Propofol, as a short-acting lipid-soluble intravenous (i.v.) anaesthetic, has become popular in paediatric day-case anaesthesia because of its anti-emetic effect and rapid recovery [1-3]. In children, propofol with varying doses of alfentanil [4,5] or lignocaine  has been used to facilitate tracheal intubation without neuromuscular block. In day-case surgery, tracheal intubation without muscle relaxants may provide several advantages: (a) it obviates the need for suxamethonium and its potential side effects, and (b) it facilitates the rapid recovery of spontaneous ventilation when the effect of conventional muscle relaxants may be too long for short surgical procedures. Furthermore, as muscle relaxants and antagonists are relative risk factors for the occurrence of post-operative nausea and vomiting (PONV) , their avoidance may reduce the incidence of PONV.
The purpose of our study was to compare i.v. induction with alfentanil/propofol and inhalational induction with halothane in order to see which method would provide satisfactory intubating conditions without neuromuscular block in short day-case anaesthesia. Intravenous induction with thiopentone/suxamethonium was included as a reference method. Because induction of anaesthesia and tracheal intubation in children are known to cause significant haemodynamic changes and alterations in cardiac rhythm [8-11], continuous Holter-ECG recording was used to detect more exactly the effect of the induction method on heart rate and rhythm. We limited this study to children 1-3 years of age, as few studies have focused on this age group in respect of tracheal intubation without neuromuscular block and cardiac dysrhythmias during induction of anaesthesia.
After approval of the Ethics Committee of the Tampere University Hospital, 90 children (ASA I-II) aged 1-3 years undergoing adenoidectomy in the ENT unit participated in the study. Informed written consent was obtained from the parents of each child.
No premedication was used. All children had EMLA® cream (Astra, Södertälje, Sweden) applied over the dorsum of the hand 1 h before venous cannulation. Holter-ECG leads were applied to the chest of the child in the waiting room at least 15 min before induction of anaesthesia. The children were accompanied into the operating room by their parent(s). After arrival in the operating room non-invasive arterial pressure, heart rate (Dinamap™, Critikon, Tampa, Florida, USA) and oxygen saturation (SpO2) (Capnomac Ultima™, Datex, Helsinki, Finland) were recorded and a 24-gauge cannula was inserted into a vein on the dorsum of the hand. Each child was randomly allocated by computer-based random listing to one of three groups: group TS received thiopentone 5 mg kg−1 and suxamethonium 1.5 mg kg−1, group PA alfentanil 10 μg kg−1 and propofol 3 mg kg−1 and group H 5 vol% halothane in 70% nitrous oxide in oxygen for induction of anaesthesia.
No routine anticholinergic drugs were used during anaesthetic induction. The i.v. anaesthetics were injected over a period of 20 s. In group TS, after thiopentone 5 mg kg−1, suxamethonium 1.5 mg kg−1 was injected and the trachea was intubated after the conclusion of muscle fasciculations. In group PA, alfentanil 10 μg kg−1 was slowly injected 60 s before propofol in order to minimize propofol-induced pain in the hand and to facilitate tracheal intubation . Tracheal intubation was performed when the children tolerated the application of a facemask and gentle manual ventilation with 100% oxygen. If tracheal intubation was not possible at first attempt, suxamethonium 1.5 mg kg−1 was given. If necessary, anaesthesia was deepened with halothane before a second attempt at laryngoscopy. In group H, anaesthesia was induced using 5 Vol.% inspired halothane with 70% nitrous oxide in oxygen with a facemask. Ventilation was gently assisted until fading of spontaneous breathing efforts. At this point tracheal intubation was performed without the use of a muscle relaxant. In all groups after tracheal intubation, anaesthesia was maintained with 1-3 vol% halothane with 70% nitrous oxide in oxygen delivered via a Bain coaxial breathing system.
Pain on injection after propofol was evaluated by the same assisting nurse using a 4-point scoring system (1-none, 2-mild (grimacing), 3-moderate (crying), 4-severe (crying, withdraws hand) . Tracheal intubation was always preformed by the same senior anaesthetist (GB), who was unaware of the induction method. A 4-point scoring system for ease of laryngoscopy, position of vocal cords and degree of coughing was used (Table 1). Overall intubating conditions were judged excellent if all scores were 3, moderate if they were 4-6 and poor if scores were ≥ 7. Tracheal intubation was considered acceptable, if conditions were moderate or excellent, and unacceptable if conditions were poor.
Non-invasive arterial pressures, heart rate and SpO2 were recorded before laryngoscopy and 1 and 3 min after tracheal intubation. Desaturation was defined as an SpO2 value lower than 92%. The study period extended from the application of the Holter-ECG leads until 3 min after tracheal intubation, after which anaesthesia was continued in accordance with the preferences of the consultant anaesthetist.
The Holter-ECG recordings were analysed separately by a physician (PR) who was unaware of the induction method. Isolated supraventricular or ventricular beats were regarded as dysrhythmia only if there were three or more during a 20-s period. For the purpose of the study, bradycardia was defined as a heart rate below 70 beats min−1 and tachycardia over 140 beats min−1 lasting more than three or more beats. If the heart rate at any moment decreased below 60 beats min−1 and persisted for more than 5 s, atropine 0.01 μg kg−1 i.v. was given.
Statistical analysis was performed using one-way ANOVA with Bonferroni's correction for continuous variables and χ2-test for discrete variables. Haemodynamic variables were analysed using two-way ANOVA for repeated measurements with Bonferroni's and Tukey's post hoc tests for intergroup comparisons. A P-value of <0.05 was considered significant. Results are presented as mean (SD) (95% confidence interval or range) or number (%) where appropriate.
The three groups were comparable in age, weight and sex of the children (Table 2).
Pain on injection after propofol in group PA occurred in 44% of children, who experienced mild or moderate pain (score of two or three). None experienced severe pain. In four patients scoring was not reliable because the child cried before induction.
Tracheal intubation was successful in 100% of children in groups TS and H. In group PA, halothane was not needed to deepen the level of anaesthesia, but six out of 30 children were given suxamethonium because of impossible laryngoscopy and one child for coughing after placement of the tracheal tube. Thus, the success rate for tracheal intubation was 80% (P = 0.001 group PA vs. TS and H). The intubating conditions are described in Fig. 1. Conditions were excellent in 22 (73%) children in groups TS and H compared with one (3%) child in group PA (P = 0.001). The overall conditions for tracheal intubation were acceptable in 29 (97%), 13 (43%) and 30 (100%) of children in groups TS, PA and H, respectively (P = 0.0001).
Figure 2 shows mean heart rates during induction of anaesthesia. Heart rate in group TS increased after induction and decreased below base-line values 3 min after tracheal intubation. In groups PA and H, heart rate decreased during induction and remained lower than pre-induction values until the end of the study period. Mean heart rate remained higher in group TS than in groups PA and H at all data points after baseline (Fig. 2). Statistical analysis showed a significant effect for the repeated measurement factor time (P = 0.0001) and induction agent (P = 0.002).
Mean arterial pressure (MAP) in the three groups during anaesthesia are presented in Fig. 3. In group TS, MAP increased in response to induction of anaesthesia and persisted at this level until 1 min after tracheal intubation, after which it decreased to a lower than pre-induction value. In group PA, MAP remained unchanged during induction and after laryngoscopy but decreased below pre-induction values at 3 min after tracheal intubation. In group H, MAP decreased before and after laryngoscopy and remained at that level until the end of the study period. Mean arterial pressure was higher in group TS than in groups PA and H before and 1 min after laryngoscopy (Fig. 3). Statistical analysis showed a significant effect for factor time (P = 0.017) and induction agent (P = 0.0001).
The Holter-ECG recordings were not readable due to technical disturbances in two patients in groups PA and H. Tachycardia (heart rate >140 beats min−1) during the pre-induction period was seen in 20 (69%), 14 (50%) and 15 (58%) children in group TS, PA and H, respectively (P = 0.3). The overall incidence of dysrhythmias during induction of anaesthesia was 5%. One patient in group PA and two patients in group H had supraventricular extrasystoles (SVES) at the end of induction and this dysrhythmia continued for 1-3 min after tracheal intubation (Table 3). One patient in group PA had junctional rhythm (heart rate 89 beats min−1), lasting for 10 s 3 min after laryngoscopy. The preceding heart rate before junctional rhythm was 78 beats min−1. The total incidence of bradycardia during the study period was higher in groups PA 6 (21%) and H 4 (14%) than in group TS 0 (0%) (P = 0.007 PA vs. TS, P = 0.03 H vs. TS) (Table 3). Of the seven patients receiving suxamethonium to facilitate tracheal intubation in group PA, one patient developed transient bradycardia (69 beats min−1) 1 min after laryngoscopy. All the bradycardia episodes lasted less than 5 s and no anticholinergics were needed.
Desaturation to values less than 92% during induction of anaesthesia was seen in two patients. One patient in group PA receiving suxamethonium to facilitate tracheal intubation and another in group H associated with bradycardia and laryngospasm during induction.
The results of the present study show that tracheal intubation without neuromuscular block using a fixed dose of propofol 3 mg kg−1 preceded by alfentanil 10 μg kg−1 resulted in unacceptable intubating conditions in the majority of patients, while inhalation induction with halothane provided excellent intubating conditions similar to those with thiopentone/suxamethonium. The incidence of cardiac dysrhythmias was low. Transient bradycardia was most often seen after propofol/alfentanil.
Successful tracheal intubation at the first attempt was achieved in all the patients when using i.v. induction with thiopentone/suxamethonium or inhalational induction with halothane, but in only 80% of patients when propofol/alfentanil was used. Our success rate for tracheal intubation is slightly lower than in several previous studies where a dose of alfentanil 10-40 μg kg−1 with varying doses of propofol for induction of anaesthesia provided successful intubating conditions in 95%  and 100% [4,6] of children. We used a fixed dose of propofol 3 mg kg−1 and 20% of the patients required suxamethonium to facilitate intubation. The induction dose of propofol for children has varied from 2.88 mg kg−1 to as high as 5.2 mg kg−1 taking acceptance of the facemask as a reference point. Age , premedication  and ethnic background  have been reported to influence the induction dose of propofol in children. We chose to use the higher range of the dose recommended by Hannallah et al. (2.5-3.0 mg kg−1) for unpremedicated children of 3-12 years of age  as the children in the present study belonged to a younger age group. Furthermore, because alfentanil reduces the amount of propofol needed for induction of anaesthesia [5,18], we postulated that 3 mg kg−1 would be an appropriate dose for induction of anaesthesia as well as tracheal intubation. However, in a recent study based on pharmacokinetic measurements, it was suggested that children of 1 to 3 years required a higher dose of propofol for induction of anaesthesia due to a larger central compartment volume and a more rapid clearance . A larger dose of propofol may have altered the success rate for tracheal intubation.
Also, a higher dose of alfentanil (20-40 μg kg−1) may have improved intubation conditions. However, the optimal dose of alfentanil for facilitating tracheal intubation with propofol is not clear. In the study by Hopkinson et al., 50 μg kg−1 of alfentanil is required to produce uniformly excellent intubation conditions when administered after thiopentone . With propofol, an increase in the dose of alfentanil from 10 μg kg−1−15 μg kg−1 did not improve intubating conditions significantly . However, alfentanil 40 μg kg−1 compared with 20 μg kg−1 improved intubation conditions with propofol in children under 3 years of age but not in school-age children . Increasing the dose of alfentanil may increase the incidence of side effects, namely bradycardia, arterial hypotension and central nervous excitation [6,21,22]. We chose to use 10 μg kg−1 in accordance with the study by McConaghy and Bunting  because we wanted to use the lowest possible dose to facilitate tracheal intubation without compromising the recovery of spontaneous ventilation after a short procedure.
The haemodynamic response to tracheal intubation was attenuated more effectively after an inhalation induction with halothane and i.v. induction with alfentanil/propofol than thiopentone/suxamethonium but bradycardia was most often seen after alfentanil/propofol. Propofol may have a sympatholytic effect  and even moderate doses of alfentanil in conjunction with propofol can cause severe bradycardia in children . Suxamethonium also causes bradycardia in children  and it probably contributed to the significant decrease in heart rate in one patient in the propofol/alfentanil group. We did not use anticholinergics as we wanted to investigate the sole effect of the induction method on the occurrence of bradycardia. All the cases of bradycardia were transient and subsided quickly without the need for anti-cholinergic drugs but careful monitoring of the heart rate is strongly recommended, with atropine at hand in case immediate intervention is needed. Forty-four percent of children experienced mild or moderate pain on injection with propofol. This may have an influence on the haemodynamic response to induction of anaesthesia in some children.
The haemodynamic response to induction and tracheal intubation in the TS group probably reflects the increase in noradrenaline levels after thiopentone and suxamethonium [10,25,26], and is consistent with previous studies in children [12,21]. Suxamethonium in conjunction with thiopentone did not cause bradycardia in any of the children, which is in accordance with the study by McAuliffe et al.. In their study, and comparable with ours, the children were unpremedicated and this may further have increased the level of catecholamines due to anxiety. The incidence of tachycardia before induction of anaesthesia in all groups probably reflected the level of anxiety in the children.
Rapid inhalation induction with 5 vol% inspired halothane caused a significant decrease in heart rate and MAP after tracheal intubation. Halothane causes a dose-dependent depression of the myocardial function resulting in a decrease in arterial pressure  and heart rate . It has been suggested that the greatest risk for bradycardia and hypotension in infants during halothane induction occurs during the 'silent period' between intubation and incision when the concentration of halothane is still high and the level of stimulus low . In our study, the decrease in heart rate and MAP persisted for the first 3 min after tracheal intubation, after which surgery was started. Although our study period ended at the start of surgery, consequent haemodynamic measurements showed that the cardiovascular depression responded quickly to surgery and to a decreasing concentration of halothane.
The overall incidence of cardiac dysrhythmia during induction of anaesthesia in our study was low. Two children in groups PA and H each had short-lasting dysrhythmias which all subsided before the end of the study period. In earlier studies, bradycardia or junctional rhythm occurred in 19-29% of children after induction with propofol . Thiopentone together with suxamethonium and atropine was associated with junctional rhythm in 4-11% [8,9] and ventricular extrasystoles in 22% of children . Using halothane alone for induction and tracheal intubation, Lindgren and colleagues did not detect any dysrhythmia in atropine premedicated patients . In the study by Annila et al., the use of anticholinergic drugs did not influence the occurrence of dysrhythmia in children aged 1-3 years. Therefore, studies with and without anticholinergics can be compared. In addition, cardiac dysrhythmia is thought to be directly associated with age and children under 2 years rarely have dysrhythmia during anaesthesia . This may account for the low incidence of dysrhythmia in our study. In small children the autonomic nervous system may react differently from that of adults and older children in whom increased sympathetic activity measured by catecholamine levels is shown to predispose to cardiac dysrhythmias [33,34]. In our study no dysrhythmias were seen in TS group, when sympathetic activity was obviously increased supporting the fact, that small children may have protective neural mechanisms against dysrhythmias.
We conclude that induction of anaesthesia in children 1-3 years with alfentanil 10 μg kg−1 and propofol 3 mg kg−1 did not provide acceptable intubating conditions in this age group. Propofol/alfentanil attenuated the arterial pressure response to tracheal intubation better than thiopentone/suxamethonium but was associated with significant bradycardia. Rapid inhalation induction with 5 vol% halothane provided excellent intubating conditions similar to thiopentone/suxamethonium. The incidence of dysrhythmias was low and was not associated with the induction technique.
Our warm thanks to the personnel of the ENT Surgery Unit in the Tampere University Hospital for their co-operation and help during this study.
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