Abstract

Background

Postoperative sore throat is a common problem. The efficacy of topical application of non-steroidal anti-inflammatory drugs in alleviating postoperative sore throat has not been established. Our aim was to evaluate the analgesic effects of diclofenac epolamine patch on postoperative sore throat.

Methods

The study was conducted in a prospective, randomized, double-blind, and placebo-controlled manner. Two hundred and twenty women undergoing elective cesarean section (because of previous cesarean section) were randomized into two equal groups: the diclofenac epolamine patch group and the placebo group. The surgery was performed under general anesthesia after rapid sequence induction. Data of the baseline characteristics, the incidence and severity of sore throat and the adverse effects of diclofenac patch were collected.

Results

The participants were similar in baseline characteristics. The incidence of sore throat, as assessed 12, 24 and 48 hours after using the patch was significantly lower in the diclofenac patch group than in the placebo patch group, with p values 0.04, < 0.001 and 0.015, respectively. None of the participants dropped out of the study because of complications.

Conclusion

The diclofenac epolamine patch is effective and safe in prevention of sore throat following intubation general anesthesia in cesarean section.

Keywords

diclofenac; postoperative complications; sore throat;

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1. Introduction

Sore throat is a common problem after general anesthesia, and the reported incidence varies from 6.6% to 90%.¹⁻³ The incidence of sore throat is affected by the endotracheal tube (size, type, cuff design, cuff pressure), dryness of inspiratory gases, rough suction and endotracheal tube lubricants. Sore throat is more common in the following conditions: use of a larger size tube or red rubber tube (in comparison with polyurethane tubes), a higher cuff pressure applied, use of an uncuffed tube (drawing non-humidified gas across the airway mucosa during spontaneous respiration), the form of intubation (in comparison with mask or laryngeal mask airway ventilation), difficult intubation, and the use of depolarizing muscle relaxants.⁴⁻¹² Female sex,^13,14 younger age, and gynecological surgical procedures¹⁵ have been suggested as factors in sore throats but this is controversial. It is therefore logical to study this problem in a susceptible patient group for clarification. In our country, general anesthesia is usually applied for cesarean section at the patient’s request.

The topical application of non-steroidal antiinflam matory drugs (NSAIDs) is effective in decreasing both acute and chronic pain,¹⁶ but the evidence supporting the use of transdermal NSAIDs for postoperative sore throat is limited.²

Our aim was to determine if the application of a diclofenac patch at the beginning of the surgery had an effect on postoperative sore throat.

2. Methods

The study protocol was approved by our university ethics committee. Informed consent was obtained from all patients before their enrolment in the study. 

Participants were ASA physical status I or II women, scheduled for elective repetition of cesarean section. They all preferred general anesthesia during surgery. Exclusion criteria included history of asthma, smoking, known hypersensitivity to NSAIDs, coagulopathy, anticipated difficult airway, evidence of preeclamp sia, history of gastrointestinal bleeding, significant liver or renal disease, history of psychological disorders, steroid consumption, and recent upper respiratory tract infection or irritation.

Patients were randomly allocated to two equal groups of 110 each (Figure 1). Randomization was made by using 220 sequentially numbered opaque envelopes, each containing a small piece of paper on which either diclofenac or placebo was printed. The two differently labeled pieces of paper were equal in number, 110 in either form.

Before the induction of general anesthesia, an epidural catheter was inserted for postoperative pain control. After preoxygenation, rapid sequence induction of general anesthesia was done, using intravenous thiopental sodium (5 mg/kg) and succinylcholine (1.5 mg/kg).

All patients were intubated with a 7-mm inner diameter endotracheal tube incorporated with a low-pressure cuff (with eyelet; Supa Inc., Tehran, Iran). All intubations were performed by a unique anesthesiologist, using a size 3 Macintosh blade, and were successful at the first attempt. No lidocaine gel or other lubricant was used to glide the endotracheal tube. The cuff was inflated to the point just capable of sealing leakage (approximately at a pressure of 20 mmHg). Intracuff pressure was checked and adjusted every 10 minutes using a pressure gauge (Digital P-V Gauge™; IMP Inc., Cleveland, OH, USA) to avoid nitrous oxide-related intracuff pressure increase. Anesthesia was maintained with 0.6% isoflurane and nitrous oxide in 50% oxygen. After the resumption of muscle activity from succinylcholine blockade, atracurium (0.2 mg/kg) was administered for subsequent muscle relaxation. The ventilator setting was adjusted to maintain PtCO₂ at 35−40 mmHg.

The anesthesiologist and patients were not aware of the allocation. Diclofenac or placebo patch was applied to the skin of the anterior aspect of the neck just before the induction of anesthesia. The tested patch was made of non-woven polyester (Flector Tissuegel^®; IBSA IBSA Institut Biochimique SA, Lugano, Switzerland), whose working surface was smeared with a layer of 1.3% diclofenac epolamine (equivalent to 1% diclofenac free acid) with hydrophilic adhesive. Each patch was 10 ˜ 14 cm in size. The placebo patch (Daru Pakhsh, Tehran, Iran) was of identical appearance to the diclofenac patch. All patches were removed 12 hours later.

Midazolam (0.03 mg/kg) was administered intravenously after clamping of the fetal umbilical cord. Neuromuscular blockade was reversed by neostigmine (40 μg/kg) and atropine (20 μg/kg) given intravenously. All patients were extubated when they became fully awake. Cough and straining during extubation were recorded. Continuous epidural infusion of local anesthetics was started for postoperative pain, and no narcotic was administered intraoperatively or postoperatively. Rescue analgesia for sore throat was a gargle containing benzydamine hydrochloride. A nasogastric tube was not inserted. Oropharyngeal and tracheal cleansing was done gently to avoid trauma to the pharyngeal tissue before extubation.

Adverse reactions of the skin (pruritus, dermatitis) and gastrointestinal system (dyspepsia, nausea) to the patches were recorded, if there were any.

Soreness of the throat was evaluated 12, 24, and 48 hours after applying the patches by the assessor who was blinded to the type of patch applied. A visual analog scale (VAS) with score from 0 to 10 was used to determine the severity of sore throat: 0, no pain; 1, pain needing no analgesic (verbal numerical rating score ≤ 4); 2, pain needing an analgesic (verbal numerical rating score > 4).^17,18

In our pilot study, the incidence of sore throat was 40%. Our goal was to achieve a 50% decrease in the frequency of sore throat with a significance level of 0.05 and a power of 90%. The sample size calculated for each group was 110. Patients’ characteristics such as age, weight, duration of anesthesia and mean cuff pressure were compared using Student’s t test. The χ² test was used to identify the differences in the incidence and severity of sore throat, frequency of cough/straining during extubation and postoperative nausea and vomiting. Repeated measures ANOVA was applied to evaluate the effect of time and intervention simultaneously on sore throat. SPSS version 14 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. A p value less than 0.05 was accepted as statistically significant.

3. Results

None of the 220 patients was excluded from the study. All the cases were intubated at the first attempt. All the patients were similar in baseline characteristics (Table 1).

The VAS scores for sore throat were compared between intervention and placebo groups at designated time points (Figure 2). The incidence and severity of sore throat were lower in the diclofenac patch group than in the placebo group at all the study time points (Table 2). Cough and straining during extubation occurred in 6.4% and 9.1% of diclofenac and placebo groups, respectively (p= 0.61). Postoperative nausea and vomiting was not significantly different between the groups (13.6% vs. 11.8% in the diclofenac patch group and placebo patch group, respectively, p= 0.84).

Complications are listed in Table 3. There were no dropouts because of any complications.

4. Discussion

Sore throat is one of the main complaints related to anesthesia postpartum following cesarean section.¹⁹ An unrecognized difficult airway is eight to 10 times more common in obstetric patients than in non-obstetric patients, rendering more trauma to the mouth and pharyngeal and laryngeal structures.²⁰ Anatomic and physiologic factors that place the pregnant patient at increased risk of difficult intubation with ensuing complications necessitating airway management include pregnancy-induced generalized weight gain and increase in breast size, respiratory tract mucosal edema, decreased functional residual capacity, and increased oxygen consumption.²¹ As mentioned previously, difficulties in airway management, female sex, young age, high body mass index, edematous and brisk respiratory tract mucosal membranes and use of depolarizing muscle relaxants are probable risk factors predisposing parturients to sore throat after anesthesia. It means that parturients subjected to cesarean delivery under general anesthesia are at high risk of developing a sore throat.

In this study, reductions in the incidence and severity of sore throat after application of a diclofenac patch compared with the placebo patch are the major findings. Generally, mild postoperative sore throat would resolve spontaneously without specific treatment. In moderate to severe cases, it could be rational to treat the pain and/or dysphagia with an approved and acceptable analgesic agent.³ Many measures have been introduced for treatment and prevention of postoperative sore throat, of which administration of a NSAID such as benzydamine hydrochloride or ketoprofen, application of a local anesthetic, inhalation of steroids, the use of steroid-coated endotracheal tubes, endotracheal tubes with lower intracuff pressure, smaller endotracheal tubes, smooth suction of the pharynx with a round-headed suction catheter and appropriate applied pressure stand out.^2−12,17

Ozaki et al showed that a ketoprofen patch could decrease the severity but not the incidence of sore throat.² Ozaki et al studied 63 patients and the power of their study was not sufficient for detection of statistically significant differences in the incidence of sore throat between the two groups (nearly 22% for the comparison), but we studied 220 patients. In the report by Ozaki et al, the patients presenting for major elective orthopedic and gynecologic surgeries were included, but they did not mention the distribution of the surgeries in each group. As mentioned previously, gynecologic surgery could be a risk factor for postoperative sore throat¹⁵ and might confound Ozaki et al’s results. On the other hand, we studied only patients admitted for elective cesarean sections (only one kind of gynecologic surgery). The distribution of sex and mean age were different in the populations of two other studies; but both were concerned with sore throat.^13,14 Race differences in perception of sore throat as well as in response to NSAIDs and different effects of various transdermal NSAIDs on sore throat could be other explanations for differences in outcomes. We studied succinylcholine-related sore throat, but they administered vecuronium as a muscle relaxant [2], such that the basic pathophysiology of sore throat and the response to NSAIDs might be different.

Diclofenac hydroxyl ethyl pyrrolidine (DHEP), also known as diclofenac epolamine (EP) is a patented salt of diclofenac. This diclofenac salt has very pecu liar characteristics that distinguish it from other diclofenac salts as well as from other available NSAIDs. The main peculiar characteristic of this product is its very high solubility in both lipidic and hydrophilic tissues. No other salt derivative of this drug has such a property.²² This property allows the drug to be ef fectively absorbed by regional tissues and to maintain a low but sustained circulating level. Such a low cir culatory level, whilst locally effective, is very unlikely to induce the known side effects of its systemic administration as reported.²³ Minimal systemic effects and high local concentrations of diclofenac could be jointly effective in reducing sore throat. However, the systemic effect of the drug could also be beneficial to other organs. The analgesic activity of NSAIDs can be dissociated from their anti-inflammatory effect, and this may reflect additional spinal and supraspinal effects of NSAIDs to inhibit various aspects of central pain processing.²⁴

The use of diclofenac in prevention of postoperative sore throat was safe for the patients as there was no complication which caused exclusion of patients from the study.

It will be interesting to compare the effects of different transdermal NSAIDs on sore throat. Measurement of serum levels of inflammatory mediators help to determine physiologic mechanisms of transdermal NSAIDs. Thus, we conclude that intraoperative application of diclofenac epolamine patch is effective and safe in the prevention of sore throat after anesthesia in cesarean delivery.