title: Effect of heliox on albuterol delivery by metered-dose inhaler in pediatric in vitro models of mechanical ventilation.
abstract: OBJECTIVE
  To determine the effect of varying concentrations of heliox, a mixture of helium and oxygen, on albuterol delivery administered by metered-dose inhaler (MDI) in pediatric mechanically ventilated models.
  
  
  METHODS
  Prospective in vitro laboratory study.
  
  
  METHODS
  University-affiliated research laboratory.
  
  
  METHODS
  The lungs of a 10-kg infant and 30-kg child receiving humidified pressure-regulated volume-controlled ventilation were simulated. The infant settings were an endotracheal tube (ETT) of 4.0 mm, tidal volume of 150 ml, positive end-expiratory pressure of 2 cm H(2)O, rate of 20 breaths/minute, inspiratory time of 0.7 second; the child settings were an ETT of 6.0 mm, tidal volume of 450 ml, positive end-expiratory pressure of 2 cm H(2)O, rate of 16 breaths/minute, and inspiratory time of 0.8 second.
  
  
  RESULTS
  Ten albuterol MDI canisters with chlorofluorocarbon propellants were each actuated once sequentially (total dose 1000 mug) with a commercially available aerosol holding chamber. Albuterol was collected onto a filter proximal to a lung simulator. The filter was rinsed, and concentrations were determined by high-performance liquid chromatography. In the infant model, heliox mixtures of 70:30, 60:40, and 50:50 were compared with nitrogen:oxygen (N(2):O(2)) mixtures in the same ratios. The effect of the 70:30 mixtures was also explored in a child model. Each gas mixture was tested 5 times. At all three ratios, albuterol delivery to the end of the ETT was improved with heliox compared with N(2):O(2) (approximately 7% vs 3-4%, p<0.0001, one-way analysis of variance [ANOVA] with a Bonferroni correction for multiple comparisons). No significant difference was noted in mean percentage albuterol delivery among the varying ratios of heliox studied. By two-way ANOVA, significantly greater albuterol delivery was noted with 70:30 heliox compared with 70:30 N(2):O(2) (7-8% vs 3%, p<0.0001), with no significant difference between the infant and child model (p=0.21). The gas mixture, model, and interaction of the two explained 88% of the variability in mean percentage albuterol delivery.
  
  
  CONCLUSIONS
  Heliox increased albuterol delivery administered by MDI to the end of the ETT in these in vitro pediatric models of mechanical ventilation. Further studies are needed to determine if the improved albuterol delivery with heliox enhances clinical response in infants and children needing mechanical ventilation.
authors.affiliation: Department of Pharmacy, Medical University of South Carolina, Charleston, South Carolina 29425, USA. garnerss@musc.edu
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Garner
authors.forename: Donald B
authors.initials: DB
authors.lastname: Wiest
authors.forename: Charles E
authors.initials: CE
authors.lastname: Stevens
authors.forename: David M
authors.initials: DM
authors.lastname: Habib
mesh_terms: D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D006371:Helium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008168:Lung / Q000187:drug effects*; D036501:Metered Dose Inhalers; D010100:Oxygen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012121:Respiration, Artificial
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D006371:Helium; C038949:heliox; D000420:Albuterol; D010100:Oxygen