Author’s note:
“Films, mirrors, ABGs, and inhalation and inhalation”, once worked with Rotary Pulmonary The friends discussed several weapons commonly used in respiratory department, among which “inhalation” includes atomization inhalation therapy. Today, I just took this opportunity to chat with you about some things about atomization inhalation therapy.
What is nebulizer therapy?
The essence of atomization inhalation therapy is that the drug is converted from liquid form to aerosol, and then inhaled through the mouth and nose, and it acts on the respiratory tract and lungs. Local direct administration method. Therefore, it also has the advantages of less dosage, rapid onset of action, and less systemic adverse reactions.
How is the atomized fog produced?
Fog is a form of aerosol. To convert a liquid into a fog, the liquid needs to be “broken” into small-diameter droplets. There are currently three devices in clinical practice that can achieve this effect: jet nebulizer, ultrasonic nebulizer, and vibrating mesh nebulizer.
Jet Atomizer
The most commonly used nebulizer in clinic, its principle is shown in Figure 1. The jet atomizer can be used only with a compressed air source, and it is easy to use. Generally speaking, the larger the pressure and flow rate of the driving gas, the smaller the diameter of the formed aerosol and the more mist released per unit time. It should be noted that an extension tube is connected to the far end of the mouthpiece in Figure 1, which is actually to reduce the waste of medicine mist during exhalation; if you inhale through your mouth and exhale through your nose, it can further reduce the waste of medicine. But the experience may be slightly worse (there is a new type of device, the proximal valve of the mouthpiece is opened, which does not affect the drug mist when exhaling).
Figure 1 Jet atomization device and schematic diagram (Source: Modified from network) span>When the compressed air source passes through the open thin tube mouth, the flow rate is high, and a relative negative pressure is formed near the mouth of the tube. The high-speed airflow is impacted and shattered to form an aerosol. The aerosol is driven by the airflow and hits the baffle upwards. The large particles of aerosol are further fragmented or fall back to the storage tank, while the small particles of aerosol overflow successfully and enter the pipeline system.
Ultrasonic Nebulizer
Using the cavitation effect of ultrasonic waves (as the shock wave changes, the air micronuclei in the water will become larger due to pressure changes and tension, or even burst and shrink) to destroy the liquid medicine Surface tension, a large number of broken aerosol particles are formed (Figure 2), but this process is also accompanied by certain thermal and chemical effects, which have a relatively large impact on the stability of protein or peptide drugs. In addition, due to the weak effect of cavitation on non-aqueous liquids, the atomization efficiency is low. Release limited and concentrated.
Fig. 2 Ultrasonic reference nebulizer device and schematic diagram 1 )The ultrasonic wave at the bottom passes through the sound-transmitting membrane and then transmits to the surface of the liquid medicine, destroying the surface tension of the liquid medicine, producing a large number of fine aerosols, which are transported to the mist outlet pipe with the air pump .
Shaker Fog The atomizer
is actually a modified version of the ultrasonic atomizer. Funnel-like micropores, the funnel hole on the liquid side is larger. During the rapid vibration of the diaphragm, due to the pressure difference between the two sides of the funnel hole, the liquid medicine is ejected from the small hole side in the form of small droplets, forming an aerosol (2). Because this process does not involve cavitation effects, it is generally not accompanied by thermal effects, and it is also friendly to suspensions. In addition, because the design of the liquid medicine is on the top and the mist is on the bottom, it is convenient to add medicine or adjust the amount of medicine on the top at any time (Figure 3).
Fig. )The equipment in the picture on the left is not easy to buy in China. Among them, a is a vibrating mesh nebulizer for oral use, and picture b is a vibrating mesh nebulizer connected to a ventilator.< /span>
Comparison of three types of atomizing devices
< /li>
What are the characteristics of commonly used aerosol inhalation drugs?
The commonly used aerosol inhalation drugs include four categories:Inhaled corticosteroids (ICS), short-acting bronchodilators [including short-acting β2 agonists (SABA) and short-acting choline receptor antagonists (SAMA)], expectorants and antibiotics, the specific commonly used drugs and their characteristics are shown in Figure 4.
4 Commonly Approved Fog in China Chemical inhalation drugs and their characteristics (source: author)ICS has a good overall safety, and the conventional treatment dose does not significantly inhibit the hypothalamic-pituitary-adrenal axis The adverse reactions are lower than those of systemic glucocorticoid therapy.Among them, the MVP of ICS is febudesonide (precise, rapid, safe, and widely used, Figure 4), while beclomethasone propionate It is a first-generation ICS and is a prodrug with a slow onset of action.The nebulized form of fluticasone propionate is only approved for use in children and adolescents aged 4-16. All three ICSs are suspensions.
In addition, the nebulized formulation of N-acetylcysteine has a special “Smelly smell” (some people feel like sulfur smell, rotten eggs, maybe because the drug contains sulfhydryl group), if the ampoule is atomized immediately after opening, some patients will not tolerate it or have symptoms such as nausea, try to put the drug solution After adding the atomizing device, the number of open openings Minutes before starting aerosol inhalation may improve.
Aerosol inhalation antibiotics are characterized by high pulmonary concentration after inhalation and few systemic adverse reactions. There are many clinical trials and some evidence has been accumulated, especially It is mainly aerosol inhalation of aminoglycoside antibiotics, which is mostly used for bronchiectasis patients with long-term Pseudomonas aeruginosa infection; Inhaled antibiotics are still off-label use, and it is not recommended to use intravenous antibiotics instead of aerosols. We hope that with the increase of evidence, we can have a clearer understanding.
Can aerosol inhalation drugs be combined freely?
According to the 2019 “Expert Consensus on Rational Use of Aerosol Inhalation Therapy” and the 2021 “Chinese Expert Consensus on the Clinical Application of Aerosol expectoration” (Figure 5), the current There is no contraindication to any combination and compatibility of the four drugs of ICS, SABA, SAMA and expectorant (double, triple and quadruple combinations are possible), but the same drugs should not be used in combination.
It should be noted that the current only compound SABA/SAMA preparation compound ipratropium bromide is an “exception”. 2010 version of the instruction manual of compound ipratropium bromide (approval number H20120544) emphasizes: “Do not mix this product with other drugs in the same nebulizer”, The subsequent instructions (approval number H20150173) further explained the reason: “Because this product is developed as a “ready-to-use” formulation, it does not need to be mixed with any other aerosol inhalation solution formulations.As a result, the clinical development protocol did not include studies of mixing this product with other drugs.Therefore, it is recommended not to mix this product with other drugs in the same nebulizer for use.”
< Compatibility of inhaled drugs (modified from the 2019 Expert Consensus on Rational Drug Use in Atomization Inhalation Therapy)
The reasoning is understood, When to use it and how to use it?
First of all, let’s talk about some common scenarios for the use of these drugs in atomization, especially those in internal medicine/emergency/on-duty/perioperative management: Asthma, exacerbation or exacerbation of COPD, acute laryngitis/epiglottis, and perioperative patients are expected to be at high risk for pulmonary complications.
Aerosolized SABA/SAMA at the beginning of an asthma attack or acute exacerbation (single and double as needed, first Density and sparseness, generally up to 4 times a day) + high-dose ICS (2-4 times the base dose, budesonide is preferred, usually 1 mg bid starting), which can reduce hospitalization in patients who have not received systemic glucocorticoid therapy demand, in which high-dose ICS can replace or partially replace systemic hormones.
In acute exacerbation of COPD (AECOPD), repeated inhalation of SABA/SAMA is an effective treatment for COPD exacerbations of different degrees ( roughly the same as asthma). Budesonide nebulized 6-8mg per day (3mg, 2 times/day or 2mg, 1 time/6 hours) can achieve the same efficacy as intravenous methylprednisolone (40mg), Now In clinical studies, the course of treatment is usually 10 to 14 days, and the dose and course of treatment are adjusted according to the severity of acute exacerbations.
Acute laryngitis/epiglottis is an emergency of the ear, nose and throat. If not treated in time, it may be life-threatening due to suffocation. Treatment is based on systemic antibiotics and glucocorticoids, combined with high-dose inhaled corticosteroids. Budesonide suspension 2-4 mg/time can quickly relieve epiglottis and laryngeal edema. It is recommended to repeat it once every half hour. If the dyspnea cannot be relieved after 2-3 times, tracheotomy should be done in time.
For patients with high risk of postoperative pulmonary complications, it is recommended to perform aerosol inhalation of glucocorticoids 3-7 days before surgery and 3-7 days after surgery. Hormonal combined bronchodilator therapy, daily2 to 3 times; for patients with poor respiratory function or chronic pulmonary diseases such as COPD, it is recommended to apply expectorant drugs preventively before surgery until after surgery.
In addition, inhalation therapy is also commonly used in pediatric patients. Nebulized inhalation is the inhalation therapy that requires the least cooperation of children and is suitable for children of any age. Nebulized inhalation of ICS is used for the treatment of children with airway inflammatory diseases, which can effectively improve the condition. It can be used not only as the main treatment method for relieving acute episodes in the hospital, but also for long-term control treatment in the family.
For patients with a large amount of sputum and thick sputum that is difficult to expectorate, the combined use of expectorants, inhaled glucocorticoids and bronchodilators can improve respiratory symptoms and promote Respiratory function recovery plays an important role. Therefore, it can be used as needed according to the patient’s condition, and the importance of physical expectoration should also be paid attention to.
What precautions are there to ensure the atomization effect?
Volume
< span>The medicine storage tanks of the aforementioned atomization devices are generally used in small capacity (mostly <10ml). Too little liquid medicine will cause more loss in the atomization process, while too much liquid medicine may cause too much water inhalation in a short period of time and induce pulmonary edema (mostly in severe or elderly patients). Currently, the recommended dosage for a single nebulization is 4-6ml. If a single nebulized drug is less than 4ml, it can be diluted to 4-6ml with normal saline.
Preferred buccal device
If the patient can cooperate, preferred buccal device to nebulizer Inhalation does not need to pass through the nasal cavity and facial deposition, and the utilization rate of the drug is higher. When using the mouthpiece, the main thing is to breathe calmly, and take deep and slow breathing intermittently. Face coverings are a good solution if the patient is very sick or unable to fit the mouthpiece.
Pay attention to cleanliness
The mouth should be cleaned before inhalation therapy, and the mouth should be rinsed after inhalation (especially ICS) to prevent oropharyngeal accumulation of drugs cause local adverse reactions. Patients with mask nebulization should also clean their face after nebulization treatment.
Special preparations
1. Non-aerosol preparations such as intravenous preparations are not recommended for inhalation use: Particles with aerosolized particle diameter of 0.5-5μm are more likely to enter the lower respiratory tract and lungs. Non-aerosolized formulations (off-label use), nebulized use may reduce the efficacy of aerosol inhalation therapy; may also fail to clear the airways and deposit in the lungs, thereby increasing risk of infection. Clinical use of non-atomized preparations as aerosolized preparations should follow the principle of “off-label use”.
2. Ultrasonic nebulizers are not recommended for inhalation of protein or peptide liquids (such as rhGM-CSF), nor for suspensions (such as budesonide). De et al. nebulized inhalation therapy with ICS).
References
1.Auvinen M, Kuula J , Grönholm T, Sühring M, Hellsten A. High-resolution large-eddy simulation of indoor turbulence and its effect on airborne transmission of respiratory pathogens-Model validation and infection probability analysis. Physics of fluids (Woodbury, NY : 1994). 2022; 34(1):015124.
2. Vecellio L. The mesh nebuliser: a recent technical innovation for aerosol delivery. Breathe. 2006;2(3) :252-60.
3. A Guide To Aerosol Delivery Devices for Respiratory Therapists. 4th Edition, American Association for Respiratory Care.
4. Expert consensus on the application of aerosol inhalation therapy in severe respiratory diseases, Chinese Medical Journal, 2016.
5. Expert consensus on the emergency clinical application of aerosol inhalation therapy (2018), China Emergency Medicine, 2018.
6. Expert consensus on rational drug use of aerosol inhalation therapy (2019 edition), Medical Herald, 2019
7. Chinese expert consensus on the clinical application of nebulization and expectoration, Chinese Journal of Tuberculosis and Respiratory Medicine, 2021
Author: Peking Union Medical College Hospital Cheng Chongsheng, a 2020 doctoral student in the Department of Respiratory and Critical Care Medicine
Review:
strong>Yang Yanli, Attending Physician, Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital
Editor:Vanlamin Blue