Physiologic responses to emergence and tracheal extubation include unwanted airway and circulatory reflexes, which result in coughing, laryngospasm, bronchospasm, tachycardia, and hypertension. Lidocaine has long been used to modulate these responses. The administration of lidocaine has been given via several routes including IV injection (1–3), endotracheal tube (ETT) cuff (4,5), or laryngotracheal instillation of topical anesthesia (LITA™) (6). However, IV lidocaine (IVL) may prolong emergence from general anesthesia (6). Lidocaine administration using LITA™ would block supraglottic reflexes, leading to the risk of aspiration in addition to increased cost. The administration of 4% or 10% lidocaine through the ETT cuff may be dangerous should the cuff rupture as a consequence of damage.
Lidocaine sprayed down the ETT before and during extubation prevents increases in blood pressure (BP) and heart rate (HR) (7). However, it is unknown whether this effect is from local anesthetizing of the airway mucosa or systemic absorption with a secondary deeper plane of general anesthesia. Some authors have suggested that local anesthetics are absorbed rapidly into the circulation when they are applied to the tracheobronchial tree and the concentrations in the blood are thought to be nearly the same as those that follow IV injection within 2–5 min (8,9). Although lidocaine sprayed down the ETT is effective in blunting hyperdynamic responses, it has not been established whether this mode of lidocaine administration can also blunt airway reflexes. Furthermore, it is not known whether the efficacy of lidocaine sprayed down the ETT is comparable with that of IVL. The aim of this study was to investigate whether lidocaine sprayed down the ETT attenuates airway-circulatory reflex during emergence, and compare this with IVL.
With institutional approval and written informed consent, 75 healthy consecutive fasting patients, aged 18–50 yr, using general anesthesia for elective minor orthopedic surgery, plastic superficial surgery, or lower abdominal surgery, were studied. Patients with the following criteria were excluded form the study: history of laryngeal or tracheal surgery or pathology; patients with coexisting systemic illness and those taking cardiovascular medications; history of bronchial asthma; patients requiring major abdominal surgery with a nasogastric tube in place. We defined cough reflex as bucking, expiration reflex, or a true cough.
Atropine 0.01 mg/kg and fentanyl 1 μg/kg were given IM 1 h preoperatively. Before general anesthesia, HR and BP were taken. All patients received a standardized anesthetic protocol. Anesthesia was induced with thiopental (4 mg/kg IV). Vecuronium (0.1 mg/kg IV) was used for muscle relaxation for tracheal intubation of ETT, size of 7.5 mm inside diameter, and was given in 1-mg increments. Patients were ventilated to ETco2 of 32–35 mm Hg with enflurane 2.0–2.5 vol% in 50% nitrous oxide in oxygen. No opioids were used throughout the surgery. Peripheral arterial oxygen saturation, arterial BP using an automated noninvasive BP monitor, and HR using electrocardiography (lead II) were monitored throughout anesthesia. At the end of surgery, enflurane and nitrous oxide were discontinued and 10 mg of pyridostigmine and 0.4 mg of glycopyrrolate were given to reverse neuromuscular blockade.
The patients were randomly divided into 3 groups (n = 25 for each). Group 1 was the control group and was given nothing; Group 2 patients received 1 mg/kg of 2% lidocaine intratracheally by injection from a syringe into the outer aperture of the ETT 5 min before extubation; Group 3 patients received the same dose of 2% lidocaine IV 3 min before tracheal extubation. In practice, the drug was administered 4–5 min in Group 2, and 2–4 min in Group 3 before extubation (Fig. 1). Extubation was performed when the patients could breathe spontaneously and open their eyes on command, perform facial grimace, or attempt self-extubation. The recovery from muscle relaxation was assessed by tidal volume >300 mL. Oropharyngeal secretions were aspirated gently before extubation. Immediately after tracheal extubation, oxygen was supplemented via a facemask 5 min after extubation.
Systolic BP (SBP) and diastolic BP (DBP) were meascured at the end of surgery, which was 5 min before extubation, and served as baseline values. Subsequent meascurements were taken at 3 min, immediately before extubation, immediately after extubation, at 3 min, and at 5 min after extubation and compared with baseline values. Occurrence of cough, laryngospasm, and bronchospasm were continuously monitored and recorded during the observational period. Then, the number of coughs per patient and the rate of coughing within each group were recorded during the observational period. The observers were unaware of the study treatment.
Statistical analysis was performed by using one-way analysis of variance with post hoc Scheffé, paired t-test, and repeated meascures analysis of variance for parametric data, and by using χ2 test, Fisher’s exact test, and McNemar test for nonparametric data. P < 0.05 was considered significant.
Of 85 patients enrolled in the study, 75 completed it. Ten patients were excluded from analysis of the results because of gross protocol deviations (2 in Group1, 4 in Group 2, and 4 in Group 3). No statistical differences were found among the three groups with respect to weight, height, age, duration of anesthesia, and type of surgery, or with respect to preoperative SBP, DBP, or HR values (Table 1).
No patients experienced laryngospasm or bronchospasm after extubation in all the groups. The number of coughs per patient in Group 2 was significantly decreased compared with that of the control (P < 0.01) or Group 3 (P = 0.015) with no significant difference for the control versus Group 3 for 5 min before extubation (Table 2). However, there was no difference in the number of coughs among the three groups for 5 min after extubation. The number of coughs after extubation was decreased significantly compared with those before extubation (P < 0.01, respectively in each group). The number of coughs per patient was decreased in Group 2 compared with the control (P < 0.01), but with a tendency of difference for Group 2 versus Group 3 (P = 0.06) during the whole observational period before and after extubation. There was no statistical difference in the number of coughs between the control and Group 3 during this period. The rate of coughing among the three groups was significantly different during 5 min before extubation or during the whole observational period (P < 0.05) with no significant difference during the 5 min after extubation (Table 2). Lidocaine sprayed down the ETT suppressed the cough reflex effectively whereas IVL did not.
SBP, DBP, and HR were increased in all groups compared with their baseline values (Fig. 2). The increase in SBP and DBP was attenuated immediately only before extubation (P < 0.05) with the tendency of attenuation immediately after extubation (P = 0.056 for SBP, P = 0.077 for DBP) in Group 2 compared with the control. The increase in HR was attenuated at all time points in Group 2 compared with the control (P < 0.05) with no significant difference for the control versus Group 3. Lidocaine sprayed down the ETT decreased circulatory reflexes, but IVL did not.
Coughing and hyperdynamic responses during emergence from general anesthesia are common and are potential clinical problems. In the present study, we found that the coughing reflex was attenuated by lidocaine sprayed down the ETT, but not by IVL. We noticed that patients receiving lidocaine sprayed down the ETT suppressed hyperdynamic responses to the presence of ETT, whereas IVL patients did not. The mechanism responsible for the results that cough and circulatory responses are attenuated by this mode of administration of endotracheal lidocaine is not clear. However, because only lidocaine sprayed down the ETT was effective in blunting the reflexes, the results suggest that lidocaine sprayed down the ETT may provoke mucosal anesthesia to some part of the trachea in contact with the tube and cuff.
We do not understand how lidocaine sprayed down the ETT anesthetized the airway mucosa in contact with the tube, thus resulting in the suppression of the reflexes. We could not find a report that supports that lidocaine sprayed down the ETT blunts the cough reflex. The results of the present study give us the indirect evidence of local anesthesia to the airway mucosa by lidocaine injected from the outer aperture of the ETT. Most lidocaine sprayed down the ETT spreads distally down in the trachea, because lidocaine is expected to spread down the trachea by gravity with patients in the supine position. However, the mucous blanket is wet and this might permit lidocaine to diffuse proximally from the distal end of the ETT, thus blocking the receptors involved in the reflexes in the airway mucosa or anesthetizing some part of the mucosa in contact with the tube directly. Further investigation is required.
Although some authors have suggested that local anesthetics instilled into the trachea are absorbed as rapidly as after IV administration (8,9), several reports show that lidocaine administration to the airways leads to variable plasma concentrations depending on the mode of delivery and dose, and the plasma concentrations are smaller than those of IVL (10–13). Plasma concentrations of lidocaine required to suppress the cough reflex under general anesthesia and during emergence are reported to be between 2.3 and 3 μg/mL (1). Because the plasma concentration of lidocaine from endotracheal administration is the same as or less than that from IVL (1,10–13) and IVL did not affect the reflex responses in our results, we argue that the administration of 1 mg/kg of 2% lidocaine sprayed down the ETT would not lead to peak plasma concentrations sufficient to suppress the reflexes. Thus, the reflex suppression of endotracheal lidocaine is probably attributable to the mucosa-anesthetizing effect.
We chose the times of drug administration depending on previous reports. However, the onset for the reflex suppression and the time to peak plasma concentration after IVL and endotracheal lidocaine are reported to be quite variable depending on the investigators. Mikawa et al. (2) reported that IVL two minutes before tracheal extubation attenuated increases in SBP, DBP, HR, and the cough reflex, whereas others (14) did not. Hamaya and Dohi (15) reported that the maximal plasma lidocaine concentration was 4.3 ± 2.5 μg/mL 5 minutes after IV injection of lidocaine 1 mg/kg, which is more than the plasma concentration (2.3 μg/mL) of lidocaine that is reported to suppress the cough reflex (16). Wilson et al. (14) reported that IVL given four minutes before laryngoscopy prevented an increase in mean arterial BP. Tam et al. (17) found that there was complete attenuation in HR and BP changes when IVL was given only at three minutes before tracheal intubation. From these reports, we determined the time to administration of IVL, i.e., three minutes before extubation. However, local anesthesia is achieved within 2–3 minutes of endotracheal lidocaine application (18,19), and Denlinger et al. (19) reported that topical lidocaine given 5 minutes before intubation blunted the reflex responses effectively. Based on these reports, we administered endotracheal lidocaine five minutes before extubation. Because the airway-circulatory reflex responses occurred around extubation, and because the expected time to effective action for lidocaine via the two routes seemed to be at the time of extubation, we speculate that the time-point difference of the lidocaine administration in Groups 2 and 3 would not cause the different results.
One might argue that the dose of IVL is inappropriately small. IVL 1 mg/kg did not blunt the reflexes during emergence and extubation in the present study, and also in the study of Gonzalez et al. (6). Although the dose for IVL is within the range that other investigators have chosen, we could not exclude the possibility that the dose of IVL might be inadequate for the suppression of the reflexes. However, lack of opioid use that can increase tolerance to the presence of ETT might be a factor. Reflex suppression from IVL might be more influenced by systemic opioid: However, mucosal anesthesia is not affected by opioid use. In fact, we intended to eliminate opioids intraoperatively.
We chose the dose of 1 mg/kg for endotracheal lidocaine to compare IVL at the same dose: If lidocaine sprayed down the ETT is used in a larger dose, the amount of lidocaine absorbed from the airway mucosa would reach peak blood level enough to have the systemic effect like IVL. The larger dose of lidocaine would cause more systemic absorption from the tracheal mucosa, thus blunting the reflexes by systemic effect. In that case, it is not possible to differentiate the local anesthetic effect and the systemic effect that might occur as a result of systemic absorption.
It was not easy to make the patient conform to the timetable in the protocol. We allowed 1 minute from the time of extubation. This is why we administered lidocaine 4–5 minutes in Group 2, and 2–4 minutes in Group 3, before extubation. Of 85 patients enrolled in the study, 10 patients failed to complete it because of inability to remove the ETT in time.
In summary, lidocaine sprayed down the ETT attenuates the airway-circulatory reflexes whereas IVL at the same dose does not. This attenuation seems to be from direct local anesthesia rather than from systemic absorption from the airway. Furthermore, this technique is a simple effective way to suppress the cough and hyperdynamic reflex responses without additional cost.
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