Egan's Fundamentals of Respiratory Care Chapter 39 PDF

CHAPTER 39 Aerosol Drug Therapy JAMES B. FINK AND ARZU ARI CHAPTER OBJECTIVES After reading this chapter you will be able to: ◆ Define the term aerosol. ◆ Describe how particle size, motion, and airway characteristics affect aerosol deposition. ◆ Describe how aerosols are g...

CHAPTER 39 Aerosol Drug Therapy JAMES B. FINK AND ARZU ARI CHAPTER OBJECTIVES After reading this chapter you will be able to: ◆ Define the term aerosol. ◆ Describe how particle size, motion, and airway characteristics affect aerosol deposition. ◆ Describe how aerosols are generated. ◆ List the hazards associated with aerosol drug therapy. ◆ Describe how to select the best aerosol drug delivery system for a patient. ◆ Describe how to initiate and modify aerosol drug therapy. ◆ State the information patients need to know to self-administer drug aerosol therapy properly. ◆ Describe how to assess patient response to bronchodilator therapy at the point of care. ◆ Describe how to apply aerosol therapy in special circumstances. ◆ Describe how to protect patients and caregivers from exposure to aerosolized drugs. CHAPTER OUTLINE Characteristics of Therapeutic Aerosols Dry Powder Inhalers Aerosol Output Equipment Design and Function Particle Size Factors Affecting Dry Powder Inhaler Performance Deposition and Drug Delivery Inertial Impaction New Dry Powder Inhaler Technologies Sedimentation Nebulizers Diffusion Pneumatic (Jet) Nebulizers Aging Small Volume Nebulizers Quantifying Aerosol Delivery Large Volume Jet Nebulizers Hazards of Aerosol Therapy Hand-Bulb Atomizers and Spray Pumps Infection Ultrasonic Nebulizers Airway Reactivity Vibrating Mesh Nebulizers Pulmonary and Systemic Effects New-Generation Nebulizers Drug Concentration Advantages and Disadvantages of Aerosol Systems Eye Irritation Special Medication Delivery Issues for Infants and Secondhand Exposure to Aerosol Drugs Children Aerosol Drug Delivery Systems Selecting an Aerosol Drug Delivery System Pressurized Metered Dose Inhalers Assessment-Based Bronchodilator Therapy New Pressurized Metered Dose Inhaler Protocols Technologies Sample Protocol Breath-Actuated Pressurized Metered Dose Inhaler Assessing Patient Response Dose Counters Use and Limitations of Peak Flow Monitoring Factors Affecting Pressurized Metered Dose Inhaler Other Components of Patient Assessment Performance and Drug Delivery Dose-Response Assessment Aerosol Delivery Characteristics Frequency of Patient Assessment Technique Patient Education Pressurized Metered Dose Inhaler Accessory Special Considerations Devices Aerosol Therapy for Treatment of Pulmonary Arterial Cost Hypertension 843 844 SECTION V Basic Therapeutics Acute Care and Off-Label Use Aerosol Generator Placement Continuous Nebulization for Refractory Placement During Noninvasive Ventilation Bronchospasm Placement During High-Flow Nasal Cannula Aerosol Administration to Mechanically Ventilated Placement During Intrapulmonary Percussive Patients Ventilation Use of a Small Volume Nebulizer During Mechanical Placement During High-Frequency Oscillatory Ventilation Ventilation Use of a Vibrating Mesh Nebulizer During Controlling Environmental Contamination Mechanical Ventilation Negative Pressure Rooms Use of a Pressurized Metered Dose Inhaler During Booths and Stations Mechanical Ventilation Personal Protective Equipment KEY TERMS aerosol fine-particle fraction monodisperse aerosol output geometric standard deviation (GSD) nebulizer aging heterodisperse propellant atomizer hydrofluoroalkane (HFA) residual drug volume baffle hygroscopic respirable mass breath-actuated nebulizer inertial impaction scintigraphy breath-enhanced nebulizer inhaled mass sedimentation chlorofluorocarbons (CFCs) mass median aerodynamic therapeutic index deposition diameter (MMAD) volume median diameter (VMD) emitted dose A n aerosol is a suspension of solid or liquid particles in liquid emitted (leaving) from the aerosol generator. For nebu- gas. Aerosols occur in nature as pollens, spores, dust, lizers the output rate is the mass of aerosol generated per unit smoke, smog, fog, and mist.1 The upper airway and of time. Output varies greatly among different nebulizers and respiratory tract filter out larger particles to protect the lungs inhalers. For drug delivery systems, emitted dose describes the from invasion by these aerosols. In the clinical setting, medical mass of drug leaving the mouthpiece of a nebulizer or inhaler aerosols are generated with atomizers, nebulizers, and inhalers. as aerosol. Aerosols can be used to deliver bland water solutions to the Aerosol output can be measured by collecting the aerosol respiratory tract (see Chapter 38) or to administer drugs to the that leaves the nebulizer on filters and measuring either their lungs, throat, or nose for local and systemic effect. This chapter weight (gravimetric analysis) or quantity of drug (assay). Gravi- focuses on the principles of medical aerosol drug therapy. metric measurements of aerosols are easier but less reliable than The aim of aerosol therapy is to deliver a therapeutic dose drug assay techniques because weight changes with water evap- of the selected agent (drug) to the desired site of action (nose, oration while drug mass does not. A drug assay provides the throat, airways, or deep lung). The indication for any specific most reliable measure of aerosol output. aerosol is based on the need for the specific drug.1 Administra- A large proportion of particles that leave a nebulizer may tion of drugs by aerosol offers higher local drug concentrations never reach the lungs. The ability of aerosols to travel through in the lung with lower systemic levels compared with other the air, enter the airways, and become deposited in the lungs is forms of administration. Improved therapeutic action with based on numerous variables ranging from particle size to fewer systemic side effects provides a higher therapeutic index.2 breathing pattern. Understanding and skillful manipulation of these variables can greatly improve pulmonary delivery of CHARACTERISTICS OF aerosols. THERAPEUTIC AEROSOLS Particle Size Effective use of medical aerosols requires an understanding of Aerosol particle size depends on the substance for nebulization, the characteristics of aerosols and their effect on drug delivery the method used to generate the aerosol, and the environmental to the desired site of action. Key concepts include aerosol conditions surrounding the particle.3 It is impossible to deter- output, particle size, deposition, and changes in the aerosol over mine visually whether a nebulizer is producing an optimal par- time (aging). ticle size. The unaided human eye cannot see particles less than 50 to 100 µm in diameter (equivalent to a small grain of sand). Aerosol Output The only reliable way to determine the characteristics of an Aerosol output is the mass of fluid or drug produced by an aerosol suspension is laboratory measurement. The two most aerosol generator. Output is described as the mass of drug or common laboratory methods used to measure medical aerosol  Aerosol Drug Therapy CHAPTER 39 845 particle size distribution are cascade impaction and laser dif- fraction. Cascade impactors are designed to collect aerosols of different size ranges on a series of stages or plates. The mass of aerosol deposited on each plate is quantified by drug assay, and a distribution of drug mass across particle sizes is calculated. In laser diffraction, a computer is used to estimate the range and frequency of droplet volumes crossing the laser beam. Because medical aerosols contain particles of many different sizes (heterodisperse), the average particle size is expressed with a measure of central tendency, such as mass median aero- dynamic diameter (MMAD) for cascade impaction or volume median diameter (VMD) for laser diffraction. These measure- ment techniques of the same aerosol may report different sizes, so it is important to know which measurement is used. The MMAD and VMD both describe the particle diameter in micrometers (µm). In an aerosol distribution with a specific FIGURE 39-1 Inertial impaction of large particles, the masses of which tend to maintain their motion in straight lines. As airway MMAD, 50% of the particles are smaller and have less mass, direction changes, the particles are deposited on nearby walls. and 50% are larger and have greater mass. Smaller particles are carried around corners by the airstream and The geometric standard deviation (GSD) describes the fall out less readily. variability of particle sizes in an aerosol distribution set at 1 standard deviation above or below the median (15.8% and 84.13%). Most aerosols found in nature and used in respiratory changes direction, the particle tends to remain on its initial path care are composed of particles of different sizes, described as and collide with the airway surface. heterodisperse. The greater the GSD, the wider the range of Because inertia involves both mass and velocity, the higher particle sizes, and the more heterodisperse the aerosol. Aerosols the flow of a gas stream, the greater the tendency for particles consisting of particles of similar size (GSD ≤1.2) are referred to to impact and be deposited in the airways. Turbulent flow pat- as monodisperse. Nebulizers that produce monodisperse aero- terns, obstructed or tortuous pathways, and inspiratory flow sols are used mainly in laboratory research and in nonmedical rates greater than 30 L/min are associated with increased iner- industries. tial impaction. Turbulent flow and convoluted passageways in the nose cause most particles larger than 10 µm to impact and Deposition become deposited. This process produces an effective filter that When aerosol particles leave suspension in gas, they deposit on protects the lower airway from particulates such as dust and (attach to) a surface. Only a portion of the aerosol generated pollen. However, particles 5 to 10 µm tend to become deposited and emitted from a nebulizer (emitted dose) may be inhaled in the oropharynx and hypopharynx, especially with the turbu- (inhaled dose). A fraction of the inhaled dose is deposited in lence created by the transition of air as it passes around the the lungs (respirable dose). Inhaled mass is the amount of drug tongue and into the larynx. inhaled. The proportion of the drug mass in particles that are small enough (fine-particle fraction) to reach the lower respi- Sedimentation ratory tract is the respirable mass. Not all aerosol particles Sedimentation occurs when aerosol particles settle out of sus- delivered to the lung are retained, or deposited. A small percent- pension and are deposited owing to gravity. The greater the age (1% to 5%) of inhaled drug may be exhaled. Whether mass of the particle, the faster it settles (Figure 39-2). During aerosol particles that are inhaled into the lung are deposited in normal breathing, sedimentation is the primary mechanism for the respiratory tract depends on the size, shape, and motion of deposition of particles 1 to 5 µm. Sedimentation occurs mostly the particles and on the physical characteristics of the airways in the central airways and increases with time, affecting particles and breathing pattern. Key mechanisms of aerosol deposition 1 µm in diameter. Breath holding after inhalation of an aerosol include inertial impaction, gravimetric sedimentation, and increases the residence time for the particles in the lung and brownian diffusion.1,3 enhances distribution across the lungs and sedimentation. A 10-second breath hold can increase aerosol deposition 10% and Inertial Impaction increase the ratio of aerosol deposited in lung parenchyma to Inertial impaction occurs when suspended particles in motion central airway by fourfold.4 collide with and are deposited on a surface; this is the primary deposition mechanism for particles larger than 5 µm. The Diffusion greater the mass and velocity of a moving object, the greater its Brownian diffusion is the primary mechanism for deposition of inertia, and the greater the tendency of that object to continue small particles (50 µm Lower airways 2 to 5 µm Parenchyma: alveolar region 1 to 3 µm Parenchyma 3 years by,” it may be more efficient to take the time to condition the pMDI alone >4 years infant or child to tolerate the mask without crying or to deliver Breath-actuated Neb >4 years medication with a close-fitting mask when the patient is asleep.56 DPI ≥4 years A pediatric mask with an integrated pacifier uses the infant’s pull on the pacifier to hold the mask in place with improved face-mask seal which may reduce agitation and crying associ- Spontaneous breathing in all patient populations results in ated with standard masks (Soothermask InspiRx Inc, Somerset, greater deposition of aerosol from an SVN than occurs with NJ). Given the cognitive and functional limitations of very positive pressure breaths (e.g., intermittent positive pressure young patients, not all delivery devices are suitable for these ventilation [IPPB]). IPPB reduces aerosol deposition more than patients. To help guide clinicians, the accompanying Rule of 30% compared with spontaneously inhaled aerosols.57  Aerosol Drug Therapy CHAPTER 39 869 TABLE 39-3 Box 39-7 Factors Associated With Advantages and Disadvantages of Aerosol Drug Reduced Aerosol Drug Delivery Systems Deposition in the Lung Advantages Disadvantages Mechanical ventilation pMDI Artificial airways Convenient Patient coordination required Reduced airway caliber (e.g., infants and children) Inexpensive Patient activation required Severe airway obstruction Portable High percentage of pharyngeal High gas flows No drug preparation required deposition Low minute volumes Difficult to contaminate Risk of abuse Poor patient compliance or technique Difficult to deliver high doses Limitation of specific delivery device Not all medications are available Most units still use ozone-depleting CFCs Expensive caregiver is trained to use the device properly.51 Figure 39-28 pMDI With Accessory Device is an algorithm that provides guidance regarding device Less patient coordination More complex for some patients selection. required More expensive than MDI alone Regardless of the device used, the clinician must be aware of Less pharyngeal deposition Less portable than MDI alone No drug preparation required Not all medications available the limitations of aerosol drug therapy. First, depending on the device and patient, 10% or less of drug emitted from an aerosol DPI Less patient coordination Requires high inspiratory flow device may be deposited in the lungs (Figure 39-29). As indi- required Most units are single dose cated in Box 39-7, additional reductions in lung deposition can Breath-activated Risk of pharyngeal deposition occur in many clinical situations that sometimes necessitate the Breath hold not required Not all medications are available use of higher dosages. Clinical efficacy varies according to both Can provide accurate dose Difficult to deliver high doses patient technique and device design. For these reasons, the best counts Expensive No CFCs approach to aerosol drug therapy is to use an assessment-based protocol that emphasizes individually tailored therapy modified SVN Inexpensive Wasteful according to patient response. Less patient coordination Drug preparation required required Contamination possible if device ASSESSMENT-BASED High doses possible (even not cleaned carefully continuous) Not all medications available BRONCHODILATOR No CFC release Pressurized gas source required THERAPY PROTOCOLS Long treatment times Although the choice of delivery system affects how well an USN Moderate residual volume Expensive aerosolized drug works, it is ultimately the patient’s response Quiet Prone to electrical or mechanical that determines the therapeutic outcome. Because patients vary Smaller residual drug volume breakdown markedly in response to the dose and route of drug administra- than SVN Not all medications available tion, it makes sense to tailor aerosol drug therapy to each Aerosol accumulates during Drug preparation required patient. This approach is best determined with an assessment- exhalation based protocol. VM Nebulizer Low residual volume Expensive Sample Protocol Quiet Not all medications available Does not require gas or Drug preparation required Figure 39-30 is an algorithm of a bronchodilator therapy pro- propellant tocol for acutely ill adults or children admitted to an emergency Flow-independent delivery department.61 The protocol relies heavily on bedside assessment Shorter treatment times of the severity of airway obstruction based on the patient’s response to varying drug dosages. Modified from Hess D: Aerosol delivery. Respir Care Clin N Am 1:235, 1995. According to the algorithm, a patient with acute airway obstruction (wheezing, cough, dyspnea, and peak expiratory flow rate [PEFR] 40-60 LMP? E use DPI? R E N No No No C E Solution Solution Solution Yes nebulizes heat Yes SVN available? well? labile? No No No USN Contact physician recommend substitution of available formulation FIGURE 39-28 Selecting an aerosol drug delivery system. When the need is established for aerosol drug delivery, the formulations available for the prescribed medication should be determined. If a pMDI is available, it is the first choice for cost and convenience. The patient’s ability to coordinate actuation with inspiration and the need to reduce oropharyngeal deposition (e.g., steroids) determine need for a holding chamber or a breath-actuated unit. Nebulizers are the first choice when the formulation is available only as a solution. When the ordered medication is unavailable for inhalation use, the RT should recommend a substitution to the ordering physician. of airway obstruction but must not be confused with broncho- indicates worsening airway obstruction or patient fatigue. dilator overdose. Improvement is indicated when wheezing decreases and the Increased cough has been associated with the onset of overall intensity of breath sounds increases. asthma. The frequency, severity, and effectiveness of cough All patients with acute airway obstruction should be moni- should be assessed before and after therapy. tored for oxygenation status with pulse oximetry. This value can In terms of breath sounds, a decrease in wheezing accompa- be used in conjunction with observational assessment to titrate nied by an overall decrease in the intensity of breath sounds the level of inspired O2 given to the patient (see Chapter 38). 872 SECTION V Basic Therapeutics 2 µg (1%) 2 µg (1%) 2 µg (1%) 500 µg (20%) Exhaled 36 µg (18%) 20 µg (10%) 156 µg (78%) Apparatus 108 µg (54%) 160 µg (80%) 1650 µg (66%) Oropharyngeal 2 µg (1%) 50 µg (2%) 54 µg (27%) 40 µg (20%) Lungs 18 µg (9%) 300 µg (12%) DPI MDI MDI/HC NEB Nominal Dose 200 µg 200 µg 200 µg 2500 µg FIGURE 39-29 Distribution of albuterol via nebulizer, pMDI, pMDI with a holding chamber, and DPI. (Modified from Fink J: Metered-dose inhalers, dry powder inhalers and transitions. Respir Care 45:623, 2000.) Aerosol mask IV pump Oxygen blender IV drip tubing Nebulizer Flow- Plug meter A B FIGURE 39-30 Algorithm underlying a bronchodilator therapy protocol for acutely ill adults or children admitted to an emergency department. PEFR, Peak expiratory flow rate; VS, vital signs. Arterial blood gases are not essential for determining patient determine the “best” dose for patients with moderate obstruc- response to bronchodilator therapy but may be needed for tion, the respiratory therapist should conduct a dose-response patients in severe distress to assess for hypercapnic respiratory titration. failure. A simple albuterol dose-response titration involves giving an initial 4 puffs (90 mcg/puff) at 1-minute intervals through a Dose-Response Assessment pMDI with a holding chamber. After 5 minutes, if airway Poor patient response to bronchodilator therapy often occurs obstruction is not relieved, the RT gives 1 puff per minute until because an inadequate amount of drug reaches the airway. To symptoms are relieved, heart rate increases by more than  Aerosol Drug Therapy CHAPTER 39 873 Box 39-8 Frequency of Assessment of the options and actions required to reduce or eliminate these Bronchodilator Therapy effects. In addition, patients should be able to demonstrate good technique regarding the use of each aerosol device that they are FOR PATIENT WITH AN ACUTE DISORDER WHO IS expected to use in self-care. Practitioner demonstration fol- IN UNSTABLE CONDITION lowed by repeated patient return demonstration is a must and Whenever possible, perform a full assessment and obtain a pretreatment baseline. should be done frequently, with each office or clinic visit. Assess and document all appropriate variables before and after each treatment (breath sounds, vital signs, side effects during therapy, and PEFR or FEV1). SPECIAL CONSIDERATIONS The frequency with which physical examination and PEFR or FEV1 are repeated should be based on the acuteness of the Aerosol Therapy for Treatment of disorder and the severity of the patient’s condition. Pulmonary Arterial Hypertension SpO2 should be monitored continuously, if possible. Assessment should continue as dosages are changed to Epoprostenol (Veletri®, Actelion Pharmaceuticals US, Inc, optimize patient response (e.g., if an asthmatic patient South San Francisco, CA), epoprostenol sodium (Flolan®, Glax- achieves 70% to 90% of predicted or “personal best” or oSmithKline, Research Triangle Park, NC), iloprost (Ventavis®, becomes symptom-free). Actelion Pharmaceuticals US Inc, South San Francisco, CA), FOR STABLE PATIENT and treprostinil (Tyvaso) are inhaled prostacyclins used for In the hospital, PEFR should be measured initially before and treatment of pulmonary arterial hypertension. Whereas epo- after each bronchodilator administration. Thereafter, twice-daily determinations may be adequate. prostenol administration is associated with positive effects on In the home, PEFR ideally should be measured three or four symptoms, hemodynamics, exercise capacity, disease progres- times a day: on rising, at noon, between 4 PM and 7 PM, sion and survival,62-64 it has not been approved for inhalation, and at bedtime. and due to its short half-life of 30 to 90 seconds, requires con- For a stable COPD patient at home, measuring PEFR twice tinuous nebulization. In contrast, iloprost and treprostinil are a day may be adequate. Patients with asthma should adjust the frequency of PEFR approved for inhalation with a half-life of 60 to 90 minutes, measurement according to the severity of symptoms. allowing more convenient dosing to ambulatory patients. PEFR levels before and after bronchodilator use, medication dose, date and time, and dyspnea score should be Acute Care and Off-Label Use documented. Every drug approved for inhalation to date has been designed The patient should be reevaluated periodically for response to therapy. for and tested in populations of ambulatory patients with mod- erate disease. As patients with lung disease become acutely and critically ill, the approved label doses, frequency of administra- tion, and devices may not be practical or effective, especially 20 beats/min, tremors increase, or 12 puffs are delivered. The for treatment of patients requiring ventilatory support. In best dose is the dose that provides maximum relief of symptoms such cases, clinicians may explore and consider nonstandard and the highest PEFR without side effects. methods (doses, frequency, and devices) for administration of approved inhaled drugs to patients in the acute care environ- Frequency of Patient Assessment ment, known as off-label use. Another type of off-label use How frequently patients should undergo assessment for bron- involves drugs that have not been approved for inhalation, chodilator therapy depends primarily on the acuity of the con- ranging from heparin to certain antibiotics. Although physi- dition. An unstable patient in acute distress should undergo cians may order such drugs via inhalation, the risk to the patient closer and more frequent scrutiny than a patient in stable condi- and institution is greater when the administration of such drugs tion. Box 39-8 provides guidance regarding the frequency of via inhalation has not been thoroughly studied. All forms of assessment according to acuity. off-label use should be avoided when approved and viable alter- natives exist. Likewise, off-label administration should always Patient Education be backed by appropriate departmental or institutional policies The desired outcome of all bronchodilator protocols is restora- and procedures. tion of normal airflow and cessation of therapy. For patients who need ongoing maintenance therapy after the acute phase Continuous Nebulization for of illness, the goal should be effective self-administration. An Refractory Bronchospasm effective program of aerosol drug self-administration depends Patients in the emergency department with severe exacerbation on thorough patient education. of asthma or acute bronchospasm often have been taking stan- The patient’s ability to understand the therapy and its goals dard doses of their bronchodilators for 24 to 36 hours before significantly affects the therapeutic efficacy of any treatment. admission without response. Giving nebulizer treatments with Whenever possible, patients should be taught to understand the standard bronchodilator doses and repeating the treatments basic administration techniques, to keep track of dosing require- until the symptoms are relieved can require hours of staff time. ments, to recognize undesirable side effects, and to understand Administering higher doses of albuterol in short time frames 874 SECTION V Basic Therapeutics can be accomplished by nebulization of undiluted albuterol (8 to 20 breaths) or by protocol titration with a pMDI and holding chamber (up to 12 puffs). If these strategies fail to provide relief, CBT with albuterol nebulization doses ranging from 5 to 20 mg/ hr have proved safe and effective for adult and pediatric patients (Figure 39-31). Figure 39-32 is a treatment algorithm for high-dose therapy and CBT for pediatric patients with status asthmaticus who are unable to perform peak flow maneuvers.65 Candidates for this protocol are children who, despite frequent beta agonist treat- ments, remain in extremis with bronchospasm, dyspnea, cough, chest tightness, and diminished breath sounds. According to this protocol, children older than 6 years with tachypnea, hypoxemia, increased work of breathing, and rest- FIGURE 39-31 Continuous line from a syringe pump attached lessness who do not respond to standard therapy are given CBT to a nebulizer. Assess clinical score Albuterol treatment Clinical SVN 2.5 mg 4 Repeat in >3 Clinical Better 1 hour score then Q4 prn SVN 2.5 mg SVN with MDI + HC Albuterol to fill undiluted Albuterol Titrate to 12 puffs volume 4-5 ml 8-20 breaths or relief Q20 min x 3 Clinical 4 Start CBT at 15 mg/hr monitored unit with EKG, SpO2, and K+ Q4h >4 Clinical 70 mm Hg