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Year : 2012  |  Volume : 15  |  Issue : 4  |  Page : 453-457

Prevalence of ototoxicity in University of Benin Teaching Hospital, Benin city: A 5-year review

1 Department of Surgery, E. N. T. Division, Irrua Specialist Teaching Hospital, Benin City, Edo State, Nigeria
2 Department of Oto-Rhino-Laryngology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
3 Department of surgery Central Hospital Benin, Benin City, Edo State, Nigeria

Date of Acceptance23-Jan-2012
Date of Web Publication12-Dec-2012

Correspondence Address:
G Obasikene
E. N. T Division, Irrua Specialist Teaching Hospital, P. M. B. 008, Edo State
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1119-3077.104527

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Background : Ototoxicity refers to damage of the cochlea and/or vestibular apparatus from exposure to chemical substances, resulting in hearing impairment and or disequilibrium. An earlier study carried out at University of Benin Teaching Hospital (UBTH) in 2000 implicated chloramphenicol as the commonest ototoxic drug, followed by antimalarials (Quinine).
Aim: To identify the commonly implicated drugs in patients diagnosed with ototoxicity in Ear, Nose and Throat (ENT) Clinic of UBTH.
Materials and Methods: One-hundred and three patients' case notes, diagnosed as having ototoxicity, between June 2005 and July 2010 at the ENT Clinic of UBTH were reviewed. Seventy-nine cases met the criteria for diagnosis of ototoxicity in this study.
Results: Intravenous quinine (19.0%) was the commonest implicated drug, followed by oral chloroquine (6.3%), antihypertensive drugs (nifedipine, moduretics, artenolol [6.3%]), native herbal medicine (13.9%), chloramphenicol (1.3%), and unidentifiable drugs accounted for 53.2%. Most patients had severe to profound hearing loss at 4000 Hz and at 8000 Hz. Tinnitus was found in 84.8% of the patients.
Conclusion: Quinine is still the commonest implicated ototoxic drug in this part of the country.

Keywords: Hearing loss, ototoxicity, prevalence

How to cite this article:
Obasikene G, Adobamen P, Okundia P, Ogusi F O. Prevalence of ototoxicity in University of Benin Teaching Hospital, Benin city: A 5-year review. Niger J Clin Pract 2012;15:453-7

How to cite this URL:
Obasikene G, Adobamen P, Okundia P, Ogusi F O. Prevalence of ototoxicity in University of Benin Teaching Hospital, Benin city: A 5-year review. Niger J Clin Pract [serial online] 2012 [cited 2022 Dec 3];15:453-7. Available from:

   Introduction Top

Ototoxicity refers to damage of the cochlea and/or vestibular apparatus from exposure to chemical substances, resulting in hearing impairment and/or disequilibrium. Ototoxicity may be reversible or irreversible. It is different from neurotoxicity where the site of action of the drug is on the central nervous system (i.e. on the cranial nerve VIII). Ototoxicity came to forefront in 1944 when streptomycin was discovered to have caused hearing and vestibular disequilibrium in patients where it was used to treat tuberculosis (Kahlmet 1984). [1] Quinine therapy was also found to be associated with hearing loss, tinnitus, and disequilibrium for more than two centuries. [2] Since then, other drugs like aspirin, calcium channel blockers, moduretic, cisplatin, etc, were added onto the ototoxic drug list. [3],[4],[5],[6] [Table 1]. The mechanism of oto- and vestibular toxicity has been elusive. Mechanisms for acute and chronic toxicity may be different. Blood quinine levels of 0.2 mg/mL found in pilots who died in aviation accidents suggested that quinine toxicity may have played a causative role. [7] Ototoxic effect of quinine is due to vasoconstriction in the small vessels of the cochlea and stria vascularis. Prolonged administration of high-dose quinine in many patients led to loss of outer hair cells. There may also be an effect on cochlear blood flow. [8]
Table 1: List of drugs causing hearing impairment and/or balance problems

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Aminoglycosides cause selective destruction of the outer hair cells, starting from the basal coil and progressing onto the apex of the cochlea. The incidence of clinical and functional hearing loss due to aminoglycosides has been significantly diminished because some of the newer derivatives have lower ototoxic potential and, perhaps, efficient monitoring of serum levels of drugs has allowed for better dosing schedules. However, the problem is a significant one as they are still widely used in the treatment of serious gram-negative infections as pointed out by Schacht. [9] In 1979, Mukhajee and Mukhajee reported antimalarials as the commonest cause of ototoxicity. [10] However, there is paucity of literature on the prevalence of ototoxicity in Nigeria. In 2000, F. O. Ogisi in a prospective study of 49 patients with ototoxicity at ENT Clinic of University of Benin Teaching Hospital (UBTH) reported that chloramphenicol was the commonest ototoxic drug, incriminated in 43% of their patients. [11]

Aim of the study

To identify the ototoxic drugs currently responsible for ototoxicity at UBTH.

   Materials and Methods Top

This study was a review of patients who presented at UBTH with a history of hearing loss following drug intake. The patients were assessed based on the type of drugs they took and/or were taking within the 3 weeks he or she noticed the hearing loss. The route and the length of period the drug was being taken were also considered. The patient's type and degree of hearing loss were obtained where possible because infants less than 4 years could not give a reliable PTA (pure tone audiometry) response. The illness that resulted in the intake of the accused drug was also reviewed. Out of 6420 patients seen in ENT Clinic of UBTH between June 2005 and July 2010, 103 patients were diagnosed as having ototoxicity. Out of the 103 patients diagnosed as having ototoxicity, only 79 of them met the criteria for this study. Inclusion criteria for this study include patients who presented with sudden or progressive hearing loss of less than 3 weeks' duration following drug intake for any illness and patients who did pure tone audiometry following the hearing loss. However, children below 5 years of age were assessed using distraction test because most of them could not give a reliable pure tone audiometric response. Patients with previous history of hearing impairment from any other cause and patients with incomplete data were excluded from the study.

   Results Top

The results of 79 patients were analyzed. There were 40 males and 39 females. The age ranged from 6 months to 70 years, with a mean age of 31-40 years and STD ± 1.89.The commonest affected age group was 20-30 years (21.5%) while the least affected age was less than 1 year (1.3%) [Figure 1]. Majority of the patients (84.8%) had tinnitus. Others stated either they did not have tinnitus (3.8%) or could not say whether they have tinnitus or not (11.4%). The treatment outcome showed that 82.3% absconded from treatment and 10.1% had no improvement while only 7.6% got better. The commonest implicated drug was quinine (19%) followed by native herbal medicine drugs (13.9%). Other implicated drugs were chloroquine (6.3%), antihypertensives (6.3%), chloramphenicol (1.3%), and others (53.2%). All the patients had severe-to-profound hearing loss on both high and low frequencies.
Figure 1: Age histogram

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   Discussion Top

The study showed that almost all age groups were affected but people in their most productive years of life (15- 49 years) had the highest (51.9%) incidence of ototoxicity, followed by children below 10 years old [Table 2]. [12] The elderly patients and infants below 1 year were the least affected though assessing the type and degree of hearing loss in patients of less than 4 year was difficult, especially without otoacoustic emission. In this study, children of less than 4 years were assessed by verbal speech and distraction method.
Table 2: Age frequency

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The commonest illness that necessitated the intake of the offending drug was malaria, followed by febrile illness. However, most of the diagnoses and treatment were made in peripheral hospitals and by non-experts. All patients in this study live in a malaria endemic area. Young adults are known to suffer drug-resistant malaria compared to infants). [13] Other studies also showed that young adults are worst hit by malaria. [14],[15] It has been documented that about 95-99% of the adult population carry the malaria parasite with less than 30% of this number coming down with illness. [16] This could partially explain the higher incidence of ototoxicity seen in young adults. The commonest implicating substance in our study was intravenous quinine [Table 3]. In 2000, a similar study by Ogisi et al. in the same center revealed quinine to be the 2 nd most common cause of ototoxicity after chloramphenicol. [11] During that period, typhoid fever was treated most commonly with chloramphenicol. Today, because of the awareness of the ototoxicity and other side effects of the drug, it has been replaced by ciprofloxacin and other safer antibiotics.
Table 3: Frequency of implicated drugs

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This study, however, found quinine to be the commonest offending drug, which is not unexpected in a malaria endemic area like Nigeria, especially where quinine is mostly used in the treatment of resistant and cerebral malaria. [17] Tinnitus was present and bilateral in 84.8% of all the patients [Table 4]. Tinnitus is one of the commonest side effects of quinine, which is the most common drug used in treatment of drug-resistant malaria. Because only 19% of patients in this study took quinine, other drugs are also implicated for this high percentage of tinnitus noted in the study.
Table 4: Frequency of tinnitus

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One of the major determinants for choice of treatment is the most affordable drugs, usually not the safest. [18] Quinine being one of the most available and affordable drugs, when other cheap drugs for resistant malaria have failed, will continue to dominate in the hands of non-medical experts for treatment of resistant malaria. It has also been reported that sub-standard drugs are readily available. In a study in two developing countries for instance, of 96 samples of chloroquine collected from Nigeria and Thailand for analysis, the results indicated that 36.5% were sub-standard. [19] Not only does this imply discrepancies in clinical studies, but this may, in itself, be a cause of ototoxicity in developing countries. The 53% who had no idea of the drugs given to them and could not fix their hearing loss to any cause may be due to the problems of a developing country [Table 5]. This problem includes low or no education, which denies an individual the power to know, lack of funds or facility to diagnose or seek medical attention, and patients having little or no knowledge of the drugs given to him. [20],[21],[22] 13.9% were on native herbal medicine. Herbal medicine was introduced into National Health Service (NHS) many years ago. It started when the Royal London Homeopathic Hospital (RLHH), founded in 1849, joined the National Health Service (NHS) at its inception in 1948 and became part of University College Hospitals NHS Foundation Trust (UCLH), one of the UK's leading academic medical centers, in 2003. Despite its title, it offers a range of complementary medicine (CM) services, not only homeopathy. Until around 1980, it was a small general hospital with a specialist homeopathic department. The surgical and other facilities were replaced by a range of CM services including the NHS's first complementary cancer (1960), acupuncture (1977), autogenic training (1986), musculoskeletal (1993), herbal medicine services (2008), and others. [23] Many people mistakenly think that all medicinal herbs, being natural, are generally safe and free from undesirable side effects while acting as an effective agent. However, very often, herbs may interact with medications that result in adverse effects. The use of herbal medicine is still poorly understood by the public. Nowadays, toxicity and safety of medicinal herbs is one of the most discussed topics as herbal products have become popular in the developed and developing countries.
Table 5: Treatment outcome Frequency

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More research work is needed on ototoxic drugs, especially among the 53% who had ototoxicity but were not able to identify the drugs they were given. 6.3% of both antihypertensives and chloroquine and the 1.3% of the chloramphenicol are equally of great importance, considering the population on these drugs and at the risk of developing ototoxicity. These drugs are also in the ototoxic drug list. [24] Over 80% of patients were lost to follow-up; this could be because they were not getting better or that they could not afford the cost of their treatment. The severe-to-profound hearing loss seen in all the patients could also be attributed to the problems of the developing world where medical attention is not sort on time because of lack of funds and unavailability of specialists in many places.

   Conclusion Top

Quinine has been found to be the commonest ototoxic drug in our environment. As part of a health campaign to prevent quinine ototoxicity, quinine should be prescribed with caution, and if possible, with audiometric and quinine serum level monitoring. There should be a drug policy guiding the dosage prescription and potency of herbal drugs. Above all, the side effects of herbal drugs must be specified on the drug container. There should be an unrelenting effort to get the best alternative to drugs with unavoidable severe side effects and a health policy that can give everybody the opportunity of receiving good health care, irrespective of the patients' financial status. Also, a massive health campaign on side effects of drugs and herbal medicine should be made to all primary healthcare providers, patent medicine dealers, herbalists, homeopaths, and pharmacists.

   References Top

1.Walter E. Heck, MD; H. Corwin Hinshaw, MD; Harry G. and Parsons, MD. Auditory Ototoxicity in Tuberculosis Patients Treated with Dihydrostreptomycin A Report of the Incidence of Hearing Loss in a Series of 1,150 Cases. JAMA. 1963;186:18-20.   Back to cited text no. 1
2.Buszman E, Wrzesniok D, Matusinski B. Ototoxic drugs. I. Aminoglycoside antibiotics. Wiad Lek 2003;56:254-9.  Back to cited text no. 2
3.Jung TT, Rhee CK, Lee CS, Park YS, Choi DC. Ototoxicity of salicylate, nonsteroidal antiinflammatory drugs, and quinine. Otolaryngol Clin North Am 1993;26:791-810.  Back to cited text no. 3
4.Hayes DM, Cvitkovic E, Globey RB, Scheiner E, Helson L, Krakoff IH. High dose cis-platum diammine dichloride: amelioration of renal toxicity by mannitol diuresis. Cancer 1977;39:1372-81.  Back to cited text no. 4
5.Jarvis JE. A case of unilateral permanent deafness following acetylsalicylic acid. J Laryngol Otol 1966;80:318-20.  Back to cited text no. 5
6.Maher JF, Schreiner JE. Studies on ethacrynic acid in patients with refractory edema. Ann Intern Med 1965;62:15-29.  Back to cited text no. 6
7.Balfour AJ. The bite of Jesuits' bark. Aviat Space Environ Med 1989;60:A4-5.  Back to cited text no. 7
8.Lee CS, Heinrich J, Jung TT. Quinine-induced ototoxicity: Alterations in cochlear blood flow. Otolaryngol Head Neck Surg 1992;107:233.  Back to cited text no. 8
9.Schacht J. Biochemical Basis of Aminoglycoside Ototoxicity. In: Rybak LP, editor. Ototoxicity. The Otolaryngologic Clinics of North America. Philadelphia: W.B. Saunders; 1993. p. 845-56.  Back to cited text no. 9
10.Mukherjee, DK, Mukherjee K. Ototoxicity of commonly used pharmaceutical preparations. Niger Med J 1979;9:52-7.  Back to cited text no. 10
11.Ogisi FO. Chloramphenicol induced Hearing loss. Niger J Surg Res 2001;3:75-80.  Back to cited text no. 11
12.Sharma P, Swarup D, Saxena GN, Bhandari S, Sharma UB, Tuteja R. An open study to evaluate the efficacy of artemether in severe falciparum malaria. J Assoc Physicians India 1999;47:883-5.  Back to cited text no. 12
13.Dodoo D, Theander TG, Kurtzhals JA, Koram K, Riley E, Akanmori BD, et al. Levels of antibody to conserved parts of Plasmodium falciparum merozoite surface protein 1 in Ghanaian children are not associated with protection from clinical malaria. Infect Immun 1999;67:2131-7.  Back to cited text no. 13
14.Maude RJ, Dondoro AM, Faiz MA, Yanus EB, Samad R, Hossain A, et al. Malaria in southeast Bangladesh. A descriptive study. Bangladesh Med Res Counc Bull 2008;34:87-9.  Back to cited text no. 14
15.Sagara I, Sangaré D, Dolo G, Guindo A, Sissoko M, Sogoba M, et al. A high malaria reinfection rate in children and young adults living under a low entomological inoculation rate in aperiurban area of bamako, mali. Am J Trop Med Hyg 2002;66:310-3.  Back to cited text no. 15
16.Coker HA, Chukwuani CM, Ifudu ND, Aina BA. The malaria scourge: Concepts in disease management. Niger J Pharmacol 2001;32:19-46.  Back to cited text no. 16
17.White, N.J.; Looareesuwan, S.; Warrell, D.A.; Warrell, M.J.; Bunnag, D.; Harinasuta, T. Quinine pharmacokinetics and toxicity in cerebral and uncomplicated Falciparum malaria. Am. J. Med. 1982, 73, 564-572.  Back to cited text no. 17
18.World Health Organization. Strategies for prevention of hearing impairment from ototoxic drugs. Report of a WHO informal consultation. WHO/PDH/95.2. Geneva: World Health Organization; 1994.  Back to cited text no. 18
19.Shakoor O, Taylor RB, Behrens RH. Assessment of the incidence of substandard drugs in developing countries. Trop Med Int Health 1997;2:839-45.  Back to cited text no. 19
20.World Health Organization. Prevention of blindness and deafness. Report of the ninth meeting of the WHO Alliance for the Global Elimination of Blinding Trachoma. WHO/PBD/GET/05.1. Geneva: World Health Organization, 2005.  Back to cited text no. 20
21.Rajan N Patel. Deafness Caused by Ototoxicity in Developing Countries. Community ear and hearing health: 2006; 3: 18-22  Back to cited text no. 21
22.Schacht J, Hawkins JE. Sketches of otohistory. Part 11 Ototoxicity: drug-induced hearing loss. Audiol Neurootol 2006;11:1-6.  Back to cited text no. 22
23.Fisher P. The Royal London Homoeopathic Hospital: Dimensions of integration. Eur J Integr Med 2009;1:167-8.  Back to cited text no. 23
24.Joerg G. PDR for Herbal Medicines. 2 nd ed. Montvale, New Jersey: Thomson PDR. ISBN: 1563633612; 2000.  Back to cited text no. 24


  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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