Epinephrine, Dexamethasone, and Hypertonic Saline in Bronchiolitis, Randomised Clinical Trial of Efficacy and Safety
Condition: Bronchiolitis
MeSH terms: Bronchiolitis
Study type: Interventional
Phase: Phase 4

Summary: 
      In infancy, bronchiolitis is the most common acute infection of the lower respiratory Tract.
      The current treatment of bronchiolitis is controversial. Bronchodilators and corticosteroids
      are widely used but not routinely recommended. Hypertonic saline is currently the only drug
      recommended by the Spanish Association of Pediatrics in treatment guidelines.

      The purpose of this study is quantify whether epinephrine, dexamethasone, and hypertonic
      saline are effective to decrease the rate of hospital admissions at seven day, also verify
      adverse effects in patients submitted.
    

Detailed description: 
      Infections remain the leading cause of death globally, in 2010 from 7.6 million deaths in
      children under 5 years, 64% is attributed to an infectious cause, acute lower respiratory
      tract include 14.1% of all deaths, representing the leading cause of global mortality in
      children. In Mexico in children under 15 years the leading cause of death are conditions
      originating in the perinatal period, congenital malformations deformities and chromosomal
      abnormalities and third lower airway infections.

      Bronchiolitis being the leading cause of lower respiratory tract infection in infants, with a
      global load elevated, represented by a hospitalization rate of 3% of the total population of
      children under one year. Estimated that only in the United States of America, the annual cost
      of hospitalizations of patients under one year with bronchiolitis exceeds $ 700 million /
      year. Unfortunately, there is evidence that hospital admission rates have increased almost
      twice in the last 10-15 years in the United States and Canada, and it occurs most impact in
      developing countries, where befall 99% of deaths related to Respiratory Syncytial Virus
      (RSV), the leading cause of infection of lower airways.

      The etiology of the disease is attributed by 50 to 80% of all cases the RSV worldwide, has
      been reported in Mexico RSV as a cause of just over 80% of infections lower airway requiring
      hospitalization.

      Given such alarming morbidity figures, note that the mortality from this disease is low,
      representing less than 400 deaths annually, perhaps explained by the wide clinical spectrum
      that presents.

      Currently no management guide recommends specific treatment for bronchiolitis, in particular,
      it is necessary to mention the national clinical practice guideline, which emphasizes that
      there is no consensus on proper drug treatment for this disease.

      Until 2006, the American Academic of Pediatrics guidelines and Scottish Intercollegiate
      Guidelines Network recommend not using any systemic or inhaled drug for the management of
      bronchiolitis, this widely shown including bronchodilators, corticosteroids, antivirals and
      antitussive.

      Recent review of Cochrane Acute Respiratory Infections Group about benefit of glucocorticoids
      for acute viral bronchiolitis, concluded not significantly reduce outpatient admissions by
      days 1 and 7 when compared to placebo and there was no benefit in length of stay for
      inpatients; however unadjusted results from a large factorial low risk o bias Randomized
      Controlled Trial found combined high-dose systemic dexamethasone and inhaled epinephrine
      reduced admissions 26% with no differences in short-term adverse effects.

      L. Hartling et al, in 2011 review demonstrates the superiority of epinephrine compared to
      placebo for short-term outcomes for outpatients, particularly in the first 24 hours of care.

      In Mexico there is evidence of the use of dexamethasone in combination with inhaled
      salbutamol in the management of patients with bronchiolitis with decreased hospital stay to
      24hrs 96% vs 75% at P <0.05

      Furthermore, hypertonic saline (HS) has proven effective with minimal adverse effects and
      thus, currently the clinical practice guidelines of Spain in 2010, are the only recommended
      method.

      A study conducted by Ipek et al, a comparative study with four treatment groups I Salbutamol
      + Normal Saline 0.9% (NS), Group II Salbutamol + HS, Group III HS and Group IV NS, with the
      measurement variables heart rate, respiratory difficulty scale, and oxygen saturation, found
      that after treatment in all groups were significant improvement in breathlessness p <0.0001.
      These findings demonstrate the self-limiting nature of disease, bringing the ethical basis
      using NS as a control group because, per se, significantly reduces respiratory distress and
      as indicated by the clinical practice guidelines as part of management symptomatic.

      Therefore this research aims to be a pilot study to the population of Marina, first, get the
      best treatment evidence, using treatments that have reported better results in order to
      establish optimal treatment to reduce the rate of hospital admissions and with minimal
      adverse effects.

      Included in the study, patients with mild to moderate bronchiolitis, defining it as the first
      event of wheezing in infants under two years with a history of viral infection prodrome
      attending the emergency department (ED) the period January to April in 2013.

      Supportive care including oxygen supplementation if oxygen saturation less than 92% while
      breathing ambient; aspiration, temperature control and hydration when necessary were provided
      to all patients. Infants 2 to 24 months of age with bronchiolitis who were seen at emergency
      department were eligible for the study if they had a score of 2 to 8 on the Clinical
      Bronchiolitis Severity Scores (CBSS). The CBSS values the respiratory distress with
      respiratory rate, wheezing, general condition and presence of retractions on a scale from 0
      to 12, with higher scores indicating more severe illness; an a score above 9 very severe
      illness.

      All eligible patients were randomly assigned to one of three groups according to the
      consecutive order of their admission to the ED: group I received first day one treatment of
      nebulized dexamethasone and two treatments of epinephrine, followed by three days one
      treatment nebulized dexamethasone; Group II the first day received three nebulized HS
      followed by treatment with HS every 24 hours for 3 days and group 3 received only NS first
      day 3 treatments followed one treatment every 24hrs for 3 days. The nebulized solution was
      administered in a double-blind setting every 20 min until 3 doses had been administered (0,
      20 and 40th min).

      The research recorded the patient's CBSS score, respiratory rate, heart rate, and oxygen
      saturation in ambient air at baseline, between the three nebulizations, and at 60 and 90
      minutes; rectal temperature at baseline and 90 minutes; blood pressure at baseline and 90
      minutes; and any side effects throughout the observation period in the emergency department.

      Followed up each patient to record the admission rate in each group at 7 days of the study,
      as measure of efficacy of treatment. Likewise measured the potential adverse effects of each
      group, including hypertension, bronchospasm, tachycardia and any eventuality, as a security
      measure
    

Intervention name(s): Epinephrine and Dexamethasone; Hypertonic Saline; Normal Saline
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Dexamethasone; Epinephrine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: Bronchiolitis; Epinephrine; Dexamethasone; Hospitalization; Hypertonic Saline