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Anesth Essays Res. 2017 Jan-Mar; 11(1): 94–100.
PMCID: PMC5341650

Postoperative Sore Throat Prevention in Ambulatory Surgery: A Comparison between Preoperative Aspirin and Magnesium Sulfate Gargle – A Prospective, Randomized, Double-blind Study

Abstract

Background:

Postoperative sore throat (POST) frequently hampers the positive feedback of ambulatory surgery in spite of so many measures. This study was carried out to compare the efficacy of preoperative magnesium sulfate and aspirin gargle in preventing POST after ambulatory surgery.

Materials and Methods:

It was a prospective, randomized, and double-blinded study. Fifty-six adult patients of either sex, aged 25–50, of American Society of Anesthesiologists physical status I–II, scheduled for day care surgery, were randomly allocated to Group A ([n = 28] receiving aspirin gargle [325 mg tablet]) and Group M ([n = 28] receiving magnesium sulfate [20 mg/kg] gargle). In both groups, the medications were made into 20 mL of (5% dextrose) solution. Patients were asked to gargle with this mixture for 30 s, 15 min before induction of anesthesia. Episodes of POST were measured at 0, 2, 4, 6, 9, 12, and 16 h postoperatively with a four-point scale.

Results:

Both groups had a similar demographic profile with comparable oxygen saturation, hemodynamics, and consciousness status at immediate postoperative period. Number of patients with sore throat was significantly lower in magnesium group compared to aspirin group at 0 h (P = 0.0376), 2 h (P = 0.0429), 4 h (P = 0.0394) after the operation. POST pain score (visual analog scale) was significantly (P < 0.05) lower in magnesium group compared to aspirin group after the operation at 0, 2, 4 h after operation.

Conclusion:

It is evident that preoperative magnesium sulfate gargle significantly attenuated the incidence and severity of POST, especially in the early postoperative period, with no adverse effects in patients undergoing day care surgery under general anesthesia.

Keywords: Aspirin, day care surgery (ambulatory surgery) magnesium sulfate, postoperative sore throat

INTRODUCTION

Postoperative sore throat (POST), one of the most common minor complication and distressing adverse events experienced by patients receiving general anesthesia (GA) with tracheal intubation especially while undergoing short stay ambulatory surgery.[1,2] Although considered as a minor complication, but it may cause significant postoperative morbidity and patient dissatisfaction.[3] POST had been rated by patients as the eighth most adverse effect in the postoperative period after general surgery with incidence of 21–65%.[3,4] Many factors can contribute to POST, and the incidence has been found to vary with the method of airway management.[5] The incidence is the highest after tracheal intubation (45.4%), whereas after laryngeal mask airway use the incidence is lower (17.5%) and much less (3.3%) when a facemask is used for the maintenance of anesthesia.[1,5,6] Female sex increases the incidence and severity of POST.[1]

Various nonpharmacological and pharmacological trials have been used for attenuating POST with no proven single modality having a successful outcome. Among nonpharmacological methods, small sized endotracheal tubes (ETTs),[7] smooth laryngoscopy and intubation, cuff design minimizing cuff pressure,[8] lubricating the tubes with water soluble jelly,[9] gentle oropharyngeal suctioning and extubation when the cuff is fully deflated have been reported to decrease the incidence of POST.

Although many preventive protocols have been offered, none has gained much attention. However, drug-based preemptive treatment for pain and dysphagia is the mainstay of treatment for POST prevention. Various pre-, intra-, and post-operative pharmacological agents such as steroids (dexamethasone, betamethasone, fluticasone, methyl prednisolone),[10,11,12,13] opioids,[14] local anesthetic agents,[15] nonsteroidal anti-inflammatory drugs (NSAIDs),[16] α2 agonists,[17] and ketamine[18] were used with the aim of reducing the occurrence of POST after GA.

Aspirin (NSAID) gargles are reportedly effective in relieving POST has already been evaluated.[16] Again preoperative magnesium (N-methyl-D-aspartate receptor antagonist [NMDA]) lozenge effectively reduces both incidence and severity of POST.[19] Topically applied magnesium sulfate is famous for its therapeutic application on tissue suffering from thrombophlebitis as well as it has a preventive role in the similar conditions.[20]

From these above-mentioned two studies, we hypothesize that preoperative oral magnesium gargle treatment would be effective in reducing sore throat because of its anti-inflammatory and antinociceptive effects. Therefore, to test that hypothesis, this current study was planned to compare the efficacy of magnesium and aspirin gargle given 15 min before induction of anesthesia on reducing POST during 24 h after surgery, when POST was caused by oral tracheal intubation in patients undergoing day care surgeries.

MATERIALS AND METHODS

From December 2009 to June 2011, after obtaining permission from Institutional Ethics Committee, written informed consent was taken. A total 56 adult patients were randomly allocated to two equal groups (n = 28 in each group) using computer generated random number list. American Society of Anesthesiologists (ASA) physical status I and II, aged between 25 and 50 years of both sexes undergoing short stay ambulatory surgery were enrolled in the study.

Patients in Group A received aspirin gargle (ECOSPRIN® 325, USV Limited, Mumbai, Maharashtra, India) (325 mg tablet was dissolved into 20 mL of [5% dextrose] solution). Group M received magnesium sulfate gargle (MAGNEON® 50% w/v, Neon Laboratories Limited, Thane, Maharashtra, India) ([20 mg/kg] magnesium sulfate solution was dissolved into 20 mL of [5% dextrose] solution). Patients were asked to gargle with this mixture for 30 s, 15 min before induction of anesthesia.

Exclusion criteria

Patient refusal, any known hypersensitivity or contraindication to aspirin, magnesium sulfate, pregnancy, lactating mothers, hepatic, renal or cardiopulmonary abnormality, alcoholism, diabetes, long-term analgesic therapy were excluded from the study. Patients having a history of significant neurological, psychiatric, or neuromuscular disorders were also excluded from this study.

In preoperative assessment, the patients were enquired about any history of drug allergy, recent sore throat, previous operations, or prolonged drug treatment. General examination, systemic examinations and assessment of the airway were done. Preoperative fasting of minimum 6 h was ensured before the operation. All patients received premedication of tablet diazepam 10 mg orally the night before surgery as per preanesthetic check-up direction to allay anxiety, apprehension, and for sound sleep. The patients also received tablet ranitidine 150 mg in the previous night and the morning of operation with sips of water.

All patients were clinically examined in the preoperative period when whole procedure was explained. Patients were allowed to gurgle slowly for 30 s, 15 min before induction of anesthesia with the solution as per allotment of the group and drug. The gargles were wrapped in colored nontransparent glasses to ensure blinding. The anesthesiologist distributing the solution for gurgling was unaware of the constituent of the drug and allotment of the group and similarly resident doctors keeping records of different parameters were also unaware of group allotment. Thus, blinding was properly maintained.

All patients are investigated for Hb%, total leukocyte count, differential leukocyte count, erythrocyte sedimentation rate, platelet count, blood sugar, blood urea, serum creatinine, and liver function tests. A 12 lead electrocardiogram (ECG) and chest X-ray were also taken. On entering the patient in the operative room standard intraoperative monitors such as ECG, pulse oximeter, noninvasive blood pressure (BP) were attached, and baseline parameter were recorded. Intravenous (IV) infusion of Ringers’ lactate started. After intubation end-tidal carbon dioxide (EtCO2) monitor was attached.

The patients were preoxygenated with 100% oxygen for 5 min. Injection fentanyl (2 μg/kg) and glycopyrrolate (0.01 mg/kg) were given intravenously 3 min before induction of anesthesia. For induction, injection propofol was administered up to loss of verbal command. Injection atracurium 0.5 mg/kg IV was used for intubation. After 3 min of atracurium administration, laryngoscopy and intubation were performed. The trachea was intubated with a soft seal cuffed sterile polyvinyl chloride ETT with a standard cuff (Fuzhou Kanglite Medical Apparatus Co. Ltd., Fuzhou, China) and an internal diameter of 7–8 mm for women and 8–9 mm for men. Tracheal intubation was performed by an experienced anesthesiologist after ensuring maximum neuromuscular blocking effect as assessed by train-of-four guard. All the patients received IV paracetamol 1000 mg, 30 min after tracheal intubation. Anesthesia was be maintained with nitrous oxide 66% in oxygen and isoflurane up to 1–2 minimal alveolar concentration. The tracheal tube cuff was inflated until no air leakage could be heard with a peak airway pressure at 20 cm H2O and cuff pressure was maintained between 18 cm and 22 cm H2O using handheld pressure gauge (Endotest; Rüsch, Kernen, Germany). Those patients who required more than one attempt for passage of the tube were excluded from the study. After completion of surgery, neuromuscular block was reversed with injection glycopyrrolate 0.01 mg/kg and injection neostigmine 0.05 mg/kg and extubated when adequate spontaneous ventilation was established. Oropharyngeal suction was performed under direct vision to avoid trauma to the tissues before extubation and to confirm that the clearance of secretions was complete.

The patients were interviewed in a standard fashion by an anesthesiologist (blinded investigator) who is unaware of the group allocation. On arrival in the postanesthesia care unit (0 h), and at 1, 2, 4, 6, 9, 12, 16, and 24 h thereafter, POST was graded on a four-point scale (0–3).[16] Grade 0 = no sore throat; Grade 1 = mild sore throat (complains of sore throat only on asking); Grade 2 = moderate sore throat (complains of sore throat on his/her own); Grade 3 = severe sore throat (change of voice or hoarseness, associated with throat pain). Other side-effects, if any, were also noted. ECG (lead-II) and heart rate, SpO2, systolic BP (SBP), diastolic BP, mean BP, EtCO2, respiratory rate, temperature were recorded throughout the operative procedure. Multichannel monitors (Philips IntelliVue MP20) were used for measuring above mentioned parameters. Visual analog scale (VAS) for postoperative pain score ([0–10 cm], 0 = no pain, 10 cm = worst pain imaginable).

Statistical analysis

Calculation of sample size was based on the assumption that the incidence of POST is 60% and to show a 40% reduction in the incidence at α = 0.05, confidence interval of 95%, and a power 90% we required a sample size of 25 patients per group. On adding 10% patients for possible loss to follow-up, the sample size required was 28 patients per group. The collected data were analyzed using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA, version 15.0 for windows). Categorical variables were analyzed using the Pearson's Chi-square test. Normally, distributed continuous variables were analyzed using the independent sample t-test. Hemodynamic variables between the groups were compared with t-test. Differences in the incidence of POST among the groups were compared with Mann–Whitney U-test and severity of POST with Fisher's exact test. P <0.05 was considered as statistically significant.

Results and Analysis

We recruited 28 subjects per group, more than the calculated sample size. There were no dropouts. The age, sex distribution, body weight, ASA status, and duration of surgery and anesthesia in both groups were found to be comparable [Table 1]. Duration of surgery and anesthesia was not significantly different between two groups (P = 0.217 and P = 0.130). Number of patients with sore throat were significantly lower in the magnesium group compared to aspirin group starting from immediate recovery (P = 0.0376), 2 h (P = 0.0429), 4 h (P = 0.0394) [Table 2]. However, from 6 h (P = 0.6592), 9 h (P = 0.1266), 12 h (P = 0.1010), and 16 h (P = 0.1010) after operation both groups were quite comparable in regard of incidence of sore throat. The severity of sore throat was also significantly higher in Aspirin group at immediate recovery, 2 h, 4 h but at other time intervals, the severity was quite comparable. Heart rate, SBP, respiratory rate, oxygen saturation, and consciousness status among two groups were quite comparable [Table 3]. No any group had shown any appreciable side effect to be mentioned separately. Figure 1 shows that VAS score was of much higher value in Group A than M Group. Consort flow diagram shows the patient enrollment, allocation, follow up, analysis of all the patients in the study [Flow Chart 1].

Table 1
Comparison of demographic data between the two study groups
Table 2
Comparison of postoperative sore throat with severity at 0, 2, 4, 6, 9, 12, 16 h in patients
Table 3
Comparison of oxygen saturation, hemodynamics, and consciousness status among two groups
Figure 1
Comparison of visual analog scale score among Groups M and A.
Flow Chart 1
Consort 2010 flow diagram.

DISCUSSION

Day care surgery has proven over the years as the best method to reduce the burden on the health care resources, as well as achievement of extreme patient satisfaction.[21] In developing countries, most of the patients avoid bearing expenses of prolonged hospital stay. In the daycare scenario, especially after intubation in GA POST in the immediate and delayed postoperative period is the most frequent (14.4–50%) cause of delayed discharge and discomfort.[21] Sometimes, it causes unplanned revisit and subsequently delayed return to work.[21]

The cause of sore throat related to ETT cuff might be a consequence of localized trauma, leading to aseptic inflammation which leads to congestion and edema of pharyngolaryngeal mucosa. Coughing and soreness of throat induced by an ETT can complicate emergence from GA, thus resulting in potentially dangerous hyperdynamic responses in the postoperative period. Such responses include tachycardia, hypertension, dysrhythmia, raised intraocular pressure, increased intracranial pressure, wound dehiscence, and bronchospasm. It has been well documented that coughing and its sequelae can be harmful for patients.[22,23,24] Intracuff pressure increases when nitrous oxide is used in GA and this pressure may also aggravate POST.[25]

Hence, in an ambulatory care set up management for preventing POST is still advised because it promotes the patient's satisfaction and affects the activities after discharge from the hospital.[1] Therefore, different agents with variable success have been used for decreasing both the incidence and severity of POST in daycare set up.[10,11,12,13,14,15,16,17,18] but the results are either inconclusive or associated with side effects.

Aspirin; having analgesic, antipyretic, local anesthetic, anti-inflammatory properties; gets rapidly converted in the body to salicylic acid with a terminal half-life of the anti-inflammatory dose being 8–12 h.[26] These actions are mediated by inhibition of prostaglandin system. Aspirin gargle has been reported to be effective for relieving pain of oral lesions.[27]

Magnesium has antinociceptive effects that are primarily based on the inhibition of calcium entry into the cell, and blocks the NMDA-type glutamate receptors.[28] There has been substantial evidence that magnesium therapy given via IV route, either preoperatively or perioperatively, has the adjuvant effects on decreasing postoperative pain and analgesic requirements.[29] After topical application, anti-inflammatory and antinociceptive properties of magnesium were evident from a study conducted by Schempp et al. and available data suggested that magnesium may have a potential role in reducing POST.[30] At the time, the current trial was designed, no study on magnesium gurgle was available for preventing POST in day care setting.

In this prospective, randomized, and double-blinded trial, we had compared the effect of preoperative gargle with magnesium and aspirin given 15 min before surgery on incidence and severity of POST, hemodynamic parameters and pain associated with sore throat and side effects, if any.

The demographic profile, between two groups, which was statistically insignificant (P > 0.05) of our patients was quite similar with other research investigations and provided us the uniform platform to evenly compare the results obtained. A study on the role of magnesium gargle for prevention of POST was conducted by Teymourian et al. in a total of 100 patients yielded similar results.[31] The mean duration of surgery and anesthesia time were also almost comparable in both groups with no significant statistical difference [Table 1].

In a previous study, Agarwal et al.[16] compared the efficacy of dispersible aspirin gargle with benzydamine hydrochloride gargles for prevention of POST. They found that aspirin and benzydamine hydrochloride gargles significantly reduced the incidence and severity of POST. In another placebo-controlled study, Borazan et al.[19] found that oral magnesium lozenges had significantly reduced the severity and incidence of POST. In our study, we have found that magnesium gargle, whereas compared with aspirin gargle, had more effectively reduced the incidence and severity of POST after GA at 2nd and 4th h (P = 0.042 and P = 0.039 respectively). During this period, the difference was statistically significant. However, after 4th h, the difference was quite comparable among two groups.

The primary outcome of the study was the incidence of POST at 4 h as by this time the patents are generally awake, alert, and more cooperative to participate in the study. This is clearly in line with earlier studies.

Both groups showed comparable (P > 0.05) hemodynamic parameters throughout the study duration [Table 3]. Magnesium treated group had a relatively low BP and heart rate probably this is due to anti-adrenergic effect of magnesium.[29]

In our study, the pharmaceutical form of magnesium is a magnesium sulfate solution form that magnesium becomes readily ionized, which is the active form of magnesium used by tissues. This is essential for local adsorption. In addition, we think that the direct contact of magnesium ions with pharyngeal wall is an important issue. Nevertheless, we suggest that magnesium works locally, and it is adhered to the pharyngeal wall. In case of POST, when the process of passing through to the tissue begins, it can also decrease the edema if it is used as a preoperative gargle form. Thus, its effect might begin immediately when it is contacted with the wall and absorbed from there as long as it stays in the pharyngeal tissue.

Several hypothesized mechanisms of action have been suggested to explain the analgesic effect of magnesium. Magnesium exerts its analgesic action as a noncompetitive NMDA receptor antagonist, blocking ion channels in a voltage-dependent manner.[32] The addition of magnesium reduces the activation of C-fibers by inhibiting the slow excitatory postsynaptic currents produced by NMDA receptor activation.[33] NMDA receptor antagonists abolish calcium and sodium influx into cells leading to central sensitization and wind-up attributed to peripheral nociceptive stimulation.[32,33,34] They abolish hypersensitization by blocking NDMA receptor activation in the dorsal horn by excitatory amino acid transmitters, notably glutamate, and aspartate.[34] Magnesium is also known as “nature's physiological calcium channel blocker.” In animals, calcium channel blockers have demonstrated an antinociceptive effect and in chronic pain patients, they potentiate the effects of morphine.[35]

Several potential limitations of our study should be considered. First, although the sample size seems to be relatively small, we were able to successfully test our desired outcomes. However, to avoid type I error, it would be better if the sample size was computed from the incidence derived from a meta-analysis of POST. Second, the mechanism of the novel therapy of oral aspirin and magnesium gargle is still unknown. Data concerning the pharmacokinetic effects of aspirin and magnesium sulfate gargle are limited; therefore, it is difficult to point out the exact administration time and dosage of drug in the gargle. Based on previous data in which different pharmaceutical forms of aspirin and magnesium sulfate were used, the estimated peak effect and duration of action of oral aspirin and magnesium gargle was stated. Third, in our study, the dosage was empirical, with no pilot data. We used a single dose of aspirin or magnesium sulfate slightly lower than the recommended daily allowance of both the drugs and we also examined its effectiveness on reducing POST.

CONCLUSION

Concerning therapeutic effects, a single dose of preoperative oral gargle with magnesium administered 15 min preoperatively can more effectively decrease the incidence and attenuate the severity of POST in the immediate postoperative period, especially while compared with similar form of aspirin.

Further studies, regarding time and dose-ranging studies with larger study populations, are needed to compare magnesium with aspirin in the gargle form to prevent the POST after GA in an ambulatory care setting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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