AIM OF AEROSOL THERAPY• To deliver a therapeutic dose of the selected agents to the desired site of action.• Choice of route for drug delivery -Directly to the site of action -Therapeutic action with side Effects: high therapeutic index, greater efficacy & safety
AEROSOL• Definition A suspension of very fine liquid or solid particles in a gas.• Key to aerosol therapy is aerosol particle• Respirable range:1-5 micron• 80%drugs deposited in oropharynx• 10% in walls of inhaler• 10% in the lungs ( SP Newman et.al.1985 )
• In mechanically ventilated patients -51%within nebulizer unit -2.2%IN Rt LUNG &0.9% IN Lt LUNG (SH Thomas M fiddler et.Al.1993)• In clinical settings, medical aerosols are generated with atomizer, nebulizer or inhalers – devices that physically disperse matter into small particles & suspend them into a gas.
AEROSOL DELIVERY SYSTEMSThe three principle types of devices widelyused are : 1.MDI-metered dose inhalers 2.DPI-dry powder inhalers 3.Nebulizers
METERED DOSE INHALERS• Most widely used• Aerosol flow rate 30 m/s or 100 km/h• Propellants were CFC
ADVANTAGES OF MDI• Inexpensive• Light, compact• Quick delivery of drugs• Precise and consistent doses
DISADVANTAGES OF MDI• Difficulty in coordination of activation & inspiration• Time consuming to teach• Contains CFC• Cannot be used in children & elderly• Cannot be used in seriously ill patients• Cannot be used in mechanically ventilated patients
SPACERS• Holding chambers or reservoirs• Attachment to a MDI• Advantages : 1.No need to activate coordination With inspiration 2.Increases drug deposition in lung 3.Reduces drug deposition in mouth 4.Used in children with face mask 5.Decreases incidence of oral thrush
DRY POWDER INHALERS• Introduced in 1960’s• No propellants• Requires patient’s own Inspiratory effort to form aerosol• Powder is delivered only when patient inhales
ADVANTAGES OF DPI• Light weight• No hand breath coordination• Quick delivery of drugs• Useful in children above 5 yrs of age Disadvantages of DPI• Require high inspiration flow >28 l/min
COMPARISION BETWEEN MDI &DPI• High velocity aerosols • Aerosol velocity depends on inspiratory flow rate • No coordination• Requires coordination needed• Time consuming to • Easy to teach teach• Requires slow & deep • Requires high insp breathing only flow >28 l/min
CHARACTERISTICS OF THERAPEUTIC AEROSOLS• Effective use of aerosols requires an understanding of characteristics of the aerosols.• Aerosol output (wt /minute)• Emitted dose This tells little about the amount of drug reaching the targeted site of action.
• A substantial proportion of particles that leave a nebulizer may never reach the lungs.• Effectiveness of medical aerosols depends on amount of aerosol particles deposition to the lower respiratory tract & deposition of aerosol influenced by many other factors.
FACTORS INFLUENCING DEPOSITION• Physical & chemical properties of aerosols• Anatomy of the respiratory tract• Physiological factors (J E Agnew, D Pavian, S W Clarke et.al.1984)
PHYSICAL & CHEMICAL PROPERTIES OF AEROSOLS GRAVITY• Aerosol size must be >1 microns because at this mass gravity loses its influence on particles. ( Chantal Darquenne , G Kim Prisk et.al.2000 )• Gravity influence is in direct relation with particle mass• Greater mass—tendency to undergo proximal airway deposition
INERTIAL IMPACTIONWater particles Gas molecules
PARTICLE SIZE• Aerosol particle size depends upon : -- nebulizer chosen --Method used to generate aerosol• It is not possible to visually determine whether a nebulizer is producing an optimal size particles…• Aerosols traverse tubular strs in which turbulent flow is the rule…• >Particle size---- gravity influence
• 1-5 micron MMAD important determinant of its deposition efficacy in LRT• 1-3 micron greater deposition
TONICITY OF THE FLUID• Hypertonic fluid tend to absorb water.• Hypotonic aerosols may evaporate• Normally, mucous membrane is neutral in relation to electrical charges
ANATOMY OF THE RESPIRATORY TRACT• Diameter Infants and children have small diameter of an airway suggest that having low level of drug deposition , even that is adequate when considered in terms of body weight (mg of drug deposited per kg of BW ). (Fok T F , S.Monkman , M Dolvich et.al.1996 )• Length• Branching angles of airway segments
PHYSIOLOGICAL FACTORS• Airflow Increasing flow 6,8,10 L / min increased the mass output of particles in the respirable range of 1-5 microns.( D Hess , P Williams , S Pooler et.al. 1996 )• Breathing pattern Deposition of particles are directly related to inhaled volume & inversely related to ventilatory rate.• Inspiratory hold
• 1872 - NEBULIZER derived from the Latin “nebula” meaning “mist”• 1874 –definition as “an instrument for converting a liquid into a fine spray, especially for medical purposes”• The logic of creating a vapor or aerosol for the inhalation treatment of lung disease is at least as old as written records of medicine.
• The Ayurvedic tradition of medicine in India which dates back perhaps 4,000 yrs or more , used inhaled substances for managing respiratory disorders.• 19th century-inhalation devices were described• 1930-atomizers
• 1940-collison nebulizer It used baffle to filter out larger particles, thus distinguishing a “nebulizer” from “atomizer”.• 1950-wright nebulizer Much more compact than collison, closely resembled today’s pneumatically powered neb.• 1960-ultrasonic nebulizer A diff method of creating liquid aerosols .
TYPES OF NEBULIZERS 1. Jet nebulizer 2. Ultrasonic nebulizer
• It is a system in which high velocity gas flow is directed into a tube that is immersed in a water reservoir.• It operates from a pressurized gas• working mechanism : Venturi Principle : As the gas flow through the tube, water is drawn up in between the surfaces and come across the way of gas flow through fine spore. this gas stream impacts upon the fluid surface and dispersing liquid as an aerosol.
FEATURES OF JET NEBULIZER• Cools during operation• Less expensive• More noise• More Rx time• small particle size• Small output rate
• It is an electric nebulizer• Working principle : piezoelectric effect ultrahigh frequency current piezoelectric transducer ultrahigh frequency vibrations disk vibration couplant (water bath)
FEATURES OF ULTRASONIC NEBULIZER•More expensive•Heats up during operation , Less noise•Less Rx time•Large average particle size ( Joseph L Rau et.al.2002 )•Large output rate•0.5 to 3 microns – 90 % of particles within effectiverange
INDICATIONS FOR NEBULIZER• Useful in children ,Handicapped person , Seriously ill patients• Ventilated patients• Elderly individuals• High doses can be given• Combination drugs can be given
• Enhancement of secretion clearance• Sputum induction• Humidification of respired gases• Prevent dehydration• Prevent or relieve bronchospasm
HAZARDS OF NEBULIZER• Bronchospasm• Over hydration• Delivery of contaminated aerosols• Tubing condensation• Swelling of retained secretions
DRUGS FOR NEBULIZATION• Distilled water or normal saline• Mucolytics : mesna , acetylcysteine• Beta 2 agonists : salbutamol , terbutalin , fometerol , salmeterol• Antimuscarinic : ipratropium bromide• Steroids : budesonide• Antibiotics• Antifungal
Distilled water/NS• Cheapest / very economical• Easily available• Effective Mucolytic• Free of ions (distilled water)• Routinely used in practice
Mucolytic agents• Mucomyst• Drug action• Side effects• How to counteract
Beta-2 agonists• Mechanism of action beta receptor stimulation adenylcyclase IC ATP IC cAMP smooth muscle relaxation
salbutamol• Short acting• Selective beta 2 agonist• Peak of action• Long term use effects• Side effects
Epinephrine• Classic catecholamine• Strong alpha & beta-1 beta-2 action• Available 1:100 solution• 0.25 to 0.5 ml in 4ml NS• Lasting effect , side effects
Anticholinergic agent• Ipratropium bromide• Site of action• Usually given through mouthpiece
Nebulizer as an adjunct to chest physiotherapy• Nebulized NS enhances mucociliary clearance , given thrice in a day before chest physiotherapy & also salbutamol before NS to prevent bronchoconstriction ( J.Morton , J.A.Douglass , J.Reidler et.al.1996 )• With the patient resting in an upright position; chest physiotherapy, by the forced expiration technique with postural drainage; and chest physiotherapy following five minutes inhalation of either nebulized normal saline or nebulized terbutaline 5 mg
• Use of both nebulized saline and nebulized terbutaline immediately before chest physiotherapy gave a significantly greater yield of sputum than did physiotherapy alone, and terbutaline. (Sutton PP, Davidson J , Smith FW et.al.1988 )• In mechanically ventilated patients , those having low lung volume chest PNF technique should be used to improve lung volume & thus maximum aerosols can be administered.• Lung segment which is to be drained out require to positioned up so that aerosols reach to upper area.
TECHNIQUE FOR USING NEBULIZER• 1. Place drug solution in nebulizer, employing a fill volume 2-6 ml• 2. Place nebulizer in Inspiratory line• 3. Ensure airflow of 6-8 L/min through the nebulizer.• 4. Ensure adequate tidal volume ( 500 ml in adults). Attempt to use duty cycle > 0.3, if possible.
• 5. Observe nebulizer for adequate aerosol generation throughout use.• 6. Disconnect nebulizer when all medication is nebulized or when no more aerosol is being produced.
CONCLUSION• Nebulizer is the key component as a rule for gaining chest clearance on mech.vent Pts.• physiotherapist must give chest physiotherapy following neb to augment secretion drainage• Ensure proper position for nebulization.• Choice of a nebulizer on the basis of need of therapeutic effectiveness & availability of a device.• Only about <10% drug reaches to the desired site , so try to optimize drug deposition.• use cleaned nebulizer & prepare fresh solution.
• Adjust adequate oxygen flow 6-8 L/min to produce particles in respirable range.• Aerosol particle deposition is directly related to inhaled volume & inversely related to ventilatory rate , so maintain inspiration for 3-5 sec & breath holding for 2-4 sec or as long as possible.• Determine the therapeutic effectiveness following nebulization + chest physiotherapy.