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Anesth Analg 2004;98:60-63 © 2004 International Anesthesia Research Society
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Abstract |
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Emergence agitation is a common side effect of sevoflurane anesthesia in children. Dexmedetomidine, because of its sedative and analgesic properties, might be useful for the management of this adverse effect. We studied the effect of dexmedetomidine on recovery characteristics in 90 children aged 1 to 10 yr scheduled to undergo superficial lower abdominal and genital surgery. After inhaled induction with sevoflurane, patients were randomly assigned to receive saline (Group 1, n = 30), dexmedetomidine 0.15 µg/kg (Group 2, n = 30), or dexmedetomidine 0.30 µg/kg (Group 3, n = 30). After a laryngeal mask airway insertion a caudal block was performed in all patients. Maintenance of anesthesia was with 1% end-tidal sevoflurane and 50% nitrous oxide and spontaneous ventilation. Intraoperative hemodynamic and respiratory variables were recorded every 5 min. At the end of anesthesia time to eyes opening (TEO) and characteristics of emergence were recorded. General and intraoperative variables were similar in the 3 groups. The TEO was 7.5 ± 5.0 min in Group 1, 8.2 ± 5.0 min in Group 2, and 9.8 ± 4.0 min in Group 3 (NS). The incidence (95% confidence interval) of agitation was 37% (20%–54%) in Group 1, 17% (4%–30%) in Group 2, and 10% (0%–21%) in Group 3 (P < 0.05). Paired comparisons showed a significant difference for Group 1 versus Group 3 (P < 0.05, 95% confidence interval of the difference: 7%–47%). The time to discharge from the postanesthesia care unit was similar for the 3 groups. We conclude that a dose of dexmedetomidine 0.3 µg/kg administered after induction of anesthesia reduces the postsevoflurane agitation in children and with no adverse effects.
IMPLICATIONS: In children undergoing surgery using sevoflurane anesthesia, dexmedetomidine 0.3 µg/kg administered in 10 min after induction reduced the incidence of emergence agitation from 37% in the control group to 10%. No adverse effects attributable to dexmedetomidine were observed.
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Introduction |
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Sevoflurane is widely used in pediatric anesthesia because of a fast and well tolerated inhaled induction, low hepatotoxicity, hemodynamic stability, and rapid emergence from anesthesia. However, the occurrence of emergence agitation is a common phenomenon in children, with a reported incidence up to 80% (1). Different drugs such as analgesics (2), opioids (3), benzodiazepines (4,5), and clonidine (1,6) have been used either prophylactically or as a treatment with variable success. Dexmedetomidine, a more selective
2 adrenoceptor agonist than clonidine, has been used as an adjuvant in general anesthesia and for postoperative sedation and analgesia (7). The objective of this study was to test the hypothesis that because of its sedative effects, the prophylactic use of dexmedetomidine reduces the incidence of emergence agitation after sevoflurane-based anesthesia in children. |
Methods |
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After institutional ethics committee approval and informed parental consent, 90 pediatric patients aged 1–10 yr scheduled to undergo inguinal hernia repair, orchiopexy, or circumcision under general anesthesia and caudal block were prospectively studied. All were ASA physical status I and did not receive any premedication. Exclusion criteria included chronic or acute intake of any sedative and analgesic drug, any known adverse effect to the study drugs, previous anesthesia experience, and failure of the caudal block. Induction of anesthesia was with 50% nitrous oxide and 8% sevoflurane in oxygen and spontaneous ventilation. After anesthetic induction and placement of the IV line, patients were assigned to one of three groups by means of random numbers generated by a computer. Group 1 (n = 30) received saline 10 mL, Group 2 (n = 30) received dexmedetomidine 0.15 µg/kg, and Group 3 (n = 30) received dexmedetomidine 0.30 µg/kg. Dexmedetomidine was diluted in saline 10 mL and the study drug and placebo were administered IV in 10 min. After insertion of a laryngeal mask airway (LMA), sevoflurane was reduced to 3% in 50% nitrous oxide, patients were left in spontaneous ventilation, and a caudal block with 0.5–1.0 mL/kg 0.25% bupivacaine was performed in all patients. Then, the concentration of sevoflurane was set at 1% end-tidal (ET) in 50% nitrous oxide until the end of surgery. Failure of the caudal block was defined as any increase in heart rate (HR) and/or mean arterial blood pressure (MAP) >10% than preincision values with the beginning of surgery. After closure, anesthetic gases were discontinued (T0) and replaced with O2 100%
5 L/min. The LMA was removed when patients were awake. Intraoperatively, HR, MAP, respiratory rate (RR), and ETCO2 were recorded every 5 min. From the end of anesthesia (T0) the time to eye opening (defined as the time until eye opening on command) was recorded. Behavior during both pre- and postoperative periods was rated on a four-point scale: 1 = calm; 2 = not calm but could be easily calmed; 3 = not easily calmed, moderately agitated or restless; and 4 = combative, excited, or disoriented (8). In the postanesthesia care unit (PACU), parents were allowed to be with their children and behavior, modified Aldrete score and pain with the Children’s and Infants’ Postoperative Pain Scale (CHIPPS) score (9) were evaluated by a blinded nurse (AM). This nurse stayed with the patients until discharge to the ward and recorded every 15 min the worst rating for each score observed during the previous 15 min. Criteria for transfer to the ward included a patient with no pain, calm, and with a modified Aldrete score >10. The time to meet these criteria was also recorded. In case of agitation in the PACU the first measure was to facilitate parental contact and when this failed fentanyl 1 µg/kg IV was administered. All syringes with dexmedetomidine or placebo were prepared by the same investigator (HM). Administration of anesthesia and study drugs and intraoperative data collection were made by two investigators (ME, VB) blinded as to the study drugs.
For purposes of analysis, grades 1 and 2 in the scale of behavior were considered no agitation and grades 3 and 4 were considered presence of agitation (8). The sample size was calculated to detect a 66% reduction of the incidence of agitation from 45% in control group with = 0.05 and ß = 0.80. One- and two-way ANOVA and 
2 were used for statistical analysis. Paired comparisons were corrected with Bonferronis’ test. A P < 0.05 was considered significant.
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Results |
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There were no significant differences regarding general and anesthetic data among the 3 groups (Table 1). The incidence of agitation during induction of anesthesia was 13% in Group 1, 10% in Group 2, and 17% in Group 3 (NS). Intraoperatively, the HR, MAP (Fig. 1), RR, and ETCO2 decreased in all groups with no significant differences among them. The time to eye opening was similar in the 3 groups (Table 2). The incidence (95% confidence interval [CI95%]) of agitation was 37% (20%–54%) in Group 1, 17% (4%–30%) in Group 2, and 10% (0%–21%) in Group 3 (P < 0.05). Paired comparisons between groups showed a significant difference only for Group 1 versus Group 3 (P < 0.05, CI95% of the difference = 7%–47%). There was no association between the occurrence of agitation during induction and during the emergence of anesthesia. During the period with no agitation, all patients presented a CHIPPS score <3. "Ready to discharge" and actual discharge from PACU times were similar in the 3 groups (Table 2).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The results of this study show that, in children, dexmedetomidine 0.3 µg/kg IV administered after anesthetic induction reduces the incidence of emergence agitation after sevoflurane anesthesia.
Emergence agitation is a frequent side effect of sevoflurane anesthesia in children (1). Although there is no clinical evidence that this adverse effect affects long term outcome, it is a source of dissatisfaction for parents. As genesis of agitation after sevoflurane anesthesia is uncertain, there is no well-established prophylaxis or treatment, although the incidence of this excitatory behavior seems to be reduced by the perioperative use of sedative and analgesic drugs.
Compared with placebo, midazolam 0.5 mg/kg orally administered 15 to 30 minutes before surgery reduced the incidence of agitation postsevoflurane from 67% to 39% after myringotomy surgery (4) but not after adenoidectomy (47% versus 60% with placebo) (5). In both studies, however, the early recovery from anesthesia was slightly prolonged with midazolam.
The presence of pain as a predisposing factor for postoperative agitation explains the effectiveness of analgesic drugs such as ketorolac and fentanyl given either as prophylaxis or for treatment of agitation. Thus, in myringotomy surgery lasting around 10 minutes, Galinkin et al. (3) observed that the use of intranasal fentanyl 2 µg/kg IV administered after induction reduced the incidence of agitation after sevoflurane anesthesia from 23% to 2% without increasing the discharge times. In children premedicated with intranasal midazolam 0.2 mg/kg undergoing myringotomy, the intraoperative use of ketorolac 1 mg/kg IV resulted in a 14% incidence of emergence agitation compared with 38% with saline (2).
Because of its sedative and analgesic effects, clonidine has also been used for the management of sevoflurane agitation. The administration after induction of clonidine 3 µg/kg IV reduced the incidence of agitation after sevoflurane from 39% in the control group to 0% in children without postoperative pain (6), and no delay in fitness for discharge was observed with clonidine. Kulka et al. (1) found a reduction of agitation with clonidine 2 µg/kg IV administered 5 minutes after the start of surgery from 80% in controls to 10% in treated, supposedly pain-free patients. Although the "discharged ready" times were not evaluated, all patients met the discharge criteria 2 hours after the end of surgery. In children undergoing minor surgery, oral clonidine 4 µg/kg given 30–60 minutes before anesthesia reduced the agitation score (incidence not given) postsevoflurane compared with clonidine 2 µg/kg, midazolam 0.5 µg/kg, diazepam 0.4 µg/kg, and placebo without increasing discharge times (10).
Dexmedetomidine has similar actions to clonidine and in our study, when administered IV after induction, resulted in a reduction of postoperative agitation from 37% in the control group to 17% and 10% with 0.15 µg/kg and 0.3 µg/kg, respectively. This reduction seems to be less than that reported for clonidine, and larger doses might provide further protection from agitation. However, the potential increase in side effects must be determined before making such a recommendation. In the case of clonidine, the previous studies did not find a significant effect of clonidine on the discharge times from PACU (2,10); however, the awakening times in the operating room, which might be prolonged secondary to the sedative effects of clonidine, were not evaluated. Although the administration of clonidine 2 and 4 µg/kg orally 100 min before the induction of anesthesia did not result in prolonged awakening times compared with placebo (11), different times and/or routes of administration and duration of surgery made comparisons difficult, and a delayed awakening time with clonidine was possible. In our study, the time to eye opening, considered an index of early recovery of anesthesia, was not significantly affected by dexmedetomidine. Similarly to the studies with clonidine, dexmedetomidine did not result in either prolonged "ready to discharge" nor actual discharge times compared with the control group.
Dexmedetomidine is a 2 adrenergic agonist with a larger ratio of 2/1 activity (1600:1) than clonidine (200:1). The hemodynamic effects of dexmedetomidine are similar to that of clonidine and the effects can vary depending on the dose, rate, and route of administration (12). The administration of dexmedetomidine 2 µg/kg in 5 minutes in volunteers resulted in a biphasic response consisting of an initial increase in MAP of 22% along with a reduction in HR of 27% during the period of infusion, followed by stabilization of MAP at lower values than baseline and an almost unchanged HR (12). In contrast, the preoperative administration of 1 µg/kg in 10 minutes resulted in <20% reductions of HR and MAP in adults (13,14).
Based on their experience with four cases from 10 weeks to 14 years of age, Tobias and Berkenbosch (15) recommend infusion rates ranging from 0.25–0.75 µg · kg-1 · h-1 for sedation during mechanical ventilation in these patients. Although the authors did not make recommendations on bolus doses, they did use them in two patients. One was a 14-year-old patient admitted to the intensive care unit for postoperative care; dexmedetomidine was given for sedation starting with a bolus dose of 0.50 µg/kg that resulted in a decrease in HR from 136 to 96 bpm and a decrease in MAP from 158/108 mm Hg to 126/66 mm Hg. In contrast, the administration of dexmedetomidine 0.60 µg/kg over 2 minutes in an 11-year-old patient scheduled for endoscopic gastroscopy resulted in essentially unchanged HR and MAP (15). We decided to be cautious with the doses chosen, and 0.15 and 0.30 µg/kg appear to be safe for intraoperative use in children. We found that dexmedetomidine had no significant hemodynamic effects when compared to placebo. In addition, the RR and ETCO2 were similar in the three groups, results that agree with the slight respiratory effects of dexmedetomidine in adults (16).
In summary, our study demonstrates that dexmedetomidine 0.30 µg/kg IV after anesthetic induction significantly decreases the occurrence of emergence agitation in children undergoing sevoflurane anesthesia. The bolus administration of dexmedetomidine in this dose was safe, and it did not lead to an increased incidence of side effects. However, more studies are needed to determine both the efficacy and safety of dexmedetomidine either in different types of surgery or at larger doses.
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Acknowledgments |
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Supported, in part, by departmental funding.
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Footnotes |
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Presented, in part, as a poster presentation at the 2003 Annual Meeting of the European Society of Anaesthesiologists, May 31-June 3, Glasgow, Scotland.
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References |
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- Kulka PJ, Bressem M, Tryba M. Clonidine prevents sevoflurane-induced agitation in children. Anesth Analg 2001; 93: 335–8.
[Abstract/Free Full Text] - Davis PJ, Greenberg JA, Gendelman M, Fertal K. Recovery characteristics of sevoflurane and halothane in preschool-aged children undergoing bilateral myringotomy and pressure equalization tube insertion. Anesth Analg 1999; 88: 34–8.
[Abstract/Free Full Text] - Galinkin JL, Fazi LM, Cuy RM, et al. Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia. Anesthesiology 2000; 93: 1378–83.[Web of Science][Medline]
- Lapin SL, Auden SM, Goldsmith LJ, Reynolds AM. Effects of sevoflurane anaesthesia on recovery in children: a comparison with halothane. Paediatr Anaesth 1999; 9: 299–304.[Web of Science][Medline]
- Viitanen H, Annila P, Viitanen M, Tarkkila P. Premedication with midazolam delays recovery after ambulatory sevoflurane anesthesia in children. Anesth Analg 1999; 89: 75–9.
[Abstract/Free Full Text] - Bock M, Kunz P, Schreckenberger R, et al. Comparison of caudal and intravenous clonidine in the prevention of agitation after sevoflurane in children. Br J Anaesth 2002; 88: 790–6.
[Abstract/Free Full Text] - Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000; 59: 263–8.[Web of Science][Medline]
- 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]
- Buttner W, Finke W. Analysis of behavioural and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young children: a comprehensive report on seven consecutive studies. Paediatr Anaesth 2000; 10: 303–18.[Web of Science][Medline]
- Mikawa K, Nishina K, Shiga M. Prevention of sevoflurane-induced agitation with oral clonidine premedication. Anesth Analg 2002; 94: 1675–6.
[Free Full Text] - Yaguchi Y, Inomata S, Kihara S, et al. The reduction in minimum alveolar concentration for tracheal extubation after clonidine premedication in children. Anesth Analg 2002; 94: 863–6.
[Abstract/Free Full Text] - Dyck JB, Maze M, Haack C, et al. The pharmacokinetics and hemodynamic effects of intravenous and intramuscular dexmedetomidine hydrochloride in adult human volunteers. Anesthesiology 1993; 78: 813–20.[Web of Science][Medline]
- Jaakola ML. Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J Clin Anesth 1994; 6: 204–11.[Web of Science][Medline]
- Arain SR, Ebert TJ. The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation. Anesth Analg 2002; 95: 461–6.
[Abstract/Free Full Text] - Tobias JD, Berkenbosch JW. Initial experience with dexmedetomidine in paediatric-aged patients. Paediatr Anaesth 2002; 12: 171–5.[Web of Science][Medline]
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