Eur Arch Otorhinolaryngol DOI 10.1007/s00405-015-3845-9
OTOLOGY
Otological complications associated with hyperbaric oxygen therapy Yoko Yamamoto1 • Yoshihiro Noguchi1,2 Ken Kitamura1
•
Mitsuhiro Enomoto3 • Kazuyoshi Yagishita3 •
Received: 20 September 2015 / Accepted: 25 November 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract The objective of the present study was to clarify the features of otological complications for hyperbaric oxygen therapy (HBOT) and the risk factors for these complications. We enrolled 1115 patients (776 males and 339 females; age 5–89 years) who underwent HBOT. All otological symptoms experienced during HBOT sessions were evaluated, and risk factors were analysed using multivariate logistic regression analysis. Otoscopic findings and interventions for otological complications were assessed in 58 symptomatic patients who visited the Otolaryngology Department. Otological symptoms were experienced by 165 (14.8 %) of the 1115 patients. The multivariate logistic regression analysis identified ages of [60 years and female sex as independent risk factors, whereas patients with sports injuries were at lower risk than those with other primary diseases, except for severe infectious disease. Eighty-two patients (49.7 %) suffered from symptoms at the first HBOT session. The most prevalent symptoms were otalgia (157/165), followed by ear fullness (13/165), hearing loss (12/165) and tinnitus (3/ 165). One patient experienced vertigo and deterioration of the bone-conduction pure-tone thresholds, suggesting inner ear barotrauma. In 116 ears of the 58 symptomatic patients, abnormal otoscopic findings were recognized in 58 ears
& Yoshihiro Noguchi [email protected] 1
Department of Otolaryngology, Tokyo Medical and Dental University, Tokyo, Japan
2
Department of Hearing Implant Sciences, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
3
Hyperbaric Medical Center, Tokyo Medical and Dental University, Tokyo, Japan
(50.0 %). Twenty-seven of the 58 ears required myringotomy or tube insertion, and HBOT was stopped in eight ears in four patients. Of the remaining 58 ears with normal otoscopic findings, 51 received no treatment. Physicians should be aware of both middle and inner ear barotrauma as potential complications of HBOT. Keywords Complication Hyperbaric oxygen therapy Barotrauma Ear Vertigo Multivariate logistic regression analysis
Introduction Hyperbaric oxygen therapy (HBOT) is a treatment in which the patient breathes 100 % oxygen intermittently while inside a treatment chamber at a pressure higher than that observed at sea level (one atmosphere absolute, ATA). HBOT produces combined effects on immunity, oxygen transport and haemodynamics, thus reducing hypoxia and oedema and enabling normal host responses to infection and ischaemia [1]. Indications for this treatment include air or gas embolism, carbon monoxide poisoning, decompression sickness, severe infection and idiopathic sudden sensorineural hearing loss (ISSNHL). HBOT is a relatively safe therapy [1]; however, it is associated with various complications, including (1) oxygen toxicity and (2) barotrauma to the middle and/or inner ear, paranasal sinuses, teeth and lungs. Although several techniques, such as the Valsalva manoeuvre, Toynbee manoeuvre, swallowing and movement of the jaw from side to side, can be applied to prevent ear barotrauma [2], middle ear barotrauma reportedly occurs at a frequency of 8.9–66.7 % in patients who receive HBOT [3–14]. Inner ear barotrauma may be caused by round and/or oval
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Eur Arch Otorhinolaryngol
window rupture, leading to the sudden onset of hearing loss, tinnitus, vertigo and/or dizziness, although this complication has not been reported in hyperbaric medicine practice [2]. Complications associated with HBOT, including middle ear barotrauma, have been reported in the literature. However, only one previous study enrolled more than 1000 patients, and further, it did not focus on otological symptoms [13]. In the present study, we conducted a retrospective analysis of the otological complications of HBOT in a large series of 1115 patients. The aims of this study were to clarify the features of these complications and to determine the significant risk factors using multivariate logistic regression analysis.
Methods Patients This study was approved by the Institutional Review Board of Tokyo Medical and Dental University Faculty of Medicine (No. 1552). A flowchart of the study procedure is shown in Fig. 1. A total of 1594 consecutive patients received HBOT at the Hyperbaric Medical Center at our university hospital from January 2010 to December 2012. Among the 1594 patients, 479 individuals with decompression sickness were excluded due to the use of a different HBOT protocol. The remaining 1115 patients (776 males and 339 females) were enrolled in the present study. The patients’ ages ranged from 5 to 89 years (median 46 years; interquartile range 28–65 years).
HBOT protocol HBOT was performed after obtaining written informed consent from each patient. A multiplace chamber (NHC412-A; Nakamura Tekko-Sho Corp., Tokyo, Japan) was pressurized with air up to 2.5 ATA, and the patients breathed 100 % oxygen via a mask delivery system. The duration of each treatment session was 105 min, including 15 min of compression during the starting period and 20 min of decompression during the ending period. The patients were carefully interviewed regarding their medical history and were instructed to communicate any problems, such as otalgia, ear fullness, hearing loss, tinnitus, vertigo, or dizziness to the staff of the Hyperbaric Medical Center. When a problem was experienced, the compression time was prolonged or the HBOT session was stopped. Pulmonary function tests and chest X-ray examinations were performed prior to HBOT, and patients with severe pulmonary disease and/or a history of emphysema were excluded as candidates for HBOT. Vasoconstrictor nasal spray, myringotomy and/or tympanic tube insertion were not applied prior to HBOT. The patients generally underwent HBOT once a day, 5 days a week. The total number of treatment sessions ranged from 1 to 216 (median 7; interquartile range 3–19). Otological symptom analysis The otological symptoms experienced during HBOT sessions were analysed based on the medical charts of the 1115 enrolled patients. An otological symptom was considered to be associated with HBOT if the symptom occurred or deteriorated during the treatment session. In the statistical analyses of factors associated with otological symptoms, we divided the enrolled patients according to the factors of age, gender, total number of HBOT sessions and primary disease. The incidences of detailed otological symptoms, including otalgia, ear fullness, hearing loss, tinnitus, vertigo and dizziness were evaluated in the patients who experienced otological complications. The number of sessions at which the otological symptoms first presented was assessed in each patient. Otoscopic finding and intervention for otological complications
Fig. 1 Diagram showing the flowchart of the study protocol. HBOT hyperbaric oxygen therapy
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The otoscopic findings and interventions for the otological complications were analysed in the patients who visited the otolaryngology department. The otoscopic findings were categorized into six grades according to the TEED grading system [9]. One modification was made for the Grade 0 symptoms and signs: namely, ‘normal tympanic
Eur Arch Otorhinolaryngol
membrane’ was used instead of ‘symptoms with no otological signs’. The interventions included myringotomy, tympanic tube insertion or HBOT cessation. Statistical analysis Statistical analyses were conducted using JMP 11.2 (SAS Institute, Inc., Cary, NC, USA) on a Macintosh computer. The univariate relationships between the independent factors and otological complications were analysed using Pearson’s Chi square test and analysis of an m 9 n contingency table for categorical variables. To test the independence of the risk factors for otological complications, the factors of age, gender, total number of HBOT sessions and primary disease were entered into a multivariate logistic regression model. Odds ratio and their corresponding 95 % confidence intervals were calculated. For all tests, the criterion for statistical significance was a P value of \0.05.
Results Otological complications and their risk factors Otological symptoms occurred in 165 (14.8 %) of the 1115 patients. The incidences of otological symptoms according to the factors of age, gender, total number of HBOT sessions and primary disease are shown in Table 1. Univariate analysis showed significant differences for each factor. Multivariate logistic regression analysis identified ages of [60 years and female sex as independent risk factors for otological complications (Table 2). In contrast, patients with a sports injury were at lower risk than those with other diseases, except for severe infectious disease. No significant difference was found in terms of the total session numbers between B10, 11–29 and C30, which differed from the results of the univariate analysis. Detailed otological symptoms Detailed otological symptoms were examined in 165 patients. The most prevalent symptom was otalgia in 157 patients (95.2 %), followed by ear fullness in 13 patients (7.9 %), hearing loss in 12 patients (7.3 %), tinnitus in three patients (1.8 %) and vertigo in one patient (0.6 %). The symptoms occurred at the first HBOT session in 82 patients (49.7 %), at the second to fifth sessions in 51 patients (30.9 %) and at the sixth to ninth sessions in 16 patients (9.7 %). A 63-year-old female patient experienced vertigo with left otalgia during the seventh HBOT session for her left ISSNHL. She was found to have bilateral abnormal
tympanic membranes categorized as TEED Grade 1. Her air- and bone-conduction pure-tone averages at the frequencies of 0.5, 1, 2 and 4 kHz deteriorated from 58.8 to 83.8 dB and from 53.8 to 68.8 dB in the left ear, respectively. Horizontal nystagmus towards the left was detected using an infrared charge-coupled device camera. Taken together, these findings suggested inner ear barotrauma. HBOT was stopped; however, her hearing loss persisted. Otoscopic findings and interventions for otological complications Otoscopic findings and interventions for otological complications were evaluated in 58 patients of the 165 patients with otological symptoms. None of the patients had a previous history of ear surgery and/or chronic otitis media. The symptoms were in the bilateral ears in 15 patients (25.8 %), the right ear in 15 patients (25.8 %), the left ear in 15 patients (25.8 %) and the side was unknown in 13 patients (22.4 %). The otoscopic findings of the 116 ears in the 58 patients are shown in Table 3. Among 60 ears with otological symptoms, a normal tympanic membrane categorized as Grade 0 was detected in 13 ears (21.7 %). Among the 30 ears without symptoms, an abnormal tympanic membrane was detected in seven ears (23.3 %). Of the 13 patients who exhibited otological symptoms for which the side was unknown, 10 patients showed bilateral Grade 0 tympanic membranes, one patient showed bilateral Grade 3 tympanic membranes and the remaining two patients showed a unilateral Grade 1 tympanic membrane. In total, 58 (50.0 %) of the 116 ears demonstrated abnormal otoscopic findings; however, no ears were classified as having a Grade 5 tympanic membrane. The interventions for the otological complications are shown in Fig. 2. Among the 58 ears with a Grade 0 TEED score, no treatment was performed in 51 ears (87.9 %), five ears (8.6 %) underwent myringotomy or tympanic tube insertion and HBOT was stopped in one patient with bilateral otological complications. In contrast, among the 58 ears with a Grade 1–4 TEED score, 27 ears (46.6 %) required myringotomy or tube insertion, while four patients stopped receiving HBOT in both ears (13.8 %) and no treatment was performed in 23 ears (39.7 %). A small perforation of the tympanic membrane persisted in two of the 32 ears treated with myringotomy or tube placement.
Discussion Middle ear barotrauma was the most common complication of HBOT in the present study. Table 4 summarizes the otological complications of HBOT noted in previous
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Eur Arch Otorhinolaryngol Table 1 Incidence of otological symptoms according to the factors of age, gender, total HBOT session number and primary disease
Factors
Patients with otological symptoms No.
P value
%
Age (years)
0.000
\20 (n = 44)
6
13.6
20–60 (n = 713)
71
10.0
[60 (n = 358)
88
24.6
Male (n = 776)
84
10.8
Female (n = 339)
81
23.9
B10 (n = 698)
74
10.6
11–29 (n = 281)
61
21.7
30
22.1
9
2.6
Gender
0.000
Number of HBOT sessions
0.000
C30 (n = 136) Disease
0.000
Sports injury (n = 346) ISSNHL (n = 169)
42
24.9
Osteomyelitis (n = 103)
18
17.5
Spinal cord injury/nerve root disease (n = 92)
17
18.5
Peripheral vascular disease (n = 74)
15
20.3
Carbon monoxide poisoning (n = 56) Haemorrhagic cystitis/proctitis (n = 53) Radiation-induced osteomyelitis/necrosis (n = 28) Severe infectious disease (n = 27) Others (n = 167)
8
14.3
18
34.0
5
17.9
4
14.8
29
17.4
HBOT hyperbaric oxygen therapy, ISSNHL idiopathic sudden sensorineural hearing loss
Table 2 Multivariate logistic regression analysis results: significant risk factors associated with HBOT
Factors
Reference category
Odds ratio (95 % CI)
P value
20–60
1.7 (1.2–2.5)
0.004
Male
1.8 (1.2–2.5)
0.002
Age (years) [60 Gender Female Disease ISSNHL
Sports injury
7.7 (3.6–17.9)
0.000
ISSNHL
Others
1.7 (1.0–3.0)
0.049
Osteomyelitis
Sports injury
4.2 (1.7–10.8)
0.002
Spinal cord injury/nerve root disease
Sports injury
5.0 (2.1–12.7)
0.000
Peripheral vascular disease
Sports injury
5.1 (2.0–13.7)
0.000
Carbon monoxide poisoning
Sports injury
4.3 (1.5–12.2)
0.007
Haemorrhagic cystitis/proctitis
Sports injury
8.8 (3.2–24.9)
0.000
Radiation-induced osteomyelitis/necrosis Others
Sports injury Sports injury
4.1 (1.1–14.2) 4.5 (2.0–10.8)
0.039 0.000
CI confidence interval
reports [3–16]. The incidence of otological symptoms ranges widely, from 8.9 to 66.7 %. Ambiru et al. [13] mentioned several possible reasons for the variation in the complication rates, including (1) differences in population and the characteristics of the patients, (2) differences in the
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definitions of complications in terms of severity and (3) differences in the HBOT protocol and the chamber type (monoplace or multiplace chamber). In the present study, all patients were informed regarding possible symptoms and complications, including otalgia, ear fullness, hearing
Eur Arch Otorhinolaryngol Table 3 Modified TEED’s score grading and ear numbers (%) Grade
Symptoms and signs
Ear with symptom (n = 60 ears)
Ear without symptom (n = 30 ears)
Ear with or without symptoma (n = 26 ears)
Total (n = 116 ears)
0
Normal tympanic membrane
13 (21.7)
23 (76.7)
22 (84.6)
58 (50.0)
1
Diffuse redness and retraction of the tympanic membrane
13 (21.7)
3 (10.0)
2 (7.7)
18 (15.5)
2 3
Grade 1 plus slight haemorrhage within the tympanic membrane Grade 1 plus gross haemorrhage within the tympanic membrane
7 (11.7) 19 (31.7)
2 (6.7) 2 (6.7)
0 (0.0) 2 (7.7)
9 (7.8) 23 (19.8)
4
Dark and slightly bulging tympanic membrane due to free blood in the middle ear, fluid may be present
8 (13.3)
0 (0.0)
0 (0.0)
8 (6.9)
5
Free haemorrhage into the middle ear, with tympanic membrane perforation; blood may be seen outside or within the external auditory canal
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
a
An ear of a patient who had an otological symptom for which the side was unknown
Fig. 2 Interventions for barotrauma according to the TEED score. Of the 58 ears with a Grade 0 TEED score, no treatment was performed in 51 ears (87.9 %). In contrast, of the 58 ears with a Grade 1–4 TEED score, 27 ears (46.6 %) required myringotomy or tube insertion and eight ears (13.8 %) in four patients stopped receiving HBOT. HBOT hyperbaric oxygen therapy
loss, tinnitus, vertigo and dizziness and were instructed to let the medical staff know if and when any of these symptoms occurred. Consequently, the incidence of detailed otological symptoms could be clarified in our large study population of more than 1000. Otological symptoms occurred at the first session in approximately 50 % of the patients and during the first to fifth sessions in 80 % of the patients in the present study. These findings are consistent with those of previous reports [7, 8]. The performance of an otoscopic examination immediately after the first HBOT session is thought to be useful for predicting ear barotrauma [12]. Although it may be challenging to carry out such examinations in all patients undergoing HBOT, a good cooperative relationship between the Departments of Hyperbaric Medicine and Otolaryngology is essential.
Patients with radiation-induced injuries to the head and neck area are reportedly at high risk for otological complications [10, 16]. Other possible risk factors include female sex [7], older age [8], abnormal findings on anterior rhinoscopy or X-rays of the paranasal sinuses [4] and the presence of an artificial airway (endotracheal or tracheostomy tube) [5]. Although conflicting observations have been reported with respect to age and sex [4, 14], the multivariate logistic regression analysis in the present study identified age of [60 years and female sex as independent risk factors. With regard to primary disease, a previous study using multivariate logistic regression analysis noted that peripheral circulatory disorders with refractory ulcers and non-healing wounds are independent risk factors [13]. In the present study, patients with sports injuries were found to be at low risk for otological complications. Although the reason was unclear, most of our patients with sports injuries are top athletes and had no trouble with general conditions. Some of these patients were accustomed to the Valsalva manoeuvre because they had received HBOT for previous sports injuries. In otoscopic examinations, no ears showed tympanic membrane perforation categorized as TEED Grade 5, which is an extremely rare observation [4, 6, 9, 16, 18]. In contrast, abnormal otoscopic findings were recognized in the asymptomatic ears at an incidence of 23.3 %. Igarashi et al. [4] found that the rate of middle ear barotrauma assessed on otoscopic examination is higher than that assessed based on clinical symptoms. Taken together, the possibility of ear barotrauma cannot be excluded even if the patient does not complain of symptoms. The most reliable method for preventing ear barotrauma is tympanic tube insertion. In the present study, myringotomy, tympanic tube insertion and/or cancellation of the HBOT were performed in seven ears (12.1 %) with TEED Grade 0 tympanic membranes and 35 ears (60.3 %) with
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Eur Arch Otorhinolaryngol Table 4 Summary of otological complications of HBOT from previous studies Year (reference no.)
Total patient no.
Patients with otological symptoms
Detailed otological symptoms
No.
Otalgia
%
Ear fullness
1992 [15]
33
8
27
1992 [3]
60
39
65.0
15
29
1993 [4] 1994 [5]
67 267
36 131
53.7 49.1
31
23
1996 [16]
82
30
1997 [6]
30
18
60.0
1999 [7]
111
35
31.5
2000 [8]
782
139
17.8
2006 [9]
42
17
40.0
2006 [10]
325
50
15.4
2006 [11]
111
43
38.7 66.7
2008 [12]
18
12
2008 [13]
1609
143
8.9
2010 [14]
130
18
13.6
1115
165
14.7
Present study
35
34
157
13
Hearing loss
Tinnitus
12
3
2
2
12
3
Vertigo/dizziness
1
HBOT hyperbaric oxygen therapy
TEED Grades 1–4 tympanic membranes. Moreover, Clements et al. [17] retrospectively analysed complications occurring secondary to tympanic tube insertion in 45 patients undergoing HBOT and reported that 17 (38 %) of the patients experienced otorrhoea, otalgia, hearing loss and/or persistent tympanic membrane perforations. In our series, two ears demonstrated persistent tympanic membrane perforation. Therefore, the insertion of a tympanic tube should be considered in selected patients, such as those with radiation-induced injuries to the head and neck area, an artificial airway or severe eustachian tube dysfunction. Inner ear barotrauma is a possible complication of HBOT. Beuerlein et al. [6] used distortion-product otoacoustic emissions (DPOAEs) to evaluate whether they can provide information regarding subtle cochlear injury. The authors found a significant change in the DPOAE amplitudes without parallel changes on conventional audiometry in six of 22 patients. However, no patients with apparent inner ear barotrauma have been reported [2]. In the present study, one (0.1 %) of the 1115 patients experienced deterioration of their hearing with otalgia and abnormal tympanic membranes, as well as vertigo with horizontal nystagmus to the side of the deteriorated ear, which is suggestive of inner ear barotrauma. Therefore, all medical staff should remain aware that inner ear barotrauma, although extremely rare, is a possible complication of HBOT. Some of the limitations associated with the present study include the fact that no patients underwent X-ray
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examinations of the paranasal sinuses or eustachian tube function testing prior to HBOT, and that few of the symptomatic patients visited the Otolaryngology Department. Therefore, further prospective study is needed to increase the understanding around the otological complications of HBOT.
Conclusion Ear barotrauma is the most common complication of HBOT and was detected in 165 (14.8 %) of the 1115 patients in the present study. In addition, inner ear barotrauma, which has not been reported previously, was detected in one patient (0.1 %). Hence, a good cooperative relationship between the Departments of Hyperbaric Medicine and Otolaryngology is indispensable for reducing the incidence of otological complications associated with HBOT. Compliance with ethical standards Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Gill AL, Bell CN (2004) Hyperbaric oxygen: its uses, mechanisms of action and outcomes. QJM 97:385–395 2. Hamilton-Farrell M, Bhattacharyya A (2004) Barotrauma. Injury 35:359–370
Eur Arch Otorhinolaryngol 3. Carlson S, Jones J, Brown M, Hess C (1992) Prevention of hyperbaric-associated middle ear barotrauma. Ann Emerg Med 21:1468–1471 4. Igarashi Y, Watanabe Y, Mizukoshi K (1993) Middle ear barotrauma associated with hyperbaric oxygenation treatment. Acta Otolaryngol Suppl 504:143–145 5. Presswood G, Zamboni AZ, Stephenson LL, Santos PM (1994) Effect of artificial airway on ear complications from hyperbaric oxygen. Laryngoscope 104:1383–1384 6. Beuerlein M, Nelson RN, Welling DB (1997) Inner and middle ear hyperbaric oxygen-induced barotrauma. Laryngoscope 107:1350–1356 7. Fitzpatrick DT, Franck BA, Mason KT, Shannon SG (1999) Risk factors for symptomatic otic and sinus barotrauma in a multiplace hyperbaric chamber. Undersea Hyperb Med 26:243–247 8. Plafki C, Peters P, Almeling M, Welslau W, Busch R (2000) Complications and side effects of hyperbaric oxygen therapy. Aviat Space Environ Med 71:119–124 9. Vahidova D, Sen P, Papesch M, Zein-Sanchez MP, Mueller PH (2006) Does the slow compression technique of hyperbaric oxygen therapy decrease the incidence of middle-ear barotrauma? J Laryngol Otol 120:446–449 10. Fiesseler FW, Silverman ME, Riggs RL, Szucs PA (2006) Indication for hyperbaric oxygen treatment as a predictor of tympanostomy tube placement. Undersea Hyperb Med 33:231–235 11. Muller-Bolla M, Collet JP, Ducruet T, Robinson A (2006) Side effect of hyervaric oxygen therapy in children with cerebral palsy. Undersea Hyperb Med 33:237–244
12. Karahatay S, Yilmaz YF, Birkent H, Ay H, Satar B (2008) Middle ear barotrauma with hyperbaric oxygen therapy: incidence and the predictive value of the nine-step inflation/deflation test and otoscopy. Ear Nose Throat J 87:684–688 13. Ambiru S, Furuyama N, Aono M, Otsuka H, Suzuki T, Miyazaki M (2008) Analysis of risk factors associated with complications of hyperbaric oxygen therapy. J Crit Care 23:295–300. doi:10. 1016/j.jcrc.2007.08.002 14. Bessereau J, Tabah A, Genotelle N, Francais A, Coulange M (2010) Middle-ear barotrauma after hyperbaric oxygen therapy. Undersea Hyperb Med 37:203–208 15. Fernau JL, Hirsh BE, Derkey C, Ramasastry S, Schaefer SE (1992) Hyperbaric oxygen therapy: effect on middle ear and eustachian tube function. Laryngoscope 102:48–52 16. Blanshard J, Toma A, Bryson P, Williamson P (1996) Middle ear barotrauma in patients undergoing hyperbaric oxygen therapy. Clin Otolaryngol Allied Sci 21:400–403 17. Clements KS, Vrabec JT, Mader JT (1998) Complications of tympanostomy tubes inserted for facilitation of hyperbaric oxygen therapy. Arch Otolaryngol Head Neck Surg 124:278–280 18. Sloan EP, Murphy DG, Hart R, Cooper MA, Turnbull T, Barreca RS, Ellerson B (1989) Complications and protocol considerations in carbon monoxide-poisoned patients who required hyperbaric oxygen therapy: report from a ten-year experience. Ann Emerg Med 18:629–634
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OTOLOGY
Otological complications associated with hyperbaric oxygen therapy Yoko Yamamoto1 • Yoshihiro Noguchi1,2 Ken Kitamura1
•
Mitsuhiro Enomoto3 • Kazuyoshi Yagishita3 •
Received: 20 September 2015 / Accepted: 25 November 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract The objective of the present study was to clarify the features of otological complications for hyperbaric oxygen therapy (HBOT) and the risk factors for these complications. We enrolled 1115 patients (776 males and 339 females; age 5–89 years) who underwent HBOT. All otological symptoms experienced during HBOT sessions were evaluated, and risk factors were analysed using multivariate logistic regression analysis. Otoscopic findings and interventions for otological complications were assessed in 58 symptomatic patients who visited the Otolaryngology Department. Otological symptoms were experienced by 165 (14.8 %) of the 1115 patients. The multivariate logistic regression analysis identified ages of [60 years and female sex as independent risk factors, whereas patients with sports injuries were at lower risk than those with other primary diseases, except for severe infectious disease. Eighty-two patients (49.7 %) suffered from symptoms at the first HBOT session. The most prevalent symptoms were otalgia (157/165), followed by ear fullness (13/165), hearing loss (12/165) and tinnitus (3/ 165). One patient experienced vertigo and deterioration of the bone-conduction pure-tone thresholds, suggesting inner ear barotrauma. In 116 ears of the 58 symptomatic patients, abnormal otoscopic findings were recognized in 58 ears
& Yoshihiro Noguchi [email protected] 1
Department of Otolaryngology, Tokyo Medical and Dental University, Tokyo, Japan
2
Department of Hearing Implant Sciences, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
3
Hyperbaric Medical Center, Tokyo Medical and Dental University, Tokyo, Japan
(50.0 %). Twenty-seven of the 58 ears required myringotomy or tube insertion, and HBOT was stopped in eight ears in four patients. Of the remaining 58 ears with normal otoscopic findings, 51 received no treatment. Physicians should be aware of both middle and inner ear barotrauma as potential complications of HBOT. Keywords Complication Hyperbaric oxygen therapy Barotrauma Ear Vertigo Multivariate logistic regression analysis
Introduction Hyperbaric oxygen therapy (HBOT) is a treatment in which the patient breathes 100 % oxygen intermittently while inside a treatment chamber at a pressure higher than that observed at sea level (one atmosphere absolute, ATA). HBOT produces combined effects on immunity, oxygen transport and haemodynamics, thus reducing hypoxia and oedema and enabling normal host responses to infection and ischaemia [1]. Indications for this treatment include air or gas embolism, carbon monoxide poisoning, decompression sickness, severe infection and idiopathic sudden sensorineural hearing loss (ISSNHL). HBOT is a relatively safe therapy [1]; however, it is associated with various complications, including (1) oxygen toxicity and (2) barotrauma to the middle and/or inner ear, paranasal sinuses, teeth and lungs. Although several techniques, such as the Valsalva manoeuvre, Toynbee manoeuvre, swallowing and movement of the jaw from side to side, can be applied to prevent ear barotrauma [2], middle ear barotrauma reportedly occurs at a frequency of 8.9–66.7 % in patients who receive HBOT [3–14]. Inner ear barotrauma may be caused by round and/or oval
123
Eur Arch Otorhinolaryngol
window rupture, leading to the sudden onset of hearing loss, tinnitus, vertigo and/or dizziness, although this complication has not been reported in hyperbaric medicine practice [2]. Complications associated with HBOT, including middle ear barotrauma, have been reported in the literature. However, only one previous study enrolled more than 1000 patients, and further, it did not focus on otological symptoms [13]. In the present study, we conducted a retrospective analysis of the otological complications of HBOT in a large series of 1115 patients. The aims of this study were to clarify the features of these complications and to determine the significant risk factors using multivariate logistic regression analysis.
Methods Patients This study was approved by the Institutional Review Board of Tokyo Medical and Dental University Faculty of Medicine (No. 1552). A flowchart of the study procedure is shown in Fig. 1. A total of 1594 consecutive patients received HBOT at the Hyperbaric Medical Center at our university hospital from January 2010 to December 2012. Among the 1594 patients, 479 individuals with decompression sickness were excluded due to the use of a different HBOT protocol. The remaining 1115 patients (776 males and 339 females) were enrolled in the present study. The patients’ ages ranged from 5 to 89 years (median 46 years; interquartile range 28–65 years).
HBOT protocol HBOT was performed after obtaining written informed consent from each patient. A multiplace chamber (NHC412-A; Nakamura Tekko-Sho Corp., Tokyo, Japan) was pressurized with air up to 2.5 ATA, and the patients breathed 100 % oxygen via a mask delivery system. The duration of each treatment session was 105 min, including 15 min of compression during the starting period and 20 min of decompression during the ending period. The patients were carefully interviewed regarding their medical history and were instructed to communicate any problems, such as otalgia, ear fullness, hearing loss, tinnitus, vertigo, or dizziness to the staff of the Hyperbaric Medical Center. When a problem was experienced, the compression time was prolonged or the HBOT session was stopped. Pulmonary function tests and chest X-ray examinations were performed prior to HBOT, and patients with severe pulmonary disease and/or a history of emphysema were excluded as candidates for HBOT. Vasoconstrictor nasal spray, myringotomy and/or tympanic tube insertion were not applied prior to HBOT. The patients generally underwent HBOT once a day, 5 days a week. The total number of treatment sessions ranged from 1 to 216 (median 7; interquartile range 3–19). Otological symptom analysis The otological symptoms experienced during HBOT sessions were analysed based on the medical charts of the 1115 enrolled patients. An otological symptom was considered to be associated with HBOT if the symptom occurred or deteriorated during the treatment session. In the statistical analyses of factors associated with otological symptoms, we divided the enrolled patients according to the factors of age, gender, total number of HBOT sessions and primary disease. The incidences of detailed otological symptoms, including otalgia, ear fullness, hearing loss, tinnitus, vertigo and dizziness were evaluated in the patients who experienced otological complications. The number of sessions at which the otological symptoms first presented was assessed in each patient. Otoscopic finding and intervention for otological complications
Fig. 1 Diagram showing the flowchart of the study protocol. HBOT hyperbaric oxygen therapy
123
The otoscopic findings and interventions for the otological complications were analysed in the patients who visited the otolaryngology department. The otoscopic findings were categorized into six grades according to the TEED grading system [9]. One modification was made for the Grade 0 symptoms and signs: namely, ‘normal tympanic
Eur Arch Otorhinolaryngol
membrane’ was used instead of ‘symptoms with no otological signs’. The interventions included myringotomy, tympanic tube insertion or HBOT cessation. Statistical analysis Statistical analyses were conducted using JMP 11.2 (SAS Institute, Inc., Cary, NC, USA) on a Macintosh computer. The univariate relationships between the independent factors and otological complications were analysed using Pearson’s Chi square test and analysis of an m 9 n contingency table for categorical variables. To test the independence of the risk factors for otological complications, the factors of age, gender, total number of HBOT sessions and primary disease were entered into a multivariate logistic regression model. Odds ratio and their corresponding 95 % confidence intervals were calculated. For all tests, the criterion for statistical significance was a P value of \0.05.
Results Otological complications and their risk factors Otological symptoms occurred in 165 (14.8 %) of the 1115 patients. The incidences of otological symptoms according to the factors of age, gender, total number of HBOT sessions and primary disease are shown in Table 1. Univariate analysis showed significant differences for each factor. Multivariate logistic regression analysis identified ages of [60 years and female sex as independent risk factors for otological complications (Table 2). In contrast, patients with a sports injury were at lower risk than those with other diseases, except for severe infectious disease. No significant difference was found in terms of the total session numbers between B10, 11–29 and C30, which differed from the results of the univariate analysis. Detailed otological symptoms Detailed otological symptoms were examined in 165 patients. The most prevalent symptom was otalgia in 157 patients (95.2 %), followed by ear fullness in 13 patients (7.9 %), hearing loss in 12 patients (7.3 %), tinnitus in three patients (1.8 %) and vertigo in one patient (0.6 %). The symptoms occurred at the first HBOT session in 82 patients (49.7 %), at the second to fifth sessions in 51 patients (30.9 %) and at the sixth to ninth sessions in 16 patients (9.7 %). A 63-year-old female patient experienced vertigo with left otalgia during the seventh HBOT session for her left ISSNHL. She was found to have bilateral abnormal
tympanic membranes categorized as TEED Grade 1. Her air- and bone-conduction pure-tone averages at the frequencies of 0.5, 1, 2 and 4 kHz deteriorated from 58.8 to 83.8 dB and from 53.8 to 68.8 dB in the left ear, respectively. Horizontal nystagmus towards the left was detected using an infrared charge-coupled device camera. Taken together, these findings suggested inner ear barotrauma. HBOT was stopped; however, her hearing loss persisted. Otoscopic findings and interventions for otological complications Otoscopic findings and interventions for otological complications were evaluated in 58 patients of the 165 patients with otological symptoms. None of the patients had a previous history of ear surgery and/or chronic otitis media. The symptoms were in the bilateral ears in 15 patients (25.8 %), the right ear in 15 patients (25.8 %), the left ear in 15 patients (25.8 %) and the side was unknown in 13 patients (22.4 %). The otoscopic findings of the 116 ears in the 58 patients are shown in Table 3. Among 60 ears with otological symptoms, a normal tympanic membrane categorized as Grade 0 was detected in 13 ears (21.7 %). Among the 30 ears without symptoms, an abnormal tympanic membrane was detected in seven ears (23.3 %). Of the 13 patients who exhibited otological symptoms for which the side was unknown, 10 patients showed bilateral Grade 0 tympanic membranes, one patient showed bilateral Grade 3 tympanic membranes and the remaining two patients showed a unilateral Grade 1 tympanic membrane. In total, 58 (50.0 %) of the 116 ears demonstrated abnormal otoscopic findings; however, no ears were classified as having a Grade 5 tympanic membrane. The interventions for the otological complications are shown in Fig. 2. Among the 58 ears with a Grade 0 TEED score, no treatment was performed in 51 ears (87.9 %), five ears (8.6 %) underwent myringotomy or tympanic tube insertion and HBOT was stopped in one patient with bilateral otological complications. In contrast, among the 58 ears with a Grade 1–4 TEED score, 27 ears (46.6 %) required myringotomy or tube insertion, while four patients stopped receiving HBOT in both ears (13.8 %) and no treatment was performed in 23 ears (39.7 %). A small perforation of the tympanic membrane persisted in two of the 32 ears treated with myringotomy or tube placement.
Discussion Middle ear barotrauma was the most common complication of HBOT in the present study. Table 4 summarizes the otological complications of HBOT noted in previous
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Eur Arch Otorhinolaryngol Table 1 Incidence of otological symptoms according to the factors of age, gender, total HBOT session number and primary disease
Factors
Patients with otological symptoms No.
P value
%
Age (years)
0.000
\20 (n = 44)
6
13.6
20–60 (n = 713)
71
10.0
[60 (n = 358)
88
24.6
Male (n = 776)
84
10.8
Female (n = 339)
81
23.9
B10 (n = 698)
74
10.6
11–29 (n = 281)
61
21.7
30
22.1
9
2.6
Gender
0.000
Number of HBOT sessions
0.000
C30 (n = 136) Disease
0.000
Sports injury (n = 346) ISSNHL (n = 169)
42
24.9
Osteomyelitis (n = 103)
18
17.5
Spinal cord injury/nerve root disease (n = 92)
17
18.5
Peripheral vascular disease (n = 74)
15
20.3
Carbon monoxide poisoning (n = 56) Haemorrhagic cystitis/proctitis (n = 53) Radiation-induced osteomyelitis/necrosis (n = 28) Severe infectious disease (n = 27) Others (n = 167)
8
14.3
18
34.0
5
17.9
4
14.8
29
17.4
HBOT hyperbaric oxygen therapy, ISSNHL idiopathic sudden sensorineural hearing loss
Table 2 Multivariate logistic regression analysis results: significant risk factors associated with HBOT
Factors
Reference category
Odds ratio (95 % CI)
P value
20–60
1.7 (1.2–2.5)
0.004
Male
1.8 (1.2–2.5)
0.002
Age (years) [60 Gender Female Disease ISSNHL
Sports injury
7.7 (3.6–17.9)
0.000
ISSNHL
Others
1.7 (1.0–3.0)
0.049
Osteomyelitis
Sports injury
4.2 (1.7–10.8)
0.002
Spinal cord injury/nerve root disease
Sports injury
5.0 (2.1–12.7)
0.000
Peripheral vascular disease
Sports injury
5.1 (2.0–13.7)
0.000
Carbon monoxide poisoning
Sports injury
4.3 (1.5–12.2)
0.007
Haemorrhagic cystitis/proctitis
Sports injury
8.8 (3.2–24.9)
0.000
Radiation-induced osteomyelitis/necrosis Others
Sports injury Sports injury
4.1 (1.1–14.2) 4.5 (2.0–10.8)
0.039 0.000
CI confidence interval
reports [3–16]. The incidence of otological symptoms ranges widely, from 8.9 to 66.7 %. Ambiru et al. [13] mentioned several possible reasons for the variation in the complication rates, including (1) differences in population and the characteristics of the patients, (2) differences in the
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definitions of complications in terms of severity and (3) differences in the HBOT protocol and the chamber type (monoplace or multiplace chamber). In the present study, all patients were informed regarding possible symptoms and complications, including otalgia, ear fullness, hearing
Eur Arch Otorhinolaryngol Table 3 Modified TEED’s score grading and ear numbers (%) Grade
Symptoms and signs
Ear with symptom (n = 60 ears)
Ear without symptom (n = 30 ears)
Ear with or without symptoma (n = 26 ears)
Total (n = 116 ears)
0
Normal tympanic membrane
13 (21.7)
23 (76.7)
22 (84.6)
58 (50.0)
1
Diffuse redness and retraction of the tympanic membrane
13 (21.7)
3 (10.0)
2 (7.7)
18 (15.5)
2 3
Grade 1 plus slight haemorrhage within the tympanic membrane Grade 1 plus gross haemorrhage within the tympanic membrane
7 (11.7) 19 (31.7)
2 (6.7) 2 (6.7)
0 (0.0) 2 (7.7)
9 (7.8) 23 (19.8)
4
Dark and slightly bulging tympanic membrane due to free blood in the middle ear, fluid may be present
8 (13.3)
0 (0.0)
0 (0.0)
8 (6.9)
5
Free haemorrhage into the middle ear, with tympanic membrane perforation; blood may be seen outside or within the external auditory canal
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
a
An ear of a patient who had an otological symptom for which the side was unknown
Fig. 2 Interventions for barotrauma according to the TEED score. Of the 58 ears with a Grade 0 TEED score, no treatment was performed in 51 ears (87.9 %). In contrast, of the 58 ears with a Grade 1–4 TEED score, 27 ears (46.6 %) required myringotomy or tube insertion and eight ears (13.8 %) in four patients stopped receiving HBOT. HBOT hyperbaric oxygen therapy
loss, tinnitus, vertigo and dizziness and were instructed to let the medical staff know if and when any of these symptoms occurred. Consequently, the incidence of detailed otological symptoms could be clarified in our large study population of more than 1000. Otological symptoms occurred at the first session in approximately 50 % of the patients and during the first to fifth sessions in 80 % of the patients in the present study. These findings are consistent with those of previous reports [7, 8]. The performance of an otoscopic examination immediately after the first HBOT session is thought to be useful for predicting ear barotrauma [12]. Although it may be challenging to carry out such examinations in all patients undergoing HBOT, a good cooperative relationship between the Departments of Hyperbaric Medicine and Otolaryngology is essential.
Patients with radiation-induced injuries to the head and neck area are reportedly at high risk for otological complications [10, 16]. Other possible risk factors include female sex [7], older age [8], abnormal findings on anterior rhinoscopy or X-rays of the paranasal sinuses [4] and the presence of an artificial airway (endotracheal or tracheostomy tube) [5]. Although conflicting observations have been reported with respect to age and sex [4, 14], the multivariate logistic regression analysis in the present study identified age of [60 years and female sex as independent risk factors. With regard to primary disease, a previous study using multivariate logistic regression analysis noted that peripheral circulatory disorders with refractory ulcers and non-healing wounds are independent risk factors [13]. In the present study, patients with sports injuries were found to be at low risk for otological complications. Although the reason was unclear, most of our patients with sports injuries are top athletes and had no trouble with general conditions. Some of these patients were accustomed to the Valsalva manoeuvre because they had received HBOT for previous sports injuries. In otoscopic examinations, no ears showed tympanic membrane perforation categorized as TEED Grade 5, which is an extremely rare observation [4, 6, 9, 16, 18]. In contrast, abnormal otoscopic findings were recognized in the asymptomatic ears at an incidence of 23.3 %. Igarashi et al. [4] found that the rate of middle ear barotrauma assessed on otoscopic examination is higher than that assessed based on clinical symptoms. Taken together, the possibility of ear barotrauma cannot be excluded even if the patient does not complain of symptoms. The most reliable method for preventing ear barotrauma is tympanic tube insertion. In the present study, myringotomy, tympanic tube insertion and/or cancellation of the HBOT were performed in seven ears (12.1 %) with TEED Grade 0 tympanic membranes and 35 ears (60.3 %) with
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Eur Arch Otorhinolaryngol Table 4 Summary of otological complications of HBOT from previous studies Year (reference no.)
Total patient no.
Patients with otological symptoms
Detailed otological symptoms
No.
Otalgia
%
Ear fullness
1992 [15]
33
8
27
1992 [3]
60
39
65.0
15
29
1993 [4] 1994 [5]
67 267
36 131
53.7 49.1
31
23
1996 [16]
82
30
1997 [6]
30
18
60.0
1999 [7]
111
35
31.5
2000 [8]
782
139
17.8
2006 [9]
42
17
40.0
2006 [10]
325
50
15.4
2006 [11]
111
43
38.7 66.7
2008 [12]
18
12
2008 [13]
1609
143
8.9
2010 [14]
130
18
13.6
1115
165
14.7
Present study
35
34
157
13
Hearing loss
Tinnitus
12
3
2
2
12
3
Vertigo/dizziness
1
HBOT hyperbaric oxygen therapy
TEED Grades 1–4 tympanic membranes. Moreover, Clements et al. [17] retrospectively analysed complications occurring secondary to tympanic tube insertion in 45 patients undergoing HBOT and reported that 17 (38 %) of the patients experienced otorrhoea, otalgia, hearing loss and/or persistent tympanic membrane perforations. In our series, two ears demonstrated persistent tympanic membrane perforation. Therefore, the insertion of a tympanic tube should be considered in selected patients, such as those with radiation-induced injuries to the head and neck area, an artificial airway or severe eustachian tube dysfunction. Inner ear barotrauma is a possible complication of HBOT. Beuerlein et al. [6] used distortion-product otoacoustic emissions (DPOAEs) to evaluate whether they can provide information regarding subtle cochlear injury. The authors found a significant change in the DPOAE amplitudes without parallel changes on conventional audiometry in six of 22 patients. However, no patients with apparent inner ear barotrauma have been reported [2]. In the present study, one (0.1 %) of the 1115 patients experienced deterioration of their hearing with otalgia and abnormal tympanic membranes, as well as vertigo with horizontal nystagmus to the side of the deteriorated ear, which is suggestive of inner ear barotrauma. Therefore, all medical staff should remain aware that inner ear barotrauma, although extremely rare, is a possible complication of HBOT. Some of the limitations associated with the present study include the fact that no patients underwent X-ray
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examinations of the paranasal sinuses or eustachian tube function testing prior to HBOT, and that few of the symptomatic patients visited the Otolaryngology Department. Therefore, further prospective study is needed to increase the understanding around the otological complications of HBOT.
Conclusion Ear barotrauma is the most common complication of HBOT and was detected in 165 (14.8 %) of the 1115 patients in the present study. In addition, inner ear barotrauma, which has not been reported previously, was detected in one patient (0.1 %). Hence, a good cooperative relationship between the Departments of Hyperbaric Medicine and Otolaryngology is indispensable for reducing the incidence of otological complications associated with HBOT. Compliance with ethical standards Conflict of interest of interest.
The authors declare that they have no conflict
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