Nebulisation & Medications.pptx

A presentation on nebulisation , its history, devices..etc

1. Inhalation Devices & Medications Dr.A.Sundararajaperumal M.D (TB & RM) ; D.C.H Professor – Thoracic Medicine Institute Of Thoracic Medicine Madras Medical College & RGGGH Chennai – 600 003

2. HISTORY OF INHALATION THERAPY

3. EARLIEST KNOWN INHALATION Inhalation of vapor of black henbane (1,554 B.C.) Egyptian physicians threw this weed onto hot bricks Alkaloid contents of the plant got vaporized which the breathless patients would inhale

4. HISTORY - INHALATION South American Tobacco Pipes 2000 Years Ago

5. EARLIEST KNOWN INHALATION THERAPY IN INDIA The practice of inhaling fumes of stramonium (Datura) and hemp

6. THE FIRST ‘INHALER’ (1778) The word inhaler was first used by the English physician John Mudge in 1778, for a pewter tankard for the use of opium vapour to treat cough.

7. History The Sales-Girons “ pulverisateur ,” which won the 1858 silver prize of the Paris Academy of Science. The pump handle draws liquid from the reservoir and forces it through an atomize FIRST PRESSURISED INHALER (1858)

8. FIRST pMDI March 1956 – Launch of the first pMDI ( Medihaler -Epi, Medihaler -Iso).

9. PRINCIPLES OF INHALATIONAL THERAPY

10. > 5 Particle size (microns) Regional deposition Efficacy Safety Mouth / oesophageal region No clinical effect Absorption from GI tract if swallowed Particle size of drugs in inhaler devices: Hypothesis from available data 2 – 5 Upper / central airways Clinical effect Subsequent absorption from lung < 2 Peripheral airways / alveoli Some local clinical effect High systemic absorption

11. Three main mechanisms Inertial impaction: For larger particles Sedimentation: For the medium size particles. Diffusion: Brownian motion for smaller particles

12. Fate of Inhaled Drugs Systemic circulation 20% deposited in lung 80% swallowed URINE

13. DEVICES FOR TREATMENT OF AIRWAY DISEASE > 65 different inhaled products of more than 20 ingredients ……and many more to come

14. Devices - Types Types and function of devices available for delivery of therapeutic aerosols are reviewed here pressurized metered dose inhalers ( pMDIs ), dry powder inhalers (DPIs), soft mist inhalers (SMIs), and nebulizers

15. PRESSURIZED METERED DOSE INHALERS (pMDI) A pMDI consists of a pressurized canister, a metering valve and stem, and a mouthpiece actuator. The canister contains the drug suspended in a pressurized mixture of propellants, surfactants, preservatives, flavoring agents, and dispersal agents. The propellent is hydrofluoroalkane (HFA) Lung deposition ranges between 10 and 40 percent of the nominal dose in adults and is very technique-dependent

16. PRESSURIZED METERED DOSE INHALERS (pMDI) New pMDI technology incorporates micronized drug crystals that are co-suspended with porous phospholipid particles in the HFA propellant. The drug crystals form strong associations with the porous phospholipid particles, and the drug-to-porous-particle ratios employed minimize drug-drug interactions for multi-drug combinations within a single inhaler. Unlike conventional HFA pMDIs , no additional excipients, such as co-solvents or suspension stabilizers, are needed. This co-suspension technology was used in the development of a LAMA/LABA fixed-dose combination of glycopyrronium and formoterol in a pMDI

17. PRESSURIZED METERED DOSE INHALERS (pMDI) Difficulty is precisely coordinating device actuation with inhalation, leads to poor drug delivery, suboptimal disease control, and increased inhaler use Such problems might be overcome by employing a spacer/valved holding chamber or breath-actuated pMDI .

18. MDI WITH SPACER Decreases oropharyngeal deposition due a reduction in velocity. This reduces local as well as systemic side effects Overcomes coordination problems Decreases cold freon effect Larger particles remain in the spacer while the smaller particles are inhaled Increases drug deposition in lungs Recommended esp. : dose of inhaled steroids > 800 mcg/day administration of high dose bronchodilators Assembled Unit Inhalation chamber Mouthpiece Canister Dust cap Lock

19. Features of the Autohaler Solves the problem of patient coordination of actuation with inhalation. Autohaler senses the patient’s inhalation through the actuator and fires the inhaler automatically in synchrony. The Autohaler fires at a flow rate of 20-30 l/min Patients seem to find Autohaler easier to use than conventional pMDI Breath Actuated Inhaler

20. Press & Breath inhaler poor coordination Autohaler™ Inhalation Device same patient 20.8% 7.2% Drug Deposition with the Autohaler™ Inhalation Device MEAN Lung Deposition . Thorax. 1991; 46(10):712-716

21. Type Advantages Disadvantages Pressurized metered dose inhaler ( pMDI ) Convenient May be less expensive than nebulizer Portable More efficient than nebulizer No drug preparation required Difficult to contaminate Dose counter with some devices Patient coordination essential Patient actuation required Large pharyngeal deposition Difficult to deliver high doses Not all medications available pMDI with holding chamber Less patient coordination required Less pharyngeal deposition More expensive than pMDI alone Less portable than pMDI alone

22. DRY POWDER INHALERS (DPI) Dry powder inhalers (DPIs) create medication aerosols by drawing air through a dose of powdered medication. DPIs vary in the use of carrier molecules, internal resistance to airflow, threshold inspiratory flow needed for deaggregation of powder, particle size, and susceptibility to clumping in high ambient humidity.

23. SINGLE DOSE MULTI DOSE Reservoir Discrete Novolizer Revolizer Rotahaler Lupihaler Redihaler Multihaler Accuhaler Turbohaler CLASSIFICATION OF DPIS

24. DRY POWDER INHALERS (DPI) Carrier molecules – The micronized particles are either in the form of loose aggregates or they are bound to larger carrier particles (usually lactose or glucose). To facilitate deposition in the lungs, drug particles are deagglomerated during inhalation. Internal resistance to airflow – The internal resistance to airflow varies among DPIs over a broad range. The turbulent energy created during inhalation is the product of the patient’s inhalation flow multiplied by the DPI’s resistance. Thus , a DPI with a high resistance will require a lower inhalation flow to achieve a similar pressure difference, than a DPI with a lower resistance .

25. DRY POWDER INHALERS (DPI) Threshold inspiratory flow – For each DPI there is a minimum turbulent energy that must be achieved for sufficient deaggregation of the powder during an inhalation . Particle size – DPIs produce aerosols in which most of the drug particles are in the respirable range; however, the distribution of particle sizes differs significantly among the various DPIs. Humidity – High ambient humidity produces clumping of the powder, creating larger particles that are not as effectively aerosolized. Patients should be instructed to exhale before inhaling through their DPI device. They should not exhale into the device, but rather exhale into the room.

26. How DPI’ s work? Respir Care 2005;50(9):1209–1227

27. Type Advantages Disadvantages Dry powder inhaler (DPI) Less patient coordination required Convenient Propellant not required Portable Breath-actuated Dose counter Requires moderate to high inspiratory flow Some units are single dose and need daily loading  Can result in high pharyngeal deposition Not all medications available Cannot be used effectively in mechanically ventilated patients

28. SOFT MIST INHALERS Soft mist inhalers are aerosol delivery devices that have been formulated to aerosolize solutions through microelectronic dosimetric systems. When an SMI is manually primed a measured amount of drug solution is drawn up into the dosing system. Pressing a button releases the spring, and the buildup of pressure forces the liquid through a nozzle structure within a uniblock that has two narrow outlet channels etched using microchip technology. The two jets of solution converge and the impact generates a soft mist aerosol for approximately 1.2 seconds.

29. Type Advantages Disadvantages Soft mist inhaler (SMI) Higher lung deposition than pMDIs or jet nebulizers Less pharyngeal deposition than pMDIs Longer duration of spray Low risk of contamination Propellant not required Dose counter Requires actuation by patient Needs coordination between breathing and actuation ¶ Requires loading of cartridge into inhaler before first use Not all medications available Cannot be used effectively in mechanically ventilated patients The SMI aerosol has a high fine particle fraction, a low velocity, and more sustained duration than a pMDI

30. Nebulisation - Introduction Process of dispersing a liquid (medication) into microscopic particles and delivering into lungs as patient inhales Nebulizers convert solutions or suspensions into aerosols with a particle size that can be inhaled into the lower respiratory tract. An important component of treatment for many respiratory disorders Include delivery of medication directly to the site of action, potentially faster onset of action, and reduced systemic availability to minimize adverse effects of the medication.

31. USES Inhaled beta agonist and muscarinic antagonist (anticholinergic) bronchodilators for chronic obstructive lung diseases ( eg , asthma, COPD, bronchiectasis, bronchiolitis) Inhaled corticosteroids or ICS for asthma, eosinophilic bronchitis, and COPD Inhaled antibiotics for prevention of Pneumocystis pneumonia and treatment of respiratory syncytial virus, cystic fibrosis, and bronchiectasis Airway secretion modifying agents for cystic fibrosis Inhaled pulmonary vasodilators for pulmonary hypertension Aerosol delivery of drugs ( eg , opiates, insulin, levodopa, loxapine ) may be used to treat some non respiratory diseases

32. NEBULIZERS The three basic types of nebulizer devices are jet (also known as pneumatic), ultrasonic, and mesh. Nebulizer performance is affected by both technical and patient-related factors

33. JET NEBULIZERS Mechanism — The operation of a jet nebulizer requires an air compressor or a pressurized gas supply ( eg , compressed air, oxygen), which acts as the driving force for liquid atomization. Compressed gas is delivered as a jet through a small orifice, generating a region of negative pressure above the medication reservoir. The solution to be aerosolized is first entrained, or pulled into the gas stream (Venturi effect), and then sheared into a liquid film. This film is unstable, and rapidly breaks into droplets due to surface tension forces. A baffle placed in the aerosol stream allows formation of smaller droplets and recycling of larger droplets into the liquid reservoir. The aerosol of respirable particles is entrained into the inspiratory gas stream inhaled by the patient.

34. Mesh nebulizers The solution or suspension of medication is forced through the mesh to produce an aerosol, without need for an internal baffling system or compressed air source. A common feature of these devices is their ability to generate aerosols with a high fine-particle fraction, which results in more efficient drug delivery compared to conventional nebulizers

35. Ultrasonic nebulizers Ultrasonic nebulizers consist of a power unit and transducer, with or without an electric fan. The power unit converts electrical energy to high-frequency ultrasonic waves. A piezoelectric element in the transducer vibrates at the same frequency as the applied wave. Ultrasonic waves are transmitted to the surface of the solution to create an aerosol. The droplets produced by these devices have a slightly higher mass median aerodynamic diameter (MMAD) than droplets from a jet nebulizer Advantages are quieter medication delivery and shorter treatment time than the jet nebulizers. Disadvantages A potential issue with the use of ultrasonic nebulizers is drug inactivation by increased temperature of the solution during ultrasonic nebulization. Additionally, ultrasonic nebulizers create aerosol droplets from the surface of the liquid. In suspensions, such as budesonide, the drug particles tend to settle and ultrasonic nebulizers are inefficient for aerosolization of suspensions. Poor battery life.

36. Factors affecting drug delivery Respirable dose – The most important characteristic of nebulizer performance is the respirable dose delivered to the patient. Droplet size is usually reported as mass median aerodynamic diameter Droplet size should be 2 to 5 μm for airway deposition ( eg , bronchodilator administration) and 1 to 2 μm or smaller for parenchymal deposition ( eg , drugs intended for absorption into the bloodstream such as pulmonary vasodilators). Nebulization time – Nebulization time, the time required to deliver a dose of medication, is determined by the volume of drug to be delivered and the flow of the driving gas into the nebulizer. Nebulization time is an important determinant of patient compliance with completing a full dose in the outpatient setting. During nebulization , the solution within the nebulizer becomes increasingly concentrated as water evaporates from the solution. Thus, on a per breath basis, more medication is delivered late in the course of a treatment. Patients should be encouraged to continue the treatment until there is no further pooling of medication in the bottom of the reservoir; reservoir sputtering is a good sign that the treatment is complete.

37. Factors affecting drug delivery Dead volume – The volume of medication trapped inside the nebulizer, and therefore not available for inhalation, is referred to as the dead volume of the device. The dead volume is typically in the range of 1 to 3 mL. Increasing the amount of solution within the nebulizer (the fill volume) reduces the proportion of the dose lost as dead volume. Although nebulizer output increases with a greater fill volume, this also results in an increase in nebulization time When combining drug solutions in the nebulizer to minimize the time required for treatment, it is important to avoid a drug volume that exceeds the labelled maximum volume of the nebulizer and to avoid any incompatibility issues of the drugs.

38. Factors affecting drug delivery Driving gas – Increasing the flow of the driving gas results in an increase in nebulized output and a reduction in particle size. A flow of 6 to 8 L/min is usually selected to optimize drug delivery. Gas density – The density of the gas powering the nebulizer affects nebulizer performance. For example, the inhaled mass of salbutamol is significantly reduced when a nebulizer is powered with a mixture of helium and oxygen ( heliox ). Accordingly, in the rare situation that the nebulizer is powered with heliox , the flow to the nebulizer is increased by 50 percent to 9 to 12 L/min. Breathing pattern – The breathing pattern of the patient affects the amount of aerosol deposited in the lower respiratory tract. Airflow obstruction increases the need for inhaled bronchodilator therapy, but can decrease the effectiveness of that treatment. To improve aerosol penetration and deposition in the lungs, the patient should be encouraged to use a slow breathing pattern with a normal tidal volume and an occasional deep breath Nebulizer/compressor combination – Matching a nebulizer with a compressor is important for optimal performance and to ensure that the aerosol produced is therapeutic.

39. Enhanced nebulizer designs Newer technologies for nebulizer design address issues of medication conservation, speed of delivery of medication, portability, battery power, and administration of specialized medications. With the traditional nebulizer design, an aerosol is generated throughout the patient's respiratory cycle. This results in considerable waste of aerosol during exhalation. Newer designs reduce aerosol waste during the exhalation phase

40. Type Advantages Disadvantages Jet nebulizer Patient coordination not required High doses possible May be more expensive than pMDI More time required Contamination possible Device preparation required before treatment Not all medications available Less efficient than other devices (dead volume loss) Mesh nebulizer ( eg , Aeroneb , eFlow , Omron MicroAir , I-neb) Patient coordination not required High doses possible Quiet Faster delivery than jet nebulizer Portable, battery operated Expensive Contamination possible Device preparation required before treatment Cleaning required after dose Not all medications available Ultrasonic nebulizer ( eg , OPTI-NEB, Beetle Neb, Lumiscope , MiniBreeze ) Patient coordination not required High doses possible Small dead volume Quiet No drug loss during exhalation Faster delivery than jet nebulizer Expensive Contamination possible Prone to malfunction Device preparation required before treatment Cannot use with medications in suspension ( eg , budesonide)

41. Aerosol Therapy Administration of medication aerosols by pMDI or nebulizer to a spontaneously breathing patient with a tracheostomy tube requires use of adaptive devices For mechanically-ventilated patients who require aerosol medication, we suggest the use of pMDIs , combined with a specialized spacer that is placed in the ventilator tubing, or a mesh nebulizer, rather than a jet nebulizer . The pMDI method is technically easier than jet nebulizer treatments, involves less personnel time, provides a reliable dose of the drug, and reduces the risk of bacterial contamination that can occur with a nebulizer. Inhaled medications can also be delivered effectively to patients receiving non invasive positive pressure ventilation (NIV).

42. Special Situations Patients with tracheostomy — Techniques have been developed for the delivery of aerosol medication by nebulizer or pMDI to patients with a tracheostomy tube who are not ventilator dependent Two systems are available for delivery of nebulized medication: either a mask can be placed over the tracheostomy opening or the nebulizer chamber can be attached to the tracheostomy tube using a T-piece made of ventilator tubing and a connector. The T-piece approach is preferred because more aerosol medication is directed into the tracheostomy tube. For delivery of a pMDI aerosol, the canister is removed from its usual plastic actuator and inserted into an actuator/spacer that is attached by T shaped connector to the tracheostomy tube. This actuator/spacer is the same as that used for patients on mechanical ventilation The caregiver actuates the pMDI into the spacer and the patient inhales the aerosol through the tracheostomy tube. Adaptors have not been developed for effective administration of medication from DPIs into tracheostomy tubes. Inline metered dose inhaler spacing device

43. Special Situations Mechanically ventilated patients — A number of factors affect aerosol delivery during mechanical ventilation . One major factor is that humidification of inhaled gas decreases aerosol deposition by approximately 40 percent due to increased particle drug deposition in the ventilator circuit. For this reason, increased dosage of medication is often required to achieve a therapeutic effect in mechanically ventilated patients. Inhaled medications can be delivered to patients receiving mechanical ventilation using either a pMDI or a nebulizer. A DPI is inefficient for delivery of a dry powder during mechanical ventilation because ventilator circuit humidification impairs aerosol formation Valved T-adaptor for nebulization during mechanical ventilation

44. Special Situations The heat and moisture exchange (HME) selection device uses a rotating collar to allow switching from HME mode for heat and moisture exchange to AEROSOL mode without opening the ventilator circuit. In HME mode, the unit functions as a heat and moisture exchanger. In AEROSOL mode, the heat and moisture function is bypassed for administration of an aerosolized or MDI medication.

45. Special Situations The CircuVent ®  device allows delivery of aerosolized medications (MDI or nebulized) to mechanically ventilated patients without removing the heat and moisture exchanger (HME). Using a valve system, air bypasses the HME during delivery of the aerosol.

46. Special Situations Patients receiving noninvasive ventilation — Aerosol therapy can also be administered during noninvasive positive pressure ventilation (NIV),using devices adapted for inline administration . Effective delivery of salbutamol by MDI during NIV using a specialized spacer has been reported in patients with exacerbations of chronic obstructive pulmonary disease (COPD) . When delivering aerosol therapy during NIV, the aerosol generator should be placed between the leak port and the interface. . Aerosolized medications, either by nebulizer or MDI, can be administered during NPPV

47. Conclusion Clinicians must be aware of inhaler devices Choose a device that is suitable to the patient (which he likes) Train him (takes a few minutes) Check inhaler technique regularly (excellent investment)

48. THANK YOU

49. Aerosol Therapy For spontaneously breathing patients, pMDIs , DPIs, and nebulizers are all effective for treatment of asthma and chronic obstructive pulmonary disease (COPD) when used correctly. Thus, we advise selecting a delivery device based upon the desired beta agonist or glucocorticoid, convenience, cost, clinician and patient preferences, and the patient’s ability to use the device correctly For patients with a mild to moderate exacerbation of asthma, beta-2 agonists ( eg , salbutamol) may be administered either by nebulizer or by pMDI combined with a spacer or chamber device . For patients with a severe exacerbation of asthma not requiring mechanical ventilation, we suggest delivery of inhaled beta-2 agonists by nebulizer rather than pMDI . Use of a nebulizer for a severe asthma exacerbation may be intermittent (every 20 to 30 minutes) or continuous. Some drug preparations are only approved for delivery with specific nebulizers due to factors such as preventing contamination of the ambient environment, achieving greater precision in dosing, or preventing medication degradation by the aerosol technology. Examples of medications requiring specific nebulizers include budesonide, iloprost , pentamidine , ribavirin, DNase I, tobramycin, aztreonam , treprostinil , glycopyrrolate and liposomal amikacin

50. Factors affecting drug delivery through spacers Size : The optimum size of a spacer for a young child is approximately 250-300 ml while the adults can use both small as well as large volume spacers. Shape : The shape should be close to the shape of aerosol plume discharged from the pMDI. Electrostatic charge : Electrostatic charge is a commonly reported cause of inconsistent medication delivery from a spacer. An non static spacer significant improves the lung deposition. Multiple actuations : Preferable to fire one puff at at time in the spacer Inhalation delay : Spacers with a longer aerosol half life may be preferred S A Respir J 1998; 4: 25 Swiss Med Wkly 2001; 131: 14-18 Eur Respir J 1999; 13: 673-678

51. Special Situations iNeb nebulizer showing device and principle of operation Adaptive Aerosol Delivery

52. Drug name(s) Age range approved Preparation(s)* Adult dose Pediatric dose Short-acting, inhaled beta-2 agonists Salbutamol Salbutamol HFA ¶ ≥4 years old MDI: 90 mcg/puff 2 puffs every 4 to 6 hours as needed 2 puffs every 4 to 6 hours as needed Salbutamol DPI ¶ ≥4 years old DPI: 90 mcg/actuation 2 inhalations every 4 to 6 hours, as needed 2 inhalations every 4 to 6 hours, as needed Salbutamol solution for nebulization ≥2 years old Nebulizer solutions: 0.021% (0.63 mg/3 mL) 0.042% (1.25 mg/3 mL) 0.083% (2.5 mg/3 mL) 0.5% (2.5 mg/0.5 mL) concentrate 2.5 mg every 4 to 6 hours as needed 0.1 to 0.15 mg/kg every 4 to 6 hours as needed Levosalbutamol LevoSalbutamol HFA ¶ ≥4 years old 45 mcg/puff 2 puffs every 4 to 6 hours as needed 1 to 2 puffs every 4 to 6 hours as needed LevoSalbutamol  solution for nebulization ≥6 years old Nebulizer solution: 0.31/3 mL 0.63/3 mL 1.25 mg/3 mL 1.25 mg/0.5 mL concentrate 0.63 to 1.25 mg, 2 to 4 times daily, as needed 0.31 mg, 2 to 4 times daily, as needed Usual doses of short-acting beta-2 agonists

53. Usual doses of - ICS Drug Low dose Medium dose High dose Beclomethasone HFA 80 to 160 mcg >160 to 320 mcg >320 mcg 40 mcg per puff 2 to 4 puffs 80 mcg per puff 1 to 2 puffs 3 to 4 puffs >4 puffs Beclomethasone HFA Δ 100 to 200 mcg >200 to 400 mcg >400 mcg 50 mcg per puff 2 to 4 puffs 100 mcg per puff 1 to 2 puffs 3 to 4 puffs >4 puffs Budesonide DPI 180 to 360 mcg >360 to 720 mcg >720 mcg 90 mcg per inhalation 2 to 4 inhalations 180 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations >4 inhalations Budesonide DPI Δ 200 to 400 mcg >400 to 800 mcg >800 mcg 100 mcg per inhalation 2 to 4 inhalations 200 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations 400 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations Fluticasone propionate HFA 88 to 220 mcg >220 to 440 mcg >440 mcg 44 mcg per puff 2 to 5 puffs 110 mcg per puff 1 to 2 puffs 3 to 4 puffs 220 mcg per puff 2 puffs >2 puffs

54. Medication Low dose Medium dose High dose Budesonide- formoterol HFA 80 mcg-4.5 mcg 2 puffs twice a day     160 mcg-4.5 mcg   2 puffs twice a day   Fluticasone propionate- salmeterol DPI 100 mcg-50 mcg 1 inhalation twice a day     250 mcg-50 mcg   1 inhalation twice a day   500 mcg-50 mcg     1 inhalation twice a day Usual Doses Of LABA + ICS

55. Combination long-acting muscarinic antagonist/long-acting beta agonist inhalers for COPD Agents Dosing Combination long-acting muscarinic antagonist/long-acting beta agonist inhalers Glycopyrrolate 15.6 mcg/indacaterol 27.5 mcg 1 capsule (inhalation only) twice daily; DPI Glycopyrrolate 50 mcg/indacaterol 110 mcg 1 capsule (inhalation only), once daily; DPI Glycopyrrolate 9 mcg/ formoterol 4.8 mcg 2 inhalations twice daily; pMDI

56. AEROSOL DELIVERY IN SPECIAL SITUATIONS Medication Specialized nebulizer Comments Amikacin Lamira mesh nebulizer    Aztreonam Mesh: Altera Nebulizer System   Budesonide Jet or mesh nebulizers, but NOT ultrasonic Ultrasonic nebulizers cannot be used for budesonide Dornase alpha (DNase) Jet: Pulmo-Aide, Pari-Proneb, Mobilaire, Porta-Neb, Pari-Baby   Glycopyrrolate* Magnair mesh nebulizer    Iloprost Jet: Prodose AAD (respironics) Mesh: I-neb AAD (respironics) Specialized nebulizer needed for accurate dosing Pentamidine Jet: Respirgard II Small volume, one-way valve to prevent contamination of ambient environment Ribavirin Jet: Viratek Small-Particle Aerosol Generator (SPAG-2) Small particle size; scavenging system to minimize contamination of the ambient environment Tobramycin Jet: PARI-LC PLUS   Treprostinil Ultrasonic: Optineb Specialized nebulizer needed for accurate dosing

57. Special Situations Acute asthma exacerbation — Two issues that arise when choosing an aerosol delivery system for bronchodilator medication during exacerbations of asthma are whether to use an MDI or a nebulizer and whether to use continuous or intermittent nebulization for hospital based treatment. These choices are typically based on the severity of the exacerbation and also clinician and patient preference (algorithm 1). For patients who have an asthma exacerbation that is mild to moderate in severity ( eg , mild to no dyspnea at rest and peak expiratory flow ≥40 percent of predicted), administration of the beta 2-agonist albuterol via a pMDI (2 to 6 puffs for treatment at home, 4 to 8 puffs for emergency room or hospital treatment) combined with a spacer or chamber device ( eg , Aerochamber , Optichamber Diamond, Vortex) results in comparable improvements in lung function compared to nebulizer delivery, although the actual dose delivered by a pMDI is much lower (table 2). Similar results with pMDIs have been reported in patients with severe exacerbations, but only a small number of such patients have been studied. Generally, nebulizer treatments (every 20 minutes or continuous) are preferred for more severe asthma exacerbations. (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management", section on 'Nebulizer versus MDI'.) For patients with severe asthma exacerbations ( eg , dyspnea at rest, accessory muscle use, retractions, forced expiratory volume in one second or peak expiratory flow <40 percent predicted), beta agonists are often administered continuously ( eg , albuterol 5 to 15 mg/hour) rather than intermittently [16,88,89]. This method of bronchodilator administration is equally effective compared to frequent intermittent nebulization [8,90]. Several studies have established the safety of continuous nebulization, even when high doses ( eg , 20 mg/hour of albuterol ) are used [42,88,91]. However, continuous nebulization of albuterol (10 mg/hour) in healthy adults has been associated with a decrease in serum potassium of 0.5 mEq /L (95% CI: -0.72 to -0.28 mEq /L), which could be clinically important in patients with a low potassium level prior to therapy [92]. Continuous nebulization may be most beneficial in patients with the most severe pulmonary dysfunction [88]. The specialized delivery systems adapted for continuous nebulization are described above. (See 'Continuous nebulization' above.)

58. Metered dose inhaler — A special actuator is needed to adapt the pMDI into the ventilator circuit (picture 7) [107,108]. The size, shape, and design of these actuators have a major impact on drug delivery to the patient. A pMDI with a chamber results in a four- to six-fold greater delivery of aerosol than MDI actuation into a connector attached directly to the endotracheal tube, or into an in-line device that lacks a chamber [98]. When using a pMDI during mechanical ventilation, it is important to synchronize actuation with inspiratory airflow to optimize drug delivery. Properly used, a pMDI may deliver a more consistent dose than a nebulizer [109]. The following technique has been proposed for using pMDIs in mechanically ventilated adult patients [110]: Revefenacin - ( Yupelri ) inhalation solution is the only once-daily, nebulized bronchodilator for maintenance treatment of COPD [85,86]. Revefenacin is a LAMA and is nebulized with a standard jet nebulizer connected to a compressor. (See "Role of anticholinergic therapy in COPD", section on ' Revefenacin '.)

59. Amikacin – Amikacin ( Arikayce ) liposome inhalation suspension is delivered once daily with the Lamira mesh nebulizer system. During nebulization, approximately 70 percent of the amikacin dose remains encapsulated within liposomes while approximately 30 percent of the dose is released as free amikacin . Nebulized amikacin is indicated only for patients with refractory disease caused by Mycobacterium avium complex (MAC) who have limited or no alternative treatment options [87]. (See "Treatment of Mycobacterium avium complex lung infection in adults", section on 'Efficacy of alternative agents'. ● Shake the pMDI vigorously ● Place canister in the actuator of a cylindrical spacer situated in the inspiratory limb of ventilator circuit (picture 7) ● Actuate the pMDI once only with the onset of inspiration by the ventilator ● Repeat actuations after 15 seconds until the total dose is delivered Helium-oxygen mixtures affect aerosol deposition, and in vitro modeling has reported a 50 percent increase in deposition of albuterol from a pMDI during mechanical ventilation when heliox was used as the driving gas [111]. However, heliox can interfere with the functioning of flow sensors and oxygen levels when delivered through some ventilators, and care must be taken if this approach is employed with a ventilator that is not approved for heliox administration [112-114]. (See "Physiology and clinical use of heliox ", section on 'Instrument recalibration'.) The use of a heat and moisture exchanger (HME) in the ventilator circuit can filter out the aerosol when a pMDI (or nebulizer) is used. Commercially available devices can be used to bypass the HME when a pMDI is used (picture 8 and picture 9). Alternatively, the HME must be removed from the circuit when the aerosol is delivered [115].

60. Nebulizer — The optimal methods for delivery of nebulized medication to mechanically ventilated patients are not well-established. Delivery of a large tidal volume, use of an end-inspiratory pause, and use of a slow inspiratory flow affect aerosol delivery by jet nebulizer but not by a pMDI [95]. Nebulizer performance can be optimized by placing the nebulizer 30 cm from the endotracheal tube, rather than at the Y-piece, because the inspiratory ventilator tubing acts as a spacer. In a simulation model, delivery of albuterol via mesh nebulizer was two to four times greater than with a jet nebulizer, and placement of the mesh nebulizer in the ventilator tubing on the ventilator side of the humidifier, rather than closer to the patient, increased drug delivery [100]. Operating the nebulizer only during inspiration is more efficient for aerosol delivery compared with continuous aerosol generation throughout the respiratory cycle. When a breath-actuated nebulizer is used, the delivered dose increases by more than five-fold. In addition, when the humidifier is bypassed the delivered dose increases by a factor of nearly four [96]. Disadvantages of jet nebulizer use during mechanical ventilation include circuit contamination due to interrupting the ventilator tubing circuit, decreased ability of the patient to trigger the ventilator, and the associated increases in tidal volume and airway pressure due to nebulizer flow. Valved T-piece devices are commercially available and commonly used to allow the nebulizer to be inserted within the ventilator circuit without disconnecting the patient from the ventilator, thus avoiding interruption of mechanical ventilation for nebulizer insertion and removal The mesh nebulizer can be used effectively during mechanical ventilation and is placed between the ventilator outlet and the heated humidifier Unlike the jet nebulizer, the mesh nebulizer remains in the ventilator circuit and does not interfere with ventilator function ( eg , no additional gas flow, no effect on triggering). (See 'Mesh nebulizers' above.)

61. Choice of device — Although the jet nebulizer is less efficient than the pMDI during mechanical ventilation, the nebulizer can deliver a greater cumulative dose to the lower respiratory tract [117]. Thus, nebulizers and pMDIs produce similar therapeutic effects in mechanically ventilated patients [118]. The use of a pMDI for routine bronchodilator therapy in ventilator-supported patients has been preferred because of the problems associated with the use of nebulizers, including contamination and triggering difficulty, as well as increased pressure and volume delivery. However, use of a mesh nebulizer avoids several of the problems of the jet nebulizer and performs comparably to pMDIs . Compared with the pMDI , the mesh nebulizer is a convenient and efficient delivery method in mechanically ventilated patients [119]. Aerosol delivery by pMDI is easy to administer, involves less personnel time than a nebulizer, provides a reliable dose of the drug, and is free from the risk of bacterial contamination. When a pMDI is used with an in-line spacer, the ventilator circuit does not need to be disconnected with each treatment; this may reduce the risk of ventilator-associated pneumonia. This also prevents the loss of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

62. Patients using high flow nasal cannula — The high flow nasal cannula is increasingly used for hypoxemic respiratory failure and can also be used for aerosol delivery in the intensive care unit (ICU) [126,127]. The results of in vitro studies suggest that aerosols can be delivered by HFNC, and there is anecdotal experience suggesting benefit [65]. At high flows, the amount of aerosol delivery is likely to be very low [65,66]. In one study, pulmonary drug delivery through the high-flow nasal cannula was about 1 to 4 percent of the amount placed in the nebulizer, with a higher efficiency for a mesh nebulizer than a jet nebulizer [17]. However, in a separate study of 26 subjects with COPD, the physiologic response to inhaled bronchodilator was similar for mouthpiece and nasal cannula at a flow of 35 L/minute [128]. The lower deposition with high flow nasal cannula might also be overcome by increasing the dose [65]. A pMDI , SMI, or DPI device cannot be used with high flow nasal cannula

63. Home use — Prescription of a nebulizer for home use is usually not necessary for patients with asthma or COPD due to the efficacy of pMDIs and DPIs for delivery of bronchodilator medications. However, some patients ( eg , those with difficulty mastering the technique of pMDIs ) may have a better response to a nebulizer. The decision to prescribe a nebulizer for home use is made on a case-by-case basis. Careful instructions are provided regarding indications for coming to the emergency department if one or two nebulizer treatments do not result in reduced symptoms. Typically, jet nebulizers are provided for patients with asthma or COPD unless the patient is willing to pay extra for a smaller, more portable mesh nebulizer. For patients requiring specialized medications such as budesonide suspension, iloprost , pentamidine , ribavirin, DNase I, tobramycin, aztreonam , and treprostinil the selection of a nebulizer device depends on the requirements of the particular medication, as described above. With a jet nebulizer, the patient also needs an air compressor in addition to the nebulizer, tubing, and mouthpiece. Although the nebulizer is disposable, many patients re-use it multiple times before replacing. Proper cleaning and air-drying of the nebulizer chamber and mouthpiece are needed to prevent bacterial and fungal colonization and also contamination by allergens, such as dust mites, cockroach, and dander. The plastic tubing and medication chamber should be stored in a plastic bag between uses. Once or twice a week, the nebulizer (figure 1) should be disassembled, washed in soapy tap water, and disinfected with either a 1.25 percent acetic acid (white vinegar) mixture or a quaternary ammonium compound at a dilution of 1 ounce to 1 gallon of sterile distilled water. The acetic acid soak should be at least 1 hour, but a quaternary ammonium compound soak needs only 10 minutes. However, patients with asthma should avoid breathing the fumes of these cleaning agents. Ultrasonic and mesh nebulizers should be cleaned and disinfected per the manufacturer’s specifications. Acetic acid should not be reused, but the quaternary ammonium solution can be reused for up to one week.

64. MDI Amount of Drug Per Actuation Albuterol sulfate (Ventolin, Proventil, Ventolin HFA, Proventil HFA, ProAir HFA)** 90 mcg Beclomethasone dipropionate (QVAR) 40 or 80 mcg Ciclesonide (Alvesco) 80 or 160 mcg Cromolyn sodium (Intal) 800 mcg Flunisolide (AeroBid, AeroBid-M +) 250 mcg Flunisolide hemihydrate (Aerospan HFA) 80 mcg (78 mcg delivered) Fluticasone propionate (Flovent HFA) 44, 110, or 220 mcg Fluticasone propionate/salmeterol xinafoate (Advair HFA) 45, 115, or 230 mcg/21 mcg Ipratropium bromide (Atrovent HFA) 17 mcg Ipratropium bromide/albuterol sulfate (Combivent) 18 mcg /90 mcg Levalbuterol tartrate (Xopenex HFA) 45 mcg Pirbuterol acetate (Maxair Autohaler) 200 mcg Mometasone/formoterol (Dulera) 100 or 200 mcg/5 mcg Triamcinolone acetonide (Azmacort)* 75 mcg

65. DPI Amount of Drug Delivered Budesonide (Pulmicort Flexhaler) 90 or 180 mcg (delivers 80 or 160 mcg/inhalation) Budesonide (Pulmicort Turbuhaler)* -- Budesonide/Formoterol HFA (Symbicort) Delivers 80 or 160 mcg/4.5 mcg per actuation Fluticasone propionate (Flovent Diskus) 50 mcg/inhalation Fluticasone propionate/salmeterol xinafoate (Advair Diskus) 100, 250, or 500 mcg/50 mcg per blister Formoterol fumarate (Foradil Aerolizer) 12 mcg/capsule Mometasone furoate (Asmanex Twisthaler) 110 or 220 mcg (delivers 100 or 200 mcg/inhalation) Salmeterol xinafoate (Serevent Diskus) 50 mcg/blister Tiotropium bromide (Spiriva HandiHaler) 18 mcg/capsule Note: DPIs contain dry medication inside; patient's breathing delivers medication to lungs, no propellant inside; priming not required after activating and loading initial dose; no need to shake device; do not use with spacer; keep device dry, do not place in water; clean mouthpiece and dry immediately; do not swallow capsules for inhalation. * Pulmicort Turbuhaler has been discontinued. Pulmicort Flexhaler has replaced the phased-out product.

66. Drug Available concentrations Albuterol sulfate (Proventil, AccuNeb) 5 mg/mL; 0.63 or 1.25 mg/3 mL Arformoterol tartrate (Brovana) 15 mcg/2 mL Budesonide (Pulmicort Respules) 0.25, 0.5, or 1 mg/2 mL Cromolyn sodium (Intal) 20 mg/2 mL Formoterol fumarate (Perforomist) 20 mcg/2 mL Ipratropium bromide 500 mcg/2.5 mL Ipratropium bromide/albuterol sulfate (DuoNeb) 0.5 mg/2.5 mg/3 mL Levalbuterol hydrochloride (Xopenex) 0.31, 0.63, or 1.25 mg/3 mL; 1.25 mg/0.5 mL

67. Type Advantages Disadvantages Jet nebulizer* Patient coordination not required High doses possible May be more expensive than pMDI More time required Contamination possible Device preparation required before treatment Not all medications available Less efficient than other devices (dead volume loss) Mesh nebulizer (eg, Aeroneb, eFlow, Omron MicroAir, I-neb) Patient coordination not required High doses possible Quiet Faster delivery than jet nebulizer Portable, battery operated Expensive Contamination possible Device preparation required before treatment Cleaning required after dose Not all medications available Ultrasonic nebulizer (eg, OPTI-NEB, Beetle Neb, Lumiscope, MiniBreeze) Patient coordination not required High doses possible Small dead volume Quiet No drug loss during exhalation Faster delivery than jet nebulizer Expensive Contamination possible Prone to malfunction Device preparation required before treatment Cannot use with medications in suspension ( eg , budesonide)

68. Pressurized metered dose inhaler ( pMDI ) Convenient May be less expensive than nebulizer Portable More efficient than nebulizer No drug preparation required Difficult to contaminate Dose counter with some devices Patient coordination essential Patient actuation required Large pharyngeal deposition Difficult to deliver high doses Not all medications available pMDI with holding chamber Less patient coordination required Less pharyngeal deposition More expensive than pMDI alone Less portable than pMDI alone Dry powder inhaler (DPI) Less patient coordination required Convenient Propellant not required Portable Breath-actuated Dose counter Requires moderate to high inspiratory flow Some units are single dose and need daily loading  Can result in high pharyngeal deposition Not all medications available Cannot be used effectively in mechanically ventilated patients Soft mist inhaler (SMI) Higher lung deposition than pMDIs or jet nebulizers Less pharyngeal deposition than pMDIs Longer duration of spray Low risk of contamination Propellant not required Dose counter Requires actuation by patient Needs coordination between breathing and actuation ¶ Requires loading of cartridge into inhaler before first use Not all medications available Cannot be used effectively in mechanically ventilated patients

69. Technique for use of medication nebulizer Place patient in a comfortable position (preferably sitting up or partially supine, since there is some risk of spillage if the patient is lying flat). Assemble apparatus. Add medication to nebulizer. Use a fill volume of 3 to 6 mL. Attach a compressor or a pressurized gas supply (eg, compressed air or oxygen) with a flow of 6 to 8 L/min. Instruct patient to breathe through the mouth whether using a mask or mouthpiece. If using a mouthpiece, the patient can rest teeth on mouthpiece and close lips around it. Encourage patient to breathe with a slow inspiratory flow and an occasional deep breath. Periodically tap nebulizer to return impacted droplets to reservoir. Stop treatment when the nebulizer sputters despite tapping.

70. Usual doses of - ICS Budesonide DPI 180 to 360 mcg >360 to 720 mcg >720 mcg 90 mcg per inhalation 2 to 4 inhalations 180 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations >4 inhalations Budesonide DPI Δ 200 to 400 mcg >400 to 800 mcg >800 mcg 100 mcg per inhalation 2 to 4 inhalations 200 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations 400 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations Ciclesonide HFA 80 to 160 mcg >160 to 320 mcg >320 mcg 80 mcg per puff 1 to 2 puffs 3 to 4 puffs 160 mcg per puff 1 puff 2 puffs >2 puffs Ciclesonide HFA Δ 100 to 200 mcg >200 to 400 mcg >400 mcg 100 mcg per puff 1 to 2 puffs 3 to 4 puffs 200 mcg per puff 1 puff 2 puffs >2 puffs

71. Flunisolide MDI 320 mcg >320 to 640 mcg Insufficient data 80 mcg per puff 4 puffs 5 to 8 puffs Insufficient data Fluticasone propionate HFA 88 to 220 mcg >220 to 440 mcg >440 mcg 44 mcg per puff 2 to 5 puffs 110 mcg per puff 1 to 2 puffs 3 to 4 puffs 220 mcg per puff 2 puffs >2 puffs

72. Drug Low dose Medium dose High dose Beclomethasone HFA (Qvar and Qvar RediHaler products available in United States)* 80 to 160 mcg >160 to 320 mcg >320 mcg 40 mcg per puff 2 to 4 puffs ¶ ¶ 80 mcg per puff 1 to 2 puffs 3 to 4 puffs >4 puffs Beclomethasone HFA Δ ( Qvar product available in Canada, Europe, and elsewhere) 100 to 200 mcg >200 to 400 mcg >400 mcg 50 mcg per puff 2 to 4 puffs ¶ ¶ 100 mcg per puff 1 to 2 puffs 3 to 4 puffs >4 puffs Budesonide DPI (Pulmicort Flexhaler product available in United States)* 180 to 360 mcg >360 to 720 mcg >720 mcg 90 mcg per inhalation 2 to 4 inhalations ¶ ¶ 180 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations >4 inhalations Budesonide DPI Δ ( Pulmicort Turbuhaler product available in Canada, Europe, and elsewhere) 200 to 400 mcg >400 to 800 mcg >800 mcg 100 mcg per inhalation 2 to 4 inhalations ¶ ¶ 200 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations ¶ 400 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations Ciclesonide HFA (Alvesco product available in United States, Europe, and elsewhere)* 80 to 160 mcg >160 to 320 mcg >320 mcg 80 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶ 160 mcg per puff 1 puff 2 puffs >2 puffs Ciclesonide HFA Δ (Alvesco product available in Canada) 100 to 200 mcg >200 to 400 mcg >400 mcg 100 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶ 200 mcg per puff 1 puff 2 puffs >2 puffs Flunisolide MDI (Aerospan product available in United States)* 320 mcg >320 to 640 mcg Insufficient data 80 mcg per puff 4 puffs 5 to 8 puffs Insufficient data Fluticasone propionate HFA (Flovent HFA product available in United States)* 88 to 220 mcg >220 to 440 mcg >440 mcg 44 mcg per puff 2 to 5 puffs ¶ ¶ 110 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶ 220 mcg per puff ◊ 2 puffs >2 puffs Fluticasone propionate HFA Δ ( Flovent HFA product available in Canada, Europe, and elsewhere) 100 to 250 mcg >250 to 500 mcg >500 mcg 50 mcg per puff 2 to 5 puffs ¶ ¶ 125 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶ 250 mcg per puff ◊ 2 puffs >2 puffs Fluticasone propionate DPI ( Flovent Diskus product available in United States and Canada)* 100 to 250 mcg >250 to 500 mcg >500 mcg 50 mcg per inhalation 2 to 5 inhalations ¶ ¶ 100 mcg per inhalation 1 to 2 inhalations 3 to 5 inhalations ¶ 250 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations 500 mcg per inhalation (strength not available in United States) ◊ 1 inhalation >1 inhalation Fluticasone propionate DPI (Armonair Respiclick product available in United States)* 100 to 250 mcg >250 to 500 mcg >500 mcg 55 mcg per inhalation 2 to 4 inhalations ¶ ¶ 113 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations >4 inhalations 232 mcg per inhalation 1 inhalation 2 inhalation >2 inhalations Fluticasone furoate DPI (Arnuity Ellipta product available in United States)* NOTE:  Inhaled fluticasone furoate has a greater anti-inflammatory potency per microgram than fluticasone propionate inhalers. Thus, fluticasone furoate is administered at a lower daily dose and used only once daily. 50 mcg (by use of pediatric DPI, which is off-label in adolescents and adults) 100 mcg 200 mcg 50 mcg per inhalation 1 inhalation ¶ ¶ 100 mcg per inhalation ◊ 1 inhalation 2 inhalations 200 mcg per actuation ◊ ◊ 1 inhalation Mometasone DPI § (Asmanex DPI product available in United States)* 110 to 220 mcg >220 to 440 mcg >440 mcg 110 mcg per inhalation 1 to 2 inhalations ¶ ¶ 220 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations Mometasone HFA § (Asmanex HFA product available in United States)* 100 to 200 mcg >200 to 400 mcg >400 mcg 100 mcg per actuation 1 to 2 inhalations ¶ ¶ 200 mcg per actuation 1 inhalation 2 inhalations >2 inhalations Mometasone DPI Δ§ (Asmanex Twisthaler product available in Canada, Europe, and elsewhere) 200 mcg >200 to 400 mcg >400 mcg 200 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations 400 mcg per inhalation ◊ 1 inhalation >1 inhalation

73. Fluticasone propionate HFA ( Flovent HFA product available in United States)* 88 to 220 mcg >220 to 440 mcg >440 mcg 44 mcg per puff 2 to 5 puffs ¶ ¶ 110 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶ 220 mcg per puff ◊ 2 puffs >2 puffs Fluticasone propionate HFA Δ ( Flovent HFA product available in Canada, Europe, and elsewhere) 100 to 250 mcg >250 to 500 mcg >500 mcg 50 mcg per puff 2 to 5 puffs ¶ ¶ 125 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶ 250 mcg per puff ◊ 2 puffs >2 puffs Fluticasone propionate DPI (Flovent Diskus product available in United States and Canada)* 100 to 250 mcg >250 to 500 mcg >500 mcg 50 mcg per inhalation 2 to 5 inhalations ¶ ¶ 100 mcg per inhalation 1 to 2 inhalations 3 to 5 inhalations ¶ 250 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations 500 mcg per inhalation (strength not available in United States) ◊ 1 inhalation >1 inhalation Fluticasone propionate DPI (Armonair Respiclick product available in United States)* 100 to 250 mcg >250 to 500 mcg >500 mcg 55 mcg per inhalation 2 to 4 inhalations ¶ ¶ 113 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations >4 inhalations 232 mcg per inhalation 1 inhalation 2 inhalation >2 inhalations Fluticasone furoate DPI ( Arnuity Ellipta product available in United States)* 50 mcg (by use of pediatric DPI, which is off-label in adolescents and adults) 100 mcg 200 mcg 50 mcg per inhalation 1 inhalation ¶ ¶ 100 mcg per inhalation ◊ 1 inhalation 2 inhalations 200 mcg per actuation ◊ ◊ 1 inhalation

74. Mometasone DPI § 110 to 220 mcg >220 to 440 mcg >440 mcg 110 mcg per inhalation 1 to 2 inhalations ¶ ¶ 220 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations Mometasone HFA § 100 to 200 mcg >200 to 400 mcg >400 mcg 100 mcg per actuation 1 to 2 inhalations ¶ ¶ 200 mcg per actuation 1 inhalation 2 inhalations >2 inhalations Mometasone DPI Δ§ 200 mcg >200 to 400 mcg >400 mcg 200 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations 400 mcg per inhalation ◊ 1 inhalation >1 inhalation

75. Factors affecting aerosol delivery by nebulizer Technical factors Mechanism and manufacturer Flow rate Fill volume Solution characteristics Characteristics of driving gas Designs to enhance output Continuous versus intermittent delivery Patient factors Breathing pattern Nose versus mouth breathing Artificial airway Airway obstruction Positive pressure level

76. Factors affecting aerosol delivery during mechanical ventilation Nebulizer Position of nebulizer placement in the circuit Type of nebulizer and fill volume Treatment time Duty cycle (I:E ratio) Ventilator brand pMDI Type of actuator Timing of actuation Nebulizer and pMDI Endotracheal tube size Humidification of the inspired gas