Postoperative sore throat (POST) is a well-recognized complication after anesthesia contributing to postoperative morbidity and patient dissatisfaction.^1,2 In patients who have had an endotracheal tube inserted, the incidence of POST varies from 40% to 100%.^3–5 POST was rated by patients as the 8th most undesirable outcome in the postoperative period.⁶ Similarly, postextubation coughing (PEC) causes considerable patient discomfort and can result in a number of undesirable side effects, including hypertension, tachycardia, tachyarrhythmia, increased intracranial pressure, and increased intraocular pressure.⁷

Nonpharmacological measures for minimizing POST are smaller-sized endotracheal tubes, lubricating the endotracheal tube with water-soluble jelly, careful airway instrumentation, intubation after full relaxation, gentle oropharyngeal suctioning, minimizing intracuff pressure, and extubation in deeper plane of anesthesia and with a fully deflated tracheal tube cuff.⁸ Pharmacological measures for attenuating POST are beclomethasone inhalation and gargling with azulene sulfonate, aspirin, and benzydamine hydrochloride, local spray with lidocaine and intracuff administration of alkalized lignocaine.^4,9–12 However, all these techniques have their own limitations and variable success rate.

Licorice, derived from the root of Glycyrrhiza glabra, has been used for many millennia as an alternative medicine for treatment of inflammation, allergies, and gastric and duodenal ulcers.¹³ We therefore hypothesized that licorice could decrease POST because of its topical antiirritant, antiinflammatory, and a peripheral and central antitussive effects.¹⁴ This study was therefore planned to evaluate the efficacy of licorice gargle for prevention of POST after orotracheal intubation.

METHODS

This prospective, randomized, single-blind, placebo-controlled study was conducted after approval from the institute’s ethics committee and written informed consent from the patients. We considered patients for inclusion if they were aged between 16 and 60 yr, ASA physical status I and II, of either sex or undergoing elective lumbar laminectomy in the prone position under general anesthesia. During the preoperative visit by an anesthesiologist consultant (PG), patients with a history of preoperative sore throat, upper respiratory tract infection, common cold, gastroesophageal reflux, regurgitation, known allergy to licorice, patients with recent nonsteroidal antiinflammatory drug medication, pregnancy, anticipated difficult intubation, and Mallampati grade >2 were excluded from study.

After exclusion, patients were randomized into two groups of 20 each with the help of a computer-generated table of random numbers. The control group gargled with 30 mL of water. The licorice group gargled with 0.5 g licorice (Yastimadhu 60 g manufactured by Tansukh Herbal, Lucknow, India) made in 30 mL of water. According to their randomization, patients were asked to gargle the study medication for 30 s, 5 min before induction of anesthesia. The dose of licorice chosen for the study was based on the dosage recommended in other studies.^15–16 The gargle solution was prepared by the process of decoction, which involves boiling the licorice powder (5 g) in 300 mL of water and filtering the decoction. This decoction was used within 24 h of its preparation and was used for gargling at room temperature. The solution was not compounded with any other additives like sugar or alcohol. It has a distinct sweet taste and patients did not find it unpleasant. Patients were clearly instructed to gargle with this solution and none of the patients swallowed it. The solution was odorless and investigators were therefore blinded to the preparation used for gargle. Medications for gargle were placed in an opaque container by a staff nurse who was not involved in subsequent management of these patients. Patients requiring >1 attempt for intubation that could not be extubated at the end of the surgery because of any reason or were reintubated within the study period were considered drop-outs.

Patients were premeditated with oral lorazepam 0.04 mg/kg the night and 2 h before the induction of anesthesia with sips of water. Anesthesia was induced with fentanyl 3 μg/kg and propofol 2 mg/kg. Tracheal intubation was facilitated with vecuronium bromide 0.1 mg/kg. Direct laryngoscopy was done with the use of a Macintosh laryngoscope blade by applying minimal pressure and a soft seal cuffed sterile polyvinyl chloride endotracheal tube (Portex, CT 21 6JL,UK); 7.5 mm inner diameter for females and 8.5 mm inner diameter for males was used. Laryngoscopy and endotracheal intubation were performed by an anesthesia senior resident who was blinded to group allocation. The endotracheal tube was lubricated with sterile water-soluble jelly (Lubic (K); Neon Laboratories, Mumbai, India). The cuff was inflated with air maintaining cuff pressure of 18-22 cm of water. Cuff pressure was measured with the help of a pressure-monitoring transducer (Edward Life Sciences, LIC Irvine, CA) by connecting it to a pilot balloon of the endotracheal tube, which then provided a continuous digital display of the intracuff pressure on the monitor. All patients’ lungs were ventilated with O₂ in air (fraction of inspired oxygen [Fio₂] −0.4), keeping the end-tidal CO₂ between 32 and 35 mm Hg.

A heat and moist exchanger was used to provide humidification of the anesthetic gases. Anesthesia was maintained with propofol infusion 100-150 μg · kg⁻¹ · min⁻¹ and intermittent fentanyl and vecuronium as required. At the end of surgery, neuromuscular blockade was antagonized by a combination of neostigmine 0.05 mg/kg and glycopyrolate 0.01 mg/kg. After gentle suctioning of oral secretions by a 12 F suction catheter, patients were tracheally extubated and transferred to the postanaesthesia care unit. Patients received fentanyl via IV patient-controlled analgesia for their postoperative pain.

The primary end point was POST (incidence and severity at rest and on swallowing); secondary end points were occurrence of PEC and side effects, if any. All the end points were assessed by an independent observer (DG) who was blinded to group allocation. PEC was assessed immediately after tracheal extubation in the operation room. The incidence of POST was obtained by inquiring from the patients the presence or absence of soreness in the throat at rest and on swallowing, with the help of a question framed in local language. Severity of POST was assessed using a visual analog scale (between 0 and 100; where 0 means no sore throat and 100 means worst imaginable sore throat). POST and side effects were assessed at 0, 2, 4, and 24 h postoperatively.

Calculation of sample size was based on the presumption that the incidence of POST after licorice gargle would decline to 35% compared with 70% in the control group. For the results to be of clinical significance with α = 0.05 and β = 0.80, one needed to recruit 16 patients in each group. The method of analysis was decided prospectively and incorporated the intention-to-treat principle. Demographic data were analyzed with one way analysis of variance for continuous variables and χ² test for categorical variables. The incidence of POST was analyzed by Z test, whereas severity of POST was analyzed by Mann-Whitney test. The incidence of side effects was analyzed with Fisher’s exact test. SPSS 14.0 (SPSS, Chicago, IL) was used for statistical analysis. P < 0.05 was considered as significant.

RESULTS

Forty-nine consecutive patients were evaluated between September 2007 to April 2008, of which nine patients were excluded from the study because of a history of preoperative upper respiratory tract infection, use of recent nonsteroidal antiinflammatory drug medication, Mallampati grade >2, anticipated difficult intubation, or gastroesophageal reflux. Forty patients were included in this study and received preoperative gargles after randomization. Thirty-seven patients completed the study (18 in the control group and 19 in the licorice group) because three patients were dropped from the study (Fig. 1).

There was no difference between groups regarding to age, sex, weight, height, and duration of anesthesia (P > 0.05) (Table 1). The incidence of POST was reduced in the licorice group compared with the control group both at rest and on swallowing at all time points (P < 0.05) (Fig. 2). The severity of POST was reduced in the licorice group compared with the control group both at rest (0, 2, and 4 h) and on swallowing at (0, 2, 4, and 24 h) postoperatively (P < 0.05) (Fig. 3). The severity of POST at rest, at 24 h, was similar in both groups (P > 0.05) (Fig. 3). The number of patients having PEC was significantly reduced in the licorice group, i.e., two, when compared with six in the control group (P < 0.05). There was no significant difference regarding the side effects in any group (P > 0.05).

Absolute risk reduction and the number-needed-to-treat in the licorice group were 57% and 2%, respectively, in relation to POST during swallowing at 0 h.

DISCUSSION

We observed a significant reduction in the incidence and severity of POST and PEC after a licorice gargle with similar side effect profile compared with a control group.

The etiology of POST is multifactorial and this may be related to patient, technique of anesthesia, and type of surgery.¹⁷ POST might be a consequence of localized trauma, leading to inflammation of pharyngeal mucosa secondary to either laryngoscopy or an endotracheal intubation or both.⁴

Licorice, also known as sweet-wood or Glycyrrhiza glabra, belongs to the Leguminosae family.¹⁸ A number of active ingredients have been isolated from Licorice, such as glycyrrhizin, glycyrrhizic acid, liquilitin, liquiritigenin glabridin, and hispaglabridins.¹⁴ Licorice has been reported to have antiinflammatory and antiallergic properties due to glycyrrhizin.¹⁹ Glycyrrhizic acid has been demonstrated to retard the inflammatory process by inhibiting cyclooxygenase activity, prostaglandin formation, and inhibition of platelet aggregation.²⁰ Liquilitin and liquiritigenin have been reported to have peripheral and central antitussive properties.²¹ Glabridin has significant antioxidant and ulcer-healing properties,¹⁴ which might be helpful in minimizing the extent of ischemic injury to the pharyngeal and tracheal mucosa and expedite their healing.

Injury to the pharyngeal and tracheal mucosa might be caused secondary to laryngoscopy, intubation, and endotracheal tube cuff inflation. The observed reduction in incidence and severity of POST and PEC after licorice gargle might be because of any of these above-mentioned mechanisms in isolation or their additive or synergistic effect.

Ogata et al.¹⁰ observed that preoperative gargling with azunol reduced the incidence of POST from 65% to 25% when patients performed gargle with 4 mg azunol diluted with 100 mL tap water. Similarly, Canbay et al.²² reported a reduction in POST from 78% to 40% after ketamine gargle performed 5 min before induction of anesthesia with 40 mg in saline 30 mL mixture for 30 s. Agarwal et al.⁴ in their previous study stated that aspirin and benzydamine hydrochloride gargle made in 30 mL of water performed after patients’ arrival in the operation room for 30 s were equally effective in reducing POST from 80% to 26%. The methodology of the this study is similar to the previously conducted trials.^4,10,22 Results of the this study are also similar to earlier studies as we observed a reduction in POST (rest) from 78% to 21%. We also observed a reduction in POST (swallowing) from 83% to 21% after licorice gargle. The study conducted by Ogata et al. was double-blind, whereas the rest of the trials were performed in a single-blind fashion.^4,10,22

Licorice extract, due to its ingredient glycyrrhizin, is 50 times sweeter than sugar and is therefore used as a sugar substitute in food.¹⁹ In modern medicine, licorice extracts are often used as a flavoring agent to mask the bitter taste of medicines and as an expectorant in cough and cold preparations.¹⁴ The sweet taste of licorice increases its acceptability as a gargle and can be used without any added flavors. Licorice is cost-effective as the cost of a 60 g pack is around 1 USD (INR 50) in India, and one pack could be used in >100 patients for prevention of POST and PEC. The presence of ulcers in the mouth is not a contraindication for the use of licorice gargle; on the contrary, these patients are reported to benefit from licorice.²³

The limitations of the this study are that it could not be performed in a double-blind manner because of the distinct sweet taste of licorice. At times patients might find it inconvenient to perform gargles in the operation room, especially if they have been well premedicated. Excessive sedation during premedication could increase the chance of aspiration, thus limiting the use of licorice gargle. Licorice gargle is also difficult to perform in uncooperative patients and children.

To conclude, licorice gargle performed 5 min before induction of anesthesia is an effective method for attenuating both the incidence and severity of POST.