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Peroral Prednisolone in the Treatment of Middle-Ear Effusion in Children: A Double-Blind Study
Auris·Nasus·Larynx (Tokyo) 12 (Supp!. I) S 268-S 271, 1985
PERORAL PREDNISOLONE IN THE TREATMENT OF MIDDLE-EAR EFFUSION IN CHILDREN: A DOUBLE-BLIND STUDY Heikki PUHAKKA, Jorma HAAPANIEMI, Pekka TUOHIMAA, OUi RUUSKANEN 1 , and Jussi ESKoLA 2 Departments of Otolaryngology, 1Pediatrics and 2Microbiology, University Central Hospital, Turku, Finland
Otitis media with effusion (OME) is one of assessed in a clinical follow-up of 2 months. the most important and, with respect to treatment, one of the most problematic of Patients and Methods Seventy-five children, 26 girls and 49 boys, the common diseases of childhood. A variety of medical regimens and surgical procedures suffering from OME were admitted to the have been tried in the management of middle study. The total number of affected ears was ear effusion. Conservative treatment has 122. The ages of the children ranged from 7 included long-term chemotherapy antihista- months to II years with a mean age of 4 mines, and decongestants, but definitive years and 10 months. Children who had had evidence that the clinical course of the disease an acute otitis media episode during the is significantly shortened by any of these preceding 3 months were not admitted to the therapies has yet to be presented. Corticoster- study (Table 1). Before institution of therapy all the children oid treatment has also been used both in allergic and nonallergic children. Evaluating underwent a thorough otorhinolaryngological the results of ampicillin and prednisone ther- examination, which was carried out by an apy in 160 children with OME, PERSICO et al. ENT specialist. The children were randomly (1978) concluded that the steroid had a allocate to three therapy groups, Group A beneficial effect on Eustachian tube function. receiving prednisolone and sulfatrimethoSCHWARTZ et al. (1980a) found that middle prim, Group B sulfatrimethoprim and plaear effusion cleared in 62S% of children with cebo, and Group C placebo and placebo. secretory otitis media as a result of treatment The dosage of peroral prednisolone was I with 1 mg of prednisone per day. Following mg/kg body weight/day, divided into 3 doses treatment with intranasal beclomethasone and given as a decreasing dose, for 6 days. the middle ear effusion resolved in only 48% The dosage of peroral sulfatrimethoprim was of children (SCHWARTZ et al., 1980b). A 6 mg of trimethoprim and 18.5 mg of sulfaplacebo-controlled trial by LINDHOLDT and diazine/kg/day, divided into 2 doses, for 10 KORTHOLM (1982) also failed to show a signifi- days. Myringotomy was carried out on all cant difference in favour of intranasal beclomethasone therapy. affected ears at the first visit. At the followTo obtain information on the role of up visits 2, 4 and 8 weeks after institution of prednisolone in the management of OME, therapy, myringotomy was also performed on we performed a clinical study in children with all ears in which middle ear fluid was detected. secretory middle ear effusion. The study was Follow-up examinations were always carried designed as a double-blind trial to compare out by the ENT specialist who had examined the effects of prednisolone, sulfatrimethoprim the child initially. The mobility of the tymand placebo. The outcome of therapy was panic membrane was examined with special
Lecture
care. When necessary an otomicroscope was used. Samples for bacteriological culture were taken at the first visit both from the nasopharynx using a charcoal-coated swab (cotton-applicator) and from the middle ear at myringotomy. Standard procedures were used to cultivate bacteria. Audiological examination was not used as a parameter, as a large number of the children were under 4 years of age. Throughout the study the clinical course of the patients was closely followed by the investigation team. The condition (OME) was considered to be cured when appearance and mobility of the tympanic membrane had become normal or if effusion was no longer present at myringotomy. Results
Group A comprised 29 children (47 affected ears), Group B 22 children (35 ears), and Group C 24 children (40 ears). Table 1 shows bacteriological findings in the nasopharyngeal and middle ear fluid specimens, taken at the first visit before therapy started; pathogenic bacteria were cultured from the middle ear effusion in 26% of cases. Branhamella catarrhalis was the commonest of the pathogens isolated from the nasopharynx (30%), while Haemophilus injluenzae was the most frequent of the middle ear pathogens (14%). Twenty-one percent of the nasopharyngeal samples but only 3% of the Table 1.
S269
Treatment
effusion samples showed growth of more than one pathogen. Pathogens were isolated from which did not respond to therapy. In the group of cured ears, 8% of the cultures showed growth of H. injluenzae and in therapy-resistant ears the frequency was as high as 25%. For B. catarrhalis the corresponding figures were 11 and 10% and for Streptococcus pneumoniae 5 and 5 %, respectively. Response to treatment, as assessed at the follow-up visits at 2 and 8 weeks, are compared in Table 2. At 2 weeks after institution of therapy middle ear effusion was no longer present in 77% of Group A ears, 46% of Group Band 38% of Group C ears. At 8 weeks the proportions of cured ears were 79% in Group A, 46% in Group Band 63% in Group C. Significance levels of the differences between results of therapy in the three groups are also given in Table 2. Discussion
In this study we found pathogenic bacteria in 26% of middle ear effusions. Similar findings have been reported in earlier studies (SIPILA et al., 1981). Although efforts were made not to include children who had experienced an acute otitis media episode during the 3 months preceding present therapy, such children may have been admitted. That this was the case is suggested by the relatively freq uent growth of H. injluenzae (14%) and B. catarrhalis (10%) in the effusion samples
Bacterial findings in the nasopharynx and the middle ear fluid before treatment.
Bacteria
Middle ear fluid
Nasopharynx N
%
N
%
Streptococcus pneumoniae Haemophilus inf/uenzae Branhamella catarrhalis Staphylococcus aureus Streptococcus ,B-haemol. Negative culture/non pathogens
15 17 26 5 2 22
17.2 19.5 29.9 5.7 2.3 25.3
2 10 7 0 0 54
2.7 13.7 9.6 0 0 74.0
Total No information
87 11
N=the number of cultured pathogens.
73 9
H. J. PUHAKKA et al.
S270
Table 2. The cure rate in the different therapy groups of treatment after 2 and 8 weeks. After 2 weeks Therapy groups
Cured
After 8 weeks
Not cured
Cured
Not cured
N
%
N
%
N
%
N
%
Group A (Prednisolone + sulfatrimethoprim)
36
76.6
11
23.4
37
78.7
10
21.3
Group B (Placebo + sulfatrimethoprim)
16
45.7
19
54.3
16
45.7
19
54
Group C (Placebo +placebo)
15
37.5
25
62.5
25
62.5
15
37
67
54.9
55
45.1
78
63.9
44
36
Total N=the number of ears.
taken before the start of therapy. Haemo- that middle ear effusion may resolve sponphi/us-positive cultures were more frequent in taneously, in particular during the warm the group of therapy-resistant ears than in seasons of the year. ears responding to therapy, 25% as compared At the 2-week control examination middle with 8%. Such differences in frequencies ear effusion was no longer present in 77% of were not noted for B. catarrhalis or S. pneu- the ears treated with prednisolone and at moniae. On the other hand, sulfatrimetho- 8 weeks the percentage was 79. Prednisolone prim is known to penetrate middle ear fluid I mg/kg/day was given in a diminishing for extremely well and to particularly effective in only 6 days. Prednisolone appears to be a middle ear infections caused by H. injluenzae. fast-acting drug and its effect on middle ear The present material is too small, however, to effusion becomes apparent fairly quickly. allow a more detailed analysis of different Therefore, prolonged follow-up is not likely pathogens in relation to results of treatment. to reveal an essential increase in cure rate. In the placebo group, 38% of the ears were On the other hand, surgical treatment for mideffusion-free at the 2-week follow-up visit and dle ear effusion should not be too readily 63% had become so at 8 weeks. In the group resorted to, as the condition will clear sponreceiving sulfatrimethoprim alone the cor- taneously in part of the patients. SCHWARTZ et al. (1980a) achieved a cure responding figure was 26% at both checkups. Myringotomy was done on all ears at the rate of 70% with prednisone given in a dose first visit and was also performed at later of 1 mg/kg/day for 7 days. In our study 79% visits, if presence of effusion was suspected. of the ears were symptomfree at 2 months At myringotomy special care was taken to after peroral prednisolone therapy. Studies remove (drain) all fluid from the middle ear have also been performed to evaluate the by means of suction. It is obvious that my- effect of intranasal corticosteroids on middle ringotomy had a significant effect on the cure ear effusion. In a recent trial by LINDHOLDT rate, especially in the sulfatrimethoprim and and KORTHOLM (1982) intranasal beclomeplacebo groups (Groups B and C). Myringo- thasone could not be shown to be significantly tomy played a less important role in the superior to placebo, although inhalation recovery of prednisolone-treated children, techniques to enhance distribution of the because secondary myringotomies were clear- active drug to the nasopharynx were given ly less frequently required in this group particular attention. Our trial of prednisolone (Group A). It should also be borne in mind and placebo showed a significant difference
Lecture
in favour of the active drug. The mode of action of prednisolone in the process of middle ear clearance is not known. The steroid may have an effect both on tubal function and on the middle ear mucosa. SCHWARTZ et al. (l980a) suggested several possibilities: facilitation of production of tubal surfactants, decrease in the viscosity of mucoproteins in the effusion, and decrease in peritubous Eustachian tube oedema. More extensive well-controlled clinical studies are, however, necessary before a definitive appraisal can be made of the role of peroral steroids in the management of middle ear effusion. References T., and KORTHOLM B: Beclomethasone nasal spray in the treatment of middle-ear effu-
LINDHOLDT,
Treatment
S271
sion-a double blinded study. Int. J. Pediatr. Otorhinolaryngol. 4: 133-137, 1982. PERSICO, M., PODOSHIN, L., and FRADIS, M.: Otitis media with effusion. A steroid and antibiotic trial before surgery. Ann. 0101. 87: 191-195, 1978. SCHWARTZ, R. H., PUGLESE, J., and SCHWARTZ, D. M.: Use of a short course of prednisone for treating middle ear effusion. Ann. Otol. suppl. 68: 296-300, 1980a. SCHWARTZ, R. H., SCHWARTZ, D. M., and GRUNDFAST, K. M.: Intranasal beclomethasone in the treatment of middle ear effusion: A pilot study. Ann. Allerg. 45: 284-287, 1980b. SIPILA, P., JOKIPII, A. M. M., JOKIPII, L., and KARMA, P: Bacteria in the middle ear and ear canal of patients with secretory otitis media and with non-inflamed ears. Acta Otolaryngol. 92: 123130, 1981.
PERORAL PREDNISOLONE IN THE TREATMENT OF MIDDLE-EAR EFFUSION IN CHILDREN: A DOUBLE-BLIND STUDY Heikki PUHAKKA, Jorma HAAPANIEMI, Pekka TUOHIMAA, OUi RUUSKANEN 1 , and Jussi ESKoLA 2 Departments of Otolaryngology, 1Pediatrics and 2Microbiology, University Central Hospital, Turku, Finland
Otitis media with effusion (OME) is one of assessed in a clinical follow-up of 2 months. the most important and, with respect to treatment, one of the most problematic of Patients and Methods Seventy-five children, 26 girls and 49 boys, the common diseases of childhood. A variety of medical regimens and surgical procedures suffering from OME were admitted to the have been tried in the management of middle study. The total number of affected ears was ear effusion. Conservative treatment has 122. The ages of the children ranged from 7 included long-term chemotherapy antihista- months to II years with a mean age of 4 mines, and decongestants, but definitive years and 10 months. Children who had had evidence that the clinical course of the disease an acute otitis media episode during the is significantly shortened by any of these preceding 3 months were not admitted to the therapies has yet to be presented. Corticoster- study (Table 1). Before institution of therapy all the children oid treatment has also been used both in allergic and nonallergic children. Evaluating underwent a thorough otorhinolaryngological the results of ampicillin and prednisone ther- examination, which was carried out by an apy in 160 children with OME, PERSICO et al. ENT specialist. The children were randomly (1978) concluded that the steroid had a allocate to three therapy groups, Group A beneficial effect on Eustachian tube function. receiving prednisolone and sulfatrimethoSCHWARTZ et al. (1980a) found that middle prim, Group B sulfatrimethoprim and plaear effusion cleared in 62S% of children with cebo, and Group C placebo and placebo. secretory otitis media as a result of treatment The dosage of peroral prednisolone was I with 1 mg of prednisone per day. Following mg/kg body weight/day, divided into 3 doses treatment with intranasal beclomethasone and given as a decreasing dose, for 6 days. the middle ear effusion resolved in only 48% The dosage of peroral sulfatrimethoprim was of children (SCHWARTZ et al., 1980b). A 6 mg of trimethoprim and 18.5 mg of sulfaplacebo-controlled trial by LINDHOLDT and diazine/kg/day, divided into 2 doses, for 10 KORTHOLM (1982) also failed to show a signifi- days. Myringotomy was carried out on all cant difference in favour of intranasal beclomethasone therapy. affected ears at the first visit. At the followTo obtain information on the role of up visits 2, 4 and 8 weeks after institution of prednisolone in the management of OME, therapy, myringotomy was also performed on we performed a clinical study in children with all ears in which middle ear fluid was detected. secretory middle ear effusion. The study was Follow-up examinations were always carried designed as a double-blind trial to compare out by the ENT specialist who had examined the effects of prednisolone, sulfatrimethoprim the child initially. The mobility of the tymand placebo. The outcome of therapy was panic membrane was examined with special
Lecture
care. When necessary an otomicroscope was used. Samples for bacteriological culture were taken at the first visit both from the nasopharynx using a charcoal-coated swab (cotton-applicator) and from the middle ear at myringotomy. Standard procedures were used to cultivate bacteria. Audiological examination was not used as a parameter, as a large number of the children were under 4 years of age. Throughout the study the clinical course of the patients was closely followed by the investigation team. The condition (OME) was considered to be cured when appearance and mobility of the tympanic membrane had become normal or if effusion was no longer present at myringotomy. Results
Group A comprised 29 children (47 affected ears), Group B 22 children (35 ears), and Group C 24 children (40 ears). Table 1 shows bacteriological findings in the nasopharyngeal and middle ear fluid specimens, taken at the first visit before therapy started; pathogenic bacteria were cultured from the middle ear effusion in 26% of cases. Branhamella catarrhalis was the commonest of the pathogens isolated from the nasopharynx (30%), while Haemophilus injluenzae was the most frequent of the middle ear pathogens (14%). Twenty-one percent of the nasopharyngeal samples but only 3% of the Table 1.
S269
Treatment
effusion samples showed growth of more than one pathogen. Pathogens were isolated from which did not respond to therapy. In the group of cured ears, 8% of the cultures showed growth of H. injluenzae and in therapy-resistant ears the frequency was as high as 25%. For B. catarrhalis the corresponding figures were 11 and 10% and for Streptococcus pneumoniae 5 and 5 %, respectively. Response to treatment, as assessed at the follow-up visits at 2 and 8 weeks, are compared in Table 2. At 2 weeks after institution of therapy middle ear effusion was no longer present in 77% of Group A ears, 46% of Group Band 38% of Group C ears. At 8 weeks the proportions of cured ears were 79% in Group A, 46% in Group Band 63% in Group C. Significance levels of the differences between results of therapy in the three groups are also given in Table 2. Discussion
In this study we found pathogenic bacteria in 26% of middle ear effusions. Similar findings have been reported in earlier studies (SIPILA et al., 1981). Although efforts were made not to include children who had experienced an acute otitis media episode during the 3 months preceding present therapy, such children may have been admitted. That this was the case is suggested by the relatively freq uent growth of H. injluenzae (14%) and B. catarrhalis (10%) in the effusion samples
Bacterial findings in the nasopharynx and the middle ear fluid before treatment.
Bacteria
Middle ear fluid
Nasopharynx N
%
N
%
Streptococcus pneumoniae Haemophilus inf/uenzae Branhamella catarrhalis Staphylococcus aureus Streptococcus ,B-haemol. Negative culture/non pathogens
15 17 26 5 2 22
17.2 19.5 29.9 5.7 2.3 25.3
2 10 7 0 0 54
2.7 13.7 9.6 0 0 74.0
Total No information
87 11
N=the number of cultured pathogens.
73 9
H. J. PUHAKKA et al.
S270
Table 2. The cure rate in the different therapy groups of treatment after 2 and 8 weeks. After 2 weeks Therapy groups
Cured
After 8 weeks
Not cured
Cured
Not cured
N
%
N
%
N
%
N
%
Group A (Prednisolone + sulfatrimethoprim)
36
76.6
11
23.4
37
78.7
10
21.3
Group B (Placebo + sulfatrimethoprim)
16
45.7
19
54.3
16
45.7
19
54
Group C (Placebo +placebo)
15
37.5
25
62.5
25
62.5
15
37
67
54.9
55
45.1
78
63.9
44
36
Total N=the number of ears.
taken before the start of therapy. Haemo- that middle ear effusion may resolve sponphi/us-positive cultures were more frequent in taneously, in particular during the warm the group of therapy-resistant ears than in seasons of the year. ears responding to therapy, 25% as compared At the 2-week control examination middle with 8%. Such differences in frequencies ear effusion was no longer present in 77% of were not noted for B. catarrhalis or S. pneu- the ears treated with prednisolone and at moniae. On the other hand, sulfatrimetho- 8 weeks the percentage was 79. Prednisolone prim is known to penetrate middle ear fluid I mg/kg/day was given in a diminishing for extremely well and to particularly effective in only 6 days. Prednisolone appears to be a middle ear infections caused by H. injluenzae. fast-acting drug and its effect on middle ear The present material is too small, however, to effusion becomes apparent fairly quickly. allow a more detailed analysis of different Therefore, prolonged follow-up is not likely pathogens in relation to results of treatment. to reveal an essential increase in cure rate. In the placebo group, 38% of the ears were On the other hand, surgical treatment for mideffusion-free at the 2-week follow-up visit and dle ear effusion should not be too readily 63% had become so at 8 weeks. In the group resorted to, as the condition will clear sponreceiving sulfatrimethoprim alone the cor- taneously in part of the patients. SCHWARTZ et al. (1980a) achieved a cure responding figure was 26% at both checkups. Myringotomy was done on all ears at the rate of 70% with prednisone given in a dose first visit and was also performed at later of 1 mg/kg/day for 7 days. In our study 79% visits, if presence of effusion was suspected. of the ears were symptomfree at 2 months At myringotomy special care was taken to after peroral prednisolone therapy. Studies remove (drain) all fluid from the middle ear have also been performed to evaluate the by means of suction. It is obvious that my- effect of intranasal corticosteroids on middle ringotomy had a significant effect on the cure ear effusion. In a recent trial by LINDHOLDT rate, especially in the sulfatrimethoprim and and KORTHOLM (1982) intranasal beclomeplacebo groups (Groups B and C). Myringo- thasone could not be shown to be significantly tomy played a less important role in the superior to placebo, although inhalation recovery of prednisolone-treated children, techniques to enhance distribution of the because secondary myringotomies were clear- active drug to the nasopharynx were given ly less frequently required in this group particular attention. Our trial of prednisolone (Group A). It should also be borne in mind and placebo showed a significant difference
Lecture
in favour of the active drug. The mode of action of prednisolone in the process of middle ear clearance is not known. The steroid may have an effect both on tubal function and on the middle ear mucosa. SCHWARTZ et al. (l980a) suggested several possibilities: facilitation of production of tubal surfactants, decrease in the viscosity of mucoproteins in the effusion, and decrease in peritubous Eustachian tube oedema. More extensive well-controlled clinical studies are, however, necessary before a definitive appraisal can be made of the role of peroral steroids in the management of middle ear effusion. References T., and KORTHOLM B: Beclomethasone nasal spray in the treatment of middle-ear effu-
LINDHOLDT,
Treatment
S271
sion-a double blinded study. Int. J. Pediatr. Otorhinolaryngol. 4: 133-137, 1982. PERSICO, M., PODOSHIN, L., and FRADIS, M.: Otitis media with effusion. A steroid and antibiotic trial before surgery. Ann. 0101. 87: 191-195, 1978. SCHWARTZ, R. H., PUGLESE, J., and SCHWARTZ, D. M.: Use of a short course of prednisone for treating middle ear effusion. Ann. Otol. suppl. 68: 296-300, 1980a. SCHWARTZ, R. H., SCHWARTZ, D. M., and GRUNDFAST, K. M.: Intranasal beclomethasone in the treatment of middle ear effusion: A pilot study. Ann. Allerg. 45: 284-287, 1980b. SIPILA, P., JOKIPII, A. M. M., JOKIPII, L., and KARMA, P: Bacteria in the middle ear and ear canal of patients with secretory otitis media and with non-inflamed ears. Acta Otolaryngol. 92: 123130, 1981.