Accepted Manuscript

Effect of paracetamol/prednisolone versus paracetamol/ibuprofen

on post-operative recovery after adult tonsillectomy

Tamer M. Attia

PII: S0196-0709(18)30365-X
DOI: doi:10.1016/j.amjoto.2018.05.002
Reference: YAJOT 2021
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Received date: 29 April 2018

Please cite this article as: Tamer M. Attia , Effect of paracetamol/prednisolone versus
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 ACCEPTED MANUSCRIPT

Effect of Paracetamol / Prednisolone versus Paracetamol/ Ibuprofen

on post-operative recovery after adult tonsillectomy

Lecturer at Otolaryngology Department, Faculty of Medicine, Menoufia

University, Egypt.

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Consultant of Otolaryngology, Head & Neck Surgery – Medical Director,

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Specialized Medical Care Hospital, Al Ain, UAE.

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Correspondence Author: AN
Tamer M. Attia

MBBCh. , MSc. , MD.

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Address: Specialized Medical Care Hospital, Al Ain, UAE.

Tel No: +971 3 755 2291

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Fax No: +971 3 754 5500

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Email: tamerattia77@gmail.com
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Running Title: Post tonsillectomy medical regimen

Conflict of interest statement: No potential conflict of interest relevant to this

article was reported.

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ABSTRACT:

Objective: to compare the effect of Paracetamol / Prednisolone versus Paracetamol/ Ibuprofen

on post-operative recovery after adult tonsillectomy.

Background: Various analgesic protocols have been proposed for the control of post-

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tonsillectomy morbidity with need for better control in adult population for having higher

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severity of post-operative pain and risk of secondary post-tonsillectomy bleeding.

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Methods: This is a prospective cohort study conducted on 248 patients with age of 12 years or

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older distributed as two equal groups; the first one receiving Paracetamol / Prednisolone and the

second one receiving Paracetamol/ Ibuprofen. Both groups were compared at 7 days post-
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operative regarding pain at rest, tiredness of speech, dietary intake, and decrease in sleep

duration. Both groups were compared regarding incidence of nausea and vomiting at 2 days post-
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operative. The incidence and severity of secondary post-tonsillectomy hemorrhage was

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compared between the two groups.

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Results: Pain at rest (no swallowing - no talking) was less in group I but not reaching statistical

significance (p = 0.36). In addition, dietary intake was better in group I but not reaching
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statistical significance (P =0.17). However, talking ability was better with statistically significant
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difference (P = 0.03) in group I. Impairment of sleep was less with group II but not reaching

statistical significance (p = 0.31). The incidence of vomiting at second post-operative day was

less in group I with statistical significance (p =0.049). The incidence of secondary post-

tonsillectomy bleeding was significantly higher in group II with statistical significance (p =

0.046). The severity of bleeding episodes was also significantly higher in group II (p = 0.045)
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Conclusion: Both ibuprofen and prednisolone were effective as a part of post-operative

medication regimen after adult tonsillectomy. However, prednisolone was superior to ibuprofen

regarding improvement of pain at rest, dietary intake, tiredness of speech and post-operative

nausea and vomiting. However, ibuprofen had a better impact on sleep. The incidence and

severity of secondary post-tonsillectomy hemorrhage were significantly higher with ibuprofen

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favoring the selection of prednisolone to be combined with paracetamol in the post-operative

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medication protocol following tonsillectomy.

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Keywords: Ibuprofen, Post-tonsillectomy hemorrhage, Post-tonsillectomy pain, Prednisolone,

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Post-tonsillectomy vomiting. AN
1. INTRODUCTION:
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Tonsillectomy operation is a frequently performed operation with an estimated rate of 200,000

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procedures performed in the United Kingdom annually (1) and more than 500,000 in the United

States (2). The rate of tonsillectomy decreases beyond 12 years old but with increasing incidence
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of post-operative morbidity including post-operative pain (3), and post-operative bleeding (4).
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The increased incidence of post-operative pain after adult tonsillectomy can be attributed to the

presence of increased fibrosis from previous infections combined with larger blood vessels. As a
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result, more cauterization is typically required to control excess bleeding and may contribute to

post-operative pain. (5) Post-operative nausea and vomiting (PONV) continues to be a common

concern after tonsillectomy. It is a leading cause of dehydration and unanticipated hospital

admissions in post-tonsillectomy patients and increases the total health care cost. (6) One of the

commonest reasons for PONV in post-tonsillectomy patients is the swallowed blood which
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causes gastrointestinal irritation and thus increases the likelihood of post-operative nausea and

vomiting. (7)

Opioids are effective in controlling post-operative pain treatment but they are associated with

side effects, such as nausea, vomiting and sedation, capable of impairing patient comfort after

tonsillectomy. Non-opioid analgesics are therefore the first line analgesics for post-operative

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pain management after tonsillectomy. (8) Paracetamol has been used widely as post-operative

analgesic after tonsillectomy with comparable analgesic effect to opioids. (9) NSAIDs have

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taken an essential role in the management of post-tonsillectomy pain with various drugs and

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different dose regimens. However several studies have raised the issue of increased incidence of

secondary post-tonsillectomy hemorrhage with NSAIDs. (10) This should be considered while
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planning the post-operative medication regimen.
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Corticosteroids have been recently added to post-operative medication protocols at a wide scale
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to minimize the post-operative nausea and vomiting and augment the analgesic effect of other

non-opioid analgesics through their anti-inflammatory effects (11). The aim of this study is to
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compare the effect of two protocols of Paracetamol/Ibuprofen versus Paracetamol/Prednisolone

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on post-operative recovery after tonsillectomy with assessment of the risk of secondary post-

tonsillectomy hemorrhage with each protocol

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2. PATIENTS AND METHODS

This is a prospective cohort study conducted on 248 patients indicated for tonsillectomy

recruited at the department of Otolaryngology, Al Ain Specialized Medical Care Hospital during

the period from September 2015 to March 2018. Approval of the ethical committee of the
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hospital was taken and each patient or his legal representative had signed consent before

participating in the study.

Patients indicated for tonsillectomy with an age of 12 years old or above were included in the

study. This age was selected because of increasing perception of post-tonsillectomy pain in this

age group. Also, younger patients fail to subjectively assess their pain scores. Any patient with

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systemic disease increasing the risk of infection like diabetes mellitus was excluded from the

study. Patients with neurological disorder or taking medications with affection of the perception

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of pain were excluded from the study. Patients with contraindication to paracetamol,

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prednisolone or ibuprofen like hypersensitivity to the drug, peptic ulcer, hepatic or renal

dysfunction were excluded from the study.

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Studied patients were distributed randomly into two equal groups I and II according to the
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administered post-operative analgesic regimen utilizing block randomization method using 62

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blocks each comprising 4 patients with 6 patterns for every block one of which was selected

randomly using random numbers generated by Excel program. All patients were subjected to
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coblation tonsillectomy performed by the author under general anesthesia.

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2.1. Post-operative analgesic regimens:

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Group I: 124 patients received prednisolone in a dose of 1 mg per Kg per day with a maximum

of 60 mg per day in three divided doses for 10 days along with paracetamol in a dose of 1 gm per

dose every 4-6 hours as needed with a maximum of 5 doses per day.

Group II- Patients received 200-400 mg of ibuprofen orally every 6 hours with a maximum of

3200 mg per day for 10 days along with paracetamol in a dose of 1 gm per dose every 4-6 hours

as needed with a maximum of 5 doses per day.

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2.2. Outcomes assessment:

Four parameters were assessed at the seventh post-operative day to reflect the post-operative

pain: pain at rest (no swallowing - no talking), dietary intake, decrease in number of sleeping

hours per day and tiredness of speech. Pain at rest was assessed using numerical pain scale

ladder for adults with a score out of 10. Dietary intake and tiredness of speech were assessed

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using a visual analog scale comparing speech ability with the preoperative state giving a score

out of 10. The primary end-point was the incidence of severe morbidity defined as a score

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greater than 6. Incidence of vomiting was assessed at the second post-operative day for both

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groups.

The incidence of secondary post-tonsillectomy hemorrhage was recorded. The severity of

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secondary post-tonsillectomy hemorrhage was classified according to the scale adopted by Samy
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et al (12). They stated grade A for anamnestically recorded blood-tinged sputum. In A1; wound
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was and stayed dry with no coagulum upon inspection. In A2; there was coagulum upon

inspection with dry wound after removal. In grade B, bleeding was active under examination
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with medical treatment necessary followed by dry wound and blood count was in normal range
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and no shock. In grade C; surgical treatment with general anesthesia was indicated with blood

count still in normal range and no shock. In grade D; there was dramatic hemorrhage,
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hemoglobin decreased, blood transfusion was required with difficult surgical treatment and

intensive care may be necessary. In grade E; Exitus occurred due to hemorrhage or hemorrhage-

related complication

2.3. Statistical analysis:

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Data were collected, tabulated and statistically analyzed using an IBM personal computer with

Statistical Package of Social Science (SPSS) version 20 and Epi Info 2000 programs. Descriptive

statistics for quantitative data presented as mean (¯X) and standard deviation (SD). Qualitative

data presented as numbers and percentages (%). Data turned up to be non-normally distributed

according to Kolmogorov-Smirnov test. Mann Whitney U test was used to compare quantitative

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data of both groups. Chi- squared test (χ2) was used to study association between two qualitative

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variables. Two sided p value of (≤0.05) was considered statistically significant.

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3. RESULTS

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In the current study, two groups were studied including 124 patients in each with no significant
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difference between the two groups regarding age, sex and preoperative sleep duration indicating

uniformity of both study groups (p > 0.05 for all) (Table 1).
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In the current study pain at rest was less in group I but not reaching statistical significance (p =
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0.36). In addition, dietary intake was better in group I but not reaching statistical significance (P

=0.17). However, talking ability was better with statistically significant difference (P = 0.03) in
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group I. On the other hand, impairment of sleep was less with group II but not reaching statistical
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significance (p = 0.31) (Table 2). The incidence of vomiting at second post-operative day was

less in group I with statistical significance (p =0.049) (Table 3).

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In the current study, the incidence of secondary post-tonsillectomy bleeding was significantly

higher in group II with statistical significance (p = 0.046) (Table 4). In addition, the severity of

bleeding episodes was also significantly higher in group II (p = 0.045) according to Samy et al

classification of secondary post-tonsillectomy bleeding (Table 5).

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4. DISCUSSION

Tonsillectomy operation can be followed by several aspects of morbidity including pain,

dysphagia, impaired speech, impaired sleep, nausea and vomiting. These manifestations are

interconnected with pain being a major cause for difficult swallowing, decrease in sleep duration

and tiredness of speech. On the other hand, vomiting after tonsillectomy contributes to the post-

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operative pain and discomfort. All these aspects have a great burden on the patient with impaired

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quality of life. Several medical protocols have been proposed to improve the post-operative

recovery after tonsillectomy.

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In the current study, we evaluated two protocols for post-operative management of patients after
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tonsillectomy operation. We have chosen the age group to be >= 12 years old because patients in

such age are more cooperative than younger patients with more accurate estimation of symptom
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scores. The first protocol combined the use of prednisolone and paracetamol to combine the
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analgesic effect of paracetamol which has been found to be comparable to opioids (9) and the

established ant-inflammatory/ antioedematous effect of prednisolone together with its recorded

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analgesic effect as shown by Dan et al in 2010 (13). The second protocol combined the use of
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ibuprofen and paracetamol adding the analgesic and anti-inflammatory prosperities of ibuprofen

to the analgesic effect of paracetamol. The analgesic efficacy of ibuprofen is well known and
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also has been found to be comparable to opioids as shown by Bedwell et al in 2014 (14) and

Kelly et al in 2015 (15). This makes prednisolone and ibuprofen are the targets of evaluation by

the study.

The current study evaluated the 5 aspects of post-operative recovery after tonsillectomy. Pain at

rest, difficult swallowing, tiredness of speech and decrease in sleep duration were evaluated at
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the seventh post-operative day being the time of maximum pain intensity. However nausea and

vomiting were evaluated at two days post-operatively being at their maximum intensity in the

early post-operative period. In addition, the study evaluated the side effects of both protocols

regarding the incidence and severity of secondary post-tonsillectomy hemorrhage.

In the current study, pain at rest and dietary intake were better in group I but not reaching

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statistical significance. However, talking ability, nausea and vomiting were significantly better in

group I also. On the other hand, sleep was better in group II but not reaching statistical

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significance. The powerful antioedematous effect of prednisolone contributes to the better

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talking ability and swallowing capability as the oropharyngeal oedema following tonsillectomy

impairs the ability of speech and swallowing. In addition, corticosteroids are known to increase
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the appetite and this may contribute to the improved dietary intake. Corticosteroids also are well
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known to have a powerful antiemetic effect following anesthesia in general with similar effect

after tonsillectomy (13).

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In a similar study, Aveline et al in 2015 (16) compared the administration of

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paracetamol/prednisolone versus paracetamol/ibuprofen analgesic protocols after tonsillectomy

in 1231chidren. They found that Ibuprofen reduced the incidence of pain scores≥6 on day 7 with
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statistical significance (P=0.009). This finding is against our finding which may be attributed to
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the lower dose of prednisolone used in their study being 0.5 mg / kg compared to 1 mg /kg in our

study which led to unfortunate lower ant-inflammatory and analgesic effect. On the other hand,

Aveline et al found that Ibuprofen enhanced sleep quality on post-operative day 0 (P<0.0001)

and post-operative day 7 (P=0.02). This matches the finding of our study but it doesn't reach

statistical significance in our study. This difference may be attributed to difference in sample

size. In addition, Aveline et al stated that Ibuprofen enhanced oral intake on post-operative day 0
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(P<0.0001). This is against our finding of better improvement of dietary intake with

prednisolone. This can be clearly explained by the previously proposed improvement of pain in

their study. In addition, we attribute such better dietary intake with prednisolone to the more

decrease in oropharyngeal oedema and increased appetite with steroids. Finally, Aveline et al

found that and post-operative nausea and vomiting were significantly lower with ibuprofen (P =

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0.01). Their finding is against our finding and the finding of other studies which highlighted the

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role of steroids in minimizing post-operative nausea and vomiting. (17-19) In addition, ibuprofen

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being a non steroidal ant-inflammatory drug can provoke nausea and vomiting by its effect on

gastric mucosa.

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Other studies evaluated the use of post-operative prednisolone as a part of post-tonsillectomy
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medication regimen. Palme et al in 2000 (17) conducted a double-blind, randomized, placebo-
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controlled trial comparing a 7-day course of daily placebo or prednisolone. They found that on

post-operative days 4 to 7, the steroid group experienced significantly less nausea and vomiting.
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Paracetamol use was significantly less indicating less pain in the steroid group on days 2, 7, and
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8 Macassey et al in 2012 (18) compared a 5-day course of oral prednisolone with placebo in a

pediatric population (3- 16 years) undergoing tonsillectomy. They found that there was no
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significant difference between the 2 groups when analyzed for differences in pain, nausea and
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vomiting, return to normal diet, return to normal activity, bedtime, and number of times awake

during the night. These findings can be explained by their given lower dose of prednisolone and

the shorter duration of treatment. Park et al in 2015 (19) conducted a prospective, randomized,

controlled trial on 198 patients scheduled for elective tonsillectomy with or without

adenoidectomy comparing a post-operative course of prednisolone and no prednisolone over 7

days. No statistically significant differences in pain, diet, activity, rate of minor bleeding,
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nausea/vomiting, fever, or sleep disturbance were observed between the groups on day 1. On day

7, however, in pediatric patients, differences in pain (P = .001), diet (P = .001), activity (P =

.0040, and sleep disturbance (P = .04) were observed. These findings match our findings except

for sleep duration.

In the current study, the incidence of secondary post-tonsillectomy hemorrhage were

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significantly lower with the paracetamol – prednisolone protocol when compared with

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paracetamol - ibuprofen protocol being 2.4% and 8.1% respectively. In addition, the severity of

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secondary post-tonsillectomy hemorrhage was significantly higher in the paracetamol - ibuprofen

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group according to the classification system adopted by Samy et al in 2001. (12) This

classification system offers a practical approach for assessment of secondary post-tonsillectomy

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hemorrhage. In our study, two out of three patients with secondary post-tonsillectomy

hemorrhage in paracetamol – prednisolone group were found to have only a blood clot at the bed
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with no further bleeding after its removal. However, one patient needed medical treatment to
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stop the bleeding but with no shock. On the other hand, 7 out of 10 patients with secondary post-
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tonsillectomy hemorrhage in the paracetamol - ibuprofen group needed only medical treatment,

with one patient needed surgical intervention under general anesthesia but with no shock or
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change in blood indices. The remaining patient suffered from severe hemorrhage with shock and
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the surgical control was difficult in the operative theater with blood being transfused to the

patient.

Our finding of increased incidence of secondary post-tonsillectomy hemorrhage with ibuprofen

usage is supported by the findings of several previous studies. Smith and Wilde in 1999 (20)

found a significant increase in secondary hemorrhage rate when on regular NSAIDs. Marret et

al in 2003 (21) in a meta-analysis post-operative use of conventional NSAIDs increases the risk
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of reoperation for hemostasis after tonsillectomy. Møiniche et al in 2003 (22) in their meta-

analysis found an evidence to suggest that the likelihood of reoperation due to bleeding increases

when NSAIDs are administered, particularly in the post-operative period. D'Souza et al in 2015

(23) found that use of ibuprofen after intracapsular tonsillectomy in children is associated with

statistically significant increase in post-tonsillectomy hemorrhage requiring return to the

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operating room, as well as an increase in overall rates of both primary and secondary post-

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tonsillectomy hemorrhage. Mudd et al in 2017 (24) found that the risk for post-tonsillectomy

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hemorrhage with use of post-operative ibuprofen was increased in patients 12 years or older.

Hemorrhage severity was significantly increased with ibuprofen use when using transfusion rate

as a surrogate marker for severity.

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These findings can be explained by the fact stated by Schafer in 1995 (25) who clarified that
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non-aspirin NSAIDs produce a systemic bleeding tendency by reversibly inhibiting platelet

cyclooxygenase, thereby blocking formation of thromboxane A2. Effects of individual NSAIDs

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on ex vivo platelet function, bleeding time, and clinical bleeding depend at least in part on dose,
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serum level, and drug half-life.

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On the other hand, Krishna et al, in 2003 (26) in a meta-analysis found an increased risk of

post-tonsillectomy hemorrhage with the use of aspirin after tonsillectomy and a non significant
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increased risk of bleeding for non-aspirin NSAIDs. Riggin et al in 2013 (27) conducted a

systematic review & meta-analysis of 36 randomized controlled trials to find no apparent effects

of non steroidal anti-inflammatory agents on the risk of bleeding after tonsillectomy.

Some of the authors proposed that the use of systemic steroid was associated with increased

bleeding risk. Plante et al in 2012 (28) in a systematic review and meta-analysis found that

systemic steroids do not appear to increase bleeding events after tonsillectomy but their use was
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associated with a raised incidence of operative re-interventions for bleeding episodes, which may

be related to increased severity of bleeding events. However 28 of 29 included studies in this

meta-analysis were evaluating the intravenous dexamethasone with one study only evaluating

prednisolone. In addition, Suzuki et al in 2014 (29) in a systematic review and meta-analysis

found that the rate of reoperation for secondary post-tonsillectomy hemorrhage was significantly

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higher in the steroid group than in the control group for children (P < .001) but not for adults.

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Again this study evaluated the use of dexamethasone not prednisolone.

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On the other hand, Palme et al in 2000 (17) found a non-significant difference between a 7-day

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course of daily placebo or prednisolone regarding post-tonsillectomy bleeding. Aveline et al in

2015 (16) found that the incidence of bleeding requiring reoperation was comparable between
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paracetamol/prednisolone versus paracetamol/ibuprofen (p=0.8). Park et al in 2015 (19) found
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no statistically significant differences in rate of minor bleeding between

paracetamol/prednisolone versus paracetamol/ibuprofen analgesic protocols. The effect of

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prednisolone on hemostasis has been first proposed by Thong et al in 1978 (30). They stated
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that conventional clinical doses of prednisone did not impair platelet function and did not

enhance primary haemostatis in normal subjects as measured by the bleeding time. Although
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their results failed to support a useful clinical role for glucocorticoids in disorders of primary
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hemostasis, they did not completely exclude one.

The limitations of our study include the relatively small number of patients compared with other

studies. This can be explained by that this study included the operations performed by a single

surgeon in a single center. Also the rate of tonsillectomy decreases after 12 years. Other methods

of tonsillectomy other than coblation should be assessed for control of post-operative pain.
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5. CONCLUSION

Both ibuprofen and prednisolone were effective as a part of post-operative medication regimen

after adult tonsillectomy. However, prednisolone was superior to ibuprofen regarding

improvement of pain at rest, dietary intake, tiredness of speech and post-operative nausea and

vomiting. However ibuprofen had a better impact on sleep duration compared with prednisolone.

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The incidence and severity of secondary post-tonsillectomy hemorrhage were significantly

higher with ibuprofen favoring the selection of prednisolone to be combined with paracetamol in

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the post-operative medication protocol following tonsillectomy.

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6. REFERENCES AN
1- Glover JA. The incidence of tonsillectomy in school children. J. Alison Glover Int J

Epidemiol. 2008;37: 9–19

M

2- Baugh RF, Archer SM, Mitchell RB, Rosenfeld RM, Amin R, Burns JJ et al. Clinical
ED

Practice Guideline. Tonsillectomy in Children. Otolaryngol Head Neck Surg.

2011;144(1):S1–S30.
PT

3- Graumüller S, Laudien B. Post-operative pain after tonsillectomy—comparison of

CE

children and adults. International Congress Series. 2003;1254:469-472.

4- Windfuhr JP1, Chen YS. Incidence of post-tonsillectomy hemorrhage in children and

AC

adults: a study of 4,848 patients. Ear Nose Throat J. 2002 Sep;81(9):626-8

5- Noordzij JP, Affleck BD. Coblation versus unipolar electrocautery tonsillectomy: a

prospective, randomized, single-blind study in adult patients. Laryngoscope.

2006;116:1303–1309.
 ACCEPTED MANUSCRIPT

6- Marie TA, Sahar SS, Laudia BR, Georges MZ, Anis SB. The effect of dexamethasone on

post-operative vomiting after tonsillectomy. Anesth Anal. 2001;92:636-9.

7- Bernet AMD, Emery PJ. A significant reduction in paediatric post-tonsillectomy

vomiting through audit. Ann R Coll Surg Eng. 2008;90:226-30

8- Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. More codeine

T
fatalities after tonsillectomy in North American children. Pediatrics. 2012;129:1343–7

IP
9- Uysal HY, Takmaz SA, Yaman F, Baltaci B, Başar H. The efficacy of intravenous

CR
paracetamol versus tramadol for post-operative analgesia after adenotonsillectomy in

children. J Clin Anesth. 2011 Feb;23(1):53-7.

US
10- Michelet D, Andreu-Gallien J, Bensalah T, Hilly J, Wood C, Nivoche Y, et al. A meta-
AN
analysis of the use of nonsteroidal antiinflammatory drugs for pediatric post-operative

pain. Anesth Analg. 2012;114:393–406.

M

11- Thimmasettaiah NB1, Chandrappa RG. A prospective study to compare the effects of
ED

pre, intra and post-operative steroid (dexamethasone sodium phosphate) on post-

tonsillectomy morbidity. J Pharmacol Pharmacother. 2012 Jul;3(3):254-8.

PT

12- Sarny S, Habermann W, Ossimitz G, Schmid C, Stammberger H. Tonsilar haemorrhage

CE

and re-admission: a questionnaire based study. Eur Arch Otorhinolaryngol.

2011;268:1803–1807.
AC

13- Dan AE, Thygesen TH, Pinholt EM Corticosteroid administration in oral and

orthognathic surgery: a systematic review of the literature and meta-analysis. J Oral

Maxillofac Surg. 2010 Sep;68(9):2207-20.

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14- Bedwell JR, Pierce M, Levy M, Shah RK. Ibuprofen with acetaminophen for post-

operative pain control following tonsillectomy does not increase emergency department

utilization. Otolaryngol Head Neck Surg. 2014 Dec;151(6):963-6.

15- Kelly LE, Sommer DD, Ramakrishna J, Hoffbauer S, Arbab-Tafti S, Reid D, et al.

Morphine or Ibuprofen for post-tonsillectomy analgesia: a randomized trial. Pediatrics.

T
2015 Feb;135(2):307-13.

IP
16- Aveline C, Le Hetet H, Le Roux A, Bonnet F.A survey of the administration of

CR
prednisolone versus ibuprofen analgesic protocols after ambulatory tonsillectomy.

Anaesth Crit Care Pain Med. 2015 Oct;34(5):281-7.

US
17- Palme CE, Tomasevic P, Pohl DV. Evaluating the effects of oral prednisolone on
AN
recovery after tonsillectomy: a prospective, double-blind, randomized trial.

Laryngoscope. 2000 Dec;110(12):2000-4.

M

18- Macassey E, Dawes P, Taylor B, Gray A. The effect of a post-operative course of oral
ED

prednisone on post-operative morbidity following childhood tonsillectomy. Otolaryngol

Head Neck Surg. 2012 Sep;147(3):551-6

PT

19- Park SK, Kim J, Kim JM, Yeon JY, Shim WS, Lee DW. Effects of oral prednisolone on
CE

recovery after tonsillectomy. Laryngoscope. 2015 Jan;125(1):111-7.

20- Smith I1, Wilde A. Secondary tonsillectomy haemorrhage and non-steroidal anti-
AC

inflammatory drugs. J Laryngol Otol. 1999 Jan;113(1):28-30.

21- Marret E, Flahault A, Samama CM, Bonnet F. Effects of post-operative, nonsteroidal,

antiinflammatory drugs on bleeding risk after tonsillectomy: meta-analysis of

randomized, controlled trials. Anesthesiology. 2003 Jun;98(6):1497-502.

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22- Møiniche S, Rømsing J, Dahl JB, Tramèr MR. Nonsteroidal antiinflammatory drugs and

the risk of operative site bleeding after tonsillectomy: a quantitative systematic review.

Anesth Analg. 2003 Jan;96(1):68-77

23- D'Souza JN, Schmidt RJ, Xie L, Adelman JP, Nardone HC. Post-operative nonsteroidal

anti-inflammatory drugs and risk of bleeding in pediatric intracapsular tonsillectomy. Int

T
J Pediatr Otorhinolaryngol. 2015 Sep;79(9):1472-6.

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24- Mudd PA, Thottathil P, Giordano T, Wetmore RF, Elden L, Jawad AF, et al. Association

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Between Ibuprofen Use and Severity of Surgically Managed Posttonsillectomy

Hemorrhage. JAMA Otolaryngol Head Neck Surg. 2017 Jul 1;143(7):712-717

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25- Schafer A. Effects of nonsteroidal antiinflammatory drugs on platelet function and
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systemic hemostasis. J Clin Pharmacol. 1995 Mar;35(3):209-19.

26- Krishna S, Hughes LF, Lin SY. Post-operative hemorrhage with nonsteroidal anti-
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inflammatory drug use after tonsillectomy: a meta-analysis. Arch Otolaryngol Head Neck
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Surg. 2003 Oct;129(10):1086-9.

27- Riggin L, Ramakrishna J, Sommer DD, Koren G. A 2013 updated systematic review &
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meta-analysis of 36 randomized controlled trials; no apparent effects of non steroidal

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anti-inflammatory agents on the risk of bleeding after tonsillectomy. Clin Otolaryngol.

2013 Apr;38(2):115-29.
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28- Plante J, Turgeon AF, Zarychanski R, Lauzier F, Vigneault L, Moore L, Boutin A,

Fergusson DA. Effect of systemic steroids on post-tonsillectomy bleeding and

reinterventions: systematic review and meta-analysis of randomised controlled trials.

BMJ. 2012 Aug 28;345:e5389.

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29- Suzuki S, Yasunaga H, Matsui H, Horiguchi H, Fushimi K, Yamasoba T. Impact of

systemic steroids on posttonsillectomy bleeding: analysis of 61 430 patients using a

national inpatient database in Japan. JAMA Otolaryngol Head Neck Surg. 2014

Oct;140(10):906-10.

30- Thong KL, Mant MJ, Grace MG. Lack of effect of prednisone administration on bleeding

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time and platelet function of normal subjects. Br J Haematol. 1978 Mar;38(3):373-80

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7. TABLES

Table 1: Demographic and clinical data of both study groups:

Item Group I Group II Statistical test P value

Age 18.65 ± 6.24 19.02 ± 6.13 U = 7261 0.45

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Sex

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Male 76 66 Chi = 1.6476 0.2

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Female 48 58

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Preoperative
7.5 ± 0.94 7.69 ± 0.69 U = 7055.5 0.23
sleep duration
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Chi: Chi square test
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U: U value of Mann Whitney U test

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Table 2: Comparison groups I and II regarding parameters of post-operative pain

assessment:

Group I
Group II Test of
Parameter p value
significance
No. % No. %

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High pain 21 16.9 28 22.6
Pain at rest Chi =1.25 0.36

CR
Low pain 103 83.1 96 77.4

Highly

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24 19.4 33 26.6
Dietary impaired
Chi =1.85 0.17
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habits Minimally
100 80.6 91 73.4
impaired
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Tiredness High tiredness 10 8.1 21 16.9

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Chi = 4.46 0.03

of Speech Low tiredness 114 91.9 103 83.1
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Decrease of sleeping hours

per day 1.33 ± 0.49 1.25 ± 0.43 U= 7114.5 0.31

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(Mean ± SD)
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Chi: Chi square test

U: U value of Mann Whitney U test

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Table 3: Comparison between study groups regarding incidence of vomiting at first post-

operative day:

Incidence of Group I Group II

Chi square test p value
vomiting No. % No. %

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Vomiting 7 5.6 16 12.9

IP
No vomiting 117 94.4 108 87.1 3.88 0.049

CR
Total 124 100 124 100

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Table 4: Comparison between study groups regarding incidence of secondary post-

tonsillectomy bleeding:

Incidence of Group I Group II

Chi square test p value
bleeding No. % No. %

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Bleeding 3 2.4 10 8.1

IP
No Bleeding 121 97.6 114 91.9 3.98 0.046

CR
Total 124 100 124 100

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Table 5: Comparison between groups I and II regarding severity of secondary post-

tonsillectomy bleeding

Chi square
Grade Group I Group II p value
test

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Grade A2 2 0

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Grade B 1 7

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Grade C 0 2 8.07 0.045

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Grade D 0 AN 1

Total 3 10
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