Recently, quality assurance of anesthesia has become increasingly important for improving postoperative outcome. Postoperative sore throat (POST) is a minor complication that is unresolved in patients undergoing endotracheal intubation (1–12). Avoiding POST is a major priority for these patients because preventing postoperative complications contributes to patient satisfaction (1,2). Many factors are potentially associated with POST, including patient characteristics (2–4), methods (3–9), and materials (9–12). Moreover, there are some interventions that effectively attenuate POST (13–16).
Azulene, a chamomile extract, has antiinflammatory effects (17–20). Sodium 1,4-dimethyl-7-isopropylazulene-3-sulfonate monohydrate (sodium azulene sulfonate, Azunol) is derived from azulene. Sodium azulene sulfonate is used to treat chronic gastritis and ulcers (21,22). Gargling with Azunol might be a simple, effective way to prevent POST.
In this study, we investigated whether preoperative gargling with Azunol reduced POST after endotracheal intubation.
After obtaining the approval of our IRB and the patients’ informed consent, 40 patients (ASA physical status I–II) scheduled for elective orthopedic surgery of the lower extremities under general anesthesia were enrolled in this study. There were no restrictions on recruiting the patients by type of surgery. Patients with a history of a reaction to herbs, upper respiratory tract disease, or gastroesophageal reflux or regurgitation were excluded from this study. Before the study, we explained the nature of the study to the patients using documents approved by our IRB.
None of the patients received any sedative drugs preoperatively. In the Azunol group, the patients gargled with 4 mg Azunol diluted with 100 mL tap water (40 μg/mL). The Azunol was a gift from Nippon Shinyaku CO, Ltd. In the control group, the patients gargled with 100 mL of tap water. We prepared two opaque cups covered with a lid and each patient selected one of these cups randomly; the patients could not determine whether the solution was tap water or Azunol by color or smell. Using the selection, the patients were randomized into two groups: one group gargled with Azunol (Azunol group) and one with tap water (control group).
General anesthesia was induced with 1.5 mg/kg propofol and 0.1 mg fentanyl IV, and maintained with 1.5%∼2% sevoflurane in 5 L/min oxygen. Vecuronium (1 mg/kg IV) was used to facilitate tracheal intubation. Endotracheal tubes with inner diameters of 7.5 mm and 8.0 mm with low-pressure cuffs (Sheridan; Kendall Healthcare Products CO, Inc., Mansfield, MA) were inserted orally. The endotracheal tubes were lubricated with tap water. Using sterilized gloves, one skilled anesthesiologist blinded as to group assignment performed all the intubations with an autoclaved laryngoscope. Patients who required more than two attempts at endotracheal intubation were excluded from the study. The cuff was inflated and maintained to the point of obtaining a seal at 20 cm H2O of peak airway pressure. The intracuff pressure was reconfirmed intermittently. No nasogastric tube was inserted in any patient. After emergence from general anesthesia, we aspirated saliva from the pharynx before tracheal extubation. After this, all the patients were tracheally extubated gently. Patients in whom extubation provoked bucking or coughing were excluded from this study.
The patients with POST were counted, and POST was evaluated using a verbal analog pain scale (VAS) (Table 1) immediately after tracheal extubation and 2, 4, and 24 h after the operation by another anesthesiologist blinded as to the two groups.
All the results are expressed as means ± sd. To compare patient characteristics, including age, height, body weight, and duration of anesthesia and surgery, Student’s t-test was performed. The Mann-Whitney U-test was used for multiple paired comparisons of counts and VAS in patients with POST. P < 0.05 was considered statistically significant.
The study population consisted of 40 patients: 20 patients gargled with Azunol (Azunol group), and the remaining 20 patients gargled with tap water (control group). There were no significant differences between the groups in terms of age, height, body weight, gender distribution, or duration of anesthesia or surgery (Table 2). There were no severe complications or adverse reactions in either group.
In the control group, 13 patients (65%) complained of POST, which remained 24 h later in nine patients (45%) (Table 3). In the Azunol group, five patients (25%) also complained of POST, which disappeared completely by 24 h later (Table 3). Both the incidence of POST and VAS scores were significantly lower in the Azunol group than in the control group (Table 3, Fig. 1).
In the control group, the incidence of POST 2, 4, and 24 hours after surgery in the control group was 90%, 55%, and 45%, respectively (Table 3). The reported incidence of POST is between 45.4% and >90% (2–5,10,11). Our results in the control group were consistent with previous findings. In our study, both the incidence and VAS of POST were significantly lower in the Azunol group than in the control group. There were no adverse reactions in the Azunol group. This is the first report of the efficacy of gargling with Azunol in reducing POST.
In the Azunol group, patients gargled with 4 mg Azunol diluted with 100 mL tap water (40 μg/mL). Azulene is absorbed from the nasal cavity rather than the oral cavity (23). Seki et al. (24) reported that the absorption rate of azulene was trivial at concentrations less than 1 mg/mL. Moreover, azulene transfers into the systemic circulation only via the small intestine after clinical application to the oral cavity (25). Therefore, at the small concentration of 40 μg/mL, systemic absorption of Azunol is avoided and no systemic reaction was evoked.
In contrast to our results, Kyokong et al. (26) demonstrated that 111 mg chamomile extract administered before tracheal intubation did not prevent POST or hoarseness. They postulated that use of an oral airway was the cause of POST. Although postoperative use of an oral airway, in addition to an endotracheal tube, would theoretically increase the incidence and VAS scores of POST, their results (63.9%) were consistent with previous findings. Therefore, we postulate that they did not consider complaints of mild POST, given that a severe, significant reaction in patients with an oral airway could hinder identification in patients without an oral airway. Conversely, at small concentrations, the toxicological safety of Azunol preparations in the oral cavity has been well described (23–25). We used a single application of 4 mg Azunol (40 μg/mL), and no patient had a cytotoxic reaction. A cytotoxic reaction with our protocol would be rare, but care should be taken to detect allergic reactions.
In conclusion, we demonstrated that gargling with Azunol effectively attenuated POST, with no adverse reactions. Azunol gargling might reduce the incidence of complications associated with endotracheal intubation.
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© 2005 International Anesthesia Research Society
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