The presence of an endotracheal tube in the trachea acts as a continuous mechanical stimulant to the airway mucosa and elicits airway reflex responses including coughing, expiration reflex, apnoeic reflex and swallowing reflex . It is our experience that patients adapt to endotracheal intubation by becoming less sensitive to the tube with the passage of time. Furthermore, it is our impression that the types of airway reflex responses observed during emergence from general anaesthesia in the presence of the endotracheal tube are quite different from those observed immediately after intubation.
Despite these general impressions, to our knowledge, no clinical study has been performed to elucidate temporal changes in airway protective reflexes with intubation in surgical patients. The purpose of this study is to characterize changes in airway reflex responses to tracheal intubation immediately before and after surgical procedures in patients anaesthetized with sevoflurane. We hypothesized that, in the absence of temporal adaptation of airway protective reflexes during anaesthesia and surgery, the concentration of sevoflurane required to maintain quiet breathing would be much higher after surgery in intubated patients than before surgery, as the effects of surgery would be to cause arousal of the central nervous system.
Fourteen ASA physical status I or II patients (five men and nine women), aged 26-59 years, were studied. All were scheduled for elective surgery, including mastectomy (one patient), lower abdominal surgery (10 patients) and minor orthopaedic procedures (three patients). The protocol was approved by the hospital ethics committee, and each patient gave informed consent. No patient was premedicated.
Anaesthesia was induced with 5% inspired sevoflurane followed by suxamethonium (1 mg kg−1 i.v.), and the trachea was intubated with an endotracheal tube (7.5-mm tube for women; 8.5-mm tube for men). After tracheal intubation, anaesthesia was maintained with 3% inspired sevoflurane in oxygen with spontaneous breathing. The patients did not receive any preoperative or intraoperative opiates. Ventilatory airflow was measured with a pneumotachograph (CP-100; Allied Health Care Product, St Louis, MO, USA) and a differential pressure transducer (Nihon Koden, AB-601, Tokyo, Japan); tidal volume was obtained by electrical integration of the inspired flow. Airway pressure (PAW) was measured continuously with a pressure transducer (Transpac IV; Abbott Critical Care Systems, Chicago, IL, USA). Endtidal PCO2 and end-tidal sevoflurane concentrations were monitored continuously with an infrared CO2 analyser (Aika, RSA-41, Tokyo, Japan) and an anaesthetic gas analyzer (Acoma, model 303, Tokyo, Japan) respectively. The submental electromyogram (EMG) was recorded from surface electrodes placed on the hyoid bone and on the chin, and the resulting signals were filtered and amplified (Nihon Koden bioelectric amplifier, Tokyo, Japan). All of these data were recorded on a thermal array recorder (Omniace RT3424; NEC, Tokyo, Japan).
When the patient was breathing spontaneously and all of the respiratory variables were stable, inspired sevoflurane concentrations were set to achieve and maintain a constant end-tidal concentration (1.3%), and at least 15 min were allowed to elapse before any measurements were made. After confirmation of the absence of airway irritation at this level of sevoflurane anaesthesia, the end-tidal concentration of sevoflurane was slowly decreased with an average continual decrease rate of 0.06% min−1 until signs of airway irritation such as apnoea, forceful expiratory efforts, spasmodic panting and swallowing were observed. The criterion for apnoea used in this study was the absence of inspiration for >10 s. Forceful expiratory efforts included coughing and expiration reflex. Spasmodic panting was defined as a period of >10 s when respiratory frequency was 60 breaths min−1. The swallowing reflex was identified by submental EMG changes and observation of characteristic laryngeal movements.
The value of the end-tidal sevoflurane concentation at the occurrence of airway reflexes was defined as the airway reflex threshold (Tar) of sevoflurane. After the onset of airway reflex responses, the measurements of respiratory variables were continued for 30 s, and the types of airway reflex responses were determined. The determination of Tar and the types of airway reflex response were usually completed within 30 min after tracheal intubation. This period was designated as the 'presurgical period'.
Anaesthesia was maintained with sevoflurane (2-3% inspired concentration) and nitrous oxide (50-70%) during surgery. Ten patients who underwent lower abdominal surgery received vecuronium (0.3-0.4 mg kg−1 i.v.) for approximately 3-6 h for muscle relaxation. Immediately after the completion of surgery, spontaneous respiration was allowed to resume while the patients were breathing 3% inspired sevoflurane in oxygen. For those who received vecuronium, the effect of the muscle relaxant was reversed with atropine (0.02 mg kg−1) and neostigmine (0.04 mg kg−1). The reversal of the muscle relaxant was confirmed by measurements of the train of four (TOF) ratio with an accelerometer fixed to the thumb (TOF Guard; Biometer, Odense, Denmark).
The same procedure as performed in the presurgical period for determining Tar and the types of airway reflex response was repeated, and this measurement period was designated as the 'post-surgical period'.
Statistical analysis was performed using a paired t-test and a Fisher's exact test when appropriate. P<0.05 was considered significant.
All patients showed regular and quiet patterns of breathing during an end-tidal sevoflurane concentration of 1.3%. A gradual decrease in sevoflurane concentration resulted in airway reflex responses in all patients during both pre- and post-surgical periods.
Figure 1 shows experimental records illustrating the appearance of airway reflex responses during the course of decreasing end-tidal sevoflurane concentration in an intubated patient. During the presurgical period (Fig. 1), airway reflex responses characterized by apnoea, spasmodic panting and expiratory efforts were observed at 0.5% end-tidal concentration of sevoflurane. In the post-surgical period (Fig. 1), the end-tidal sevoflurane concentration at the onset of the reflex response was nearly identical to that of the presurgical period. However, the initial response elicited during the progressive decrease in sevoflurane concentration was the swallowing reflex. Similar results were obtained from the majority of patients. The values of Tar for sevoflurane during the pre- and post-surgical periods were 0.6±0.3% (mean±SD, range 0.1-1.0%) and 0.7±0.1% (range 0.4-0.9%), respectively, and there was no statistically significant difference in Tar values between the two periods. The relation between the changes in Tar and the duration of tracheal intubation is shown in Fig. 2. There was no significant correlation between the two variables.
Figure 3 summarizes the incidence of airway reflex responses observed during both the pre- and post-surgical periods. In 11 of the 14 patients, the initial reflex response during the presurgical period was the apnoeic reflex and, in 10 of these 11 patients, the apnoeic reflex was followed by forceful expiratory efforts. Two patients demonstrated expiratory efforts without preceding apnoea. The swallowing reflex was observed in only one patient during this period. In contrast, during the post-surgical period, the initial reflex response was the swallowing reflex in 12 of the 14 patients. In six of these 12 patients, the swallowing reflex was followed by apnoea and/or forceful expiratory efforts shortly after the onset of reflex swallowing at the time of emergence from sevoflurane anaesthesia. The swallowing reflex was not observed in two patients. These two patients demonstrated either spasmodic panting or forceful expiratory efforts as the initial response.
The values of respiratory variables obtained immediately before the appearance of airway reflexes during the two measurement periods are summarized in Table 1. The breathing patterns immediately before the onset of airway responses during the post-surgical period were quite different from those observed during the presurgical period. There were significant differences in the values of minute ventilation (1), respiratory frequency (f) and end-tidal CO2 concentration (ETCO2) between the two periods.
We have demonstrated that a regular and quiet breathing pattern is maintained with an end-tidal sevoflurane concentration higher than 1.0% despite the presence of an endotracheal tube in all patients. A gradual decrease in the sevoflurane concentration causes a sudden onset of irregular breathing patterns, indicating the existence of a certain threshold for the appearance of airway reflex responses. The presence of an endotracheal tube in the airway provided continuous stimulation to the airway mucosa and was responsible for the appearance of the airway reflex responses.
The values of Tar obtained during both the pre- and post-surgical periods ranged from 0.1% to 1.0% sevoflurane. These values are much smaller than the minimum alveolar concentration (MAC) of sevoflurane (1.7-2.05%) in adults [2,3]. This difference between Tar and MAC values indicates that the presence of the endotracheal tube serves as a less effective noxious stimulus than somatic noxious stimuli, particularly surgical skin incision. Two possibilities have to be considered with regard to the finding that low concentrations of sevoflurane are sufficient to maintain quiet breathing in the presence of the endotracheal tube. First, the presence of an endotracheal tube per se cannot be a strong noxious stimulant in anaesthetized patients. Secondly, it is possible that endotracheal intubation has an effect on laryngeal and tracheal receptors responsible for stimulation of airway protective reflexes , which in turn results in the impairment of airway reflex responses.
In the present study, we also observed that the values of Tar obtained during the presurgical period were not different from those obtained during the post-surgical period. Furthermore, Tar had no correlation with the duration of intubation. However, these results do not necessarily deny the possibility of modification of airway reflex responses during prolonged endotracheal intubation. We observed that the types of reflex responses elicited first during the presurgical period were quite different from those during the post-surgical period, indicating that some modification of airway reflexes might occur during the prolonged presence of an endotracheal tube.
According to the classical Guedel system modified by Gillespie , the swallowing reflex is more sensitive to increasing depth of ether anaesthesia than glottic reflexes. Thus, the occurrence of the glottic reflexes usually precedes that of the swallowing reflex during emergence from general anaesthesia. We observed that the initial responses during the presurgical period were the apnoeic reflex and/or forceful expiratory efforts. Assuming that the swallowing reflex is more easily depressed by sevoflurane than the glottic reflex responses, the initial responses during emergence from anaesthesia should be glottic reflexes, which is compatible with our observation in the presurgical period. However, the predominant occurrence of the swallowing reflex during the post-surgical period cannot be fully explained by the differences in the sensitivity of reflex responses to general anaesthesia. Thus, there may be some other mechanisms that modify the airway reflex responses after prolonged endotracheal intubation in surgical patients.
It is possible that the observed modification of airway reflexes may occur at a peripheral site, as the prolonged presence of an endotracheal tube may cause some pathyphysiological changes in airway receptors in the mucosa and result in alterations in airway reflex responses. However, in 6 out of 12 patients whose initial response was the swallowing reflex, this was eventually followed by glottic reflex responses at emergence from general anaesthesia, suggesting that the receptors responsible for the appearance of apnoea and forceful expiratory efforts are intact in these patients. Thus, it is unlikely that such modification may occur only at the peripheral site.
It is quite likely that the residual effects of surgery may cause arousal of the central nervous system during the post-surgical period. In this study, there was a considerable increase in minute ventilation with a concomitant decrease in end-tidal CO2 concentration during the post-surgical period. The increase in minute ventilation was achieved primarily through an increase in respiratory frequency, as there was no significant change in tidal volume. A similar change in breathing pattern has been observed in patients anesthetized with isoflurane during surgical stimulation . The change in breathing patterns during the post-surgical period suggests that the residual effects of surgery act as a ventilatory stimulant. These might be expected to increase airway responsiveness and Tar, although this did not occur. An alternative central mechanism capable of counteracting the arousal effects, which then causes the predominant occurrence of the swallowing reflex, probably exists. Although there is no definite evidence, we speculate that this may result from continuous stress including noxious stimulation from the site of surgery and/or continuous mechanical stimulation of the airway mucosa resulting from the presence of the endotracheal tube. If this is the case, modification of airway reflex responses after prolonged intubation may possibly involve some adaptation mechanisms occurring in the central nervous system.
In conclusion, we have demonstrated that the threshold concentration of sevoflurane for the appearance of airway reflexes during emergence from anaesthesia is remarkably low, compared with the MAC of sevoflurane. Tar did not change during the duration of intubation (2-7 h), although a difference in the types of reflex response elicited during emergence from anaesthesia between the pre- and the post-surgical periods was evident. These results suggest that there may be adaptation mechanisms responsible for temporal changes in airway reflex responses after prolonged endotracheal intubation in surgical patients.
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