4073

Nephrol Dial Transplant (2011) 26: 4073–4078

doi: 10.1093/ndt/gfr211
Advance Access publication 6 May 2011

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Protective effect of N-acetylcysteine from drug-induced ototoxicity in
uraemic patients with CAPD peritonitis

Bulent Tokgoz1, Cahit Ucar2, Ismail Kocyigit1, Mehmet Somdas3, Aydin Unal1, Alperen Vural3,
Murat Sipahioglu1, Oktay Oymak1 and Cengiz Utas1
1
Department of Nephrology, Erciyes University Medical Faculty, Kayseri, Turkey, 2Department of Internal Medicine, Erciyes
University Medical Faculty, Kayseri, Turkey and 3Department of Otorhinolaryngology, Erciyes University Medical Faculty,
Kayseri, Turkey
Correspondence and offprint requests to: Bulent Tokgoz; E-mail: [email protected]

Abstract pared with the baseline low-frequency results in the control

Aim. Peritonitis is currently one of the leading complica- group (P < 0.001). It was found that NAC had a protective
tions of continuous ambulatory peritoneal dialysis (CAPD) effect against ototoxicity on low-frequency (0.25–8 KHz) hear-
treatment. Aminoglycosides and vancomycin are used in ing functions. The first and the fourth week’s high-frequency
the treatment of CAPD peritonitis despite their potential hearing functions improved when compared with baseline
risk for ototoxicity. N-acetylcysteine (NAC) is a molecule high-frequency hearing functions in patients taking NAC
used in the treatment and prophylaxis of many diseases (P < 0.05), while they worsened. The first and fourth week’s
related to oxidative stress. The aim of this study was to high-frequency tests worsened when compared with the base-
examine whether ototoxicity due to antibiotics used in the line high-frequency tests in the control group (P < 0.001).
treatment of CAPD peritonitis can be prevented by NAC. Conclusions. The present study suggests that intraperito-
Methods. Sixty patients, who first developed CAPD neal aminoglycoside and vancomycin administration in
peritonitis attacks from February 2008 to April 2010 were CAPD patients may cause low- and high-frequency hearing
included in this study. Patients were divided into two groups, loss, and this ototoxic effect is related to the dose given. It
those taking an additional NAC treatment (n ¼ 30) and a was found that when the antioxidant NAC is administered
control group (n ¼ 30). Low- and high-frequency hearing alone, it prevents ototoxicity, associated with intraperitoneal
function tests were performed on the two groups before treat- amikacin and vancomycin in patients with CAPD peritonitis.
ment (baseline), at the end of the first (early follow-up) and In addition, it was revealed that NAC may also have a cu-
the fourth week after the treatment (late follow-up). Total rative effect on impaired high-frequency hearing functions.
doses of vancomycin and amikacin were recorded. Keywords: amikacin; CAPD peritonitis; NAC; ototoxicity; vancomycin
Results. There was no statistically significant difference be-
tween the groups in terms of hearing functions at the begin-
ning. However, patients taking NAC had better hearing
function test results 4 weeks after the treatment compared with Introduction
those of the control group (P < 0.05). There were no statistical
differences between posttreatment low-frequency hearing Peritonitis is currently one of the leading complications of
function tests conducted at the baseline and the first and the continuous ambulatory peritoneal dialysis (CAPD) [1–5]. It
fourth weeks in patients taking NAC. The first and the fourth is not only a reason for technical failure, but it also leads to
week’s low-frequency hearing functions worsened when com- considerable morbidity and mortality. Its incidence varies

The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: [email protected]
4074 B. Tokgoz et al.

from centre to centre, and it resulted in death in 3% of the phonuclear leucocytes. Patients with impaired tympanic membrane integ-
episodes in our cohort [6]. Many patients are hospitalized rity were excluded. Each patient was queried in terms of complaints such
as tinnitus, vertigo and dizziness, and their responses were recorded.
due to peritonitis and may have to stop receiving CAPD This is a prospective, randomized, controlled, open-label study. The
therapy [7]. According to the recommendations of the patients were randomly assigned to receive treatment for CAPD peritonitis
International Society for Peritoneal Dialysis, as soon as a _
either with NAC (Asist; Bilim Ilac Sanayi Ticaret A.S., Istanbul, Turkey)
patient is diagnosed with peritonitis, cultures must be taken 600 mg twice daily (treatment group) or with treatment for CAPD peritonitis
alone (control group). After the patient was informed and consent for the
and empirical antibiotic therapy should be started without enrollment in the study was given he/she was requested to choose a sealed
delay [8–11]. Empirical therapy has to cover both Gram- envelope in which ‘NAC Group’ or ‘Control Group’ was written. Thus, the
positive and Gram-negative microorganisms. Each perito- groups were developed.
neal dialysis (PD) centre should determine which antibiotics Threshold values for hearing were identified through ‘pure-tone audio-
should be used in empirical therapy by being aware of the metry’ measurements with the AC 40 Audiometer (Interacoustics, Assens,
Denmark) using a standard technique of pure-tone air and bone conduction
efficacies and sensitivities of the microorganisms causing threshold measurements at frequencies of 250, 500, 1000, 2000, 3000,
peritonitis in its own patient population. Gram-positive or- 4000, 6000, 8000, 10 000, 12 000, 14 000 and 16 000 Hz in the Audiol-
ganisms may be covered by vancomycin or cephalosporin ogy Laboratory in the Otorhinolaryngology Department. Recordings of the
and Gram-negative organisms by a third-generation cepha- threshold hearing values obtained from the ear with lower hearing were

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retained for analysis. The measured frequencies were separated into two
losporin or aminoglycoside [11]. Although aminoglycosides groups and pure-tone averages (PTA) were gathered as follows:
and vancomycin are recommended for only short-term use
because of the risk of ototoxicity [11], there is enough data  lower frequencies, PTA-1: 250, 500, 1000, 2000, 3000, 4000, 6000 and
regarding the correlation between the usage of aminoglyco- 8000 Hz,
sides and the frequency of hearing loss even with short-term  higher frequencies, PTA-2: 10 000, 12 000, 14 000 and 16 000 Hz.
treatments. We have established that hearing loss is a much Hearing function tests were performed on the two groups before treat-
more overlooked complication during CAPD treatment in a ment (baseline). Follow-up otologic examinations were carried out 8  2
recent study [12]. We found that PD patients with a history days (early follow-up) and 28  2 days (late follow-up) after starting
of peritonitis had significantly higher incidence of hearing treatment for CAPD peritonitis. Hearing impairment was evaluated by
using the criteria of the American Speech-Language-Hearing Association
loss according to the median hearing values for both lower (ASHA 1994) [17]. Ototoxicity was defined as an increase in the auditory
and higher frequency sounds as compared to those PD pa- threshold by at least 20 dB at any one test frequency or at least 10 dB at any
tients with no history of peritonitis, and the administration of two adjacent frequencies or loss of response at three consecutive
aminoglycoside antibiotic was directly associated with the frequencies between the baseline and follow-up studies in the worse ear.
development of the hearing loss [12]. The most frequently Statistical considerations
emphasized mechanism responsible for aminoglycoside and SPSS 15.0 software was used for the statistical analysis. The Kolmo-
vancomycin ototoxicity is reactive oxygen types resulting in gorov–Smirnov test was used to determine the normality of variable dis-
damage to the internal ear. In animal studies, coadministra- tributions. Continuous variables with normal distribution were presented
tion of antioxidant therapy ameliorated aminoglycoside- as mean SD. Where normal distribution was absent, the median value
was used. Statistical analysis of the parametric variables was performed by
induced ototoxicity [13]. N-acetylcysteine (NAC) is a a Student’s t-test between two groups and by a one-way analysis of var-
molecule used in the treatment and prophylaxis of many iance, with Scheffe’s post hoc test among more than two groups. The
diseases related to oxidative stress. It has been suggested that Mann–Whitney U-test was used to compare nonparametric variables
NAC might prevent hearing loss associated with bacterial between the two groups. The Kruskal–Wallis test was used to compare
nonparametric variables among more than two groups. Then, the Mann–
meningitis [14] and auditory hair cell damage from cisplatin Whitney U-test with Bonferroni correction was used to assess the
[15]. NAC has also been shown to ameliorate gentamicin- differences among more than two groups. The correlation analysis was
induced nephrotoxicity [16]. In this study, we aimed to exam- evaluated by the Pearson’s correlation test for parametric variables and by
ine whether ototoxicity due to antibiotics used in the treatment the Spearman’s correlation test for nonparametric variables. Qualitative
of CAPD peritonitis can be prevented by NAC. variables were given as percentages, and the correlation between catego-
rical variables was examined by the chi-square test. A P-value of <0.05
was considered to be significant.
Methods
This study was performed on monitored patients with CAPD in the Neph- Results
rology Department of the Medical Faculty of Erciyes University for a
period of 26 months between February 2008 and April 2010. In the centre,
the majority (~90%) of dialysis patients are on PD. Two hundred and A total of 63 CAPD patients were enrolled in the study.
sixty-four PD patients are currently being followed. In the study period, Three patients were excluded from the study due to a
164 new patients have started receiving PD, and 127 patients have dropped perforated tympanic membrane. There were 30 patients in
out from this population for several different reasons. Additionally, during
the study, 191 peritonitis attacks were diagnosed (6779 patient-month/191 the NAC-treated group and 30 patients in the control group.
peritonitis attack, 1 peritonitis every 35 months in the centre) and 83 of There was no statistically significant difference between
these were having a first peritonitis episode. the groups in any of the patients’ baseline clinical and
From these 83 patients, a total of 60 CAPD patients were enrolled in the demographic characteristics. The demographic and clinical
study. Three patients were excluded from the study due to a perforated
tympanic membrane, and eight patients were rejected for enrollment in the
characteristics of the patients are summarized in Table 1.
study. Also, 12 patients applied after office hours and were excluded from The most common cause of ESRD in patients in the
the study because of the inability to perform audiometric tests at the study was diabetes mellitus. The causes of ESRD are
admission. Patients >18 years of age with end-stage renal disease (ESRD), summarized in Table 2.
on CAPD therapy, experiencing their first peritonitis episode, and being The cultures from the peritoneal fluids were evaluated.
treated with cephalozine or vancomycin and/or amikacin were included in
the study. CAPD peritonitis was diagnosed when the peritoneal fluid white No microorganisms grew in the peritoneal fluid cultures in
cell count was 100/mm3 and when 50% of these cells were polymor- 7 patients in the NAC-treated group, whereas 11 in the
NAC for ototoxicity in CAPD patients 4075
a
Table 1. Demographic, biochemical, clinical and audiometric parameters in all patients

Parameters NAC-treated group Control group P

Age (year) 45.0 6 13.2 49.9 6 15.2 0.19

Duration of CAPD (month) 31 (13.50–68.25) 40 (15.5–72.0) 0.51
Body surface area (m2) 1.68 6 0.24 1.68 6 0.18 0.97
Blood WBC (mm3) 7960 6 2558 8410 6 2276 0.47
Haemoglobin (g/dL) 9.5 6 1.0 9.2 6 1.2 0.33
Albumin (g/dL) 2.9 6 0.4 3.0 6 0.4 0.17
Residual urine volume (mL/day) 125 (0–700) 100 (0–787) 0.80
Cumulative cephazolin dosage (g) 14 (10–28) 18 (10–28) 0.15
Cumulative amikacin dosage (g) 1.5 (1–1.5) 1.25 (1.0–1.6) 0.66
Cumulative vancomycin dosage (g) 4 (1.5–6) 4 (0–6) 0.70
Peritoneal fluid WBC (mm3) 3175 (1547–5325) 2350 (1700–4225) 0.09
Kt/Vurea 2.34 6 0.46 2.46 6 0.75 0.48
D/P creatinine 0.72 6 0.13 0.79 6 0.11 0.06

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Baseline hearing level, dB
PTA-1 27.5 6 13.2 24.4 6 12.1 0.36
PTA-2 48.7 6 17.5 38.3 6 17.7 0.06
a
WBC, white blood cell.

control group had no microorganisms. Table 3 summarizes Table 2. Underlying causes for ESRD
the causative microorganisms in the peritoneal fluid cultures.
When the treatment and the control groups were compared, NAC-treated Control group Total
Causes of ESRD group (n ¼ 30) (n ¼ 30) (n ¼ 60)
late follow-up test results of low- and high-frequency hearing
functions showed a statistically significant difference (Table 4). Diabetic nephropathy 9 (30%) 11 (36.7%) 20 (33.3%)
At the early follow-up, low-frequency (PTA-1) exami- Hypertension 6 (20%) 6 (20%) 12 (20%)
nation, three patients (10%) in the control group and one Glomerulonephritis 0 (0%) 2 (6.7%) 2 (3.3%)
patient (3.3%) in the NAC group, and in the high-frequency Polycystic kidney disease 1 (3.3%) 0 (0%) 1 (1.7%)
(PTA-2) examination, nine patients (30%) in the control Amyloidosis 3 (10%) 1 (3.3%) 4 (6.7%)
Others/unknown 11 (36.7%) 10 (33.3%) 21 (35%)
group and one patient (3.3%) in the NAC group fulfilled
the criteria for ototoxicity (P ¼ 0.11 and P ¼ 0.021,
respectively). At the late follow-up, low-frequency (PTA-1)
Table 3. Causative organisms isolated from peritoneal effluent fluida
examination, 15 patients (50%) in the control group and 1
patient (3.3%) in the NAC group, and in the high-frequency NAC-treated group Control group
(PTA-2) examination, 21 patients (70%) in the control group Microorganisms (n ¼ 30) (n ¼ 30)
and 1 patient (3.3%) in the NAC group fulfilled the criteria for
ototoxicity (P < 0.001). Gram positive
The mean change in PTA-1 at early follow-up was 3.16 Staphylococcus epidermidis 5 (16.6%) 4 (13.3%)
 6.25 in the control group and 1.36  5.85 in the NAC- MSSA 4 (13.3%) 3 (10.0%)
MRSA 3 (10%) 4 (13.3%)
treated group (P ¼ 0.25), while in PTA-2 at early follow- CNS 5 (16.6%) 2 (6.7%)
up, it was 5.43  8.56 in the control group and 4.73  Enterococcus 0 (0%) 2 (6.7%)
7.40 in the NAC-treated group (P < 0.001). As for the Gram negative
mean change in PTA-1 at late follow-up, it was 12.76  Pseudomonas 3 (10%) 1 (3.3%)
E. coli 1 (3.3%) 2 (6.7%)
6.22 in the control group and 1.86  5.98 in the NAC-treated Others 1 (3.3%) 1 (3.3%)
group (P < 0.001). Finally, the mean change in PTA-2 Fungus 1 (3.3%) 0 (0%)
at late follow-up was 16.93  8.10 in the control group Culture negative 7 (23.3%) 11 (36.7%)
and 5.96  8.89 in the NAC-treated group (P < 0.001)
a
(Tables 5 and 6). MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-
resistant Staphylococcus. aureus; CNS, coagulase-negative Staphylococcus.
There was no statistically significant difference between
the groups in terms of hearing functions at the beginning.
However, patients taking NAC had better hearing function
test results at the end of the fourth week after treatment Table 4. Early and late follow-up hearing levels between groups
compared with those of the control group (P < 0.05). There
Hearing function NAC-treated Control group
were no statistical differences between the baseline low- test (dB) group (n ¼ 30) (n ¼ 30) P
frequency hearing function tests and the first and the fourth
week’s low-frequency results tests in patients taking NAC. Early follow-up
The first and the fourth week’s low-frequency hearing PTA-1 28.8 6 12.0 27.6 6 14.1 0.71
functions worsened compared with the baseline low fre- PTA-2 44.0 6 14.9 43.8 6 19.2 0.95
quency tests in the control group (P < 0.001). It was seen Late follow-up
PTA-1 25.6 6 11.6 37.2 6 13.8 <0.05
that NAC had a protective effect against ototoxicity on PTA-2 42.8 6 14.7 55.3 6 17.1 <0.05
low-frequency (0.25–8 KHz) hearing functions. The comparison
4076 B. Tokgoz et al.
Table 5. Mean hearing loss at early and late follow-up In another study, the same researchers reported that
repeated intraperitoneal gentamicin administration
NAC group Control group increased the risk of ototoxicity [23].
(n ¼ 30) (n ¼ 30) P
Mars et al. [21] reported no hearing loss in the study in
Early follow-up
which they performed audiogram tests at the start of intra-
PTA-1 1.36 6 5.85 3.16 6 6.25 0.25 peritoneal aminoglycoside treatment (within the first 24 h of
PTA-2 4.73 6 7.40 5.43 6 8.56 <0.001 administration) and after the completion of therapy (within
Late follow-up 17 days on average) in patients with CAPD. This study was
PTA-1 1.86 6 5.98 12.76 6 6.22 <0.001 conducted on only six patients although it had a prospective
PTA-2 5.96 6 8.89 16.93 6 8.10 <0.001
design. Another study performed on 19 patients with CAPD
indicated that clinical ototoxicity occurred even if gentami-
Table 6. Number of patients who developed ototoxicity cin blood levels did not specifically increase after intraper-
itoneal administration [22].
NAC group Control group This study revealed that hearing loss was observed par-
(n ¼ 30) (n ¼ 30) P
ticularly at higher frequencies. Gendeh et al. [24] found

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Early follow-up
that vancomycin could produce hearing impairment in
PTA-1 1 (% 3.3) 3 (% 10) 0.11 CAPD patients when administered in combination with
PTA-2 1 (% 3.3) 9 (% 30) <0.05 aminoglycoside. It has been suggested that ototoxicity
Late follow-up may be attributable to the possible synergistic effect of
PTA-1 0 (% 0) 15 (% 50) <0.001 the two drugs. Taking into consideration that hearing loss
PTA-2 1 (% 3.3) 21 (% 70) <0.001
can negatively affect quality of life, unnecessary repetitive
usage of aminoglycoside antibiotics should be avoided, and
between the first and the fourth week’s high-frequency therapy should be stopped as soon as possible. Patients
hearing functions and the baseline high-frequency tests with CAPD who are treated with ototoxic drugs should
yielded that the former improved in patients taking NAC be followed up in terms of complaints regarding hearing
(P < 0.05) and worsened in the control group (P < 0.001) loss such as tinnitus, dizziness or vertigo.
(see Figure 1). Correlation between hearing loss and total Of the mechanisms that are held responsible for amino-
antibiotics dosage in control groups is shown in Figure 2. glycoside ototoxicity, the most frequently emphasized
This results suggest that NAC may have a curative effect mechanism is the reactive oxygen type, which results in
on impaired hearing functions in addition to a protective damage to the internal ear [25]. NAC, a thiol-containing
effect on high-frequency hearing functions. antioxidant, was originally used as a mucolytic drug in a
variety of pulmonary diseases. Later, it became the drug
of choice for acute acetaminophen poisoning [26].
Discussion Recently, it has been used successfully in several models
of ischaemic and toxic injuries to the heart, kidney, liver
Aminoglycosides have been used in the management of and lung [16, 27–29]. In each of these conditions, it is
peritonitis in patients with CAPD despite a well-known presumed that NAC activity is mediated, at least in part,
ototoxicity risk. In spite of their side effects, the absence by its antioxidant properties.
of safe alternatives to aminoglycosides is the main cause On the basis of the free radical theory of Aminoglycosides
for using these antibiotics. On the other hand, aminoglyco- (AG) and vancomycin-induced ototoxicity, it is logical to
sides are highly advantageous drugs since they are suggest that NAC would be more beneficial in uraemic pa-
inexpensive, their bacterial resistance lower, and the tients than in the general population, because uraemia is
allergic reactions rare [18]. In patients with CAPD, amino- associated with a high level of oxidative stress.
glycosides are frequently used in peritonitis therapy In the study carried out by Okur et al. using the animal
through the intraperitoneal route. The correlation between model, carboplatin-induced ototoxicity was evaluated. Car-
usage of intraperitoneal aminoglycosides and ototoxicity in boplatin was applied to the rats, and it was shown that
patients with CAPD has been frequently studied in patients carboplatin-induced hearing loss by increasing nitric oxide
treated with tobramycin and gentamicin [19–23]. (NO) levels. It was reported that NAC, which was applied
In one of the early studies on this issue, Nikolaidis et al. 30 min before the carboplatin application, had protective
[19] suggested that the administration of intraperitoneal effects by decreasing NO production [30]. In a study
tobramycin in patients with CAPD peritonitis did not lead performed by Theneshkumar et al. [31], using an animal
to any increase in hearing loss. A possible reason for fail- model, it was shown that intraperitoneally administered
ure to determine the specific ototoxicity related to amino- NAC prevented cisplatin-induced ototoxicity.
glycosides in that study may be due to limited frequency Thomas Dickey et al. reported that the protective
range measurements (i.e. between 250 and 10 000 Hz effects of infusion of NAC and isotonic saline infusion
only). against cisplatin-induced ototoxicity were compared and
Similarly, by measuring serum drug levels in the patients it was observed in the group to which NAC was applied
with CAPD, Gendeh et al. [20] suggested that the treatment that the results were better at low-frequency audiometric
with intraperitoneal gentamicin did not increase ototoxicity examinations on the 7th day than baseline auditory
risk. However, it should be emphasized that only ordinary examinations. These data show that treatment with
frequencies (1288000 Hz) were examined in that study. NAC can prevent cisplatin-induced ototoxicity in rats
NAC for ototoxicity in CAPD patients 4077

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Fig. 1. Comparison of mean hearing loss between control and NAC groups.

Fig. 2. Correlation between hearing loss and total antibiotics dosage in control groups.

[32]. Additionally, Sinswat and et al. [13] designed a cytometry method that cochlear cell death was reduced
study in guinea pigs and intraperitoneal coadministration with the addition of NAC at 72 h after the radiotherapy. It
of antioxidant therapy recovered intraperitoneal AG- was found that the use of NAC was safe and effective,
induced ototoxicity. and it reduced hearing loss in radiotherapy patients be-
In a study performed by Low et al. [33], radiation- cause of head–neck cancer. In another study performed
induced ototoxicity was evaluated in patients who were by Feghali et al., the protective effects of NAC on cis-
on radiotherapy because of head–neck cancer and it was platin-induced ototoxicity was evaluated. It was shown
found that NAC significantly reduced both cochlear cell that NAC was protective against both cisplatin-induced
apoptosis and the production of free oxygen radicals in damage to auditory neuronal cells and to auditory hair
the inner ear after the radiation. It was shown by the flow cells [15].
4078 B. Tokgoz et al.

One of the most important recent studies showed that 12. Tokgoz B, Somdas MA, Ucar C et al. Correlation between hearing
antioxidant therapy using NAC was otoprotective in loss and peritonitis frequency and administration of ototoxic intraper-
itoneal antibiotics in patients with CAPD. Ren Fail 2010; 32: 179–184
patients undergoing haemodialysis. Feldman et al. inves-
13. Sinswat P, Wu W, Sha S et al. Protection from ototoxicity of intra-
tigated the possible protective effect of the antioxidant peritoneal gentamicin in guinea pigs. Kidney Int 2000; 58: 2525–2532
NAC in gentamicin-induced hearing loss in 53 haemodial- 14. Klein M, Koedel U, Pfister H et al. Meningitis-associated hearing
ysis patients. These patients were randomized consecu- loss: protection by adjunctive antioxidant therapy. Ann Neurol
tively, depending on whether or not they received NAC; 2003; 54: 451–458
hence, the demographic, biochemical and clinical features 15. Feghali J, Liu W, Van De Water T. L-n-acetyl-cysteine protection
of both groups were similar. In consequence, the otopro- against cisplatin-induced auditory neuronal and hair cell toxicity.
Laryngoscope 2001; 111: 1147–1155
tective effect of NAC was established in the high audio- 16. Mazzon E, Britti D, De Sarro A et al. Effect of N-acetylcysteine on
metric tone frequencies [34]. gentamycin-mediated nephropathy in rats. Eur J Pharmacol 2001;
In conclusion, our data suggest that NAC may be used as 424: 75–83
a cheap, effective and safe drug for the prevention of AG 17. American Speech-Language-Hearing Association. Guidelines for the
and vancomycin-induced ototoxicity in CAPD patients. audiologic management of individuals receiving cochleotoxic drug
The present study has several limitations. First of all, therapy. ASHA 1994; 36 (Suppl): 11–19

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18. Gilbert D. Aminoglycosides. In: Mandell GL, Bennet JE, Dolin R
blood AG and vancomycin levels were not measured. Also, (eds). Principles and Practice of Infectious Diseases. 6th edn.
the study did not address either laboratory investigation of New York: Churchill Livingstone, 2005; 328–356
vestibular ototoxicity by electronystagmography or evalu- 19. Nikolaidis P, Vas S, Lawson W et al. Is intraperitoneal tobramycin
ation of cochlear function by otoacoustic emissions meas- ototoxic in CAPD patients? Perit Dial Int 1991; 11: 156–161
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dant therapy against ototoxicity are required in a larger
21. Mars RL, Moles K, Pope K et al. Use of bolus intraperitoneal amino-
cohort of CAPD patients. glycosides for treating peritonitis in endstage renal disease patients
Acknowledgements. This study is registered with a name of ‘Prevention of receiving continuous ambulatory peritoneal dialysis and continuous
Drug-Induced Ototoxicity in PD Patients by NAC’ on ClinicalTrials.gov cycling peritoneal dialysis. Adv Perit Dial 2000; 16: 280–284
and its ClinicalTrials.gov identifier number is NCT01131468. 22. van der Hulst RJ, Boeschoten EW, Nielsen FW et al. Otototoxicity
Funding. No funding has been received for this study. monitoring with ultra-high frequency audiometry in peritoneal
dialysis patients treated with vancomycin or gentamicin. ORL
Conflict of interest statement. None declared. J Otorhinolaryngol Relat Spec 1991; 53: 19–22
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ambulatory peritoneal dialysis. J Laryngol Otol 1993; 107: 681–685
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