Aerosols and devices.

The success of aerosol therapy depends upon the delivery of ample amounts of the drug to appropriate sites in the lung with minimal side effects. Successful aerosol therapy delivery systems must provide sufficient respirable particles or droplets, with minimal loss of the drug. Ultimately, the patient must be able to use the device easily, maintain it, and derive clinical benefit from the drug delivered from the system.

Aerosol therapy for children.

Pediatric aerosol therapy encompasses a range of patients from premature neonates with birth weights as low as 500 grams to adult size teenagers. This article focuses on the care of smaller infants and children in whom anatomic differences present substantial challenges for aerosol delivery.

Inhalation therapy during mechanical ventilation.

An increasing number of pharmacologic agents, including bronchodilators, prostaglandin, proteins, surfactant, mucolytics, and antibiotics are administered to mechanically ventilated patients by the inhalation route. To achieve a therapeutic effect, adequate amounts of an inhaled agent must be delivered to the desired site of action. The delivery of inhaled drugs to the lower respiratory tract of mechanically ventilated patients is complicated by deposition of the aerosol particles in the ventilator circuit and endotracheal tube, and the factors governing pulmonary deposition in mechanically ventilated patients are different from those in ambulatory patients. Meticulous adherence to several steps in the technique of aerosol administration is necessary for successful aerosol therapy in mechanically ventilated patients. With a proper technique of administration, an increasing number of inhaled drugs may be administered safely, conveniently, and effectively to mechanically ventilated patients.

Promoting adherence to inhaled therapy: building partnerships through patient education.

Optimal treatment outcomes are dependent upon patient adherence to therapy. Problems in adherence can be overcome by developing a professional-patient partnership that has the goal of developing communication between the partners, mutual accountability, respect for personal values and viewpoints, and shared decision making. The process of patient education is shaped by the needs of this developing partnership rather than a-priori goals established by the professional.

Laboratory evaluation of metered-dose inhalers with models that simulate interaction with the patient.

Laboratory evaluation of aerosol generating-devices is usually performed under conditions of constant airflow. The performance of aerosol-generating devices with different tidal volumes and inspiratory airflows encountered in clinical practice cannot be determined by these methods. To overcome this problem, models have been developed that simulate patients' breathing pattern, provide measurements of inhaled or respirable mass, and the proportion of aerosol exhaled. This article explores the development of such a model.

Improvement in aerosol delivery with helium-oxygen mixtures during mechanical ventilation.

In mechanically ventilated patients with airway obstruction, helium-oxygen (He-O2) mixtures reduce airway resistance and improve ventilation, but their influence on aerosol delivery is unknown. Accordingly, we determined the effect of various He-O2 mixtures on albuterol delivery from metered-dose inhalers (MDIs) and jet nebulizers in an in vitro model of mechanical ventilation. Albuterol delivery from a MDI was increased when the ventilator circuit contained 80% helium and 20% oxygen (He-O2 80/20) versus O2: 46.7 +/- 3.3 versus 30.2 +/- 1.3 (SE)% of the nominal dose (p < 0.001)-the difference was mainly due to decreased drug deposition in the spacer chamber, mean 39.2% and 55.2%, respectively (p < 0.001). Nebulizer efficiency at a flow rate of 6 L/min was five times lower with He-O2 80/20 than O2, and the amount of nebulized drug was inversely correlated with gas density (r = 0.94, p < 0.0001). When the nebulizer was operated with O2, greater albuterol delivery was achieved when the ventilator circuit contained He-O2 rather than O2. In summary, He-O2 mixtures in the circuit increased aerosol delivery for both MDIs and nebulizers in the mechanically ventilated model by as much as 50%. In conclusion, at appropriate flow rates and concentrations, He-O2 in the ventilator circuit may improve aerosol delivery in mechanically ventilated patients with severe airway obstruction.

Aerosol device selection: evidence to practice.

Therapeutic aerosols are generated by pneumatic jet nebulizers, ultrasonic nebulizers, pressurized metered-dose inhalers, and dry powder inhalers. Some of the drug preparations used in these devices are formulated to work with specific devices. Although design improvements in aerosol devices have led to improved lung deposition, decreased oropharyngeal deposition, decreased waste of drug, greater ease of use, and lower environmental impact, optimizing the use of aerosol devices requires patient and caregiver instruction, in combination with proper device use and maintenance. Optimizing aerosol delivery requires knowledge of a number of technical details, and caregivers should stay abreast of the continuing advancement of technologies and techniques associated with aerosol delivery, especially in light of emerging devices and formulations.

Metered-dose inhalers, dry powder inhalers, and transitions.

Since 1956, the pMDI has become the most commonly prescribed and used aerosol device in the world. While concerns about global warming have led to a worldwide ban of CFCs, new HFA-propelled pMDIs are in development, requiring an evolutionary transition in the technology. The phase-out of CFC-propelled pMDIs has stimulated the development of more efficient DPIs, but issues such as cost of device production, inspiratory flow requirement, and the effects of ambient humidity on drug delivery may limit DPI acceptance, and industry projections suggest that the DPI will not completely replace the pMDI. Holding chambers may perform differently with HFA-propelled pMDIs, but HFA-propelled pMDIs generally appear to cause less oropharyngeal deposition and to improve lung delivery while continuing to provide protection from poor hand-breath coordination. The initial offerings of the emerging HFA-propelled pMDI technology appear to be resulting in an improved pMDI.

Aerosol therapy in mechanically ventilated patients: recent advances and new techniques.

Therapeutic aerosols are commonly used in mechanically ventilated patients, yet information regarding their efficacy and optimal technique of administration has been limited. The advantages of aerosol therapy include a smaller dose, efficacy comparable with that observed with systemic administration of the drug, and a rapid onset of action. Inhaled drugs are delivered directly to the respiratory tract, their systemic absorption is limited, and systemic side effects are minimized. Inhaled bronchodilators are routinely used with mechanically ventilated patients in the intensive care unit, but a variety of drugs ranging from antibiotics to surfactants has been administered. Nebulizers and metered-dose inhalers (MDIs) are commonly used aerosol generators because they produce respirable particles with a mass median aerodynamic diameter (MMAD) between 1 and 5 mum. Due to the limitation of available formulations, MDIs are chiefly used to deliver bronchodilators and steroids, whereas nebulizers have greater versatility and can be used to administer bronchodilators, antibiotics, surfactant, mucokinetic agents, and other drugs. The delivery of inhaled drugs in mechanically ventilated patients differs from that in ambulatory patients in several respects. Until recently, the consensus of opinion was that the efficiency of aerosol delivery to the lower respiratory tract in mechanically ventilated patients was much lower that that in ambulatory patients. Data suggest that this might be overly pessimistic and that the endotracheal tube may actually facilitate greater aerosol delivery compared with the normal airway when a variety of variables effecting aerosol delivery during mechanical ventilation are optimized.

Preferential pulmonary retention of (S)-albuterol after inhalation of racemic albuterol.

The (R)-enantiomer of racemic albuterol produces bronchodilation, whereas the (S)-enantiomer may increase airway reactivity. After oral or intravenous administration of racemic albuterol, the (R)- enantiomer is metabolized several times faster than the (S)-enantiomer; however, enantiomer disposition after inhaling racemic albuterol with a metered-dose inhaler (MDI) is not known. Accordingly, 10 healthy subjects inhaled racemic albuterol with a MDI alone and with a MDI and holding chamber. We measured plasma levels of unchanged (R)- and (S)-albuterol before and up to 4 h after inhalation of racemic albuterol, and determined the unchanged R/S ratio in urine before and at 0.5, 4, 8, and 24 h later. The disposition of albuterol's enantiomers with a MDI and holding chamber was similar to that with a MDI alone. The area under the curve (AUC) of the plasma levels over time was significantly lower for the (S)- than for the (R)-enantiomer-395.5 +/- 141.0 (SE) versus 882.7 +/- 126.4 ng. ml(-)(1). min (p < 0.05)-indicating preferential retention of (S)-albuterol in the lung. The R/S ratio in urine at 0. 5 h after albuterol was > 1, reflecting the higher plasma level of the (R)-enantiomer. In conclusion, preferential retention of the (S)- compared with the (R)-enantiomer in the lung could lead to accumulation of the (S)-enantiomer after long-term use of racemic albuterol.

Reconciling in vitro and in vivo measurements of aerosol delivery from a metered-dose inhaler during mechanical ventilation and defining efficiency-enhancing factors.

We attempted to resolve the discrepancies in reported data on aerosol deposition from a chlorofluorocarbon (CFC)-propelled metered-dose inhaler (MDI) during mechanical ventilation, obtained by in vivo and in vitro methodologies. Albuterol delivery to the lower respiratory tract was decreased in a humidified versus a dry circuit (16.2 versus 30.4%, respectively; p < 0.01). In 10 mechanically ventilated patients, 4.8% of the nominal dose was exhaled. When the exhaled aerosol was subtracted from the in vitro delivery of 16.2% achieved in a humidified ventilator circuit, the resulting value (16.2 - 4.8 = 11.4%) was similar to in vivo estimates of aerosol deposition. Having reconciled in vitro with in vivo findings, we then evaluated factors influencing aerosol delivery. A lower inspiratory flow rate (40 versus 80 L/min; p < 0.001), a longer duty cycle (0.50 versus 0.25; p < 0.04), and a shorter interval between successive MDI actuations (15 versus 60 s; p < 0.02) increased aerosol delivery, whereas use of a hydrofluoroalkane (HFA)-propelled MDI decreased aerosol delivery compared with the CFC-propelled MDI. A MDI and actuator combination other than that designed by the manufacturer altered aerosol particle size and decreased drug delivery. In conclusion, aerosol delivery in an in vitro model accurately reflects in vivo delivery, providing a means for investigating methods to improve the efficiency of aerosol therapy during mechanical ventilation.

Extending ventilator circuit change interval beyond 2 days reduces the likelihood of ventilator-associated pneumonia.

OBJECTIVE: To determine the risk of acquiring ventilator-associated pneumonia (VAP) and the impact on costs when extending ventilator circuit change intervals beyond 2 days to 7 and 30 days. DESIGN: Prospective 4-year review of mechanically ventilated patients. SETTING: The respiratory and medical ICUs of an 800-bed tertiary teaching Veterans Affairs hospital. PATIENTS: All adult patients receiving mechanical ventilation from January 1991 through December 1994. INTERVENTIONS: Ventilator circuits with active heated water humidifiers were changed at 2-day intervals during a 2-year control period, followed by 7-day and 30-day intervals (for 1 year each). Heated wire circuits were adopted with the 30-day interval. The rate of VAP per 1,000 ventilator days was calculated for each circuit change interval group. Survival analysis was used to model VAP with ventilator circuit change to determine risk. RESULTS: During the study period, 637 patients received mechanical ventilation. During the 2 years with 2-day change intervals, the VAP per 1,000 ventilator days was 11.88 (n=343), compared with 3.34 (n=137) and 6.28 (n=157) for 7-day and 30-day change intervals, respectively. The risk of acquiring a VAP for those with a circuit change every 2 days was significantly greater (relative risk, 3.1; p=0.0004; 95% confidence interval, 1.662, 5.812) than those with the 7- and 30-day circuit changes. Extending circuit change intervals reduced supply and labor costs averaging $4,231/yr for each ventilator in use. CONCLUSIONS: Circuit change intervals of 7 and 30 days have lower risks for VAP than the 2-day intervals, yielding substantial reductions in morbidity as well labor and supply costs.

Serum albuterol levels in mechanically ventilated patients and healthy subjects after metered-dose inhaler administration.

In mechanically ventilated patients, systemic blood levels of inhaled drugs reflect absorption from the lower respiratory tract alone since, unlike nonintubated patients, oropharyngeal and gastrointestinal absorption cannot occur. To determine the efficiency of aerosol administration by a metered-dose inhaler (MDI), we measured serum albuterol levels after administration by a MDI and spacer to nine mechanically ventilated patients (10 puffs) and to 10 healthy subjects (six puffs). Serum albuterol levels (+/- SEM) quantitated by high-performance liquid chromatography and electrochemical detection were: 0.09 +/- 0.04 mg/ml/puff at baseline, 0.66 +/- 0.10 at 5 min, 0.98 +/- 0.10 at 10 min, 0.56 +/- 0.08 at 15 min, and 0.37 +/- 0.03 at 30 min in mechanically ventilated patients versus zero at baseline, 0.89 +/- 0.12 at 5 min, 1.27 +/- 0.13 at 10 min, 0.84 +/- 0.09 at 15 min, and 0.53 +/- 0.07 at 30 min in control subjects (p > or = 0.07 at 5, 10, and 30 min; p < or = 0.05 at baseline and at 15 min). Area under the curve (AUC0-30) in the mechanically ventilated patients was 16.8 +/- 1.4 versus 23.4 +/- 1.9 ng/ml/puff x min in control subjects (p = 0.014). In summary, administration of albuterol with a MDI achieved a profile of serum levels in mechanically ventilated patients similar to that in healthy control subjects, but the peak serum level and systemic bioavailability (AUC0-30) were lower in the patients. In conclusion, serum levels reliably assess lower respiratory tract deposition of albuterol, and show that MDIs are more efficient for aerosol delivery in mechanically ventilated patients than was previously reported in studies using radiolabeled aerosols.