Inhalers in ICU - Welcome to MSICmsic.org.my/sfnag402ndfbqzxn33084mn90a78aas0s9g/asmic2017...with optimal use without spacer in ambulatory patient Reference : Dhand et al. 2008. Journal

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 Example

Anti-infective agents Amikacin, Colistin

Bronchodilators Salbutamol, Fenoterol, Salmeterol, Formoterol

Corticosteroids Beclomethasone, Budesonide

Mucolytics Acetylcysteine

Ionic solutions Isotonic sodium chloride

Miscellaneous Tranexemic acid

Ari 2015 Respir Care 2015; 60(6): 858-879

Efficiency of Aerosol Therapy

Drug Deposition in

Lung

Patient

Drug Device

Ventilator circuit &

other parameters

Aerosol particle size & Lung Deposition

(From Gardenhire DS: Rau’s respiratory care pharmacology, ed 8, St. Louis, MO, 2012, Mosby http://www.medscape.org/viewarticle/757312_3

Factors affecting aerosol delivery Ventilator Related

Circuit Related

Patient Related

Drug Related Device Related-MDI

Device Related-Nebulizer

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 anti-

muscarinic

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,

Count the puffs Medicine 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]

200 / 36 5.5 days

6 puffs 2 hourly [ 72 puffs a day]

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

“ 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

How effective drug delivery improve patient outcome

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 Anti-infective Therapy 2017; 15: 3, 211-229

Nebulised antibiotic & Expiratory filter

• Monitor for Bronchospasm & obstruction of expiratory filters

• Regular change may be needed

G Poulakou et al. Expert Review of Anti-infective Therapy 2017; 15: 3, 211-229

Ehrmann et al. Ann. Intensive Care (2017) 7:78

Nebulised antibiotic

White crystals on Exhalation membrane

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,

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

Conclusion

• Aerosol therapy is frequently used in Critical ill patients

• Essential to optimize as many factors as possible for effective drug delivery

Drug

Deposition in Lung

Patient

Drug 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