Episodio Paroxístico Asmático

Recomendaciones Basadas en la Evidencia
Dr. Alfredo Pachas Q.

Médico Neumólogo
British Guideline on the Management of Asthma
2009
www.sign.ac.uk/guidelines/published/numlist.html
Clin Exp Allergy. 2009 February ; 39(2): 193–202.
BRITTLE ASMA
Tipo 1: Gran variabilidad de PEF: > 40% de variación diurna en más de la mitad del
tiempo durante más 150 días, a pesar de terapia intensa
Tipo 2: Ataques severos súbitos en pacientes aparentemente bien controlados
ASMA SEVERA AGUDA

EXACERBACIÓN MODERADA
Cualquiera de los siguientes:
Aumento de síntomas
PEF: 33-50%
PEF >50-75%
FR >25 ó FC >110
Ninguna característica de Asma Aguda
No puede completar frases en una sola
Severa
respiración
British Guideline on the Management of Asthma 2009

RIESGO DE VIDA:
PEF < 33 %
Sat O2 < 92%
pO2 < 60 mmHg
CO2 normal ASMA CASI FATAL:
Tórax silente
Hipotensión CO2 aumentada y/o
Cianosis
Esfuerzo respiratorio Requiere Ventilación Mecánica con
pobre Presiones altas

Arritmia
Extenuación o
agotamiento
Nivel de conciencia
alterado
Incapacidad para hablar en frases completas
VEF1 <40% o PEF <40% (<25% asma con
peligro de vida)
Saturación de oxígeno <90-92%
PaO 2 <60 mmHg
PaCO 2> 45 mmHg
Uso de músculos accesorios o tiraje traqueal
Pulso paradojal (disminuye > 15 mmHg durante
la inspiración). Con fatiga muscular severa podría
estar ausente
Torax silente
Ortopnea
Cianosis y sudoración
Confusión o disminución del nivel de conciencia
Hipotensión o bradicardia
Emergency Medicine Australasia (2009) 21, 259–268
Signos Leve Moderada Severa Paro Inminente
Disnea Al caminar, puede Al hablar, prefiere Al acostarse

acostarse sentarse
Habla Frases Parte de frases Palabras No puede hablar
Nivel de Puede estar agitado Usualmente agitado Siempre agitado Somnolencia o

conciencia confusión
Frec Resp Incrementada Incrementada A menudo > 30 /

min
Retracciones NO Usualmente Usualmente Movimientos

paradójicos
Sibilancias Moderados, al final de Fuertes Muy fuertes Ausente

la expiracion
FC < 100 100 - 120 > 120 Bradicardia
PEF luego del > 70% 50 – 70 % < 50 % Imposible de medir

tratamiento ( < 100 L /min)
N. Behbehani,J. M. FitzGerald. Int J Tuberc Lung Dis 10(4):356–364. 2006

1. Asma pobremente controlada con síntomas crónicos
2. Exacerbaciones episódicas
3. Obstrucción de las vías respiratorias persistente y variable
4. Requiere continuamente de B2 agonistas de corta acción
a pesar de usar corticosteroides inhalados
5. Requieren cursos o dosis regulares de corticosteroides orales
para control del asma
6. Control del asma no es influenciada por la terapia con
corticosteroides
7. Diagnóstico reconfirmado: características de asma difícil de
tratar y adherencia a la terapia se volvieron a confirmar.
Kaza et al.Acute severe asthma.Current Opinion in Pulmonary Medicine 2007, 13:1–7

Am J Respir Crit Care Med Vol 162. pp 2341–2351, 2000
Am J Respir Crit Care Med Vol 172. pp 149–160, 2005
Ruben D. Restrepo,Jay Peters .Near-fatal asthma: recognition and management.Current Opinion in Pulmonary Medicine 2008, 14:13–23
A. Obstrucción persistente
B. Episodios recurrentes de estrechamiento severo de vías aéreas en minuotss u horas sin triggers
reconocidos (Brittle asthma tipo I).
C. Asma Fatal o casi fatal ( Brittle asthma tipo II)
Urs Frey. Current Opinion in Allergy and Clinical Immunology 2007, 7:223–230
Sally Wenzel . Severe Asthma in Adults. Am J Respir Crit Care Med Vol 172. pp 149–160, 2005
Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for betaagonist treatment of acute asthma.
Cochrane Database of Systematic Reviews 2006
No hay diferencias
entre NBZ y MDI con
aerocámara
Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for betaagonist treatment of acute asthma. Cochrane Database of Systematic Reviews 2006,
Los niños que usan MDI con aerocámara
demoran menos en la EMG
Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for betaagonist treatment of acute asthma. Cochrane Database of
Systematic Reviews 2006
Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for betaagonist treatment of acute asthma. Cochrane Database of
Systematic Reviews 2006
Los B2 agonistas inhalados a altas dosis son los
agentes de primera línea en asma aguda y deben ser
usados tan pronto como sea posible (A).
Reservar β2 agonistas intravenosos para aquellos

casos en los cuales la terapia inhalada no pueda ser
usada (A).
Travers AA, Jones AP, Kelly KD, Camargo CA, Barker SJ, Rowe BH. Intravenous beta2-agonists for acute
asthma in the emergency department. Cochrane Database of Systematic Reviews 2001
4–8 puffs cada 20 minutos hasta por 4
horas
Luego inhalar cada 1-4 horas según
necesidad .
National Asthma Education and Prevention Program Expert Panel Report 3 Guidelines for the Diagnosis and
Management of Asthma. 2007
La evidencia recomienda el uso de NBZ con B2 agonistas de uso continuo en
pacientes con asma aguda severa para incrementar su función pulmonar y reducir
las hospitalizaciones. Es un tratamiento seguro y bien tolerado. (A)
Deben usarse en aquellos con pobre respuesta a tratamiento inicial con B2 (MDI o
NBZ) (A)
Camargo CA, Spooner C, Rowe BH. Continuous versus intermittent beta-agonists for acute asthma. Cochrane Database
of Systematic Reviews 2003
Solución al 5%:
1 gota = 0,25 mg.
Fenoterol 1.25 mg -2.5mg dosis ( 5 -10 gotas) cada 20 min por 3 veces ,
y luego cada 1-4 horas según necesidad
o
NBZ contínua Fenoterol 5 - 7.5 mg / hora
Management
Primer Consenso Uruguayo para el Manejo del of Asthma.
Asma 2007
(1998-1999)
Camargo CA, Spooner C, Rowe BH. Continuous versus intermittent beta-agonists for acute asthma.
La NBZ contínua diminuye los valores de
PEFR mejor que la NBZ intermitente
Camargo CA, Spooner C, Rowe BH. Continuous versus intermittent beta-agonists for acute asthma.
No hay datos de RCT que provean evidencia a favor o en
contra de usar B2 agonistas inhalados en asmáticos
quienes están intubados en VM
Jones AP, Camargo CA, Rowe BH. Inhaled beta2-agonists for asthma in mechanically
ventilated patients. Cochrane Database of Systematic Reviews 2001
No hay diferencia en las recaidas entre los que usan CI o LABA /CI
p = 0.42
Acad Emerg Med October 2007, Vol. 14, No. 10

No hay diferencia en la calidad de vida entre
los que usan CI o LABA /CI
p = 0.43

Adding Long-acting b-agonists to Inhaled Corticosteroids after
Discharge from the Emergency Department for Acute Asthma:
No hay diferencia entre los

que usan CI o LABA /CI al
alta de la Emergencia

• Usar corticoides dentro de la primera hora de presentación reduce
significativamente la necesidad de hospitalización
• Los beneficios son mayores en pacientes con asma más severa

y en aquellos que no estaban recibiendo esteroides.
Rowe BH, Spooner C, Ducharme F, Bretzlaff J, Bota G. Early emergency department treatment of acute asthma with systemic
corticosteroids. Cochrane Database of Systematic Reviews 2001
• Iniciar con Prednisolona 40-50 mg diarios o
Hidrocortisona 100 mg cada 6 horas
• Al alta continuar con Prednisolona 40-50 mg diarios

por mínimo 5 días o hasta la recuperación total.

Rowe BH, Spooner C, Ducharme F, Bretzlaff J, Bota G. Early emergency department treatment of acute
asthma with systemic corticosteroids. Cochrane Database of Systematic Reviews 2001
Un curso corto de corticoides en una exacerbación de asma
reduce significativamente el número de recaidas ,
hospitalizaciones y uso de B2 agonistas de acción corta sin
incrementar los efectos colaterales.
Corticoides orales o parenterales son igual de efectivos
Rowe BH, Spooner C, Ducharme F, Bretzlaff J, Bota G. Corticosteroids for preventing relapse following acute
exacerbations of asthma. Cochrane Database of Systematic Reviews 2007.
Smith M, Iqbal SMSI, Rowe BH, N’Diaye T. Corticosteroids for hospitalised children with acute asthma. Cochrane Database
of Systematic Reviews 2003
 A significant number of steroid treated children were discharged
early after admission (>4 hours) with an OR of 7.00 (95% CI: 2.98
to 16.45) and NNT of 3 (95%CI: 2 to 8).
 The length of stay was shorter in the steroid groups with a WMD
of -8.75 hours (95% CI: -19.23 to 1.74).
 There were no significant differences between groups in

pulmonary function or oxygen saturation measurements.
 Children treated with steroids in hospital were less likely to

relapse within one to three months with OR 0.19 (95%CI: 0.07 to
0.55) and NNT of 3 (95%CI: 2 to 7).
 The single small study that compared nebulised budesonide to
oral prednisone failed to demonstrate equivalence or a difference
between each therapy.
Smith M, Iqbal SMSI, Rowe BH, N’Diaye T. Corticosteroids for hospitalised children with acute asthma. Cochrane Database of Systematic
Reviews 2003
Hay insuficiente evidencia que los CI provean beneficios
adicionales cuando son usados en combinación con terapia
corticoide oral estandar , luego del alta de la EMG por asma
exacerbada.
Existe evidencia que CI a dosis altas puede ser tan efectivo

como los Corticoides orales en asmáticos leves al alta de la
EMG.
Edmonds M, Brenner BE, Camargo CA, Rowe BH. Inhaled steroids for acute asthma following emergency department discharge. Cochrane
Database of Systematic Reviews 2000
Database of Systematic Reviews 2000, Issue 3. Art. No.: CD002316. DOI: 10.1002/14651858.CD002316.
• Systemic corticosteroids should be given to all patients with acute asthma
presenting to the emergency department.
• Inhaled steroid therapy decreases admission rates in patients compared to
treatment with placebo.
• The additive benefit of inhaled steroids when used with systemic corticosteroids
remains uncertain, although the results of this systematic review suggest an
additive effect.
• Inhaled steroid are well tolerated with few short term side-effects.
• There is insufficient evidence to determine whether the effect of ICS therapy is
different in certain populations, such as children Vs adults, or in mild Vs severe
asthmatics.
• There is insufficient evidence that ICS therapy alone can be used to replace
systemic CS therapy.
 Inhaled steroids reduced admission rates in patients with acute asthma, but it is
unclear if there is a benefit of ICS when used in addition to systemic
corticosteroids. There is insufficient evidence that ICS therapy results in clinically
important changes in pulmonary function or clinical scores when used in acute
asthma.
 Similarly, there is insufficient evidence that ICS alone is as effective as CS. Further
research is needed to clarify if there is a benefit of ICS when used in addition to CS.
Edmonds M, Camargo CA, Pollack CV, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma.
Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD002308. DOI: 10.1002/14651858.CD002308.
Rowe BH, Spooner C, Ducharme F, Bretzlaff J, Bota G. Corticosteroids for preventing relapse following acute exacerbations of asthma.
Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD000195. DOI: 10.1002/14651858.CD000195.pub2.
 The evidence suggests that ICS, in conjunction with standard treatment, may be beneficial for
the early treatment of acute exacerbations of asthma among adults and children. Multiple doses
should be administered at least half hourly for 90 to 120 minutes.
 Inhaled fluticasone or budesonide should be administered to adults and children with acute
exacerbations of asthma at minimum doses of 500 microg every 15 minutes or 800
microg every 30 minutes, respectively, via a metered-dose inhaler and spacer or
nebuliser for 90 to 120 minutes.
Rodrigo G J. Rapid effects of inhaled corticosteroids in acute asthma: an evidence-based evaluation. Chest 2006; 130(5): 1301-1311
 In preschool-age children with moderate-to-severe virus-induced wheezing,
preemptive treatment with high-dose fluticasone as compared with placebo reduced
the use of rescue oral corticosteroids.
 Treatment with fluticasone was associated with a smaller gain in height and
weight.
 Given the potential for overuse, this preventive approach should not be
adopted in clinical practice until long-term adverse effects are clarified.
N Engl J Med 2009;360:339-53.

MJA 2008; 189: 306–310
 La combinación de B2 y anticolinérgicos está indicada en asma aguda severa o
con riesgo de vida o en aquellos con pobre respuesta inicial a B2 agonistas.
 La combinación mejora la función pulmonar , reduce en 25% el riesgo de

hospitalización y en 19% la necesidad de uso de broncodilatador adicional.
 Los anticolinérgicos no son necesarios ni beneficiosos en exacerbaciones leves

o luego de la estabilización.
Plotnick L, Ducharme F. Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children. Cochrane
Database of Systematic Reviews 2000.
NBZ : Ipratropio 500 ug (40 gotas) cada 20 min
por 3 veces y luego a necesidad
1 gota = 0.0125 mg de Bromuro anhidro de

Ipratropio
Aerosol: 4-8 inhalaciones cada 20 minutos como

sea necesario hasta por 3 horas
Cada Inhalación = 20 ug
Management of Asthma. 2007
Adding inhaled anti-cholinergics to beta 2-agonists in the
treatment of acute asthma in children presenting to the
Emergency Department reduces time to recovery and discharge
and may reduce admissions for moderate to severe groups
Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review. Thorax
2005;60:740-6.
2005;60:740-6.
2005;60:740-6.
2005;60:740-6.
2005;60:740-6.
La evidencia actual no recomienda uso de rutina de
Sulfato de Magnesio EV en todos los pacientes con
asma aguda.
Sulfato de Magnesio EV es seguro y beneficioso en

pacientes que presentan asma aguda SEVERA.
Rowe BH, Bretzlaff J, Bourdon C, Bota G, Blitz S, Camargo CA. Magnesium sulfate for treating exacerbations of acute asthma in the emergency
department.CochraneDatabase of Systematic Reviews 2000
En esta revisión se usó Mg SO4 :
 2 gm EV pasados en 20 minutos en adultos y
 25 - 100 mg/kg EV en niños
En pacientes con asma aguda SEVERA (PEFR < 25-30% luego de terapia usual con
B2 agonistas y/o no respondedores) mejoran su función pulmonar y reducen el
número de hospitalizaciones
Rowe BH, Bretzlaff J, Bourdon C, Bota G, Blitz S, Camargo CA. Magnesium sulfate for treating exacerbations of acute asthma in the emergency
department.CochraneDatabase of Systematic Reviews 2000
 Intravenous magnesium sulphate is likely to
provide additional benefit in children with
moderate to severe acute asthma who are being
treated with bronchodilators and steroids.
Cheuk D K, Chau T C, Lee S L. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Archives of Disease in
Childhood 2005; 90(1): 74-77
Childhood 2005; 90(1): 74-77
Childhood 2005; 90(1): 74-77
 El tratamiento con MgSO4 debe ser considerado en adición a B2
agonistas inhalados en exacerbaciones de asma SEVERAS
 En asmáticos SEVEROS la mejoría de función pulmonar fue
significativa (SMD: 0.55; 95% CI: 0.12 to 0.98).
 Dosis usadas NBZ 135 mg-1152 mg
Blitz M, Blitz S, Beasely R, Diner B, Hughes R, Knopp JA, Rowe BH. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane
Database of Systematic Reviews 2005.
Emerg. Med. J. 2007;24;823-830
Emerg. Med. J. 2007;24;823-830
Emerg. Med. J. 2007;24;823-830
Emerg. Med. J. 2007;24;823-830
Emerg. Med. J. 2007;24;823-830
 The addition of aminophylline to steroids and ß2-agonist significantly
improved FEV1%predicted over placebo at 6-8 hours, 12-18 hours and 24
hours.
 Aminophylline led to a greater improvement in PEF%predicted over

placebo at 12-18 hours.
 There was no significant difference in length of hospital stay, symptoms,

frequency of nebulisations and mechanical ventilation rates.
 There were insufficient data to permit aggregation for oxygenation and

duration of supplemental oxygen therapy.
 Aminophylline led to a three-fold increase in the risk of vomiting.
 There was no significant difference between treatment groups with regard

to hypokalaemia, headaches, tremor, seizures, arrhythmias and deaths.
Mitra AAD, Bassler D, Watts K, Lasserson TJ, Ducharme FM. Intravenous aminophylline for acute severe asthma in children over two years
receiving inhaled bronchodilators. Cochrane Database of Systematic Reviews 2005.
1. There is insufficient evidence to support the routine use of
aminophylline in the management of acute asthma when
adequate beta-agonist treatment is provided.
2. The development of side effects is significantly higher with

aminophylline treatment than beta2-agonist therapy alone.
Parameswaran K, Belda J, Rowe BH. Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma. Cochrane Database
of Systematic Reviews 2000.
Parameswaran K, Belda J, Rowe BH. Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma. Cochrane Database of Systematic Reviews 2000.
P < 0.05
Teofilina EV Suero Salino
Respirology (2005) 10, 491–496

P < 0.05

Respirology (2005) 10, 491–496
P < 0.05

Respirology (2005) 10, 491–496
P < 0.05

Respirology (2005) 10, 491–496
 Pacientes con asma casi fatal o con riesgo de vida con
una pobre respuesta a terapia inicial
 Aminofilina EV :
 Dosis de carga: 5 mg/kg pasados en 20 min .
 Luego : 0.5-0.7 mg/kg/hr en infusión

Al momento no existe evidencia que apoyen el
uso de ATB durante el asma aguda
Graham V, Lasserson TJ, Rowe BH. Antibiotics for acute asthma. Cochrane Database of Systematic
Reviews 2001.
• No existe evidencia que soporte la administración de Helio-
Oxígeno a todos los pacientes con Asma Aguda
• Evidencia sugiere ciertos beneficios en pacientes con

obstrucción más severa.Sin embargo no es recomendado
para uso de asma aguda.
Rodrigo GJ, Pollack CV, Rodrigo C, Rowe BH. Heliox for nonintubated acute asthma patients. Cochrane Database of Systematic Reviews 2006.
 The one included trial, on 30 patients, showed benefit withNPPV when compared to
usualmedical care alone with significant improvements in hospitalisation rate,
number of patients discharged fromemergency department, percent predicted FEV1,
FVC, PEFR and respiratory rate.
 This review provides some promising results in favour of the use of NPPV in severe
acute asthma; however, the weaknesses described above and the concern with
prolonged hospitalisation suggest that the regular use of NPPV in status asthmaticus
still remains controversial.
 Until large randomised controlled trials are completed, this therapy should be
restricted and routine clinical use cannot be recommended.
Rowe BH, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of
asthma. Cochrane Database of Systematic Reviews 2005.
Changes of FEV1 along with the time course (mean 1 SD).
There was a significant difference between NPPV-H and control group (*: p=0.009).
NPPV-H: High pressure group, NPPV-L: Low pressure group
Inter Med 47: 493-501, 2008

Changes in the Borg scale along with the time course (mean 1 SD).
There were significant differences between NPPV-L and control group (*: p<0.001),
and between NPPV-H and control group (**: p=0.023)
Inter Med 47: 493-501, 2008
There is currently insufficient evidence to support the routine addition of nebulised
furosemide to standard beta agonist therapy in acute asthma in adults.
http://www.bestbets.org/bets/bet.php?id=00969
Emergency Department Management
Acute Asthma
Initial Assessment
History, Physical Examination, PEFR
Initial Therapy
Inhaled B2-agonist • O2 if needed
Good Response
Incomplete/Poor response Respiratory failure
Observe for at
least 1 hour Add Systemic Corticosteroids
Good Response Poor Response

If Stable,
Discharge to
Home Discharge Admit to Hospital Admit to ICU
VNI o VM
+
Sally Wenzel . Severe Asthma in Adults. Am J Respir Crit Care Med Vol 172. pp 149–160, 2005
Emergency Medicine Australasia (2009) 21, 259–268
Gracias Totales !!
alf0305@yahoo.com
alfredopachas0305@hotmail
.com

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Recomendaciones Basadas en la Evidencia

Dr. Alfredo Pachas Q.

Tipo 2: Ataques severos súbitos en pacientes aparentemente bien controlados

ASMA SEVERA AGUDA

British Guideline on the Management of Asthma 2009

pobre Presiones altas

Disnea Al caminar, puede Al hablar, prefiere Al acostarse

Habla Frases Parte de frases Palabras No puede hablar

Nivel de Puede estar agitado Usualmente agitado Siempre agitado Somnolencia o

Frec Resp Incrementada Incrementada A menudo > 30 /

Retracciones NO Usualmente Usualmente Movimientos

Sibilancias Moderados, al final de Fuertes Muy fuertes Ausente

FC < 100 100 - 120 > 120 Bradicardia

PEF luego del > 70% 50 – 70 % < 50 % Imposible de medir

N. Behbehani,J. M. FitzGerald. Int J Tuberc Lung Dis 10(4):356–364. 2006

Kaza et al.Acute severe asthma.Current Opinion in Pulmonary Medicine 2007, 13:1–7

C. Asma Fatal o casi fatal ( Brittle asthma tipo II)

Reservar β2 agonistas intravenosos para aquellos

British Guideline on the Management of Asthma 2009

Luego inhalar cada 1-4 horas según

las hospitalizaciones. Es un tratamiento seguro y bien tolerado. (A)

contra de usar B2 agonistas inhalados en asmáticos

quienes están intubados en VM

Acad Emerg Med October 2007, Vol. 14, No. 10

Acad Emerg Med October 2007, Vol. 14, No. 10

No hay diferencia entre los

Acad Emerg Med October 2007, Vol. 14, No. 10

• Los beneficios son mayores en pacientes con asma más severa

• Al alta continuar con Prednisolona 40-50 mg diarios

British Guideline on the Management of Asthma 2009

Corticoides orales o parenterales son igual de efectivos

 There were no significant differences between groups in

 Children treated with steroids in hospital were less likely to

Existe evidencia que CI a dosis altas puede ser tan efectivo

preemptive treatment with high-dose fluticasone as compared with placebo reduced

the use of rescue oral corticosteroids.

adopted in clinical practice until long-term adverse effects are clarified.

N Engl J Med 2009;360:339-53.

 La combinación mejora la función pulmonar , reduce en 25% el riesgo de

 Los anticolinérgicos no son necesarios ni beneficiosos en exacerbaciones leves

British Guideline on the Management of Asthma 2009

1 gota = 0.0125 mg de Bromuro anhidro de

Aerosol: 4-8 inhalaciones cada 20 minutos como

British Guideline on the Management of Asthma 2009

treatment of acute asthma in children presenting to the

Emergency Department reduces time to recovery and discharge

and may reduce admissions for moderate to severe groups

Sulfato de Magnesio EV es seguro y beneficioso en

 2 gm EV pasados en 20 minutos en adultos y

 25 - 100 mg/kg EV en niños

B2 agonistas y/o no respondedores) mejoran su función pulmonar y reducen el

provide additional benefit in children with

moderate to severe acute asthma who are being

treated with bronchodilators and steroids.

agonistas inhalados en exacerbaciones de asma SEVERAS

 En asmáticos SEVEROS la mejoría de función pulmonar fue

significativa (SMD: 0.55; 95% CI: 0.12 to 0.98).

 Dosis usadas NBZ 135 mg-1152 mg

 Aminophylline led to a greater improvement in PEF%predicted over

 There was no significant difference in length of hospital stay, symptoms,

 There were insufficient data to permit aggregation for oxygenation and

 Aminophylline led to a three-fold increase in the risk of vomiting.

 There was no significant difference between treatment groups with regard

2. The development of side effects is significantly higher with