Anesth Analg 2002;94:863-866
© 2002 International Anesthesia Research Society
PEDIATRIC ANESTHESIA
The Reduction in Minimum Alveolar Concentration for Tracheal Extubation After Clonidine Premedication in Children
Yuichi Yaguchi, MD*,
Shinichi Inomata, MD*,
Shin-ichi Kihara, MD*,
Yasuyuki Baba, PhD ,
Yukinao Kohda, PhD, and
Hidenori Toyooka, MD*
*Department of Anesthesiology, Institute of Clinical Medicine, and Department of Clinical Pharmacy, University of Tsukuba, Tsukuba City, Ibaraki, Japan
Address correspondence and reprint requests to Shinichi Inomata, MD, Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki 305-8575, Japan. Address e-mail to inomatas{at}md.tsukuba.ac.jp
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Abstract
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The effects of clonidine on minimum alveolar concentration for tracheal extubation (MAC-ex) have not been elucidated. Clonidine may lead to prolonged emergence from anesthesia. We investigated the effects of oral clonidine premedication on MAC-ex and examined the emergence properties of sevoflurane in children. Sixty ASA physical status I pediatric patients, aged from 2 to 9 yr, were randomly divided into one of three groups and received placebo, clonidine 2 µg/kg, or clonidine 4 µg/kg (n = 20 each) orally, 100 min before the induction of anesthesia. The induction of anesthesia, tracheal intubation, and maintenance of anesthesia were performed with sevoflurane in air and oxygen. MAC-ex was defined according to the modification of Dixon’s up-and-down method, with 0.25% as a step size. In addition, in the Control and 4 µg/kg groups, the time from tracheal extubation to spontaneous eye opening (eye-opening time) and the time from tracheal extubation to leaving the operating room (awakening time) were recorded. MAC-ex for sevoflurane (mean ± SD) was 1.63% ± 0.13%, 1.04% ± 0.26%, and 0.66% ± 0.09% respectively in the Control group, 2 µg/kg group, and 4 µg/kg group. Significant differences were observed among the three groups. The eye-opening times were 5.7 ± 3.5 min in the Control group and 5.1 ± 1.0 min in the 4 µg/kg group. The awakening times were 9.7 ± 3.7 min in the Control group and 9.2 ± 3.8 min in the 4 µg/kg group. No significant differences were observed among the groups.
IMPLICATIONS: Oral clonidine premedication decreased MAC for tracheal extubation for sevoflurane dose dependency and did not prolong emergence from anesthesia.
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Introduction
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Clonidine, an  2-adrenoceptor agonist, is an effective premedicant. Clonidine produces anxiolysis, sedation, and hemodynamic stability and reduces analgesic and volatile anesthetic requirements in adults (1–3). In children, oral clonidine premedication also provides preoperative sedation and postoperative analgesia and attenuates the cardiovascular responses to tracheal intubation (4,5). As a side effect, however, clonidine may prolong emergence from anesthesia.
We previously reported that the minimum alveolar concentrations for tracheal extubation (MAC-ex) for sevoflurane were 1.64% (6) and 1.07% (7) for children and adults, respectively. However, the effects of clonidine on MAC-ex for sevoflurane have not been elucidated. The purpose of this study was to investigate the effects of a placebo and oral clonidine premedication (2 or 4 µg/kg) on MAC-ex for sevoflurane on airway-related complications and on emergence from anesthesia in children.
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Methods
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This study was approved by the review board of the Tsukuba University School of Medicine. Informed consent was obtained from the parents of each child. Preoperative examination disclosed no airway malformation, clinical evidence of a difficult airway, asthma, or any sign of upper respiratory infection in any patient.
Sixty pediatric patients were enrolled in this study. The patients, aged 2 to 9 yr (ASA physical status I), were scheduled to have general anesthesia for repair of an inguinal hernia. The patients were randomly divided into one of three groups by an envelope method (n = 20 each). The patients in each of these groups were premedicated with placebo, clonidine 2 µg/kg, or clonidine 4 µg/kg (n = 20 each) orally, 100 min before the estimated time of the induction of anesthesia. The children’s parents were not told beforehand which premedication their child was going to receive, and the children themselves were not informed. All of the patients fasted for a minimum of 5 h before the induction of anesthesia. Opioids or benzodiazepines were not used during the study period. The patients were monitored with an electrocardiogram, a pulse oximeter, and indirect blood pressure. Throughout the study, the inspired and end-tidal gases were measured with a gas monitor (AS/3TM; Datex, Helsinki, Finland), which was calibrated before each use. Inspired and end-tidal gases for measurements were sampled from the distal end of the tracheal tube by using a cannula inserted through the elbow of the circuit so that its tip was within 1 cm of the tip of the tracheal tube. Inspired and end-tidal gases were sampled from the cannula, which was placed within the face mask applied to the patient’s face after tracheal extubation. Accuracy of end-tidal measurements was maximized by confirming the return of the end-tidal CO2 trace to zero and by a square wave configuration to the capnograph tracing.
General anesthesia was induced with up to 5% sevoflurane in an incremental manner, in oxygen, via a face mask with 6 L/min of fresh gas flow. After loss of consciousness, venous access was obtained for the injection of drugs and for infusion. The trachea was intubated with an uncuffed tracheal tube, without any neuromuscular relaxants, by an anesthesiologist who was not informed of the nature of the patient’s premedication. After an airway was secured, a nasogastric tube was advanced into the stomach. The anesthesia depth was judged and adjusted clinically during surgery by using sevoflurane inspired in air and oxygen without neuromuscular relaxants. At the end of the surgery, 0.2 mL/kg of 1% lidocaine was injected around the surgical wound to avoid the effects wound pain has on MAC-ex. The stomach contents were then suctioned via the indwelling nasogastric tube, and the tube was removed from each patient with continuous suction to clear the pharyngeal contents. When the end-tidal sevoflurane concentration reached a predetermined value, the ratio of the end-tidal to inspiratory anesthetic concentration was maintained at 0.95–1.00 for at least 15 min to ensure equilibration with the cerebral anesthetic partial pressure. The trachea was extubated gently by an anesthesiologist who was not informed of the nature of the premedication received by the patient, and then the patient was subsequently administered pure oxygen 6 L/min via a face mask. A smooth tracheal extubation was defined as one without gross purposeful muscular movements within 1 min after extubation. Coughing was considered a purpose-ful movement. Additionally, patients who developed breath-holding or laryngospasm immediately after tracheal extubation were regarded as not having been extubated smoothly. Patients were observed for respiratory complications, such as breath-holding and laryngospasm. Arterial oxygen saturation during emergence from anesthesia was monitored until awakening. The adequacy of the airway was assessed by SpO2 levels, auscultation, observation of the patient’s chest movement, and the end-tidal CO2 wave form with the sampling cannula placed within the face mask. Each sevoflurane concentration at which extubation was attempted was predetermined according to the modification of Dixon’s up-and-down method (8), with 0.25% as a step size, and the starting concentrations were decided in a preliminary trial. A single measurement was obtained per patient. In the Control group and the 4 µg/kg group (which seemed to be the most sedated), the times from tracheal extubation to spontaneous eye opening (eye-opening time) and to leaving the operating room (awakening time) were recorded.
We analyzed values for MAC-ex obtained by calculating the midpoint concentration of all independent pairs of patients involving a cross-over (i.e., smooth extubation to not smooth extubation). MAC-ex was defined as the average of the cross-over midpoints in each cross-over subgroup. In addition, the SD of MAC-ex was the SD of the cross-over midpoint in each group. Patient demographics (age, weight, and height), eye-opening time, and awakening time were expressed as mean ± SD. Statistical comparisons among the three groups were performed with analysis of variance with Fisher’s least significant difference test for post hoc analysis. Statistical comparisons between the two groups were performed with the Mann-Whitney U-test. In all cases, differences were considered statistically significant when P < 0.05.
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Results
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There were no significant differences in the demographic data among the three groups (Table 1). Rectal temperatures were similar among the groups. There were no episodes of hypotension (systolic blood pressure <90 mm Hg) or bradycardia (heart rate <70 bpm). The MAC-ex for sevoflurane was 1.63% ± 0.13%, 1.04% ± 0.26%, and 0.66% ± 0.09% (mean ± SD) in the Control group, the 2 µg/kg group, and the 4 µg/kg group, respectively (Fig. 1). Significant differences were observed in MAC-ex values among the three groups. During emergence from anesthesia, none of the patients exhibited breath-holding or went into laryngospasm. One patient in the subgroup at 1.5% had some coughing before the tracheal extubation. All of the patients with smooth tracheal extubation exhibited a 98% or more hemoglobin oxygen saturation level during the study period. The eye opening times were 5.7 ± 3.5 min in the Control group and 5.1 ± 1.0 min in 4 µg/kg group. The awakening times were 9.7 ± 3.7 min in the Control group and 9.2 ± 3.8 min in the 4 µg/kg group.
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Figure 1. The responses of 20 consecutive patients in whom tracheal extubation was attempted and the end-tidal sevoflurane concentration in oxygen. Each patient’s data were represented with a circle. Minimum alveolar concentrations for tracheal extubation at which a smooth tracheal extubation was possible in 50% of patients were 1.63% ± 0.13% (mean ± SD) in the Control group (top), 1.04% ± 0.26% in the Clonidine 2 µg/kg group (middle), and 0.66% ± 0.09% in the Clonidine 4 µg/kg group (bottom).
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Discussion
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We have shown that MAC-ex for sevoflurane was 1.63% in unpremedicated children. Oral clonidine premedication at 2 or 4 µg/kg successfully decreased MAC-ex for sevoflurane by 36% and 60%, respectively. We previously reported that clonidine decreases sevoflurane requirements in adults (9). In children, oral clonidine 4 µg/kg also reduced the halothane requirement by 45% to attenuate fluctuation of blood pressure and heart rate (10). Furthermore, in our previous study, oral clonidine 4 µg/kg premedication reduced MAC-endotracheal intubation for sevoflurane by approximately 30% (11). MAC-ex for sevoflurane decreased 60% in the 4 µg/kg group in this study.
Stimuli to the mucosa of the larynx and tracheobronchial tree by the tracheal tube are transmitted to the central nervous system by the afferent branches of the superior pharyngeal, glossopharyngeal, and vagus nerves (12). The reason for the difference between the decreasing ratios of MAC for intubation and extubation is unclear. One possibility is that the intensity of the mechanical stimuli produced by tracheal intubation is greater than that produced by tracheal extubation. 2-Adrenoceptor agonists have a sedative effect produced by the activation of the locus ceruleus (13,14) and also have an analgesic effect involving both supraspinal and spinal sites (15–17). However, whether supraspinal or spinal sites influence the MAC could not be elucidated in this study.
In this study, we used oral clonidine premedication at a maximal dose of 4 µg/kg because Mikawa et al. (5) reported that oral clonidine 5 µg/kg premedication caused severe bradycardia requiring treatment with IV atropine. Clonidine alone may cause hypotension or bradycardia. We used clonidine without oral atropine in the 60 children in this study, and the baseline hemodynamic values in the three groups were comparable.
In conclusion, the MAC-ex for sevoflurane (mean ± SD) was 1.63% ± 0.13%, 1.04% ± 0.26%, and 0.66% ± 0.09% in the Control group, Clonidine 2 µg/kg group, and Clonidine 4 µg/kg group, respectively. Oral clonidine did not prolong emergence from anesthesia and not produce airway-related complications.
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References
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Woodcock TE, Millard RK, Dixon J, Prys-Roberts C. Clonidine premedication for isoflurane-induced hypotension. Br J Anaesth 1988; 60: 388–94.[Abstract/Free Full Text]
-
Ghignone M, Calvillo O, Quintin L. Anesthesia and hypertension: the effect of clonidine on perioperative hemodynamics and isoflurane requirements. Anesthesiology 1987; 67: 3–10.[Web of Science][Medline]
-
Ghignone M, Quintin L, Duke PC, et al. Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia and endotracheal intubation. Anesthesiology 1986; 64: 36–42.[Web of Science][Medline]
-
Mikawa K, Maekawa N, Nishina K, et al. Efficacy of oral clonidine premedication in children. Anesthesiology 1993; 79: 926–31.[Web of Science][Medline]
-
Mikawa K, Nishina K, Maekawa N, et al. Oral clonidine premedication reduces postoperative pain in children. Anesth Analg 1996; 82: 225–30.[Abstract]
-
Inomata S, Suwa T, Toyooka H, Suto Y. End-tidal sevoflurane concentration for tracheal extubation and skin incision in children. Anesth Analg 1998; 87: 1263–7.[Abstract/Free Full Text]
-
Inomata S, Yaguchi Y, Taguchi M, Toyooka H. End-tidal sevoflurane concentration for tracheal extubation (MACEX) in adults: comparison with isoflurane. B J Anaesth 1999; 82: 852–6.[Abstract/Free Full Text]
-
Dixon WJ. Quantal response to variable experimentation: the up-and-down method. In: McArthur JW, Colton T, eds. Statistics in endocrinology. Cambridge: MIT Press, 1967: 251–64.
-
Inomata S, Yaguchi Y, Toyooka H. The effects of clonidine premedication on sevoflurane requirements and anesthetic induction time. Anesth Analg 1999; 89: 204–8.[Abstract/Free Full Text]
-
Nishina K, Mikawa K, Maekawa N, Obura H. The efficacy of clonidine for reducing perioperative haemodynamics changes and volatile anaesthetic requirements in children. Acta Anaesthesiol Scand 1996; 40: 746–51.[Web of Science][Medline]
-
Inomata S, Kihara S, Yaguchi Y, et al. Reduction in standard MAC and MAC for intubation after clonidine premedication in children. Br J Anaesth 2000; 85: 700–4.[Abstract/Free Full Text]
-
Harris GD, Johanson WG. Infectivity and respiratory defense mechanisms. In: Guenter CA, ed. Pulmonary medicine. 2nd ed. Philadelphia: JB Lippincott Company, 1982: 297–308.
-
Correa-Sales C, Rabin B, Maze M. A hypnotic response to dexmedetomidine, an agonist, is mediated in the locus coeruleus in rats. Anesthesiology 1992; 76: 948–52.[Web of Science][Medline]
-
de Sarro GB, Ascioti C, Froio F, et al. Evidence that locus coeruleus is the site where clonidine and drugs acting at alpha1 and alpha2 adrenoceptors affect sleep and arousal mechanisms. Br J Pharmacol 1987; 90: 675–85.[Web of Science][Medline]
-
Pertovaara A, Kauppila T, Jyasjarvi E, Kalso E. Involvement of supraspinal and spinal segmental alpha-2 adrenergic mechanisms in the medetomidine-induced antinociception. Neuroscience 1991; 44: 705–14.[Web of Science][Medline]
-
Wang YC, Su SR, Lin MT. The site and mode of analgesic actions exerted by clonidine in monkeys. Environ Neurol 1985; 90: 479–88.
-
Yaksh TL, Reddy SVR. Studies in primate on the analgesic effects associated with intrathecal actions of opiates, alpha2 adrenergic agonists, and baclofen. Anesthesiology 1981; 54: 451–67.[Web of Science][Medline]
Accepted for publication December 18, 2001.
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Abstract
Introduction
