Delivering Aerosol Medication in ICU 18th Aug 2017 Lau Chee Lan Pharmacist HCTM PPUKM ASMIC 2017
Aerosol Therapy Part of the treatment for a variety of respiratory disease * asthma and chronic obstructive pulmonary disease. Offer advantage over systemic therapy High concentration in airways Fewer systemic side effects Require optimal technique for optimal delivery delivery of aerosols to critically ill patients is more complex, especially in ventilated patients,
Medication administered as aerosol Drug class Anti-infective agents Bronchodilators Corticosteroids Mucolytics Ionic solutions Miscellaneous Example Amikacin, Colistin Salbutamol, Fenoterol, Salmeterol, Formoterol Beclomethasone, Budesonide Acetylcysteine Isotonic sodium chloride Tranexemic acid Ari 2015 Respir Care 2015; 60(6): 858-879
Efficiency of Aerosol Therapy Patient Drug Drug Deposition in Lung Device Ventilator circuit & other parameters
Aerosol particle size & Lung Deposition http://www.medscape.org/viewarticle/757312_3 (From Gardenhire DS: Rau s respiratory care pharmacology, ed 8, St. Louis, MO, 2012, Mosby
Factors affecting aerosol delivery Ventilator Related Device Related-MDI Drug Related Device Related-Nebulizer Patient Related Circuit Related Reference: Dhand & Guntur. 2008. Clin Chest Med 29 (2008) 277 296 Ari 2015 Respir Care 2015; 60(6): 858-879
Common Aerosol Devices/ Generator Type Advantages Disadvantages MDI - No need drug preparation - Short treatment time - No contamination -Coordination with inspiration --medium cost Jet nebulizer Cheap Easy to use -Inefficient [ droplet > 5um] -Cleaning required -Need additional tubing -Residual volume Ultrasonic nebulizer - More efficient than Jet Large residual volume High cost Vibrating mesh nebulizer Efficient [ droplet < 5um] -deliver 40-60% drug to lung Easy to use Not for viscous liquids Cleaning required High cost Dhanani et al. 2016. Critical Care; 20: 269-284 Ari 2015 Respir Care 2015; 60(6): 858-879
INHALERS Metered Dose Inhaler (MDI)/ evohaler MDI/ evohaler + Aerochamber/ Optichamber Accuhaler Turbuhaler Handihaler Respimat Breezhaler
MDI inhalers Bronchodilators (Reliever) Short acting beta-2 agonists Short acting antimuscarinic MDI Ventolin (Salbutamol sulfate 100mcg) MDI Berodual N ( Ipratropium Br 20 mcg, fenoterol HBr 50 mcg) Controler/Preventor Inhaled Corticosteroid MDI Pulmicort (Budesonide) MDI Becotide ( Beclomethasone)
DPI: Turbuhaler-controller/preventor Inhaler / Active ingredient per metered dose Symbicort 160/4.5 mcg/dose (Budesonide 160 mcg, formoterol 4.5 mcg.) Symbicort 320/9 mcg/dose (Budesonide 320 mcg, formoterol 9 mcg.) Inhaler / Active ingredient per metered dose Seretide 50/250 accuhaler (Salmeterol xinafoate 50 mcg, fluticasone propionate 250 mcg.) Seretide 50/500 accuhaler ( Salmeterol xinafoate 50 mcg, fluticasone propionate 500 mcg. )
Spiriva (Tiotropium) 18mcg Onbrez 150mcg (Indacaterol)
Optimal Technique for using pmdi in ventilated patient 1. Review order, identify patient, and assess need for bronchodilator. 2. Suction endotracheal tube and airway secretions. 3. Shake pmdi and warm to hand temperature. 4. Place pmdi in space chamber adapter in ventilator circuit. 5.? heat and moisture exchanger.* Do not disconnect humidifier. 6. Coordinate pmdi actuation with beginning of inspiration. 7. Wait at least 15 s between actuations; administer total dose. 8. Monitor for adverse response. 9. Reconnect. 10. Document clinical outcome. Dhand 2007. Curr Opin Crit Care 13:27 38. Ari et al. 2015. Respir Care; 60(6) 858-879)
Priming and Shaking the Canister Prior to first use If not used > 24 hours. Shake for 3 to 5 times Prime by depress the valve several actuation/ puffs Reference: Fink J, Dhand R. Bronchodilator resuscitation in the emergency department, part 2: dosing. Respir Care. 2000;45(5):497. Ari et al. 2015. Aerosol Therapy in Pulmonary Critical Care. Respir Care; 60(6) 858-879)
MDI inhalers-controllers/preventors Inhaled corticosteroids with long acting beta agonists (ICS + LABA) Seretide 25/50 evohaler (Salmeterol 25 mcg, fluticasone propionate 50 mcg) Seretide 25/125 evohaler ( Salmeterol 25 mcg, fluticasone propionate 125 mcg)
Why need to shake inhaler Without shaking, the drug may separate from the propellants in MDI, which reduces aerosol delivery. Ari et al. 2015. Aerosol Therapy in Pulmonary Critical Care. Respir Care; 60(6) 858-879)
How to tell if inhaler is empty? A.? Floating the metal canister in water B.? Listening as you shake it C.? See if a spray come out American Thoracic Society. 2014. Am J Respir Crit Care Med, Vol. 190, P5-P6,
Medicine Count the puffs Number of doses per canister Salbutamol [ Ventolin ] 200 Berodual 200 Seretide [ Salmeterol + Fluticasone] 120 Prescriptions If using Salbutamol T0 change canister after 4 puffs QID [ 16 puffs a day] 200 / 16 12 days 6 puffs 4 hourly [ 36 puffs a day] 6 puffs 2 hourly [ 72 puffs a day] 200 / 36 5.5 days 200 / 72 2.5 days
Arrow towards patients [ For unidirection connector] Match the canister
Spacers Uptodate 2017
Synchronize with inspiration onset synchronizing the actuation of pmdi with the beginning of inspiration. 1 to 1.5 sec delay can reduce the efficiency of drug delivery Failure to synchronize can reduce drug mass ( by 35% ) Reference: Diot P, Morra L, Smaldone GC. Albuterol delivery in a model of mechanical ventilation. Comparison of metered-dose inhaler and nebulizer efficiency. Am J Respir Crit Care Med. Oct 1995;152(4 Pt 1):1391-1394
Interval between actuation.at 15s successive actuations of a MDI without an intervening pause reduced drug delivery Puff ------15s-----puff again.. Repeat till all puffs prescribed done. Ie, 6 puffs will take around 1 min. Reference: 1. Diot, P., L. Morra, and G. C. Smaldone. 1995. Albuterol delivery in a model of mechanical ventilation: comparison of metered-dose inhaler and nebulizer efficiency. Am. J. Respir. Crit. Care Med. 152:1391 1394 2. Fink et al. 1999. Am J Respir Crit Care Med;159:63 68.
Chambers [non-intubated] Aerochamber Optichamber Not suitable for intubated patients
pmdi with chamber
How effective drug delivery improve patient outcome With standardized technique of administration, approximately 11% of dose from pmdi and spacer chamber deposits in the lower respiratory tract of ventilated patients. This value is remarkably close to values observed (10-14%) with optimal use without spacer in ambulatory patient Reference : Dhand et al. 2008. Journal of Aerosol medicine and pulmonary drug delivery. (21) pp 45-60
Nebulisers Jet / Ultrasonic / Vibrating Mesh Transform liquid & suspension into aerosol form Deliver wider range of drugs than pmdi Efficiency : ability to generate aerosol of desired particle size Optimal droplet size Concern Inadequate cleaning may lead to pneumonia Dhanani et al. Critical Care (2016) 20: 269
Comparing Common Aerosol Devices Type Advantages Disadvantages Jet nebulizer Cheap Easy to use -Inefficient [ droplet > 5um] -Cleaning required -Need additional tubing -Residual volume Ultrasonic nebulizer - More efficient than Jet Large residual volume High cost Vibrating mesh nebulizer Efficient [ droplet < 5um] -deliver 40-60% drug to lung Easy to use Not for viscous liquids Cleaning required High cost Dhanani et al. 2016. Critical Care; 20: 269-284 Ari 2015 Respir Care 2015; 60(6): 858-879
Optimal Technique for nebulizing drug in ventilated patients 1. Review order, identify patient, and assess need for bronchodilator. 2. Assess airway, remove excess secretions 3. Place drug in nebulizer [ volume for Jet vs Vibrating mesh] 4. Place nebulizer in inspiratory limb [ 10 to 15 cm from Y piece]* 5.? HME [ do not disconnect humidifier]* 6. Connect to power source [ for Jet, set gas flow accordingly] 7. Observe aerosol cloud 8. Remove device from the ventilator circuit 9.? HME* 10. Return ventilator settings and alarms to previous values 11. Monitor patients. 12. Change of expiratory filter* Dhand 2007. Curr Opin Crit Care 13:27 38. Ari et al. 2015. Respir Care; 60(6) 858-879)
Influence of the nebulizer position Ehrmann et al. Ann. Intensive Care (2017) 7:78
Nebulizing antibiotics: Optimal delivery is important! Efficient Nebulization Optimal drug deposition in lung
Nebulizing antibiotic Prepare solution aseptically Prepare freshly just before the nebulisation E.g CMS [ prodrug] convert into Colistin [active & toxic form] Direct Lung toxicity Appropriate volume Nebulised over 30-60 mins Frequency : Amikacin ---- Once daily CMS ----------- 2 to 3 times daily Lu Q, Am J Respir Crit Care Med. 2011; 184: 106-115. G Poulakou et al. Expert Review of Antiinfective Therapy 2017; 15: 3, 211-229
Nebulised antibiotic & Expiratory filter Monitor for Bronchospasm & obstruction of expiratory filters Regular change may be needed Ehrmann et al. Ann. Intensive Care (2017) 7:78 G Poulakou et al. Expert Review of Antiinfective Therapy 2017; 15: 3, 211-229
Nebulised antibiotic White crystals on Exhalation membrane White crystals on flow sensor after nebulized colistin -Median duration of Neb : 10 days -Median duration to formation of white crystals : 4 days - Change of flow sensor : 82% of case Ghonimat I.M., Nazer L.H., Aqel F., Mohammad M. K., Hawari F. I., Le J. Effect of Nebulized Colistin on the Ventilator Circuit: a Prospective Pilot Case-Control Study from a Single Cancer Center. Mediterr J Hematol Infect Dis 2015, 7(1): e2015032,
Conclusion Aerosol therapy is frequently used in Critical ill patients Essential to optimize as many factors as possible for effective drug delivery Patient Drug Drug Deposition in Lung Device Ventilator circuit & other parameters
Acknowledgement: En. Khairul Mubarak Osman Pn Parimala Devi a/p Munusamy
1192 physicians in ICU from REVA network 99% use aerosol therapy in mechanical ventilated patients 43% use nebulizers 55% use MDI inhaler Mostly Bronchodilators & steroids 30% nebulized antibiotics ( 5 patients a year)
Spacers/adapters Dhand. 2008. Journal Of Aerosol Medicine And Pulmonary Drug Delivery; 21 (1) : Pp. 45 60
Place the space device Reference: Dhand. 2012. Aerosol therapy in patient receiving noninvasive positive pressure ventilation. Journal of aerosol medicine and pulmonary delivery; 25(2): 63-78