Jahanshahi J, Pazira S, Farahani F, Hashemian F, Shokri N, Karkhanei B, Poorolajal J. Effect of Topical Sucralfate vs Clindamycin on Posttonsillectomy Pain in Children Aged 6 to 12 YearsA Triple-Blind Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2014;140(8):698-703. doi:10.1001/jamaoto.2014.979
Postoperative sore throat is one of the most common problems after tonsillectomy. Antibiotics remove the local flora and reduce inflammation and thus may reduce postoperative pain after tonsillectomy.
To assess the effect of topical sucralfate and clindamycin on local pain reduction after tonsillectomy in children aged 6 to 12 years.
Design, Setting, and Participants
Triple-blind randomized clinical trial of children aged 6 to 12 years with sleep apnea or snoring due to adenotonsillar hypertrophy and chronic airway obstruction or with chronic infections who were candidates for tonsillectomy at Besat Hospital, Hamadan University of Medical Sciences, from May to October 2013.
Patients were randomly assigned to receive sucralfate mouthwash, clindamycin mouthwash, or placebo (cellulose). The oral cavity was washed before and immediately after surgery with 10 mL of the prepared solution for 1 minute and then suctioned. Then, 8 hours after surgery, the patients were asked to keep 10 mL of the prepared mouthwash solution in their mouths for 1 minute 3 times a day for 3 days.
Main Outcomes and Measures
Postoperative sore throat evaluated daily for 5 days using the Faces Pain Scale–Revised.
Of 110 patients enrolled, 101 patients remained for analysis. Patients in the placebo group had significantly higher mean (SD) throat pain scores than did patients in both drug groups on postsurgery days 1 through 4. Day 1 scores were 8.00 (1.84) for placebo and 6.00 (1.84) for sucralfate and 6.79 (1.87) for clindamycin (P = .001). Pain scores were not significantly different on day 5. Acetaminophen use was more common in the placebo group on days 3 and 4 (2.97 and 2.44) vs the sucralfate group (2.24 and 2.15) and the clindamycin group (2.36 and 2.12) (P = .001 and .02, respectively). Bleeding on day 1 was more common in the placebo group (3 of 34) vs none in the drug groups. Food intolerance on day 1 was less common in patients receiving sucralfate (2 of 34) than placebo (9 of 34) or clindamycin (11 of 33) (P = .02). There was no significant difference among the 3 groups in numbers of episodes of nocturnal waking, halitosis, earache, nausea, and vomiting.
Conclusions and Relevance
This trial indicated that topical sucralfate and clindamycin are safe drugs with no important adverse effects that can significantly reduce posttonsillectomy pain in children and help them return to normal life sooner.
Iranian Registry of Clinical Trials registration number: IRCT201303209014N16
Tonsillectomy with or without adenoidectomy is one of the most common surgical procedures performed among children in the field of otolaryngology–head and neck surgery.1 Tonsillectomy is associated with a number of complications including pain, bleeding, nausea, vomiting, and inadequate food intake.2 Postoperative sore throat is one of the most common problems after tonsillectomy.1 Severe pain can cause reduced food intake and dehydration that may delay hospital discharge, thus postponing the child’s return to normal activity.3
Concerns about the quality of life in patients who undergo tonsillectomy are increasing. In recent years, extensive investigations have been conducted to reduce pain after tonsillectomy.4 Postoperative pain in adults who undergo tonsillectomy usually lasts for approximately 9 days, whereas the pain generally resolves within 6 days in children. However, the pain on the first day after surgery is severe and similar in adults and children despite the use of analgesics.5
Postoperative pain after tonsillectomy is caused by inflammation, stimulation of the nerve endings, and muscle spasms of the throat area. The pain may last as long as 10 to 14 days after surgery while the muscles of the operated area are not covered by the mucosa.6
Various surgical and medical approaches have been suggested to relieve postoperative pain such as local anesthetic drugs, fibrin glue, fusafungine, narcotics, acetaminophen, nonsteroidal anti-inflammatory drugs, and honey. Nonetheless, persistent pain is still the most common complaint after tonsillectomy.2,7 The visual analogue scale is the best method for assessing pain severity, although it needs to be adjusted with the patient’s age. The Faces Pain Scale–Revised is easily understood by children.8
Sucralfate is a disaccharide used to treat peptic ulcer. It binds the wound protein matrix and acts as a protective barrier against stomach acid, pepsin, and bile. It is believed to have a cytoprotective effect that accelerates mucosal healing.9
Antibiotics remove the local flora and reduce inflammation and thus can reduce postoperative pain after tonsillectomy.10 However, some studies have indicated that antibiotic therapy has no effect on postoperative pain.11- 13 Conversely, several studies have reported that use of topical antibiotics, covering aerobic and anaerobic agents, has a positive effect in reducing the bacterial count in the surgical wound compared with systemic antibiotics.14,15 In addition, use of topical clindamycin mouthwash can reduce bacteria counts in the oral cavity.14 This study was designed to assess and compare the effect of topical sucralfate and clindamycin on local pain reduction after surgery in children aged 6 to 12 years who underwent tonsillectomy with or without adenoidectomy.
This triple-blind randomized clinical trial was conducted in Besat Hospital, affiliated with Hamadan University of Medical Sciences, in the west of Iran, from May to October 2013. Written informed consent was received from all parents. The ethics committee of the university approved the consent procedure, as well as the whole trial. The protocol was registered with the Iranian Registry of Clinical Trials on April 23, 2013 (IRCT201303209014N16).
According to the results of a clinical trial conducted by Miura et al,16 the mean (SD) level of postoperative pain on the third day was 1.44 (1.71) and 3.27 (2.85) in the intervention and control groups, respectively, on a scale of 0 to 10. On the basis of these results, we arrived at a sample size of 35 for each group and a total sample size of 105 at 95% significance level and 90% statistical power. Anticipating a 5% loss to follow-up, we increased the sample size to a maximum of 110, of which 37 were randomly allocated to the placebo group, 37 to the sucralfate group, and 36 to the clindamycin group.
The study population included patients aged 6 to 12 years with sleep apnea or snoring due to adenotonsillar hypertrophy and chronic airway obstruction or with chronic infections, such as chronic recurrent tonsillitis, who were candidates for tonsillectomy with or without adenoidectomy.17
Patients with any of the following characteristics were excluded from the study: (1) hypersensitivity to clindamycin, sucralfate, or any of the macrolide group of antibiotics; (2) known systemic diseases such as congenital malformations, hemorrhagic disease, type 1 diabetes mellitus, or kidney disease; (3) common cold or fever at the time of enrollment; (4) inability to understand the picture of the children's pain scale; (5) cautery was used during the surgical procedure; or (6) bleeding of the adenoid site that necessitated nasopharyngeal packing.
The eligible patients were randomly assigned to 3 groups using the balance block randomization method. For this purpose, we prepared 6 sheets of paper, writing on 2 sheets “S” for “sucralfate,” on 2 “C” for “clindamycin,” and on 2 “P” for “placebo.” The paper sheets were pooled, placed in a container, and randomly drawn 1 at a time for each patient without replacement until all 6 sheets were drawn. The 6 paper sheets were then placed back into the container and this action repeated until the sample size was reached. The allocations remained concealed during the study. For this purpose, the random allocation was conducted by a pharmacologist (N.S.), who was the coordinator of the trial group, so that neither the patients nor the surgeon, who evaluated the effect of the interventions, were aware of the administered drugs. In addition, the statistical analyst was unaware of the trial groups until the data were analyzed and the labels were decoded.
The 3 groups received 120 mL normal saline solution containing the medicine or placebo with similar smell, taste, and color. The sucralfate group received 120 mL normal saline plus 3 g sucralfate, the clindamycin group received normal saline plus 3 g clindamycin, and the placebo group received 120 mL saline plus 3 g cellulose (placebo). The solutions were prepared by the Department of Pharmacy and labeled by a pharmacologist (N.S.).
The method of anesthesia was the same for all patients, without premedication. The cold dissection method was used for the tonsillectomy procedure, and bleeding was controlled with wet gas and suture. The oral cavity was washed before and immediately after surgery with 10 mL of the prepared solution for 1 minute and then suctioned.
Starting 8 hours after surgery, patients were asked to keep 10 mL of the prepared mouthwash solution in their mouth for 1 minute, 3 times a day, for 3 days. All patients received a liquid diet on the first day after surgery and then received a soft diet for 1 week. They were treated with oral acetaminophen 15 mg/kg/dose 4 times a day on the first day and 3 times a day on the second day and then twice a day thereafter until the fifth day, with a maximum dosage of 5 times a day if the pain did not resolve. They also received oral amoxicillin 40 mg/kg/dose, 3 times a day, for 5 days. The sore throat was evaluated by the parents at noon every day.
The primary outcome of interest was postoperative sore throat, which was evaluated daily for 5 days using the Faces Pain Scale–Revised, on a scale of 0 to 10. Zero denoted no pain, and 10 denoted the most severe pain that the patient had ever experienced. The secondary outcomes of interest were episodes of nocturnal waking, frequency of acetaminophen use, nausea, vomiting, bleeding, halitosis, food intake intolerance, and earache. These were evaluated by the researchers on the first, third, and fifth days after surgery and by the parents on the second and fourth days.
The analysis of variance test was used for analysis of continuous variables and the χ2 test for nominal variables. All statistical analyses were performed at a significance level of .05 using Stata software, version 11 (StataCorp).
Of 127 patients identified, 11 were ineligible and 6 declined to participate. The randomization was based on the remaining 110 patients, of whom 37 patients were allocated to the placebo group, 37 to the sucralfate group, and 36 to the clindamycin group. Eight patients declined follow-up including 3 patients in the placebo group, 3 patients in the sucralfate group, and 2 patients in the clindamycin group. One additional patient in the clindamycin group was excluded from the study because of bleeding from the adenoid site. The bleeding was controlled using nasopharyngeal packing. The analysis was based on data from the remaining 101 patients (44 boys and 57 girls) including 34 in the placebo group, 34 in the sucralfate group, and 33 in the clindamycin group (Figure). The mean (SD) age of the patients was 8 (1.77) years.
The effects of topical sucralfate and clindamycin vs placebo on postoperative clinical signs and symptoms are given in Table 1 and Table 2. The effect of both drugs on postoperative sore throat was statistically significant on the first 4 days after surgery (P = .001), but on the fifth day, the pain was mild in all 3 groups and there was no significant difference. There was no statistically significant difference in the numbers of episodes of nocturnal waking among the 3 groups.
The frequency of acetaminophen use on the first, second, and fifth days after surgery was nearly the same in the 3 groups. However, the frequency of acetaminophen use on the third and fourth days after surgery was significantly higher in the placebo group than in the sucralfate and clindamycin groups.
A small number of patients in the 3 groups had nausea and vomiting on the first and second postoperative days, but the difference was not statistically significant. From the third day onward, nausea and vomiting accrued in no group. Bleeding occurred in 3 patients of the placebo group on the first day, whereas no bleeding occurred in the 2 other groups (P = .048). Some patients in the 3 groups had halitosis during the 5 days after surgery. However, halitosis was less often reported in the clindamycin group than in the other 2 groups, although the difference was not statistically significant.
Food intake intolerance occurred in all 3 groups on the first and second days after surgery. Intolerance of diet was less common in the sucralfate group on the first and second days, but the difference was statistically significant only on day 1. No food intake intolerance occurred in any group from the third day onward. Earache occurred in all 3 groups during the 5 days after surgery, but the difference was not statistically significant.
The use of topical antibiotics covering both aerobic and anaerobic agents is taken into consideration in head and neck surgery because they are safe and well tolerated by the patients and can reduce the bacterial counts in the surgical wound.18 Reduction of the bacterial count can reduce inflammatory reactions and thus reduce postoperative pain.6
Mann et al19 conducted a pilot study on 36 patients to assess and compare the effects of (1) systemic amoxicillin sodium–ampicillin sodium, (2) placebo, (3) topical amoxicillin–clavulanate potassium and ticarcillin disodium–clavulanate potassium, and (4) topical clindamycin on recovery after tonsillectomy. They concluded that the patients in the last 2 groups (who received topical antibiotic therapy) had less postoperative pain than those in the first 2 groups. In addition, aerobic and anaerobic bacterial counts were lower in the last 2 groups. After the conclusion of the pilot study, Miura et al16 performed a clinical trial to assess the effect of local clindamycin vs placebo on postoperative pain reduction in children aged 4 to 12 years. They administered mouthwash solutions including clindamycin or placebo immediately before surgery, during surgery, and 8 to 12 hours after surgery. Then, they evaluated sore throat during the first 5 days after surgery using the Faces Pain Scale–Revised and concluded that topical clindamycin therapy can reduce postoperative pain only in the first day after surgery. They reported no adverse effects. However, they did not report whether prescribing clindamycin with different doses in the subsequent days after surgery could further reduce postoperative pain.20
In 2013, Baradaranfar et al21 conducted a double-blind randomized clinical trial to assess the effect of clindamycin therapy on posttonsillectomy pain in 30 adults. They prescribed clindamycin mouthwash, 1 g/100 mL normal saline, once a day, for 6 days after surgery and concluded that clindamycin had no significant effect on postoperative pain. Two reasons can be put forward for the lack of effectiveness of clindamycin in this trial. The first may be inadequate clindamycin concentration or administration frequency. Another reason may be the small sample size of the trial, which might introduce random error into the results.
In the present trial, we continued treatment with the mouthwash solutions for 3 days after surgery and observed the patients for 5 days. We found that both sucralfate and clindamycin could reduce postoperative pain significantly compared with placebo during the 4 days after surgery. Because the pain usually decreases after 4 days, no significant difference was seen among the 3 groups on day 5. This may indicate a short-term effect of the treatment. Furthermore, the number of times that patients in the clindamycin group used acetaminophen had decreased significantly on the third and fourth days after surgery compared with the placebo group, which indicates the effectiveness of clindamycin in reducing the need for analgesics. However, sucralfate therapy had a greater effect on pain reduction and the number of times that acetaminophen was used than did clindamycin. Conversely, halitosis occurred less frequently in the clindamycin group than in the other 2 groups, although the difference was not statistically significant. This indicates that clindamycin could effectively diminish the population of anaerobic agents, which are the main source of halitosis.
Sucralfate is a synthetic disaccharide in combination with aluminum salts that is prescribed as an antacid supplement in the treatment of peptic ulcers. Anions of sucralfate create a polyvalent bond with positively charged proteins of the damaged mucus and help the drug bind with the wound, providing a protective coating against acid, bile, and pepsin.22 This process accelerates the formation of mucosa by stimulating prostaglandin E synthesis23 and results in improvement in the mucosal healing process.24
Up to now, a few studies have evaluated the effect of sucralfate on pain reduction after tonsillectomy among adults.6,23 However, the pattern of pain in adults is different from that in children. Therefore, the results of these studies are not generalizable to children. Conversely, 3 trials have investigated the effect of sucralfate therapy on postoperative pain in children.16,25,26
Sampaio et al26 conducted a double-blind randomized clinical trial to compare the effect of sucralfate vs lactulose on postoperative pain in 69 children aged 3 to 12 years who underwent tonsillectomy. They reported that patients who received sucralfate for 7 days after surgery had significantly lower pain scores in the initial 6 postoperative hours than patients in the control group. However, the difference between the 2 groups was statistically significant neither for the other periods (24 hours and 7 days after the procedure) nor for the other indices.
Miura et al16 performed a double-blind randomized clinical trial to assess the effect of topical sucralfate on reduction of postoperative pain in children who underwent adenotonsillectomy. They reported that pain reduction in the sucralfate group was significantly greater than in the control group during the first 5 days of evaluation. However, there was no difference in the other outcomes.
Taşkın et al25 evaluated the effect of sucralfate with the thermal welding technique on posttonsillectomy pain in children. They reported that postoperative pain decreased continuously over the entire 7 days after surgery compared with the control group who received placebo.
The main limitation of the present study was the small sample size of the study groups. If the sample size were large enough, the difference between the trial groups could be indicated more clearly with less possibility of random error. Another limitation of this study was the difficulty of training the parents to measure the signs and symptoms of the children after hospital discharge. We tried to train the parents to measure the clinical findings in a uniform manner, but this might have introduced information bias. Also, our study sample included patients aged 6 to 12 years and may not be generalizable to children outside that age range. Despite its limitations, this trial was able to efficiently assess and compare the efficacy of topical sucralfate and clindamycin for postoperative pain in children who underwent tonsillectomy.
The results of this trial indicated that topical sucralfate and clindamycin are safe drugs with no important adverse effects. These medications can significantly reduce postoperative pain in children who undergo tonsillectomy. They efficiently reduce sore throat after tonsillectomy and help children return to normal life sooner. Sucralfate was more effective in pain reduction than clindamycin. Furthermore, because of the different mechanisms of the 2 drugs, sucralfate and clindamycin may reduce postoperative pain synergistically if used in combination with each other. However, this issue must be investigated in future investigations.
Corresponding Author: Jalal Poorolajal, MD, PhD, Modeling of Noncommunicable Diseases Research Center, Department of Epidemiology and Biostatistics, School of Public Health, Hamadan University of Medical Sciences, Shahid Fahmideh Ave, Hamadan, Iran 6517838695 (firstname.lastname@example.org).
Published Online: June 19, 2014. doi:10.1001/jamaoto.2014.979.
Author Contributions: Drs Pazira and Poorolajal had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: All authors.
Acquisition, analysis, or interpretation of data: Jahanshahi, Pazira, Poorolajal.
Drafting of the manuscript: Jahanshahi, Pazira, Farahani, Karkhanei, Poorolajal.
Critical revision of the manuscript for important intellectual content: Jahanshahi, Pazira, Hashemian, Shokri, Poorolajal.
Statistical analysis: Poorolajal.
Obtained funding: Jahanshahi.
Administrative, technical, or material support: All authors.
Study supervision: Jahanshahi, Poorolajal.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was funded by the Vice Chancellor of Research and Technology, Hamadan University of Medical Sciences.
Role of the Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Information: This study was part of an MD thesis in ear-nose-throat surgery. We thank the Vice Chancellor of Research and Technology of Hamadan University of Medical Sciences for financial support of this work.
Additional Contributions: The Vice Chancellor of Education, Hamadan University of Medical Sciences, provided technical support.