Acta Pædiatrica, 2006; 95: 359
/363

Disappearance of middle ear effusion in acute otitis media monitored

daily with tympanometry

MARJO RENKO1, TERO KONTIOKARI1, KATARIINA JOUNIO-ERVASTI2, HEIKKI

RANTALA1 & MATTI UHARI1

Departments of 1Paediatrics and 2Otorhinolaryngology, University of Oulu, Oulu, Finland

Abstract
Background: Disappearance of middle ear effusion is one of the most important outcomes in the treatment of acute otitis
media (AOM). Aim: To evaluate the duration of effusion in AOM treated by antimicrobials and to find factors influencing
it. Methods: Parents of 90 children with AOM monitored daily the disappearance of effusion with tympanometry. The
children were randomly allocated to be treated with either oral amoxicillin or cefuroxime-axetil for 10 d. Daily monitoring
lasted for 14 d or until the tympanogram was normal (curve A or C) in both ears. Pneumatic otoscopy was carried out every
2 wk. Results: Normal tympanograms were obtained after a median time of 7.5 d (range 1
/58 d) among 75 successfully
monitored patients. In two-thirds (69%) of them, effusion resolved in 14 d. The median duration of effusion did not differ
significantly between the two treatment groups (8 vs 7 days, p/0.7). The children who had unilateral AOM cured more
rapidly than those with bilateral AOM (5 vs 19 d, p B/0.001). In logistic regression analysis adjusted for age, bilaterality
explained treatment failure at 2 wk with an odds ratio of 28.1 (95% CI 4.6
/169.5, p B/0.001).
Conclusion: The choice of antimicrobials did not influence the duration of middle ear effusion, which was much shorter
than had been thought previously. Children with unilateral AOM were cured much more quickly than those with bilateral
AOM.

Key Words: Acute otitis media, antimicrobials, bilaterality, effusion, tympanogram

Introduction Since tympanometry has been shown to be a valid

Acute otitis media (AOM) is one of the most common
paediatric infectious diseases, demanding substantial
clinical resources [1]. Trials concerned with its treat-
ment often lack accurate, clinically significant out-
come measures, and symptomatic relief or treatment
failure are widely and variably used as endpoints
[2
/4]. These are difficult to define, however, and are
often too crude to detect moderate but still clinically
important differences between treatment strategies.
The main aim of the treatment of AOM is to eradicate
bacteria from the middle ear and to normalize
hearing. Middle ear effusion (MEE) causes hearing
impairment [5] and is thus responsible for the long-
term consequences of AOM, i.e. impairment of
speech development and other cognitive disabilities
[6
/8]. Thus, the duration of MEE would be an ideal
outcome measure if it could be assessed reliably and
accurately. In most studies, the duration of MEE, if
considered at all, has been monitored only during
control visits made weekly or at even longer intervals.
method for diagnosing MEE that is serious enough to
cause hearing impairment, in cases of both chronic
effusion and the healing of AOM [9,10], we decided
to evaluate the possibility of using daily tympanome-
try performed at home by parents to measure the
resolution of MEE after AOM. We aimed in this way
to analyse the duration of MEE with microbiologically
optimized treatment (cefuroxime-axetil) compared to
the duration of MEE with standard treatment (amox-
icillin) and to investigate other factors influencing the
duration of MEE.
Methods
Children with no chronic disease at the age of 3 mo to
7 y and with no known allergy to amoxicillin or
cephalosporins who had AOM and whose parents
accepted the protocol and gave their informed con-
sent were included in the study. AOM was diagnosed
if the child had acute symptoms of infection, signs of

Correspondence: Marjo Renko, Department of Paediatrics, University of Oulu, PO Box 5000, FIN-90014, Finland. Tel: /358 8 315 2011. Fax: /358 8 315
5559. E-mail: marjo.renko@oulu.fi

(Received 26 May 2005; revised 2 September 2005; accepted 26 October 2005)

ISSN 0803-5253 print/ISSN 1651-2227 online # 2006 Taylor & Francis
DOI: 10.1080/08035250500437531
360 M. Renko et al.
inflammation on tympanic membrane in pneumatic
otoscopy, and evidence of MEE in both tympanome-
try and pneumatic otoscopy. The diagnoses were
made in primary healthcare settings by members of
the research team. All the participating physicians
were trained in using tympanometry and validated in
using pneumatic otoscopy. After the diagnosis of
AOM, the children were randomly allocated to be
treated with either cefuroxime-axetil (30 mg/kg/d) or
amoxicillin (40 mg/kg/d), both in two divided doses,
for 10 d (Figure 1). Parents filled in a questionnaire
on the child’s history of ear infections, atopic or
allergic diseases, snoring, adenoidectomy and tympa-
notomy tube insertion, day-care attendance, and their
own smoking habits. The duration of symptoms due
to AOM, i.e. otalgia, fever, restlessness, rhinitis and
cough, and information about any signs and symp-
toms of side effects were collected using a symptom
sheet filled in daily by the parents.
Parents were taught to use a hand-held tympan-
ometer (MicroTymp† , Welch Allyn) when they were
recruited to the trial. This training usually took about
15 min. They then performed tympanometric exam-
inations on their children at home daily and printed
out the results with a printer connected to the device.
The monitoring was continued for at least 14 d or
until the tympanometry was normal (curve A or C) in
both ears. Clinical control examinations using pneu-
matic otoscopy were carried out during a control visit
to the clinic every 2 wk. If the child was symptomatic
and the findings in pneumatic otoscopy and tympa-
Figure 1. Flow chart of the study.
nometry were abnormal at the first 2-wk control visit,
amoxicillin (40 mg/kg/d) was given for a further 10 d.
Resolution of MEE, the primary endpoint in the
trial, was defined as conversion from a B curve to an A
or C curve in tympanogram monitoring for at least
two consecutive days. Tympanograms were classified
as peaked (A or C curve) or non-peaked (B curve) or
noisy independently by three investigators. In the case
of disagreement, a consensus was reached through
group discussion. We used a hand-held MicroTymp†
(Welch-Alley) tympanometer, which we have pre-
viously validated against the weights of the MEE
among children anaesthetized for adenoidectomy or
tympanostomy [10]. According to our validation, we
made some minor modifications to the published
recommendation and classified tympanogram A if
the static admittance was ]/ 0.2 mmho and the
tympanic peak pressure /200 to /100 daPa, as C
if the pressure was less than /200 daPa, and as B if
the static admittance was B/ 0.2 mmho [10,11]. The
duration of symptoms was analysed as a secondary
endpoint. All analyses were performed per child, i.e.
the effusion was regarded as resolved when both ears
were free of effusion. The treatment was considered to
have failed if the duration of both MEE and symp-
toms were more than 14 d.
A 30% faster resolution of effusion with cefurox-
ime-axetil than with amoxicillin, i.e. a 30% difference
in the duration of effusion as a continuous variable,
was used as the basis for sample size calculations. We
wanted to be 80% sure whether our results showed
this difference between the groups. With a 0.05 type I
error (a), the calculated sample size for each group
was 36. To ensure that this sample size was reached by
the end of the follow-up, it was planned that 45
patients should be recruited to each treatment group.
The duration of MEE in each group was analysed as a
primary outcome by Kaplan-Meier survival analysis,
and the differences between the groups were tested
with the log-rank test. Associations between binomial
background variables and treatment failure (whether
or not MEE was resolved in 2 wk) were analysed with
the binomial (SND) test and logistic regression
analysis. Odds ratios and 95% confidence intervals
(95%CI) were calculated for individual risk factors.
The duration of symptoms was expressed in terms of
means and ranges, but because of skewed distribu-
tions the differences between groups were tested with
the Mann-Whitney U-test. Associations between the
duration of symptoms and MEE were tested with the
Pearson correlation test. All analyses were performed
with SPSS for Windows, version 11.5, except for the
95% CIs for the results of the binomial tests, which
were calculated by Confidence Interval Analysis,
version 2.0.0. The protocol was ethically acceptable
to the ethical committee of the Medical Faculty of
Oulu University.
 Disappearance of middle ear effusion after otitis media 361
Results with an odds ratio of 28.1 (95% CI 4.6
/169.5, p B/
0.001) (Table II). The other known risk factors for
The background characteristics of the 90 children
AOM entered in the model, i.e. season, number of
allocated randomly to the two treatment groups were
previous AOM episodes, history of adenoidectomy or
similar, except that adenoidectomy had been per-
tympanostomy, sex, day care and parental smoking,
formed more often in the cefuroxime-axetil group were not significantly associated with the cure rate
(Table I). The initial clinical diagnosis was bilateral (Table II).
AOM in 42 children (46%), right-sided AOM in 29 There were seven children (9%) with primary
(32%) and left-sided in 19 (21%). Three children, unilateral AOM, all in the amoxicillin group, in
one randomized to receive cefuroxime-axetil and two whom MEE appeared in the contralateral ear during
amoxicillin, did not actually have AOM according to the treatment. This occurred 3
/10 d after the primary
our criteria, and they were excluded from the analyses diagnosis of AOM and lasted for 2
/10 d, but did not
(Figure 1). impair the cure rate. These seven children were
Daily tympanometry at home was performed suc- analysed according to primary diagnosis, i.e. in the
cessfully on 75 (86%) children for at least 14 d (range unilateral AOM group.
14
/60 d). The reason for failure with the other Symptoms after diagnosis were similar in both
children was resistance of the child in 10 cases and treatment groups, except for fever, which was shorter
reluctance of the parents to continue in two cases. In in duration in the cefuroxime-axetil group, and
two-thirds (69%) of cases, MEE resolved in 14 d. In diarrhoea, which was more common in the cefurox-
the total series, the mean duration of MEE was 10.2 d ime-axetil group. The symptoms which correlated
from diagnosis (median 7.5 d, range 1
/58 d). Our significantly with the duration of MEE were cough
primary outcome, the duration of MEE, did not differ (r /0.45, p B/0.001), rhinitis (r /0.37, p /0.002) and
significantly between the two treatment groups (med- poor appetite (r /0.31, p /0.01). Side effects severe
ian 8.0 vs 7.0 d, p /0.7) (Figure 2). Ten patients enough to result in change of medication occurred in
(13%) finished the monitoring with MEE still present, two children, both of whom had diarrhoea and were in
determined by non-peaked tympanogram and abnor- the cefuroxime-axetil group.
mal otoscopy, five of them at 14 d and five at 29
/43 d.
Children who had unilateral AOM were cured more Discussion
rapidly than those with bilateral AOM (median 5 vs
19 d, pB/ 0.001) (Figure 2). The 23 children with We found that 69% of our children with AOM treated
MEE lasting longer than 14 d (21%) were younger with antimicrobials and monitored daily were effusion
than those recovering faster (mean age 2.7 vs 3.6 y, free within 2 wk of diagnosis. The duration of MEE in
p /0.03). In logistic regression analysis adjusted for the present trial appeared to be much shorter than
that published earlier [12]. We believe that this is a
age, bilaterality explained treatment failure at 2 wk
genuine finding which could at least partly be
Table I. Background characteristics of the 90 children with acute explained by the older age of the children. However,
otitis media allocated randomly to either amoxicillin or cefuroxime- without daily monitoring, as in this trial, those
axetil treatment. patients with quick recurrences would be interpreted
as patients with long-lasting MEE. Most of the
Amoxicillin Cefuroxime unilateral cases resolved in a week, while the resolu-
Characteristic (n /44) (n /46) tion of bilateral MEE took twice as long. MEE has
previously been found at 2 wk after the diagnosis of
Number of boys (%) 27 (61%) 29 (63%)
Mean age in years (range) 3.2 (0.6
/7.0) 3.1 (0.7
/6.9)
AOM in 50
/70% of children treated with antibiotics,
Adenoidectomy performed 10 (23%) 15 (33%) and at 1 mo in 30
/50% [13
/16], and the median
Tympanostomy performed 2 (5%) 3 (7%) duration has been as long as 50 d [17]. In these
Mean number of AOM episodes studies the existence of MEE was checked at an
(range) 6.2 (0
/20) 6.7 (0
/40) interval of several weeks, and thus at least some of the
Atopic eczema 10 (23%) 9 (20%)
History of wheezing 5 (11%) 1 (2%)
MEEs found could have been due to re-infection.
Mode of day care Home 21 (48%) 17 (37%) Daily evaluation of the resolution of otorrhoea has
Family day care 2 (5%) 4 (9%) been performed in patients with tympanostomy tubes
Day care centre 19 (43%) 22 (48%) [18,19], yielding cure rates varying from 1 to 8 d
Mother smokes 4 (9%) 9 (20%) according to the therapy, which is in line with our
Father smokes 10 (23%) 9 (20%)
Snoring 12 (27%) 7 (15%)
results even though these patients are not fully
Mean duration (range) of symptoms before diagnosis (d) comparable.
Rhinitis 6.3 (0
/28) 8.4 (0
/60) Re-analysis of previous reports in which the later-
Cough 5.8 (0
/21) 7.6 (0
/60) ality of AOM has been stated shows unilateral AOM
Fever 1.1 (0
/7) 0.9 (0
/6) episodes to achieve a better bacteriological cure [20],
362 M. Renko et al.

Figure 2. A) Probability of MEE after AOM in 75 children treated with antimicrobials, by laterality. P in log-rank testB/0.001. B)
Probability of MEE after AOM in 75 children treated with antimicrobials, by treatment group. P in log-rank test 0.7.

to lead less often to chronic effusion [21] and to be
effusion free more often 1 mo after diagnosis than
bilateral episodes [15]. In two studies in which a cure
was defined by means of otoscopy twice a month or
tympanometry 1 mo after diagnosis, laterality had no
effect on the prognosis [22,23]. The patients in our
trial, the first in which the resolution of unilateral and
bilateral episodes of AOM has been monitored daily,
had a mean age of 3 y, which is higher than the age at
which the peak incidence of AOM occurs [1]. Other-
wise, they are representative of unselected AOM
patients in primary care, with symptoms comparable
to our previous series [24,25]. As children younger
than 2 y have a higher risk of bilateral MEE [26],
symptomatic and bacteriological failure [20], and
prolonged MEE after AOM [15,17] than older
children, age is a confounding factor. In our logistic
multivariate modelling, laterality was a strong inde-
pendent risk factor for the resolution of MEE even
after adjusting for age.
Amoxicillin was still efficacious against about 90%
and cefuroxime-axetil against almost all of the oto-
pathogenic bacteria in our area during the trial. Since
we used the duration of MEE as the primary endpoint
and the efficacy of the treatment, we should have been
able to see even small differences between the
compared antimicrobials.
Daily tympanometric monitoring during treatment
for AOM was successful in over 80% of the cases
recruited and produced new information about the
recovery process and the resolution of effusion.
Tympanometry is a well-documented method for
diagnosing MEE, with a sensitivity varying between
79 and 90% and specificity between 58 and 98%
relative to findings in myringotomy [9,10,27,28]. A
peaked tympanogram (type A or C) eliminates the

Table II. Characteristics of the children followed up with daily tympanograms after the diagnosis of AOM, by disappearance of effusion
from both ears within 14 d. Odds ratios from a multivariate logistic regression model for the disappearance of effusion, adjusted for age.

Both ears effusion free in 14 d

Characteristic Yes (n /52) No (n/23) Odds ratio (95% CI) p -value

Laterality of AOM Bilateral 14 (27%) 20 (87%) 1

Unilateral 38 (73%) 3 (13%) 28.1 (4.6
/169.5) B/0.001
Number of boys 30 (58%) 16 (70%) 0.2 (0.04
/1.3) 0.09
Mean number of previous
AOM episodes (range) 7.2 (0
/20) 5.5 (0
/40) 1.0 (0.9
/1.1) 0.9
Adenoidectomy performed 17 (33%) 5 (22%) 1.0 (0.1
/8.3) 0.9
Tympanostomy performed 2 (4%) 2 (9%) 0.6 (0.03
/10.3) 0.7
Day care Home 21 (40%) 13 (57%) 1
Family 5 (10%) 1 (4%) 2.1 (0.3
/13.5) 0.4
Centre 25 (48%) 9 (39%) 0.4 (0.1
/12.9) 0.6
Mother smokes 7 (14%) 3 (13%) 1.4 (0.1
/20.9) 0.8
Father smokes 11 (21%) 6 (26%) 2.1 (0.3
/14.7) 0.5
Treatment group Amoxicillin 27 (52%) 13 (57%) 1
Cefuroxime 25 (48%) 10 (44%) 0.9 (0.2
/3.6) 0.9
 Disappearance of middle ear effusion after otitis media
possibility of hearing impairment due to MEE with
98% certainty [9], and thus the method can be used
to assess the main risk of long-term complications.
Tympanometry is easy to perform, even on infants
[10,28], and hand-held devices can be used by
parents at home. Daily monitoring of tympanograms
is an easy, accurate, objective and reliable way of
monitoring the resolution of AOM, and should be
used more often in research to compare alternative
treatments for AOM.
We found no difference in efficacy between the
antimicrobials used in this trial. It is appealing to
hypothesize that a favourable outcome could have
been achieved with the children with unilateral AOM
even without antimicrobials. This practice would
reduce the need for antimicrobials by half.
Acknowledgement
The tympanometers were kindly donated by Glaxo-
SmithKlein.
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