Bradycardia in Anesthetized Children : Experience over an 8-Year Period at Songklanagarind Hospital Witthaya Loetwiriyakul M.D.,* Mayuree Vasinanukorn M.D.,* Thida Ua-kritdathikarn M.D.* àõ : «À «µâπ â π Á Ë â ß «Ÿâ : ª å 8 ªï π ßæ ß π π å «ÿ æ..,* ÿ π πÿ æ..,* Õ ÈÕ ƒ æ..* * «««æ» µ å À «ß π π å Õ. À À à. ß 90110 À Ë : âõ 54 Õß «À «À ÿ ß π Ë Èπ π Á Ë â ß «Ÿâ «À «µâπ â π àõπ µà ß à» ß «À «µâπ â π Á Ë â ß «Ÿâ π ßæ ß - π π å «µ ÿª ß å : æ ËÕ» Õÿ µ å Àµÿ º Ÿ π Á Ë â ß «Ÿâ «À «µâπ â π ßæ ß π π å ºŸâªÉ««: Á Õ ÿ ßÕ ÿ 15 ªï Ë â ß «Ÿâ À«à ߪï æ.». 2541-2548 π«π 13,075 æ Á 362 Ë «À «µâπ â» âõπà ß ß Õÿ µ å Àµÿ º Ÿ º» : æ Õÿ µ å Õß «À «µâπ â π Á Ë â ß «Ÿâ âõ 2.8 Õ Ÿà π American Society of Anesthesiologists (ASA) 1, 2 âõ 77.9 3-5 âõ 22.1 Àµÿ Õß «À «µâπ â π Á Ë ß «Ÿâ ß «Ÿâ âõ 51.9 Èπ π à«ß π âõ 50.8 Àµÿ Õß ªØ ø Á å ( âõ 16.3) æ π ºà µ µ ( âõ 7.2) ß ÈßÕ««π àõß âõß ( âõ 4.1) æ «À «µâπ â π Á Õ ÿµë «à 1 ªï Ÿß «à Á Õ ÿµ Èß µà 1 ªï Èπ ª Õ à ß π ß µ (Odds ratio = 1.96, 95% confidence interval = 1.51-2.54, p 0.001) æ «À «µâπ â π Á ËÕ Ÿà π ASA 3-5 Ÿß «à Á ËÕ Ÿà π ASA 1, 2 Õ à ß π ß µ (Odds ratio = 2.41, 95% confidence interval = 1.87-3.11, p 0.001) µà àæ «µ µà ß Õß «À «µâπ â À«à ߺŸâªÉ«Ë â ºà µ ª µ ÿ π Á Ë «À «µâπ â âõ 93.1 à Õ πµ ÈπµàÕÕ««Õß ºŸâªÉ«À ß Ÿ àæ Á Ë «À «µâπ â Õ π Àµÿ ß «Ÿâ «µ ÿª : æ Õÿ µ - å Õß «À «µâπ â π Á Ë ß «Ÿâ âõ 2.8 Àµÿ à«π À à ß «Ÿâ Á ÿà Ë ß â à Á Ë Õ ÿπâõ «à 1 ªï Õ Ÿà π ASA 3-5 µà à«π À à à Õ πµ ÈπµàÕÕ««Õß ºŸâªÉ«À ß Ÿ Keywords : anesthesia, bradycardia, children, Song klanagarind Hospital Thai J Anesthesiology 2006 ; 32(2) : 76-85. * Department of Anesthesia, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110 76 «76 ªï Ë 32 Ë 2 π- ÿπ π 2549
The care of children during anesthesia challenges all anesthesiologists, because a straightforward surgical procedure can suddenly become a critical incident at anytime. Cardiac arrest is the most critical incident during anesthesia and can lead to deterioration in the neurological status of the patient and subsequent death. In children, progressive bradycardia is the most common antecedent of cardiac arrest during anesthesia. 1,2 The maintenance of systemic blood pressure in children is dependent on a trinity of factors: cardiac output, the production of stroke volume and heart rate. Because stroke volume is relatively fixed when the left ventricle is noncompliant and poorly developed, especially in neonates and infants, the cardiac output will therefore become very dependent on heart rate. 3,4 Bradycardia can have a profound effect on organ perfusion and oxygenation, particularly in anesthetized children whose homeostatic mechanism may be impaired by anesthetic agents. 3 It had been estimated in previous reports that the incidence of bradycardia in anesthetized children was 0.13-3.7%, according to the patients status. 5-7 Throughout the past eight-year period (1998-2005), the Department of Anesthesia at Songklanagarind Hospital, under the auspices of the Faculty of Medicine, at Prince of Songkla University, had administered anesthesia to 13,075 children for various operative procedures, from minor surgical procedures as outpatients to open heart surgery. However, the incidence, the causes and the outcomes of bradycardia during anesthesia in anesthetized children at our hospital have not been studied. As a consequence, we decided to conduct this study aimed at determining the incidence, the causes and the outcomes of anesthetized children in relation to the occurrence of bradycardia. Methods The study was approved by the Faculty of Medicine, Prince of Songkla University s institutional review committee. A descriptive, retrospective study was conducted on 362 anesthetized children, aged between birth and 15 years of age who had had bradycardia, at the Department of Anesthesia, Songklanagarind Hospital, over an 8-year period from January 1, 1998 to December 31, 2005. As practiced at our hospital, bradycardia in anesthetized children is defined by generally accepted heart rates less than the average value for their age, but not at a child s lowest limit because an anesthetized child s homeostatic mechanism may be required to overcome the impairment by anesthetic agents. A heart rate less than 100 beats/min in children aged under 8 years old, or a heart rate less than 80 beats/min in children aged over 8 years old, and/or requiring the treatment of atropine administration by anesthesia providers in each situation were noted. Throughout the eight-year period at our hospital, anesthetic record forms, both paper-based and computerbased, had continued to improve the completion of patient details. For this study, we accessed information comprised of anesthetic records, medical records and the departmental database. This database contained information filled out at the time the events occurred in anesthesia and operative care, and focused particularly on intraoperative complications by anesthesia providers. We recorded the following data: a) patient factors: age, sex, weight, associated problems, and the American Society of Anesthesiologists (ASA) physical status, b) operative factors : case characteristics (elective/emergency or outpatient/inpatient), operative site (anatomic), and c) anesthetic factors from the induction state to the post-anesthesia state, involving the anesthetic technique, airway maintenance, and anesthetic agents. For the analysis of influencing factors, each incident of bradycardia was examined for possible remarkable causes, the phase of anesthesia at the time of bradycardia, and its outcome. After reviewing all data, we categorized each bradycardia incident as patient-related, operation-related, anesthesia-related or combined-related according to the primary cause of bradycardia noted at the time of occurrence. In cases where data could not be determined as cause and Vol. 32, No. 2, April-June 2006 Thai Journal of Anesthesiology 77
factor-related, we classified them as undetermined. The outcomes of patients with an occurrence of bradycardia in our study were directly related to the causes of bradycardia. They were classified into 5 groups : (1) no harm: complete recovery after prompt treatment ; (2) minor: small physiological changes without serious morbidity, such as transient hypotension, delayed emergence, etc. ; (3) major : a serious situation which contributed to postoperative morbidity, such as ICU admission, operative postponement, neurological events, etc. ; (4) cardiac arrest, but without subsequent death ; and (5) death on the operating table or postoperatively. Descriptive statistics were used to describe the frequency in patients data, shown as number and percent (%). The degree of risk factors for bradycardia are shown as Odds ratio (OR) and were compared by using a Chisquare test. Values of p < 0.05 were considered statistically significant. Results During the 8-year period of this study from January 1, 1998 to December 31, 2005, 13,075 children were anesthetized at our hospital. Of these, 362 cases were reported with bradycardia, an incidence of 2.8%, which occurred across the spectrum of operative procedures (Table 1). However, during the period of study, 2 cases were reported of patients who had not had an operation. One case was from succinylcholine-induced bradycardia, which resulted in subsequent cardiac arrest. The second case involved inadequate ventilation due to anesthesia machine leakage at the sevoflurane vaporizer position, which had been attached to the machine after a completed daily machine check. This caused severe hypoxia and bradycardia. Both of them did not have bad outcome and re-scheduled for an uneventful operation several weeks later. These 362 incidents were composed of 208 males and 154 females with a weight range of 0.8 to 71.0 Kg and a height range of 30.0 to 156.0 cm. General anesthesia (GA) or GA combined with a nerve block was administered in 90.0% of cases ; GA combined with caudal analgesia was administered in 9.7% of cases ; and spinal anesthesia alone was administered in only one case (0.3%), which had had a high spinal block-another cause of bradycardia. Of a total of 381 associated problems in our particular Table 1 Site of operative procedures for the 362 incidents Site of operative procedures number (%) Cardiac, major vascular 63 (17.4) Airway 60 (16.6) Eye 48 (13.3) Intra-abdomen 42 (11.6) Orthopedic 36 (9.9) Urologic 36 (9.9) Head and Neck 28 (7.7) Intra-cranium 22 (6.1) Thoracic 4 (1.1) Non operative 2 (0.6) Miscellaneous 21 (5.8) 78 «ªï Ë 32 Ë 2 π- ÿπ π 2549
cases, the three most commonly associated problems were anemia at 31.6% (n = 121), cyanotic congenital heart disease at 11.5% (n = 44), and increased intracranial pressure at 6.8% (n = 26) (Table 2). Bradycardia occurred regardless of airway maintenance techniques : the trachea was intubated in 69.6% of cases, laryngeal masks (LMA) were used in 5.8% of cases, the under-mask technique was performed in 14.4% of cases, and bronchoscopy or tracheostomy was used in 9.6% of cases. Two patients breathed spontaneously, one having spinal anesthesia and the other having total intravenous anesthesia (TIVA) with an oxygen supplement. Bradycardia occurred during all phases of anesthesia, with 50.8% occurring in the induction phase, 43.1% in the main- tenance phase, 4.7% in the emergence phase and 1.4% in the post-anesthesia phase. It is likely that the most common cause of bradycardia was as a result of medication, 51.9% (n = 188). The etiology of the other cases were cardiovascular, 28.7% (n = 104) ; respiratory, 11.3% (n = 41) ; central nervous system, 2.8% (n = 10) ; multiple causes, 2.2% (n = 8) ; the anesthesia machine, 0.3% (n = 1) ; and those with an unknown etiology 2.8% (n = 10), in that order (Figure 1). Details of all causes are shown in Table 3. With regards to cardiovascular causes (n = 104), vagal reflexes were the most common cause of bradycardia (n = 59). These reflexes are comprised of the oculocardiac reflex (n = 26), peritoneal traction (n = 15), laryn- Table 2 The frequency of 382 associated problems for the 362 incidents Associated problems number (%) Cardiovascular system Cyanotic congenital heart disease 44 (11.5) Acyanotic congenital heart disease 21 (5.5) Heart failure 18 (4.7) Respiratory system Upper respiratory tract infection 12 (3.2) Lower respiratory tract infection 21 (5.5) Obstructive airway disease (asthma, etc.) 9 (2.4) Central nervous system Increased intracranial pressure 26 (6.8) Delayed development 16 (4.3) Down syndrome 5 (1.3) Weakness 4 (1.1) Hematological system Anemia 121 (31.6) Fever 9 (2.4) Others Pre-maturity 22 (5.8) Obesity 18 (4.7) Liver disease (jaundice, hepatitis, etc.) 6 (1.6) Miscellaneous 29 (7.6) Vol. 32, No. 2, April-June 2006 Thai Journal of Anesthesiology 79
Figure 1 Causes of bradycardia for 362 incidents Figure 2 Factors related to bradycardia for 352 children (10 children with undetermined cause) Table 3 Details of causes of bradycardia for the 362 incidents Causes of bradycardia Medications Sevoflurane Halothane Succinylcholine Others Non-medication Cardiovascular system Severe cardiac disease Oculocardiac reflex Peritoneal traction Laryngoscopy Hypotension Vagus nerve traction Respiratory system Laryngospasm Airway obstruction Severe lung disease-hypoxia Accidental extubation Apnea of prematurity Esophageal intubation Difficult intubation Central nervous system Multiple systems Anesthesia machine Unknown 80 «number (%) 188 (51.9) 57 (15.7) 57 (15.7) 53 (14.6) 21 (5.8) 174 (48.1) 104 (28.7) 35 (9.7) 26 (7.2) 15 (4.1) 14 (3.9) 10 (2.8) 4 (1.1) 41 (11.3) 12 (3.3) 8 (2.2) 8 (2.2) 4 (1.1) 4 (1.1) 3 (0.8) 2 (0.6) 10 (2.8) 8 (2.2) 1 (0.3) 10 (2.8) ªï Ë 32 Ë 2 π- ÿπ π 2549
goscopy (n =14), and vagus nerve traction (n = 4). Furthermore, our study showed that laryngospasm was the most common cause of respiratory events of bradycardia, in which five patients occurred during induction, two pa-tients occurred during maintenance and five patients ex-perienced during emergence. Of all causes of bradycardia, 58.3% were anesthesiarelated, 18.8% operation-related, 4.1% patient-related, 16.0% combined-related and 2.8% undetermined (Figure 2). For ASA physical status 1 and 2, the most common causes were anesthesia related. The outcomes of anesthetized children with bradycardia were related to primary causes. Therefore, we categorized them according to ASA physical status, as shown in Figure 3. There was no cardiac arrest or death in ASA physical status 1. There were two cardiac arrests in ASA physical status 2, one from succinylcholine and another from accidental systemic toxicity during caudal injection. However, both completely recovered after resuscitation. One patient in ASA physical status 2 died postoperatively from a possible secretion obstruction in the airway. The remaining cardiac arrests and deaths occurred in ASA physical status 3 to 5 patients in which most were patient-, operation- or combined-related to bradycardia. The frequency of the presence or absence of brady- Figure 3 Outcome of bradycardia for 362 children categorized by ASA physical status cardia as categorized by age, ASA physical status, service and case is shown in Table 4. The frequency of bradycardia in children under 1 year of age was significantly higher than for children over 1 year of age (Odds ratio = 1.96, 95% confidence interval = 1.51-2.54, p 0.001). The frequency of bradycardia in ASA physical status 3 to 5 children was significantly higher than for children in ASA physical status 1 and 2 (Odds ratio = 2.41, 95% confidence interval = 1.87-3.11, p 0.001). There was no significant difference in the frequency of bradycardia between emergency and elective cases or between inpatient and outpatient cases (Table 5). Discussion Bradycardia is the most common antecedent event for cardiac arrest in children, at 54%, during anesthesia. 8 Incidences of bradycardia in anesthetized children vary for age group and are estimated to be from 0.13 to 3.7%. 5-7 Some patients have a greater risk of bradycardia during anesthesia. These include patients with Down syndrome, due to the considerable number having congenital heart disease, 38.6-50.0%. 7,9,10 They may also exhibit airway difficulties and pulmonary hypertension which causes hypoxia during anesthesia administration. 7 This study mainly describes the characteristics of anesthetized children with bradycardia during an 8-year period (1998-2005) at Songklanagarind Hospital. During this period, 13,075 children were anesthetized and 362 cases of bradycardia from all causes were detected, yielding a low incidence of 2.8%. This degree of incidence is in the estimated range of a previous study. However, this low rate of incidence may underestimate the real incident rate for two reasons. First, some anesthesiologists at our hospital prefer to administer atropine prior to succinylcholine during intubation for patients under the age of 7 years, especially in sick children with an ASA physical status of 3 to 5. Second, anesthesia providers generally tend to report more accurately cases of severe bradycardia or bradycardia requiring atropine treatment and Vol. 32, No. 2, April-June 2006 Thai Journal of Anesthesiology 81
Table 4 The frequency of presence and absence of bradycardia categorized by patient factors for 362 incidents from 13,075 anesthetized children Bradycardia No bradycardia Age * number (%) number (%) < 1 mo 22 (6) 326 (2.6) 1 mo to < 1 yr 55 (15.2) 1217 (9.5) 1 yr to < 8 yr 195 (53.9) 6670 (52.5) 8 yr to 15 yr 90 (24.9) 4500 (35.4) ASA * 1, 2 282 (77.9) 11373 (89.5) 3-5 80 (22.1) 1340 (10.5) Service Inpatient 329 (90.9) 11531 (90.1) Outpatient 33 (9.1) 1182 (9.9) Case Emergency 72 (19.9) 3074 (24.2) Elective 290 (80.1) 9639 (75.8) * p < 0.001 Table 5 Comparison of the frequency of bradycardia for 362 incidents Odds ratio 95% Confidence interval p-value Age < 1 yr 1.96 1.51-2.54 0.001 ASA 3-5 2.41 1.87-3.11 0.001 underreport cases of bradycardia without adverse effects or where recovery was spontaneous. Our study showed that anesthesia-related cases were the most common cause of bradycardia with a 58.3% rate of frequency. Of these, medication-related bradycardia cases were the most frequent at 51.9%, while other cases were mostly respiratory-related bradycardia causing hypoxia, such as laryngospam, airway obstruction, and 82 «ªï Ë 32 Ë 2 π- ÿπ π 2549
difficult or esophageal intubation. In addition to anesthesia-related bradycardia, vagal stimulation (16.3%) during an operative procedure was the next most common cause of bradycardia. Our study concurs with a previous study by Watterson et al. 3 and Keenan et al., 6 which reported that the major causes of bradycardia were medications, airway problems and autonomic reflexes-related events. For medication-related bradycardia, the frequency is equal for both halothane and sevoflurane. The majority of sevoflurane-induced bradycardia was caused by the induction of sevoflurane (8% concentration), but was not a factor during sevoflurane maintenance. Conversely, children who were induced with halothane experienced bradycardia both during induction (4% concentration) and during maintenance where some patients were switched to isoflurane, to prevent the recurrence of bradycardia. Currently, inhalation induction of anesthesia by sevoflurane is a widely used and generally accepted technique in clinical practice. This drug has markedly improved the safety of patients because of reduced cardiovascular side-effects compared with halothane. 11,12 However, Green et al. 13 reported that the onset of a nodal rhythm, associated with bradycardia began significantly earlier in children who had received an 8% induction concentration of sevoflurane compared with incremental amounts of 2% sevoflurane, every four to six breaths. Our study confirmed that an anesthetic overdose, especially during the induction of anesthesia, for both sevoflurane and halothane, could cause bradycardia and subsequent hypotension. Halothane is still commonly used throughout Thailand, and is an induction agent frequently used at our hospital. In order to induce anesthesia rapidly with high dose of inhalation, in addition to hyperventilation, markedly increases blood and myocardium concentrations, and can progress to bradycardia and cardiac arrest. Desalu et al. 14 reported that children induced with incremental amounts of halothane of up to 3% with 33% oxygen and nitrous oxide, had a significant drop in blood pressure for all patients, although heart rate values were significantly less during postinduction in children older than one year. Of these, no patient experienced bradycardia. In our study, induction with 4% halothane had a profoundly depressive effect on myocardium and caused bradycardia. As a consequence, we needed to use incremental induction. Annila et al. 15 reported that the incidence of bradycardia was 24% during the halothane maintenance of anesthesia when no patient had received atropine pretreatment. However, these bradycardia events were shortlived and patients were able to recover spontaneously whereas the administration of atropine as a pretreatment to prevent bradycardia caused persistent tachycardia. Therefore, the routine prevention of bradycardia by atropine is not necessary in children undergoing halothane anesthesia. In addition to inhalation anesthetics, succinylcholine was the third most common medication-related bradycardia in our study. The occurrence of bradycardia with a rapid progression to a cardiac arrest within a few minutes following the use of succinylcholine was the case for one child scheduled for a tonsillectomy. This case also attests to the cause not being related to occult neuromuscular disease. Early recovery in this patient was uneventful with no neurological sequelae. A previous report showed that succinylcholine could itself induce unexpected bradycardia and tachyarrhythmias, but rarely asystole 16,17 or secondary to succinylcholine-induced rhabdomyolysis in patients with undiagnosed muscle disease. 18 It is suggested that when faced with sudden, life-threatening arrhythmias following succinylcholine during the induction of anesthesia for children, clinicians should include occult myopathy in the differential diagnosis, and thus consider the aggressive management of hyperkalemia in addition to basic resuscitative efforts. 18 Some have suggested that anesthesia for healthy children, when used as a muscle relaxant, should not be achieved by succinylcholine. 19 Atropine, at 0.02 mg/kg or glycopyrrolate, at 0.01 mg/kg are equally effective in attenuating succinylcholine-induced bradycardia in children. 20 Currently, atro- Vol. 32, No. 2, April-June 2006 Thai Journal of Anesthesiology 83
pine, at 0.1 mg is offered as adequate protection against this type of bradycardia in all age groups for infants and children. 21 In our study, vagal stimulation accounted for 16.3% of the various types of stimuli such as oculocardiac reflex, peritoneal traction, laryngoscopy, and vagus nerve traction. The presence of increased intracranial pressure may enhance the vagal tone, which is precipitated by operative procedures such as burr holes or ventriculostomy, which has an incidence of 10.2-41.0% of bradyarrhythmia. 22,23 It is also important to note that we should be particularly careful when administering anesthesia to children with increased intracranial pressure. The major finding in our study indicates that the frequency of bradycardia in patients under 1 year of age was significantly higher than for patients over 1 year of age (Odds ratio = 1.96, 95% confidence interval = 1.51-2.54, p 0.001). Moreover, the frequency of bradycardia in ASA physical status 3 to 5 children was significantly higher than for children with an ASA physical status of 1 or 2 (Odds ratio = 2.41, 95% confidence interval = 1.87-3.11, p 0.001). Our study concurs with the study by Keenan et al., 6 in that the frequency of bradycardia was higher in the first year of age, compared with children aged three and four years of age. Bradycardia is more frequent in anesthetized infants compared to older anesthetized children and is more likely in ill infants. Sick infants who frequently undergo emergency or prolonged surgical procedures together with an immature sympathetic nervous system and a baroreceptor reflex appear particularly prone to episodes of bradycardia, cardiac arrest, and death. Additionally, a sick infant s cardiovascular system maintains lower catecholamine stores, displays a blunted response to exogenous catecholamine, and is more sensitive to calcium channel blocking properties of volatiles anesthetic which induces bradycardia. 4 Surprisingly, our results showed that there was no significant difference in the frequency of bradycardia between emergency and elective cases. One explanation for the low incidence of emergency cases may be that emergency operating procedures during our period of study were of a minor nature and so usually used an intravenous induction of anesthesia rather than inhalation induction. The outcome of anesthetized children with bradycardia in our study commonly caused by anesthesia, resulted in no adverse effects in the majority of cases or minor physiological changes at 93.1%. Nevertheless, if it progressed to cardiac arrest for any unrecognized reason, and where the cause was uncorrectable, the prognosis for a patient was poor. A previous report showed that the incidence of cardiac arrest due solely to anesthesia was 1.7 per 10,000 anesthetics, with 0.9 per 10,000 who subsequently died. 1 Although basal heart rate in children is higher than in adults, anesthetic overdose, hypoxia or the activation of the parasympatic nervous system can cause bradycardia. A bolus injection of atropine is the first pharmacologic form of intervention and may attenuate excessive vagal tone. Moreover, bradycardia should be immediately treated with oxygen and, if necessary with ventilation. If severe bradycardia occurs suddenly during anesthesia, it is essential that anesthesiologists clarify the underlying cause, as in the administration of oxygen, ensuring a clear and patent airway, and administration of atropine. Precordial stethoscopy is still a useful monitor for the early detection of heart rate changes, and may be an early warning sign of a reduction in cardiac output. 24 Conclusions The overall incidence of bradycardia in anesthetized children was low at 2.8%. Anesthesia-related incidents were the most common cause and were more likely to occur during the induction phase of anesthesia, due to the overdose of both sevoflurane and halothane. Bradycardia due to anesthetics happened very early and patients were able to recover from the administration of atropine. Anesthetized children under 1 year of age or with an ASA physical status of 3 to 5 had a significantly higher risk 84 «ªï Ë 32 Ë 2 π- ÿπ π 2549
than other children. Acknowledgement The authors would like to gratefully thank Tom Gapic for editing and checking this manuscript. References 1. Keenan RL, Boyan CP. Cardiac arrest due to anesthesia. A study of incidence and causes. JAMA 1985 ; 253 : 2373-7. 2. Morray JP, Geiduschek JM, Caplan RA, Posner KL, Gild WM, Cheney FW. A comparison of pediatric and adult anesthesia closed malpractice claims. Anesthesiology 1993 ; 78 : 461-7. 3. Watterson LM, Morris RW, Westhorpe RN, Williamson JA. Crisis management during anaesthesia : bradycardia. Qual Saf Health Care 2005 ; 14 : e9. 4. de Armendi AJ, Todres ID. Postanesthesia Care Unit. In : Cote CJ, Todres ID, Goudsouzian NG, Ryan JF, editors. The practice of anesthesia for infants and children. 3 rd ed. Philadelphia: W.B. Saunders, 2001 : 698-714. 5. Murat I, Constant I, Maud huy H. Perioperative anaesthetic morbidity in children : a database of 24,165 anaesthetics over a 30-month period. Paediatr Anaesth 2004 ; 14 : 158-66. 6. Keenan RL, Shapiro JH, Kane FR, Simpson PM. Bradycardia during anesthesia in infants. An epidemiologic study. Anesthesiology 1994 ; 80 : 976-82. 7. Borland LM, Colligan J, Brandom BW. Frequency of anesthesia-related complications in children with Down syndrome under general anesthesia for noncardiac procedures. Paediatr Anaesth 2004 ; 14 : 733-8. 8. Morray JP, Geiduschek JM, Ramamoorthy C, Haberkern CM, Hackel A, Caplan RA, et al. Anesthesia-related cardiac arrest in children : initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) registry. Anesthesiology 2000 ; 93 : 6-14. 9. Roodman S, Bothwell M, Tobias JD. Bradycardia with sevoflurane induction in patients with trisomy 21. Paediatr Anaesth 2003; 13: 538-40. 10. Jaruratanasirikul S, Soponthammarak S, Chanvitan P, Limprasert P, Sriplung H, Leelasamran W, et al. Clinical abnormalities, intervention program, and school attendance of Down syndrome children in Southern Thailand. J Med Assoc Thai 2004 ; 87: 1199-204. 11. Johr M. Paediatri c anaesthesia : inhaled or intravenous technique. [Abstract]. Anaesthesiol Reanim 2004 ; 29 : 64-8. 12. Mason LJ. An update on the etiology and prevention of anesthesia-related cardiac arrest in children. Paediatr Anaesth 2004 ; 14 : 412-6. 13. Green DH, Townsend P, Bagshaw O, Stokes MA. Nodal rhythm and bradycardia during inhalation induction with sevoflurane in infants : a comparison of incremental and high-concentration techniques. Br J Anaesth 2000 ; 85 : 368-70. 14. Desalu I, Kushimo OT, Odelola MA. Cardiovascular changes during halothane induction in children [Abstract]. Niger Postgrad Med J 2004; 11: 173-8. 15. Annila P, Rorarius M, Reinikainen P, Oikkonen M, Baer G. Effect of pre-treatment with intravenous atropine or glycopyrrolate on cardiac arrhythmias during halothane anaesthesia for adenoidectomy in children. Br J Anaesth 1998 ; 80 : 756-60. 16. McAuliffe G, Bissonnette B, Boutin C. Should the routine use of atropine before succinylcholine in children be reconsidered? Can J Anaesth 1995 ; 42 : 724-9. 17. Shorten GD, Bissonnette B, Hartley E, Nelson W, Carr AS. It is not necessary to administer more than 10 micrograms. kg -1 of atropine to older children before succinylcholine. Can J Anaesth 1995 ; 42 : 8-11. 18. Sullivan M, Thompson WK, Hill GD. Succinylcholine-induced cardiac arrest in children with undiagnosed myopathy. Can J Anaesth 1994 ; 41 : 497-501. 19. Schulte-Sasse U, Eberlein HJ, Schmucker I, Underwood D, Wolbert R. Should the use of succinylcholine in pediatric anesthesia be re-evaluated? [Abstract]. Anaesthesiol Reanim 1993 ; 18 : 13-9. 20. Lerman J, Chinyanga HM. The heart rate response to succinylcholine in children: a comparison of atropine and glycopyrrolate. Can Anaesth Soc J 1983 ; 30 : 377-81. 21. Davis PJ, Lerman J, Tofovic SP, Cook DR. Pharmacology of pediatric anesthesia. In : Motoyama EK, Davis PJ, editors. Anesthesia for infants and children. 7 th ed. Philadelphia : Mosby, 2006 : 177-238. 22. Baykan N, Isbir O, Gercek A, Dagcnar A, Ozek MM. Ten years of experience with pediatric neuroendoscopic third ventriculostomy : features and perioperative complications of 210 cases. J Neurosurg Anesthesiol 2005 ; 17 : 33-7. 23. El- Dawlatly AA, Murshid WR, Elshimy A, Magboul MA, Samarkandi A, Takrouri MS. The incidence of bradycardia during endoscopic third ventriculostomy. Anesth Analg 2000 ; 91 : 1142-4. 24. Manecke GR, Nemirov MA, Bicker AA, Adsumelli RN, Poppers PJ. The effect of halothane on the amplitude and frequency characteristics of heart sounds in children. Anesth Analg 1999 ; 88 : 263-7. Vol. 32, No. 2, April-June 2006 Thai Journal of Anesthesiology 85