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PEDIATRIC ANESTHESIA

The Effect of Caudal Analgesia on Emergence Agitation in Children After Sevoflurane Versus Halothane Anesthesia

B. Craig Weldon, MD^*, Martin Bell, MD, and Thomas Craddock, MD

*Departments of Anesthesiology and Pediatrics, University of Florida College of Medicine, Gainesville, Florida; and Department of Pediatric Surgery, St. John’s Mercy Medical Center, St. Louis, Missouri

Address correspondence and reprint requests to B. Craig Weldon, MD, Department of Anesthesiology, PO Box 100254, Gainesville, FL 32610-0254. Address e-mail to cweldon{at}anest.ufl.edu

	Abstract

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Sevoflurane anesthesia in young children has been associated with an increased incidence of emergence agitation compared with halothane. Postoperative pain may be an etiologic factor. We designed a study to compare the incidence of emergence agitation after halothane and sevoflurane anesthesia in children whose pain was managed with caudal analgesia. Eighty children undergoing inguinal hernia repair between the ages of 12 mo and 6 yr were randomly assigned to receive either halothane or sevoflurane anesthesia. Baseline preoperative anxiety was assessed with the Yale Preoperative Anxiety Scale. The children were sedated with oral midazolam, underwent a mask induction, and had a caudal block placed for postoperative analgesia. After surgery, the children’s behavior was assessed with a four-point agitation scale. At 5 min after arrival in the postanesthesia care unit (PACU), sevoflurane was associated with a greater incidence of emergence agitation than halothane (26% vs 6%; P < 0.05), but not during the remainder of the PACU stay. Higher levels of preoperative anxiety were associated with difficult mask induction, agitation on admission to the PACU, and more severe agitation episodes. Emergence agitation appears to be an early and transient phenomenon after sevoflurane anesthesia in children with effective postoperative analgesia.

IMPLICATIONS: Effective postoperative analgesia may reduce the incidence of emergence agitation reported with sevoflurane anesthesia. The Yale Preoperative Anxiety Scale appears to be helpful in identifying young children who are at risk for developing emergence agitation.

	Introduction

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Sevoflurane is often used for anesthetic induction in pediatric patients because mask induction with sevoflurane is faster (1–5) and produces less cardiovascular depression (1,3–8) and fewer dysrhythmias (1,3,5,9) than with halothane. Sevoflurane, when used as a maintenance anesthetic, also provides a more rapid emergence than halothane (2,3,8,10–14).

Young children emerging from sevoflurane anesthesia appear to have an increased incidence of agitation compared with halothane (2,8,15–19). This unfavorable characteristic has been attributed to rapid emergence (2,8,15), an inherent excitatory property of the drug (20,21), and inadequate postoperative analgesia (10,22,23). The contribution of postoperative pain to emergence agitation after inhaled anesthesia is not clear because many studies may have failed to provide adequate postoperative pain control. Pain is a recognized cause of postoperative distress and agitation in children and may complicate the assessment of emergence agitation. We, therefore, designed a study to compare the incidence of emergence agitation after halothane and sevoflurane anesthesia in children who were known to have complete analgesia as a result of a caudal block. We also assessed preoperative behavior to determine the influence of preoperative anxiety on postoperative agitation.

	Methods

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This study was approved by the IRB, and parental informed consent was obtained. Eighty ASA physical status I children undergoing inguinal hernia repair were enrolled. Exclusion criteria included emergency procedures, medical contraindication to placement of a caudal block, mental retardation, developmental delay, attention-deficit/hyperactivity disorder, psychiatric illness, a history of paradoxical excitation with sedatives, or a previous episode of emergence delirium.

The children were premedicated orally with midazolam 0.5 mg/kg mixed with ibuprofen suspension (10 mg/kg). Twenty to 30 min after receiving the sedative, they were separated from their parents and transported to the operating room. Children were assigned by a computer-generated randomization program to receive a mask induction with either halothane or sevoflurane in a 70% nitrous oxide and 30% oxygen mixture with a 10 L/min fresh gas flow. After anesthetic induction, an IV cannula, caudal block, and laryngeal mask airway (LMA) were placed. The caudal block was performed by using a sterile technique to administer 1 mL/kg of equal volumes of 0.25% bupivacaine with 1:200,000 epinephrine and 1% lidocaine with 1:200,000 epinephrine. The children were allowed to breathe spontaneously throughout the entire anesthetic. After LMA placement, the nitrous oxide in oxygen concentration was reduced to 60%, and the total fresh gas flow rate was reduced to 5 L/min. A standardized general anesthetic was provided to both groups by adjusting inhaled end-tidal concentrations to deliver a minimum alveolar anesthetic concentration (MAC) of 1. Age and nitrous oxide affect the MAC of halothane and sevoflurane to different degrees (24,25); therefore, an age/nitrous-adjusted MAC anesthetic level was provided for each child before surgical incision and throughout the procedure.

Skin incision served as the test of analgesic adequacy of the caudal block. The block was judged inadequate if the child’s heart rate increased >20% within 60 s of skin incision. Only the children judged to have a functioning block were continued in the study. They were not given intraoperative analgesics or other sedating drugs, and their age/nitrous-adjusted MAC of inhaled anesthetic was immediately reduced by 50%. Children who had a heart rate response to skin incision were given IV opioid analgesia and were not assessed for agitation or pain in the postanesthesia care unit (PACU). At the start of surgical closure (bilateral hernias were closed simultaneously), the inhaled anesthetic was discontinued. The nitrous oxide was discontinued, and the oxygen flow rate was increased to 10 L/min when wound closure was complete. The LMA was removed in the operating room when any two of the following events occurred: eye opening, vocalization, grimacing, swallowing, biting, coughing, gagging, spontaneous turning of the head, or hands brought up to the face. The children were then transported to the PACU and examined to confirm that they had a functioning caudal block. Children with lower extremity weakness and no response to toe pinch were considered to have a functioning block.

Behavior was assessed during the admission process to the ambulatory surgery unit (ASU), at the time of separation from parents, at the application of the anesthetic mask, and in the PACU by a trained observer blinded to the inhaled anesthetic group. The following scoring systems were used:

1. The Yale Preoperative Anxiety Scale score (YPAS) (26) was used for all subjects. The YPAS measures anxiety-related behavior in 5 domains that result in a total raw score of 5 (lowest anxiety) to 21 (highest anxiety). YPAS scoring was performed as the preoperative nurse took the child’s vital signs.
   
2. A separation scale (27) was used to assess behavior at the time of separation from parents (1 = excellent [separates easily]; 2 = good [not clinging, whimpers, calms with reassurance]; 3 = fair [not clinging, cries, will not calm or quiet]; and 4 = poor [crying, clinging to parent]). A separation score of 1 or 2 was considered satisfactory, whereas a score of 3 or 4 was considered unsatisfactory.
   
3. An induction scale (27) was used to assess acceptance of the anesthetic mask (1 = excellent [unafraid, cooperative, accepts mask readily]; 2 = good [slight fear of mask, easily calmed]; 3 = fair [moderate fear, not calmed with reassurance]; 4 = poor [terrified, crying, agitated]). An induction score of 1 or 2 was considered satisfactory, whereas a score of 3 or 4 was considered unsatisfactory.
   
4. An emergence agitation scale was measured on admission to the PACU, every 5 min thereafter, and on arrival of the parent in the PACU (1 = awake and calm, cooperative; 2 = crying, requires consoling; 3 = irritable/restless, screaming, inconsolable; 4 = combative, disoriented, thrashing). Children with an agitation score of 3 or 4 were classified as agitated. Although scoring agitation at 5-min intervals may not be ideal, in the busy milieu of our pediatric PACU, it was the most expedient and practical approach.
   

Parents were reunited with their children in the PACU after an initial admission and stabilization phase. Children were considered severely agitated if they had an agitation score that remained >3 for 5 min after the arrival of their parent. Severely agitated children were treated with either morphine 0.05 mg/kg or midazolam 0.05 mg/kg IV. All children were scored for agitation 30 min after transfer from the PACU to the ASU and just before discharge from the ASU. Parents were given a brief questionnaire to be completed on the second postoperative day that assessed the child’s recovery and parent satisfaction with the perioperative experience. Parents who did not return their questionnaire within a week were contacted by phone.

The duration of anesthesia was defined as the time from mask induction to the discontinuation of the inhaled anesthetic. The emergence time was defined as the time from discontinuation of the inhaled anesthetic to removal of the LMA. The incision time was defined as the time from mask induction to skin incision. The time for caudal block to set up was defined as the time from completion of the block to skin incision.

The sample size for this study was designed to evaluate the difference in the incidence of emergence agitation during the PACU stay in children receiving sevoflurane or halothane anesthesia. Aono et al. (15) reported that the incidence of emergence delirium in preschool children after sevoflurane anesthesia was 40% but was only 10% after halothane anesthesia. We calculated that a sample size of 36 subjects per treatment arm would have at least an 80% power to detect a difference of 30% in the incidence of emergence agitation. A P value of 0.05 was used for statistical significance. We estimated that as many as 10% of the children might have equivocal caudal analgesia at skin incision, so 80 children were enrolled in the study. Unless otherwise noted, data are reported as mean ± SD. Continuous data were analyzed by using the unpaired Student’s t-test. Nominal data were analyzed by using the ² or Fisher’s exact test. Maximum agitation scores at each time point for the two study groups were compared by using a two-sample Wil- coxon’s ranked sum (Mann-Whitney) test. All statistical tests were two tailed.

	Results

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Informed consent was obtained for 80 children who were randomized to receive either halothane or sevoflurane, but only 68 were included in the study. No children were excluded because of a history of emergence agitation. However, 12 children (6 in the halothane group and 6 in the sevoflurane group) who were excluded from the study demonstrated a heart rate response to skin incision. Nine of the 12 were found to have functioning caudal blocks when they were examined later in the PACU. These children had similar PACU and ASU times compared with the children with functioning blocks who were kept in the study and did not require pharmacologic treatment for agitation. Two of the nine (both in the halothane group) were given morphine by the PACU nurses for apparent pain. The 68 children who completed the study had a functioning caudal block (no reaction to toe pinch and positive withdrawal to finger pinch) when examined in the PACU.

The two treatment groups had similar demographic data, preoperative YPAS score, and history of surgery (Table 1). The ease of separation from parents and the quality of mask induction were also similar between the groups (Table 2). The total anesthesia time, the time allowed for the caudal block to set up before incision, and time to emergence between the groups were not different (Table 2). There were also no differences between the groups in the time that elapsed before parents rejoined their children in the PACU (14 ± 6 min for the halothane group versus 12 ± 5 min for the sevoflurane group; P = 0.14).

View larger version (22K): [in this window] [in a new window]   Figure 1. Percentage of children with agitation on admission to the postanesthesia care unit (PACU), 5 min after PACU admission, on parent arrival in the PACU, 5 min after parent arrival, and 10 min after parent arrival. *P < 0.05.

	Discussion

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This study demonstrates that sevoflurane is associated with an early, short-lived increase in the incidence of emergence agitation compared with halothane when reliable postoperative pain control is provided with a caudal block. This finding supports the notion that inadequate postoperative pain control may have contributed to the large differences in emergence agitation between the two drugs noted in other studies (2,8,15–18). Our study also suggests that higher levels of preoperative anxiety in young children are associated with more emergence agitation.

Some investigators have failed to find any difference in the incidence of emergence agitation between halothane and sevoflurane (22,23,28). Welborn et al. (28) compared the emergence characteristics of halothane, sevoflurane, and desflurane in a population of children aged 1–7 years who were undergoing adenoidectomy and bilateral myringotomy and tubes (BMT) placement. The children were premedicated with oral midazolam, and no intraoperative analgesics were administered. The sevoflurane and halothane groups had significantly less postoperative agitation compared with desflurane, which had the most rapid emergence time (28). These findings suggest that the rapidity of emergence may play a role in emergence agitation. Davis et al. (22) compared sevoflurane and halothane anesthesia for BMT placement in young children. The investigators specifically addressed the role of pain in postoperative agitation by administering intraoperative ketorolac or placebo to both anesthetic groups. All children were given preoperative intranasal midazolam. Although there were no differences in emergence agitation between the anesthetic groups, the administration of ketorolac reduced the incidence of agitation in both the halothane and sevoflurane groups. The authors concluded that inadequate analgesia was a major factor in the development of emergence agitation (22). A similar study demonstrated that intraoperative intranasal fentanyl improved agitation and pain scores in children after BMT placement (23). All children received preoperative oral midazolam, and there was no difference in agitation between halothane and sevoflurane (23).

The above-mentioned studies (22,23,28) used oral midazolam as a preoperative sedative—a factor that might have influenced the emergence behavior of their subjects. We used oral midazolam premedication because it was the standard of care at our institution at the time of the study and because we believed that it would reduce the children’s anxiety at the time of separation and induction. Our aim was to avoid a stormy mask induction, which has been shown to contribute to emergence agitation (29,30). There are conflicting data on the effects of midazolam premedication on the postoperative behavior of young children. Lapin et al. (17) found that midazolam premedication significantly decreased the incidence of emergence agitation after sevoflurane, but not halothane, anesthesia. Other investigators have shown that midazolam slows the emergence of children from sevoflurane anesthesia but does not appear to influence the incidence of emergence agitation (31). We found no difference in the speed of emergence between the sevoflurane and halothane groups. However, all of our patients received midazolam premedication, and it is possible that residual sedation slowed the emergence in the sevoflurane group. The combination of the midazolam premedication and effective postoperative analgesia, and not effective analgesia alone, may explain the similar agitation rates between the study groups. Although this is a limitation of our study design, we believed that it would be unethical to withhold preoperative sedation in this patient population.

Previous studies have reported an increased incidence of emergence agitation with sevoflurane compared with halothane (2,8,15–19). These studies are difficult to compare because of their different methodologies. Children undergoing a variety of procedures—(2,16) myringotomy tube placement (17,18) and inguinal or urologic surgery (8,15)—have been reported to have increased agitation with sevoflurane. Preoperative sedation was not universally given, no attempt was made to measure preoperative anxiety, and the subjects’ behavior at induction was not documented. Control of postoperative pain was usually addressed in these studies, but it was not clear whether the analgesic regimen used was successful in all of the study subjects. Cravero et al. (19) avoided the issue of inadequate postoperative pain control by studying children who required anesthesia for nonpainful neuroimaging studies. The authors concluded that sevoflurane was associated with more emergence agitation than halothane. However, the study design did not include preoperative sedation (19).

We elected to treat severe, unremitting agitation to minimize injury to the child and reduce parental anxiety and the general disruption of the PACU environment. This was required in more children in the sevoflurane group and likely shortened the duration of their agitation. Midazolam or morphine was not administered until 15 to 20 minutes into the PACU stay and, thus, would not have affected the incidence of agitation before parental arrival at the bedside. Sedating the most severely agitated children may have played a role in decreasing the incidence of agitation in the sevoflurane group at the 10 minutes after parent arrival time point (Fig. 1).

The assessment of emergence agitation has been addressed in a variety of ways by previous investigators. The fact that there are no widely accepted emergence agitation or delirium scales for children has led to the use of subjective assessment methods (2,8,17) and various agitation rating systems (15,16,18,19). We constructed an agitation scale based on our extended observation of children emerging from anesthesia as well as on the work of others (32,33). Our agitation scale closely resembles that used by Aono et al. (15).

We attempted to ensure that the children had similar baseline levels of anxiety in both study groups by measuring their YPAS score before the administration of midazolam. The fact that the two study groups had similar baseline YPAS scores may also help to explain why we found smaller differences in agitation between the groups. The other two observation points (separation from parents and acceptance of a mask induction) were used to measure the effectiveness of the preanesthetic sedative in reducing anxiety and facilitating anesthetic induction. Distressed behavior in unpremedicated children during induction may be a predictor of postoperative agitation (29,30). We found no differences in separation or induction scores between the study groups, but higher preoperative YPAS scores were associated with a difficult mask induction regardless of the inhaled anesthetic used.

One potential limitation of our study was our use of the original YPAS instrument in children between 12 months and 2 years of age in the preoperative holding area. The YPAS has not been validated in children <24 months and was originally developed as a measure of anxiety in children undergoing anesthetic induction (26). Kain et al. (34) later modified the YPAS (mYPAS) and showed that it could serve as a convenient measure of anxiety in children before they underwent separation from their parents and anesthetic induction. We did not have access to the mYPAS at the time that we designed and performed the study, so we used the original YPAS to measure preoperative anxiety. It is interesting to note that we found that higher scores (higher levels of anxiety) on the original YPAS were associated with difficult mask induction, an increased incidence of agitation on admission to the PACU, and more severe episodes of emergence agitation. Further study of the mYPAS to measure baseline anxiety as a predictor of emergence behavior in young children seems warranted.

In summary, our findings indicate that sevoflurane is associated with a brief period of emergence agitation in young children. These results also indicate that the combination of midazolam premedication and effective postoperative analgesia minimizes emergence agitation after sevoflurane anesthesia. Additionally, YPAS scoring early in the preoperative period could be valuable in identifying children who are at risk of developing postoperative agitation.

	Acknowledgments

 
Funding was provided by the Department of Anesthesiology.

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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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Weldon, B. C. Articles by Craddock, T. Search for Related Content PubMed PubMed Citation Articles by Weldon, B. C. Articles by Craddock, T. Related Collections Anesthetic Techniques Complications Pediatrics Regional Anesthesia

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