Intratympanic corticosteroids for sudden sensorineural hearing loss

Stefan K Plontke<sup>a</sup>; Christoph Meisner<sup>a</sup>; Sumit Agrawal; Per Cayé-Thomasen; Kevin Galbraith; Anthony A Mikulec; Lorne Parnes; Yaamini Premakumar; Julia Reiber; Anne GM Schilder; Arne Liebau<sup>a</sup>

doi:10.1002/14651858.CD008080.pub2

Scolaris Content Display Scolaris Content Display

Contenido relacionado

Ir a:

Revisiones y protocolos relacionados
Respuestas clínicas Cochrane
Guías
Temas

Revisiones y protocolos relacionados

Respuestas clínicas Cochrane

Topics

Temas

Figure 1

Process of selection of studies for inclusion in the review.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 5

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 6

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1: Intratympanic compared to systemic corticosteroids as primary therapy, Outcome 1: Mean change in pure tone average (PTA)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1: Intratympanic compared to systemic corticosteroids as primary therapy, Outcome 2: Proportion improved

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1: Intratympanic compared to systemic corticosteroids as primary therapy, Outcome 3: Final PTA

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1: Intratympanic compared to systemic corticosteroids as primary therapy, Outcome 4: Change in hearing threshold with speech audiometry

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1: Intratympanic compared to systemic corticosteroids as primary therapy, Outcome 5: Speech audiometry: additional outcomes

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1: Intratympanic compared to systemic corticosteroids as primary therapy, Outcome 6: Frequency‐specific changes in PTA

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1: Intratympanic compared to systemic corticosteroids as primary therapy, Outcome 7: Adverse events

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2: Combined compared to systemic corticosteroids as primary therapy, Outcome 1: Mean change in pure tone average (PTA)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2: Combined compared to systemic corticosteroids as primary therapy, Outcome 2: Proportion improved

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2: Combined compared to systemic corticosteroids as primary therapy, Outcome 3: Final PTA

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.4

Comparison 2: Combined compared to systemic corticosteroids as primary therapy, Outcome 4: Change in hearing threshold with speech audiometry

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.5

Comparison 2: Combined compared to systemic corticosteroids as primary therapy, Outcome 5: Speech audiometry: additional outcomes

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.6

Comparison 2: Combined compared to systemic corticosteroids as primary therapy, Outcome 6: Frequency‐specific changes with PTA

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.1

Comparison 3: Intratympanic corticosteroids compared to no treatment/placebo as secondary therapy, Outcome 1: Mean change in PTA

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.2

Comparison 3: Intratympanic corticosteroids compared to no treatment/placebo as secondary therapy, Outcome 2: Proportion improved

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.3

Comparison 3: Intratympanic corticosteroids compared to no treatment/placebo as secondary therapy, Outcome 3: Final PTA

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.4

Comparison 3: Intratympanic corticosteroids compared to no treatment/placebo as secondary therapy, Outcome 4: Change in hearing threshold with speech audiometry

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.5

Comparison 3: Intratympanic corticosteroids compared to no treatment/placebo as secondary therapy, Outcome 5: Speech audiometry: additional outcomes

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.6

Comparison 3: Intratympanic corticosteroids compared to no treatment/placebo as secondary therapy, Outcome 6: Frequency‐specific changes with PTA

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.1

Comparison 4: Combined compared to systemic corticosteroids as secondary treatment, Outcome 1: Proportion improved

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.2

Comparison 4: Combined compared to systemic corticosteroids as secondary treatment, Outcome 2: Speech audiometry: additional outcomes

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings 1. Intratympanic corticosteroids versus systemic corticosteroids as primary therapy

Outcomes	*Anticipated absolute effects (95% CI)**		No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Intratympanic corticosteroids versus systemic corticosteroids as primary therapy
Patient or population: sudden sensorineural hearing loss Settings: initial therapy Intervention: intratympanic steroid therapy Comparison: systemic steroid therapy
Outcomes	Systemic therapy (assumed risk)	Intratympanic therapy (corresponding risk)	No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Change in hearing threshold determined by PTA Range 0 dB to 140 dB Negative values represent lowering and positive values represent raising of the hearing threshold. A lower hearing threshold represents hearing improvement).	The mean change in PTA ranged across control groups from ‐30.07 dB to ‐15.1 dB	The mean change in PTA in the intervention groups was on average ‐5.93 dB greater (from ‐4.26 greater to ‐7.61 greater)	701 (10 studies)	MD ‐5.93 dB (95% CI ‐7.61 to ‐4.26)	⊕⊕⊝⊝ low¹	Intratympanic therapy may have a trivial/no effect on the change in hearing threshold when compared to systemic steroids (as primary therapy).
Proportion of patients whose hearing is improved	731 per 1000^a	760 per 1000 (709 to 818)	972 (14 studies)	RR 1.04 (95% CI 0.97 to 1.12)	⊕⊕⊕⊝ moderate²	Intratympanic therapy probably results in little to no difference in the proportion of patients whose hearing is improved compared to systemic corticosteroids (as primary therapy).
Final hearing threshold determined by PTA (a lower value represents better hearing)	The mean final PTA ranged across control groups from 25.1 dB to 59 dB	The mean final PTA in the intervention groups was on average ‐3.31 dB lower (‐6.16 lower to ‐0.47 lower)	516 (7 studies)	MD ‐3.31 dB (95% CI ‐6.16 to ‐0.47)	⊕⊕⊝⊝ low³	Intratympanic therapy may result in little to no difference in the final hearing threshold (as primary therapy).
Adverse events^b	Events in control group	Events in intervention group	No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Tympanic membrane perforation	Comparison not applicable^c	Ranged from 0% (0/30) to 3.9% (5/129)	463 (4 studies)	Not calculable	⊕⊝⊝⊝ very low⁴	The evidence is very uncertain regarding the risk of tympanic membrane perforation for those who received intratympanic corticosteroid as primary treatment.
Vertigo/dizziness: timing not reported^d	13/121 (10.7%)	35/129 (27.1%)	250 (1 study)	RR 2.53 (1.41 to 4.54)	⊕⊕⊝⊝ low⁵	Intratympanic therapy may increase the risk of vertigo/dizziness of unspecified timing as compared to systemic corticosteroid.
Vertigo/dizziness: at the time of injection	Comparison not applicable^c	3 studies reported a rate between 1.5% (1/67) and 21% (4/19) for those who received an intratympanic injection^e	301 (4 studies)	Not calculable	⊕⊝⊝⊝ very low⁶	The evidence is very uncertain regarding the risk of vertigo/dizziness at the time of intratympanic injection of corticosteroid as primary treatment.
Ear pain: timing not reported^f	4/141 (2.8%)	74/148 (50%)	289 (2 studies)	RR 15.68 (95% CI 6.22 to 39.49)	⊕⊕⊕⊝ moderate⁷	Intratympanic corticosteroid injection probably increases the risk of ear pain of unspecified timing as compared to systemic corticosteroid when used as primary treatment.
Ear pain: at the time of injection^f	Comparison not applicable^c	3 studies reported a rate between 4.8% (5/104) and 27.1% (35/129)	393 (3 studies)	Not calculable	⊕⊕⊝⊝ low⁸	The evidence suggests that there may be a risk of ear pain at the time of intratympanic injection of corticosteroid as primary treatment.
The basis for the assumed risk* is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; PTA: pure tone audiometry; RR: risk ratio
^aFourteen studies recruited participants suffering from sudden sensorineural hearing loss. The incidence of improvement for the systemic corticosteroid group in these 14 studies was 73.07%. We have used 731 per 1000 to express the assumed risk. ^bOnly the most widely reported adverse events are described here. For adverse events that could feasibly occur in either group, we have only included the studies that provided a rate for both groups. For adverse events that could only occur in one group, we have only included the studies that reported the rate in that group, and presented these as a range. A full description of adverse event data is available for reference in Table 1. ^cComparisons between patients receiving intratympanic therapy and those receiving only systemic therapy were regarded as invalid for the following adverse events: persistent tympanic membrane perforation, vertigo observed at the time of intratympanic injection and ear pain observed at the time of intratympanic injection. This is explained in Data extraction and management. ^dA single study reported a rate for both intratympanic and systemic corticosteroid (Rauch 2011). However, it is not specified whether all of the patients in the intratympanic corticosteroid group experiencing vertigo did so at the time of injection. We have therefore reported this outcome separately from vertigo/dizziness interpreted as having occurred specifically at the time of injection. ^eIn two studies, two groups received intratympanic injection: in Tsounis 2018, one group received intratympanic corticosteroid and the other received intratympanic and systemic corticosteroid; in Huang 2021, one group received intratympanic corticosteroid and the other received intravenous followed by intratympanic corticosteroid. ^fIn each study contributing data, the number of participants with ear pain/earache was presented separately from the numbers with ear pain at intratympanic injection. It was assumed, therefore that those participants with pain at injection were not included among those with ear pain/earache. GRADE Working Group grades of evidence High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: We are very uncertain about the estimate.
¹Downgraded one level due to risk of bias: eight studies were at high risk of other bias, three studies were at risk of attrition bias and three studies were at risk of selection bias. Downgraded one level due to inconsistency: the size and direction of effect varied between the studies and the I² value was 80%. ²Downgraded one level due to risk of bias: we judged 11 of 14 studies to be at unclear or high risk of selection bias and we judged 12 of 14 studies to be at high risk of other bias. ³Downgraded one level due to risk of bias: we judged six studies to be at high risk of other bias; two studies were at high risk of selection bias. Downgraded one level due to inconsistency: the I² value was moderate (41%). ⁴Downgraded one level due to risk of bias: we judged one study to be at high risk of bias because of concern about random sequence generation and allocation concealment. Downgraded two levels due to imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated. ⁵Downgraded one level due to imprecision: the number of events is smaller than the optimal information size (taken as 300 events). Downgraded one level because of indirectness: provision of data by only a single study from a single setting, which may not adequately represent all patients with ISSNHL. ⁶Downgraded two levels due to risk of bias: we judged two studies to be at high risk of bias because of incomplete outcome data; we judged one study to be at high risk of bias because of concern about random sequence generation and allocation concealment. Downgraded two levels due to imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated. ⁷Downgraded one level due to imprecision: the number of events is smaller than the optimal information size (taken as 300 events). ⁸Downgraded two levels because of imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated.

Summary of findings 1. Intratympanic corticosteroids versus systemic corticosteroids as primary therapy

Ir a la tabla de la revisión

Table 1. Adverse events: intratympanic compared to systemic corticosteroids as primary therapy

Adverse event reported	Study	How reported	Details of recovery	Rate in intervention group (%)	Rate in comparator group (%)	RR (95% CI)
Tympanic membrane (TM) perforation	Huang 2021*	There were no cases of [...] perforation of the tympanic membrane	NA	0/52 (0)	0/52 (0)*	NA
	Kosyakov 2011	No residual TM perforations	All patients demonstrated a complete healing of TM after the tympanostomy tube removal	0/24 (0)	NA	NA
	Rauch 2011	Persistent TM perforation	By the 6‐month follow‐up most adverse events had resolved	5/129 (3.9)	NA	NA
	Tong 2021	No residual tympanic membrane perforations were observed in any of the individuals at their final visit	NA	0/30 (0)	NA	NA
Vertigo/dizziness	Ermutlu 2017	Four patients in the ITS group had transient vertigo during the procedure	NR	4/19 (21)	NA	NA
	Huang 2021*	[...] complained of brief dizziness after IT injection [...]	No patients stopped the treatment	7/52 (13.5)	8/52 (15.4)*	NA
	Rauch 2011	The intratympanic group experienced adverse effects typical of local injection, most often transient pain at the injection site and brief caloric vertigo. Note, it is unclear whether all reported instances of vertigo in the intervention group occurred at the time of injection.	By the 6‐month follow‐up most adverse events had resolved	35/129 (27.1)	13/121 (10.7)	2.53 (1.41 to 4.54); favours systemic corticosteroid; P = 0.002
	Swachia 2016	Temporary adverse events in 22.7% of patients treated with oral prednisolone which included [...] and dizziness. In 35% of patients treated with intratympanic corticosteroid, adverse events occurred including [...] and dizziness.	NR	NR	NR	NA
	Tong 2021	Six of 30 patients in the intratympanic injection group complained of a transient dizziness lasting about a minute during treatment	NR	6/30 (20)	NA	NA
	Tsounis 2018	One patient experienced transient dizziness as a result of caloric stimulation from the injected steroid solution (unclear which of 2 groups receiving intratympanic injection)	Symptoms resolved completely within 15 minutes and there was no need to discontinue the treatment. The injections that followed caused no further side effect.	NR	NR	NA
Tinnitus	Swachia 2016	In 35% of patients treated with intratympanic corticosteroid, adverse events occurred including [...] ringing sensation in the ear	NR	NR	NR	NA
Ear pain	Al‐Shehri 2015	Pain due to injection	NR	2/19 (10.5)	NA	NA
		Earache	NR	4/19 (21.1)	0/20 (0)	9.45 (0.54 to 164.49); favours systemic corticosteroid; P = 0.12
	Huang 2021	[...] refused repeated IT injections due to unbearable pain	NR	3/52 (5.8)	2/52 (3.8)	NA
	Rauch 2011	The intratympanic group experienced adverse effects typical of local injection, most often transient pain at the injection site [...]	By the 6‐month follow‐up most adverse events had resolved	35/129 (27.1)	NA	NA
		Experienced ear pain at least once	By the 6‐month follow‐up most adverse events had resolved	70/129 (54.3)	4/121 (3.3)	16.41 (6.18 to 43.59); favours systemic corticosteroid; P < 0.00001
	Swachia 2016	In 35% of patients treated with intratympanic corticosteroid adverse events occurred including […] mild ear pain, severe ear pain (3 patients)	NR	3/20 (15) severe ear pain	NR	NA
	Tong 2021	Some patients had a tolerable pain reaction after the injection	NR	NR	NA	NA
Other	Al‐Shehri 2015	Mood change	NR	2/19 (10.5)	8/20 (40)	0.26 (0.06 to 1.08); favours IT corticosteroid; P = 0.06
		Blood glucose problem	NR	3/19 (15.8)	6/20 (30)	0.53 (0.15 to 1.81); favours IT corticosteroid; P = 0.31
		Sleep change	NR	1/19 (5.3)	6/20 (30)	0.18 (0.02 to 1.32); favours IT corticosteroid; P = 0.09
		Increased appetite	NR	1/19 (5.3)	5/20 (25)	0.21 (0.03 to 1.64); favours IT corticosteroid; P = 0.14
		Mouth dryness/thirst	NR	0/19 (0)	5/20 (25)	0.10 (0.01 to 1.62); favours IT corticosteroid; P = 0.10
		Weight gain	NR	0/19 (0)	3/20 (15)	0.15 (0.01 to 2.72); favours IT corticosteroid; P = 0.20
	Dispenza 2011	No complications related to the treatment were noted in both the groups	NA	0/25 (0)	0/21 (0)	NA
	Ermutlu 2017	No long‐term complications were observed in any of the patients	NA	0/19 (0)	0/16 (0)	NA
	Hong 2009	No side effects were observed in either group	NA	0/32 (0)	0/31 (0)	NA
	Huang 2021*	Apparent bleeding at intratympanic injection site	NR	0/52 (0)	0/52 (0)	NA
		External otitis or myringitis	NR	0/52 (0)	0/52 (0)	NA
		Otitis media	NR	0/52 (0)	0/52 (0)	NA
		Fluctuation of basal blood pressure (> 10 mmHg)	NR	2/52 (3.8)	7/52 (13.5)	NA
		Fluctuation of fasting blood glucose (> 2 mmol/L)	NR	5/52 (9.6)	12/52 (23.1)	NA
		Emotional change	NR	8/52 (15.4)	15/52 (28.8)	NA
		Appetite change	NR	13/52 (25.0)	25/52 (48.1)	NA
		Dyssomnia	NR	23/52 (44.2)	38/52 (73.1)	NA
		Water‐sodium retention	NR	9/52 (17.3)	24/52 (46.1)	NA
		Acne on face and body	NR	2/52 (3.8)	6/52 (11.5)	NA
		Irregular menstruation	NR	5/21 (23.8)	11/23 (47.8)	NA
		Cushing's syndrome	NR	0/52 (0)	1/52 (1.9)	NA
		Osteoporotic fracture		0	0
	Kosyakov 2011	In one case an acute suppurative otitis media developed that was eliminated by local antibacterial therapy. This patient was excluded from the study.	NA	NA	NA	NA
		Nine patients in the ST (standard therapy) group and 12 patients in the intravenous corticosteroid group complained of sleep loss	Completely corrected after withdrawal	NR	9/24 (37.5) in ST group and 12/25 (48) in intravenous corticosteroid group	NA
		No systemic adverse effects related to intratympanic application of steroids were noticed	NA	0/24 (0)	NA	NA
		No serious side effects related to systemic administration of steroids were observed in the study	NA	NA	0/49 (0)	NA
	Qu 2015	No complications were seen in patients (unclear which group), including those with hypertension or diabetes	NA	NR	NR	NA
	Rauch 2011	Mood change	By the 6‐month follow‐up most adverse events had resolved	12/129 (9.3)	54/121 (44.6)	0.21 (0.12 to 0.37); favours IT corticosteroid; P < 0.00001
		Blood glucose problem	By the 6‐month follow‐up most adverse events had resolved	21/129 (16.3)	36/121 (29.8)	0.55 (0.34 to 0.88); favours IT corticosteroid; P = 0.01
		Sleep change	By the 6‐month follow‐up most adverse events had resolved	9/129 (7)	44/121 (36.4)	0.19 (0.1 to 0.38); favours IT corticosteroid; P < 0.00001
		Appetite change	By the 6‐month follow‐up most adverse events had resolved	6/129 (4.7)	28/121 (23.1)	0.2 (0.09 to 0.47); favours IT corticosteroid; P = 0.0002
		Dry mouth/thirst	By the 6‐month follow‐up most adverse events had resolved	5/129 (3.9)	30/121 (24.8)	0.16 (0.06 to 0.39); favours IT corticosteroid; P < 0.0001
		Weight change	By the 6‐month follow‐up most adverse events had resolved	7/129 (5.4)	22/121 (18.2)	0.3 (0.13 to 0.67); favours IT corticosteroid; P = 0.004
		Ear infection	By the 6‐month follow‐up most adverse events had resolved	7/129 (5.4)	2/121 (1.7)	3.28 (0.7 to 15.49); favours systemic corticosteroid; P = 0.13
		Any adverse event: "Adverse events were reported by 87.6% (106 of 121) of participants in the oral group and 89.9% (116 of 129) in the intratympanic group." Note: it is unclear whether 'adverse events' refers to those already reported (and listed for this study in this table).	By the 6‐month follow‐up most adverse events had resolved	116/129 (89.9)	106/121 (87.6)	1.03 (0.94 to 1.12); favours systemic corticosteroid; P = 0.56
		Serious adverse events: "In the intratympanic treatment group, these included osteomyelitis of the toe, leukemia, myocardial infarction, bladder cancer, chest pain due to possible endocarditis, and exacerbation of pre‐existing chronic obstructive pulmonary disease. In the oral treatment group, the serious adverse events were myocardial infarction, cerebral hemorrhage, hyponatremia, hospitalization for possible transient ischemic attack, and syncope. The case of hyponatremia arose from worsening of pre‐existent mild renal insufficiency in a patient with type 2 diabetes that was deemed study‐related."	NR	6/129 (4.7)	5/121 (4.1)	1.13 (0.35 to 3.59); favours systemic corticosteroid; P = 0.84
	Rupasinghe 2017	No adverse effects were reported in either study group during the study period	NA	NA	NA	NA
	Swachia 2016	Temporary adverse events: temporary adverse events in 22.7% of patients treated with oral prednisolone which included puffiness of face, ulcers in mouth, increased appetite, diarrhea [...]	NR	NR	5/22 (22.7)	NA
		Adverse events: in 35% of patients treated with intratympanic methylprednisolone adverse events occurred including mild ear pain, severe ear pain (3 patients), ringing sensation in ear and dizziness	NR	7/20 (35)	NR	NA
	Tong 2021	No otitis media […] observed in any of the individuals at their final visit	NA	0/30 (0)	0/30 (0)	NA
	Tsounis 2018	No significant complications during the intratympanic injections or the follow‐up period	NA	0/33 (0)	NA	NA
*Patients in the comparator group for this trial also received intratympanic (IT) corticosteroid at a later time point in the trial, therefore complications of IT treatment are included here (Huang 2021). The intervention group received 24 days of IT corticosteroid and the comparator group received 12 days of systemic (intravenous corticosteroid) followed by 12 days of IT corticosteroid. Rate ratios are not presented as they are not applicable to the comparison of interest (IT compared to systemic as primary therapy). CI: confidence interval; IT: intratympanic; NA: not applicable; NR: not reported; RR: risk ratio; TM: tympanic membrane

Table 1. Adverse events: intratympanic compared to systemic corticosteroids as primary therapy

Ir a la tabla de la revisión

Summary of findings 2. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy

Outcomes	*Anticipated absolute effects (95% CI)**		No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy
Patient or population: sudden sensorineural hearing loss Settings: initial therapy Intervention: combination of intratympanic and systemic steroid therapy Comparison: systemic steroid therapy
Outcomes	Systemic therapy (assumed risk)	Combined therapy (corresponding risk)	No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Change in hearing threshold determined by PTA Range 0 dB to 140 dB Negative values represent lowering and positive values represent raising of the hearing threshold. A lower hearing threshold represents hearing improvement.	The mean change in PTA ranged across control groups from ‐33.0 dB to ‐13.0 dB	The mean change in PTA in the intervention groups was on average ‐8.55 dB greater (‐4.61 greater to ‐12.48 greater)	435 (6 studies)	MD ‐8.55 dB (95% CI ‐12.48 to ‐4.61)	⊕⊕⊝⊝ low¹	The change in hearing threshold may be slightly increased in participants who receive combined therapy. However, it is unclear whether this increase would be noticeable to patients.
Proportion of patients whose hearing is improved	579 per 1000^a	735 per 1000 (666 to 816)	788 (10 studies)	RR 1.27 (95% CI 1.15 to 1.41)	⊕⊝⊝⊝ very low²	The evidence is very uncertain as to whether combined therapy changes the proportion of participants whose hearing is improved.
Final hearing threshold determined by PTA A lower value represents better hearing	The mean final PTA ranged across control groups from 39.1 dB to 59 dB	The mean final PTA in the intervention groups was on average 9.11 dB lower (1.67 lower to 16.56 lower)	194 (3 studies)	MD ‐9.11 dB (95% CI ‐16.56 to ‐1.67)	⊕⊝⊝⊝ very low³	Combined therapy may result in slightly lower (more favourable) final hearing thresholds compared to systemic corticosteroids alone (as primary therapy) but the evidence is very uncertain, and it is not clear whether the change would be of importance to patients.
Adverse events^b	Events in control group	Events in intervention group	No of Participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Persistent tympanic membrane perforation	Comparison not applicable^c	5 studies reported a rate between 0% (0/85) and 5.5% (2/36) for those who received an intratympanic injection	474 (5 studies)	Not calculable	⊕⊝⊝⊝ very low⁴	The evidence is very uncertain regarding the risk of tympanic membrane perforation for those who received intratympanic steroids.
Vertigo/dizziness: timing not reported	No study reported on this outcome for both the intervention and comparator groups.
Vertigo/dizziness: at the time of injection	Comparison not applicable^c	4 studies reported a rate between 0% (0/60) and 8.1% (3/37) for those who received an intratympanic injection^d	341 (4 studies)	Not calculable	⊕⊝⊝⊝ very low⁵	The evidence is very uncertain regarding the risk of vertigo/dizziness at the time of intratympanic injection for those who received intratympanic corticosteroid as primary treatment.
Ear pain: timing not reported	No study reported on this outcome for both the intervention and comparator groups.
Ear pain: at the time of injection	Comparison not applicable^c	One study reported a rate of 5/37 (13.5%)	73 (1 study)	Not calculable	⊕⊝⊝⊝ very low⁶	The evidence is very uncertain regarding the risk of ear pain at the time of intratympanic injection for those who received combined treatment as primary treatment.
The basis for the assumed risk* is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; PTA: pure tone audiometry; RR: risk ratio
^aTen studies recruited participants suffering from sudden sensorineural hearing loss. The incidence of improvement for the 10 studies was 57.86%. We have used 579 per 1000 to express the assumed risk. ^bOnly the most widely reported adverse events are described here. For adverse events that could feasibly occur in either group, we have only included the studies that provided a rate for both groups. For adverse events that could only occur in one group, we have only included the studies that reported the rate in that group, and presented these as a range. A full description of adverse event data is available for reference in Table 2. ^cComparisons between patients receiving intratympanic therapy and those receiving only systemic therapy were regarded as invalid for the following adverse events: persistent tympanic membrane perforation, vertigo observed at the time of intratympanic injection and ear pain observed at the time of intratympanic injection. This is explained in Data extraction and management. ^dIn one study, two groups received intratympanic injection: one group received intratympanic corticosteroid and the other received intratympanic and systemic corticosteroid (Tsounis 2018). GRADE Working Group grades of evidence High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: We are very uncertain about the estimate.
¹Downgraded one level due to risk of bias: we rated a study contributing moderate weight to the overall effect estimate as high risk of bias due to concern about random sequence generation and allocation concealment. Five studies were at high risk of other bias, and one study was at risk of attrition bias. Downgraded one level due to imprecision: the 95% CI overlaps the threshold for clinical relevance, taken to be 10 dB. ²Downgraded one level due to risk of bias: we judged 8 of 10 studies to be at high or unclear risk of selection bias and at high risk of other bias. Downgraded one level due to imprecision: the 95% CI overlaps the threshold for clinical relevance. Downgraded one level due to inconsistency: the I² value was moderate (47%). ³Downgraded two levels due to risk of bias: we judged all three studies to be at high or unclear risk of selection bias and high risk of other bias. We also judged one of three studies to be at high risk of bias for incomplete outcome data and selective reporting. Downgraded one level due to imprecision: the 95% CI overlaps the threshold for clinical relevance and the sample size is smaller than the optimal information size (taken as 400 participants). ⁴Downgraded two levels due to risk of bias: we judged two studies to be at high risk of bias because of concern about random sequence generation, two studies because of selective reporting, one study because of concern about blinding and one study because of concern about allocation concealment. ⁵Downgraded two levels due to risk of bias: we judged one study to be at high risk of bias because of concern about random sequence generation and blinding, one study because of selective reporting and one study because of incomplete outcome data. Downgraded two levels due to imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated. ⁶Downgraded two levels due to imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated. Downgraded one level because of indirectness: provision of data by only a single study from a single setting, which may not adequately represent all patients with ISSNHL.

Summary of findings 2. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy

Ir a la tabla de la revisión

Table 2. Adverse events: combined compared to systemic as primary therapy

Adverse event reported	Study	How reported	Details of recovery	Rate in intervention group (%)	Rate in comparator group (%)	RR (95% CI)
TM perforation	Ahn 2008	No significant complications during or after IT dexamethasone, including TM perforation […]	NR	0/60 (0)	NA	NA
	Arastou 2013	Two patients developed tympanic perforation (reported as 2.6% of whole study sample; unclear how many from each group)	Treated with cauterisation and paper patch (n = 1) and tympanoplasty (n = 1)	NR	NR	NA
	Arslan 2011	None of the patients had an important complication, namely […] TM perforation (unclear which group)	NR	NR	NR	NA
	Choi 2011	No significant complications during or after IT steroid injection including TM perforation	NR	0/19 (0)	NA	NA
	Gundogan 2013	No case of residual TM perforation […] was noted	No long‐term complications resulting from either oral steroid or IT steroid in any of the patients	0/37 (0)	NA	NA
Vertigo/dizziness	Ahn 2008	No significant complications during or after IT dexamethasone, including […] vertigo […]	NR	0/60 (0)	NA	NA
	Arslan 2011	None of the patients had an important complication, namely, […] vertigo […] (unclear which group)	NR	NR	NR	NA
	Choi 2011	No significant complications during or after IT steroid injection, including […] vertigo […]	NR	0/19 (0)	NA	NA
	Gundogan 2013	Three patients complained of vertigo immediately after injection	Recovered after 2 hours of rest	3/37 (8.1)	NA	NA
	Tsounis 2018	One patient experienced transient dizziness as a result of caloric stimulation from the injected steroid solution (unclear which of two groups receiving intratympanic injection)	Symptoms resolved completely within 15 minutes and there was no need to discontinue the treatment. The injections that followed caused no further side effects.	NR	NR	NA
Tinnitus	Ahn 2008	No significant complications during or after IT dexamethasone, including […] and tinnitus	NR	0/60 (0)	NA	NA
	Arslan 2011	None of the patients had an important complication, namely, […] tinnitus […] (unclear which group)	NR	NR	NR	NA
	Choi 2011	No significant complications during or after IT steroid injection, including […] tinnitus […]	NR	0/19 (0)	NA	NA
Ear pain	Arslan 2011	None of the patients had an important complication, namely, […] otalgia […] (unclear which group)	NR	NR	NR	NA
	Gundogan 2013	Otalgia occurred in 5 patients after IT corticosteroid injection	Relieved after 1 hour	5/37 (13.5)	NA	NA
Other	Ahn 2008	No significant complications during or after IT dexamethasone, including […] otitis media […]	NR	0/60 (0)	NA	NA
	Arslan 2011	None of the patients had an important complication, namely, […] nystagmus, otitis media […] (unclear which group)	NR	NR	NR	NA
	Battaglia 2008	No long‐term complications resulted from either the prednisone taper or the IT corticosteroid in any of the patients enrolled in the study	NR	0/16 (0)	0/18 (0)	NA
	Choi 2011	No significant complications during or after IT steroid injection, including […] otitis media […]	NR	0/19 (0)	NA	NA
	Gundogan 2013	No case of […] otitis media was noted	No long‐term complications resulted from either oral steroid or IT steroid in any of the patients	0/37	NA	NA
		No long‐ term complications resulted from either oral steroid or IT steroid in any of the patients	NA	0/37 (0)	0/36 (0)	NA
	Tsounis 2018	No significant complications during the intratympanic injections or the follow‐up period	NA	0/33 (0)	NA	NA
	Koltsidopoulos 2013	No significant complications occurred during IT injections or the follow‐up period. One case of otitis media was encountered (unclear which group)	NR	0/46 (0) (significant complications)	NA	NA
IT: intratympanic; NA: not applicable; NR: not reported; TM: tympanic membrane

Table 2. Adverse events: combined compared to systemic as primary therapy

Ir a la tabla de la revisión

Summary of findings 3. Intratympanic corticosteroids versus no treatment or versus placebo as secondary therapy

Outcomes	*Anticipated absolute effects (95% CI)**		No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Intratympanic corticosteroids versus no treatment or versus placebo as secondary therapy
Patient or population: sudden sensorineural hearing loss Settings: after treatment failure with systemic steroids Intervention: intratympanic steroid therapy Comparison: no treatment/placebo
Outcomes	No treatment/placebo (assumed risk)	Intratympanic therapy (corresponding risk)	No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Change in hearing threshold determined by PTA Range 0 dB to 140 dB Negative values represent lowering and positive values represent raising of the hearing threshold. A lower hearing threshold represents hearing improvement.	The mean change in PTA ranged across control groups from ‐13.21 dB to 0.8 dB	The mean change in PTA in the intervention groups was on average ‐9.07 dB greater (‐6.66 greater to ‐11.47 greater)	280 (7 studies)	MD ‐9.07 dB (95% CI ‐11.47 to ‐6.66)	⊕⊕⊝⊝ low¹	Intratympanic therapy may have a small effect on hearing threshold compared to no treatment or placebo (as secondary therapy), but it is not clear whether this change would be important to patients.
Proportion of patients whose hearing is improved	70 per 1000^a	385 per 1000 (203 to 747)	232 (6 studies)	RR 5.55 (95% CI 2.89 to 10.68)	⊕⊕⊝⊝ low²	Intratympanic therapy may result in a much higher proportion of patients whose hearing is improved, compared to no treatment or placebo (as secondary therapy).
Final hearing threshold determined by PTA (a lower value represents better hearing)	The mean final PTA ranged across control groups from 59.9 to 90.5 dB HL	The mean final PTA in the intervention groups was on average ‐11.09 dB lower (‐4.72 lower to ‐17.46 lower)	203 (5 studies)	MD ‐11.09 dB (95% CI ‐17.46 to ‐4.72)	⊕⊕⊝⊝ low³	Intratympanic therapy may result in lower (more favourable) final hearing thresholds compared to no treatment or placebo (as secondary therapy).
Adverse events^b	Events in control group	Events in intervention group	No of Participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Persistent tympanic membrane perforation	Comparison not applicable^c	5 studies reported a rate between 0% (0/19) and 4.2% (1/24) for those who received an intratympanic injection^d	185 (5 studies)	Not calculable	⊕⊝⊝⊝ very low⁴	The evidence is very uncertain regarding the risk of tympanic membrane perforation for those who received intratympanic injection (either corticosteroid or placebo) as secondary treatment.
Vertigo/dizziness: timing not reported	No study reported on this outcome for both the intervention and comparator groups.
Vertigo/dizziness at the time of intratympanic injection	Comparison not applicable^c	3 studies reported a rate between 6.7% (1/15) and 33% (number not reported) for those who received an intratympanic injection.^d	128 (3 studies)	Not calculable	⊕⊝⊝⊝ very low⁵	The evidence is very uncertain regarding the risk of vertigo/dizziness at the time of intratympanic injection (either corticosteroid or placebo) as secondary treatment.
Ear pain: timing not reported	No study reported on this outcome for both the intervention and comparator groups.
Ear pain at the time of intratympanic injection	Comparison not applicable^c	One study reported no participants with ear pain at the time of intratympanic injection (0/24)	44 (one study)	Not calculable	⊕⊝⊝⊝ very low⁶	The evidence is very uncertain regarding the risk of ear pain at the time of intratympanic corticosteroid injection as secondary treatment.
The basis for the assumed risk* is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; PTA: pure tone audiometry; RR: risk ratio
^aSix studies recruited participants suffering from sudden sensorineural hearing loss after treatment failure with systemic steroids. The incidence of improvement for the control group in these six studies was 6.96%. We have used 70 per 1000 to express the assumed risk. ^bOnly the most widely reported adverse events are described here. For adverse events that could feasibly occur in either group, we have only included the studies that provided a rate for both groups. For adverse events that could only occur in one group, we have only included the studies that reported the rate in that group, and presented these as a range. A full description of adverse event data is available for reference in Table 3. ^cComparisons between patients receiving intratympanic therapy and those receiving only systemic therapy were regarded as invalid for the following adverse events: persistent tympanic membrane perforation, vertigo observed at the time of intratympanic injection and ear pain observed at the time of intratympanic injection. This is explained in Data extraction and management. ^dThis includes participants who received placebo intratympanic injection. GRADE Working Group grades of evidence High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: We are very uncertain about the estimate.
¹Downgraded one level due to risk of bias: we rated one study contributing moderate weight to the overall effect estimate as having high risk of bias due to incomplete outcome data. All studies were at high risk of other bias. Downgraded one level due to imprecision: the 95% CI for the effect overlaps the threshold for clinical relevance and the sample size is smaller than the optimal information size (taken as 400 participants). One study included treatment in the comparator arm with vitamin B, vasodilators and benzodiazepines (Ho 2004). However, as the weight of this study in the meta‐analysis was low and exclusion of the study made little difference to the effect estimate we did not downgrade for indirectness. ²Downgraded one level due to risk of bias: we rated two studies as being at high risk of bias due to selective reporting and one study was at high risk of bias for incomplete outcome data. All studies were at high risk of other bias. Downgraded one level due to imprecision: the total number of events is smaller than the optimal information size (taken as 300 events). ³Downgraded one level due to risk of bias: we rated one study contributing moderate weight to the overall effect estimate as high risk of bias due to incomplete outcome data, and one other study as high risk of bias because of selective reporting. All studies were at high risk of other bias. Downgraded one level due to imprecision: the 95% CI for the effect overlaps the threshold for clinical relevance and the sample size is smaller than the optimal information size (taken as 400 participants). ⁴Downgraded one level due to risk of bias: we rated one study as high risk of bias because of selective reporting; we rated one study as high risk of bias because of incomplete outcome data; we rated three studies as uncertain for random sequence generation, allocation concealment and blinding. Downgraded two levels because of imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated. ⁵Downgraded one level due to risk of bias: we rated one study as high risk of bias because of selective reporting; we rated one study as high risk of bias because of incomplete outcome data; we rated two studies as uncertain for random sequence generation, allocation concealment and blinding. Downgraded two levels because of imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated. ⁶Downgraded two levels because of imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated. Downgraded one level due to indirectness: single study from a single setting, which may not adequately represent all patients with ISSNHL.

Summary of findings 3. Intratympanic corticosteroids versus no treatment or versus placebo as secondary therapy

Ir a la tabla de la revisión

Table 3. Adverse events: intratympanic compared to no treatment/placebo as secondary therapy

Adverse event reported	Study	How reported	Details of recovery	Rate in intervention group (%)	Rate in comparator group (%)	RR (95% CI)
TM perforation	Ho 2004	No residual TM perforation	NA	0/15 (0)	NA	NA
	Li 2011	Persistent TM perforation	No hearing loss in the affected ear. The perforation was treated successfully with a paper patch.	1/24 (4.2)	NA	NA
	Plontke 2009	One patient (unclear which group) had a major catheter dislocation with perforation of ear drum. Note: both groups received IT injection, either corticosteroid or normal saline.	Small ear drum perforation was closed with a myringoplasty	NR	NR	NA
	Wu 2011	Transient TM perforation	Healed spontaneously by follow‐up 1 month later	1/27 (3.7)	NR	NA
	Xenellis 2006	No TM perforation was noticed at last visit	NA	0/19 (0)	NA	NA
Vertigo/dizziness	Ho 2004	Complained of vertigo immediately after injection	Recovered after 2 hours of rest	1/15 (6.7)	NA	NA
	Li 2011	Three patients complained of vertigo [...] during the injections	Resolved within minutes	3/24 (12.5)	NA	NA
		No disequilibrium	NA	0/24 (0)	NR	NA
		No dizziness for more than 24 hours	NA	0/24 (0)	NR	NA
	Plontke 2009	One patient (unclear which group) with increase in vertigo	Resolved	NR	NR	NA
	Wu 2011	Temporary dizziness experienced by one‐third of subjects (unclear how many each group). Note: both groups received IT injection, either corticosteroid or normal saline.	Relieved by resting for a short time. Three participants quit the trial because of uncomfortable dizziness (unclear how many each group).	NR	NR	NA
Tinnitus	Li 2011	Three patients complained of vertigo or an increase in tinnitus during the injections	Resolved within minutes	3/24 (12.5)	NA	NA
Hearing loss	Li 2011	The injection did not induce an increase in […] hearing loss […] for greater than 24 h	NA	0/24 (0)	NR	NA
	Wu 2011	No participant experienced a decrease in hearing of 10 dB or more	NA	0/27	0/28	NA
Ear pain	Li 2011	The injection did not induce an increase in ear pain […]	NA	0/24 (0)	NA	NA
	Plontke 2009	Two patients (unclear how many each group) with ear pain. Note: both groups received IT injection, either corticosteroid or normal saline.	Resolved	NR	NR	NA
	Xenellis 2006	A mild ear pain occurring the first hour post‐injection	Easily controlled with common analgesics	NR	NA	NA
Other	Ho 2004	One of 15 patients had acne	NR	1/15 (6.7)	NR	NA
	Li 2011	No serious complications such as chronic otitis media, disequilibrium or dysgeusia developed	NA	0/24 (0)	NR	NA
	Plontke 2009	One patient (unclear which group) with each of: ear canal skin defect, steroid acne, nausea after antibiotic intake, gastroenteritis, hypokalaemia, pump battery failure and viral conjunctivitis. Three patients with headache (unclear how many in each group; one considered as 'possibly', 'probably' or 'very likely' related to the study) and 3 (unclear how many each group) with increased liver function tests (probably due to antibiotics).	Resolved	NR	NR	NA
	Wu 2011	Severe nausea or vomiting was not experienced by any of the participants after the injection therapy	NA	0/27	0/28	NA
	Xenellis 2006	No infection was noticed in any of the patients at their last visit	NA	0/19 (0)	0/18 (0)	NA
TM: tympanic membrane; NA: not applicable; NR: not reported; IT: intratympanic

Table 3. Adverse events: intratympanic compared to no treatment/placebo as secondary therapy

Ir a la tabla de la revisión

Summary of findings 4. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy

Outcomes	*Anticipated absolute effects (95% CI)**		No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy
Patient or population: sudden sensorineural hearing loss Settings: after treatment failure with systemic steroids Intervention: combination of intratympanic and systemic steroid therapy Comparison: systemic steroid therapy
Outcomes	Systemic therapy (assumed risk)	Combined therapy (corresponding risk)	No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Change in hearing threshold determined by PTA	No studies reported this outcome.
Proportion of patients whose hearing is improved	205 per 1000^a	459 per 1000 (226 to 933)	76 (1 study)	RR 2.24 (95% CI 1.10 to 4.55)	⊕⊝⊝⊝ very low¹	Combined therapy may increase the proportion of patients whose hearing is improved compared to systemic corticosteroids alone (as secondary therapy), but the evidence is very uncertain.
Final hearing threshold determined by PTA	No studies reported this outcome.
Adverse events^b	Events in control group	Events in intervention group	No of participants (studies)	Relative effect (95% CI)	Certainty of the evidence (GRADE)	Comments
Persistent tympanic membrane perforation	Comparison not appropriate^c	One study reported a rate of 8.1% (3/37)	76 (1 study)	Not calculable	⊕⊝⊝⊝ very low²	The risk of tympanic membrane perforation among those who receive intratympanic corticosteroid combined with systemic corticosteroid as primary treatment is very uncertain.
Vertigo/dizziness: timing not reported	No studies reported this outcome.
Vertigo/dizziness: at the time of injection	Comparison not appropriate^c	No study reported a rate in the intervention group.
Ear pain: timing not reported	No studies reported this outcome.
Ear pain: at the time of injection	Comparison not appropriate^c	No study reported a rate in the intervention group.
The basis for the assumed risk* is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; PTA: pure tone audiometry; RR: risk ratio
^aOne study recruited participants suffering from sudden sensorineural hearing loss after treatment failure with systemic steroids. The incidence of improvements was 20.51%. We have used 205 per 1000 to express the assumed risk. ^bOnly the most widely reported adverse events are described here. For adverse events that could feasibly occur in either group, we have only included the studies that provided a rate for both groups. For adverse events that could only occur in one group, we have only included the studies that reported the rate in that group, and presented these as a range. A full description of adverse event data is available for reference in Table 4. ^cComparisons between patients receiving intratympanic therapy and those receiving only systemic therapy were regarded as invalid for the following adverse events: persistent tympanic membrane perforation, vertigo observed at the time of intratympanic injection and ear pain observed at the time of intratympanic injection. This is explained in Data extraction and management. GRADE Working Group grades of evidence High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: We are very uncertain about the estimate.
¹Downgraded two levels due to risk of bias: we judged the study to be at high risk of selection bias, performance bias, incomplete outcome data, selective reporting and other bias. Downgraded two levels due to imprecision: the 95% CI overlaps the threshold for clinical relevance and the total number of events is smaller than the optimal information size (taken as 300 events). ²Downgraded two levels due to risk of bias: we judged the study to be at high risk of bias because of selection bias, concern about blinding, incomplete outcome data and selective reporting. Downgraded two levels due to imprecision: the number of events is smaller than the optimal information size (taken as 300 events) and an effect estimate could not be calculated. Downgraded one level because of indirectness: provision of data by only a single study from a single setting, which may not adequately represent all patients with ISSNHL.

Summary of findings 4. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy

Ir a la tabla de la revisión

Table 4. Adverse events: combined compared to systemic as secondary treatment

Adverse event reported	Study	How reported	Details of recovery	Rate in intervention group (%)	Rate in comparator group (%)	RR (95% CI)
TM perforation	Zhou 2011	Three patients had small eardrum perforations	Successful closure by simple treatment	3/37 (8.1)	NA	NA
Vertigo	Zhou 2011	Second frequent complaint: transient vertigo after the drug had been injected into the ear	Not a severe problem if the drug was heated in 37°C water before injection and the vertigo disappeared after a few minutes or under 30 minutes	NR	NA	NA
Ear pain	Zhou 2011	Most frequent complaint	Easily controlled by the oral administration of paracetamol 30 minutes before the local infusion of the methylprednisolone	NR	NA	NA
Hearing loss*	Zhou 2011	No loss in hearing related to the treatment (in either group)	NA	0/37 (0)	0/39 (0)	NA
Other	Zhou 2011	One patient had tongue paresthesia (unclear which group)	Resolved after 2 weeks	NR	NR	NA
		No infections were observed (unclear which group)	NA	NR	NR	NA
		Long‐term complications did not occur in any patients who received the transtympanic injections	NA	0/37 (0)	NR	NA
*Hearing loss defined as ≥ 15 dB worsening in pure tone audiometry or ≥ 15% worsening of speech discrimination score. NA: not applicable; NR: not reported; TM: tympanic membrane

Table 4. Adverse events: combined compared to systemic as secondary treatment

Ir a la tabla de la revisión

Comparison 1. Intratympanic compared to systemic corticosteroids as primary therapy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Mean change in pure tone average (PTA) Show forest plot	10	701	Mean Difference (IV, Fixed, 95% CI)	‐5.93 [‐7.61, ‐4.26]

1.2 Proportion improved Show forest plot	14	972	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.97, 1.12]

1.3 Final PTA Show forest plot	7	516	Mean Difference (IV, Fixed, 95% CI)	‐3.31 [‐6.16, ‐0.47]

1.4 Change in hearing threshold with speech audiometry Show forest plot	1	98	Mean Difference (IV, Fixed, 95% CI)	‐8.85 [‐19.58, 1.88]

1.5 Speech audiometry: additional outcomes Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.5.1 Speech discrimination score: change from baseline	1	98	Mean Difference (IV, Fixed, 95% CI)	15.64 [1.57, 29.71]
1.5.2 Speech discrimination score: endpoint	1	35	Mean Difference (IV, Fixed, 95% CI)	6.00 [‐20.88, 32.88]
1.5.3 Word recognition score: change from baseline	1	250	Mean Difference (IV, Fixed, 95% CI)	‐0.60 [‐9.28, 8.08]
1.6 Frequency‐specific changes in PTA Show forest plot	6		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.6.1 0.25 kHz	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.2 0.5 kHz	3		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.3 1 kHz	3		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.4 2 kHz	3		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.5 3 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.6 4 kHz	3		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.7 8 kHz	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.8 Frequency range: low	3		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.9 Frequency range: mid	3		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6.10 Frequency range: high	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.7 Adverse events Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.7.1 Ear pain	2	289	Risk Ratio (M‐H, Fixed, 95% CI)	15.68 [6.22, 39.49]
1.7.2 Otitis media	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	3.28 [0.70, 15.49]
1.7.3 Vertigo/dizziness	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	2.53 [1.41, 4.54]
1.7.4 Blood glucose problems	2	289	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.35, 0.85]
1.7.5 Mood change	2	289	Risk Ratio (M‐H, Fixed, 95% CI)	0.22 [0.13, 0.37]
1.7.6 Sleep change	2	289	Risk Ratio (M‐H, Fixed, 95% CI)	0.19 [0.10, 0.36]
1.7.7 Appetite change	2	289	Risk Ratio (M‐H, Fixed, 95% CI)	0.20 [0.09, 0.44]
1.7.8 Weight change	2	289	Risk Ratio (M‐H, Fixed, 95% CI)	0.28 [0.13, 0.61]
1.7.9 Dry mouth	2	289	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.06, 0.35]
1.7.10 Any adverse event	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.94, 1.12]
1.7.11 Serious adverse event	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [0.35, 3.59]

Comparison 1. Intratympanic compared to systemic corticosteroids as primary therapy

Ir a la tabla de la revisión

Comparison 2. Combined compared to systemic corticosteroids as primary therapy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Mean change in pure tone average (PTA) Show forest plot	6	435	Mean Difference (IV, Fixed, 95% CI)	‐8.55 [‐12.48, ‐4.61]

2.2 Proportion improved Show forest plot	10	788	Risk Ratio (M‐H, Fixed, 95% CI)	1.27 [1.15, 1.41]

2.3 Final PTA Show forest plot	3	194	Mean Difference (IV, Fixed, 95% CI)	‐9.11 [‐16.56, ‐1.67]

2.4 Change in hearing threshold with speech audiometry Show forest plot	1	98	Mean Difference (IV, Fixed, 95% CI)	‐7.59 [‐20.22, 5.04]

2.5 Speech audiometry: additional outcomes Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.5.1 Speech discrimination score: change from baseline	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.5.2 Speech discrimination score: endpoint	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6 Frequency‐specific changes with PTA Show forest plot	4		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.6.1 0.25 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.2 0.5 kHz	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.3 1 kHz	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.4 2 kHz	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.5 3 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.6 4 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.7 8 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.8 Frequency range: low	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.9 Frequency range: mid	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.6.10 Frequency range: high	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 2. Combined compared to systemic corticosteroids as primary therapy

Ir a la tabla de la revisión

Comparison 3. Intratympanic corticosteroids compared to no treatment/placebo as secondary therapy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Mean change in PTA Show forest plot	7	280	Mean Difference (IV, Fixed, 95% CI)	‐9.07 [‐11.47, ‐6.66]

3.2 Proportion improved Show forest plot	6	232	Risk Ratio (M‐H, Fixed, 95% CI)	5.55 [2.89, 10.68]

3.3 Final PTA Show forest plot	5	203	Mean Difference (IV, Fixed, 95% CI)	‐11.09 [‐17.46, ‐4.72]

3.4 Change in hearing threshold with speech audiometry Show forest plot	1	21	Mean Difference (IV, Fixed, 95% CI)	‐12.80 [‐30.17, 4.57]

3.5 Speech audiometry: additional outcomes Show forest plot	1	21	Mean Difference (IV, Fixed, 95% CI)	19.90 [0.41, 39.39]

3.5.1 Maximum speech discrimination: change from baseline	1	21	Mean Difference (IV, Fixed, 95% CI)	19.90 [0.41, 39.39]
3.6 Frequency‐specific changes with PTA Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.6.1 0.25 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.6.2 0.5 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.6.3 1 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.6.4 2 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.6.5 3 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.6.6 4 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.6.7 6 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.6.8 8 kHz	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 3. Intratympanic corticosteroids compared to no treatment/placebo as secondary therapy

Ir a la tabla de la revisión

Comparison 4. Combined compared to systemic corticosteroids as secondary treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Proportion improved Show forest plot	1	76	Risk Ratio (M‐H, Fixed, 95% CI)	2.24 [1.10, 4.55]

4.2 Speech audiometry: additional outcomes Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.2.1 Improvement in speech discrimination score	1	76	Risk Ratio (M‐H, Fixed, 95% CI)	2.41 [1.12, 5.18]

Comparison 4. Combined compared to systemic corticosteroids as secondary treatment

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet