PEDIATRIC PHARMACOLOGY AND THERAPEUTICS
Nebulized albuterol in a c u t e bronchiolitis S u z a n n e Schuh, MD, FRCP(C), G e r a r d C a n n y , MB,BCh, FRCP(C), J o s e p h J. Reisman, MD, FRCP(C), Eitan K e r e m , MD, L e a Bentur, MD, M a r t i n Petric, PhD, a n d Henry Levison, MD, FRCP(C) From the Divisions of Emergency and Chest, Department of Pediatrics, and the Department of Microbiology, Hospital for Sick Children, Toronto, Ontario, Canada In a d o u b l e - b l i n d , p l a c e b o - c o n t r o l l e d trial, 40 infants b e t w e e n 6 w e e k s a n d 24 months of a g e w h o h a d a first e p i s o d e of w h e e z i n g a n d other signs a n d symptoms of bronchiolitis w e r e r a n d o m l y a s s i g n e d to r e c e i v e e i t h e r n e b u l i z e d a l b u t e r o l (0.15 m g / k g / d o s e ) or p l a c e b o (saline solution) for two administrations I hour apart. The a l b u t e r o l t h e r a p y resulted in a significantly g r e a t e r i m p r o v e m e n t in the a c c e s s o r y muscle score (~0.70 vs ~0.30; p = 0.03), o x y g e n saturation (I'0.71% vs ~0.47%; p = 0.01) after o n e dose, a n d in the a c c e s s o r y muscle s c o r e (~0.86 vs ~0.37; p = 0.02), respiratory rate (~19.6% vs ~8.0%; p = 0.016), a n d oxyg e n saturation (~0.76% vs ~0.79%; p = 0.015) after t w o doses of the drug. The res p o n s e to t h e r a p y was similar in infants y o u n g e r a n d those o l d e r than 6 months of a g e . The heart rate rose slightly m o r e in the a l b u t e r o l g r o u p (~7.76 from b a s e line) versus the p l a c e b o g r o u p (~6.79). There w e r e n o other side effects of the treatment. Of the 34 c h i l d r e n from w h o m nasal s p e c i m e n s w e r e o b t a i n e d by s w a b for viral identification, 24 had positive test results (21 for respiratory syncytial virus, I for p a r a i n f l u e n z a , I for p a r a m y x o v i r u s , a n d 1 for influenza A). We c o n c l u d e that n e b u l i z e d a l b u t e r o l constitutes a safe a n d e f f e c t i v e t r e a t m e n t of infants with bronchiolitis. (J PEDIATR1990;117:633-7)
Therapy for acute bronchiolitis includes supportive measures, such as supplementary oxygen and adequate hydration, 1'2 in addition to antiviral chemotherapy in selected patients. 3, 4 The role of bronchodilators, including sympathomimetic agents, theophylline, and anticholinergic agents, remains controversial. Although a few studies suggest a positive response to bronchodilators,57 most reports discourage their use because of a lack of proven therapeutic effect. 814 Some of these studies, however, had methodologic and technical problems, such as low drug doses, non-
Supported by the pediatric consultants of the Hospital for Sick Ghildren, Toronto. Presented in part at the American Academy of Pediatrics Meeting (Scientific Section), Chicago, Ill., Oct. 22, 1989. Submitted for publication Nov. 22, 1989; accepted April 2, 1990. Reprint requests: Suzanne Schuh, MD, Emergency Department, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. 9/25/21362
clinical assessment of respiratory status, and the need for sedation, and many were performed during the recovery phase of the illness. Nebulized albuterol continues to be used successfully for bronchiolitis at our institution, and some authors recommend its use in the treatment of this disease.15, 16 Moreover, a good response to subcutaneous administration of epinephrine in young wheezy infants has been recently demonstrated. 17 The objective of our doubleblind, placebo-controlled study was to evaluate the clinical response to nebulized albuterol in infants and young children with acute bronchiolitis who were seen in our emergency department. METHODS The study was conducted in our emergency department during the period from December 1988 to April 1989. Patients between 6 weeks and 24 months of age, whose history and clinical findings were compatible with a diagnosis of acute bronchiolitis, were eligible for the study. Enrollment occurred between approximately 8 AM and 12 midnight,
633
634
S c h u h et al.
The Journal o f Pediatrics October 1990
T a b l e I. Initial characteristics of the two study groups Group I Group 2 (albuterol) ( p l a c e b o ) (n = 21) (n = 19) Age (mo)* 6.1 _+ 1.3 Temperature (~ C)* 37.9 + 0.2 Duration of illness 96 Hr 4 Coryza 20 Contact with URI (within 1 week) 16 Family history of atopy 11 Positive viral isolation 14 (nasal swab) Medications (within 48 hr) Orciprenaline 4 Albuterol 3 Antibiotics 3 None 11 Respiratory rate (breaths/rain)* 58.3 _+ 2.4 Accessory muscle score* 1.7 _+ 0.1 Median 2 Range 1-3 Wheeze score* 1.6 _+ 0.1 Median 2 Range 1-3 Oxygen saturation (%)* 95.4 _+ 0.5 Heart rate (beats/min)* 153.2 _+ 3.3
5.3 _+ 1.2 37.7 +_ 1.1 11 5 3 19 14 8 10
4 1 4 10 56.4 _+ 3.0 1.6 _+ 0.1 2 1-2 1.8 _+ 0.1 2 1-3 96.4 _+ 0.5 155.4 _+ 4.1
URI, Upper respiratory tract infection. *Values are expressed as mean _+ SEM.
when, after the initial assessment, the attending emergency d e p a r t m e n t pediatrician called one of the investigators (S.S., G.C., J.J.R., E.K., or L.B.). Exclusion criteria included a history of p r e m a t u r i t y or mechanical ventilation after birth; a history of lower respiratory tract disease, wheezing, or bronchodilator therapy; a history suggestive of chronic aspiration or cardiac disease; or current episode t h a t started more t h a n 2 weeks before the present emergency d e p a r t m e n t visit. I n f o r m e d consent was obtained in all cases, and the study was approved by the h u m a n subjects ethics committee of this hospital. After arrival in the emergency d e p a r t m e n t , the child was seen by one of the five investigators. History was obtained regarding the recent symptoms, infectious contact, family history of atopy, medical and atopic history, and medications taken within 48 hours of arrival. All children had a complete physical examination performed, including temperature, vital signs, accessory muscle score (0 = no indrawing; 1 = mild intercostal indrawing; 2 = m o d e r a t e indrawing with tracheosternal retractions; 3 = severe retractions with nasal flaring) and wheeze score (0 = no wheezing; 1 = end-expiratory wheeze only; 2 = wheeze
Table II. M e a n change in clinical m e a s u r e m e n t s from baseline after t r e a t m e n t
Respiratory rate (%~) After dose 1 After dose 2 At
Nebulized albuterol in a c u t e bronchiolitis S u z a n n e Schuh, MD, FRCP(C), G e r a r d C a n n y , MB,BCh, FRCP(C), J o s e p h J. Reisman, MD, FRCP(C), Eitan K e r e m , MD, L e a Bentur, MD, M a r t i n Petric, PhD, a n d Henry Levison, MD, FRCP(C) From the Divisions of Emergency and Chest, Department of Pediatrics, and the Department of Microbiology, Hospital for Sick Children, Toronto, Ontario, Canada In a d o u b l e - b l i n d , p l a c e b o - c o n t r o l l e d trial, 40 infants b e t w e e n 6 w e e k s a n d 24 months of a g e w h o h a d a first e p i s o d e of w h e e z i n g a n d other signs a n d symptoms of bronchiolitis w e r e r a n d o m l y a s s i g n e d to r e c e i v e e i t h e r n e b u l i z e d a l b u t e r o l (0.15 m g / k g / d o s e ) or p l a c e b o (saline solution) for two administrations I hour apart. The a l b u t e r o l t h e r a p y resulted in a significantly g r e a t e r i m p r o v e m e n t in the a c c e s s o r y muscle score (~0.70 vs ~0.30; p = 0.03), o x y g e n saturation (I'0.71% vs ~0.47%; p = 0.01) after o n e dose, a n d in the a c c e s s o r y muscle s c o r e (~0.86 vs ~0.37; p = 0.02), respiratory rate (~19.6% vs ~8.0%; p = 0.016), a n d oxyg e n saturation (~0.76% vs ~0.79%; p = 0.015) after t w o doses of the drug. The res p o n s e to t h e r a p y was similar in infants y o u n g e r a n d those o l d e r than 6 months of a g e . The heart rate rose slightly m o r e in the a l b u t e r o l g r o u p (~7.76 from b a s e line) versus the p l a c e b o g r o u p (~6.79). There w e r e n o other side effects of the treatment. Of the 34 c h i l d r e n from w h o m nasal s p e c i m e n s w e r e o b t a i n e d by s w a b for viral identification, 24 had positive test results (21 for respiratory syncytial virus, I for p a r a i n f l u e n z a , I for p a r a m y x o v i r u s , a n d 1 for influenza A). We c o n c l u d e that n e b u l i z e d a l b u t e r o l constitutes a safe a n d e f f e c t i v e t r e a t m e n t of infants with bronchiolitis. (J PEDIATR1990;117:633-7)
Therapy for acute bronchiolitis includes supportive measures, such as supplementary oxygen and adequate hydration, 1'2 in addition to antiviral chemotherapy in selected patients. 3, 4 The role of bronchodilators, including sympathomimetic agents, theophylline, and anticholinergic agents, remains controversial. Although a few studies suggest a positive response to bronchodilators,57 most reports discourage their use because of a lack of proven therapeutic effect. 814 Some of these studies, however, had methodologic and technical problems, such as low drug doses, non-
Supported by the pediatric consultants of the Hospital for Sick Ghildren, Toronto. Presented in part at the American Academy of Pediatrics Meeting (Scientific Section), Chicago, Ill., Oct. 22, 1989. Submitted for publication Nov. 22, 1989; accepted April 2, 1990. Reprint requests: Suzanne Schuh, MD, Emergency Department, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. 9/25/21362
clinical assessment of respiratory status, and the need for sedation, and many were performed during the recovery phase of the illness. Nebulized albuterol continues to be used successfully for bronchiolitis at our institution, and some authors recommend its use in the treatment of this disease.15, 16 Moreover, a good response to subcutaneous administration of epinephrine in young wheezy infants has been recently demonstrated. 17 The objective of our doubleblind, placebo-controlled study was to evaluate the clinical response to nebulized albuterol in infants and young children with acute bronchiolitis who were seen in our emergency department. METHODS The study was conducted in our emergency department during the period from December 1988 to April 1989. Patients between 6 weeks and 24 months of age, whose history and clinical findings were compatible with a diagnosis of acute bronchiolitis, were eligible for the study. Enrollment occurred between approximately 8 AM and 12 midnight,
633
634
S c h u h et al.
The Journal o f Pediatrics October 1990
T a b l e I. Initial characteristics of the two study groups Group I Group 2 (albuterol) ( p l a c e b o ) (n = 21) (n = 19) Age (mo)* 6.1 _+ 1.3 Temperature (~ C)* 37.9 + 0.2 Duration of illness 96 Hr 4 Coryza 20 Contact with URI (within 1 week) 16 Family history of atopy 11 Positive viral isolation 14 (nasal swab) Medications (within 48 hr) Orciprenaline 4 Albuterol 3 Antibiotics 3 None 11 Respiratory rate (breaths/rain)* 58.3 _+ 2.4 Accessory muscle score* 1.7 _+ 0.1 Median 2 Range 1-3 Wheeze score* 1.6 _+ 0.1 Median 2 Range 1-3 Oxygen saturation (%)* 95.4 _+ 0.5 Heart rate (beats/min)* 153.2 _+ 3.3
5.3 _+ 1.2 37.7 +_ 1.1 11 5 3 19 14 8 10
4 1 4 10 56.4 _+ 3.0 1.6 _+ 0.1 2 1-2 1.8 _+ 0.1 2 1-3 96.4 _+ 0.5 155.4 _+ 4.1
URI, Upper respiratory tract infection. *Values are expressed as mean _+ SEM.
when, after the initial assessment, the attending emergency d e p a r t m e n t pediatrician called one of the investigators (S.S., G.C., J.J.R., E.K., or L.B.). Exclusion criteria included a history of p r e m a t u r i t y or mechanical ventilation after birth; a history of lower respiratory tract disease, wheezing, or bronchodilator therapy; a history suggestive of chronic aspiration or cardiac disease; or current episode t h a t started more t h a n 2 weeks before the present emergency d e p a r t m e n t visit. I n f o r m e d consent was obtained in all cases, and the study was approved by the h u m a n subjects ethics committee of this hospital. After arrival in the emergency d e p a r t m e n t , the child was seen by one of the five investigators. History was obtained regarding the recent symptoms, infectious contact, family history of atopy, medical and atopic history, and medications taken within 48 hours of arrival. All children had a complete physical examination performed, including temperature, vital signs, accessory muscle score (0 = no indrawing; 1 = mild intercostal indrawing; 2 = m o d e r a t e indrawing with tracheosternal retractions; 3 = severe retractions with nasal flaring) and wheeze score (0 = no wheezing; 1 = end-expiratory wheeze only; 2 = wheeze
Table II. M e a n change in clinical m e a s u r e m e n t s from baseline after t r e a t m e n t
Respiratory rate (%~) After dose 1 After dose 2 At
