CIPROFLOXACIN OTIC DROPS FOR PREVENTION OF OTORRHOEA FOLLOWING MYRINGOTOMY AND VENTILATION TUBE INSERTION AMONG CHILDREN

This study aimed to determine the effect of topical otic drops on the rates of postoperative ventilation tube otorrhoea and ventilation tube occlusion in children after myringotomy and ventilation tube insertion in children. A randomized comparative interventional study was carried out on 45 children (84 years) attending Basrah General Hospital, they were 32 males (71%) and 13 females (28.9%), 39 cases have bilateral otitis media with effusion and 6 with unilateral disease, the age range was 3-17 years old. After full assessment of patients, myringotomy and ventilation tube insertion was done for every one with or without adenoidectomy and tonsillectomy or both. They were divided into three groups: first group with no local intervention, second group with single application of ciprofloxacin otic drops at surgery, third group with continuous application of ciprofloxacin otic drops for four days after surgery. A follow-up visit was instructed after 14 days for all. The rates of postoperative ventilation tube otorrhoea and ventilation tube occlusion were recorded. With application of statistical analysis on the results, there was a statistically significant reduction in the rate of postoperative otorrhoea with using the ciprofloxacin otic drops for four days after surgery (P-value 0.043) with a reduction in the incidence of otorrhoea from 29.6% to 7.6% as compared to the group without using the drops. No significant results obtained with a single drops application at time of surgery. There were no statistically significant results in regard to the rates of postoperative ventilation tube occlusion among the study groups. In conclusion, ciprofloxacin otic drops application for few days after myringotomy and ventilation tube insertion appears to be effective to reduce the rate of postoperative ventilation tube otorrhoea. Neither the single nor the continuous otic drops applications could reduce the rates of postoperative ventilation tube occlusion. Introduction O titis media with effusion is a chronic accumulation of fluid within the middle ear and sometimes the mastoid air cells system, without evidence of infection. Symptoms usually involve hearing loss or aural fullness but typically do not involve pain or fever. In children, hearing loss is generally mild and is often detected only with an audiogram, it is thought to be due to acute and later chronic inflammatory changes in the middle ear mucosa, induced by upper respiratory tract infections, acute otitis media and/or allergy, followed by mucous production in the middle ear. Other important factor is eustachian tube dysfunction due to mechanical obstruction or physiological interference with the mucous clearance. The most common bacteria in acute otitis media, in order of frequency, are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. These pathogens are also the most frequent organisms associated with sinusitis and pneumonia. Together, these pathogens account for 85% of acute ear infections. Additional bacterial pathogens include Strept.pyogenes, Staphyl. aureus, gram-negative enteric bacteria, and anaerobes. When an effusion is present for longer than 3 months, Pseudomonas species predominate. The only


Introduction
O titis media with effusion is a chronic accumulation of fluid within the middle ear and sometimes the mastoid air cells system, without evidence of infection.Symptoms usually involve hearing loss or aural fullness but typically do not involve pain or fever.In children, hearing loss is generally mild and is often detected only with an audiogram 1,2 , it is thought to be due to acute and later chronic inflammatory changes in the middle ear mucosa, induced by upper respiratory tract infections, acute otitis media and/or allergy, followed by mucous production in the middle ear.Other important factor is eustachian tube dysfunction due to mechanical obstruction or physiological interference with the mucous clearance 3 .The most common bacteria in acute otitis media, in order of frequency, are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.These pathogens are also the most frequent organisms associated with sinusitis and pneumonia.Together, these pathogens account for 85% of acute ear infections.Additional bacterial pathogens include Strept.pyogenes,Staphyl.aureus, gram-negative enteric bacteria, and anaerobes.When an effusion is present for longer than 3 months, Pseudomonas species predominate.The only difference with the pathogens in otitis media with effusion compared with acute otitis media is that the frequency of S. pneumoniae is not as high, and H. influenzae and Moraxella, catarrhalis are moderately more common 2 .The disease has a bimodal distribution with first peak at 2 years of age, second peak at 5 years of age.At 6 or 7 years old, the incidence decreases substantially, and by 11 years old, the annual incidence is 2%.Fifty percent of the episodes are lasting about 3 months 3 .However, middle ear effusion can be present without preceding acute otitis media, as in the case of serous otitis media after barotrauma.The most common presentations are features consistent with decrease hearing.Parents may notice that television volume is too loud and that the child sits close to the television, does not respond when called (new onset), and often asks "What?.Associated findings during history taking may include a recent upper respiratory tract infection (URTI), a recent plane trip, or current environmental allergies.Otoscopic findings are air-fluid levels (which may be vertically oriented), a translucent membrane with diminished mobility, prominence of the lateral process, a more horizontal orientation of the malleus, and movement only with negative pneumatoscopy( Figure 1).Management involves full evaluation of the patient's language, speech, behavior, and learning abilities.Three main management options for otitis media with effusion According to these criteria, 7 cases (14 ears) were excluded for the following reasons: Noncompliance-4 cases.Cleft palate-2 cases.Previous ventilation tube placement-1 case.After taking a fully informed consent from each child parents or close relative caregivers regarding the explanation of the disease process, its complications, the surgical maneuver intended, the complications of both the surgery and general anesthesia, the postoperative care, each child patient was subjected for full evaluation by a detailed history that involved the chief complaint and duration with full analysis of the hearing status and the severity of hearing difficulty with its implications on the patient general activities, interaction with parents and siblings, school performance, speech and language development and the associated manifestations like any recurrent ear discharges, recurrent sore throat, difficulty swallowing, fever, malaise, nasal obstruction, nasal discharge, mouth breathing, snoring at night, and a history of repeated upper respiratory tract infections, as well as the past medical and surgical history, social history, and any history of drug allergy or chronic drug intake.
The patient's previous investigations were reviewed, including the previous audiological tests, like the pure tone audiograms and tympanograms or other hearing evaluations for the patient's previous visits.Then a thorough ear, nose and throat and head and neck examinations were done, with a special concentration on ear examination, otoscopic examination of the external auditory canal and tympanic membrane, and tuning fork testing of hearing, Rinne's and Weber's tests were done on the cooperative group.After that, each was sent for preoperative recent hearing assessment in the Department of Audiology.In the majority of patients, the pure tone audiometry and tympanometry were performed.The machine which was used for both of these tests is called Impedance Audiometer AA222, by Interacoustics A/S ( Figure 2).Then each patient was sent for the Department of Radiology to perform radiological images of the chest and the post-nasal space to assess the patient's cardiopulmonary status and the presence or absence of adenoidal hypertrophy, respectively.Then a prepared study questionnaire is filled and the patient's information was taken as in the next page.After completing assessment, each case was divided into one of the three study groups: First group: no local intervention after tube insertion, to be regarded as a comparative group Second group: instilling ciprofloxacin ear drops 0.2%, 4-6 drops/ear immediately after tube insertion.Third group: same as the second group with the same drops, but with continuous application for 4 days, in a dose of 3 drops per ear twice daily.During surgery, myringotomy with ventilation tube insertion was done for each single case; the type of tube used is Shepard tube (with wire) that is made of fluoroplastic material, of white color (Figure 3).The ear drops were the same in regard to the chemical constituents and pharmaceutical industry.All patients were given systemic antibiotics and analgesia in the day of surgery and to be continued for at least one week after surgery.All the patients were instructed to avoid water ear contamination during swimming in the postoperative period, and to consult their surgeon urgently if any ear discharge developed.
Follow-up visits were instructed by 14th days postoperatively.During that visit, each patient was evaluated by his or her surgeon and resident with taking a history of ear discharge, duration, color, and amount of the discharge if present, hearing status, any treatment side effects.Also otoscopic and microscopic ear examinations were done to assess the tympanic membrane status, ventilation tubes, and to examine for invisible scanty discharges.Tymanometry was ordered to assess the patency of the tube inserted.All the data was recorded in the patient's specific questionnaire.

Results
The study sample is divided into three age groups; the majority of the patients, 73.3% of children with persistent otitis media and effusion are located within 3-7 years old age group.While 17.8% are within 8-12 years old, and 8.9% are within 13-17 years old, as shown in Table I.While in regard to sex distribution, the majority of the study sample, 71% are males and 28.9% are females (Figure 4).There were no great differences between the three study groups in regard to age and sex of the participants( Table II).In regard to the postoperative otorrhoea rate, there was a higher rate in the first group as compared to the second and third groups, as shown in table III.In regard to the ventilation tube patency, using the type of tympanograms of the patients as indicators for tubes patency, there was a higher rate of ventilation tubes plugging among the first group as compared to the second and third groups (Table V). for speech and language developmental delay, especially in case of persistent otitis media with effusion that further provides an exceptional risk for the proliferation of bacteria 2 .One of the most important management options is surgery that is myringotomy and ventilation tube insertion.The commonest complication of that surgery is postoperative otorrhoea after ventilation tube placement.Other important complication of concern is ventilation tube occlusion that occurs in about three times more commonly in presence of middle ear fluid than in cases of absent middle ear fluid after placement of ventilation tube 2 .This study is designed to deal mainly with these two complications by using a prophylactic topical ear drops in group of patients with persistent otitis media with effusion and compares their efficacy to decrease the postoperative otorrhoea rate and ventilation tube occlusion with another studied group that did not given the topical medication.A ciprofloxacin otic drop 0.2% was chosen for two reasons, because it is a fluoroquinolone antibiotic that has a broad spectrum antibacterial activity and it does not cause vestibular or cochlear toxicity that is recognized with aminoglycosides 4, 5 .In this study, the postoperative ventilation tube otorrhoea rate was reduced with using the otic drops; both for single application at time of surgery (9.7%) or for continuous application for four days later (7.6%) in comparison to non-using the drops (29.6%).This reduction in otorrhoea rate appears to be statistically significant only for continuous otic drops application for four days after surgery (Pvalue 0.043).This result may be similar to the following studies: Nawasreh and Al-wedyan I A (2004) 6 used ciprofloxacin otic drops that resulted in a significant reduction in the postoperative otorrhoea rate from 16.5% for control group (no intervention) to 8.4% for single application at time of surgery, and to 8.2% for prolong application for five days after surgery.He advised for a prolong application if the middle ear content was mucoid at time of surgery.Giles et al (2007) 7 compared the use of ciprodex otic drops (ciprofloxacin 0.3% plus dexamethasone 0.1%) with a prolong application for 5 days against control in cases of otitis media with effusion.The otorrhoea rate was reduced from 34.39% in control to 4.95% in study group.Poetker et al (2006)  8 , a comparison was made between control and prolong applications of ofloxacin otic drops; the result was reduction in postoperative otorrhoea rate from 15% to 8% in the ofloxacin group.Heslop A et al (2010) 9 , a comparative study was made between the use of oral amoxicillin, topical saline and topical ciprofloxacin drops.The result reflects a significant reduction in the postoperative otorrhoea rate in the group of ciprofloxacin drops as compared to the other interventions.Zipfel et al (1999)  10 , control cases were compared with a single application of ciprofloxacin otic drops at time of surgery.They found that the rate of otorrhoea was significantly reduced from 9.1% among control to 3.9% among the study group.This result may be due to a bigger sample of patients involved in the study.In a review study of Garcia P et al (1994) 11 , it was recommended to use a prolong application of topical antimicrobial drops after ventilation tube insertion especially in cases of mucoid or purulent middle ear effusion present at surgery.A more recent review study of Syed M I et al (2013) 12 , they recommended the single use of isotonic saline irrigation or topical antibiotics otic drops at time of surgery and not prolong thereafter in order to reduce the risk of ototoxicity potential.In a further review study of Vaile L et al  (2006)  13 , the authors neither could identify the most effective intervention nor to assess the associated risks of these interventions.As well, they concluded that there was no significant long term benefit obtained with addition of topical or systemic corticosteroids to the antibiotics.Regarding the other important complication of ventilation tube insertion which is the postoperative ventilation tube plugging, there was a higher plugging rate among the first group than the second and third groups, although none of these values were statistically significant during the statistical analysis.This result was not consistent with the study of Poetker et al  (2006)  8 that compares the use of ofloxacin drops against control cases and the result was a significant reduction in the ventilation tube plugging in comparison to control cases.This may be explained by a bigger study sample involved.In another study of Kumar VV et al  (2005)  14 , they found that oxymetazolin solution is as effective as ciprofloxacin solution in prevention of postoperative otorrhoea and tympanostomy tube occlusion.
According to the results of the study, application of topical otic drops after myringotomy and placement of ventilation tube in cases of persistent otitis media with effusion appears to be effective if used continuously for few days after surgery, which gives a good result for reducing the rate of postoperative ventilation tube otorrhoea.A ciprofloxacin otic drop appears to be a good choice to achieve the desired effects since it's a broad spectrum antibiotic and a free of potential for cochlear and vestibular ototoxicity.A future suggestion for research is to study the relationship between the grades of adenoid hypertrophy in the preoperative period and the rate of postoperative ventilation tube otorrhoea and tube occlusion.A second important suggestion of view is to study the relationship between the types of middle ear aspiration at time of surgery, namely serous or mucoid and the rate of postoperative ventilation tube otorrhoea and tube occlusion with further comparing the effects of various interventions on these parameters.Lastly, a third suggestion is to study the optimum duration of topical otic drops application after surgery.

Figure 1 :
Figure 1: Endoscopic view of left ear shows retracted position of malleus handle in otitis media with effusion.