Influences of cannula size and flow rate on aerosol drug delivery through the Vapotherm humidified high-flow nasal cannula system.

OBJECTIVE: We investigated the in vitro inspired dose and particle size distribution of albuterol delivered by a vibrating mesh nebulizer through the Vapotherm (Stevensville, MD) humidified high-flow nasal cannula system. DESIGN: Albuterol (2.5 mg/3 mL) was delivered by an Aeroneb Solo (Aerogen, Galway, Ireland) nebulizer that was connected via adaptor proximal to the nasal cannula and downstream from the Vapotherm 2000i. Albuterol was collected onto an inspiratory filter mounted to a breath simulator programmed with age-appropriate breathing patterns. Particle sizing was completed by cascade impaction. Albuterol was quantified using ultraviolet spectrometry. Measurements were made using varying flow rates through infant, pediatric, and adult nasal cannulae. SETTING: Aerosol research laboratory. MEASUREMENTS AND MAIN RESULTS: The inspired dose (percent of nominal dose) for each cannula size and flow rate was 2.5%, 0.8%, 0.4%, and 0.2% for the adult cannula at 5, 10, 20, and 40 L/min, respectively; 1.2%, 0.6%, 0.1%, and 0.0% for the pediatric cannula at 3, 5, 10, and 20 L/min, respectively; and 0.6%, 0.6%, and 0.5% for the infant cannula at 3, 5, and 8 L/min, respectively. Most (62-80%) of the loaded albuterol dose accumulated within the adaptor. For each cannula size, there was a significant decrease in the inspired dose with increasing flow rates, p = 0.026 (infant), p = 0.001 (pediatric), and p < 0.001(adult). The inspired dose increased with increasing cannula size for 5, 10, and 20 L/min (p = 0.007, p < 0.001, and p = 0.005, respectively). The mass median aerodynamic diameter for all trials was less than 5 µm. CONCLUSION: The amount of albuterol delivered with the Vapotherm system using this model was lower than the amount expected for a clinical response for the majority of flow rates and cannula size combinations. Further studies are needed before routine use of aerosolized albuterol through a Vapotherm high-flow system can be recommended.

A technical feasibility study of dornase alfa delivery with eFlow® vibrating membrane nebulizers: aerosol characteristics and physicochemical stability.

Dornase alfa (Pulmozyme®) is an inhaled mucus-active drug that decreases viscoelasticity of sputum in vitro, improves lung function and reduces respiratory exacerbations in cystic fibrosis (CF) patients of 5 years age and older. The regulatory approval of dornase alfa 15 years ago stipulated that only certain jet nebulizer-compressor combinations should be used to deliver the drug. Since that time there have been significant advances in aerosol delivery technology, including development of electronic perforated vibrating membrane devices. Three independent laboratories studied aerosol characteristics, nebulization time, dose delivery, and stability of dornase alfa after nebulization to determine the feasibility of using perforated vibrating membrane devices to deliver the drug. These studies determined that the eFlow® vibrating membrane technology delivers dornase alfa more rapidly and efficiently than jet nebulizers, and does not affect the physicochemical properties of the drug. These in vitro results demonstrate only the technical feasibility of using vibrating membrane devices to deliver dornase alfa. Clinical studies will be required before any conclusions can be made regarding clinical safety and efficacy of these drug-device combinations for cystic fibrosis.

The I-neb Adaptive Aerosol Delivery System enhances delivery of alpha1-antitrypsin with controlled inhalation.

BACKGROUND: Inhaled alpha1-antitrypsin (AAT) is being developed for treatment of cystic fibrosis to protect the lungs from excessive free elastase. High drug costs mandate a very efficient aerosol system to deliver a high payload to the airways. The I-neb Adaptive Aerosol Delivery (AAD) System is a portable, electronic, vibrating mesh nebulizer that delivers aerosol only during inhalation. It can be operated in conventional tidal breathing mode (TBM) or in target inhalation mode (TIM) that guides the patient to inhale deeply and slowly. The purposes of this in vitro study were to determine aerosol characteristics, device efficiency, and delivery time of AAT using the I-neb AAD System with TBM and TIM. METHODS: We studied the I-neb AAD System in TBM and TIM (inspiratory time 6 or 9 sec) using a breath simulator. The loaded dose was 0.5 mL AAT (50 mg/mL). Nebulized drug captured on an inspiratory filter was reported as emitted dose. Particle size was measured by laser diffraction. Predicted lung doses were calculated based on the results of a prior scintigraphy study of the I-neb AAD System. RESULTS: Particle size (VMD) for TBM and TIM was similar (4.4-4.8 microm). The emitted doses were very high and similar between modes (82-90% of loaded dose). Predicted lung dose of AAT (percent of loaded dose) and delivery times were: TBM 56.6% in 7.5 min; TIM-6 59.9% in 4.4 min; and TIM-9 64.5% in 2.5 min. CONCLUSIONS: The I-neb AAD System enhanced AAT delivery by inhalation-only aerosol generation and a low-residual dose. Predicted lung dose was high for both TBM and TIM, but longer inspiratory times with TIM reduced the administration time to one-third that of tidal breathing. We conclude that slow, deep, controlled inspirations using the I-neb AAD System is an efficient method to deliver AAT.

New aerosol delivery devices for cystic fibrosis.

Cystic fibrosis (CF) patients use several therapies to treat chronic inflammation and infection in the lungs and to improve airway clearance. Inhaled therapies in CF typically include bronchodilators, airway wetting agents, mucus-active agents, and antibiotics, among others. There are many variables to take into account when prescribing aerosolized therapies to CF patients, including aerosol factors, patient variables (eg, age, disease severity, and breathing patterns), and the limitations of current aerosol delivery systems. The greatest challenge for patients is dealing with the time burden placed on them to try to fit all the treatments into their day-a burden that is likely to be even greater in the near future due to the exciting pipeline of novel therapies that target the genetic defect of CF as well as the pathophysiologic consequences. Fortunately, novel aerosol delivery systems and drug formulations are being developed to tackle the many challenges of aerosol delivery in CF. If successful, these systems will reduce the time burden and improve the clinical outcomes for the CF community.

Primary use of the venovenous approach for extracorporeal membrane oxygenation in pediatric acute respiratory failure.

OBJECTIVES: To describe a single center's experience with the primary use of venovenous cannulation for supporting pediatric acute respiratory failure patients with extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective chart review of all patients receiving extracorporeal life support at a single institution. SETTING: Pediatric intensive care unit at a tertiary care children's hospital. PATIENTS: Eighty-two patients between the ages of 2 wks and 18 yrs with severe acute respiratory failure. INTERVENTIONS: ECMO for acute respiratory failure. MEASUREMENTS AND MAIN RESULTS: From January 1991 until April 2002, 82 pediatric patients with acute respiratory failure were cannulated for ECMO support. Median duration of ventilation before ECMO was 5 days (range, 1-17 days). Sixty-eight of these patients (82%) initially were placed on venovenous ECMO. Fourteen patients were initiated and remained on venoarterial support, including six in whom venovenous cannulae could not be placed. One patient was converted from venovenous to venoarterial support due to inadequate oxygenation. Venoarterial patients had significantly greater alveolar-arterial oxygen gradients and lower PaO(2)/FIO(2) ratios than venovenous patients (p <.03). Fifty-five of 81 venovenous patients received additional drainage cannulae (46 of 55 with an internal jugular cephalad catheter). Thirty-five percent of venovenous patients and 36% of venoarterial patients required at least one vasopressor infusion at time of cannulation (p = nonsignificant); vasopressor dependence decreased over the course of ECMO in both groups. Median duration on venovenous ECMO for acute hypoxemic respiratory failure was 218 hrs (range, 24-921). Venovenous ECMO survivors remained cannulated for significantly shorter time than nonsurvivors did (median, 212 vs. 350 hrs; p =.04). Sixty-three of 82 ECMO (77%) patients survived to discharge-56 of 68 venovenous ECMO (81%) and nine of 14 venoarterial ECMO (64%). CONCLUSIONS: Venovenous ECMO can effectively provide adequate oxygenation for pediatric patients with severe acute respiratory failure receiving ECMO support. Additional cannulae placed at the initiation of venovenous ECMO could be beneficial in achieving flow rates necessary for adequate oxygenation and lung rest.