10.14639/0392-100X-N1369
Objective. Nowadays, povidone-iodine is commonly used as a disinfectant in head and neck procedures. The present study investigated the effect of povidone-iodine, which is used as a disinfectant solution in tympanoplasty, on patients’ hearing.Methods. A povidone-iodine solution was used as disinfection in chronic otitis media patients undergoing tympanoplasty. In the intervention group, 5% povidone-iodine, was applied to the external auditory canal and remained there for 10 minutes. In the control group, povidone- iodine was used but not allowed to enter the external auditory canal by inserting cotton wool into the canal. To evaluate the adverse effect of povidone-iodine on hearing, the bone conduc- tion level was compared between groups at baseline and one month after exposure.Results. Bone conduction levels at frequencies 500 Hz, 1 kHz, 2 kHz, 3 kHz, 4 kHz and 8 kHz and mean of bone conduction level in 500 Hz, 1 kHz and 2 kHz were measured and com- pared respectively between intervention and control group. No significant difference was seen between bone conduction levels of above frequencies and mean frequencies before and one month after surgery. (P-value = 0.321, 0.432, 0.219, 0.489, 0.61, 0.112, 0.324 respectively).Conclusions. According to the present study, currently available 5% povidone-iodine did not affect hearing and therefore, can be comfortably used for preparation and disinfection&nbsp;in otologic surgeries.
text/xml
1827-675X
1369
en
Ghazal Norouzi
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
otitis media
The safety of povidone-iodine solution in tympanoplasty: a randomised, triple-blind, placebo-controlled study
Text.Serial.Journal
https://www.actaitalica.it/
41
Otology
2021-09-14
2021-01-09
2021-09-15
2021-09-15
377-382
1
Ghazal Norouzi
2021/09/14
10.14639/0392-100X-N1369
377
Otolaryngology Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran
1827-675X
otitis media
382
The safety of povidone-iodine solution in tympanoplasty: a randomised, triple-blind, placebo-controlled study
https://www.actaitalica.it/article/download/1369/658
41
ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41:377-382; doi: 10.14639/0392-100X-N1369




Otology


The safety of povidone-iodine solution
in tympanoplasty: a randomised, triple-blind,
placebo-controlled study
Valutazione della sicurezza nell’utilizzo della soluzione con iodopovidone
nella timpanoplastica: studio placebo-controllo, in triplo cieco randomizzato
Behrouz Barati, Mahboobe Asadi, Matin Ghazizadeh, Ghazal Norouzi
Otolaryngology Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran


SUMMARY
Objective. Nowadays, povidone-iodine is commonly used as a disinfectant in head and
neck procedures. The present study investigated the effect of povidone-iodine, which is
used as a disinfectant solution in tympanoplasty, on patients’ hearing.
Methods. A povidone-iodine solution was used as disinfection in chronic otitis media patients
undergoing tympanoplasty. In the intervention group, 5% povidone-iodine, was applied to the
external auditory canal and remained there for 10 minutes. In the control group, povidone-
iodine was used but not allowed to enter the external auditory canal by inserting cotton wool
into the canal. To evaluate the adverse effect of povidone-iodine on hearing, the bone conduc-
tion level was compared between groups at baseline and one month after exposure.
Results. Bone conduction levels at frequencies 500 Hz, 1 kHz, 2 kHz, 3 kHz, 4 kHz and 8
kHz and mean of bone conduction level in 500 Hz, 1 kHz and 2 kHz were measured and com-             Received: January 9, 2021
pared respectively between intervention and control group. No significant difference was seen       Accepted: February 27, 2021
between bone conduction levels of above frequencies and mean frequencies before and one
month after surgery. (P-value = 0.321, 0.432, 0.219, 0.489, 0.61, 0.112, 0.324 respectively)        Correspondence
                                                                                                    Mahboobe Asadi
Conclusions. According to the present study, currently available 5% povidone-iodine did
                                                                                                    Taleghani Educational Hospital,Tabnak St. Velenjak
not affect hearing and therefore, can be comfortably used for preparation and disinfection          Region, Chamran High Way, Tehran, Iran
in otologic surgeries.                                                                              Tel. +98 21230311 Fax +98 2122432570
KEY WORDS: povidone- iodine, tympanoplasty, otitis media                                            E-mail: mahboobeh_farvardin@yahoo.com

                                                                                                    Funding
RIASSUNTO                                                                                           None.
Obiettivo. Al giorno d’oggi, lo iodio-povidone è comunemente usato come disinfettante nelle
procedure della testa e del collo. Il presente studio ha esaminato l’effetto del povidone-iodio,    Conflict of interest
che viene utilizzato come soluzione disinfettante nella timpanoplastica, sull’udito dei pazienti.   The Authors declare no conflict of interest.
Metodi. La soluzione di iodio-povidone è stata utilizzata come disinfettante in pazienti con
otite media cronica sottoposti a timpanoplastica. Nel gruppo di intervento, lo iodio povi-            How to cite this article: Barati B, Asadi M,
done al 5% è stato applicato al canale uditivo esterno e vi è rimasto per dieci minuti. Nel           Ghazizadeh M, et al. The safety of povidone-
gruppo di controllo, è stato usato iodio-povidone ma non gli è stato permesso di entrare              iodine solution in tympanoplasty: a randomised,
nel canale uditivo esterno inserendo un batuffolo di cotone nel canale. Per valutare l’effetto        triple-blind, placebo-controlled study. Acta
avverso dello iodio-povidone sull’udito, è stato valutato il livello di conduzione ossea nei          Otorhinolaryngol Ital 2021;41:377-382. https://
gruppi di trattamento, prima dell’intervento e un mese dopo l’esposizione.                            doi.org/10.14639/0392-100X-N1369
Risultati. Vengono misurati e confrontati i livelli di conduzione ossea a frequenze di 500 Hz
(hertz), 1 kHz (kilohertz), 2 kHz, 3 kHz, 4 kHz e 8 kHz e il livello medio di conduzione ossea      © Società Italiana di Otorinolaringoiatria
                                                                                                    e Chirurgia Cervico-Facciale
a 500 Hz, 1 kHz e 2 kHz rispettivamente tra gruppo di intervento e gruppo di controllo.
Non è stata osservata alcuna differenza significativa tra i livelli di conduzione ossea delle
                                                                                                                   OPEN ACCESS
singole frequenze e delle frequenze medie prima e un mese dopo l’intervento chirurgico.
(Valore P = 0,321, 0,432, 0,219, 0,489, 0,61, 0,112, 0,324 rispettivamente).                        This is an open access article distributed in accordance with
                                                                                                    the CC-BY-NC-ND (Creative Commons Attribution-Non-
Conclusioni. Secondo il presente studio, iodio-povidone al 5% attualmente disponibile non           Commercial-NoDerivatives 4.0 International) license. The
ha diminuito l’udito e quindi può essere tranquillamente utilizzato per la preparazione e la        article can be used by giving appropriate credit and mentio-
disinfezione nella chirurgia otologica.                                                             ning the license, but only for non-commercial purposes and
                                                                                                    only in the original version. For further information: https://
PAROLE CHIAVE: povidone, iodio, timpanoplastica, otite media                                        creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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B. Barati et al.




Introduction                                                     sion if they had chronic otitis media with tympanic mem-
                                                                 brane perforation and were a surgical candidate. Exclusion
Pre-surgical antiseptics are known materials that reduce
                                                                 criteria were: 1) cholesteatoma, 2) previous middle ear
the number of wound infections when used adequately
                                                                 surgery, 3) local skin disturbance, 4) uncontrolled hyper-
and safely 1-3. Standard antiseptic preparations may cause
                                                                 glycaemia, 5) concurrent ossicular chain manipulation or
toxicity to the eyes and ears in head and neck surgeries 4.
                                                                 mastoidectomy during tympanoplasty.
Currently, there is much uncertainty regarding the safety of
                                                                 All patients underwent temporal high-resolution computed
surgical antiseptic preparations in the ear. This concern has
                                                                 tomography before surgery to rule-out any underlying mid-
been a longstanding area of research. In the early 1960s,
                                                                 dle or inner ear malformations caused hearing loss.
Bicknell et al. described varying degrees of morbidity fol-
lowing tympanoplasty with the pre-surgical preparation of
                                                                 Randomisation and interventions
the ear with chlorhexidine 5.
                                                                 Patients were randomly assigned to two groups with the
In addition, iodine has been proven to be antiseptic for
                                                                 block randomisation method. In the intervention group, 5 cc
many years and has been used for a long time. At the end of
                                                                 of povidone-iodine (5% povidone-iodine solution, Medip-
the 19th century, the bactericidal effect of iodine was estab-
                                                                 harma, Iran) was applied in the external auditory canal just
lished 4,6,7. Although it is effective against a wide range of
microbes, no resistance has been reported up to now. Poly-       before tympanoplasty and allowed to stay in the canal for
vinyl pyrrolidone (povidone)-bound iodine is an effective        10 minutes. In the control group, 5% povidone-iodine solu-
formulation of iodine which was proven by in vivo testing        tion was administered before surgery and was not allowed
to be faster acting and more effective against a large num-      to enter the external auditory canal by inserting cotton wool
ber of pathogens than topical antibiotics. This formulation’s    into the canal. After prepping, the ear was irrigated with sa-
broad-spectrum antimicrobial activity and efficacy are well      line by the surgeon’s assistant and the main surgeon started
documented, especially against resistant microorganisms,         tympanoplasty, so that the main surgeon was not aware of
such as methicillin-resistant Staphylococcus aureus 8,9.         the patient’s group. Patients, researchers, and study statis-
Moreover, studying the effect of povidone-iodine on the          ticians were also masked to treatment allocation. All sur-
treatment of chronic otitis media showed that topical povi-      geries were done by the senior author of this article in the
done-iodine is as effective as topical ciprofloxacin 4. How-     standard academic settings. Other probable confounding
ever, it was proven to be ototoxic in many animal studies        factors such as pre-operative ototoxic drug use, excessive
and a small number of human case reports 2,7, and to our         noise exposure, infections, etc. were adjusted.
best of knowledge there is no documented trial reporting
the human ototoxicity of povidone-iodine. Given its valu-        Outcomes and follow-up
able antiseptic properties, in the present study, we assessed    We assessed hearing status at baseline and one month after
the ototoxic effect of povidone-iodine during surgery for        surgery with bone conduction level. Standard bone conduc-
chronic otitis media.                                            tion levels (frequencies 500 Hz, 1 kHz, 2 kHz, 3 kHz, 4
                                                                 kHz, and 8 kHz) and mean of bone conduction levels (fre-
                                                                 quencies 500 Hz, 1 kHz, and 2 kHz) were measured and
Materials and methods                                            compared between groups. Patients were followed on the
This trial was conducted according to the CONSORT state-         seventh day for any surgical complications.
ment 10.
                                                                 Statistical analysis
Design overview                                                  All data were analysed using IBM SPSS Statistics for Win-
This study was a randomised, triple-blind, controlled tri-       dows, Version 20.0. Chi-square test and exact Fischer test
al, approved by the local ethics committee of Shahid Be-         was used to compare the results. A two-sided P value of
heshti University of medical sciences (IR.SBMU.MSP.              ≤ 0.05 was set as a statistically significant threshold.
REC.1396.581), the Iran randomised clinical trial (IRCT)
database (IRCT20200926048841N1). All participants gave
written informed consent.
                                                                 Results
                                                                 Patients were recruited from July 2018 to December 2019.
Setting and participants                                         The CONSORT flow diagram (Fig. 1) shows the alloca-
The study was conducted at the Department of Otolaryn-           tion, follow-up and analysis process. Eighty patients were
gology and Head and Neck Surgery, Taleghani Hospital,            assessed for eligibility, 14 were excluded due to cholestea-
Tehran, Iran. In this trial, patients were eligible for inclu-   toma (n = 3), previous middle ear surgery (n = 5), con-



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                                                                                               The safety of povidone-iodine solution in tympanoplasty




Figure 1. Consort diagram showed the participants allocation, intervention and follow-up.



current ossicular chain manipulation or mastoidectomy                           15 females), control group (16 males and 17 females), all
(n = 6). Thus, the remaining 66 patients were randomised                        undergoing tympanoplasty.
to the intervention (n = 33) or control group (n = 33). The                     Evaluating the bone conduction levels in a wide range fre-
primary assessment demonstrated that the baseline charac-                       quency (500 Hz, 1 kHz, 2 kHz, 3 kHz, 4 kHz and 8 kHz)
teristics were similar between groups. None of the patients                     with attaining the mean value of bone conduction level
reported a history of ototoxic drug consumption during the                      (500 Hz, 1 kHz and 2 kHz) was done for each patient. No
preoperative period based on the history and medical re-                        significant difference was seen between frequency-specific
cords assessment.                                                               bone conduction levels and mean bone conduction levels
In this trial, 66 patients (32 females and 34 males) with a                     between the intervention and control groups before (P-val-
mean age of 42.12 ± 11.33 were enrolled. The youngest                           ue = 0.321, 0.432, 0.219, 0.489, 0.612, 0.112, 0.324, re-
patient was 20 years old and the oldest one was 65 years.                       spectively) and one month after surgery (Tab. I).
There was no significant age difference between the two                         The mean of bone conduction threshold in different fre-
groups (P value = 0.455). All patients were randomised                          quencies was also compared in the intervention and control
into two groups of 33: intervention group (18 males and                         groups before and one month after surgery. No significant



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B. Barati et al.




Table I. Mean of bone conduction threshold in intervention and control group (one month after surgery).
 Bone threshold conduction (frequency)                        Intervention                          Control                P-value
 500 Hz                                                           7.14                              11.07                   0.221
 1 kHz                                                            8.57                              11.64                   0.442
 2 kHz                                                           12.14                              17.14                   0.249
 3 kHz                                                           16.79                              22.14                   0.149
 4 kHz                                                           18.93                              27.14                   0.615
 8 kHz                                                           20.71                              35.23                   0.192
 Mean: 500 Hz,1 kHz, 2 kHz                                       11.68                              12.68                   0.754



difference was seen (respective P values were presented in                      bad physical conditions (age, underlying diseases, etc.),
Table II and Table III).                                                        there is a need for drugs with low and acceptable ototoxic-
Postoperative otorrhoea was seen in 2 patients in the con-                      ity that can be used in the long term. Although there is con-
trol group and ciprofloxacin drop was given for one week.                       cern regarding the safety of antiseptic preparations in the
Both patients showed clinical response on the seventh day                       case of surgical candidate COM, different materials have
and the treatment was stopped, and patients were advised                        used as pre-surgical prepping such as povidone-iodine,
to keep the ear dry.                                                            chlorhexidine gluconate, ethanol and hydrogen peroxide.
                                                                                When reviewing the literature, we found a common con-
Discussion                                                                      cern about the ototoxic effect of this antiseptic solution.
Chronic otitis media (COM) refers to chronic inflammation                       Historically, the primary concern mentioned by Bicknell
of the middle ear persistent for at least 3 months. Since                       in the early 1960s who described pre-surgical preparation
COM is a common cause of reference to otolaryngology                            of the ear with chlorhexidine as a disturber factor in tym-
clinics, its treatment is one of the major health problems                      panoplasty that caused ototoxic effects ranging from high-
among otolaryngologists 1,2. With this in mind, considering                     frequency hearing loss to “dead ears”. Comparing variant
hearing loss and its serious complications proper treatment                     antiseptic agents demonstrate that iodine based solutions
is necessary. The definitive treatment for COM is surgery                       have the least harm effect in the ear, while chlorhexidine
with a probable need for reconstruction of the middle ear.                      and high concentrations of alcohol-based solutions show
Ultimately when there is no possibility of surgery due to                       the most harm 11. Because of the widespread use of povi-


Table II. Mean bone conduction threshold in intervention group (before and one month after surgery).
 Bone conduction threshold (frequency)                       Pre-operation                     Post-operation              P-value
 500 Hz                                                           9.29                               7.14                   0.142
 1 kHz                                                           10.36                               8.57                   0.441
 2 kHz                                                            12.5                              12.14                   0.554
 3 kHz                                                           15.36                              16.79                   0.213
 4 kHz                                                           18.57                              18.93                   0.128
 8 kHz                                                           21.79                              20.71                   0.118



Table III. Mean bone conduction threshold in control group (before and one month after surgery).
 Bone conduction threshold (frequency)                       Pre-operation                      Post-operation             P-value
 500 Hz                                                          11.43                              11.07                    0.21
 1 kHz                                                           13.93                              14.64                   0.232
 2 kHz                                                           17.86                              17.14                   0.519
 3 kHz                                                           22.50                              22.14                    0.89
 4 kHz                                                           27.50                              27.14                   0.712
 8 kHz                                                           35.83                              35.23                   0.312




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done-iodine during interventions, in this study we focused       topical povidone-iodine is as effective as topical ciproflox-
on its ototoxic effect.                                          acin. The same result concluded comparing povidone-io-
Povidone-iodine is a suitable form of iodine that is used        dine and neomycin. Topical povidone-iodine showed effect
commonly as a pre-surgical disinfection method 4,6,7. Disin-     similar to neomycin solution in the treatment of COM 4.
fection with iodine has been demonstrated for many years         Currently, povidone-iodine solution is available in concen-
and different solutions based on iodine have been used for       trations of 5%, 7.5% and 10% weight/volume. The con-
this purpose. Not only it is effective against gram-negative,    centration might affect the severity of the hearing loss.
gram-positive, mycobacterium, treponema, fungi, viruses          Moreover, based on the properties of the solvent, different
and protozoa but also its unique biological effect is charac-    effects of povidone-iodine (aqueous solution or alcoholic
terised by the lack of resistance 2.                             solution) may be expected. Although the alcoholic solution
When preparing the patient with tympanic membrane per-           may show greater antimicrobial potential, its ototoxic ef-
foration, some of the povidone-iodine can potentially enter      fect seems to be higher as well 16.
the middle ear, which theoretically may be harmful to the        To our knowledge, no previous study has directly as-
exposed middle and inner ear. All evidence pertaining to         sessed the potentially toxic effects of povidone-iodine on
the ototoxic effect of povidone-iodine has come from a few
                                                                 the human ear. In this trial, we studied the toxic effects of
animal studies and a small number of human case reports.
                                                                 povidone-iodine used as a disinfection solution for the pre-
In 1982, Aursnes demonstrated that middle ear exposure
                                                                 surgical preparation of patients undergoing tympanoplasty.
for more than 10 min with alcohol-based povidone-iodine
                                                                 Although povidone-iodine showed an ototoxic effect in
solutions showed a histopathologic change in the vestibu-
                                                                 animal studies and some toxic effects at high concentra-
locochlear system of guinea pigs 6. Moreover, the ototoxic-
ity of 10% povidone-iodine was assessed in guinea pigs of        tions in case reports in humans, in our survey no short term
different ages, finding that the cochlea of infants or young     cochlear toxicity of povidone-iodine was detected based on
pigs is more sensitive than that in adults. Ultimately, they     audiometric evaluation.
proposed that the possible reason could be the increased         This study has some limitations. First, this is a single-
permeability of the round window membrane in younger             centre study with a small sample size. Thus, it may not be
versus adult guinea pigs as the membrane thickens with           representative of the overall population. Second, there was
age 7. However, different materials can cross the round win-     a short follow-up time, and patients were observed for one
dow membrane and cause toxic effects on the cochlea. In          month.
humans, no thickness change of round window membrane             Although there is some evidence that iodine antiseptics
is apparent with aging, although this thickness can double       have ototoxicity, the conclusive evidence for the human
under conditions of inflammation 12. This can explain why        ototoxic effect of the povidone-iodine solution is weak.
5% povidone-iodine does not have a toxic effect on cochlea       To increase the statistical accuracy and ensure the use of
in COM in the present study.                                     povidone-iodine, a larger study with prolonged follow-up
Among the literature reviewing the short- and long-term          should be considered.
effects of iodine solution related ototoxicity, Ozkiris men-
tioned that 5% povidone-iodine solution led to significant       Conclusions
short-term hearing loss on the first day that resolved by day
10 while, at 7.5% and 10%, there was a decrease in hearing       Based on our findings, no povidone-iodine related hear-
that persisted for at least 10 days in rats 13. Yagiz detected   ing impairment was detected during short term follow-up.
no effects following 10% povidone-iodine exposure at 10          Thus, povidone-iodine can be considered as a safe disin-
days and 4 weeks in guinea pigs 14.                              fectant solution for otologic surgery.
Another animal study showed that commercially available
high concentration povidone-iodine solutions may cause           Acknowledgements
significant ototoxic effects when applied topically through
a perforated eardrum in rats. Based on this experiment,          The authors would like to thank Dr. Alimohammad Fakhr
high concentration povidone-iodine solutions should not          Yasseri for his dedicated support and guidance.
be used for preoperative surgical site cleaning for otologic
surgery 15. However, this result related to rats and may not     References
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