Malignant otitis externa is a potentially fatal infection of the external auditory canal. This condition was originally described by Chandler in 1968 (Chandler 1968) and is also known as necrotising external otitis (Kraus 1988). Diagnosis is made upon clinical, microbiological and radiological grounds. For the purpose of this review, we define malignant otitis externa broadly as "a necrotising infection of the external ear canal including surrounding soft tissue and bone" (Hickham 1996).
Patients with this condition are typically elderly, diabetic men but other groups have been described (Giamarellou 1992). The precise aetiology of this condition is unknown, but theories related to altered host immunity, local tissue microangiopathy (Doroghazi 1981) and even altered cerumen biochemistry (Driscoll 1993) have been proposed. The disease originates in the external auditory canal and spreads through the osteocartilaginous junction to involve the soft tissues beneath the temporal bone. Initially osteomyelitis of the skull base ensues, followed by involvement of the facial and other cranial nerves. Malignant otitis externa is also complicated by parotitis, mastoiditis, jugular vein thrombosis, meningitis and death (Giamarellou 1992). Diagnosis is made on clinical grounds and is suspected in any diabetic or immunocompromised patient with pseudomonal otitis externa, especially when pain is a prominent feature. Technicium bone scanning has been described as the single most useful diagnostic tool (Parisier 1982), but other forms of radiological imaging play a role in indicating disease progression (Hickham 1996). The mortality for this condition has been reported to be as high as one-third (Chandler 1972), but when cranial nerves are affected it may be as high as 80% (Aldous 1973).
Traditionally the mainstay of treatment for malignant otitis externa has been prolonged antibiotic therapy (Strauss 1982), stringent diabetes control (Resouly 1982), repeated debridement of necrotic tissue and sometimes aggressive surgical management (Reines 1980). Hyperbaric oxygen is gradually gaining acceptance as a beneficial adjunctive therapy and has been recommended whenever a therapeutic pressure chamber is available (Shupak 1989). There are 24 centres offering such facilities in the United Kingdom. Hyperbaric oxygen is available for and currently being used in the treatment of many other medical conditions. Hyperbaric oxygen treatment is the administration of 100% oxygen for respiration at pressures above 1 atmosphere absolute (ATA). Hyperbaric oxygen treatment involves placing the patient in a compression chamber, increasing the environmental pressure within the chamber and administering 100% oxygen for respiration. In this way, it is possible to deliver a greatly increased partial pressure of oxygen to the tissues. Typically, treatments involve pressurisation to between 2 and 3 atmospheres absolute (ATA) for periods between 60 and 120 minutes once or twice daily. A typical course might involve 15 to 30 such treatments (HMP 1994). In the United Kingdom, 30 sessions of hyperbaric oxygen would typically cost GBP 3000, i.e. GBP 100 per session or GBP 50 per hour (Laden 2005). Complications and side effects of hyperbaric oxygen treatment include barotraumas to the ear, round window blowout, 'sinus squeeze', visual refractive changes, numb fingers, dental problems, claustrophobia, seizures and pulmonary oxygen toxicity (HMP 1994). In general these effects are either very rare or are only temporary. It is postulated that hyperbaric oxygen treatment works by elevating the oxygen partial pressure from hypoxia to normal or above normal levels, which amplifies the oxygen diffusion gradient into the avascular tissues (Mader 1980). This is a prerequisite for efficient leukocyte function (Hohn 1976) and has been shown to promote fibroblastic division, collagen production and capillary angiogenesis, thus enhancing soft tissue and bone healing (Hunt 1972).
Malignant otitis externa is an uncommon condition associated with significant rates of morbidity and mortality (Shupak 1989). It is important to construct a systematic review to define the role of hyperbaric oxygen fully in the treatment of this condition.
To assess the effectiveness of adjunctive hyperbaric oxygen treatment for malignant otitis externa.
Criteria for considering studies for this review
Types of studies
Randomised controlled trials.
Types of participants
Adults (over 16) with malignant otitis externa.
Types of interventions
Any treatment(s) where hyperbaric oxygen was an adjuvant therapy versus the same treatment(s) alone.
Types of outcome measures
The secondary outcome measures were as follows.
- Time until clinical improvement. This was to be measured by resolution of pain and aural discharge.
- Time until radiological improvement. A variety of radiological techniques exist to measure the course of malignant otitis externa. Our intention was to allow improvement to be measured by whichever technique was deemed appropriate by the authors of the study.
- Recovery from cranial nerve palsies.
Search methods for identification of studies
We conducted systematic searches for randomised controlled trials. There were no language, publication year or publication status restrictions. The date of the last search was 4 April 2013, following previous search updates in 2011, 2008 and 2006.
We searched the following databases from their inception for published, unpublished and ongoing trials: the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3); PubMed; EMBASE; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Science; ISRCTN; ClinicalTrials.gov; ICTRP, Google Scholar and Google.
We modelled subject strategies for databases on the search strategy designed for CENTRAL. Where appropriate, we combined subject strategies with adaptations of the highly sensitive search strategy designed by The Cochrane Collaboration for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2, Box 6.4.b. (Handbook 2011)). Search strategies for major databases including CENTRAL are provided in Appendix 1.
Searching other resources
We scanned the reference lists of identified publications for additional trials and contacted trial authors where necessary. In addition, we searched PubMed, TRIPdatabase, Google and Google Scholar to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials. We searched for conference abstracts using the Cochrane Ear, Nose and Throat Disorders Group Trials Register.
Data collection and analysis
Selection of studies
The two review authors reviewed the articles found by the searches independently to identify studies of the types outlined above. We intended to resolve any disagreement by discussion. Should this have failed to resolve the disagreement then the final decision was to be made by JP.
Data extraction and management
We planned to extract data onto standardised, pre-piloted forms.
Assessment of risk of bias in included studies
Assessment of the risk of bias of the included trials was to be undertaken independently by the two review authors, with the following taken into consideration, as guided by the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011):
- sequence generation;
- allocation concealment;
- incomplete outcome data;
- selective outcome reporting; and
- other sources of bias.
We planned to use the Cochrane 'Risk of bias' tool in RevMan 5 (RevMan 2012), which involves describing each of these domains as reported in the trial and then assigning a judgement about the adequacy of each entry: low, high or unclear (or unknown) risk of bias.
We planned to perform statistical analysis using Review Manager 5. For dichotomous outcomes we would have calculated a risk ratio (RR). We intended to use a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes as appropriate. We were to use a fixed-effect model where non-significant heterogeneity was found between studies. We were to use a random-effects model where great heterogeneity in studies was found.
We planned subgroup analysis of the following patient characteristics:
- patients presenting with or without cranial nerve palsies;
- patients presenting with or without diabetes.
We would have used study quality for sensitivity analyses.
Should trials be included in future updates of this review, we will apply these data collection and analysis methods.
Description of studies
We identified no randomised controlled trials through the original searches for this review in 2004, nor at any of the update searches 2006, 2008, 2011 and 2013.
Risk of bias in included studies
Effects of interventions
Using our search strategy we identified some relevant articles. None fulfilled the requirements of our protocol. We retrieved them in order to search the bibliographies for other articles which might fulfil our inclusion criteria, but we identified no further articles using this method. We could therefore enter no data for analysis.
No randomised controlled trials were identified by our search strategy. The quality of the data identified was therefore not adequate to allow further discussion. We will, however, briefly describe the types of studies identified by our search strategy.
We found four case reports (Bath 1998; Lancaster 2000; Mader 1982; Shupak 1989) and five case series (Davis 1992; Lucente 1982; Lucente 1983; Robinson 1994; Tisch 2003), which included a total of 73 patients. These articles described the use of hyperbaric oxygen as adjuvant therapy with antibiotics in the majority of cases. In general, most regimens used 20 to 40 doses of hyperbaric oxygen treatment. Each treatment was of 90 minutes duration at 2.5 atmospheres absolute (ATA). Alternative regimens differed very little. There was no mention of any complications related to hyperbaric oxygen treatment.
Implications for practice
The quality of the studies identified by our literature search was poor, lacking randomisation or other controls. In view of this the effectiveness of treatment with hyperbaric oxygen therapy compared with treatment with antibiotics and surgical debridement could not be statistically assessed in this review.
Implications for research
Our findings demonstrate the need for a well-designed, randomised controlled trial to compare hyperbaric oxygen therapy with standard therapy. Any future trials would need to consider in particular the following.
With thanks to Jenny Bellorini, Carolyn Dorée and Annette Foley for their assistance with this review.
Dr Michael Bennett MB BS, FANZCA, Dip DHM
Department of Diving and Hyperbaric Medicine
Prince of Wales Hospital
Randwick NSW 2031
Mr Gerard Laden
Technical and Research Director
Hull Hyperbaric Unit
Hull and East Riding Hospital
Data and analyses
This review has no analyses.
Appendix 1. Search strategies
Last assessed as up-to-date: 4 April 2013.
Protocol first published: Issue 1, 2004
Review first published: Issue 2, 2005
Contributions of authors
JP - lead review author, protocol development, design of search strategy, review preparation, quality assessment, data extraction and analysis.
SJ - protocol development, review preparation, quality assessment, data extraction and analysis.
Declarations of interest
Sources of support
- None, Not specified.
- None, Not specified.
Differences between protocol and review
Should studies be included in future updates of this review we will now use The Cochrane Collaboration's 'Risk of bias' method for the assessment of study quality, as guided by the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011).
Medical Subject Headings (MeSH)
MeSH check words