Paediatric Anaesthesia 2000 10: 65–67

Pretreatment with oral clonidine attenuatescardiovascular responses to tracheal extubationin children

YOSHITAKA FUJII md∗ , YUHJI SAITOH md†,

HIROYOSHI TANAKA md† AND

HIDENORI TOYOOKA md∗∗Department of Anaesthesiology, University of Tsukuba Institute of Clinical Medicine,Tsukuba City, Ibaraki, Japan and †Department of Anaesthesiology, Toride Kyodo GeneralHospital, Toride City, Ibaraki, Japan

SummaryThis study was designed to evaluate the effects of diazepam and

clonidine orally given preoperatively on cardiovascular responses to

tracheal extubation in children. Fifty children, ASA physical status I,

aged 4–10 years, undergoing minor elective surgery (inguinal hernia,

phimosis) received orally, in a randomized, double-blind manner,

diazepam 0.4 mg·kg–1 or clonidine 4 lg·kg–1 (n=25 of each). These

drugs were administered 105 min before an inhalational induction of

anaesthesia. The same standard general anaesthetic technique was

employed throughout. The maximum changes in heart rate (HR),

systolic blood pressure (SBP) and diastolic blood pressure (DBP)

were less in patients who had received clonidine than in those who

had received diazepam (HR, 12 vs 24; SBP, 14 vs 26; DBP, 9 vs 16;

mean, P < 0.05). In conclusion, compared to diazepam given orally,

pretreatment with oral clonidine attenuates haemodynamic changes

associated with tracheal extubation in children.

Keywords: complications: tachycardia, hypertension; pharmacology,

clonidine, diazepam

Introduction available studies to evaluate the effect of clonidine

given orally preoperatively on haemodynamicClonidine, an a2 agonist, has been demonstrated to

changes during tracheal extubation in children. Thisbe a useful preanaesthetic medication in children

study was designed to compare cardiovascularbecause of its sedative and analgesic properties (1,

responses to tracheal extubation between paediatric2). It also attenuates cardiovascular responses to

patients receiving oral clonidine and those giventracheal intubation in paediatric patients (1,3).

orally diazepam as premedication.Tracheal extubation, as well as intubation, is often

accompanied by marked increases in heart rate andMethodsarterial blood pressure (4,5). However, there are no

After obtaining institutional approval and parental

informed consent, we studied 50 children, ASACorrespondence to: Yoshitaka Fujii, Department of Anaesthesiology,

physical status I, aged 4–10 years, undergoing generalUniversity of Tsukuba Institute of Clinical Medicine, 2–1–1,

Amakubo, Tsukuba City, Ibaraki 305, Japan. inhalation anaesthesia for minor elective surgery

65 2000 Blackwell Science Ltd

66 Y. FUJII ET AL.

Table 1(inguinal hernia, phimosis). Patients were notPatient dataallowed to have solid food after midnight before

surgery. Clear liquids were permitted up to 3 h Diazepam Clonidinepreoperatively. (n=25) (n=25)

Patients were randomly divided into two groupsAge (years) 6.8 (2.2) 6.6 (2.3)

(n=25 of each) using computer-generated randomSex (male /female) 15/10 14/11

numbers concealed in envelopes, to receive orally Height (cm) 120.8 (10.7) 120.1 (13.4)

Weight (kg) 24.4 (6.6) 24.6 (7.1)diazepam 0.4 mg·kg–1 or clonidine 4 lg·kg–1. AsDuration of surgery (min) 41 (15) 40 (19)demonstrated in several reports (1–3), these drugsDuration of anaesthesia (min) 60 (17) 61 (21)

are administered 105 min before an inhalational Types of surgery (n)

Inguinal hernia 20 21induction of anaesthesia. Syrups with diazepam orPhimosis 5 4clonidine were prepared for each study group by a

pharmacist.Values are mean (SD) or number. There were no differences

Routine monitoring, including noninvasive blood between the groups.

pressure (BP), heart rate (HR) and oxygen saturation

(SpO2), was used in the operating room. Anaesthesia

Bonferroni’s modification of t-test for parametricwas induced by increasing concentration of sevo-

data, and with chi-squared test for nonparametricflurane in nitrous oxide (N2O) and oxygen (O2) via

data. A P < 0.05 was considered significant. Data wereface mask, after which atropine 0.01 mg·kg–1 was

mean (sd) or number. Power analysis was used toadministered i.v., followed by fentanyl 1 lg·kg–1 i.v.,

determine the number of patients in the study basedand tracheal intubation was performed without

on the assumptions that: (a) the incidence ofmuscle relaxants. After tracheal intubation, anaesthesia

diazepam-treated patients experiencing coughingwas maintained with N2O/O2 (2:1) and sevoflurane

would be 45%; (b) a reduction from 45% to 15% was1.0–3.5% (endtidal concentration). Ventilation was

considered of clinical importance; and (c) a=0.05manually assisted and was adjusted to maintain PeCO2

and a power (1–b)=0.8. Based on these assumptions,between 4.6 kPa and 5.2 kPa (34–38 mmHg) with an

25 patients per group were required.anaesthetic/respiratory analyser (UltimaTM, Datex,

Helsinki, Finland). Muscle relaxants were not used

throughout surgery. The SpO2 was maintained > 95%. ResultsAll patients received a regional nerve block (caudal)

Patient profiles and information on surgery andwith 0.25% bupivacaine 0.5 mg·kg–1 administered

anaesthesia are summarized in Table 1. There were nobefore surgery, for postoperative analgesia.

difference in demographic data between the groups.After the end of surgery, patients received O2 100%

The changes in HR, SBP and DBP after trachealfor at least 5 min. The trachea was extubated when

extubation were less in patients receiving clonidinethe patient was awake (facial grimace, adequate

than in those given diazepam (P < 0.05) (Table 2).tidal volume, open eye), and when the endtidal

The number of patients experiencing coughingconcentration of sevoflurane was < 0.1%. After

was fewer in clonidine-treated patients (n=4) thantracheal extubation, 100% O2 was administered via a

in diazepam-treated patients (n=11) (P < 0.05). Noneface mask for 10 min

had laryngospasm, breath-holding, nor hypoxaemiaWe found in a previous study that HR, systolic

(SpO2 95%).BP (SBP) and diastolic BP (DBP) measured at the

completion of surgery could serve as baseline values

(6). Subsequent measurements were taken at 1, 2, 3, 5 Discussionand 10 min after tracheal extubation. Airway-related

complications (coughing, laryngospasm, breath- We confirmed that tracheal extubation caused tachy-

cardia and hypertension, and that these haemo-holding) and hypoxaemia (SpO2 < 95%) were also

recorded. dynamic changes were attenuated by clonidine given

orally and preoperatively. During and after trachealStatistical analysis was performed with two-way

(time and group) analysis of variance followed by extubation, plasma concentrations of catecholamines

2000 Blackwell Science Ltd, Paediatric Anaesthesia, 10, 65–67

PRETREATMENT WITH ORAL CLONIDINE 67

Table 2Haemodynamic data

After tracheal extubation

Variable Group Baseline 1 min 2 min 3 min 5 min 10 min

HR (b.p.m.) Diazepam 106 (10) 130 (10∗ 123 (8)∗ 119 (9)∗ 113 (8) 103 (9)

Clonidine 104 (8) 116 (8)∗† 111 (8)∗† 106 (8)† 103 (7)† 100 (7)

SBP (mmHg) Diazepam 104 (10) 130 (10)∗ 125 (10)∗ 119 (11)∗ 113 (10)∗ 104 (9)

Clonidine 106 (10) 120 (10)∗† 115 (9)∗† 111 (8)† 106 (8)† 103 (8)

DBP (mmHg) Diazepam 58 (10) 74 (9)∗ 70 (8)∗ 67 (8)∗ 63 (8)∗ 57 (9)

Clonidine 55 (8) 64 (10)∗† 61 (10)∗† 657 (10)† 55 (9)† 54 (9)

Values are mean (sd). HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure. P < 0.05 vs baseline (the completion of

surgery). †P < 0.05 vs diazepam.

(adrenaline, noradrenaline) are reported to increase complications, such as cerebral vascular accidents or

(7). The exact mechanism responsible for tachycardia cardiac dysrhythmias, due to excessive sympathetic

and hypertension after tracheal extubation is not responses (4,5). However, on the basis of our results,

known, but these haemodynamic changes may be clonidine successfully controlled haemodynamic

associated with the release of catecholamines during changes and improved haemodynamic stability

this period. In the current study, pretreatment with during tracheal extubation in children.oral clonidine was more effective than diazepam In conclusion, compared to oral diazepam,given orally and preoperatively for suppressing the pretreatment with clonidine given orally attenuatesincreases in HR and BP, which may be related to the cardiovascular responses to tracheal extubation ininhibition of catecholamine release. children undergoing inhalational anaesthesia for

We could not find any report to determine the minor elective surgery (inguinal hernia, phimosis).effective dose of oral diazepam or clonidine given

preoperatively for attenuating cardiovascular

responses to tracheal extubation in children. The Referencesdoses of oral preanaesthetic diazepam 0.4 mg·kg–1

1 Mikawa K, Maekawa N, Nishina K et al. Efficacy of oraland clonidine 4 lg·kg–1, used in this study were clonidine premedication in children. Anesthesiology 1993; 79:

926–931.chosen from the results of several studies on the2 Mikawa K, Nishina K, Maekawa N et al. Oral clonidineattenuation of haemodynamic changes associated

premedication reduces postoperative pain in children. Anesthwith tracheal intubation in paediatric patients (1,3). Analg 1996; 82: 225–230.Higher doses of this preanaesthetic medication may 3 Mikawa K, Nishina K, Maekawa N et al. Attenuation of the

catecholamine response to tracheal intubation with oralincrease clinically serious adverse effects (8).clonidine in children. Can J Anaesth 1995; 42: 869–874.

Tracheal extubation irritates airways causing4 Hartley M, Vaughan RS. Problems associated with tracheal

coughing, which is known to increase HR and BP. extubation. Br J Anaesth 1993; 71: 561–568.

5 Miller KA, Harkin CP, Baliley PL. Postoperative trachealThis notion is based on the observation that coughingextubation. Anesth Analg 1995; 80: 149–172.leads to increased intrathoracic pressure which

6 Fujii Y, Toyooka H, Tanaka H. Cardiovascular responses tointerferes with venous return to the heart (5). In this

tracheal extubation or LMA removal in normotensive andclinical trial, the number of patients who experienced hypertensive patients. Can J Anaesth 1997; 44: 1082–1086.

7 Lowrie A, Johnston PL, Fell D et al. Cardiovascular and plasmacoughing was fewer in clonidine-treated patientscatecholamine responses at tracheal extubation. Br J Anaesththan in diazepam-treated patients (P < 0.05).1992; 68: 261–263.

Therefore, it is suggested that pretreatment with oral 8 Steward DJ. Psychological preparation and premedication. In:

Gregory GA, ed. Pediatric Anesthesia, 2nd edn. New York:clonidine compared with diazepam may attenuateChurchill Livingstone, 1989: 523–538.the laryngeal irritation.

Tachycardia and hypertension following tracheal

extubation put the patient at risk of developing Accepted 26 April 1999

2000 Blackwell Science Ltd, Paediatric Anaesthesia, 10, 65–67