Comparison of caudal and intravenous clonidine in the prevention of agitation after sevoflurane in children{dagger}

M. Bock*,1, P. Kunz1,2, R. Schreckenberger1, B. M. Graf1, E. Martin1 and J. Motsch1

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

{dagger}Presented in part at the meeting of the German Society of Anaesthesiology, May 5–8, 1999, Wiesbaden, Germany and the Annual Meeting of the American Society of Anesthesiologists, October 9–13, 1999, Dallas, Texas.

Accepted for publication: February 13, 2002


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
Background. In children, sevoflurane anaesthesia is associated with postanaesthetic agitation, which is treated mainly with opioids. We compared the effectiveness of epidural and i.v. clonidine in the prevention of this postanaesthetic agitation.

Methods. Eighty children aged 3–8 yr (ASA I–II) received standardized general anaesthesia with inhaled sevoflurane and caudal epidural block with 0.175% bupivacaine 1 ml kg–1 for minor surgery. The children were assigned randomly to four groups: (I) clonidine 1 µg kg–1 added to caudal bupivacaine; (II) clonidine 3 µg kg–1 added to caudal bupivacaine; (III) clonidine 3 µg kg–1 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 kg–1 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 kg–1 failed to reduce it.

Br J Anaesth 2002; 88: 790–6

Keywords: anaesthetics volatile, sevoflurane; complications; sympathetic nervous system, {alpha}2-adrenergic agonists; anaesthesia, paediatric


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
Sevoflurane is used frequently in paediatric patients,1 2 when inhalational induction of anaesthesia is required, because of its non-irritating effects on the airway. The speed of emergence from sevoflurane anaesthesia, however, sometimes presents a dilemma to both patient and anaesthetist. In recent studies, a higher incidence of postanaesthetic agitation has been attributed to the use of this newer inhalational anaesthetic.3 However, the exact aetiology of restlessness after sevoflurane anaesthesia is still not known. Postoperative pain is regarded as a contributing factor, but the phenomenon is also present when there is adequate pain control.4 Concern about pain, the presence of strangers or a rapid return to consciousness in an unfamiliar environment might themselves further provoke postanaesthetic agitation in children. Indeed, this problem is regarded as so severe that some authors have underlined the need for further studies on the safety of sevoflurane,5 although the drug has distinct benefits in paediatric anaesthesia. The use of analgesics or sedatives has been proposed for the management of these restless postanaesthetic states. However, the side-effects of these drugs, including respiratory depression, are potentially harmful and lead to an increased length of stay in the postanaesthesia care unit (PACU), resulting in patient discomfort and increased perioperative costs. We designed this double-blind study to investigate the effect of different routes of clonidine administration on the incidence of postanaesthetic agitation in children aged 3–8 yr undergoing minor surgery under combined caudal and inhalational anaesthesia. Furthermore, time to fitness for discharge from the PACU and the cardiovascular and respiratory side-effects of clonidine were evaluated.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
After we had obtained institutional approval and informed parental consent, we enrolled 80 healthy children of American Society of Anesthesiologists (ASA) physical status I–II, aged 3–8 yr, in the study. Exclusion criteria were known endocrine disease, a family history of malignant hyperthermia, aortic stenosis, signs of infection and preoperative agitation. The children were randomized into four groups according to a computer-generated code. After induction of anaesthesia, a caudal epidural block was performed in all the children by injecting 0.175% bupivacaine 1 ml kg–1 into the caudal space. The children received the following drug combinations: (group I) clonidine 1 µg kg–1 was added to caudal 0.175% bupivacaine 1 ml kg–1; (group II) clonidine 3 µg kg–1 was added to caudal bupivacaine 0.175% (1 ml kg–1); (group III) clonidine 3 µg kg–1 was injected i.v. and caudal block was performed with 0.175% bupivacaine 1 ml kg–1; (group IV) caudal block with 0.175% bupivacaine 1 ml kg–1 without i.v. or epidural clonidine (control group).

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 3–5)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 3–5 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 kg–1 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 min–1. When the children were adequately anaesthetized, we inserted an i.v. cannula (22 or 24-gauge) and gave atropine 0.1 mg kg–1 and a single dose of atracurium 0.3 mg kg–1. After intubation of the trachea, the lungs were ventilated mechanically to adjust the end-tidal PCO2 to 4.8–5.3 kPa (PM 8060 Vitara) using a Cicero EM (Dräger). Lactated Ringer’s solution was given i.v. at an infusion rate of 6 ml kg–1 h–1 and anaesthesia was maintained with 2% sevoflurane and 70% nitrous oxide in oxygen with a fresh gas flow of 2 litre min–1. 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 child’s lungs with 100% oxygen at a fresh gas flow rate of 6 litre min–1. 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 kg–1 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 patient’s 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 Kruskal–Wallis test and the Wilcoxon test or {chi}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%.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
We enrolled 80 patients. Two patients had to be excluded from further evaluation because of preoperative excitation and in six patients the end-tidal concentration of sevoflurane could not be reduced below the predetermined threshold. Caudal block was therefore judged ineffective according to the criteria of the study protocol and these children were withdrawn from further evaluation. Seventy-two patients (18 in each group) completed the study. There were no differences between groups with respect to age, height, weight, sex, ASA classification, type and duration of surgery or end-tidal concentration of sevoflurane when starting to close the skin incision (Table 1). The time-course of the end-tidal concentration of sevoflurane did not differ between groups during anaesthesia.


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Table 1 Patient characteristics and end-tidal concentration of sevoflurane before starting to close the skin incision. No significant difference was found between groups. Data are mean (SD or range) or number of patients. All the patients received caudal 0.175% bupivacaine 1 ml kg–1
 
Postanaesthetic agitation was observed in four patients in group I, no patient in group II, one patient in group III and seven patients in group IV (P<0.05 for group II or III compared with group IV). Expressed as the number needed to treat, in group I seven patients would need to have been treated in order to prevent agitation compared with three in groups II and III respectively. During the observation period, the scores obtained using the Pain/Discomfort Scale and the scores for motor restlessness were significantly lower among patients receiving clonidine 3 µg kg–1 i.v. or caudally than among patients in the control group. The data for the items 3–5 of the Pain/Discomfort Scale are shown in Figure 1. Similar scores were obtained for the other items on this scale. The other scoring systems produced similar results.



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Fig 1 Time course of total score obtained using items 3–5 of the Pain/Discomfort Scale in the four groups (I–IV) during the first 60 min after stopping sevoflurane (P<0.01 for group II or III compared with group IV at each time-point).

 
In comparison with group I, we found a lower score for the entire Pain/Discomfort Scale in group III during the first hour after cessation of anaesthesia (P<0.05). Additionally, the values obtained for motor restlessness were significantly lower in group I than in group IV. Table 2 presents the average maximal scores obtained using all the items of the Pain/Discomfort Scale, the use of items 3–5 only of the Pain/Discomfort Scale, and the evaluation of motor restlessness during the first hour after discontinuation of the potent inhalational anaesthetic.


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Table 2 Average maximal scores obtained for the complete Pain/Discomfort Scale, using items 3–5 of the Pain/Discomfort Scale, and for motor restlessness in the first hour after cessation of anaesthesia. Data are median (75% quartile). *P<0.01 compared with group IV; {dagger}P<0.01 compared with group I
 
The maximal scores were again significantly lower among patients receiving clonidine 3 µg kg–1 i.v. or caudally (P<0.01). After caudal administration of clonidine 1 µg kg–1 (group I), we did not find a statistically significant difference with respect to the control group. Patients in group III had lower maximal scores than those in group I (P<0.01).

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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Fig 2 Time course of mean arterial pressure (MAP) and heart rate (HR). T0=baseline, without anaesthesia; T1=intubation of the trachea; T2=on entering operating theatre; T3=skin incision; T4=15 min after skin incision; T5=stopping sevoflurane; T6=end of the operation; T7=extubation. Numbers after T7 are minutes after end of administration of sevoflurane.

 

    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
In this study we have shown that clonidine 3 µg kg–1 is effective in preventing agitation after sevoflurane anaesthesia. We used various methods of measuring this postoperative state in order to quantify as precisely as possible what can be considered a mental disturbance. As a smaller dose of clonidine (1 µg kg–1) failed to prevent postanaesthetic agitation, a dose-dependent mechanism of action of the drug is likely. Clonidine is more effective in producing pain relief after epidural than after i.v. administration, and we have shown that the same is not true for the prevention of postanaesthetic agitation. However, a dose of clonidine 1 µg kg–1 might have been effective after i.v. administration. It is possible that clonidine exerts its effect after systemic absorption, so that a smaller dose would be needed by the i.v. route. The results of our study confirm those of a recently published investigation in which children were less agitated after i.v. administration of clonidine 2 µg kg–1.9 In that study, the end-tidal concentration of sevoflurane was adjusted to a minimum alveolar concentration of 1.5, whereas we investigated agitation after smaller doses of the potent inhalational anaesthetic. The effect of clonidine in reducing the incidence of postanaesthetic agitation seems to be independent of the route of administration as it was reduced by caudal and i.v. clonidine 3 µg kg–1. As all our patients were healthy, no oxygen desaturation occurred, and as fluid and pain therapy were adequate we can exclude hypoxia, pain and metabolic disturbance as causes of the agitation.

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 40–67% 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 problem—of defining exactly this delirious postoperative state—by 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 3–5 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 blood–gas 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 kg–1 failed to reduce the incidence of postoperative agitation in comparison with children who received midazolam 0.5 mg kg–1 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.


    Appendix 1
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
The Pain/Discomfort Scale6 is given in Table 3.


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Table 3 Pain/Discomfort Scale
 

    Appendix 2
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
Criteria for discharge from the PACU
The scoring system suggested by Aldrete and Kroulik8 was modified as shown in Table 4. We required a score of 12 points, the absence of bleeding and a period of at least 30 min after the last dose of piritramide.


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Table 4 Criteria for discharge from the PACU
 

    Acknowledgement
 
We thank H. Bauer of the Department of Anaesthesiology, University of Heidelberg, for performing the statistical analyses.


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
1 Johannesson GP, Florén M, Lindahl SGE. Sevoflurane for ENT surgery in children: a comparison with halothane. Acta Anaesthesiol Scand 1995; 39: 546–50[ISI][Medline]

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: 1332–40[ISI][Medline]

3 Aono J, Ueda W, Mamiya K, Takimoto E, Manabe M. Greater incidence of delirium during recovery from sevoflurane anesthesia in preschool boys. Anesthesiology 1997; 87: 1298–300[ISI][Medline]

4 Cravero J, Surgenor S, Whalen K. Emergence agitation in paediatric patients after sevoflurane anaesthesia and no surgery: a comparison with halothane. Paediatr Anaesth 2000; 10: 419–24[ISI][Medline]

5 Holzki J, Kretz FJ. Changing aspects of sevoflurane in paediatric anaesthesia: 1975–99. Paediatr Anaesth 1999; 9: 283–6

6 Hannallah RS, Broadman LM, Belmann AB, Abramowitz MD, Epstein BS. Comparison of caudal and ilioinguinal/iliohypogastric nerve blocks for control of post-orchiopexy pain in pediatric ambulatory surgery. Anesthesiology 1987; 66: 832–4[ISI][Medline]

7 Vitanen H, Baer G, Annila P. Recovery characteristics of sevoflurane or halothane for day-case anaesthesia in children aged 1–3 years. Acta Anaesthesiol Scand 2000; 44: 101–6[ISI][Medline]

8 Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg 1970; 49: 924–34[Medline]

9 Kulka PJ, Bressem M, Tryba M. Clonidine prevents sevoflurane-induced agitation in children. Anesth Analg 2001; 93: 335–8[Abstract/Free Full Text]

10 Naito Y, Tamai S, Shingu K, Fujimori R, Mori K. Comparison between sevoflurane and halothane for paediatric ambulatory anaesthesia. Br J Anaesth 1991; 67: 387–9[Abstract]

11 Lapin SL, Auden SM, Goldsmith LJ, Reynolds AN. Effects of sevoflurane anaesthesia on recovery in children: a comparison with halothane. Paediatr Anaesth 1999; 9: 299–304[ISI][Medline]

12 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]

13 Beskow A, Westrin P. Sevoflurane causes more postoperative agitation in children than does halothane. Acta Anaesthesiol Scand 1999; 43: 536–44[ISI][Medline]

14 Rieger A, Schröter G, Philippi W, Haas I, Eyrich K. A comparison of sevoflurane with halothane in outpatient adenotomy in children with mild upper respiratory tract infections. J Clin Anesth 1996; 8: 188–93[ISI][Medline]

15 Welborn LG, Hannallah RS, Norden JM, Ruttimann UE, Callan CM. Comparison of emergence and recovery characteristics of sevoflurane, desflurane, and halothane in pediatric ambulatory patients. Anesth Analg 1996; 83: 917–20[Abstract]

16 Davis PJ, Todd Cohen I, McGowan FX, Latta K. Recovery characteristics of desflurane versus halothane for maintenance of anesthesia in pediatric ambulatory patients. Anesthesiology 1994; 80: 298–302[ISI][Medline]

17 Hall JE, Uhrich TD, Ebert TJ. Sedative, analgesic and cognitive effects of clonidine infusions in humans. Br J Anaesth 2001; 86: 5–11[Abstract/Free Full Text]

18 Bock M, Kunz P, Martin E, Motsch J. Intravenous or caudal clonidine does not influence core temperature in children. J Therm Biol 2000; 25: 143–6[ISI]

19 Motsch J, Böttiger BW, Bach A, Böhrer H, Skoberne T, Martin E. Caudal clonidine and bupivacaine for combined epidural and general anaesthesia in children. Acta Anaesthesiol Scand 1997; 41: 877–83[ISI][Medline]

20 Klimscha W, Chiari A, Michalek-Sauberer A, et al. The efficacy and safety of a clonidine/bupivacaine combination in caudal blockade for pediatric hernia repair. Anesth Analg 1998; 86: 54–6[Abstract]

21 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: 56–61[Abstract/Free Full Text]