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Intratympanic Injection of Gentamicin for the Treatment of Delayed Endolymphatic Hydrops
Auris'Nasus'Larynx (Tokyo) 19 (Suppl. I) S55-S60,1992
INTRATYMPANIC INJECTION OF GENTAMICIN FOR THE TREATMENT OF DELAYED ENDOLYMPHATIC HYDROPS Tsutomu NAKASHIMA, M.D., Yumiko KASEKI, M.D., Masahide KAIDA, M.D., and Kyoji MIYAZAWA, M.D. Department of Otorhinolaryngology, Nagoya University School of Medicine, Nagoya, Japan
In three patients with ipsilateral delayed endolymphatic hydrops (DEH), ototoxic gentamicin sulfate was injected through the tympanic membrane for the ablative treatment of frequent attacks of vertigo. Two patients received six injections and one patient received two. Treatment produced complete control of vertigo attacks in one patient who received six injections, and substantial control in the other two patients. The present results showed that there was a delayed onset of the ototoxic effect of gentamicin in the treatment of ipsilateral DEH. Delayed endolymphatic hydrops (DEH) is a disease entity that has clinical manifestations similar to those of Meniere's disease but can be differentiated from the latter. l Typically, DEH occurs in patients who have sustained a profound hearing loss in one ear, usually from infection or trauma, and then after a prolonged period of time develop either episodic vertigo from the same ear (ipsilateral DEH) or fluctuating hearing loss, also sometimes with episodic vertigo, in the opposite ear (contralateral DEH). In cases of ipsilateral DEH, destructive procedures are designed to eliminate abnormal vestibular activity if the patient has not responded to medical treatment. This concept of treatment may be considered similar to that in Meniere's disease with profound hearing loss and frequent attacks of vertigo. In incapacitating Meniere's disease, intratympanic administration of aminoglycosides has been used by various authors as a destructive procedure since Schuknecht suggested chemical ablation with aminoglycosides in 1957. 2 In contrast, there have been few reports of intratYJIlpanic administration of aminoglycosides for the treatment of DEH. We used intratympanic administration of gentamicin in three patients with ipsilateral Received for publication September 1, 1992 Presented at the 51th Annual Meeting of Japan Society for Equilibrium Research, Maebashi, November 5-6, 1992. S55
T. NAKASHIMA et al
S56
DEH. The details are as follows. CASE REPORTS
Case 1
A 33-year-old female came to our clinic on March 4, 1989, because of frequent attacks of vertigo since February, 1988. Hearing ability in her right ear had been poor for l;lS long as she could remember. Her audiogram showed flat-type perceptive hearing loss on the right side as illustrated in Fig. 1, while left hearing ability was normal. Caloric response was weak on the right side but not absent. The patient experienced attacks of rotatory vertigo four times in 1989, six times from January through May, of 1990, and eight times from June through November in spite of continuous administration of anti-vertigo drugs. Each attack of vertigo persisted for several hours. Besides rotatory vertigo, she occasionally felt unsteady and was unable to work. Gentamicin sulfate was injected intratympanically six times from November 27 through December 3, 1990, with the patient in a recumbent position. The amount of gentamicin injected was 12 mg (0.3 ml) each time. After treatment, the patient felt unsteady until the end of December 1990, during which so-called paralytic nystagmus beating toward the left side was clearly observed. Since the intratympanic injections, she has not experienced any attacks of vertigo for more than 15 months. Although she has complained of neither vertigo attacks nor unsteadiness since the beginning of 1991, the so-called paralytic nystagmus was observed until July 1991 through a noctovision using infrared rays. No caloric response was obtained in September 1991 even when the right external ear canal was irrigated with ice water. The patient's audiogram did not show deterioration immediately after intratympanic injection was completed (Fig. 1). dB
-10 10 20
30
40 50 .I.~
60
70 80 90
100
:.: (D
A~
L
0 ./ --
llO 250
500
:---,
.......;
.I'r\'\.. \"1 A
Fig.
./7
,~
fe-
--
IK
2K
4K
8K
Hz
1. Audiogram indicated by A was taken immediately before intratympanic injection of gentamicin (November 27, 1990). Audiogram indicated by B was taken immediately after the intratympanic injection (December 4, 1990). Audiogram indicated by C was taken on September 18, 1991.
DELAYED ENDOLYMPHATIC HYDROPS
S57
dB -10
--
10
--
20 30
I
4r
40 f-----50
60 70 80
90 100
+
-~
!
- - - --
+---~
r~~
~~ ~~ ~±
110 f---
,
I I
\
I
i
'a
-I-~
~+.-..i
.i. u uA-B-
~-U--U---+--i
250
500
1K
2K
I
4K
8K
Hz
Fig.
2. Audiogram indicated by A was taken on the day of his first visit to our hospital (January 25, 1991). Audiogram indicated by B was taken on October 30, 1991.
However, audiogram obtained in 1991 showed complete loss of hearing ability on the right side, although the patient did not complain of hearing deterioration. She reported that tinnitus in the right ear improved after intratympanic injection. Case 2
A junior high school boy, age 15, was referred from a city hospital to our clinic on January 25, 1991, because of vertigo that had begun in July 1990. His audiogram showed profound hearing loss on the right side (Fig. 2) while the left hearing ability was normal. The right hearing loss was detected by audiological screening before entrance into an elementary school, and profound right hearing loss had been noticed for an long as he could remember. The patient experienced vertigo attacks 26 times from September 1990 through February 1991 with no response to medical treatments. Gentamicin sulfate was injected intratympanically, while the patient was recumbent, six times from March 6 through March 12, 1991. Each injection contained up to 45 mg (1.0 ml), at which point a backflow of fluid into the external ear canal was observed. After intratympanic injection, vertigo attacks occurred twice in March, once in April, once in May, and once in June of 1991. Since then, the patient has not experienced any vertigo attacks for more than nine months. His right hearing ability showed no change after treatment (Fig. 2). Caloric response showed a tendency of right canal paresis before and after intratympanic injection of gentamicin. But even after the injections, response to ice water was observed on the right side. In this patient, so-called paralytic nystagmus was not observed clearly after treatment. Case 3
A 26-year-old male came to our clinic on April 8, 1991.
His audiogram
T. NAKASHIMA et al
S58 dB -10
/
10
20
I
30
40 50
60 70
,
lR .......-
,
, ,,
,
,
/
/
rt=-- I
.......
,,/
/
/
V\
\ \ \
:--...""""': ~
I'"
-
80
100
110
--
-
90
f---.
Fig.
-1
250
500
IK
2K
4K
8K
Hz
3. Audiogram indicated by A was taken on the day of his first visit to our hospital (April 8, 1991). Audiogram indicated by B was taken on February 26, 1992.
obtained on that day is shown in Fig. 3. He reported that his left hearing ability had been poor for more than 10 years. Since his first attack of vertigo in September 1990, he had more than fifteen attacks before his first visit to our hospital. After this visit, he had vertigo attacks twice in July and twice in August of 1991. Intratympanic injection of gentamicin sulfate was performed with the patient in a recumbent position once each day on September 7 and 8, 1991, because of the frequent attacks of vertigo; six times in six months before the injection. The amount of gentamicin injected was 14-16mg (0.35-Q.4ml) each time. We used fewer injections than in Cases 1 and 2 because of this patient's relatively good hearing level on the affected side. After treatment, the patient suffered vertigo attacks once in September and once in October of 1991 . But since then, he has had no vertigo attacks up to March 1992. There was a tendency for hearing ability on the affected side to improve after treatment (Fig. 3). COMMENT
Ototoxic effects of aminoglycosides have been recognized, with drugs such as streptomicin and gentamicin being predominantly vestibulotoxic. Since Schuknecht suggested ablation of the diseased vestibular apparatus or chemicallabyrinthectomy by ototoxic aminoglycosides for the treatment of Meniere's disease (1957), various authors have reported the intratympanic injection of aminoglycosides with relatively good results. Table 1 shows the methods described by authors using gentamicin. According to Lange/ Beck and Schmidt,4 Katzke,5 and Odkvist/ intratympanic injection of aminoglycosides was performed until symptoms of ototoxic effects such as vertigo or hearing loss appeared. Recently, however, Magnusson and Padoan reported that intratympanic injection should not be
DELAYED ENDOLYMPHATIC HYDROPS Table I.
S59
Intratympanic injection of gentamicin for the treatment of Meniere's disease.
Authors
Beck and Schmidt' Katzke S Odkvist6 Yamazaki et al*9 Magnusson and Padoan 7
Amount in each injection (interval between injections) 12mg (once daily) 30mg (once daily) 16mg (once daily) 2o-28mg (once daily) 2mg (once daily or weekly) 15-30mg (at an interval of 12hr)
Period of treatment (No. of injections) Until symptoms appear Until symptoms appear average 6 days Until symptoms appear average 5.5 days Until symptoms appear 3-11 days 4-23 times Only two injections
* Yamazaki et al administered gentamicin through the eustachian tube.
continued until symptoms develop because of potential delayed onset of ototoxic effects. 7 They performed intratympanic injection only twice and reported good results in the treatment of Meniere's disease. Our cases showed that there was a delayed onset of ototoxic effects after intratympanic injection of gentamicin even in ipsilateral DEH. Although the present series comprises only 3 patients, we feel it is important to report our findings at this stage regarding the delayed onset of ototoxic effects in DEH without awaiting the completion of a larger series. With intratympanic injection of aminoglycosides in patients with ipsilateral DEH, consideration of the maintenance of hearing ability is not extremely important in most cases because of the preceding profound hearing loss. However, exacerbation of the hearing loss should be avoided if the patient has any hearing ability. In hydropic ears, the ototoxicity of aminoglycosides is increased in both cochlear and vestibular sensory cells. 8 Accordingly, it is often difficult to determine when to discontinue the aminoglycoside injections. In our study, paralytic nystagmus was detected with noctovision using infrared rays earlier than with Frentzel's glasses. Noctovision may be useful to obtain an index as a guide for aminoglycoside management of Meniere's disease and DEH in order to resolve or ameliorate vertigo without impairment of hearing function. REFERENCES 1. Schuknecht HF: Delayed endolymphatic hydrops. Ann Otol Rhinol Laryngol 87:743-748, 1978. 2. Schuknecht HF: Ablation therapy in the management of Meniere's disease. Acta Otolaryngol (Stockh) Suppl 132:1, 1957. 3. Lange G: Die intratympanale Behandlung des Morbus Meniere mit ototoxischen Antibiotika.
T. NAKASHIMA et a1
S60
4. 5. 6. 7. 8. 9.
Laryngol Rhinol Otol 56:409-414, 1977. Beck C, Schmidt CL: 10 years of experience with intratympanically applied streptomycin (gentamycin) in the therapy of morbus Meniere. Arch Otorhino1aryngol 221:149-152, 1978. Katzke D: Die intratympanale Gentamicin-behandlung bei Morbus Meniere. Laryngol Rhinol Otol 61:4-8, 1982. Odkvist LM: Middle ear ototoxic treatment for inner ear disease. Acta Otolaryngol (Stockh) SuppI457:83-86, 1988. Magnusson M, Padoan S: Delayed onset of ototoxic effects of gentamicin in treatment of Meniere's disease. Acta Otolaryngo1 (Stockh) 111 :671-676, 1991. Kimura RS, Lee K, Nye C, et al: Effects of systemic and lateral semicircular canal administration of aminoglycosides on normal and hydropic ears. Acta Otolaryngol (Stockh) 111:1021-1030, 1991. Yamazaki T, Hayashi M, Komatsuzaki A: Intratympanic gentamicin therapy for Meniere's disease placed by a tubal catheter with systematic isosorbide. Acta Otolaryngol (Stockh) Suppl 481 :613-616, 1991.
Request reprints to:
Dr. T. Nakashima, Department of Otorhinolaryngology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan
INTRATYMPANIC INJECTION OF GENTAMICIN FOR THE TREATMENT OF DELAYED ENDOLYMPHATIC HYDROPS Tsutomu NAKASHIMA, M.D., Yumiko KASEKI, M.D., Masahide KAIDA, M.D., and Kyoji MIYAZAWA, M.D. Department of Otorhinolaryngology, Nagoya University School of Medicine, Nagoya, Japan
In three patients with ipsilateral delayed endolymphatic hydrops (DEH), ototoxic gentamicin sulfate was injected through the tympanic membrane for the ablative treatment of frequent attacks of vertigo. Two patients received six injections and one patient received two. Treatment produced complete control of vertigo attacks in one patient who received six injections, and substantial control in the other two patients. The present results showed that there was a delayed onset of the ototoxic effect of gentamicin in the treatment of ipsilateral DEH. Delayed endolymphatic hydrops (DEH) is a disease entity that has clinical manifestations similar to those of Meniere's disease but can be differentiated from the latter. l Typically, DEH occurs in patients who have sustained a profound hearing loss in one ear, usually from infection or trauma, and then after a prolonged period of time develop either episodic vertigo from the same ear (ipsilateral DEH) or fluctuating hearing loss, also sometimes with episodic vertigo, in the opposite ear (contralateral DEH). In cases of ipsilateral DEH, destructive procedures are designed to eliminate abnormal vestibular activity if the patient has not responded to medical treatment. This concept of treatment may be considered similar to that in Meniere's disease with profound hearing loss and frequent attacks of vertigo. In incapacitating Meniere's disease, intratympanic administration of aminoglycosides has been used by various authors as a destructive procedure since Schuknecht suggested chemical ablation with aminoglycosides in 1957. 2 In contrast, there have been few reports of intratYJIlpanic administration of aminoglycosides for the treatment of DEH. We used intratympanic administration of gentamicin in three patients with ipsilateral Received for publication September 1, 1992 Presented at the 51th Annual Meeting of Japan Society for Equilibrium Research, Maebashi, November 5-6, 1992. S55
T. NAKASHIMA et al
S56
DEH. The details are as follows. CASE REPORTS
Case 1
A 33-year-old female came to our clinic on March 4, 1989, because of frequent attacks of vertigo since February, 1988. Hearing ability in her right ear had been poor for l;lS long as she could remember. Her audiogram showed flat-type perceptive hearing loss on the right side as illustrated in Fig. 1, while left hearing ability was normal. Caloric response was weak on the right side but not absent. The patient experienced attacks of rotatory vertigo four times in 1989, six times from January through May, of 1990, and eight times from June through November in spite of continuous administration of anti-vertigo drugs. Each attack of vertigo persisted for several hours. Besides rotatory vertigo, she occasionally felt unsteady and was unable to work. Gentamicin sulfate was injected intratympanically six times from November 27 through December 3, 1990, with the patient in a recumbent position. The amount of gentamicin injected was 12 mg (0.3 ml) each time. After treatment, the patient felt unsteady until the end of December 1990, during which so-called paralytic nystagmus beating toward the left side was clearly observed. Since the intratympanic injections, she has not experienced any attacks of vertigo for more than 15 months. Although she has complained of neither vertigo attacks nor unsteadiness since the beginning of 1991, the so-called paralytic nystagmus was observed until July 1991 through a noctovision using infrared rays. No caloric response was obtained in September 1991 even when the right external ear canal was irrigated with ice water. The patient's audiogram did not show deterioration immediately after intratympanic injection was completed (Fig. 1). dB
-10 10 20
30
40 50 .I.~
60
70 80 90
100
:.: (D
A~
L
0 ./ --
llO 250
500
:---,
.......;
.I'r\'\.. \"1 A
Fig.
./7
,~
fe-
--
IK
2K
4K
8K
Hz
1. Audiogram indicated by A was taken immediately before intratympanic injection of gentamicin (November 27, 1990). Audiogram indicated by B was taken immediately after the intratympanic injection (December 4, 1990). Audiogram indicated by C was taken on September 18, 1991.
DELAYED ENDOLYMPHATIC HYDROPS
S57
dB -10
--
10
--
20 30
I
4r
40 f-----50
60 70 80
90 100
+
-~
!
- - - --
+---~
r~~
~~ ~~ ~±
110 f---
,
I I
\
I
i
'a
-I-~
~+.-..i
.i. u uA-B-
~-U--U---+--i
250
500
1K
2K
I
4K
8K
Hz
Fig.
2. Audiogram indicated by A was taken on the day of his first visit to our hospital (January 25, 1991). Audiogram indicated by B was taken on October 30, 1991.
However, audiogram obtained in 1991 showed complete loss of hearing ability on the right side, although the patient did not complain of hearing deterioration. She reported that tinnitus in the right ear improved after intratympanic injection. Case 2
A junior high school boy, age 15, was referred from a city hospital to our clinic on January 25, 1991, because of vertigo that had begun in July 1990. His audiogram showed profound hearing loss on the right side (Fig. 2) while the left hearing ability was normal. The right hearing loss was detected by audiological screening before entrance into an elementary school, and profound right hearing loss had been noticed for an long as he could remember. The patient experienced vertigo attacks 26 times from September 1990 through February 1991 with no response to medical treatments. Gentamicin sulfate was injected intratympanically, while the patient was recumbent, six times from March 6 through March 12, 1991. Each injection contained up to 45 mg (1.0 ml), at which point a backflow of fluid into the external ear canal was observed. After intratympanic injection, vertigo attacks occurred twice in March, once in April, once in May, and once in June of 1991. Since then, the patient has not experienced any vertigo attacks for more than nine months. His right hearing ability showed no change after treatment (Fig. 2). Caloric response showed a tendency of right canal paresis before and after intratympanic injection of gentamicin. But even after the injections, response to ice water was observed on the right side. In this patient, so-called paralytic nystagmus was not observed clearly after treatment. Case 3
A 26-year-old male came to our clinic on April 8, 1991.
His audiogram
T. NAKASHIMA et al
S58 dB -10
/
10
20
I
30
40 50
60 70
,
lR .......-
,
, ,,
,
,
/
/
rt=-- I
.......
,,/
/
/
V\
\ \ \
:--...""""': ~
I'"
-
80
100
110
--
-
90
f---.
Fig.
-1
250
500
IK
2K
4K
8K
Hz
3. Audiogram indicated by A was taken on the day of his first visit to our hospital (April 8, 1991). Audiogram indicated by B was taken on February 26, 1992.
obtained on that day is shown in Fig. 3. He reported that his left hearing ability had been poor for more than 10 years. Since his first attack of vertigo in September 1990, he had more than fifteen attacks before his first visit to our hospital. After this visit, he had vertigo attacks twice in July and twice in August of 1991. Intratympanic injection of gentamicin sulfate was performed with the patient in a recumbent position once each day on September 7 and 8, 1991, because of the frequent attacks of vertigo; six times in six months before the injection. The amount of gentamicin injected was 14-16mg (0.35-Q.4ml) each time. We used fewer injections than in Cases 1 and 2 because of this patient's relatively good hearing level on the affected side. After treatment, the patient suffered vertigo attacks once in September and once in October of 1991 . But since then, he has had no vertigo attacks up to March 1992. There was a tendency for hearing ability on the affected side to improve after treatment (Fig. 3). COMMENT
Ototoxic effects of aminoglycosides have been recognized, with drugs such as streptomicin and gentamicin being predominantly vestibulotoxic. Since Schuknecht suggested ablation of the diseased vestibular apparatus or chemicallabyrinthectomy by ototoxic aminoglycosides for the treatment of Meniere's disease (1957), various authors have reported the intratympanic injection of aminoglycosides with relatively good results. Table 1 shows the methods described by authors using gentamicin. According to Lange/ Beck and Schmidt,4 Katzke,5 and Odkvist/ intratympanic injection of aminoglycosides was performed until symptoms of ototoxic effects such as vertigo or hearing loss appeared. Recently, however, Magnusson and Padoan reported that intratympanic injection should not be
DELAYED ENDOLYMPHATIC HYDROPS Table I.
S59
Intratympanic injection of gentamicin for the treatment of Meniere's disease.
Authors
Beck and Schmidt' Katzke S Odkvist6 Yamazaki et al*9 Magnusson and Padoan 7
Amount in each injection (interval between injections) 12mg (once daily) 30mg (once daily) 16mg (once daily) 2o-28mg (once daily) 2mg (once daily or weekly) 15-30mg (at an interval of 12hr)
Period of treatment (No. of injections) Until symptoms appear Until symptoms appear average 6 days Until symptoms appear average 5.5 days Until symptoms appear 3-11 days 4-23 times Only two injections
* Yamazaki et al administered gentamicin through the eustachian tube.
continued until symptoms develop because of potential delayed onset of ototoxic effects. 7 They performed intratympanic injection only twice and reported good results in the treatment of Meniere's disease. Our cases showed that there was a delayed onset of ototoxic effects after intratympanic injection of gentamicin even in ipsilateral DEH. Although the present series comprises only 3 patients, we feel it is important to report our findings at this stage regarding the delayed onset of ototoxic effects in DEH without awaiting the completion of a larger series. With intratympanic injection of aminoglycosides in patients with ipsilateral DEH, consideration of the maintenance of hearing ability is not extremely important in most cases because of the preceding profound hearing loss. However, exacerbation of the hearing loss should be avoided if the patient has any hearing ability. In hydropic ears, the ototoxicity of aminoglycosides is increased in both cochlear and vestibular sensory cells. 8 Accordingly, it is often difficult to determine when to discontinue the aminoglycoside injections. In our study, paralytic nystagmus was detected with noctovision using infrared rays earlier than with Frentzel's glasses. Noctovision may be useful to obtain an index as a guide for aminoglycoside management of Meniere's disease and DEH in order to resolve or ameliorate vertigo without impairment of hearing function. REFERENCES 1. Schuknecht HF: Delayed endolymphatic hydrops. Ann Otol Rhinol Laryngol 87:743-748, 1978. 2. Schuknecht HF: Ablation therapy in the management of Meniere's disease. Acta Otolaryngol (Stockh) Suppl 132:1, 1957. 3. Lange G: Die intratympanale Behandlung des Morbus Meniere mit ototoxischen Antibiotika.
T. NAKASHIMA et a1
S60
4. 5. 6. 7. 8. 9.
Laryngol Rhinol Otol 56:409-414, 1977. Beck C, Schmidt CL: 10 years of experience with intratympanically applied streptomycin (gentamycin) in the therapy of morbus Meniere. Arch Otorhino1aryngol 221:149-152, 1978. Katzke D: Die intratympanale Gentamicin-behandlung bei Morbus Meniere. Laryngol Rhinol Otol 61:4-8, 1982. Odkvist LM: Middle ear ototoxic treatment for inner ear disease. Acta Otolaryngol (Stockh) SuppI457:83-86, 1988. Magnusson M, Padoan S: Delayed onset of ototoxic effects of gentamicin in treatment of Meniere's disease. Acta Otolaryngo1 (Stockh) 111 :671-676, 1991. Kimura RS, Lee K, Nye C, et al: Effects of systemic and lateral semicircular canal administration of aminoglycosides on normal and hydropic ears. Acta Otolaryngol (Stockh) 111:1021-1030, 1991. Yamazaki T, Hayashi M, Komatsuzaki A: Intratympanic gentamicin therapy for Meniere's disease placed by a tubal catheter with systematic isosorbide. Acta Otolaryngol (Stockh) Suppl 481 :613-616, 1991.
Request reprints to:
Dr. T. Nakashima, Department of Otorhinolaryngology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan