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*Division of Anaesthesia, Geneva Childrens Hospital, Geneva, Switzerland;
Division of Clinical Sciences, Institute for Child Health Research, Perth, Australia; and
Department of Anaesthesia, Princess Margaret Hospital for Children, Perth, Western Australia
Address correspondence and reprint requests to Walid Habre, MD, Division of Paediatric Anaesthesia, Geneva Childrens Hospital, 6, rue Willy Donze, 1205 Geneva, Switzerland. Address e-mail to Walid.Habre{at}hcuge.ch
| Abstract |
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Implications: Tracheal intubation using sevoflurane as sole anesthetic is possible and its frequency is increasing. When comparing children with and without asthma, tracheal intubation under sevoflurane was associated with an increase in respiratory system resistance in asthmatic children. However, no apparent clinical adverse event was observed.
| Introduction |
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With the world-wide increase in asthma prevalence (7,8), more asthmatic children are likely to require anesthesia for surgical procedures. Asthmatics are prone to bronchospasm induced by different irritant stimuli. Tracheal intubation can induce an increased release of acetylcholine from postganglionic cholinergic nerves and produce bronchospasm via vagal reflex pathways (9). Clinically, halothane has been the volatile anesthetic of choice in asthmatics because of its bronchodilator actions. Recently, we demonstrated that sevoflurane was as effective as halothane in preventing methacholine-induced increase in lung resistance in an animal model (10). The safety of the use of sevoflurane in asthmatic children has not yet been reported.
This study was designed to measure lung function in asthmatic and nonasthmatic children receiving sevoflurane for induction of anesthesia and endotracheal intubation. Measurements were performed before and after intubation to determine if sevoflurane would limit the increase in airway resistance that may occur under these circumstances.
| Methods |
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Anesthetic Management
No premedication or ß2-agonist or other asthma medication was given as per our routine. All children had anesthesia induced with sevoflurane (up to 8%) in a mixture of 50% nitrous oxide in oxygen then maintained at 3% sevoflurane (1.2 minimum alveolar anesthetic concentration [MAC]) with children breathing spontaneously via face mask and Jackson-Rees modification of the T-piece. Airway opening pressure (Pao) and flow (V') were then measured. Sevoflurane was delivered at a concentration of 5% to obtain the 95% effective dose for tracheal intubation (4.68% with 95% confidence interval [CI] of 3.91%12.74%) (11). After insertion of an oral endotracheal tube (ETT), regular spontaneous respiration was reestablished under 3% (1.2 MAC) sevoflurane in a mixture of 50% nitrous oxide in oxygen, and measurements of respiratory mechanics were repeated. Sevoflurane was then increased to 4.2% (1.7 MAC) and a final set of measurements was collected after allowing the patient to reach a new steady state. All measurements were achieved under the same concentration of carrier gas, 50% nitrous oxide in oxygen. During preliminary studies, sevoflurane concentration was measured using an AS3 Datex monitor. In the setup, a steady state, as judged from end-tidal gas concentration, was achieved after 3 min of initiating sevoflurane or changing the concentration.
Equipment
A pressure port and transducer were used to measure Pao and a heated screen pneumotachograph (Hans Rudolph, Inc., Kansas City, MO) to measure V'. This equipment was placed between the patients facial mask or tracheal tube and the Jackson-Rees modification of the T-piece. The Pao and V' signals were sampled at 100 Hz and low-pass filtered using scientific respiratory equipment (amplifier and signal conditioner SC-14C, pressure transducers TG-40 and TD-05; SCIREQ, Inc., Montreal, Quebec, Canada) and stored through a 12-bit AD converter on a PC computer (Data Translation, DT 2801-A). All data were collected and analyzed using a data acquisition software package (Anadat & Labdat, RHT Infodat, Montreal, Quebec, Canada).
Measurement of Respiratory Mechanics
Respiratory mechanics were calculated by applying a single-compartment model using multilinear regression analysis to calculate dynamic compliance (Crs,dyn) and respiratory system resistance (Rrs) during the expiration phase only, based on:
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The multilinear regression (MLR) analysis calculates the coefficients Crs,dyn, Rrs, and PA, EE by fitting the equation of motion of the model to Pao, V, and V' measured at the airway opening. The quality of fit of the model to the data is judged by the coefficient of determination r2 (Fig. 1). We only included data epochs in which r2
0.96. The MLR produces a weighted average for Crs and Rrs throughout the respiratory cycle. We used data collected in expiration only to avoid influence of leak around the tracheal tube and as subjects were spontaneously breathing.
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Statistics
A difference of 25% in Rrs between asthmatic and nonasthmatic children would be considered clinically significant. Based on our previous study in normal children under muscle relaxation (13), a group size of 2023 subjects would have 85%90% power to detect such a difference. Unpaired two-tailed t-tests were used to compare demographic data and respiratory variables between asthmatic and nonasthmatic children, and paired two-tailed t-tests were used to compare respiratory mechanical outcomes between children at different times. A multilevel modeling approach was then used to analyze differences in respiratory mechanics between asthmatics and nonasthmatics, and before and after oral tracheal intubation. The two outcomes analyzed were Rrs and Crs. The models were fitted using Mln v1.0 (14). Separate and combined effects for group (asthmatic/control) and time were considered for inclusion in the models. Time was treated as a categorical variable with three levels: baseline (3% before ETT), 3% after ETT, and 4.2% after ETT. The significance level was taken as 5%. Data are presented as means ± SD.
| Results |
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The two groups of patients were comparable with respect to age, weight, gender, and size of ETT (Table 1). Among the 22 asthmatics, 8 had salbutamol on demand, 1 had beclomethasone, and 7 had both. In addition, cromoglycate was prescribed to 1 patient, combined with beclomethasone to 2 patients and with salbutamol to 3 other patients.
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Respiratory Mechanics.
After intubation under 3% sevoflurane, there was a statistically significant increase in Rrs in children with asthma, whereas in normal children, Rrs decreased slightly (but did not reach statistical significance). The percentage change in Rrs was +17% ± 49% (95% CI for mean: -4.4%, +39.1%) in asthmatics and -4% ± 39% in children with normal lungs (95% CI for mean: -21.2%, +13.5%) (Fig. 2).
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The increase in sevoflurane concentration to 1.7 MAC resulted in a small decrease in Rrs in both groups (-4.1% ± 0.18% in children with asthma vs -5% ± 0.15 in children without asthma, P = 0.865), and no systematic changes in the Crs.
| Discussion |
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Our anesthetic management was that which would be used clinically in children with asthma (15). The major departure from normal practice was that neuromuscular blocking drugs were not administered prior to intubation. This was done to avoid the confounding effect of comparing respiratory mechanics during spontaneous breathing prior to intubation, with measurements taken during positive pressure ventilation postintubation. We would not expect our results to have been different if muscle relaxants had been used (16).
The increase in Rrs after intubation seen in asthmatic children in the present study is at odds with the findings of Rooke et al. (17), who reported that sevoflurane (1.1 MAC) decreased Rrs after intubation in a group of normal adults. The nonasthmatic children in our study also showed a small decrease (approximately 4%) in Rrs after intubation, which, although it approached statistical significance, was clinically insignificant. In contrast, the increase in Rrs after intubation in the asthmatic group was larger (approximately 18%) and was statistically significant. This difference also approached our a priori definition of clinical significance (25%). These children had stable mild to moderate asthma. One might expect the increase in Rrs after intubation to be greater in children with less stable asthma.
No systematic changes were seen in Crs after endotracheal intubation in either group. The lack of effect of sevoflurane in both groups on the compliance may be explained by the fact that changes in functional residual capacity occur immediately after induction of anesthesia (before our first set of measurements), with no further effect of the depth of anesthesia (18,19).
The second part of our study was designed to establish whether an increase in sevoflurane concentration to 1.7 MAC induced further changes in respiratory mechanics. Increasing the concentration of sevoflurane was followed by a similar decrease in Rrs in both groups. There was also a reduction in tidal volume with increased sevoflurane, which may be related to a great depression of intercostal muscle function with increasing depth of anesthesia (20). There was a significant tachypnea in both groups, which has recently been reported after induction of sevoflurane in adults (21). Whether the tachypneic properties of sevoflurane result, like halothane, from the effect of the anesthetic on the suprapontine structures is unknown (22).
Among the different techniques used to measure dynamic respiratory mechanics that have been validated for use in children under anesthesia, MLR techniques are the most easily implemented (13,23,24). Because the children in our study were spontaneously breathing, we limited our analysis to the expiratory phase only. This does not imply that respiratory mechanics are the same during inspiration and expiration; however, measurements made during expiration can be used to follow changes in lung function (25). We did not correct Rrs for the resistance of the ETT, because this required exact knowledge of the tube resistance. As demonstrated by Chang and Mortola (26), the tube resistance measured in vitro often overestimates its resistance in vivo. This is particularly true for small tubes. Because the ages of the children and the size of the tubes used were the same in both groups, we felt it was preferable not to attempt to correct Rrs for the tube resistance.
We considered only children with a definite history of physician-diagnosed asthma with at least one episode of wheezing requiring the use of ß-adrenergic agonist in the last 12 mo. This pattern is generally associated with bronchial hyperresponsiveness when assessed by a physiological test such as exercise (27). Because none of the children received a ß-adrenergic agonist on the day of surgery, we can conclude that changes in respiratory patterns and mechanics are only related to the effect of sevoflurane.
In conclusion, in asymptomatic children with mild to moderate asthma, endotracheal intubation under sevoflurane followed by maintenance at 1.2 MAC, was associated with an increase in Rrs (18%) during spontaneous breathing. Although this increase was not associated with any clinically apparent adverse event, one should be cautious when using sevoflurane for endotracheal intubation in asthmatic children, especially those with more severe or unstable asthma. Further investigation is being performed to evaluate the ability of pretreatment with a ß-adrenergic agonist to prevent the increase in Rrs seen after tracheal intubation under sevoflurane in asthmatic children.
| Footnotes |
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Presented in part at the annual meeting of the American Society of Anesthesiology Orlando, FL, October 17, 1998.
| References |
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