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Critical Care
Published in: Critical Care 1/2016

Open Access 01-12-2016 | Review

Fundamentals of aerosol therapy in critical care

Authors: Jayesh Dhanani, John F. Fraser, Hak-Kim Chan, Jordi Rello, Jeremy Cohen, Jason A. Roberts

Published in: Critical Care | Issue 1/2016

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Abstract

Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics–pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.
Literature
1.
Brewis BCRA, Geddes DM, Gibson GJ. Respiratory medicine. 2nd ed. London: W.B. Saunders; 1995.
2.
Skyler JS, Cefalu WT, Kourides IA, Landschulz WH, Balagtas CC, Cheng SL, Gelfand RA. Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study. Lancet. 2001;357(9253):331–5.PubMedCrossRef
3.
Hollinger MA. Respiratory pharmacology and toxicology. Philadelphia: W.B. Saunders; 1994.
4.
5.
6.
Anderson PJ. History of aerosol therapy: liquid nebulization to MDIs to DPIs. Respir Care. 2005;50(9):1139–50.PubMed
7.
Nielsen N. Treatment of asthmatic attacks by inhalation of adrenaline. Lancet. 1936;228(5902):848–9
8.
Klastersky J, Geuning C, Mouawad E, Daneau D. Endotracheal gentamicin in bronchial infections in patients with tracheostomy. Chest. 1972;61(2):117–20.PubMedCrossRef
9.
Klastersky J, Hensgens C, Noterman J, Mouawad E, Meunier-Carpentier F. Endotracheal antibiotics for the prevention of tracheobronchial infections in tracheotomized unconscious patients. A comparative study of gentamicin and aminosidin-polymyxin B combination. Chest. 1975;68(3):302–6.PubMedCrossRef
10.
Feeley TW, Du Moulin GC, Hedley-Whyte J, Bushnell LS, Gilbert JP, Feingold DS. Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med. 1975;293(10):471–5.PubMedCrossRef
11.
Klick JM, du Moulin GC, Hedley-Whyte J, Teres D, Bushnell LS, Feingold DS. Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients. J Clin Invest. 1975;55(3):514–9.PubMedPubMedCentralCrossRef
12.
Gough PA, Jordan NS. A review of the therapeutic efficacy of aerosolized and endotracheally instilled antibiotics. Pharmacotherapy. 1982;2(6):367–77.PubMedCrossRef
13.
Sorensen VJ, Horst HM, Obeid FN, Bivins BA. Endotracheal aminoglycosides in gram negative pneumonia. A preliminary report. Am Surg. 1986;52(7):391–4.PubMed
14.
Stillwell PC, Kearns GL, Jacobs RF. Endotracheal tobramycin in gram-negative pneumonitis. Drug Intell Clin Pharm. 1988;22(7–8):577–81.PubMed
15.
Fink JB, Dhand R. Aerosol therapy in mechanically ventilated patients: recent advances and new techniques. Semin Respir Crit Care Med. 2000;21(3):183–201.PubMedCrossRef
16.
Hess DR, Dillman C, Kacmarek RM. In vitro evaluation of aerosol bronchodilator delivery during mechanical ventilation: pressure-control vs. volume control ventilation. Intensive Care Med. 2003;29(7):1145–50.PubMedCrossRef
17.
Miller DD, Amin MM, Palmer LB, Shah AR, Smaldone GC. Aerosol delivery and modern mechanical ventilation: in vitro/in vivo evaluation. Am J Respir Crit Care Med. 2003;168(10):1205–9.PubMedCrossRef
18.
Rouby JJ, Bouhemad B, Monsel A, Brisson H, Arbelot C, Lu Q, Nebulized Antibiotics Study Group. Aerosolized antibiotics for ventilator-associated pneumonia: lessons from experimental studies. Anesthesiology. 2012;117(6):1364–80.PubMedCrossRef
19.
Ari A, Atalay OT, Harwood R, Sheard MM, Aljamhan EA, Fink JB. Influence of nebulizer type, position, and bias flow on aerosol drug delivery in simulated pediatric and adult lung models during mechanical ventilation. Respir Care. 2010;55(7):845–51.PubMed
20.
Dolovich MB, Ahrens RC, Hess DR, Anderson P, Dhand R, Rau JL, Smaldone GC, Guyatt G, American College of Chest P, American College of Asthma A, et al. Device selection and outcomes of aerosol therapy: evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005;127(1):335–71.PubMedCrossRef
21.
Ramsey BW, Dorkin HL, Eisenberg JD, Gibson RL, Harwood IR, Kravitz RM, Schidlow DV, Wilmott RW, Astley SJ, McBurnie MA, et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med. 1993;328(24):1740–6.PubMedCrossRef
22.
Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, Williams-Warren J, Vasiljev KM, Borowitz D, Bowman CM, Marshall BC, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med. 1999;340(1):23–30.PubMedCrossRef
23.
Pai VB, Nahata MC. Efficacy and safety of aerosolized tobramycin in cystic fibrosis. Pediatr Pulmonol. 2001;32(4):314–27.PubMedCrossRef
24.
Udy AA, Baptista JP, Lim NL, Joynt GM, Jarrett P, Wockner L, Boots RJ, Lipman J. Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine concentrations. Crit Care Med. 2014;42(3):520–7.PubMedCrossRef
25.
Dhand R. Inhalation therapy in invasive and noninvasive mechanical ventilation. Curr Opin Crit Care. 2007;13(1):27–38.PubMedCrossRef
26.
Stephan E, Ferran R-C, Sferrazza PGF, Daniel I, Laurent B, Gabriela A-S. Aerosol therapy during mechanical ventilation: an international survey. Intensive Care Med. 2013;39(6):1048–56.CrossRef
27.
Ehrmann S, Roche-Campo F, Bodet-Contentin L, Razazi K, Dugernier J, Trenado-Alvarez J, Donzeau A, Vermeulen F, Thevoz D, Papanikolaou M, et al. Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients. Intensive Care Med. 2016;42(2):192–201.PubMedCrossRef
28.
Sole-Lleonart C, Rouby JJ, Chastre J, Poulakou G, Palmer LB, Blot S, Felton T, Bassetti M, Luyt CE, Pereira JM, et al. Intratracheal administration of antimicrobial agents in mechanically ventilated adults: an international survey on delivery practices and safety. Respir Care. 2016;61(8):1008–14. doi:10.​4187/​respcare.​04519. Epub 2016 Mar 8.
29.
Ian Colbeck ML. Introduction in aerosol science: technology and applications. In: Aerosol Science: Technology and Applications. Chichester, UK: John Wiley & Sons; 2014;1–14.
30.
Laube BL, Janssens HM, de Jongh FH, Devadason SG, Dhand R, Diot P, Everard ML, Horvath I, Navalesi P, Voshaar T, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J. 2011;37(6):1308–31.PubMedCrossRef
31.
Shekunov BY, Chattopadhyay P, Tong HH, Chow AH. Particle size analysis in pharmaceutics: principles, methods and applications. Pharm Res. 2007;24(2):203–27.PubMedCrossRef
32.
Koushik K, Kompella UB. Particle and device engineering for inhalation drug delivery. Drug Del Technol. 2004;4:40–50.
33.
Fernandez Tena A, Casan Clara P. Deposition of inhaled particles in the lungs. Arch Bronconeumol. 2012;48(7):240–6.PubMedCrossRef
34.
Lourenco RV, Cotromanes E. Clinical aerosols. I. Characterization of aerosols and their diagnostic uses. Arch Intern Med. 1982;142(12):2163–72.PubMedCrossRef
35.
Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003;56(6):588–99.PubMedPubMedCentralCrossRef
36.
37.
Cipolla D, Chan HK. Inhaled antibiotics to treat lung infection. Pharm Pat Anal. 2013;2(5):647–63.PubMedCrossRef
38.
Dhand R, Tobin MJ. Bronchodilator delivery with metered-dose inhalers in mechanically-ventilated patients. Eur Respir J. 1996;9(3):585–95.PubMedCrossRef
39.
Lethem MI. The role of tracheobronchial mucus in drug administration to the airways. Adv Drug Deliv Rev. 1993;11:271–98.CrossRef
40.
Hashmi N, Matthews GP, Martin AB, Lansley AB, Forbes B. Effect of mucus on transepithelial drug delivery. J Aerosol Med. 1999;12:139.
41.
Lippmann M, Yeates DB, Albert RE. Deposition, retention, and clearance of inhaled particles. Br J Ind Med. 1980;37(4):337–62.PubMedPubMedCentral
42.
43.
Gerrity TR, Garrard CS, Yeates DB. Theoretic analysis of sites of aerosol deposition in the human lung. Chest. 1981;80(6 Suppl):898–901.PubMedCrossRef
44.
Baskin MI, Abd AG, Ilowite JS. Regional deposition of aerosolized pentamidine. Effects of body position and breathing pattern. Ann Intern Med. 1990;113(9):677–83.PubMedCrossRef
45.
Tiddens HA, Bos AC, Mouton JW, Devadason S, Janssens HM. Inhaled antibiotics: dry or wet? Eur Respir J. 2014;44(5):1308–18.PubMedCrossRef
46.
Ferrari F, Goldstein I, Nieszkowszka A, Elman M, Marquette CH, Rouby JJ, Experimental ICUSG. Lack of lung tissue and systemic accumulation after consecutive daily aerosols of amikacin in ventilated piglets with healthy lungs. Anesthesiology. 2003;98(4):1016–9.PubMedCrossRef
47.
Elman M, Goldstein I, Marquette CH, Wallet F, Lenaour G, Rouby JJ, Experimental ICUSG. Influence of lung aeration on pulmonary concentrations of nebulized and intravenous amikacin in ventilated piglets with severe bronchopneumonia. Anesthesiology. 2002;97(1):199–206.PubMedCrossRef
48.
Goldstein I, Wallet F, Nicolas-Robin A, Ferrari F, Marquette CH, Rouby JJ. Lung deposition and efficiency of nebulized amikacin during Escherichia coli pneumonia in ventilated piglets. Am J Respir Crit Care Med. 2002;166(10):1375–81.PubMedCrossRef
49.
Goldstein I, Bughalo MT, Marquette CH, Lenaour G, Lu Q, Rouby JJ, Experimental ICUSG. Mechanical ventilation-induced air-space enlargement during experimental pneumonia in piglets. Am J Respir Crit Care Med. 2001;163(4):958–64.PubMedCrossRef
50.
Ferrari F, Lu Q, Girardi C, Petitjean O, Marquette CH, Wallet F, Rouby JJ, Experimental ICUSG. Nebulized ceftazidime in experimental pneumonia caused by partially resistant Pseudomonas aeruginosa. Intensive Care Med. 2009;35(10):1792–800.PubMedCrossRef
51.
Nikander K, Prince I, Coughlin S, Warren S, Taylor G. Mode of breathing-tidal or slow and deep-through the I-neb Adaptive Aerosol Delivery (AAD) system affects lung deposition of (99 m)Tc-DTPA. J Aerosol Med Pulm Drug Deliv. 2010;23 Suppl 1:S37–43.PubMed
52.
Chrystyn H. Is inhalation rate important for a dry powder inhaler? Using the In-Check Dial to identify these rates. Respir Med. 2003;97(2):181–7.PubMedCrossRef
53.
Wright TW, Notter RH, Wang Z, Harmsen AG, Gigliotti F. Pulmonary inflammation disrupts surfactant function during Pneumocystis carinii pneumonia. Infect Immun. 2001;69(2):758–64.PubMedPubMedCentralCrossRef
54.
Brogden KA. Changes in pulmonary surfactant during bacterial pneumonia. Antonie Van Leeuwenhoek. 1991;59(4):215–23.PubMedCrossRef
55.
Olsson B, Bondesson E, Borgström L, Edsbäcker S, Eirefelt S, Ekelund K, Gustavsson L, Hegelund-Myrbäck T. Pulmonary drug metabolism, clearance, and absorption. In: Advances in Delivery Science and Technology. Hickey AJ, Smyth HDC, editors. New York: Springer. 2011 p. 21–50.
56.
Zhang LN, Sun JP, Xue XY, Wang JX. Exogenous pulmonary surfactant for acute respiratory distress syndrome in adults: a systematic review and meta-analysis. Exp Ther Med. 2013;5(1):237–42.PubMed
57.
Kesecioglu J, Beale R, Stewart TE, Findlay GP, Rouby JJ, Holzapfel L, Bruins P, Steenken EJ, Jeppesen OK, Lachmann B. Exogenous natural surfactant for treatment of acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2009;180(10):989–94.CrossRefPubMed
58.
Anzueto A, Jubran A, Ohar JA, Piquette CA, Rennard SI, Colice G, Pattishall EN, Barrett J, Engle M, Perret KA, et al. Effects of aerosolized surfactant in patients with stable chronic bronchitis: a prospective randomized controlled trial. JAMA. 1997;278(17):1426–31.PubMedCrossRef
59.
60.
Rubin BK. Air and soul: the science and application of aerosol therapy. Respir Care. 2010;55(7):911–21.PubMed
61.
Heyder J. Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc Am Thorac Soc. 2004;1(4):315–20.PubMedCrossRef
62.
Patton JS, Fishburn CS, Weers JG. The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc. 2004;1(4):338–44.PubMedCrossRef
63.
Smith C, Goldman RD. Nebulizers versus pressurized metered-dose inhalers in preschool children with wheezing. Can Fam Physician. 2012;58(5):528–30.PubMedCentralPubMed
64.
Khoo SM, Tan LK, Said N, Lim TK. Metered-dose inhaler with spacer instead of nebulizer during the outbreak of severe acute respiratory syndrome in Singapore. Respir Care. 2009;54(7):855–60.PubMedCrossRef
65.
66.
Thomas M, Williams AE. Are outcomes the same with all dry powder inhalers? Int J Clin Pract Suppl. 2005;149:33–5.PubMedCrossRef
67.
Selroos O, Borgstrom L, Ingelf J. Use of dry powder inhalers in acute exacerbations of asthma and COPD. Ther Adv Respir Dis. 2009;3(2):81–91.PubMedCrossRef
68.
Hess D, Fisher D, Williams P, Pooler S, Kacmarek RM. Medication nebulizer performance. Effects of diluent volume, nebulizer flow, and nebulizer brand. Chest. 1996;110(2):498–505.PubMedCrossRef
69.
Haynes JM. Randomized controlled trial of a breath-activated nebulizer in patients with exacerbation of COPD. Respir Care. 2012;57(9):1385–90.PubMedCrossRef
70.
Ari A, Fink JB. Guidelines for aerosol devices in infants, children and adults: which to choose, why and how to achieve effective aerosol therapy. Expert Rev Respir Med. 2011;5(4):561–72.PubMedCrossRef
71.
Laube BL, Benedict GW, Dobs AS. Time to peak insulin level, relative bioavailability, and effect of site of deposition of nebulized insulin in patients with noninsulin-dependent diabetes mellitus. J Aerosol Med. 1998;11(3):153–73.PubMedCrossRef
72.
73.
Corkery K. Inhalable drugs for systemic therapy. Respir Care. 2000;45(7):831–5.PubMed
74.
Anderson M, Svartengren M, Bylin G, Philipson K, Camner P. Deposition in asthmatics of particles inhaled in air or in helium-oxygen. Am Rev Respir Dis. 1993;147(3):524–8.PubMedCrossRef
75.
Goode ML, Fink JB, Dhand R, Tobin MJ. Improvement in aerosol delivery with helium-oxygen mixtures during mechanical ventilation. Am J Respir Crit Care Med. 2001;163(1):109–14.PubMedCrossRef
76.
Hess DR, Acosta FL, Ritz RH, Kacmarek RM, Camargo Jr CA. The effect of heliox on nebulizer function using a beta-agonist bronchodilator. Chest. 1999;115(1):184–9.PubMedCrossRef
77.
Tonnellier M, Ferrari F, Goldstein I, Sartorius A, Marquette CH, Rouby JJ. Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: comparative effects of helium and nitrogen. Anesthesiology. 2005;102(5):995–1000.PubMedCrossRef
78.
Mendelman PM, Smith AL, Levy J, Weber A, Ramsey B, Davis RL. Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum. Am Rev Respir Dis. 1985;132(4):761–5.PubMed
79.
VanDyke RD, McPhail GL, Huang B, Fenchel MC, Amin RS, Carle AC, Chini BA, Seid M. Inhaled tobramycin effectively reduces FEV1 decline in cystic fibrosis. An instrumental variables analysis. Ann Am Thorac Soc. 2013;10(3):205–12.PubMedCrossRef
80.
Vazquez-Espinosa E, Giron RM, Gomez-Punter RM, Garcia-Castillo E, Valenzuela C, Cisneros C, Zamora E, Garcia-Perez FJ, Ancochea J. Long-term safety and efficacy of tobramycin in the management of cystic fibrosis. Ther Clin Risk Manag. 2015;11:407–15.PubMedPubMedCentralCrossRef
81.
O'Riordan TG, Palmer LB, Smaldone GC. Aerosol deposition in mechanically ventilated patients. Optimizing nebulizer delivery. Am J Respir Crit Care Med. 1994;149(1):214–9.PubMedCrossRef
82.
Dhand R. Aerosol delivery during mechanical ventilation: from basic techniques to new devices. J Aerosol Med Pulm Drug Deliv. 2008;21(1):45–60.PubMedCrossRef
83.
Craven DE, Lichtenberg DA, Goularte TA, Make BJ, McCabe WR. Contaminated medication nebulizers in mechanical ventilator circuits. Source of bacterial aerosols. Am J Med. 1984;77(5):834–8.PubMedCrossRef
84.
Ely EW, Baker AM, Evans GW, Haponik EF. The distribution of costs of care in mechanically ventilated patients with chronic obstructive pulmonary disease. Crit Care Med. 2000;28(2):408–13.PubMedCrossRef
85.
Guerin C, Fassier T, Bayle F, Lemasson S, Richard JC. Inhaled bronchodilator administration during mechanical ventilation: how to optimize it, and for which clinical benefit? J Aerosol Med Pulm Drug Deliv. 2008;21(1):85–96.PubMedCrossRef
86.
Kondili E, Alexopoulou C, Prinianakis G, Xirouchaki N, Vaporidi K, Georgopoulos D. Effect of albuterol on expiratory resistance in mechanically ventilated patients. Respir Care. 2011;56(5):626–32.PubMedCrossRef
87.
Duarte AG. Inhaled bronchodilator administration during mechanical ventilation. Respir Care. 2004;49(6):623–34.PubMed
88.
Dhand R. Inhalation therapy with metered-dose inhalers and dry powder inhalers in mechanically ventilated patients. Respir Care. 2005;50(10):1331–4. discussion 1344–5.PubMed
89.
Boukhettala N, Poree T, Diot P, Vecellio L. In vitro performance of spacers for aerosol delivery during adult mechanical ventilation. J Aerosol Med Pulm Drug Deliv. 2015;28(2):130–6.PubMedCrossRef
90.
Harvey CJ, O'Doherty MJ, Page CJ, Thomas SH, Nunan TO, Treacher DF. Effect of a spacer on pulmonary aerosol deposition from a jet nebuliser during mechanical ventilation. Thorax. 1995;50(1):50–3.PubMedPubMedCentralCrossRef
91.
Holland A, Smith F, Penny K, McCrossan G, Veitch L, Nicholson C. Metered dose inhalers versus nebulizers for aerosol bronchodilator delivery for adult patients receiving mechanical ventilation in critical care units. Cochrane Database Syst Rev. 2013;6, CD008863.PubMed
92.
Ari A, Areabi H, Fink JB. Evaluation of aerosol generator devices at 3 locations in humidified and non-humidified circuits during adult mechanical ventilation. Respir Care. 2010;55(7):837–44.PubMed
93.
Dugernier J, Wittebole X, Roeseler J, Michotte JB, Sottiaux T, Dugernier T, Laterre PF, Reychler G. Influence of inspiratory flow pattern and nebulizer position on aerosol delivery with a vibrating-mesh nebulizer during invasive mechanical ventilation: an in vitro analysis. J Aerosol Med Pulm Drug Deliv. 2015;28(3):229–36.PubMedCrossRef
94.
Michotte JB, Jossen E, Roeseler J, Liistro G, Reychler G. In vitro comparison of five nebulizers during noninvasive ventilation: analysis of inhaled and lost doses. J Aerosol Med Pulm Drug Deliv. 2014;27(6):430–40.PubMedCrossRef
95.
Ari A, Harwood RJ, Sheard MM, Fink JB. An in vitro evaluation of aerosol delivery through tracheostomy and endotracheal tubes using different interfaces. Respir Care. 2012;57(7):1066–70.PubMedCrossRef
96.
Piccuito CM, Hess DR. Albuterol delivery via tracheostomy tube. Respir Care. 2005;50(8):1071–6.PubMed
97.
Pitance L, Vecellio L, Delval G, Reychler G, Reychler H, Liistro G. Aerosol delivery through tracheostomy tubes: an in vitro study. J Aerosol Med Pulm Drug Deliv. 2013;26(2):76–83.PubMedCrossRef
98.
Mazela J, Polin RA. Aerosol delivery to ventilated newborn infants: historical challenges and new directions. Eur J Pediatr. 2011;170(4):433–44.PubMedCrossRef
99.
Svartengren M, Philipson K, Linnman L, Camner P. Airway resistance and deposition of particles in the lung. Exp Lung Res. 1984;7(3-4):257–69.PubMedCrossRef
100.
American Association for Respiratory C, Restrepo RD, Walsh BK. Humidification during invasive and noninvasive mechanical ventilation: 2012. Respir Care. 2012;57(5):782–8.CrossRef
101.
Ferron GA, Upadhyay S, Zimmermann R, Karg E. Model of the deposition of aerosol particles in the respiratory tract of the rat. II. Hygroscopic particle deposition. J Aerosol Med Pulm Drug Deliv. 2013;26(2):101–19.PubMedCrossRef
102.
Golshahi L, Tian G, Azimi M, Son YJ, Walenga R, Longest PW, Hindle M. The use of condensational growth methods for efficient drug delivery to the lungs during noninvasive ventilation high flow therapy. Pharm Res. 2013;30(11):2917–30.PubMedPubMedCentralCrossRef
103.
Tian G, Longest PW, Li X, Hindle M. Targeting aerosol deposition to and within the lung airways using excipient enhanced growth. J Aerosol Med Pulm Drug Deliv. 2013;26(5):248–65.PubMedPubMedCentralCrossRef
104.
Dolovich MA. Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung. Respir Care. 2000;45(6):597–608.PubMed
105.
Fink JB, Dhand R, Duarte AG, Jenne JW, Tobin MJ. Aerosol delivery from a metered-dose inhaler during mechanical ventilation. An in vitro model. Am J Respir Crit Care Med. 1996;154(2 Pt 1):382–7.PubMedCrossRef
106.
Hess DR. The mask for noninvasive ventilation: principles of design and effects on aerosol delivery. J Aerosol Med. 2007;20 Suppl 1:S85–98. discussion S98–9.PubMedCrossRef
107.
Brandao DC, Lima VM, Filho VG, Silva TS, Campos TF, Dean E, de Andrade AD. Reversal of bronchial obstruction with bi-level positive airway pressure and nebulization in patients with acute asthma. J Asthma. 2009;46(4):356–61.PubMedCrossRef
108.
Dhand R. The role of aerosolized antimicrobials in the treatment of ventilator-associated pneumonia. Respir Care. 2007;52(7):866–84.PubMed
109.
Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT, National Heart L, Blood Institute ACTN. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;351(4):327–36.PubMedCrossRef
110.
Bayat S, Porra L, Albu G, Suhonen H, Strengell S, Suortti P, Sovijarvi A, Petak F, Habre W. Effect of positive end-expiratory pressure on regional ventilation distribution during mechanical ventilation after surfactant depletion. Anesthesiology. 2013;119(1):89–100.PubMedCrossRef
111.
Barrowcliffe MP, Zanelli GD, Jones JG. Pulmonary clearance of radiotracers after positive end-expiratory pressure or acute lung injury. J Appl Physiol. 1989;66(1):288–94.PubMed
112.
Lu Q, Girardi C, Zhang M, Bouhemad B, Louchahi K, Petitjean O, Wallet F, Becquemin MH, Le Naour G, Marquette CH, et al. Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa. Intensive Care Med. 2010;36(7):1147–55.PubMedCrossRef
113.
Guillon A, Mercier E, Lanotte P, Haguenoer E, Darrouzain F, Barc C, Sarradin P, Si-Tahar M, Heuze-Vourc'h N, Diot P, et al. Aerosol route to administer teicoplanin in mechanical ventilation: in vitro study, lung deposition and pharmacokinetic analyses in pigs. J Aerosol Med Pulm Drug Deliv. 2015;28(4):290–8.PubMedCrossRef
114.
Ferrari F, Liu ZH, Lu Q, Becquemin MH, Louchahi K, Aymard G, Marquette CH, Rouby JJ. Comparison of lung tissue concentrations of nebulized ceftazidime in ventilated piglets: ultrasonic versus vibrating plate nebulizers. Intensive Care Med. 2008;34(9):1718–23.PubMedCrossRef
115.
Dubus JC, Vecellio L, De Monte M, Fink JB, Grimbert D, Montharu J, Valat C, Behan N, Diot P. Aerosol deposition in neonatal ventilation. Pediatr Res. 2005;58(1):10–4.PubMedCrossRef
116.
Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185–96.PubMedCrossRef
117.
Reminiac F, Vecellio L, Heuze-Vourc’h N, Petitcollin A, Respaud R, Cabrera M, Le Pennec D, Diot P, Ehrmann S. Aerosol therapy in adults receiving high flow nasal cannula oxygen therapy. J Aerosol Med Pulm Drug Deliv. 2016;29(2):134–41. doi:10.​1089/​jamp.​2015.​1219. Epub 2015 Jul 21.
118.
Sole-Lleonart C, Roberts JA, Chastre J, Poulakou G, Palmer LB, Blot S, Felton T, Bassetti M, Luyt CE, Pereira JM, et al. Global survey on nebulization of antimicrobial agents in mechanically ventilated patients: a call for international guidelines. Clin Microbiol Infect. 2016;22(4):359–64.PubMedCrossRef
119.
Ehrmann S, Roche-Campo F, Sferrazza Papa GF, Isabey D, Brochard L, Apiou-Sbirlea G. REVA research network. Aerosol therapy during mechanical ventilation: an international survey. Intensive Care Med. 2013;39(6):1048–56.PubMedCrossRef
120.
Panidis D, Markantonis SL, Boutzouka E, Karatzas S, Baltopoulos G. Penetration of gentamicin into the alveolar lining fluid of critically ill patients with ventilator-associated pneumonia. Chest. 2005;128(2):545–52.PubMedCrossRef
121.
Lu Q, Luo R, Bodin L, Yang J, Zahr N, Aubry A, Golmard JL, Rouby JJ, Nebulized Antibiotics Study G. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology. 2012;117(6):1335–47.PubMedCrossRef
122.
Abdellatif S, Trifi A, Daly F, Mahjoub K, Nasri R, Ben LS. Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: a prospective, randomised trial. Ann Intensive Care. 2016;6(1):26.PubMedPubMedCentralCrossRef
123.
Katzman M, Meade W, Iglar K, Rachlis A, Berger P, Chan CK. High incidence of bronchospasm with regular administration of aerosolized pentamidine. Chest. 1992;101(1):79–81.PubMedCrossRef
124.
van Heerden PV, Caterina P, Filion P, Spagnolo DV, Gibbs NM. Pulmonary toxicity of inhaled aerosolized prostacyclin therapy—an observational study. Anaesth Intensive Care. 2000;28(2):161–6.PubMed
125.
Lu Q, Yang J, Liu Z, Gutierrez C, Aymard G, Rouby JJ, Nebulized Antibiotics Study Group. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011;184(1):106–15.PubMedCrossRef
126.
Palmer LB, Smaldone GC. Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med. 2014;189(10):1225–33.PubMedCrossRef
127.
Jost M, Beaudouin L, Eickmann U, Falcy M. Occupational risk prevention in aerosol therapy. In: ISSA Prevention Series No 2035 (E). Services IISotPoORiH, editors. Hamburg, Germany.
128.
Zitter JN, Maldjian P, Brimacombe M, Fennelly KP. Inhaled Dornase alfa (Pulmozyme) as a noninvasive treatment of atelectasis in mechanically ventilated patients. J Crit Care. 2013;28(2):218 e211–7.CrossRef
129.
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network, Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, Hite D, Holets S, Kallet RH, et al. Randomized, placebo-controlled clinical trial of an aerosolized beta(2)-agonist for treatment of acute lung injury. Am J Respir Crit Care Med. 2011;184(5):561–8.CrossRef
130.
Berlinski A, Willis JR. Albuterol delivery by 4 different nebulizers placed in 4 different positions in a pediatric ventilator in vitro model. Respir Care. 2013;58(7):1124–33.PubMed
131.
Watts AB, McConville JT, Williams 3rd RO. Current therapies and technological advances in aqueous aerosol drug delivery. Drug Dev Ind Pharm. 2008;34(9):913–22.PubMedCrossRef
132.
Ong HX, Traini D, Ballerin G, Morgan L, Buddle L, Scalia S, Young PM. Combined inhaled salbutamol and mannitol therapy for mucus hyper-secretion in pulmonary diseases. AAPS J. 2014;16(2):269–80.PubMedPubMedCentralCrossRef
133.
Moss RB. Administration of aerosolized antibiotics in cystic fibrosis patients. Chest. 2001;120(3 Suppl):107S–13.PubMedCrossRef
134.
135.
Weller S, Jones LS, Lou Y, Piscitelli S, Peppercorn A, Ng-Cashin J. Safety, tolerability and pharmacokinetics of orally inhaled zanamivir: a randomized study comparing Rotacap/Rotahaler and Rotadisk/Diskhaler in healthy adults. Antivir Ther. 2013;18(6):827–30.PubMedCrossRef
136.
Fauvel M, Farrugia C, Tsapis N, Gueutin C, Cabaret O, Bories C, Bretagne S, Barratt G. Aerosolized liposomal amphotericin B: prediction of lung deposition, in vitro uptake and cytotoxicity. Int J Pharm. 2012;436(1-2):106–10.PubMedCrossRef
137.
Escobar L, Gai MN, Regueira T, Andresen M. Pharmacokinetic considerations in critically ill patients. Rev Med Chil. 2012;140(6):780–8.PubMedCrossRef
138.
Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology, European Respiratory Society, International Society of Heart and Lung Transplantation, Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009;34(6):1219–63.CrossRef
139.
Mehra MR, Park MH, Landzberg MJ, Lala A, Waxman AB, International Right Heart Failure Foundation Scientific Working Group. Right heart failure: toward a common language. J Heart Lung Transplant. 2014;33(2):123–6.CrossRefPubMed
140.
Waxman AB, Zamanian RT. Pulmonary arterial hypertension: new insights into the optimal role of current and emerging prostacyclin therapies. Am J Cardiol. 2013;111(5 Suppl):1A–6. quiz 17A–9A.PubMedCrossRef
141.
Pacheo J, Arnold H, Skrupky L, Watts P, Micek ST, Kollef MH. Predictors of outcome in 216 patients with ARDS treated with inhaled epoprostenol. Respir Care. 2014;59(8):1178–85
142.
Upward JW, Strong HA, George CF, Ogilive BC, Challenor V, Conway N. Hypotension in response to iloprost, a prostacyclin analogue. Br J Clin Pharmacol. 1986;21(2):241–3.PubMedPubMedCentralCrossRef
143.
144.
Robinson BR, Athota KP, Branson RD. Inhalational therapies for the ICU. Curr Opin Crit Care. 2009;15(1):1–9.PubMedCrossRef
145.
Dorsch W, Auch E, Powerlowicz P. Adverse effects of acetylcysteine on human and guinea pig bronchial asthma in vivo and on human fibroblasts and leukocytes in vitro. Int Arch Allergy Appl Immunol. 1987;82(1):33–9.PubMedCrossRef
146.
147.
de Prost N, Ricard JD, Saumon G, Dreyfuss D. Ventilator-induced lung injury: historical perspectives and clinical implications. Ann Intensive Care. 2011;1(1):28.PubMedPubMedCentralCrossRef
148.
de Prost N, Costa EL, Wellman T, Musch G, Winkler T, Tucci MR, Harris RS, Venegas JG, Vidal Melo MF. Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation. J Appl Physiol. 2011;111(5):1249–58.PubMedPubMedCentralCrossRef
149.
Gadek JE. Consensus on surfactant and inhaled nitric oxide for ARDS. J Aerosol Med. 1996;9(1):155–62.PubMedCrossRef
150.
Willson DF, Thomas NJ, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, Jacobs BR, Jefferson LS, Conaway MR, Egan EA, et al. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA. 2005;293(4):470–6.PubMedCrossRef
151.
Kermeen FD, McNeil KD, Fraser JF, McCarthy J, Ziegenfuss MD, Mullany D, Dunning J, Hopkins PM. Resolution of severe ischemia-reperfusion injury post-lung transplantation after administration of endobronchial surfactant. J Heart Lung Transplant. 2007;26(8):850–6.PubMedCrossRef
Metadata
Title
Fundamentals of aerosol therapy in critical care
Authors
Jayesh Dhanani
John F. Fraser
Hak-Kim Chan
Jordi Rello
Jeremy Cohen
Jason A. Roberts
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1448-5

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