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Anesth Analg 2005;101:1615-1618 © 2005 International Anesthesia Research Society doi: 10.1213/01.ANE.0000184134.80849.17
Peter J. Davis |
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Abstract |
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To investigate how sevoflurane modifies airway protective reflexes in anesthetized children, we recruited patients younger than 12-yr-old for our study. Anesthesia was induced with inhaled sevoflurane in oxygen. The airway was managed with a laryngeal mask airway and the patient breathing spontaneously. Depending on the depth of anesthesia, the subjects were divided into two groups: Group 1 and Group 2 (1% and 2% of end-tidal sevoflurane concentration, respectively). Behaviors of the larynx were assessed mainly by the fiberscopic images of the larynx as well as respiratory flow and esophageal pressure. A small dose, 0.02 mL/kg of distilled water (minimum 0.2 mL) was instilled to the larynx through a channel of the scope to evoke an airway protective reflex from the larynx. The responses were categorized into passive (laryngeal closure, laryngospasm, and apnea) and active (cough, expiration reflex, and swallowing reflex) responses. Ten subjects were included in each group. In both groups, the primary responses were passive; however, in Group 1, active reflexes were also observed in 8 of 10 subjects; no subjects in Group 2 had active reflexes (P < 0.01). We concluded that, in children, the depth of general anesthesia with sevoflurane modified airway protective reflexes.
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Introduction |
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The larynx is a unique organ that has complex functions. Most of these functions are accomplished by neural control that includes reflexes elicited from the larynx itself. These reflexes consist of laryngeal closure, laryngospasm, apnea, cough or expiration reflex, and swallowing reflex. They can be categorized into the airway protective reflex, which is beneficial in protecting the lower airway from inhaling noxious substances. In addition, airway reflexes could also be harmful, especially during induction or emergence from anesthesia, because these reflexes may induce hypoxemia as a result of inadequate ventilation.
In adult subjects, general anesthesia has been reported to modify or inhibit these reflexes (1,2). In this study, we examined the effects of the depth of sevoflurane anesthesia on the protective airway reflex in children.
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Methods |
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After approval of our Institutional Ethics Committee, children younger than 12-yr-of-age were recruited to participate in this study. We obtained written informed consent from our subjects and/or their parents. All patients were undergoing elective minor surgery under general anesthesia. None of the patients had a history of smoking, asthma, recent upper airway infection, neural disease, or any other disorder that may have interfered with our study.
No preanesthetic medication was administered. Anesthesia was induced with inhaled sevoflurane in conjunction with nitrous oxide and oxygen. After obtaining adequate depth of anesthesia, a proper size of laryngeal mask airway was inserted, and anesthesia was maintained with sevoflurane in oxygen with spontaneous breathing. Routine monitoring including electrocardiogram, noninvasive arterial blood pressure monitoring, and pulse oximetry, was performed.
We used an experimental design reported in our previous studies (3,4). Briefly, a flexible fine fiberscope (3.5 mm outer diameter; FB10X, Pentax Inc., Tokyo, Japan) was passed through a custom-made elbow connector that had a self-sealing diaphragm, which enabled us to observe the glottis if the position of the laryngeal mask airway was correct. The fiberscopic image was videotaped through the course of measurements. Esophageal pressure was measured with a balloon-tipped catheter to evaluate respiratory efforts. Respiratory flow was measured with a pnuemotachogram of appropriate size. These signals were digitized at 100 Hz and stored in a hard disk of a Windows®-based personal computer. The whole body of the subject was also closely observed. The fractions of end tidal carbon dioxide and sevoflurane were also monitored through the course of the study.
Subjects were randomly assigned to either Group 1 or Group 2. Patients in Group 1 were studied at 1% of end-tidal sevoflurane concentration in oxygen, whereas those in Group 2 were at 2% in oxygen. After obtaining a stable respiratory and circulatory condition at the respective depth of anesthesia, the larynx was stimulated when a small dose of warmed distilled water was instilled into the larynx (0.01 mL/kg; 0.2 mL at the minimum) through a channel of the fiberscope under visual observation at end-expiration. Measurements and observations were recorded unless the arterial oxygen saturation decreased to less than 96%. If oxygen saturation decreased to less than 96%, then appropriate treatment was given to avoid further oxygen desaturation.
Laryngeal behaviors, such as laryngeal closure and laryngospasm, were mainly evaluated by visual observation of the larynx through the flexible fiberscope. Cough and/or expiration reflex was confirmed mainly by the flow signal with the combination of the fiberscopic image and direct visual patient observation. Other behaviors such as swallowing and body movements were confirmed by direct visual observation of the patients. The primary responses were identified and categorized as the following: Protective reflex responses of the larynx were categorized into active or passive responses. The active reflex included cough, expiration reflex (cough-like reflex without a deep inspiration before explosive expiration), and swallowing reflex. The passive reflex included apnea, laryngeal closure, and laryngospasm (prolonged closure of the larynx) (5). Apnea was defined as a pause in breathing that exceeded the duration of the 3 tidal regular breaths just before the larynx was stimulated. According to our previous study with adult subjects, the incidences of active and passive reflexes were different depending on the depth of anesthesia (3,6).
Between the two groups, the incidence of active and/or passive reflex was compared using Fisher's exact test. Determination of the sample size was difficult because we had no information about the incidences of each airway protective reflex in children. Therefore, we used the incidence of active reflex of the first 10 subjects (5 subjects from each group). We set the level of 
and 1-ß to be 0.05 and 0.8 respectively, which yielded 14 as minimum sample size (one-sided). Possible maturational effects were examined by a logistic regression. P < 0.05 was considered significant.
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Results |
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Twenty subjects participated in our study, 10 in each group. Elicited responses are presented in Table 1. The range of patient age was 14 wk to 11 yr old. We had to stop measurement and observation in three subjects in Group 1 because their oxygen saturation reached 96%; all of these subjects had vigorous cough and/or expiration reflex that caused dislocation of the laryngeal mask airway. Therefore, we treated them by administrating neuromuscular blockade and repositioning of the laryngeal mask airway, then performing artificial ventilation. No patient had oxygen desaturation below 92%.
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Figure 1 shows typical responses of children to distilled water instillation into the larynx (from subject 7 in Group 1); an endoscopic video clip of the responses from the same subject is also available online. The primary responses were passive reflexes consisting of laryngeal closure, laryngospasm, and apnea. Active reflexes, including expiration reflex and swallowing reflex, were also observed in some children of Group 1 (Table 1); however, the active reflex was not observed in children from Group 2.
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, respiratory flow. Pes, esophageal pressure. In this subject, after only a few breaths after the instillation, laryngeal closure was observed followed by laryngospasm and central apnea. Note that there were no respiratory efforts during apnea. A marked increase in esophageal pressure corresponded to swallowing reflex. The endoscopic video clip of the response observed in this subject is available online.Statistical analysis revealed that active reflex was observed more frequently in Group 1 than in Group 2 (P < 0.01), indicating that sevoflurane may inhibit active reflex more than passive reflex. The logistic regression revealed that effects of maturation were not clear in the age group we tested. Recovery time from the onset of responses to regular tidal breathing was variable and there were no differences between Groups 1 and 2. Recovery time was also not affected by age.
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Discussion |
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The main finding of our study was that, in children, the incidence of active reflex was decreased with increasing depth of anesthesia from 1% to 2% of sevoflurane, whereas that of passive reflex was not affected. Most pediatric anesthesiologists might know that inhaled anesthetics inhibit the airway protective reflex, but this was the first study that confirmed it systematically using endoscopic images in children.
The effects of volatile anesthetics on airway protective reflex in humans were previously examined by Nishino et al. in adult subjects (1,2). They reported that, at 1.0 MAC of enflurane anesthesia, tracheal injection of distilled water caused various kinds of laryngeal responses, such as laryngeal closure, apnea, expiration reflex, and cough reflex. However, by increasing depth of anesthesia to 1.4 and 1.8 MAC, only passive reflexes such as apnea and laryngeal closure were observed in the majority of subjects. These results are consistent with our findings, although the site of stimulation and anesthesia were different (2). On the other hand, they also reported that, under sevoflurane anesthesia, increasing depth of anesthesia from 1.2 MAC to 1.8 MAC has little effect on the incidence of laryngeal responses elicited by distilled water injection into the larynx (1); with either depth of anesthesia, both passive and active reflexes were observed. These conflicting results might have originated from the differences in the depth of anesthesia, in the anesthetics used, and in the sites of stimulation.
Why active laryngeal mechanisms are more affected by inhaled anesthetics is unclear. Sullivan et al. (7) reported that, in dogs, the types of airway protective reflexes were dependent on sleep stages (rapid eye movement [REM] versus non-REM). Therefore, it is naturally expected that the depth of anesthesia also determines the types of reflexes elicited by distilled water instillation into the larynx. These facts may suggest that behavioral control of breathing should play an important role in evoking these reflexes.
Although type of airway protective reflexes evoked from the larynx was not influenced by age, the interpretation of our results may be affected by the small sample size. In fact, the results of the current study were in disagreement with our previous study conducted in adult subjects (1), indicating possible maturational effects.
The results of this study may have clinical implications in airway management during general anesthesia. As traditionally recommended, airway instrumentation under a light phase of anesthesia should be avoided because it causes harmful reflexes, such as laryngospasm and apnea, that may lead to oxygen desaturation in children. Although we did not examine the effects of a deeper level of anesthesia, it is expected that increasing depth of anesthesia will blunt the response.
In conclusion, sevoflurane modifies the incidence of airway protective reflex elicited by distilled water instillation into the larynx; increasing depth of anesthesia resulted in the suppression of active reflexes such as cough, expiration, and swallowing.
The authors appreciate cooperation of staffs in Department of Pediatric Surgery, Department of Plastic Surgery, and Division of Operation Theater.
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Footnotes |
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Supplemental data available at www.anesthesia-analgesia.org.
Supported, in part, by Grant-in-Aid for Scientific Research (C)(2)-14571421 and (C)(2)-16591526 from Ministry of Education, Science, and Technology, Tokyo, Japan.
Accepted for publication June 23, 2005.
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References |
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- Nishino T, Kochi T, Ishii M. Differences in respiratory reflex responses from the larynx, trachea, and bronchi in anesthetized female subjects. Anesthesiology 1996;84:70–4.[Web of Science][Medline]
- Nishino T, Hiraga K, Yokokawa N. Laryngeal and respiratory responses to tracheal irritation at different depths of enflurane anesthesia in humans. Anesthesiology 1990;73:46–51.[Medline]
- Tagaito Y, Isono S, Nishino T. Upper airway reflexes during a combination of propofol and fentanyl anesthesia. Anesthesiology 1998;88:1459–66.[Web of Science][Medline]
- Tanaka A, Isono S, Ishikawa T, et al. Laryngeal resistance before and after minor surgery: endotracheal tube versus laryngeal mask airway. Anesthesiology 2003;99:252–8.[Medline]
- Isono S. Upper airway muscle function during sleep. In: Loughlin GM, Carroll JL, Marcus CL, eds. Sleep and breathing in children: a developmental approach. New York: Marcel Dekker, 2000:261–91.
- Nishino T, Hiraga K, Mizuguchi T, Honda Y. Respiratory reflex responses to stimulation of tracheal mucosa in enflurane-anesthetized humans. J Appl Physiol 1988;65:1069–74.
[Abstract/Free Full Text] - Sullivan CE, Murphy E, Kozar LF, Phillipson EA. Waking and ventilatory responses to laryngeal stimulation in sleeping dogs. J Appl Physiol 1978;45:681–9.
[Abstract/Free Full Text]
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