Nebulisation in Respiratory Care

Introduction

Inhalational therapy is the primary treatment for respiratory diseases like obstructive airway diseases (OADs) and other pulmonary and non-pulmonary disorders. Hand-held inhalation devices are often difficult to use, especially for children, elderly, debilitated, or distressed patients. Nebulization therapy is a suitable option for these cases, especially in-home care, emergency rooms, and critical care settings. The main goal of aerosolization is to achieve high drug concentrations in lung tissue, leading to renewed interest in aerosolized drug therapy in intensive care. Aerosolized therapy is used for various therapies, including bronchodilators and corticosteroids, with a particular interest in antibiotic administration.

Jet, Ultrasonic and Mesh       

Jet, ultrasonic, and mesh nebulizers are used to convert liquids into aerosols that can be inhaled by patients into the lungs. Ultrasonic nebulizers use a piezoelectric transducer to produce ultrasonic waves that pass through the liquid medication. Mesh nebulizers are divided into active and passive categories, with active mesh nebulizers having a vibrating mesh with multiple apertures and passive mesh nebulizers using a vibrating horn to generate aerosols. Research has shown that mesh nebulizers are superior to jet nebulizers in aerosol drug delivery due to their small residual drug volume and ability to operate without adding gas to the circuit.

Nebulization therapy is a crucial method for treating obstructive airway diseases (OAD), which are conditions that require large doses of bronchodilators to control symptoms. The ideal particle size for nebulization depends on the target site of action of the drugs to be delivered to the airways. The ideal aerosol MMAD recommended for bronchodilators in OAD is between 3 and 6 mm, with smaller particles achieving greater total lung deposition. For drugs requiring peripheral intrapulmonary deposition (antimicrobials), the ideal aerosol MMAD is < 2mm.  Ideal flow rates, fill volume, and nebulization time are also important factors to consider. High flow rates of 6 to 8 L/min are associated with the generation of higher number of particles with MMAD in the respirable range in a short nebulization time. Higher fill volumes of 4 to 6 ml are associated with better MMAD particle size in the respirable range but with a longer nebulization time. A nebulization time of up to 10 minutes is optimal or up to the point of sputtering.  Mixing various drug formulations in the nebulizer cup is recommended only after physicochemical compatibility is ensured. Mixtures that show change in color or odor, or presence of haze and precipitation are designated as incompatible and should not be used. The high flow nasal cannula (HFNC) circuit is recommended for nebulized therapy having high efficiency. 

Various nebulized drugs used in OAD include corticosteroids, bronchodilators, and some other drugs. Inhaled corticosteroids in nebulized form include budesonide, fluticasone propionate, beclomethasone dipropionate, and flunisolide. Beclomethasone dipropionate and flunisolide are not available in India. Inhaled nebulized bronchodilators include SABA (albuterol or salbutamol; levalbuterol or levo-salbutamol), LABA (formoterol; arformoterol), SAMA (ipratropium bromide), and LAMA (glycopyrronium).

Bronchodilator use in chronic obstructive pulmonary disease (COPD):

Combination formulations of inhaled corticosteroids and bronchodilators available for nebulization in India include SABA plus ICS (levalbuterol or levosalbutamol plus budesonide); and LABA plus ICS (formoterol plus budesonide).  Nebulization with combination of short acting beta agonist (SABA) and short acting muscarinic antagonist (SAMA) is not superior to either of them used alone in acute exacerbation of COPD. Nebulized levalbuterol may have some advantages over albuterol but clinically significant differences between the two in terms of efficacy, occurrence of adverse effects, or hospital admissions is not seen. Nebulized formoterol (LABA) is useful as bronchodilator for regular maintenance therapy in COPD and as-needed reliever therapy due to its rapid onset of action. Arformoterol, another potent, selective, longacting bronchodilator, acts in a way similar to formoterol but is more potent and can also be used as a rescue medication and is safe too. Nebulized glycopyrronium bromide (LAMA) is available as maintenance therapy in moderate to very severe COPD cases and shows a rapid onset of action with significant improvement in lung function and reduction in exacerbation rate.  The common adverse events with beta2-agonists are tremor, palpitations, dry mouth, headache, anxiety, and nervousness. Common adverse events with anticholinergics are tremor, palpitations, dry mouth, headache, while less common ones are alteration in taste, dizziness, anxiety, blurred vision, and urinary retention. Formoterol has been found to be safe for long term use, with no changes in laboratory values including serum potassium and glucose. Nebulized glycopyrronium has been used in dosages of 25 to 50 microg BID as a long-term maintenance therapy for moderate-to-very-severe COPD.  Nebulized corticosteroids are used as a therapeutic option in most cases of persistent asthma and during its exacerbations, especially among infants, young children, and elderly people. Budesonide (BUD) and fluticasone propionate (FP) are the two inhaled corticosteroids commonly available for nebulization, with budesonide being more often used in studies with extensive data available. When used judiciously, nebulized BUD and FP are safe with exceedingly few systemic adverse effects common with systemic steroids.

Nebulization therapy in the intensive care unit

Nebulization therapy in the intensive care unit (ICU) primarily involves the use of drugs for treating lung pathologies and systemic disorders. Bronchodilators are commonly used to reduce airway resistance and intrinsic PEEP, but their role in patients without OAD is uncertain due to lack of research on their effectiveness. Inhaled antibiotics, mostly aminoglycosides and colistin, are being developed as adjunctive therapy for ventilator-associated pneumonia (VAP), especially with resistant gram-negative organisms.

Good airway suction prior to nebulization is essential for adequate ventilation and aerosol delivery in mechanically ventilated patients. Routine use of mucolytic agents may increase inspiratory airway resistance through their mucokinetic action. Humidification is always used during mechanical ventilation to maintain normal airway mucosa function.

Various nebulized antibiotics are used in structural lung diseases (CF and non-CF bronchiectasis) including Tobramycin, Amikacin, Gentamicin, Aztreonam, Colistin, Vancomycin, and Fluoroquinolones. However, there is insufficient evidence in favor of one inhaled antibiotic over another in managing chronic infections and acute exacerbations in CF patients.

Inhaled Tobramycin remains the most efficacious and recommended antibiotic for early eradication and chronic suppression of Pseudomonas aeruginosa infection in patients with CF. Aztreonam lysine could be an alternative, but it has the disadvantage of three times dosing.