versus both sevoflurane induction and maintenance using a recently published Pediatric Anesthesia Emergence Delirium (PAED) scale. In 38 premedicated children aged 12 mo to 7 yr mask induction with sevoflurane was performed and they were randomly assigned to receive either sevoflurane (n = 19) or desflurane (n = 19) for maintenance of general anesthesia. Time to tracheal extubation, modified Aldrete score, emergence behavior, recovery complications, and pain scores were assessed. The PAED scale showed a significant advantage for desflurane (6 [0–15] versus 12 [2–20], maximum total score of 20 for severe agitation). Time to extubation was significantly shorter with desflurane than with sevoflurane (5.4 ± 1.4 versus 13.4 ± 1.8 min). The modified Aldrete score on arrival in the postanesthesia care unit (PACU) was significantly lower in children receiving sevoflurane for maintenance. Time to discharge from PACU to normal ward and the incidence of adverse effects were not significantly different between the groups. In conclusion, the use of desflurane for maintenance of anesthesia after sevoflurane induction in children is associated with less severe emergence agitation and faster emergence times.

	Introduction

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The newer volatile anesthetics, sevoflurane and desflurane, have gained increasing acceptance because of their low blood-gas and blood-tissue solubility, leading to increased control and rapid recovery after general anesthesia (1,2). Sevoflurane is an appropriate volatile anesthetic for mask induction because of its favorable smell and because it is nonirritating. Desflurane seems to be inappropriate for mask induction (2), as it may provoke complications during inhaled induction in children resulting in breath-holding, laryngospasm, and coughing. Despite this disadvantage, maintenance and emergence of anesthesia with desflurane are not associated with an increased risk of respiratory complications (3). A frequent incidence of inconsolable crying, restlessness, and agitation unrelated to pain has been noted during emergence after desflurane or sevoflurane anesthesia (4,5). This phenomenon may result in physical harm to the child (6), as well as requiring additional treatment that may prolong the postanesthesia care unit (PACU) stay, even after short surgical procedures (6). In previous investigations, the prevalence of this adverse effect have been between 20% and 80% (3,7) depending on the definition of "emergence agitation" and the observed time interval after wake-up from anesthesia (8).

However, many of these studies did not use validated scores to assess emergence agitation (EA) (8–12). More recently, the Pediatric Anesthesia Emergence Delirium (PAED) scale (13) was validated as a measure of emergence delirium. We therefore designed this study to evaluate the influence of desflurane maintenance after sevoflurane induction versus sevoflurane induction and maintenance on EA using the recently published PAED scale (13).

	Methods

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Thirty-eight children of ASA physical status I–II aged 12 mo to 7 yr scheduled for minor elective ear-nose-throat surgery (tonsillectomy and/or adenectomy with or without bilateral myringotomy) were studied with permission from Ethics committee and informed parental consent was obtained. Children with a history of airway disease, sleep apnea, developmental delay, or psychological disorders were excluded.

All patients received paracetamol 30 mg/kg rectally for perioperative pain relief 60 min before induction of anesthesia and 0.5 mg/kg (maximum dose of 12 mg) midazolam mixed with raspberry syrup orally for sedation 30 min before induction. Children who refused to take premedication were excluded. To provide a stressless and quiet environment, one parent was allowed to accompany the child into the foyer of the operating area, no IV cannula was established, and children were allowed to bring along a soft toy. Mask induction was performed in all children with sevoflurane (8 vol%) in nitrous oxide (50%) and oxygen (50%), an IV cannula was established thereafter and alfentanil (20 µg/kg) and mivacurium (0.2 mg/kg) were injected to facilitate tracheal intubation. For maintenance of anesthesia, children were randomly assigned to receive either sevoflurane (1.0 ± 0.2 MAC, age adjusted, n = 19) or desflurane (1.0 ± 0.2 MAC, age adjusted, n = 19) with a constant fresh gas flow of 1 L/min (50% nitrous oxide in oxygen) using a semiclosed circle system (Julian, Dräger, Germany). Ventilation was controlled to maintain normocapnia (P_etCO₂ 32–38 mm Hg). Standard monitoring included electrocraiogram, noninvasive arterial blood pressure, pulse oximetry, temperature, and inspiratory and expiratory gas concentrations.

Removal of the mouth gag and removal of the operating microscope with myringotomy, respectively, were defined as the end of surgery. Recovery of neuromuscular function was confirmed using the train-of-four method and volatile anesthetics were discontinued. The fresh gas flow was increased to 12 L/min in both groups. Tracheal extubation was performed when normoventilation was achieved and the patients regained gag or cough reflex. Thereafter, all patients were transferred to the PACU. The time from discontinuation to tracheal extubation, the duration of exposure to volatile anesthetics, and surgery time were recorded by an observer blinded as to anesthetic management.

The same independent PACU nurse, blinded as to anesthetic technique, repeatedly recorded the degree of agitation in a time interval from 10 min to approximately 30 min after admission. This time interval was chosen according to results of Cole et al. (8), who scored children every 10 min on arrival in PACU up to 1 h and found that the peak of agitation occurs in the first 30 min after admission. In addition, our preliminary results showed this time interval to be adequate to determine the peak of maximum agitation. We used a recently published 5-point rating scale with 5 gradations for each item (PAED scale, Table 1) that has been validated to assess EA in children (13). Scoring was obtained multiple times and the peak was recorded for evaluation. Again, a quiet environment was provided and one parent was allowed to stay with the child in the PACU.

Modified Aldrete scores (14) (Table 2) and the incidence of adverse events (nausea, vomiting, shivering, breath-holding, considerable secretions, laryngospasm) were recorded after tracheal extubation and during PACU stay. Children were considered ready for discharge from the PACU with an Aldrete score 9. Every child was contacted 24 h after surgery to evaluate pain and PAED scale.

In children 3 yr and younger, postoperative pain was scored according to a 10-point scale by an experienced and blinded PACU nurse. All children older than 3 yr were scored using the Oucher pain scale (consisting of a vertical five-photograph scale with a corresponding vertical numerical scale of 0–10 marked off in units of 1 point; 0 score indicates no pain and 10 points indicates the worst possible pain), a self-assessment pain tool that has been tested for validity and reliability in children (15).

Children who presented with PAED scale variables 4 ("The child is restless") or 5 ("The child is inconsolable") with an intensity of 3 (very much) or 4 (extremely) or experienced pain exceeding a pain score of 5, received piritramide 50 µg/kg as rescue medication (piritramid is a pure µ-receptor agonist with a potency 0.8 times that of morphine).

The number of patients required in each group was determined before the study by a power calculation based on the results of a pilot study of 10 patients. It was found that the minimum clinically important difference we wished to detect was a 40% decrease in the primary end-point PAED score after sevoflurane/desflurane anesthesia. We estimated that the sd of PAED score values would be up to 4. The error was set at 0.05 (two-sided) and type II error at 0.2. Based on these assumptions, 17 patients per group were required. To compensate for possible dropouts, we decided to include 19 patients per group. Emergence time, Aldrete scoring, and pain scoring were defined as secondary end-points.

Ordinal data (demographic data, measured time intervals) are expressed as mean ± sd and were analyzed using the Student’s t-test; nonparametric data including agitation scores, pain scores, and the incidence of adverse events are expressed as median and range and were compared by using the Wilcoxon’s ranked sum test. A P value of <0.05 was considered significant in all tests.

	Results

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Both groups were comparable with respect to age, weight, consumption of mivacurium and alfentanil, blood loss, and surgical procedure. Duration of anesthesia, surgery time, and exposition to volatile anesthetics also did not differ significantly (Table 3). PAED scale scoring in the PACU showed significant advantage for desflurane (6 [0–15] versus 12 [2–20]; P < 0.05). Time to tracheal extubation was shorter in patients who received desflurane (Table 4), and the modified Aldrete score on arrival in PACU was lower in the sevoflurane group (Table 4). No differences were found between the study groups with respect to pain, time to discharge from PACU (Table 4), the incidence of adverse effects, and the need for rescue medication (Table 5). On follow-up 24 h after surgery, scoring for EA and pain was comparable between the two groups (Table 4).

	Discussion

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The etiology of EA after general anesthesia with volatile anesthetics in children remains still unclear (1,4). New short-acting volatile anesthetics such as sevoflurane and desflurane aggravated the problem of EA (1,4,16). Predominantly appearing in young children and unrelated to gender (6,16,17), the main characteristics are mental disturbances consisting of hallucinations, delusions, and confusion (13), which may lead to restlessness, crying, involuntary physical activity, and self-injury. Despite the advantages of rapid induction of anesthesia, hemodynamic stability, and fast emergence of sevoflurane and desflurane, EA remains a considerable side effect that demands increased resources in PACU (18), increases the need to treat, and creates the possibility of having to deal with parents who are not satisfied with the quality of anesthetic management.

Data about EA comparing desflurane and sevoflurane anesthesia in children are scarce, and results are far from uniform. Welborn et al. (4) induced anesthesia with halothane and then randomized patients to receive halothane, sevoflurane, or desflurane for maintenance of anesthesia. They found sevoflurane to be superior to desflurane with respect to incidence of EA without using a score. Valley et al. (10) compared sevoflurane and desflurane for maintenance and reported less frequent agitation in children receiving sevoflurane. In contrast, Demirbilek et al. (11) and Cohen et al. (12) reported no differences between desflurane and sevoflurane maintenance. In a study of Cohen et al. (5), anesthesia was induced with halothane and desflurane was used for maintenance of anesthesia. They reported a frequent incidence of EA and concluded that the use of desflurane without adequate prevention should be avoided in children.

The discrepancy between previous studies and our data may result from the use of different scores to quantify EA and differing methods of data analysis. Most authors (8–12) used self-developed 3- to 5-point scores that have never been validated for EA as well as self-developed threshold values to calculate the incidence. The severity of EA was not compared in most studies. Sikich et al. (13) were the first to measure EA using a valid and reliable scale that describes the different aspects of EA more precisely than other scores. However, they did not provide a validated threshold value in the PAED scale to indicate EA; thus no conclusions can be drawn with respect to the incidence of EA. We decided not to implement a self-designed threshold for EA, as this, in our opinion, requires further research.

Another explanation may result from the time interval in which EA was measured. In several studies, the time of scoring was not mentioned (9–12). According to Cole et al. (8), the degree of EA is highly dependent on when it is measured after anesthesia. Further aspects that have to be considered are dosage and type of premedication (5,8).

Although it has been shown that EA also occurs in pain-free children (19), pain is still considered to be one of the factors leading to EA (6). It is difficult to discriminate between agitation caused by postoperative pain and EA resulting from anesthetics, as symptoms might be similar. This issue might bias results in all studies dealing with EA. Introducing the PAED scale has improved scoring of EA with respect to pain, as only items 4 ("The child is restless") and 5 ("The child is inconsolable") may reflect pain as well as EA (13). Item 1, 2, and 3 (Table 1) have been found to differentiate EA from pain (13). Thus concurrent use of a reliable pain scale and the PAED scale may decrease the error associated with pain (13). It may therefore be assumed that interference of pain is minor compared with other scores that have been used. In our study, comparable pain management was performed in both groups.

Various attempts have been made to reduce the problem of EA. One promising approach may be the use of opioids. Demirbilek et al. (11) found that intraoperative fentanyl (2.5 µg/kg) after premedication with midazolam did not provide any benefit on EA, whereas Cohen et al. (12) proposed that intraoperative fentanyl (2.5 µg/kg) without midazolam before anesthesia reduced the incidence of EA. The findings of Cohen et al. were confirmed by Cravero et al. (19), who administered fentanyl 1 µg/kg 10 min before discontinuation of anesthesia in children without surgery with the assertion that there is no prolonged recovery. Indeed, these findings could have been caused by the omission of midazolam. Malmgren and Akeson (20) found no differences in the incidence of EA in children receiving rectal morphine for premedication compared to midazolam. To avoid possible interference of long-acting opioids with postoperative scoring of EA, we decided to use the potent short-acting opioid alfentanil for intraoperative pain relief.

Midazolam seems to have no benefit on emergence behavior. Cohen et al. (5) proposed that neither midazolam nor propofol given intraoperatively reduced the incidence of EA but may delay emergence and recovery. Cole et al. (8) were able to demonstrate that oral midazolam for premedication aggravates disruptive behavior. Unfortunately, the dosage of midazolam was missing in this study. Although we administered midazolam as premedication to decrease preoperative anxiety, it may have contributed to EA (21,22). In our study, all children received midazolam orally 30 minutes before anesthesia. With an average anesthetic time of approximately 58 minutes and reported half-life of midazolam in children of 48-108 minutes (23), serum levels are assumed to be too low to achieve proper sedation in the PACU. Accordingly, none of our patients presented with prolonged recovery (more than 30 minutes) in the PACU.

In conclusion, maintenance of anesthesia with desflurane after mask induction with sevoflurane resulted in less severe agitation with faster emergence times. Although the time of PACU stay did not differ significantly, a more rapid immediate recovery from anesthesia could be an additional benefit in a busy operating room. This study may be a further step towards a more accurate clinical assessment of EA, but additional work must be undertaken to find strategies that prevent EA in children.

	Footnotes

 
Accepted for publication August 22, 2005.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Lerman J. Inhalational anaesthetics. Paed Anaesth 2004;14:380–3.[Medline]
2. Murat I. Is there a place for desflurane in paediatric anaesthesia? Paed Anaesth 2002;12:663–4.[Medline]
3. Davis PJ, Cohen IT, McGowan FXJ, et al. Recovery characteristics of desflurane versus halothane for maintenance of anesthesia in pediatric ambulatory patients. Anesthesiology 1994;80:298–302.[Web of Science][Medline]
4. Welborn LG, Hannallah RS, Norden JM, et al. Comparison of emergence and recovery characteristics of sevoflurane, desflurane, and halothane in pediatric ambulatory patients. Anesth Analg 1996;83:917–20.[Abstract]
5. Cohen IT, Drewsen S, Hannallah RS. Propofol or midazolam do not reduce the incidence of emergence agitation associated with desflurane anaesthesia in children undergoing adenotonsillectomy. Paed Anaesth 2002;12:604–9.[Web of Science][Medline]
6. Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit. Anesth Analg 2003;96:1625–30.[Abstract/Free Full Text]
7. Grundmann U, Uth M, Eichner A, et al. Total intravenous anaesthesia with propofol and remifentanil in paediatric patients: a comparison with desflurane-nitrous oxide inhalation anaesthesia. Acta Anaesth Scand 1998;42:845–50.[Web of Science][Medline]
8. Cole JW, Murray DJ, McAllister JD, Hirshberg GE. Emergence behaviour in children: defining the incidence of excitement and agitation following anaesthesia. Paed Anaesth 2002;12:442–7.[Web of Science][Medline]
9. Cohen IT, Finkel JC, Hannallah RS, et al. Rapid emergence does not explain agitation following sevoflurane anaesthesia in infants and children: a comparison with propofol. Paed Anaesth 2003;13:63–7.[Web of Science][Medline]
10. Valley RD, Freid EB, Bailey AG, et al. Tracheal extubation of deeply anesthetized pediatric patients: a comparison of desflurane and sevoflurane. Anesth Analg 2003;96:1320–4.[Abstract/Free Full Text]
11. Demirbilek S, Togal T, Cicek M, et al. Effects of fentanyl on the incidence of emergence agitation in children receiving desflurane or sevoflurane anaesthesia. Eur J Anaesthesiol 2004;21:538–42.[Medline]
12. Cohen IT, Finkel JC, Hannallah RS, et al. The effect of fentanyl on the emergence characteristics after desflurane or sevoflurane anesthesia in children. Anesth Analg 2002;94:1178–81.[Abstract/Free Full Text]
13. Sikich N, Lerman J. Development and psychometric evaluation of the paediatric emergence delirium scale. Anesthesiology 2004;100:1138–45.[Web of Science][Medline]
14. Aldrete JA. The postanesthesia recovery score revisited. J Clin Anesth 1995;7:89–91.[Web of Science][Medline]
15. Aradine CR, Beyer JE, Tompkins JM. Children’s pain perception before and after analgesia: a study of instrument construct validity and related issues. J Pediatr Nurs 1988;3:11–23.[Medline]
16. Jöhr M. Postanaesthesia excitation. Paed Anaesth 2002;12:293–5.[Web of Science][Medline]
17. Cravero J, Surgenor S, Whalen K. Emergence agitation in paediatric patients after sevoflurane anaesthesia and no surgery: a comparison with halothane. Paed Anaesth 2000;10:419–24.[Web of Science][Medline]
18. Uezono S, Goto T, Terui K, et al. Emergence agitation after sevoflurane versus propofol in paediatric patients. Anesth Analg 2000;91:563–6.[Abstract/Free Full Text]
19. Cravero JP, Beach M, Thyr B, Whalen K. The effect of a small dose fentanyl on emergence characteristics of pediatric patients after sevoflurane anesthesia without surgery. Anesth Analg 2003;97:364–7.[Abstract/Free Full Text]
20. Malmgren W, Akeson J. Similar excitation after sevoflurane anaesthesia in young children given rectal morphine or midazolam as premedication. Acta Anaesth Scand 2004;48:1277–82.[Medline]
21. Aono J, Mamiya K, Manabe M. Preoperative anxiety is associated with a high incidence of problematic behaviour on emergence after halothane anaesthesia in boys. Acta Anaesth Scand 1999;43:542–4.[Web of Science][Medline]
22. Kain ZN, Caldwell-Andrews A, Maranets I, et al. Preoperative anxiety and emergence delirium and postoperative maladaptive behaviour. Anesth Analg 2004;99:1648–54.[Abstract/Free Full Text]
23. Blumer JL. Clinical pharmacology of midazolam in infants and children. Clin Pharmacokinet 1998;35:37–47.[Web of Science][Medline]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Mayer, J. Articles by Suttner, S. W. Search for Related Content PubMed PubMed Citation Articles by Mayer, J. Articles by Suttner, S. W.