Introduction
In recent years, steroid application via intratympanic perfusion has become more common as a primary treatment or salvage treatment for sudden idiopathic hearing loss and for treating Ménière's disease and various inner-ear diseases such as tinnitus.Reference Crawley, Close, Canto and Harris 1 , Reference Erdur, Kayhan and Cirik 2 Intratympanic steroid treatment is often well tolerated by patients, does not require hospitalisation, and can be used as a primary, combined, or salvage treatment in the clinic. It is also inexpensive compared with systemic steroid use.Reference Fu, Zhao, Zhang and Chi 3
Animal studies have shown that application through the tympanic membrane generates higher steroid concentrations in the perilymph compared with systemic methods. Intratympanic application also avoids the side effects of systemic steroid treatment such as immunosuppression, osteoporosis and weight gain, as well as endocrine and skin changes.Reference Alles, der Gaag and Stokroos 4 Another significant advantage of intratympanic injection is that it enables treatment to be restricted to the affected ear.Reference Alles, der Gaag and Stokroos 4 However, pain due to injection, hearing loss, tympanic membrane perforation, otitis media and vertigo are clear disadvantages compared with systemic steroid use.Reference Erdur, Kayhan and Cirik 2 , Reference Choi, Lee, Lim, In, Kim and Bae 5 , Reference Barrs 6 Intratympanic steroid application can be via direct injection without anaesthesia or with local anaesthesia such as lidocaine spray, lidocaine injection, topical phenol, pantocaine or Emla cream (lidocaine plus prilocaine).Reference Belhassen and Saliba 7 – Reference Paksoy, Altin, Eken and Hardal 10 Although a number of reports have described intratympanic injection, there is no consensus on which anaesthesia technique is most comfortable for patients.Reference Belhassen and Saliba 7 Further, the least painful method of injection through the tympanic membrane has not been established.
This study aimed to compare patient comfort levels for intratympanic injections without prior anaesthesia with those performed after lidocaine injection or topical lidocaine.
Materials and methods
This retrospective study included 40 patients (17 men and 23 women) aged 18–78 years (mean 49.2 years) who underwent intratympanic injection between June 2013 and December 2014. Ethical approval was obtained from the Medical Faculty, Gaziantep University. Written consent was provided by all patients after the benefits and risks of treatment methods had been explained. In all, 24 patients with sudden idiopathic hearing loss underwent intratympanic injection. In those patients, hearing loss was sensorineural and had developed over three days or less. In all, 16 patients with refractory idiopathic tinnitus lasting for at least four weeks and who did not benefit from oral medical treatment also underwent intratympanic steroid injection.
Patients were excluded from the study if they had received painkillers within the last 24 hours, had used oral steroids, had undergone ear surgery, had chronic otitis media, had Eustachian tube dysfunction, had been diagnosed with a retrocochlear pathology, had received combined intratympanic treatment with systemic steroids for sudden idiopathic hearing loss or had received fewer than three intratympanic injections. Patient evaluation included taking a detailed anamnesis (i.e. medical history), autoscopic examination, audiological testing and magnetic resonance imaging to eliminate the possibility of a retrocochlear lesion.
Study design
All 40 patients received intratympanic injections once a week for 3 consecutive weeks. Patients were not randomised and each received three different types of premedication: lidocaine injection or lidocaine spray as a local anaesthetic or no anaesthesia. In the first method, subcutaneous injection of local anaesthetic (1 per cent lidocaine and 1:100 000 adrenaline; Jetokain; IE Ulagay, Istanbul, Turkey) was performed using a dental injector into the anterior, posterior and both lateral quadrants of the external auditory canal prior to intratympanic injection. In the second method, a 10 per cent lidocaine spray (Xylocaine; AstraZeneca, Cambridge, UK) was applied three times from the external auditory canal onto the tympanic membrane 20 minutes before intratympanic injection. Each application contained 10 mg lidocaine (total 30 mg). Lidocaine spray was aspirated from the tympanic membrane prior to injection. Prior to injections without anaesthesia, patients were not sedated. The pain level associated with each type of premedication was assessed at 5 minutes and 45 minutes after intratympanic injection.
Intratympanic injection
Prior to intratympanic injection of dexamethasone, the vial was warmed to body temperature in the palm of the hand to prevent dizziness due to a cold injection. Afterwards, patients were moved into a supine position with their head turned 45° toward the healthy ear and about 0.5 ml dexamethasone (4 mg/ml) was applied into the posterior–inferior quadrant via a 25-gauge spinal needle under microscopy so as to fill the middle ear. Patients were then asked to remain in this position for 30 minutes to ensure that the maximum amount of medication could be absorbed through the round window. Patients were also asked not to swallow after the injection to prevent leakage of the medication into the Eustachian tube. All patients were injected in the same way to control for other factors that might affect pain assessment.
Pain evaluation
The effects of anaesthesia on pain were assessed by asking patients to score the pain levels at 5 and 45 minutes after intratympanic injection using a 10-point visual analogue scale (VAS): 0 (no pain) to 10 (unbearable pain).
Statistical analysis
All 40 patients were treated with all three premedication methods. A power analysis for repeated measures of two repeated measurements found that the lidocaine injection results had a power of 0.892 (effect size = 0.65), the lidocaine spray results had a power of 0.853 (effect size = 0.57) and without anaesthesia results had a power of 0.867 (effect size = 0.60).
Statistical analyses were performed using IBM SPSS Statistics version 21.0 software (Armonk, New York, USA). The Shapiro-Wilk normality test was used to test for normally distributed data, and the Friedman (K related samples test) and Wilcoxon (two related samples tests) tests were used to test for differences between groups of non-normally distributed data. A p value of less than 0.05 was considered statistically significant.
Results
Seventeen men (42.5 per cent) and 23 women (57.5 per cent) aged 18–78 years (mean age 49.2 ± 17.4 years) were included in the study.
Comparison of premedication methods
Friedman testing of VAS pain scores at 5 minutes after intratympanic injection showed that these were significantly higher for lidocaine injection than for the other two methods (χ2 = 17.956, p < 0.05). The lowest mean pain score at 5 minutes was obtained for the lidocaine spray, but there was no significant difference between scores for the lidocaine spray and for no anaesthesia methods. There was no significant difference in 45 minute scores among all three methods (χ2 = 2.114, p = 0.347). Figure 1 shows patients' VAS scores for all three premedication methods at 5 and 45 minutes.
Fig. 1 Interval plot showing the mean visual analogue scale scores and 95 per cent confidence intervals for all three premedication methods at 5 and 45 minutes after intratympanic steroid injection. Min = minutes
Patient preferences for premedication methods
After undergoing all three premedication methods, patients were asked to indicate their order of preference: lidocaine spray was the first choice of 17 patients (42.5 per cent), no anaesthesia was the first choice of 17 (42.5 per cent) and lidocaine injection was the first choice of 6 (15 per cent). When patients were asked to state their least-preferred method, 31 (77.5 per cent) chose the lidocaine injection, 3 (7.5 per cent) chose the lidocaine spray and 6 (15 per cent) chose no anaesthesia. Table I shows the order of preference for all three premedication methods.
Table I Ranking of premedication methods by patients
Side effects of intratympanic injection
No patient experienced haemorrhage in the external auditory canal due to injection, nor was there any requirement for pain-relief medication for the intratympanic injection. Three patients experienced mild temporary vertigo; none experienced hearing loss, infection or tympanic membrane perforation.
Discussion
Intratympanic injection is a minimally-invasive procedure that is well tolerated by patients without a need for medication; it can be performed in the clinic without major complications.Reference Fu, Zhao, Zhang and Chi 3 Using this technique, steroids can pass through the blood–labyrinth barrier and reach higher concentrations in the perilymph–endolymph compared with systemic administration.Reference Parnes, Sun and Freeman 11 Side effects such as glucose intolerance, drug-induced abnormal liver function, acne, effects on the gastrointestinal system, hypertension, immunosuppression and femoral head avascular necrosis do not occur with intratympanic steroid injection.Reference Choung, Park, Shin and Cho 12 Intratympanic injection is used to treat various inner-ear diseases, including sudden idiopathic hearing loss, tinnitus and Ménière's disease.Reference Dispenza, De Stefano, Costantino, Marchese and Riggio 13 – Reference Topak, Sahin-Yilmaz, Ozdoganoglu, Yilmaz, Ozbay and Kulekci 15 Other intratympanic injection indications have been on the rise in recent years. Chung et al. demonstrated that intratympanic steroid injections are effective for treating Bell's palsy.Reference Chung, Park, Lee, Kim, Cho and Kim 16 Yang et al. reported that intratympanic steroid injections were effective for treating adolescent and adult patients with otitis media with effusion.Reference Yang, Zhao, An, Zheng, Yu and Gu 17
Patients may experience earache, caloric vertigo, dizziness, tympanic membrane perforation, hearing loss or infection due to intratympanic injections.Reference Parnes, Sun and Freeman 18 Caloric vertigo and dizziness can be prevented by adjusting the temperature of steroids to body temperature before injection. Permanent tympanic membrane perforation, infection and hearing loss rarely occur. Pain can be minimised by using thin needles.Reference Lavigne, Lavigne and Saliba 19 In the present study, each of the three premedication methods for intratympanic injection was well tolerated by patients: the only side effects were a few cases of mild temporary vertigo.
Various local anaesthetics are used to minimise pain during intratympanic injection. Lidocaine spray (applied directly to the tympanic membrane with a sponge or cotton) is the most common method.Reference Han, Park, Boo, Jo, Park and Lee 20 – Reference Gouveris, Selivanova and Mann 22 Lidocaine injection or pantocaine, topical phenol and Emla cream application to the tympanic membrane prior to steroid injection have been used as local anaesthesia.Reference Belhassen and Saliba 7 – Reference Paksoy, Altin, Eken and Hardal 10 Belhassen and Saliba reported that intratympanic injection without local anaesthesia was as well tolerated by patients as injections performed with Emla cream or a lidocaine injection.Reference Belhassen and Saliba 7 In the same study, pain was measured after 5 and 45 minutes using four different pain scales, with no difference identified between the methods. No other studies have compared pain outcomes among different intratympanic injection methods.Reference Belhassen and Saliba 7 No study has compared injection without anaesthesia or with lidocaine injection or lidocaine spray, both of which are used more frequently than Emla cream for local anaesthesia.
The present study found no significant difference in mean VAS scores at 5 minutes between patients who received intratympanic steroid injections without anaesthesia and those who received lidocaine spray anaesthesia. Lower scores were found for the lidocaine spray group than the no anaesthesia group, but the difference was not significant. However, the mean 5-minute VAS score was significantly higher in the lidocaine injection group. This was probably because the lidocaine injection needed to provide adequate anaesthesia caused a similar level of pain to that caused by the steroid injection. Administering anaesthetic agents by local injection has been shown to cause pain as well as needle anxiety, which increases the pain sensation.Reference Kaweski 23 Furthermore, haemorrhage, oedema and haematoma are possible side effects of local anaesthesia premedication administered via injection.Reference Martellucci, Pagliuca, de Vincentiis, Greco, Fusconi and De Virgilio 24 , Reference Tremont-Lukats, Challapalli, McNicol, Lau and Carr 25
After applying local anaesthetic sprays and creams, a short delay is necessary before the intratympanic steroid injection. After Emla cream is applied to the external auditory canal, a delay of about 60 minutes is necessary before intratympanic injection, and a delay of 120 minutes is recommended to achieve more effective local anaesthesia.Reference Belhassen and Saliba 7 , Reference Bierrina and Arnendt-Nielson 26 Although one study reported a delay of only 2–3 minutes after applying lidocaine spray to the tympanic membrane, a period of 20 minutes is more common.Reference Ferri, Frisina, Fasson, Armato, Spinato and Amadori 21 , Reference Filipo, Covelli, Balsamo and Attanasio 27 , Reference Filipo, Attanasio, Russo, Viccaro, Mancini and Covelli 28 The present study adopted a 20-minute delay after applying the lidocaine spray.
Advantages of intratympanic injection without anaesthesia are the lower cost and lack of a waiting period. The possible side effects and complications of local anaesthetics are also avoided.
In the present study, patients ranked the lidocaine spray premedication and injection without anaesthesia as their first preference and the lidocaine injection as their least-preferred method. The reason for the latter may be that the pain of injection was experienced twice: once during anaesthesia infiltration and again during the intratympanic injection. Belhassen and Saliba reported that injection without anaesthesia was the most preferred method.Reference Belhassen and Saliba 7 The reason given by patients for choosing to forego anaesthesia was to avoid the waiting period before intratympanic injection.
The present study and the Belhassen and Saliba study both suggest that using local anaesthesia prior to intratympanic injection (Emla cream, lidocaine spray or lidocaine injection) has no benefit over injection without anaesthesia.Reference Belhassen and Saliba 7 Intratympanic injection without anaesthesia has not been shown to be more painful than the other methods. The present results indicate that intratympanic injection can be performed without anaesthesia, thus protecting patients from the disadvantages of anaesthesia.
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• Intratympanic steroid injections are increasingly used as primary and salvage treatments for otological diseases
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• Intratympanic injection generates higher perilymph drug concentrations compared with the systemic route
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• Intratympanic treatment can avoid systemic side effects
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• Pain is the main limitation of intratympanic drug use, but can be prevented with local anaesthetics
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• Pain levels for intratympanic injection performed without anaesthesia or with the use of lidocaine injection and lidocaine spray as local anaesthetics were compared
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• Pain scores were similar for intratympanic injection with and without local anaesthesia
The small patient cohort was the main limitation of this study. Despite this, the pain score for intratympanic injection without anaesthesia was similar to that obtained with the use of local anaesthesia. However, this finding needs to be verified in a broader range of patients before generalising to the general population.
Conclusion
Different local anaesthetics have been used to control the pain of intratympanic injection. Intratympanic injection was found to be no more painful without local anaesthesia than with local anaesthesia. However, the procedure is cheaper and shorter without anaesthesia, and avoids the side effects of local anaesthetics.
