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The Journal of Emergency Medicine, Vol. 35, No. 4, pp. 363–367, 2008 doi:10.1016/j.jemermed.2007.11.029
Original
Contributions
CLINICAL EFFICACY OF DEXAMETHASONE FOR ACUTE
EXUDATIVE PHARYNGITIS
Ali Tasar, MD,* Sedat Yanturali, MD,† Hakan Topacoglu, MD,† Gurkan Ersoy, MD,† Pinar Unverir, MD,† *Department of Emergency Medicine, Nazilli General Hospital, Nazilli, Aydin, Turkey, and †Department of Emergency Medicine, University of Dokuz Eylul, School of Medicine, Izmir, Turkey Reprint Address: Ali Tasar, MD, Department of Emergency, Nazilli General Hospital, Nazilli, Aydin 35340, Turkey e Abstract—The objective of this study was to investigate
and azithromycin were observed. Sore throat and ody-
whether treatment with single-dose dexamethasone can
nophagia in patients with acute exudative pharyngitis
provide relief of symptoms in acute exudative pharyngitis.
may respond better to treatment with an 8-mg single dose
A prospective, randomized, double-blinded, placebo-
of intramuscular dexamethasone accompanied by an anti-
controlled clinical trial was undertaken over a 3-month
biotic regimen than to antibiotics alone.
2008 Elsevier
period in a university-based Emergency Department. The
study included all consecutive patients between 18 and 65
years of age presenting with acute exudative pharyngitis,
e Keywords— exudative pharyngitis; treatment; dexa-
sore throat, odynophagia, or a combination, and with more
methasone; pain
than two Centor criteria. Each patient was empirically
treated with azithromycin and paracetamol for 3 days. The
effects of placebo and a fixed single dose (8 mg) of intra-
INTRODUCTION
muscular injection of dexamethasone were compared. The
patients were asked to report the exact time to onset of pain
Acute pharyngitis is described as an inflammation of the relief and time to complete relief of pain. After completion
pharynx and surrounding lymphoid tissue Viruses of the treatment, telephone follow-up regarding the relief of
are the most common cause of acute pharyngitis. The pain was conducted. A total of 103 patients were enrolled.
most common bacteria causing pharyngitis is the group Thirty patients with a history of recent antibiotic use, preg-
of A ␤-hemolytic streptococcus (streptococcus pyo- nancy, those who were elderly (> 65 years of age) and
genes) (GABHS) The etiologic pathogen is not ob- patients who failed to give informed consent were excluded.
served in 50% of all cases of pharyngitis, even though Forty-two patients were assigned to the placebo group and
full bacteriological and virologic investigations are 31 were assigned to the intramuscular dexamethasone
group (8-mg single dose). Time to perceived onset of pain
Centor criteria, including history of fever, absence of relief was 8.06 ؎ 4.86 h in steroid-treated patients, as op-
posed to 19.90 ؎ 9.39 h in the control group (p ؍ 0.000).
cough, tender anterior cervical lymph nodes, and exu- The interval required to become pain-free was 28.97 ؎
date, are the most reliable clinical parameters for 12.00 h in the dexamethasone group, vs. 53.74 ؎ 16.23 h in
GABHS pharyngitis The presence of three or four of the placebo group (p ؍ 0.000). No significant difference was
these criteria has a positive predictive value of 40 – 60%.
observed in vital signs between the regimens. No side effects
The absence of three or four of the criteria has a negative and no new complaints attributable to the dexamethasone
predictive value of 80%. Both the sensitivity and speci- RECEIVED: 24 November 2006; FINAL SUBMISSION RECEIVED: 31 October 2007;ACCEPTED: 2 November 2007 ficity of this prediction rule are 75%, compared with the ED, vital signs (blood pressure, pulse, respiratory rate and body temperature) were recorded on the information Most adult cases of pharyngitis are limited to the infection itself and merely require supportive treatment Patients were asked to rate their pain on an ungradu- The standard approach to therapy includes antipy- ated 100-mm visual analog scale (VAS), labeled “no retics, analgesics, and antibiotics if necessary Symp- pain” at the far left and “most pain possible” at the far tomatic treatments, including gargling with warm salt- right. An initial VAS score was taken on enrollment into water, drinking warm liquids, and bed rest should be suggested to all patients with pharyngitis The acute The study medication, an 8-mg dose of dexametha- pharyngitis that is caused by GABHS is the only type sone, and the control medication, the same volume of that requires antibiotic treatment Antibiotic treat- normal saline, were prepared and randomized every day ment affects the recovery and will help protect from by the pharmacy. There was no visual difference be- tween the two drugs. Patients were randomly allocated to Convenient antibiotics fail to relieve the inflammatory either the treatment group or the control group using a symptoms in patients with GABHS pharyngitis. The random number table. All patients received either an patients who have inflammatory complaints benefit from 8-mg single-dose dexamethasone or saline placebo by anti-inflammatory drugs given within 24 h Admin- intramuscular (IM) injection. Emergency physicians who istration of steroids was based on throat cultures in most administered the drugs were blinded to the contents of previous studies. However, steroids are probably not universally used by emergency physicians. The present Throat swabs were not obtained from any patients.
study sought to identify clinical criteria that would help Each patient was empirically treated for bacterial phar- to select patients for steroid use. We aimed to select yngitis for 3 days with 500 mg azithromycin, which has patients using three or four clinical criteria and then been recommended for treatment of pharyngitis in the determine whether a single dose of steroid would relieve literature Patients were instructed to use acetamin- ophen every 6 h for analgesia for 3 days. Frequent oralhydration and rest were offered to the patients.
The patients were instructed to note the time of the initial onset of pain relief, and the time of completeresolution of pain. All patients reported a time for the In this prospective, randomized, double-blinded and pla- onset of pain relief. Telephone follow-up was performed cebo-controlled study, consecutive patients 18 – 65 years every 24 h for 96 h. A lower level of pain or the of age who were admitted to Dokuz Eylul University disappearance of pain was recorded. VAS was used to Hospital Emergency Department in the year 2002 for compare mean pain scores of the patients in the two sore throat, odynophagia, or a combination of these, were groups. On the other hand, VAS was not used repeatedly enrolled. During a 3-month study period, consecutive to evaluate changes in pain intensity. Instead, the exact patients with sore throat, odynophagia, or a combination, time point when the individual reported the pain “de- and who had more than two of the Centor criteria were creased” was used as the time of first relief from pain.
considered for the study. Informed consent was obtained The patients with increased pain or complications (e.g., from each patient who agreed to join the study. The study peritonsillar abscess) were asked to return to the ED. The protocol was approved by our Institutional Review patients who were unreachable by telephone were The patients with the following conditions were ex- The data were analyzed using the Statistical Package cluded from the study: diabetes mellitus, age under 18 or for Social Sciences for Windows, version 11.0 (SPSS over 65 years, hepatic failure, human immunodeficiency Inc., Chicago, IL). Interval data were analyzed using the virus-positive, history of immunosuppression, preg- two-tailed Student’s t-test and chi-squared test, which nancy, use of steroid within 7 days or long-term steroid were used for analysis of nominal data. p Values below use, history of malignancy, peritonsillar/retropharyngeal 0.05 were considered statistically significant. Standard abscess, active herpetic infection, systemic fungal infec- tion, return visit to the Emergency Department (ED) forthe same complaint but not initially enrolled, and use ofantibiotics within 7 days.
An information form that included patient age, sex, presenting symptoms, time seen in the ED, and telephone A total of 103 patients were evaluated in the study.
number was completed. When the patient presented to Thirty patients were excluded from the study based on Table 1. Characteristics and Vital Signs of the Patients in Groups
SD ϭ standard deviation; SBP ϭ systolic blood pressure.
exclusion criteria; 73 patients were then enrolled in the The complaints of the patients disappeared com- study. No patient was excluded from the study in the pletely within the 96-h period. Time periods until relief follow-up period. Demographic data are shown in of pain are shown in All patients used their medications within the prescribed dose and periods and Thirty-one patients were randomized to the dexameth- none of the patients took additional medication. The asone group and 42 to the placebo control group. There patients had no difficulty in the intake of the fluids and was no significant difference in distribution of age, sex, food. None of the patients was observed to have other Centor criteria, or vital signs (including body tempera- complaints or need additional consultations.
ture, respiratory rate, blood pressure, and heart rate)between groups There was no statistical dif-ference between the two groups in VAS scores for pain DISCUSSION
caused by sore throat (t-test, p ϭ 0.503).
Mean time to onset of pain relief was 8.1 Ϯ 4.9 h in Antibiotics fail to relieve the symptoms of exudative the dexamethasone group, and 19.9 Ϯ 9.4 h in the pharyngitis. The etiology is usually infectious, with placebo control group (t-test, p Ͻ 0.001) Mean 40 – 60% of cases being of viral origin and 5– 40% of times to onset of pain relief, based on time period, are cases being of bacterial origin Even in bacterial shown in Mean time until complete resolution of infections that are inflammation related, antibiotics are pain in the steroid study group was 28.9 Ϯ 12.0 h, and not effective We did not determine the etiologic 53.7 Ϯ 16.2 h in the placebo control group. Mean time agent in this study, but as the patients were enrolled in until complete resolution of pain in the steroid group was the study according to Centor criteria, it was thought that significantly earlier than in the placebo group (t-test, p Ͻ 75% of the patients had GABHS. The most predictable clinical parameter for GABHS pharyngitis is reported tobe the Centor criteria Therefore, the author believesthat in such cases there is no need to perform diagnostic Table 2. The Comparison of Our Study to Similar
tests, and antibiotics can be prescribed Although Studies for Using Dexhamethasone in
Exudative Pharyngitis
penicillin is the most prescribed antibiotic for GABSHpharyngitis, it has a failure rate of 30% Azithro- mycin is a stronger medication for GABHS eradication It also has an additional advantage to the patient in that it has a faster effect in a shorter period of time For this reason, azithromycin was preferred for this In the patient with acute pharyngitis, the main objec- tive of supportive treatment is to lower the inflammation and the pain while improving the oral intake to avoid dehydration and to avoid hospitalization Pred- nisolone and dexamethasone have been used in the treat- * 0.0 to 10.0 (100 mm) visual analog scale.
ment of acute pharyngitis in numerous studies in the †0.0 to 3.0 scale (150 mm) visual analog scale.
medical literature. In the group that was treated with the corticosteroid, we observed faster and more powerful §The group not isolated pathogen.
IM ϭ intramuscular; SD ϭ standard deviation.
relief in the severity of pain. Kiderman et al. adminis- Table 3. Time Periods in Respect of Pain Relief or Resolution
tered oral prednisolone in addition to the standard ther- suggested parenteral dose is 0.5–9 mg/kg We used apy for acute pharyngitis in adult patients and demon- 8 mg steroid in this study. Both of these studies have strated effectiveness in relieving sore throat They shown that more rapid pain relief is achieved in patients measured VAS at 12, 24, 48, and 72 h after presentation, treated with corticosteroids. There was about a 2-h dif- as well as time off work, fever, dysphagia, recurrence of ference in mean time to onset of pain relief between symptoms, and bacterial recurrence. A study by Roy O’Brien’s steroid group and our study group. This dif- et al. similarly evaluated the efficacy of a single dose of ference may have resulted from the lower dose of steroid corticosteroid for pain relief in acute exudative pharyn- we administered to the patients in our study. There was gitis associated with infectious mononucleosis in chil- also 7 h difference in mean time to onset of pain relief dren They gave patients either an oral dose of 0.3 between the two placebo groups in these two studies. As mg/kg of dexamethasone or a placebo. Thereafter, the in our study, sore throat relief was earlier in the steroid- patient’s pain was similarly measured with a visual an- treated group than in the placebo-treated group. The alog scale at 0 h, 12 h, 24 h, 48 h, 72 h, and on day 7.
steroid-treated group was free of pain an average 25 h This study reported that, in comparison with the placebo earlier than the placebo-treated group. This time interval group, a significantly greater proportion of patients given was estimated as 20 h in O’Brien et al.’s study dexamethasone achieved pain relief within the first 12 h.
Marvez-Valls et al. reported that administration of ste- But on further follow-up, the proportions of patients roids via oral and IM routes provide similar levels of achieving pain relief were found to be similar in the two pain relief in acute exudative pharyngitis groups. On the other hand, the authors of the article In the study reported by Wei et al., time to pain relief should have mentioned in their conclusion that the short- in both oral and IM steroid groups was found to be earlier lived relief of pain in exudative pharyngitis in children than in placebo groups Time to pain relief in patients with suspected infectious mononucleosis might suggest with a determined pathogen agent has been found to be that a single oral dose of dexamethasone would not be shorter than in patients with an undetermined agent.
sufficient and that additional doses could be necessary GABHS has been found to be the most frequent patho- for ensuring lasting relief. A pilot study by Niland et al.
gen in all groups Complete resolution of pain within has also demonstrated a beneficial effect of one dose of the first 24 h was reported in 33.3%, and 11.1% of steroid on the severity and duration of throat pain in patients in the IM and placebo groups, respectively, in acute pharyngitis in children They used the Wong- the Wei study This was estimated as 41.9% in the Baker FACES scale to rate patients’ symptoms at enroll- dexamethasone group in our study Both the ment. According to the reports of this study, children antibiotic used and the dose of steroid used in the Wei with GABHS pharyngitis who received oral dexametha- study were different than our study As we selected sone as add-on therapy had a more rapid improvement in study patients according to Centor criteria, the probabil- general condition and level of activity with resolution of ity of GABHS pharyngitis can be considered to be 75%.
throat pain. In the present study we only measured VAS Studies conducted on pediatric patients have also score on presentation. Our report confirms this finding of shown the effectiveness of steroid treatment in acute reports that dexamethasone is an effective treatment for pharyngitis On the other hand, Bulloch et al.
reported statistically significantly less time to onset of Wei et al. and O’Brien et al. used 10 mg steroid in pain relief in children with positive antigen detection their study, although the appropriate steroid dose is not than in all children with acute pharyngitis treated with known for exudative pharyngitis However, the LIMITATIONS
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of acetaminophen taken by patients in each group.
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