Reprinted from the December 1995 issue of RESPIRATORY CARE [Respir Care 1995;40(12):1325–1335]
AARC Clinical Practice Guideline
Selection of an Aerosol Delivery Device for Neonatal and Pediatric Patients
NPAM 1.0 PROCEDURE:
This guideline addresses the appropriate selection of a device for the administration of aerosolized medications by small volume nebulizer (SVN), large volume nebulizer (LVN), metered dose inhaler (MDI), and dry powder inhaler (DPI) to neonatal and pediatric patients. Recommendations are made for patients both with and without an artificial airway, those spontaneously breathing, and those requiring assisted positive-pressure breathing. Evidence suggests that in pediatric patients a properly used MDI is as effective for delivering medications as is an SVN.(1-5)
NPAM 2.0 DESCRIPTION:
Effective administration of medication as aerosol depends on the delivery system and its position in relation to the patient.(6,7) Aerosol particle deposition is influenced by particle size, ventilatory pattern, and airway architecture.(8) Effective medication response is also influenced by the dose of the medication used.(9-12) In the neonatal and pediatric population, the process for determining the doses of specific aerosolized medications is not completely understood.(13) Drug pharmacokinetics and pharmacodynamics are markedly altered in neonates and may require dose adjustments.(13-16) This guideline addresses characteristics of an aerosol delivery system.
This guideline provides recommendations to assist the clinician in selecting an aerosol delivery device based on the patient's ability. Identifying the ability of the patient (ie, coordination and generated flows, rather than specific age requirements) is essential to selecting the appropriate aerosol delivery device in any population.
The three principal elements of an aerosol delivery system are the generator, the power source, and the interface.(6,7) Generators include small volume nebulizers (SVN), large volume nebulizers (LVN), metered dose inhalers (MDI), and dry powder inhalers (DPI).(7,17) The power source is the mechanism by which the generator operates or is actuated and includes compressed gas for SVN and LVN and self-contained propellants for MDI.(7,17) The interface is the conduit between the generator and the patient and includes spacer devices/accessory devices with mouthpieces or face masks.(7,17) Depending on the patient's age (ability) and coordination, various interfaces are used in conjunction with SVN and MDI in order to optimize drug delivery.(7,17)
A SVN is a jet nebulizer that is powered by a compressed gas source. The medication is displaced up a capillary tube from the nebulizer's reservoir and is dispersed continuously as aerosolized particles.(7) The aerosolized particles are spontaneously inhaled by the patient or delivered in conjunction with positive-pressure breaths.(6,7) For patients > 3 years who are spontaneously breathing without an artificial airway and are able to cooperate, a mouthpiece with an extension reservoir should be used.(6,7) For patients unable to negotiate a mouthpiece (usually < 3 years), a face mask should be used.(18,19)
A MDI is a pressurized canister that contains a medication and propellant. Actuation of the MDI results in the ejection of one dose of medication as aerosolized particles, which can be spontaneously inhaled by the patient or delivered in conjunction with positive-pressure breaths.(7) A spacer device/ accessory device should be used with an MDI. A spacer device enhances delivery by decreasing the velocity of the particles and reducing the number of large particles.(20,21) A spacer device with a one-way valve, ie, holding chamber, eliminates the need for the patient to coordinate actuation and inhalation and optimizes drug delivery.(20,21) A spacer device without valves requires coordination between inhalation and actuation. The MDI with spacer device and face mask is appropriate for patients (usually < 3 years) unable to use a mouthpiece.(18,22-27)
A DPI is a breath-actuated device that uses a gelatin capsule containing a single dose of medication and a carrier substance to aid in the dispersion of the drug.(7) The capsule is inserted into the device and punctured.(28) The patient's inspiratory flow disperses the dry particles and draws them into the lower airways.(28) In spontaneously breathing patients, this device is appropriate in patients who are able to achieve an inspiratory flow > or = 50 L/min. This usually corresponds to children > 6 years of age.(13,29)
A LVN can be used to deliver a dose of medication continuously over a period of time.(30,31) A LVN is powered by a compressed gas source, and a face mask is typically used as the interface.(30) There has been only limited investigation of its use in the neonatal and pediatric population.
NPAM 3.0 SETTING:
Aerosolized medications can be administered in a number of settings including hospitals, clinics, extended care facilities, the home, and during transportation.
NPAM 4.0 INDICATIONS:
An aerosol delivery system is indicated when a medication approved for inhalation is prescribed.
NPAM 5.0 CONTRAINDICATIONS:
- 5.1 Contraindications associated with specific medications may exist. Pharmaceutical information should be consulted for relative contraindications.
- 5.2 An MDI or DPI should not be used
- 5.2.1 for patients with known allergies to medication preservatives;
- 5.2.2 for patients unable to perform the respiratory maneuver required to disperse/deliver the drug.
NPAM 6.0 HAZARDS/COMPLICATIONS:
- 6.1 Aerosol delivery
- 6.1.1 Malfunction of device and/or improper technique may result in underdosing. Overuse may result in overdosing.(32,33)
- 6.1.2 Specific pharmacologic agents can produce adverse side effects.(34)
- 6.1.3 The prescription of aerosol delivery devices for use in the home can lead to misuse if the user has not been properly trained.(33-35)
- 6.2 SVN
- 6.2.1 Continuous nebulizer flow increases tidal volume and associated pressure during volume-targeted ventilation.(36-38)
- 6.2.2 Continuous flow creates a bias flow in the ventilator circuit and may interfere with patient-triggered modes of ventilation.(36-39)
- 6.2.3Continuous flow of aerosol may damage the expiratory flow transducers found in some ventilators.(37)
- 6.2.4 The continuous flow of gas from a flowmeter or compressor to an inline nebulizer used with a continuous-flow ventilator may result in an excess of flow and may cause an increase in airway pressure and/or expiratory retard or PEEP.
- 6.2.5 The continuous flow of gas from a flowmeter or compressor to an in-line nebulizer used with a ventilator may result in variable FIO2s.
- 6.2.6 Aerosol particles may deposit and crystallize on expiratory mechanisms and may create inadvertent expiratory resistance or PEEP.(36,37)
- 6.2.7 Medication reservoirs may become contaminated and can be a source of infection.(40)
- 6.2.8 Diluents that are not isotonic may increase airway reactivity.(34)
- 6.3 MDI
- 6.3.1 The volume of gas discharged with actuation of the canister/inhaler may add a clinically important volume to tidal volume particularly in neonates.(37)
- 6.3.2 Additional dead-space volume can occur when a spacer device is placed at the end of an artificial airway.
- 6.3.3 Volume of gas discharged from MDI may affect FIO2.
- 6.3.4 Inappropriate patient use may result in underdosing or overdosing.
- 6.3.5 Reaction to propellants and other additives including coughing and wheezing may occur.(34,41,42)
- 6.3.6 Chlorofluorocarbons may contribute to ozone depletion.(43-45)
- 6.3.7 Oropharyngeal impaction from corticosteroid supplied in MDI form may result in local side effects.(7,46)
- 6.4 DPI
- 6.4.1 Airway irritation from dry powder may occur.(7,28)
- 6.4.2 Reaction to lactose or glucose carriers may occur.(7,28)
- 6.5 LVN
- 6.5.1 Side effects may occur at any time during continuous nebulization, and frequent assessment is required.(30,31)
- 6.5.2 Medication reservoirs may become contaminated and can be a source of infection.(40)
NPAM 7.0 LIMITATIONS OF PROCEDURE OR DEVICE:
- 7.1 SVN
- 7.1.1 Deposition of medication into the lungs is reduced to as little as 2-10% of the dose,(6,8,14,47-52) and may vary from brand to brand and unit to unit of the same brand.
- 220.127.116.11 Patients with smaller tidal volumes, particularly neonates(14,53-55) or dyspneic patients with shallow breathing may inhale less of the aerosolized agent and receive less of the dose when nebulization is continuous.(14,47,52)
- 18.104.22.168 Patients with airways of smaller diameter may receive a smaller fraction of the total particles produced.(14,53,55-57)
- 22.214.171.124 High inspiratory flows, as those associated with crying, may reduce deposition.
- 126.96.36.199 Approximately one half the initial solution volume is deposited on the internal walls and reservoir of the SVN.(6,8,47,58-60)
- 188.8.131.52 Concentration of the solution increases during nebulization resulting in retention of much of the dose in the SVN.(6,8,47,58,59) The effects of changing osmolality on bronchoreactivity are not clear.
- 184.108.40.206 Aerosol is lost during the expiratory phase of breathing.(6)
- 220.127.116.11 Treatment length may result in premature termination prior to complete nebulization of medication.(36)
- 18.104.22.168 Fill volume in the SVN affects the output.(58)
- 7.1.2 Use is labor intensive and costly.(61-64)
- 7.1.3 Duration of treatment is variable and may be prolonged.(6,7,61,62) (Increasing diluent volume lengthens treatment time but may improve drug delivery.(8,58))
- 7.1.4 The need for a power source makes the SVN less portable, particularly in the home setting.(6,7)
- 7.1.5 SVNs require preparation and cleaning.(7)
- 7.1.6 The brand of SVN used (ie, those that operate effectively only in the upright position).
- 7.2 SVN in conjunction with positive-pressure breathing.
- 7.2.1 Impaction of aerosol particles on artificial airways greatly reduces deposition.(37,65-71) The presence of artificial airways of smaller diameter results in a greater reduction in particle deposition and delivered dose.(6,7,67,71,72) The smaller the artificial airway, the greater the reduction in particle deposition.
- 7.2.2 Limited research on use of aerosols in neonatal and pediatric patients has been published.(37,54,73)
- 7.2.3 Aerosol delivery may be less effective in conjunction with manual ventilation than with mechanical ventilation.(13,72)
- 7.2.4 Mechanical ventilator modes, flows, and flow patterns may affect particle deposition.(25,65,66,74)
- 7.2.5 The presence of an in-line humidifier may reduce aerosol delivery by 50%.(37)
- 7.2.6 Use of SVN with continuous-flow ventilators may result in the loss of a large percentage of the aerosolized particles through the exhalation valve.(37)
- 7.2.7 Positioning of the SVN too close to the artificial airway results in less airway deposition.(37,65,66,69,75)
- 7.3 SVN with face mask
- 7.3.1 Cold, wet mist may be irritating to children and may limit the time that the treatment is tolerated.(13)
- 7.3.2 Nasal breathing results in a reduction in particle deposition.(57,76,77)
- 7.3.3 Particle deposition is reduced because of upper airway impaction.(57,76,77)
- 7.4 MDI
- 7.4.1 Use of an MDI without a spacer device with one-way valve (ie, holding chamber), requires the patient to coordinate the actuation of the canister with inhalation, which may be particularly difficult for small children (eg, < 7 years).(13,78)
- 7.4.2 Use of an MDI without a spacer device results in greater oropharyngeal impaction and a reduction in airway deposition.(6,7,78,79)
- 7.4.3Use of an MDI without a spacer device may result in a cold sensation when the propellant reaches the back of the throat (ie, cold-Freon effect) that may interfere with proper delivery technique.(7,17,80)
- 7.4.4 Inadequate or inaccurate instruction and technique may result in misuse and reduced aerosol deposition.(13,81-83)
- 7.4.5 Propellants may cause bronchospasm in some patients with reactive airway diseases.(41)
- 7.4.6 Average deposition in the lungs is 10% to 25% of the total dose.(49,84-86)
- 7.4.7 Particle size varies with operating pressure which is directly related to canister temperature.
- 7.5 MDI with spacer device
- 7.5.1 Addition of the spacer/accessory device increases cost over cost of the MDI alone.(6,7)
- 7.5.2 The spacer/accessory device is relatively cumbersome and less convenient than the MDI alone.(6,7)
- 7.5.3 All spacer/accessory devices may not fit all MDIs.
- 7.5.4 All spacer devices/accessory devices do not eliminate coordination problems.
- 22.214.171.124 A spacing/accessory device with a one-way valve (ie, holding chamber) eliminates coordination problem.
- 126.96.36.199 Open tube spacer/accessory devices (non-valved) require coordination.
- 7.6 MDI with spacer device-face mask--The inspiratory flow and the number of inhalations required by neonates and small children (< 3 years) to effectively use these devices is not completely understood.(13,52,54,87)
- 7.7 MDI with spacer device designed for mechanical ventilation
- 7.7.1 Research is limited in this population.(13,21)
- 7.7.2 The smaller the diameter of the artificial airway, the greater the reduction in particle deposition and delivered dose.(13,37,88)
- 7.7.3 Particle deposition may be as low a 2-10% of the total drug delivered.(13,3769,89-91)
- 7.7.4 Use of an elbow-type spacer results in less airway deposition than a chamber-type spacer.(36,87,89,92)
- 7.7.5 The chamber type spacer if left in-line with a ventilator circuit potentially increases the compressible volume of the ventilator circuit.
- 7.7.6 The gas discharged from the MDI may affect FIO2.
- 7.8 DPI
- 7.8.1Reduced inspiratory flow (< 50 L/ min) can lead to reduced deposition.(14,29,92,93) This may be more likely in children < 6 years(13,29) and in an acute exacerbation when peak flows are significantly reduced.
- 7.8.2 Some drug preparations are water soluble and, thus, humidity may affect DPI performance.(6,7)
- 7.8.3 Oropharyngeal impaction of much of the dose occurs and results in a reduction in lower airway deposition.(14,28)
- 7.8.4 The patient must be able to load each dose, for most medications.(47)
- 7.8.5 Average deposition in the lungs is 10-25% of the total dose.(7,13,92,94)
- 7.9 LVN with mask
- 7.9.1 The use of LVN for continuous nebulization in the pediatric population has not been widely investigated.(30,95)
- 7.9.2 Cold, wet mist may be irritating to children and may limit the time that the treatment is tolerated.(13)
- 7.9.3 Nasal breathing results in a reduction in lower airway deposition.(57,76,77)
- 7.9.4 Bronchial deposition is reduced because of upper airway impaction.(57,76,77)
- 7.9.5 Limited to use in a critical care setting. Not appropriate for home use.
- 7.10 Drug pharmacokinetics and pharmacodynamics are markedly altered in neonates and may require dose adjustments.(13-16)
NPAM 8.0 ASSESSMENT OF NEED:
- 8.1 SVN: General Indications
- 8.1.1 The need to deliver aerosolized medications that are approved in solution form to the lower airway of spontaneously breathing patients with or without an instrumented airway.(6,7,13)
- 8.1.2 The need to provide supplemental gas flow in conjunction with aerosol treatment.(7)
- 8.1.3 The need to modify drug concentration.(7)
- 8.1.4 The need to deliver a particular aerosolized medication that is only available in solution form.
- 8.1.5 The need to deliver aerosolized medications to patients in acute distress or with reduced inspiratory flow.
- 8.1.6 The need to deliver aerosolized medications to patients who are unable to coordinate or perform the necessary inspiratory maneuvers required with an MDI or DPI.
- 8.2 SVN with mouthpiece and extension reservoir--The need to deliver aerosolized medications approved in solution form to the lower airways of spontaneously breathing patients without an instrumented airway who are able to utilize a mouthpiece (patients > 3 years).(6,7)
- 8.3 SVN with face mask
- 8.3.1 The need to deliver aerosolized medications that are approved in solution form to the lower airways of spontaneously breathing patients without an instrumented airway who are unable to negotiate a mouthpiece (usually < 3 years).(18,19)
- 8.3.2 The need to deliver aerosolized medications to the upper airway.
- 8.4 SVN with T-connector (15-mm and 22-mm openings)
- 8.4.1 The need to deliver aerosolized medications approved in solution form in-line with a mechanical ventilator circuit or manual resuscitation bag.(74,96)
- 8.4.2 The need to deliver aerosolized medications approved in solution form to patients with instrumented airways who are spontaneously breathing.
- 8.5 MDI: General indications
- 8.5.1 The need to deliver aerosolized medications that are approved in MDI form.(18)
- 8.5.2 The need to deliver a particular medication that is only available in MDI form.
- 8.5.3 The need to reduce the length of time for the aerosol treatment.
- 8.5.4 The need for maximum portability.(55)
- 8.6 MDI with spacer device with one-way valve--
- 8.6.1 The spacer device with one-way valve and face mask is appropriate for small children (usually < 3 years) and others unable to use a mouthpiece.(18,22-27,97)
- 8.6.2 The need to eliminate actuation and inspiratory maneuver coordination.(20,21)
- 8.6.3 The need to reduce oropharyngeal impaction,(20,21) particularly with the delivery of corticosteroids by inhalation.(98,99)
- 8.6.4 The valved-spacer device with mouthpiece is the method of choice if patient is able to use a mouthpiece.
- 8.6.5 A specially designed spacer device is used for MDI delivery during mechanical ventilation or with manual resuscitators.(73,100)
- 8.7 MDI with a non-valved spacer device
- 8.7.1 The need to use a MDI when a patient can coordinate inspiration and actuation.
- 8.7.2 The need to reduce oropharyngeal impaction,(20,21) particularly with the delivery of corticosteroids by inhalation.(98,99)
- 8.9 DPI
- 8.9.1 The need to deliver aerosolized medications approved in DPI form.(38,101,102)
- 8.9.2 The need to deliver a particular medication that is only available in DPI form.(38,101,102)
- 8.9.3 The need to eliminate chlorofluorocarbon propellants.
- 8.10 LVN--The need to deliver continuously aerosolized medication, approved in solution form, to the lower airway of spontaneously breathing patients without an instrumented airway.(31)
NPAM 9.0 ASSESSMENT OF OUTCOME:
- 9.1 Desired medication effect is observed as indicated by an improvement in subjective (physical examination) and objective (pulmonary function measurements) assessments.(19,31,103-108)
- 9.2 Health care providers demonstrate competency with proper technique and patient instruction of aerosol delivery systems.(33)
- 9.3 Patients and patients' family members demonstrate proper technique and compliance with the application of aerosol delivery systems.(33)
NPAM 10.0 RESOURCES
- 10.1 Equipment
- 10.1.1 SVN capable of producing a high drug output, short nebulization time, aerosol particles with a mass median aerodynamic diameter (MMAD) < or = 5 microns, and with a low residual volume.(8,55,58,60) Characteristics of nebulizers may vary among brands and among units of the same brand.
- 10.1.1.1 Power source such as hospital compressed oxygen or air, portable oxygen or air cylinder, or domiciliary air compressor capable of producing a flow of at least 6-8 L/min.(6-8,58,108)
- 10.1.1.2 A blender for use with a ventilator to maintain desired FIO2.
- 10.1.2 Interface
- 10.1.2.1 Face mask for small children unable to utilize a mouthpiece which may include an additional 6-inch section of aerosol tubing.(18,19)
- 10.1.2.2 Mouthpiece with extension reservoir.(6)
- 10.1.2.3 T-connector with 15- and 22-mm openings or tracheostomy collar adaptation for patients with artificial airway and/or receiving aerosolized medications in conjunction with a manual resuscitation bag.
- 10.1.2.4 T-connector with inspiratory circuit reservoir for patients receiving aerosolized medications in conjunction with mechanical ventilation.(65)
- 10.1.3 Medication and isotonic diluent.
- 10.1.3.1 MDI, which includes the medication canister and actuator, with appropriate accessories for patient's ability and circumstances.
- 10.1.3.1.1 Chamber-style spacer with mouthpiece or mask, depending on the patient's ability.(109)
- 10.1.3.1.2 Chamber-style spacer with inspiratory circuit configuration for patients receiving aerosolized medications in conjunction with mechanical ventilation.(91)
- 10.1.3.1.3 Chamber-style spacer configured for patients with artificial airways and/or receiving aerosolized medications in conjunction with a manual resuscitation bag, placed between airway and bag.
- 10.3.1 DPI with accompanying medication capsule and dispenser.
- 10.4.1 LVN capable of producing aerosol particles with a mass median aerodynamic diameter (MMAD) < or = 5 microns with face mask.
- 10.5 Personnel
- 10.5.1 Health care providers responsible for delivery of aerosolized medications should have demonstrated and documented knowledge and skills related to
- 10.5.1.1 aerosol delivery devices and their limitations;(110)
- 10.5.1.2 assembly, care and use of aerosol delivery devices;(110)
- 10.5.1.3 provision of comprehensive patient and lay caregiver instruction;(18,111,112)
- 10.5.1.4 medications being delivered including contraindications, potential side effects and desired response;(110)
- 10.5.1.5 recognition and response to adverse reactions during medication delivery and modification of treatment accordingly;(110)
- 10.5.1.6 performance of the necessary subjective and objective assessments in order to determine medication efficacy and the patient's ability to properly utilize aerosol delivery devices.
- 10.5.2 Patient and/or family member or lay caregiver should
- 10.5.2.1 demonstrate proper use and understanding of aerosol delivery device and delivery technique;(32,108)
- 10.5.2.2 demonstrate proper assembly, cleaning, care of aerosol delivery device, and medication preparation;(32,108)
- 10.5.2.3 demonstrate an understanding of medication purpose, dosage, indications, and side effects, be able to alter medication as needed,108 and know when to report to physician or surrogate.
NPAM 11.0 MONITORING
- 11.1 Observe delivery technique of spontaneously breathing patients who are able to self-administer aerosolized medications.
- 11.1.1 A slow deep inhalation with an inspiratory pause/hold is performed during SVN treatments.(55) A flow of 6-8 L/min and fill volume of 4 mL (dependent upon the brand of SVN used) provide a maximum volume of delivered drug.(53) The sides of the SVN are periodically tapped in order to minimize the dead volume (ie, volume of solution not nebulized) and maximize the volume nebulized.(53)
- 11.1.2 MDI actuation occurs at end-exhalation followed by a slow inspiration and breath hold for 10 seconds.(55,111,112)
- 11.1.3 Patient is able to produce a rapid inhalation in order to fully activate and discharge DPI.(101)
- 11.2 Observe patient and/or patient's family member following instruction and demonstration.(108)
- 11.2.1 Proper understanding and return-demonstration of delivery device and accompanying equipment is observed.(47,108)
- 11.2.2 Proper understanding and preparation of medication is observed.(47,108)
- 11.3 Observe response to medication by performing subjective (eg, physical examination) and objective (eg, pulmonary function measurements) assessments and other diagnostic techniques that are appropriate for the specific medication being delivered.(19,31,103-107)
- 11.3.1 Ensure that medication volume is nebulized over desired amount of time when using LVN.
- 11.3.2 Continuous monitoring of ECG is recommended when delivering a bronchodilator by LVN.
- 11.4 Monitor ventilator function for inadvertent increases in tidal volume or airway pressures, changes in FIO2, difficulty with patient triggering and patient-ventilator synchrony, or other system problems.(36)
- 11.5 Documentation
- 11.5.1 Successful training of patients and/or patient's family member are documented in the patient's medical record.(33,108)
- 11.5.2 Treatments administered in a clinical setting are documented in the patient's medical record. Information on medication dose, frequency, response and adverse reactions are included.
NPAM 12.0 FREQUENCY
Aerosol delivery devices are used according to the frequency of the prescribed medication.
NPAM 13.0 INFECTION CONTROL
Perinatal-Pediatric Focus Group:
- 13.1 Universal Precautions and measures to limit the transmission of tuberculosis must be adhered to at all times.(113,114)
- 13.2 SVN are for single patient use.
- 13.2.1 Between treatments on the same patient, disinfect, rinse with sterile water, and air-dry.(40) In the home environment, cleaning, rinsing with solution of vinegar and water, and air drying may be adequate, although clear evidence to support this procedure is lacking.
- 13.2.2 Between patients, replace SVN with those that have undergone high level disinfection or sterilization.(40)
- 13.3 MDI, DPI and accessories are for single patient use only. Clean or replace when they appear dirty.
- 13.4 LVN are for single patient use. LVN should be subjected to high-level disinfection or sterilization between patients.
- 13.5 Aerosol solutions.
- 13.5.1 Use only sterile fluids and dispense them aseptically.(40)
- 13.5.2 Medications obtained from multidose vials are handled, dispensed and stored according to manufacturers' instructions.
- 13.6 Patients with a natural airway should be instructed to rinse the mouth with water following each administration of inhaled steroids.
Lynne K Bower RRT, Chairman, Boston MA
Sherry L Barnhart RRT, Cabot AR
Peter Betit BS RRT, Boston MA
Michael P Czervinske RRT, New Orleans LA
Joanne Masi-Lynch BS RRT, Salt Lake City UT
Barbara G Wilson MEd RRT, Durham NC
- Parkin PC, Saunders NR, Diamond SA, Winders PM, Macarthur C. Randomised trial spacer v nebuliser for acute asthma. Arch Dis Child 1995;72(3):239-240.
- Lin YZ, Hsieh KH. Metered dose inhaler and nebuliser in acute asthma. Arch Dis Child 1995;72(3):214-218.
- Cunningham SJ, Crain EF. Reduction of morbidity in asthmatic children given a spacer device. Chest 1994; 106(3):753-757.
- Kerem E, Levison H, Schuh S, O'Brodovich H, Reisman J, Bentur L, Canny GJ. Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma. J Pediatr 1993;123(2): 313-317.
- Chou KJ, Cunningham SJ, Crain EF. Metered-dose inhalers with spacers vs nebulizers for pediatric asthma. Arch Pediatr Adolesc Med 1995;149(2):201-205.
- Kacmarek RM, Hess D. The interface between patient and aerosol generator. Respir Care 1991;36(9):952-976.
- Newman SP. Aerosol generators and delivery systems. Respir Care 1991;36(9):939-951.
- Phipps PR, Gonda I. Droplets produced by medical nebulizers. Some factors affecting their size and solute concentration. Chest 1990;97(6):1327-1332.
- Tashkin DP. Dosing strategies for bronchodilator aerosol delivery. Respir Care 1991;36(9):977-988.
- Matthys H, Herceg R. Dosing strategies for aerosol delivery to the lung parenchyma, with specific recommendations for pentamidine. Respir Care 1991;36(9): 989-993.
- Scuch S, Parkin P, Rajan A, Canny G, Healy R, Rieder, et al. High- versus low- dose frequently nebulized albuterol in children with severe, acute asthma. Pediatrics 1989;83(4):513-518.
- Nussbaum E, Eyzaguirre M, Galant SP. Dose-response relationship of inhaled metaproterenol sulfate in preschool children with mild asthma. Pediatrics 1990;85(6):1072-1075.
- Rau JL. Delivery of aerosolized drugs to neonatal and pediatric patients. Respir Care 1991;36(6):514-542.
- Dolovich M. Clinical aspects of aerosol physics. Respir Care 1991;36(9):931-938.
- Besunder JB, Reed MD, Blumer JL. Principles of drug biodisposition in the neonate: a critical evaluation of the pharmacokinetic-pharmacodynamic interface. Clin Pharmacokinetics 1988;14(5):261-286.
- Kelly HW. Pharmacotherapy of pediatric lung disease: differences between children and adults. Clin Chest Med 1987;8(4):681-694.
- Crompton GK. New inhalation devices. Eur J Respir Dis 1988;1(8):679-680.
- Pedersen S. Choice of inhalation therapy in pediatrics. Eur Respir Rev 1994;4:85-88.
- Lowenthal D, Kattan M. Facemasks versus mouthpieces for aerosol treatment of asthmatic children. Pediatr Pulmonol 1992;14(3):192-196.
- Sackner MA, Kim CS. Recent advances in the management of obstructive airways disease. Auxiliary MDI aerosol delivery systems. Chest 1985;88(2 Suppl): 161S-170S.
- Newman SP, Millar AB, Lennard-Jones TR, Moren F, Clarke SW. Improvement of pressurized aerosol deposition with Nebuhaler spacer device. Thorax 1984;39 (12):935-941.
- Lee H, Evans HE. Evaluation of inhalation aids of metered dose inhalers in asthmatic children. Chest 1987; 91(3):366-369.
- Sly RM, Barbera JM, Middleton HB, Eby DM. Delivery of albuterol aerosol by Aerochamber to young children. Ann Allergy 1988;60(5):403-406.
- Conner WT, Dolovich MB, Frame RA, Newhouse MT. Reliable salbutamol administration in 6- to 36- month-old children by means of a metered dose inhaler and Aerochamber with mask. Pediatr Pulmonol 1989;6(4): 263-267.
- Yuksel B, Greenough A, Maconochie I. Effective bronchodilator treatment by a simple spacer device for wheezy premature infants. Arch Dis Child 1990;65 (7):782-785.
- O'Callaghan C, Milner AD, Swarbrick A. Spacer device with face mask attachment for giving bronchodilators to infants with asthma. Br Med J 1989;298(6667):160-161.
- Rachelefsky GS, Rohr AS, Wo J, Gracey V, Spector SL, Siegel SC, Katz RM, Mickey MR. Use of a tube spacer to improve the efficacy of a metered-dose inhaler in asthmatic children. Am Rev Respir Dis 1986;140(11): 1191-1193.
- Crompton GK. Clinical use of dry powder systems. Eur J Respir Dis 1982;122(Suppl):96s-99s.
- Pedersen S, Hansen OR, Fuglsang G. Influence of inspiratory flow rate upon effect of Turbuhaler. Arch Dis Child 1990;65(3):308-310.
- Sly RM. Aerosol therapy in children. Respir Care 1991;36(9)994-1007.
- Scalabrin DM, Naspitz CK. Efficacy and side effects of salbutamol in acute asthma in children: comparison of the oral route and two different nebulizer systems. J Asthma 1993;30(1):51-59.
- Cochrane GM, Bosley C. Compliance with inhaled therapy in asthma. Eur Respir Rev 1994;4:92-94.
- Bendefy IM. Home nebulisers in childhood asthma: survey of hospital supervised use. Br Med J 1991;302 (6786)1180-1181.
- Snell NJ. Adverse reactions to inhaled drugs. Respir Med 1990;84(5):345-348.
- Cochrane GM, Prior JG, Rees PJ. Home nebulisers for airflow limitation (editorial). Br Med J 1985;290 (6482):1608-1609.
- Hanhan U, Kissoon N, Payne M, Taylor C, Murphy S, DeNicola LK. Effects of in-line nebulization on preset ventilatory variables. Respir Care 1993;38(5):474-478.
- Hess D. Inhaled bronchodilators during mechanical ventilation: delivery techniques, evaluation of response, and cost effectiveness. Respir Care 1994;39(2):105-122.
- LaForce CF, Ellis EF, Kordansky DW, Cocchetto DM, Sharp JT. Use and acceptance of Ventolin Rotacaps and the Rotohaler in 1235 asthmatic patients. Clin Therapeutics 1993;15(2):321-329.
- Beaty CD, Ritz RH, Benson MS. Continuous in-line nebulizers complicate pressure support ventilation. Chest 1989;96(6):1360-1363.
- Centers for Disease Control and Prevention: Guideline for the prevention of nosocomial pneumonia. Respir Care 1994;39(12):1191-1236.
- Yarbrough J, Mansfield LE, Ting S. Metered dose inhaler-induced bronchospasm in asthmatic patients. Ann Allergy 1985;55(1):25-27.
- Rafferty P, Beasley R, Holgate ST. Comparison of the efficacy of preservative free ipratropium bromide and Atrovent nebulizer solutions. Thorax 1988;43(6):446-450.
- Newman SP. Metered dose pressurized aerosols and the ozone layer. Eur Respir J 1990;3(10)495-497.
- Pavia D, McLeod L. The environmental impact of inhaled aerosols Eur Respir Rev 1994;4:75-77.
- Balmes JR. Propellant gases in metered dose inhalers: their impact on the global environment. Respir Care 1991;36(9):1037-1044.
- Salzman GA, Pyszcynski DR. Oropharyngeal candidiasis in patients treated with beclomethasone dipropionate delivered by metered-dose inhaler alone and with Aerochamber. J Allergy Clin Immunol 1988;81(2): 424-428.
- Newman SP. Delivery of therapeutic aerosols. Probs Respir Care 1988;1:53-82.
- Lewis RA, Fleming JS. Fractional deposition from a jet nebulizer: how it differs from a metered dose inhaler. Br J Dis Chest 1985;79(4):361-367.
- Johnson MA, Newman SP, Bloom R, Talaee N, Clarke SW. Delivery of albuterol and ipratropium bromide from two nebulizer systems in chronic stable asthma: efficacy and pulmonary deposition. Chest 1989;96(1):6-10.
- Mason JW, Miller WC, Small S. Comparison of aerosol delivery via Circulaire system vs conventional small volume nebulizer. Respir Care 1994;39(12):1157-1161.
- Agnew JE. Characterizing lung aerosol penetration. J Aerosol Med 1991;4:237-249.
- Everard ML, Clark AR, Milner AD. Drug delivery from jet nebulisers. Arch Dis Child 1992;67(5):58-585.
- Xu JB, Yu CP. The effects of age on deposition of inhaled aerosols in the human lung. Aerosol Sci Technol 1986;5:349-357.
- Silverman M. Aerosol therapy in the newborn. Arch Dis Child 1990;65(8):906-908.
- Vidgren M. Factors influencing lung deposition of inhaled aerosols. Eur Respir J 1994;4:68-70.
- Chung KF, Jeyasingh K, Snashall PD. Influence of airway calibre on the intrapulmonary dose and distribution of inhaled aerosol in normal and asthmatic subjects. Eur Respir J 1988;1(10):890-895.
- Salmon B, Wilson NM, Silverman M. How much aerosol reaches the lungs of wheezy infants and toddlers? Arch Dis Child 1990;65(4):410-403.
- Hess D, Horney D, Snyder T. Medication-delivery performance of eight small-volume, hand-held nebulizers: effects of diluent volume, gas, flowrate, and nebulizer model. Respir Care 1989;34(8):717-723.
- Wood JA, Wilson RSE, Bray C. Changes in salbutamol concentration in the reservoir solution of a jet nebulizer. Br J Dis Chest 1986;80(2):164-169.
- Alvine GF, Rodgers P, Fitzsimmons KM, Ahrens RC. Disposable jet nebulizers. How reliable are they? Chest 1992;101(2):316-319.
- Tenholder MF, Bryson MJ, Whitlock WL. A model for conversion from small volume nebulizer to metered dose inhaler aerosol therapy. Chest 1992;101(3):634-637.
- Bowton DL, Goldsmith WM, Haponik EF. Substitution of metered-dose inhalers for hand-held nebulizers: success and cost savings in a large, acute-care hospital. Chest 1992;101(2):305-308.
- Jasper AC, Mohsenifar Z, Kahan S, Goldberg HS, Koerner SK. Cost-benefit comparison of aerosol bronchodilator delivery methods in hospitalized patients. Chest 1987;91(4):614-618.
- Orens DK, Kester L, Fergus LC, Stoller JK. Cost impact of metered dose inhalers vs small volume nebulizers in hospitalized patients: The Cleveland Clinic experience. Respir Care 1991;36(10):1099-1104.
- Hughes JM, Saez J. Effects of nebulizer mode and position in a mechanical ventilator circuit on dose efficiency. Respir Care 1987;32(12):1131-1135.
- Manthous CA, Hall JB. Administration of therapeutic aerosols to mechanically ventilated patients. Chest 1994;106:560-571.
- Flavin M, MacDonald M, Dolovich M, Coates G, O'Brodovich H. Aerosol delivery to the rabbit lung with an infant ventilator. Pediatr Pulmonol 1986;2(1):35-39.
- Rau JL, Harwood RJ. Comparison of nebulizer delivery methods through a neonatal endotracheal tube: a bench study. Respir Care 1992;37(11):1233-1240.
- Cameron D, Caly M, Silverman M. Evaluation of nebulizers for use in neonatal ventilator circuits. Crit Care Med 1990;18(8):866-870.
- Fuller HD, Dolovich MB, Posmituck G, Pack W, Newhouse MT. Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients: comparison of dose to the lungs. Am Rev Respir Dis 1990;141 (2):440-444.
- Ahrens RC, Ries RA, Popendorf W, Wiese JA. The delivery of therapeutic aerosols through endotracheal tubes. Pediatr Pulmonol 1986;2(1):19-26.
- Henry WD, Chatburn RL. Effects of manual versus mechanical ventilation on aerosol efficiency (abstract). Respir Care 1988;33:914.
- Watterberg KL, Clark AR, Kelly HW, Murphy S. Delivery of aerosolized medication to intubated babies. Pediatr Pulmonol 1991;10(2)136-141.
- MacIntyre NR, Silver RM, Miller CW, Schuler F, Coleman RE. Aerosol delivery in intubated, mechanically ventilated patients. Crit Care Med 1985;13(2):81-85.
- Quinn WW. Effect of a new nebulizer position on aerosol delivery during mechanical ventilation: a bench study. Respir Care 1992;37(5):423-431.
- Heyder J. Mechanism of aerosol particle deposition. Chest 1981;80(6 suppl):820-823.
- Steventon RD, Wilson RS. Facemask or mouthpiece for delivery of nebulized bronchodilator aerosols? Br J Dis Chest 1981;75(1):88-90.
- Vidgren MT, Paronen TP, Karkkainen A, Karjalainen. Effect of extension devices on the drug deposition from inhalational aerosols. Int J Pharm 1987;39:107-112.
- Kim CS, Eldridge MA, Sackner MA. Oropharyngeal deposition and delivery aspects or metered-dose inhaler aerosols. Am Rev Respir Dis 1987;135(1):157-164.
- Lindgren S, Bake B, Larsson S. Clinical consequences of inadequate inhalation technique in asthma therapy. Eur J Respir Dis 1987;70:(2)93-98.
- Pedersen S. Optimal use of tube spacer aerosols in asthmatic children. Clin Allergy 1985;15(5):473-478.
- Oprehek J, Gayrard P, Grimaud CH, Charpin J. Patient error in the use of bronchodilator metered aerosols. Br Med J 1976;1(6001):76-77.
- Kelling JS, Strohl KP, Smith RL, Altose MD. Physician knowledge in the use of canister nebulizers. Chest 1983;83(4):612-614.
- Newman SP, Moren F, Pavia D, Sheahan NF, Clarke SW. Deposition of pressurized aerosols in the human respiratory tract. Thorax 1981;36(1):52-55.
- Spiro SG, Singh CA, Tolfree SEJ, Partridge MR, Short MD. Direct labeling of ipratropium bromide aerosol and its deposition pattern in normal subjects and patients with chronic bronchitis. Thorax 1984;39(6):432-435.
- Zainudin BMZ, Biddiscombe M, Tolfree SEJ, Short M, Spiro SG. Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from pressurised metered dose inhaler, as a dry powder, and as a nebulized solution. Thorax 1990;45(6):469-473.
- SennHauser FH, Sly PD. Pressure flow characteristics of the valve in spacer devices. Arch Dis Child 1989;64 (9):1305-1307.
- Crogan SJ, Bishop MJ. Delivery efficiency of metered dose aerosols given via endotracheal tube. Anesthesiology 1989;70(6):1008-1010.
- Bishop MJ, Larson RP, Buschman DL. Metered dose inhaler aerosol characteristics are affected by the endotracheal tube actuator/adapter used. Anesthesiology 1990;73(6):1263-1265.
- Arnon S, Grigg J, Nikander K, Silverman M. Delivery of micronized budesonide suspension by metered dose inhaler and jet nebulizer into a neonatal ventilator circuit. Pediatr Pulmonol 1992;13(3):172-175
- Ebert J, Adams AB, Green-Eide B. An evaluation of MDI spacers and adapters: their effect on the respirable volume of medication. Respir Care 1992;37(8):862-868.
- Auty RM, Brown K, Neale MG, Snashall PD. Respiratory tract deposition of sodium cromoglycate is highly dependent upon technique of inhalation using the Spinhaler. Br J Dis Chest 1987;81(4):371-380.
- Richards R, Simpson SF, Renwick AG, Holgate ST. Inhalation rate of sodium cromoglycate determines plasma pharmacokinetics and protection against AMP-induced bronchoconstriction in asthma. Eur Respir J 1988;1(10):896-901.
- Vidgren MT, Karkkainen A, Karjalainen P, Paronen P, Nuutinen J. Effect of powder inhaler design on drug deposition in the respiratory tract. Int J Pharm 1988;42: 211-216.
- Portnoy J, Aggarwal J Continuous terbutaline nebulization for the treatment of severe exacerbation of asthma in children. Ann Allergy 1988;60:368-371
- Cameron D, Clay M, Silverman M. Evaluation of nebulizers for use in neonatal ventilator circuits. Crit Care Med 1990;18(8):866-870.
- Mallol J, Barrueto L, Girardi G, Toro O. Bronchodilator effect of feneterol and ipratropium bromide in infants with acute wheezing: use of MDI with a spacer device. Pediatr Pulmonol 1987;3(5):352-356.
- Canny GJ, Levison H. Childhood asthma: a rational approach to treatment. Ann Allergy 1990;64(5):406-418.
- Toogood JH, Baskerville J, Jennings B, Lefcoe NM, Johansson SA. Use of spacers to facilitate inhaled corticosteroid treatment of asthma. Am Rev Respir Dis 1984;129(5):723-729.
- Grigg J, Arnon S, Jones T, Clarke A, Silverman M. Delivery of therapeutic aerosols to intubated babies. Arch Dis Child 1992;67(1 spec no):25-30.
- Pedersen S. How to use a Rotohaler. Arch Dis Child 1986;61(1):11-14.
- Pedersen S. Treatment of acute bronchoconstriction in children with the use of a tube spacer aerosol and a dry powder inhaler. Allergy 1985;40(4):300-304.
- Mallol J, Barrueto L, Girardi G, Munoz R, Puppo H, Ulloa V, Toro O, Quevado F. Use of nebulized bronchodilators in infants under 1 year of age: analysis of four forms of therapy. Pediatr Pulmonol 1987;3(5): 298-303.
- Lyttle BD, Hollestelle AM. Asthma: assessment and management in a pediatric hospital. Can Fam Physician 1993;39:793-798.
- Spier S, Drblik SP, Lamarre A, Lapierre G, Marcotte JE, Bourgeois M. A protocol for aerosol therapy in acute hospitalized asthmatics. J Asthma 1992;29(6):401-405.
- Brudno DS, Parker DH, Slaton G. Response of pulmonary mechanics to terbutaline in patients with bronchopulmonary dysplasia. Am J Med Sci 1989;297 (3):166-168.
- Wilkie RA, Bryan MH. Effect of bronchodilators on airway resistance in ventilator-dependent neonates with chronic lung disease. J Pediatr 1987;111(2):278-282.
- Caldwell NA. Nebulization in hospitals and home: standardizing the variables. Eur Respir Rev 1994;4:99-101.
- Everard ML, Clark AR, Milner AD. Drug delivery from holding chambers with attached facemask. Arch Dis Child 1992;67(5):580-585.
- Henney HR III, Blatt RS. Knowledge of nurse and respiratory therapists about using canister nebulizers. Am J Hops Pharm 1984;41(11):2403-2405.
- Roberts RJ, Robinson JD, Doering PL, Dallman JJ, Steeves RA. A comparison of various types of patient instruction in the proper administration of metered inhalers. Drug Intell Clin Pharm 1982;16(1):53-55, 59.
- Self TH, Brooks JB, Lieberman P, Ryan MR. The value of demonstration and role of the pharmacist in teaching the correct use of pressurized bronchodilators. Can Med Assoc J 1986;128:129-131.
- Centers for Disease Control. Update: Universal Precautions for prevention and transmission of human immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in health care settings. MMWR 1988;37:377-388.
- Centers for Disease Control/Guidelines for preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related tissues. MMWR 1990;39(RR-17):1-29.
Interested persons may copy these Guidelines for noncommercial
purposes of scientific or educational advancement. Please credit AARC and Respiratory
Reprinted from the December 1995 issue of RESPIRATORY CARE [Respir Care 1995;40(12):1325–1335]