1Department of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110,D-69120 Heidelberg, Germany 2Present address: Department of Anaesthesiology, University of Tübingen, Germany*Corresponding author
Presented in part at the meeting of the German Society of Anaesthesiology, May 58, 1999, Wiesbaden, Germany and the Annual Meeting of the American Society of Anesthesiologists, October 913, 1999, Dallas, Texas.
Accepted for publication: February 13, 2002
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Abstract |
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Methods. Eighty children aged 38 yr (ASA III) received standardized general anaesthesia with inhaled sevoflurane and caudal epidural block with 0.175% bupivacaine 1 ml kg1 for minor surgery. The children were assigned randomly to four groups: (I) clonidine 1 µg kg1 added to caudal bupivacaine; (II) clonidine 3 µg kg1 added to caudal bupivacaine; (III) clonidine 3 µg kg1 i.v. and caudal bupivacaine; and (IV) caudal block with bupivacaine, no clonidine (control). A blinded observer assessed the behaviour of the children during the first postoperative hour. Secondary end-points were the time to fitness for discharge from the postanaesthesia care unit, and haemodynamic and respiratory variables.
Results. The incidence of agitation was 22, 0, 5 and 39% in groups I, II, III and IV respectively (P<0.05 for groups II and III compared with group IV). During the first hour after surgery, patients in groups II and III had significantly lower scores for agitation than group IV patients. Time to fitness for discharge did not differ between the four groups.
Conclusions. Clonidine 3 µg kg1 prevented agitation after sevoflurane anaesthesia, independently of the route of administration. The effect of clonidine appears to be dose-dependent, as an epidural dose of 1 µg kg1 failed to reduce it.
Br J Anaesth 2002; 88: 7906
Keywords: anaesthetics volatile, sevoflurane; complications; sympathetic nervous system, 2-adrenergic agonists; anaesthesia, paediatric
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Introduction |
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Methods |
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Patients allocated to group I, II or IV received i.v. saline as placebo. All the drug combinations in the study were prepared before induction of anaesthesia, leaving the observer unaware of the group assignment.
Measurements
We defined the primary end-point of the study as the incidence of postanaesthetic agitation. The Pain/Discomfort Scale6 (see Appendix 1) was used to determine agitation. This scale evaluates postoperative pain or discomfort in children. Due to the technique used, we could exclude pain as the cause of agitation in the first postoperative hour. We noted the maximum score during the first hour after the end of administration of sevoflurane and the scores at four fixed time-points: 15, 30, 45 and 60 min after administration of the inhalational anaesthetic ceased. The scores for movement, agitation and posture on the Pain/Discomfort Scale (items 35)6 and the results of a scoring system for motor restlessness (graded as none, moderate and restless) were determined at these four time-points during the first hour after emergence from anaesthesia. As in other studies, we defined a total score of 3 at any time-point for items 35 of the Pain/Discomfort Scale as an indication of postanaesthetic agitation.7 The time the patient was ready to be discharged from the PACU was regarded as a secondary end-point. To determine fitness for discharge, the Aldrete and Kroulik scoring system8 was modified as described in Appendix 2. The incidences of cardiocirculatory and respiratory depression also served as secondary end-points.
Study protocol
Anaesthetic management was standardized in all children. We measured blood pressure by oscillometry (PM 8060 Vitara; Dräger, Lübeck, Germany) at 5 min intervals, heart rate continuously using the ECG (PM 8060 Vitara) and peripheral arterial oxygen saturation (SaO2) by pulse oximetry (PM 8060 Vitara). Thirty minutes after the patients had received midazolam 0.4 mg kg1 orally as premedication, anaesthesia was induced with 4% sevoflurane and 50% nitrous oxide in oxygen using the mask technique with a fresh gas flow of 6 litre min1. When the children were adequately anaesthetized, we inserted an i.v. cannula (22 or 24-gauge) and gave atropine 0.1 mg kg1 and a single dose of atracurium 0.3 mg kg1. After intubation of the trachea, the lungs were ventilated mechanically to adjust the end-tidal PCO2 to 4.85.3 kPa (PM 8060 Vitara) using a Cicero EM (Dräger). Lactated Ringers solution was given i.v. at an infusion rate of 6 ml kg1 h1 and anaesthesia was maintained with 2% sevoflurane and 70% nitrous oxide in oxygen with a fresh gas flow of 2 litre min1. We then turned the children to the right lateral position and inserted a 20-gauge short-bevel needle (PlexofixTM; Braun Melsungen Medical, Melsungen, Germany) into the caudal space through the sacrococcygeal ligament using an aseptic technique. If no blood or cerebrospinal fluid was aspirated, the randomized study drug was given. No further analgesic or sedative drugs were given.
After induction of anaesthesia, the children were transferred from the anaesthesia induction room to the operating theatre, where they were draped using a double layer of cotton blankets. After skin incision, we reduced the inspired sevoflurane concentration to the level at which the patient did not respond to a surgical stimulus with either movement or an increase in heart rate or blood pressure by more than 15% of the presurgical level. If the resulting end-tidal concentration of sevoflurane was 1.0% or lower, we judged the caudal block to be effective. At the beginning of skin closure, we turned off the sevoflurane and nitrous oxide and ventilated the childs lungs with 100% oxygen at a fresh gas flow rate of 6 litre min1. As we used a single dose of atracurium, neuromuscular block was not antagonized. After exclusion of signs of residual neuromuscular block and the return of sufficient spontaneous ventilation and the gag reflex, the tracheal tube was removed and the child was transferred to the recovery room, where heart rate and SaO2 were monitored continuously for 3 h. Blood pressure was recorded non-invasively at 30 min intervals. All children had at least one parent in attendance during recovery. As rescue medication against agitation, the patients received piritramide (incremental doses of 0.05 mg kg1 i.v.) on request or when the Pain/Discomfort Scale score was 6 or higher. One blinded observer, who was introduced to the patients and their parents the day before surgery and who stayed with the patients throughout the study period, recorded all the data. This observer was not involved in the perioperative anaesthetic management of the patients. Parental satisfaction and possible complications after the observation period were recorded by a later telephone interview and by reviewing the patients records.
Data analysis
Data are presented as mean (SD). Time-dependent results were evaluated using two-factorial analysis of variance with repeated measurements followed by the post hoc Scheffé test. The unpaired two-tailed t-test, the KruskalWallis test and the Wilcoxon test or 2 test, as appropriate, were used to compare results in the treatment groups. For the calculations, a personal computer and MedCalc software version 6.0 (MedCalc, Mariakerke, Belgium) were used. P<0.05 was taken to indicate statistical significance. According to a power analysis (with correction for four groups of patients to be compared), a sample size of 19 patients per group would have a power of 80% to detect a reduction in the incidence of agitation from 50 to 5%.
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Results |
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Fitness for discharge from the PACU was achieved after 93 (40) min in group I compared with 81 (48) min in group II, 104 (42) min in group III and 89 (50) min in group IV (not significant). During the study period, four children in group I required piritramide compared with one child in group II, two children in group III and seven children in group IV (P<0.05 for group II in comparison with group IV). The patient in group II received piritramide 102 min after stopping sevoflurane for recurrence of pain. One patient in group III was treated with piritramide immediately after extubation of the trachea because of postoperative agitation, and the second patient in this group received piritramide 110 min after extubation for pain relief, not to treat postoperative agitation. In groups I and IV, piritramide was given solely for agitation.
Before and during the operation, the mean arterial pressure (Fig. 2) was significantly lower in group II and III than in group IV (P<0.05). During the first 120 min after surgery, only patients receiving clonidine i.v. (group III) had significantly lower mean arterial pressures (P<0.05). Heart rates in patients receiving caudal or i.v. clonidine did not differ significantly from those in the control group (group IV) (Fig. 2). However, there was a trend among children in group III towards lower heart rates. No respiratory depression was found in any group. Nausea or vomiting was observed in three patients in group I, two patients in group II, four patients in group III and three patients in group IV (no significant difference). One patient in group II complained of not being able to urinate during the first 24 h after surgery. In all groups, more than 85% of the parents were satisfied with anaesthesia and there were no significant differences between the groups.
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Discussion |
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Involuntary jerking movements combined with muscular hypertonia of the trunk and extremities characterize agitation after anaesthesia with sevoflurane. This kind of restlessness has been observed in 4067% of patients in the majority of sevoflurane studies.3 7 1012 Agitation in 38% of the patients receiving i.v. and epidural placebo in our study confirms these findings. However, in a review of all the sevoflurane literature, the incidence of postanaesthetic agitation varied from 8%2 to 100%,1 depending in particular on the definition of the phenomenon and the primary end-points of the investigation. We attempted to solve this methodological problemof defining exactly this delirious postoperative stateby using different scoring systems and a definition of agitation closely related to that used in previous investigations.7 Moreover, we examined both the time-course of the values obtained by the scoring systems and the maximal score registered during the observation period. As items 1, 2 and 6 of the Pain/Discomfort Scale address haemodynamic variables and pain (Appendix 1), we also performed a separate evaluation of items 35 of the scale, in accordance with other authors.7 As involuntary movements characterize excitement after sevoflurane, we additionally evaluated a classification of motor restlessness. Our study therefore addresses several aspects of this problem for the first time. Moreover, we only evaluated the children during the first postanaesthetic hour, in order to rule out any influence of other disturbances and the occurrence of pain on the behaviour of the children.
Postanaesthetic agitation seems to be a problem closely related to the use of sevoflurane, as it occurred more frequently after sevoflurane than after halothane anaesthesia in the majority of studies.14 7 11 13 14 In two investigations,10 12 no significant difference in the incidence of agitation was found, whereas only one study15 reported a higher incidence of delirium after halothane than after sevoflurane. In particular, potent inhalational anaesthetics with a low bloodgas partition coefficient and a rapid speed of emergence seem to be associated with agitation, as a higher incidence of delirium was also found after desflurane than after halothane.15 16 After anaesthesia with the newer potent inhalational anaesthetics, such as sevoflurane and desflurane, rapid waking in an unknown, potentially frightening environment with no parent present might provoke agitation further. In order to exclude this prospectively, we allowed parental presence in the PACU. Pain seems to be another factor which influences postanaesthetic agitation as its incidence was lower in children receiving adequate analgesia before emergence from anaesthesia.1 12 However, a high incidence of agitation was also observed after sevoflurane among children receiving anaesthesia for an intervention which was not painful;4 this supports the results from our control group (group IV), in which agitation was present despite adequate pain therapy from caudal analgesia and a parental presence in the recovery room.
For the management of these delirious states, opioids15 and non-steroidal analgesics10 12 or sedatives are often proposed, but they carry the risk of respiratory depression, increased bleeding and a longer period of postoperative observation. In contrast, we did not observe either clinically relevant circulatory side-effects or respiratory side-effects when we used clonidine to prevent postanaesthetic agitation. This is in accordance with another report,17 in which the sedative effect of clonidine was not associated with respiratory depression in adult volunteers, and data on the use of clonidine in children with18 or without concomitant administration of atropine during induction of anaesthesia.19 20 When given as oral premedication, clonidine 4 µg kg1 failed to reduce the incidence of postoperative agitation in comparison with children who received midazolam 0.5 mg kg1 orally as premedication.21 The authors explained their observation by the superior preoperative anxiolytic effect of midazolam. We, therefore, also used midazolam for preoperative anxiolysis. However, on the basis of our results we recommend the use of clonidine after induction of anaesthesia.
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Appendix 1 |
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Appendix 2 |
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Acknowledgement |
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References |
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2 Lerman J, Davis PF, Welborn LG, et al. Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery: a comparison with halothane. Anesthesiology 1996; 84: 133240[ISI][Medline]
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Hall JE, Uhrich TD, Ebert TJ. Sedative, analgesic and cognitive effects of clonidine infusions in humans. Br J Anaesth 2001; 86: 511
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Fazi L, Jantzen EC, Rose JB, Kurth D, Watcha MF. A comparison of oral clonidine and oral midazolam medications in the pediatric tonsillectomy patient. Anesth Analg 2001; 92: 5661