Introduction
Tonsillectomy is a common operation performed in children and young adults.Reference Blair, McKerrow, Carter and Fenton1 It is associated with various kinds of post-operation morbidity, including nausea, vomiting, haemorrhage, sore throat and otalgia.Reference Handler, Miller, Richmond and Baranak2, Reference Lee and Sharp3 Pain and post-operation haemorrhage are the complications which most commonly result in a follow-up visit to the emergency department or out-patient clinic after discharge.Reference Valtonen, Qvarnberg and Blomgren4 Children undergoing tonsillectomy experience considerable post-operative pain, for which optimal management has yet to be established.Reference Fredelius, Olin, Grenrot, Axelsson and Hemlin5–Reference Warnock and Lander7
Throat pain associated with tonsillectomy impairs swallowing and delays the patient's return to a normal diet, causing dehydration.Reference Robinson and Purdie8 Nerve irritation, inflammation and pharyngeal muscle spasm have been proposed as the underlying mechanisms responsible for this complication of tonsillectomy.Reference Ernst and Fialka9
Various analgesic methods and drugs have been used to reduce morbidity following tonsillectomy, including peritonsillar infiltration of analgesia,Reference Johansen, Harbo and Illum10 cryoanalgesia,Reference Robinson and Purdie8 paracetamol,Reference Moir, Bair, Shinnick and Messner11 steroidsReference April, Callan, Nowak and Hausdorff12–Reference Ohlms, Wilder and Weston14 and antibiotics.Reference Dhiwakar, Eng, Selvaraj and McKerrow15 However, trial results have been inconsistent.
The rationale for the use of antibiotics as a possible method of analgesia in this setting is based upon the hypothesis that reducing oral bacterial load at the site of surgery will diminish inflammation, resulting in better pain control.Reference Mann, Blair, Levy and Chang16 The efficacy of pre- or post-operative antibiotic administration in reducing post-operation morbidity has been assessed in various trials, but results have been controversial. Some authors have reported a significant decline in post-operative morbidity in patients receiving antibiotics,Reference Mann, Blair, Levy and Chang16–Reference Jurkiewicz, Wojdas, Rapiejko, Kantor, Hermanowski and Usowski18 while others have observed little benefit.Reference O'Reilly, Black, Fernandes and Panesar19 Moreover, a systematic review by Dhiwakar et al. Reference Dhiwakar, Eng, Selvaraj and McKerrow15 concluded that systemic antibiotics are beneficial in reducing some but not all post-operative symptoms.
To our knowledge, most studies on this topic have evaluated the efficacy of local antibiotic administration in paediatric populations.Reference Colreavy, Nanan, Benamer, Donnelly, Blaney and O'Dwyer20–Reference Miura, Saleh, de Andrade, Assmann, Lima and Lubianca Neto22 In the available studies of adult patients, the quality of results has been hindered by design flaws (e.g. lack of adequate blinding).Reference Jurkiewicz, Wojdas, Rapiejko, Kantor, Hermanowski and Usowski18, Reference Lukan23
Given the current knowledge gap in this setting, we undertook the present study with the aim of evaluating the efficacy of topical antibiotic administration in pain reduction following tonsillectomy in Iranian adult patients.
Materials and methods
Patients
A double-blind, placebo-controlled, randomised clinical trial was conducted to assess the effect of clindamycin on pain reduction following tonsillectomy undertaken at Shahid Sadoughi General Hospital, Yazd, Iran.
Patients older than 18 years who were scheduled to undergo tonsillectomy because of recurrent tonsillitis, peritonsillar abscess or chronic tonsillitis were enrolled in the study. We excluded patients with (1) a known allergy to clindamycin, or (2) a history of antibiotic use in the week prior to surgery, or a history of any medical condition requiring antibiotic therapy.
Cold-dissection tonsillectomy was performed by the same surgeon (MHB) for all patients. Anaesthetic technique was similar in all operations. Haemostasis was achieved by packing wet gauze over the operative site, rather than using electrocautery.
A total of 30 patients were recruited. Written, informed consent was obtained from all patients. The local ethics committee of the Shahid Sadoughi University approved the study protocol. All procedures were conducted in accordance with the guidelines of the Declaration of Helsinki regarding human subjects.
Study design
Patients were randomly assigned to two groups using a computer-generated randomisation code, and received either clindamycin (cases) or isotonic saline as placebo (controls).
Clindamycin (1 g) was dissolved in 100 ml normal saline. The placebo solution was prepared in an identical manner to the active medication, and the two preparations had the same colour, odour and taste. Patients received either 100 ml normal saline alone or 100 ml normal saline with clindamycin, in bottles with the same appearance. The solutions were prepared by a nurse who was blinded to the study protocol. Clindamycin or normal saline alone was applied at the surgical site prior to incision and again at the end of the operation, after the achievement of complete haemostasis.
Post-operatively, patients were asked to gargle with 10 ml of the relevant prepared solution, once daily for six days.
As adjunctive analgesia, patients were also prescribed paracetamol tablets (325 mg, four times daily).
Assessment
The severity of patients' throat pain was evaluated 1, 4 and 7 days after surgery using a 100 mm visual analogue scale (VAS). The two extremes of the scale were designated as indicating no pain (giving a score of 0) and severely debilitating pain (giving a score of 10). Scores of 1 to 4 were taken to indicate mild pain, 5 to 6 moderate pain and 7 to 9 significant pain.
At each follow-up visit, patients were also asked whether they had used extra doses of paracetamol, and whether they had developed any treatment complications such as bleeding, otalgia, skin rash, diarrhoea, nausea or vomiting.
Statistical analysis
Statistical analyses were performed using the SPSS version 17.0 software program (SPSS Inc, Chicago, Illinois, USA). Continuous variables are presented as means ± standard deviations, and categorical variables as percentages. Repeated measures analysis of variance (ANOVA) was conducted to compare treatment efficacy between groups. Additionally, posthoc analysis was conducted using Bonferroni correction to evaluate the difference between each time point. The effect size was computed using partial η2. Based on Cohen's recommendations, η2 values of 1, 6 and 13.8 per cent were taken to demonstrate small, medium and large effect sizes, respectively.Reference Cohen24 The median VAS scores for each day were compared between trial arms using the Mann–Whitney U test.
Results and analysis
Thirty patients were enrolled in the study and were divided into two groups: clindamycin and placebo. Each group consisted of 15 patients. The mean patient age was 25.76 ± 6.32 years (range, 18 to 42 years) (Table I). The study group consisted of 15 (50 per cent) women and 15 (50 per cent) men.
Table I Patients' baseline characteristics
SD = standard deviation; yr = years
The most common reasons for tonsillectomy were chronic tonsillitis (22 patients, 73.3 per cent) and recurrent tonsillitis (7 patients, 23.3 per cent). One patient (3.3 per cent) had a peritonsillar abscess and therefore underwent delayed surgery after resolution of the abscess.
Placebo group
The mean age of the placebo group patients was 25.4 ± 6.06 years (range, 18 to 34 years).
The mean VAS pain score on the first day after surgery was 6.73 ± 1.88, decreasing to 4.26 ± 0.96 on the fourth day and 2.06 ± 0.7 on the seventh day (at the final follow-up visit). One-way repeated measures ANOVA was conducted to compare VAS scores at different time points. There was a significant effect for time (Wilks' λ = 0.057; F (2, 13) = 106.676; p < 0.001). Post hoc analysis using Bonferroni correction revealed that the difference between all three time points was statistically significant (p < 0.001 for all time to time comparisons).
Clindamycin group
The mean age of patients in this group was 26.13 ± 6.75 years.
The mean VAS score on the first day after surgery was 7.00 ± 1.13, decreasing to 4.26 ± 1.38 on the fourth day and 1.73 ± 1.03 on the seventh day. One-way repeated measures ANOVA revealed that there was a significant effect for time (Wilks' λ = 0.052; F (2, 13) = 118.533; p < 0.001; multivariate partial η2 = 0.948). Post hoc analysis using Bonferroni correction showed that the VAS score reduction was statistically significant when comparing all pairs of time points (p < 0.001 for all time to time comparisons).
Treatment efficacy
On the first day after surgery, the mean VAS scores in the placebo and clindamycin groups were comparable (p = 0.625) (Table II). Similar results were observed when comparing the two groups' VAS scores on the fourth day (p = 0.844) and on the seventh day (p = 0.172). Repeated measures ANOVA revealed no statistically significant difference between the reduction in VAS scores in the placebo versus clindamycin groups, during the study course (Wilks' λ = 0.938; F (2, 27) = 0.886; p = 0.424; multivariate partial η2 = 0.062 for between-group comparison).
Table II Subjective pain severity: VAS scores
*Mann–Whitney U test, placebo vs clindamycin group. †Repeated measures analysis of variance. VAS = visual analogue scale; SD = standard deviation; grp = group; Clind = clindamycin
Discussion
This study evaluated the effectiveness of local antibiotic therapy in reducing pain after adult tonsillectomy. Patients were randomly assigned to receive either isotonic saline or clindamycin. Clindamycin has been shown to be an effective prophylactic medication for head and neck surgical procedures.Reference Swanson, Maxwell, Johnson, Wagner and Yu25 There are no current data concerning the sensitivity of oropharyngeal flora to clindamycin in an Iranian population. However, previous reports from several countries have shown promising findings in this regard, and have even proposed that antibiotic treatment be considered as an alternative to tonsillectomy in patients with recurrent tonsillitis.Reference Orrling, Stjernquist-Desatnik and Schalen26, Reference Jensen and Larsen27 It has been suggested that clindamycin is an effective agent against β-lactamase producing bacteria which show resistance to penicillin.Reference Brook28
Previous studies have compared various analgesic techniques and medications, but have often presented inconsistent and contrasting results.
A number of studies have used peri-operative injection of analgesic medication to reduce pain; bupivacaine,Reference Jebeles, Reilly, Gutierrez, Bradley and Kissin29 lignocaineReference Boliston and Upton30 and ropivacaineReference Giannoni, White, Enneking and Morey31 have all been used in this regard. Jebeles et al. Reference Jebeles, Reilly, Gutierrez, Bradley and Kissin32 used pre-incisional infiltration of bupivacaine to reduce post-tonsillectomy pain in children. Their results indicated that patients receiving bupivacaine had significantly less pain on the fourth to fifth day after surgery, compared with the placebo group. Similar results regarding the efficacy of bupivacaine have been reported by other research groups.Reference Molliex, Haond, Baylot, Prades, Navez and Elkhoury33 In contrast, Ørntoft et al. Reference Ørntoft, Løngreen, Møiniche and Dhal34 found that pre-operative infiltration of bupivacaine produced no significant reduction in post-tonsillectomy pain in adults. Other studies have concluded that local infiltration of anaesthetics has little or no benefit.Reference Ohlms35
The use of systemic steroids for pain reduction after tonsillectomy has provoked heated debate in several studies. The most common corticosteroid used in this setting is dexamethasone.Reference Steward, Welge and Myer36 Some investigators have reported no significant difference in pain reduction in patients receiving steroids versus placebo,Reference Catlin and Grimes37–Reference Vosdoganis and Baines40 while others have concluded that steroids are a good choice for reduction of post-tonsillectomy pain.Reference Papangelou41
Antibiotics have been used as alternative analgesic medication prior to or following tonsillectomy. However, similarly to other classes of analgesics and steroids, substantial controversy exists regarding their efficacy.
Telian et al. Reference Telian, Handler, Fleisher, Baranak, Wetmore and Potsic42 evaluated the efficacy of antibiotic therapy by administering intravenous ampicillin at the time of surgery and for 12 to 24 hours afterwards; patients also received oral ampicillin for 7 days post-operatively. The authors assessed pain severity by comparing the mean number of continuous days with reported pain (assessed subjectively), in the ampicillin versus placebo groups. They concluded that administration of antibiotics leads to a significant reduction in throat pain.
Colreavy et al. Reference Colreavy, Nanan, Benamer, Donnelly, Blaney and O'Dwyer20 administered amoxicillin and clavulanic acid for one week after tonsillectomy, and reported a significant reduction in analgesia requirement and pain analogue score.
Contrarily, other authors have reported that antibiotic administration after tonsillectomy has no significant effect on pain severity, in agreement with our own observations. O'Reilly et al. Reference O'Reilly, Black, Fernandes and Panesar19 examined the efficacy of pre-operative amoxicillin administration and concluded that pain severity was not affected by antibiotic therapy.
Dhiwakar et al. Reference Dhiwakar, Eng, Selvaraj and McKerrow15 conducted a systematic review including five double-blind, placebo-controlled clinical trials that assessed the efficacy of systemic antibiotic administration in reducing post-operation morbidity. They concluded that patients who received antibiotics returned to their normal activity sooner, were less likely to experience fever and had a shorter duration of halitosis, compared with placebo patients. However, antibiotics had no effect on the degree of pain or the need for rescue analgesia. We observed similar results with respect to the ineffectiveness of antibiotics in reducing post-operative pain.
A few authors have reported that local antibiotics can reduce post-tonsillectomy morbidity in paediatric populations.Reference Colreavy, Nanan, Benamer, Donnelly, Blaney and O'Dwyer20–Reference Miura, Saleh, de Andrade, Assmann, Lima and Lubianca Neto22 However, our study did not replicate these results in adult patients.
Previous studies have indicated that both Gram-positive and Gram-negative bacteria can induce a host inflammatory response. The pro-inflammatory activity of Gram-negative bacteria is caused by the lipopolysaccharide component of the cell wall outer membrane. Lipopolysaccharide can activate the release of various inflammatory cytokines from host cells, such as interleukin (IL) 1, IL-6 and tumour necrosis factor α.Reference Luderitz, Tanamoto, Galanos, McKenzie, Brade and Zahringer43, Reference Luderitz, Brandenburg, Seydel, Roth, Galanos and Rietschel44 The cell walls of Gram-positive bacteria have different chemical components, such as lipoteichoic acid and peptidoglycan, but these trigger a pro-inflammatory response in a similar manner to lipopolysaccharide.Reference Bhakdi, Klonisch, Nuber and Fischer45, Reference Card, Jasuja and Gustafson46 The inflammation induced by these various chemicals results in nerve irritation, leading to significant pain and discomfort.Reference Chacur, Milligan, Gazda, Armstrong, Wang and Tracey47, Reference Eliav, Herzberg, Ruda and Bennett48 In theory, reducing oropharyngeal bacterial growth hinders the inflammatory cascade, thus reducing the severity of post-tonsillectomy pain.
• Pain and post-operative haemorrhage are the commonest complications of tonsillectomy
• The effect of pre- or post-operative antibiotics on post-operative morbidity is controversial
• In this adult study, local antibiotics did not reduce post-tonsillectomy throat pain more than placebo
One limitation of our study was the relatively small number of patients enrolled. This limited number of patients reduced the chance of detecting a difference between the two groups, hence increasing the risk of type II error. In future studies, the probability of this error could be minimised by using larger sample sizes.
Conclusion
Our results indicate that local antibiotic administration has no greater efficacy in reducing throat pain after tonsillectomy in adults, compared with placebo. Further investigation is warranted.
