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PEDIATRIC ANESTHESIA

The Incidence of Emergence Agitation Associated with Desflurane Anesthesia in Children is Reduced by Fentanyl

Departments of Anesthesiology and Pediatrics, Children’s National Medical Center and George Washington University Medical Center, Washington, DC

Address correspondence and reprint requests to Ira Todd Cohen, MD, Children’s National Medical Center, 111 Michigan Ave., N.W., Washington, DC 20010. Address e-mail to icohen{at}cnmc.org

	Abstract

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The rapid emergence and recovery from general anesthesia provided by desflurane is associated with a frequent incidence of emergence agitation in children. We sought to determine the mean effective dose of fentanyl that would significantly reduce the incidence of emergence agitation while preserving rapid recovery. Thirty-two children undergoing adenoidectomy received general anesthesia with desflurane and a dose of fentanyl (1.25, 1.87, 2.8, and 4.2 µg/kg) determined by the classic up-down method. Recovery characteristics, including time to extubation, recovery, hospital discharge, agitation, pain, and vomiting, were recorded. Demographics and recovery features were assessed by analysis of variance and Kruskal-Wallis tests. The mean effective dose of fentanyl to reduce agitation was calculated with the Dixon-Massey method to be 2.5 ± 6.2 µg. There were no significant differences when treatment groups were compared for recovery criteria. Postoperative emesis occurred in 75% of patients. The results of this study demonstrate that a dose of 2.5 µg/kg of fentanyl is sufficient to prevent emergence agitation while preserving the rapid recovery associated with desflurane anesthesia in children undergoing adenoidectomy.

Implications: A dose of 2.5 µg/kg of fentanyl prevents emergence agitation associatedwith desflurane anesthesia in children undergoing adenoidectomy withoutdelaying emergence.

	Introduction

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Desflurane’s low blood and tissue solubility allows for rapid emergence from general anesthesia. This, however, has been associated with a 50% to 80% incidence of agitation in children (1,2). A similarly frequent incidence of agitation is reported with other insoluble anesthetics, such as sevoflurane (3,4). Although the severity of agitation varies, it often requires treatment with additional analgesics or sedatives in the postanesthesia care unit (PACU) (1,5). The use of these medications and the need for additional observation prolong and complicate postanesthesia care and delay discharge (5,6). Concurrent use of sedative or hypnotic drugs, such as midazolam or propofol, does not effectively reduce emergence agitation (7). The use of supplemental fentanyl with desflurane, however, has been effective in clinical practice (Dennis Fisher, Department of Anesthesia, University of California, San Francisco, personal communication, 1997).

The purpose of this study was to determine a dose of fentanyl that will significantly decrease the incidence of emergence agitation in children undergoing adenoidectomy, while preserving rapid (3- to 5-min) emergence. Adenoidectomy, with or without bilateral myringotomy and tube insertion, is common in pediatric surgery. It is a brief procedure and is associated with constant but moderate surgical stimulation. Rapid emergence is desirable to allow the child full airway control after extubation. These features make it an appropriate setting for the use of desflurane. Opioid supplementation, i.e., fentanyl, is usually indicated for analgesia. Fentanyl, when incorporated into the anesthetic technique was shown, in an unpublished pilot study of 20 patients, to be effective in reducing agitation without delaying emergence.

	Methods

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Informed consent and institutional approval were obtained. Thirty-two (ASA physical status I and II) children, 2–9 yr old, undergoing adenoidectomy with or without bilateral myringotomy and insertion of tubes, were studied. None of the patients had a history of sleep apnea, developmental delay, or psychological disorders.

Patients were not premedicated. Anesthesia was induced with an inhalation technique consisting of nitrous oxide and oxygen (70%:30%) and sevoflurane. An IV catheter was placed, and mivacurium (0.25 mg/kg) was given to facilitate endotracheal intubation. For anesthesia maintenance, all patients were administered desflurane 4%–6%, N₂O 2 L/min, and oxygen 1 L/min via the endotracheal tube with controlled ventilation, resulting in an end-tidal CO₂ of 35 ± 4 mm Hg. The experimental design used the classic up-down dosing method to determine the mean effective dose of fentanyl that decreases the incidence of emergence agitation and preserves rapid emergence (8). Each patient received one of four possible doses of fentanyl: 1.25, 1.87, 2.8, or 4.2 µg/kg. The dose was determined by the previous patient’s dose and response. The first patient received the smallest dose, 1.25 µg/kg. If the previous patient’s response was positive (i.e., no agitation), then the next lower dose was given, and if the response was negative (i.e., severe agitation), then the next larger dose was administered. Vital signs were monitored and recorded throughout the case. Standard monitoring included electrocardiogram, blood pressure cuff, pulse oximeter, capnography, temperature, and end-tidal anesthetic gas measurements.

The cessation of electrocautery and removal of the mouth gag defined completion of surgery. At this time, recovery of neuromuscular function was confirmed, and desflurane and nitrous oxide were discontinued simultaneously. No alterations were made to the ventilation settings, and no attempt was made to stimulate the patient. With the return of the cough reflex, patients were allowed to breathe spontaneously. When patients demonstrated complete emergence from anesthesia by displaying a regular respiratory pattern, facial grimacing, gag reflex, and purposeful movement, extubation and transfer to the PACU occurred. A blinded observer recorded time to first cough, facial grimacing and gagging, purposeful movement, eye opening, and extubation. Agitation was scored on simple three-point scale (1 = calm, 2 = agitated but consolable, and 3 = severely agitated and inconsolable), pain was assessed by using the Objective Pain Scale (severe pain 6), and recovery was determined by using the Steward Recovery Score (9,10). The same observer preformed all evaluations and scoring. Discharge times from the PACU to the short-stay recovery unit (SSRU) and from the SSRU to home were recorded. Each patient was contacted 24 h after surgery to follow up on the incidence of vomiting, agitation, pain, and the need for treatment at home. A yes-no questionnaire was used to collect these additional data.

By using the classic up-down method, the effective fentanyl dose was determined. For a select accuracy (SE), this method allows for a smaller sample size than the common method of investigating patient groups of equal size with preassigned dose levels. The sample size can be reduced by 30% to 40%, which is an important benefit when a large proportion of patients may be undertreated (11). An SD of 1 µg was chosen for the fentanyl dose levels to reflect standard clinical use. The four dose levels—1.25, 1.87, 2.8, and 4.2 µg/kg, as required—were chosen from a logarithmic scale. The initial dose and the smallest dose were calculated from the 1 µg/kg standard. To attain an accuracy of SE = 0.25, 32 patients were required. Emergence agitation was divided into two groups: no to moderate agitation and severe agitation. Severe agitation was designated as treatment failure. Demographic data, time intervals, and incidence of side effects were analyzed by analysis of variance and the Kruskal-Wallis test.

	Results

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Of the 32 patients, 9 received 1.25 µg/kg, with five treatment failures; 14 received 1.87 µg/kg, with seven treatment failures; 8 received 2.8 µg/kg, with one treatment failure; and 1 received 4.2 µg/kg, with no treatment failures (Fig. 1). Because there were fewer failures than successes, the number of failures was used to determine the appropriate fentanyl dose, as described by Dixon and Massey (11). An effective dose of 2.5 µg/kg with an SD of 0.62 was determined. A confidence interval of 0.38 was also determined for the calculated mean value.

View larger version (18K): [in this window] [in a new window]   Figure 1. Emergence agitation results for the four doses of fentanyl.

	Discussion

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Emergence delirium and agitation are well described phenomena seen after the use of general anesthesia. Eckenhoff et al. (12), in their seminal article, retrospectively examined the incidence of emergence excitation. They reported an increased incidence with particular anesthetics, such as ether, cyclopropane, ketamine, and scopolamine, when used in certain surgical procedures, including tonsillectomy, thyroidectomy, and circumcision, and in children. Since 1961, the discontinued or decreased use of these older anesthetics and the increased use of short-acting opioids, sedatives, and regional techniques rendered this problem one of mere historical interest. With the introduction of the new, relatively insoluble volatile anesthetics, desflurane and sevoflurane, emergence delirium and agitation have reappeared, particularly in children (1–4).

The frequent incidence of excitation during emergence after a desflurane anesthetic was initially described in children undergoing a variety of surgical procedures (1–3). A similar emergence profile has been described for sevoflurane anesthetics in children (3,4,13,14). Because it is not feasible to fully evaluate a young child’s psychological state during emergence, the term "delirium" is often replaced with the descriptive terms "agitation" or "excitation." Proposed explanations for this occurrence have included rapid emergence not allowing for acclimation to a strange environment, variable rates of neurologic recovery resulting in a dissociative state, sympathetic activation, increased pain sensation, and a yet-to-be-defined psychomotor side effect (1,3–5,15–17). In our study, as in others, no psychological evaluation was made, nor was there any attempt to delineate the underlying cause or causes of this phenomenon.

In our study, we reasoned that incorporating an appropriate dose of an opioid as a part of the general anesthetic would prevent or at least lower the risk emergence agitation. Fentanyl, a commonly used, highly potent, and short-acting narcotic, should be ideally suited for this purpose. A pilot study demonstrated that a considerably larger dose than often given for analgesia was required to prevent emergence agitation.

By using the up-down method, a dose of 2.5 µg/kg (SD ± 0.62 µg/kg) was determined to be effective. A dose of 2.5 µg/kg should reduce the overall incidence of emergence agitation seen in children undergoing moderately painful procedures with a desflurane anesthetic. These results cannot be extrapolated to longer or more painful surgical procedures. Because the incidence of emergence agitation is unacceptably frequent in unmedicated patients, no control group was used.

This study was designed to find a dose of fentanyl that would prevent the extreme states of agitation that can be seen with emergence from general anesthesia with desflurane. In these states, patients pose a danger to themselves and their caregivers. Treatment in the PACU can be effective but results in delaying discharge. By experimental design, the incidence of emergence delirium is the same throughout the treatment groups. Because of this design, no significant differences in emergence agitation were found when comparing the patients who received 1.25, 1.87, and 2.5 µg/kg. Emergence times overall may appear longer than those seen in practice because the anesthetics were not tapered as the case was ending but discontinued simultaneously with the completion of surgery. This was designed to establish uniformity in emergence. The 75% incidence of vomiting is more than that reported for adenotonsillectomy (18). Antiemetic prophylaxis should be considered when using this technique (19).

It is difficult to differentiate between pain and agitation in these patients. It has been suggested that pain plays a role in the incidence of emergence. Previous studies, though, have demonstrated a frequent incidence of emergence agitation in presumably pain-free patients: those who received desflurane for genitourinary surgery with adequate caudal blocks and those who received sevoflurane for noninvasive procedures and magnetic resonance imaging (1,14,16,17). Our results show pain scores to be similar between the treatment groups. These results suggest another mechanism as the cause of emergence agitation.

In conclusion, a dose of 2.5 µg/kg of fentanyl, given after induction, successfully reduces the incidence of severe agitation associated with desflurane anesthesia in children without delaying emergence. Further studies are required to help delineate the underlying cause or causes of this problem.

	Acknowledgments

 
Supported by a grant from Baxter Pharmaceutical Products, Providence, NJ.

We acknowledge the efforts of Urs Ruttimann, PhD, who was the statistician for this study.

	Footnotes

 
Presented in part at the annual meeting of the American Society of Anesthesiologists, Dallas, TX, October, 1999.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Davis PJ, Cohen IT, McGowan FX Jr, Latta K. Recovery characteristics of desflurane versus halothane for maintenance of anesthesia in pediatric ambulatory patients. Anesthesiology 1994; 80: 298–302.[Web of Science][Medline]
2. Grundmann U, Uth M, Eichner A, et al. Total intravenous anaesthesia with propofol and remifentanil in paediatric patients: a comparison with a desflurane-nitrous oxide inhalation anaesthesia. Acta Anaesthesiol Scand 1998; 42: 845–50.[Web of Science][Medline]
3. Walker SM, Haugen RD, Richards A. A comparison of sevoflurane with halothane for paediatric day case surgery. Anaesth Intensive Care 1997; 25: 643–9.[Web of Science][Medline]
4. Aono J, Ueda W, Mamiya K, et al. Greater incidence of delirium during recovery from sevoflurane anesthesia in preschool boys. Anesthesiology 1997; 87: 1298–300.[Web of Science][Medline]
5. 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]
6. Welborn LG, Hannallah RS, McGill WA, et al. Induction and recovery characteristics of desflurane and halothane anaesthesia in paediatric outpatients. Paediatr Anaesth 1994; 4: 359–64.
7. Cohen IT, Janutka S, Norden J, Hannallah R. Emergence delirium following desflurane anesthesia in children is not modified by the concurrent use of sedatives/hypnotics. Anesth Analg 1997; 84: S421.
8. Dixon WJ. The up and down methods for small samples. J Am Stat Soc 1965; 60: 967–78.
9. Hannallah RS, Broadman LM, Belman AB, et al. Comparison of caudal and ilioinguinal/iliohypogastric nerve blocks for control of post-orchiopexy pain in pediatric ambulatory surgery. Anesthesiology 1987; 66: 832–4.[Web of Science][Medline]
10. Steward DJ. A simplified scoring system for the postoperative recovery room. Can J Anaesth 1975; 22: 111–3.
11. Dixon WJ, Massey FJ. Introduction to statistical analysis. 4th ed. New York: McGraw-Hill, 1998: 428–39.
12. Eckenhoff JE, Kneale DH, Dripps RD. The incidence and etiology of postanesthetic excitement. Anesthesiology 1961; 22: 667.
13. Sarner JB, Levine M, Davis PJ, et al. Clinical characteristics of sevoflurane in children: a comparison with halothane. Anesthesiology 1995; 82: 38–46.[Web of Science][Medline]
14. Wells LT, Rasch DK. Emergence " delirium" after sevoflurane anesthesia: a paranoid delusion? Anesth Analg 1999; 88: 1308–10.[Free Full Text]
15. Ebert TJ, Muzi M. Sympathetic hyperactivity during desflurane anesthesia in healthy volunteers. Anesthesia 1993; 79: 444–53.
16. Uezono S, Goto T, Terui K, et al. Emergence agitation after sevoflurane versus propofol in pediatric patients. Anesth Analg 2000; 91: 563–6.[Abstract/Free Full Text]
17. Cravero JP, Surgenor SD, Whalen K. Emergence agitation in pediatric patients after sevoflurane anesthesia and no surgery: a comparison with halothane [abstract]. Anesthesiology 2000; 91: A1247.
18. Pandit UA, Malviya S, Lewis IH. Vomiting after outpatient tonsillectomy and adenoidectomy in children: the role of nitrous oxide. Anesth Analg 1995; 80: 230–8.[Abstract]
19. Ericksson H, Korttila K. Recovery profile after desflurane with or without ondansetron compared with propofol in patients undergoing outpatient gynecological laparoscopy. Anesth Analg 1996; 82: 533–8.[Abstract]

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999