JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY

Volume 30, Number 0, 2017

Mary Ann Liebert, Inc.
Pp. 116
DOI: 10.1089/jamp.2016.1348

Workshop Report:
Aerosol Delivery to Spontaneously Breathing
Tracheostomized Patients

Ariel Berlinski, MD (co-chair),1 Arzu Ari, PhD,2 Phil Davies, MD,3 Jim Fink, PhD,4 Carina Majaesic, MD,5
Gregory Reychler, PhD,6 Taran Tatla, MD,7 and Israel Amirav, MD (co-chair)5

Abstract

The number of pediatric and adult patients requiring tracheostomy has increased. Many of them require aerosol
therapy as part of their treatment. Practitioners have little guidance on how to optimize drug delivery in this
population. The following is a report of a workshop dedicated to review the current status of aerosol delivery to
spontaneously breathing tracheostomized patients and to provide practice recommendations.

Keywords: aerosol, metered dose inhaler, nebulizer, tracheostomy, valved holding chamber

Introduction consisted of Pediatric Pulmonologists (I.A., A.B., P.D., and

C.M.), Respiratory Therapists (A.A. and J.F.), Physiothera-

T racheostomies have become increasingly common

in recent years in both pediatric and adult populations.(13)
Tracheostomies are indicated when long-term cardiorespira-
tory support is anticipated or when a fixed airway obstruction
is present and is unlikely to resolve quickly.(4) Although many
of these patients receive aerosol medications during the course
of their care, there is relatively little literature on this topic and
guidelines or consensus statements are lacking.(5,6) Moreover,
there are little in vivo data and despite increasing amount of
in vitro background data about efficacy of various modes of
administration, this has also not been incorporated into sci-
entific guidelines.(730)
A workshop was convened to review the best available
evidence and to establish recommendations for what are
currently rather uninformed and often less than optimal ap-
proaches to therapy. The workshop panel consisted of dif-
ferent health professionals, from North America and Europe,
with clinical and/or research expertise in aerosol delivery to
spontaneously breathing tracheostomized patients. The group
pist (G.R.), and Adult Ear Nose and Throat Specialist (T.T.).
The workshop took place before the 20th International So-
ciety for Aerosols in Medicine (ISAM) Conference (Munich,
May 28th29th, 2015). The face-to-face meeting was sup-
ported, in part, by the International Society for Aerosol in
Medicine.
The panel members performed a systematic literature
search, reviewed statements on the basis of best available
evidence, and finally convened for the workshop. The first
day of the workshop was devoted to individual presentations
from each participant summarizing existing data on various
aspects of the topic. These included the following: (1) Clin-
ical indications and challenges for tracheostomy; (2) clinical
indications and objectives for aerosol therapy in tracheosto-
mized patients; (3) principles of aerosol therapy; (4) special
issues and challenges (barriers) of aerosol therapy through
artificial airways; (5) aerosol delivery through tracheostomies
in adults, children, and infants; and (6) aerosol in vitro/in vivo
correlations, implications for clinical practice. The second

1
Department of Pediatrics, University of Arkansas for Medical Sciences, and Pediatric Aerosol Research Laboratory at Arkansas
Childrens Research Institute, Little Rock, Arkansas.
2
Department of Respiratory Therapy, Georgia State University, Atlanta, Georgia.
3
Department of Respiratory Paediatrics, Royal Hospital for Children, Glasgow, United Kingdom.
4
Aerogen Pharma Corp., San Mateo, California.
5
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
6
Institut de Recherche Experimentale et Clinique (IREC), Pole de Pneumologie, ORL & Dermatologie, Universite Catholique de
Louvain, Brussels, Belgium.
7
Department of ENT-Head & Neck Surgery, London North West Healthcare NHS Trust, London, United Kingdom.
This workshop report has been reviewed and endorsed by the International Society for Aerosols in Medicine (ISAM) Board.

1
2 BERLINSKI ET AL.
day of the workshop was devoted to ongoing discussions to
distill key issues for the present report. Based on the material
discussed in the meeting, the participants engaged in writing
the present report.
Recommendations are based on the best current evidence
to aid physicians and healthcare providers administering
aerosolized medications to patients with tracheostomies.
The current document outlines consensus recommendations
for aerosol delivery to patients with tracheostomies, along
with the scientific and practical justifications for these rec-
ommendations, resulting from a series of discussions among
various experts in the field. All participants agreed on the
best practice recommendations.
Clinical Indications and Challenges for Tracheostomy
It is estimated that *12,000 adult tracheostomies are
performed in England and Wales annually.(31) Further reports
suggest that more than 100,000 tracheostomies may be per-
formed annually in the United States, with 5% of them per-
formed in pediatric patients.(2,32)
Although not common in the pediatric population, many
adults undergo laryngectomies. A clear understanding of the
anatomical and functional differences between these two
types of neck breathing patients (tracheostomy vs. laryn-
gectomy) is required to provide safe and efficacious inhaled
therapies (Fig. 1).
An opening into the trachea, through the soft tissues of the
anterior neck, is termed tracheostomy (a.k.a. tracheotomy).
This may be performed surgically through an open technique
or through less invasive, percutaneous means. There are es-
sentially five main indications: (1) Bypass upper airway ob-
struction, (2) protect the lower respiratory tract from upper
airway secretions/bleeding, (3) permit lower respiratory tract
secretion clearance/suctioning, (4) permit long-term me-
chanical ventilation or ventilatory weaning, and (5) elective
insertion in head and neck surgery where one or more of what
has been cited earlier may be anticipated.
As part of a total laryngectomy procedure, the tracheal lu-
men is diverted out to the skin and a permanent stoma is cre-
ated. This stoma has no connection to the upper aerodigestive
FIG. 1. Diagram comparing airflow paths of tracheostomy and laryngectomy (A) tracheostomized patient; (B) tra-
cheostomized patient with cuff inflated; and (C) laryngectomized patient. Dashes lines with arrowheads represent airflow.
tract once the larynx is removed and is the sole passage-way for
pulmonary ventilation and inhaled or nebulized pulmonary
drug delivery (Fig. 1).
The tracheostomy and laryngectomy stoma acts as a con-
duit for ventilation of the lungs. The upper aerodigestive tract
plays additional roles that are compromised through trache-
ostomy formation. These include warming, humidification,
and filtering of particulate matter from inspired air. In colder
and temperate climates, (also air-conditioned and other dry air
environments), the air entering a tracheostomy stoma directly
into the lower respiratory tract will be cooler and less humid,
causing desiccation to the tracheal respiratory mucosa. This
local trauma, resulting from alteration in air flow, tempera-
ture, and humidity characteristics, alters the viscosity and
quantity of mucus secretions from mucin-secreting, goblet
epithelial cells. The respiratory tract mucociliary clearance
is adversely affected with depressed ciliary function, and a
tendency to increased amounts of thicker and more tenacious
airway secretions that need to be cleared readily.(33) If not, as
the secretions dry, they form plugs that obstruct the trachea
and lower airways of the lungs, as well as tracheostomy tube
obstruction and propensity to respiratory tract infections.
The tenacity and volume of secretions is further com-
pounded by the presence of a foreign body tracheostomy tube.
The inertness of tube material, the presence or absence of
a tube cuff, the tube cuff pressure, the presence or absence of
tube fenestrations, the intraluminal position/alignment of the
tube tip, and the snugness of tube fit (determined by tube size;
diameter, length and curvature) all impact and compound this
issue. Patient-related factors may further add to the issue of
problematic secretions; for example, chronic obstructive
pulmonary disease (COPD) patients would be predisposed to
different secretion volume and tenacity of secretions com-
pared with other patients. The risk of developing tracheo-
bronchitis is further compounded by the bodys immune
response in the presence of an airway foreign body.
The role of biofilms in this regard, that is, tendency to
significant or repeated airway and chest infections, is still
being realized.(34) Tracheostomy tubes and prosthetic
speaking valves readily establish biofilm colonization, which
increases the foreign body reaction and immune response of
AEROSOL DELIVERY THROUGH TRACHEOSTOMIES 3

the host. The elevation of the larynx may also be adversely
affected through the anchoring effect of the tracheostomy
tube on the trachea, increasing the risk of aspiration. The
development of biofilm as well as accumulation of secretions
in artificial airways has been associated with decreased in-
ternal diameters (IDs) and contribution to an increase in air-
way resistance and obstruction.
Within a pediatric setting, the role of tracheostomies has
changed markedly in recent years. Historically, they were
primarily used to treat acute airway obstruction for infec-
tious causes such as diphtheria, Hemophilus B epiglottis, or
croup, but with improved immunization and intensive care
techniques these cases have diminished and new indications
have become more common. The expansion of neonatal
services and the survival of preterm infants have meant that
complications of endotracheal intubation such as subglottic
stenosis have become more common. Many children are
now surviving with neurological conditions that can lead to
upper airway obstruction or the need for prolonged me-
chanical ventilator support. Other children with craniofacial
syndromes or congenital abnormalities are also being ac-
tively managed with a tracheostomy.(35,36)
This shift in patient groups with tracheostomies now means
that the majority of tracheostomies in children are in infants in
their first year of life. Given the complexity of many of these
children, it is unsurprising that many will have significant co-
morbidity beyond their airways, with Perez-Ruiz et al. re-
porting that in their cohort of children half of the children had
underlying neurological disease and 39% had respiratory
disease, primarily bronchopulmonary dysplasia.(37)
The choice of tracheostomy size is determined to suit the
functional needs of the patient and must, therefore, be of an
appropriate length beyond the stoma to secure the airway
while not being too close to the carina (Fig. 2). The di-
ameter needs to be large enough to allow adequate flow of
air and to minimize the work of breathing while not dam-
aging the tracheal wall and ideally allowing sufficient air to
pass around the tracheostomy tube to allow for translar-
yngeal airflow and vocalization. All tubes should have a
universal 15 mm adapter to allow for bag and mask venti-
lation in an emergency. In younger children, the use of dual
lumen tubes is uncommon, since the inner tube diameter
would be too narrow; similarly, fenestrated tubes are not
commonly used.
There are several strategies to improve humidification
of the airways in children with tracheostomies.(5) A heated
passover humidifier that has a source of gas flowing over a
heated water bath with a large surface-air ratio is primarily
used at night time in some centers. Heat moisture ex-
changers collect humidity from the patients own exhaled
breath, and this will moisten the inspired air. This is used
during day time to allow more independence for ambulatory
patients. Also, jet nebulizers with normal or half normal
saline (heated or room temperature) may be used several
times a day to hydrate the airway and secretions. Little data
are available that compare the efficacy and efficiency of
these different strategies.
Clinical Indications and Objectives for Aerosol
Therapy in Tracheostomized Patients
Aerosolized therapies are important treatments in the
management of airway disorders that can deliver medication
directly to where it is required.

FIG. 2. Examples of different types of tracheostomies ID, internal diameter; OD, external diameter, and L, length.
Pediatric size tracheostomy tubes: (A) Portex Bivona Pediatric silicone standard tube ID = 3.5 mm, OD = 5.3 mm,
L = 40 mm; (B) Portex Bivona Pediatric air cuff silicone tube ID = 5.5 mm, OD = 8.0 mm; (C) Portex Bivona Pediatric Tight
to Shaft water cuff tube (uninflated) ID = 5.0 mm, OD 7.3 mm, L = 42 mm; (D) Shiley Neonatal PVC tube ID = 3.0 mm,
OD = 4.5 mm; (E) Portex Bivona Neonatal Flextend silicone tube ID = 2.5 mm, OD = 4.0 mm, L = 30 mm; and (F) Portex
Bivona Customised Flextend silicone tube ID = 4.5 mm, OD = 5.7 mm, L = 54 mm. Adult size tracheostomy tubes: (G)
Portex BlueLine Ultra PVC tube (soft-seal air cufflow pressure, high volume), ID 7.0 mm, OD 10.5 mm, L 70.0 mm; (H)
Portex BlueLine Ultra PVC tube (soft seal air cuff and fenestrated, with red fenestrated inner cannula in situ), ID 7.0 mm,
OD 10.5 mm, L 70.0 mm; (I) Portex Uniperc Adjustable Flange Reinforced PVC tube (soft seal air cuff and PTFE inner
cannula in situ), ID 9.0 mm, OD 13.6 mm, L variable 80.0 to 140.0 mm; ( J) Portex BlueLine Ultra Suction (soft seal air
cuff, inner cannula in situ and integral suction port for secretions above cuff), ID 8.0 mm, OD 11.9 mm, C 75.5 mm. (K)
Portex Bivona Aire Soft Silicone Tube (air cuff), ID 8.0 mm, OD 11.0 mm, L 88 mm.
4 BERLINSKI ET AL.

Aerosolized treatment comes into several broad cate- In contrast to the widespread use of inhaled medication in
gories: (1) Bronchodilator treatmentmost commonly, this the tracheostomized populations, there is scant information
would be a short-acting beta2 agonist such as albuterol but on the effectiveness of inhaled medications and aerosol
longer-acting beta2 agonists such as salmeterol may also be delivery systems used in this population.(730)
used. Anti-cholinergic therapy such as ipratropium bromide
may form part of the acute treatment of asthma. These may Principles of Aerosol Therapy
be used in either nebulized or metered dose inhaler (MDI)
Inhaled therapies are frequently the treatment of choice for
form. (2) Inhaled steroids may also form part of anti-asthma
intrapulmonary conditions, because they can deliver high
therapy, with inhaled beclomethasone, fluticasone, and bu-
in situ drug concentration with minimal systemic expo-
desonide being used. Combination inhalers (fluticasone +
sure.(39,40)
salmeterol) may form part of regular treatments. (3) Inhaled
Therapeutic aerosols may be generated and delivered by
antimicrobial therapy may be nebulized. This most commonly
large- or small-volume liquid nebulizers, pMDIs, or by dry
includes not only antibiotics such as the aminoglycosides
powder inhalers (DPI) (Figs. 3 and 4).(39,40) Nebulizers and
tobramycin, amikacin, and gentamicin, but also other antibi-
pMDIs are considered active devices, as they generate
otics such as colomycin and meropenem. Antifungals such
the aerosol particles independent of the patients effort.
as amphotericin/ambisome can be nebulized as can anti-
Large-volume nebulizers are not only often used for ad-
pneumocystis jirovecii treatment such as pentamidine. (4)
ministration of aerosols to augment humidification of in-
Mucolytic therapy may be nebulizedthis includes dornase
haled gas, but they may also be used for administration of
alfa, hypertonic saline, N-acetyl cysteine, and carbocisteine.
more active pharmaceutical agents such as bronchodilators
(5) Pulmonary hypertension medicationepoprostenol and
and antivirals (e.g., ribavirin). DPIs are typically passive
prostacycline. (6) Palliative carefentanyl, diamorphine,
devices. These devices require vigorous inhalation by the
and morphine.
patient to release and de-aggregate the powder from its
A recent survey of aerosol use in spontaneously breathing
container/reservoir while simultaneously inhaling the med-
tracheostomized children included 47 institutions in the
ication. Most common devices used in tracheostomized
United States that trained pediatric pulmonologists, and 81%
patients are small-volume nebulizers and pMDIs with either
(38) replied.(38) They found that almost all centers (97%) used
a spacer or a valved holding chamber (VHC).
nebulizers and also used MDIs (92%) in children with tra-
For a more thorough review of aerosol delivery devices,
cheostomies. In terms of medication actually usedall used
the readers are referred to two recent comprehensive re-
inhaled corticosteroids (11% used MDI only, 16% used neb-
views.(41,42)
ulized only, and 73% used both). All institutions used short-
acting beta agonists, with 8% using MDI only, 11% using jet
Many Challenges/Barriers
nebulizer only, and 81% using both. Combination therapy
(long-acting bronchodilator + corticosteroid) was used by Aerosol drug delivery through tracheostomy is a challenge.
32% of institutions, with 83% of them using MDI only, and There are many factors affecting aerosol therapy to this pa-
17% of them using both. Most institutions delivered muco- tient population, and little is known due to a lack of literature
lytics (84%) and antibiotics (82%) via jet nebulizer. The au- in this area of research. Only a few in vitro and case reports
thors also inquired about the use of the assisted technique that have been published that are specific to aerosol therapy in
was defined as the use of a resuscitation bag in conjunction patients with tracheostomy.(730) According to these in vitro
with aerosol delivery with the goal of increasing tidal volume. studies, aerosol drug delivery efficiency through tracheos-
They reported that 68% of the institutions used the assisted tomy ranges from 1% to 45% of the nominal or emitted dose,
technique, either pressurized MDI (pMDI) or nebulizers. depending on the experimental variables.(2030) Many factors,

FIG. 3. Examples of nebulizers used for aerosol delivery (A) Continuous output jet
nebulizer (Hudson); (B) Continuous output jet nebulizer with reservoir (Hudson); (C)
Breath-enhanced jet nebulizer (Pari LC Plus); (D) Breath-actuated jet nebulizer (BAN
II); and (E) Vibrating mesh nebulizer (Aeroneb Solo).
AEROSOL DELIVERY THROUGH TRACHEOSTOMIES
FIG. 4. Examples of adapter, spacers, and valved holding chambers used to deliver
pMDIs and Soft Mist Inhalers. (A) Aerochamber Plus; (B) Aerochamber MV; (C)
Aerochamber Mini; (D) Inline adapter with reservoir; and (E) Vortex Trachoe. pMDI,
pressurized metered dose inhaler.
such as the ID, inner cannula, and fenestration of the tra-
cheostomy tube, type of aerosol device and patient interface,
type of ventilator and oxygen support, use of bias or contin-
uous flow, pattern of breathing, and delivery technique affect
aerosol drug delivery to patients with a tracheostomy.(2030)
Each of these factors have been explored to some extent with
in vitro studies that are described in the next section.
In vitro studies showed that drug delivery is not similar
between different types of artificial airways. A study com-
paring lung delivery of a jet nebulizer between a tracheos-
tomy tube and an endotracheal tube (ETT) in a model of a
spontaneously breathing tracheostomized adult showed that
drug delivery distal to the bronchi was greater with a tra-
cheostomy tube than with an ETT.(21) This finding suggests
that aerosol delivery via a tracheostomy tube may provide
greater drug delivery than the ETT of the same diameter,
presumably due to the difference in length. It also under-
scores the fact that results obtained by using ETTs cannot be
strictly extrapolated to tracheostomy tubes.
In Vivo Studies
As previously noted, little in vivo data are available
regarding aerosol drug delivery through tracheostomies in
spontaneously breathing tracheostomized patients.(719) Baran
et al. compared drug delivery of gentamicin between intra-
muscular injection, endotracheal instillation, and aerosoliza-
tion.(7) They evaluated blood and sputum drug concentration
1 hour after administration. Their subjects included six chil-
dren with tracheostomies. They found that the sputum con-
centration was 451- and 19-fold higher than the intramuscular
administration for the instillation and aerosolization routes,
5
respectively. They also reported that blood levels were 79- and
28-fold higher than the aerosolized route for the intramuscular
and endotracheal administration methods, respectively.
Garcia Pachon et al. compared, in a cross-over design, the
bronchodilator response to terbutaline (peak expiratory flow
through tracheostomy) between a pMDI and a DPI in nine
adults with tracheostomy.(15) They found no difference be-
tween devices (16 16% and 18 17% for pMDI and DPI).
Johnson evaluated the ability of 23 adults with tracheostomy
to empty the content of powder capsules of tiotropium and
formoterol (Handihaler and Aerolizer devices, respec-
tively).(18) The devices were adapted to the tracheostomy tube,
and delivery occurred on most occasions with an inflated cuff.
Eighty-three percent of subjects were able to successfully
empty the capsule. More recently, Pitance et al. compared,
with a cross-over design, drug delivery of nebulized amikacin
in nine adults during mouth and tracheostomy delivery by
using a pharmacokinetic method.(19) They found no differ-
ences in urinary amikacin between both delivery methods.
Several case reports, mostly describing modification of
devices to allow pMDI administration to tracheostomized
patients, have also been published.(814,16,17)
In Vitro/In Vivo Correlations
The discrepancy between in vitro and in vivo estimates of
aerosol delivery has been reconciled by comparing data
from bench models with in vivo scintigraphic studies.(43)
In vitro models using an absolute filter to collect drug distal
to the artificial airway tend to overestimate in vivo deposi-
tion, because the filter collects all drug exiting the ETT and
is unable to simulate the proportion of drug that is exhaled
6 BERLINSKI ET AL.

by the patient. When the difference between drug exhaled
in vitro and in vivo is subtracted from the in vitro drug
deposited distal to the ETT, the calculated dose is compa-
rable to pulmonary deposition of radiolabeled aerosol in
mechanically ventilated patients after adjusting for tissue
absorption of radioactivity.(44) When amikacin was admin-
istered to intubated, mechanically ventilated patients with
three different nebulizers, both sputum concentration and
urinary excretion of amikacin correlated with the in vitro
findings under similar conditions.(45)
Consequently, it is reasonable to conclude that in vitro/
in vivo correlations of aerosol delivery via artificial airways
are sufficient to support relevance of in vitro studies in
providing insights as to the impact of specific variables on
aerosol delivery through artificial airways.
In Vitro Studies
In vitro setups
Since there are no universally accepted in vitro models
used to study drug delivery through tracheostomies during
spontaneous breathing, different models have been used.
The conclusions obtained with one type of model may not
be directly extrapolated to others. There are differences in
the investigational setups: breathing patterns (pediatric vs.
adult), type of connection (direct vs. sideways), tracheostomy
size, type of nebulizer, type of MDI formulation, type of
spacer/VHC, type of adapter, and use of active versus passive
breathing, use of additional flow, and use of additional hu-
midity in both inhaled and exhaled gas (Fig. 5).(2030)
Authors usually express their data as lung dose (drug
captured in filter distal to the airway) or tracheal dose (drug
captured in the trachea located before the distal filter). In
addition, authors express results as an absolute amount of
captured drug or as delivery efficiency (amount of drug
captured/nominal or emitted dose amount 100). Although
efficiency is a good outcome to compare drugs/devices with
the same amount of nominal drug, it could be misleading
when the differences in nominal amount are several fold.
Practitioners need to also consider the cost of the delivery
device and formulation to be used before deciding on the
combination that will be prescribed to a particular patient.
Tables 1 and 2 summarize the published data obtained by
using adult and pediatric in vitro models, respectively.

FIG. 5. Different types of connections used for in vitro studies. The delivery efficiencies
for each connection/study were as follows: (A) 1.4%5%20, and 13.8%21; (B) 1.4%3.7%
for jet nebulizer and 3.1%4.8% for vibrating mesh nebulizer28; (C) 12.9%15.3%20 (D)
5.9% for jet nebulizer and 19.8% for vibrating jet nebulizer25, and 6.6% for jet nebulizer
and 15.8%17.7% for vibrating mesh nebulizer28; (E) 8.8%15.8%23 1.6%5.2% (breath
enhanced), 0.2%2.1% (breath actuated), and 1%1.7% (continuous output) for lung dose,
and 7.1%10.5% (breath enhanced), 0.4%1.6% (breath actuated), and 0.4%3.1% for
tracheal dose24 and 24.1%30; (F) 9.9%19.2%23, 1.3%2.3%24, and 1.9%4%27; (G)
27.2%21; (H) 2.5%3.1% lung dose and 5.5%8.5% tracheal dose24 and 3%4.6%27; (I)
5.3% for jet nebulizer and 17.5% for vibrating mesh nebulizer25; ( J) 12.7%50.3%22,
47.2%25, 1.8%17.6%27, and 2.6%24.8% for pMDI and 7.1%31.4% for soft mist in-
haler29; (K) 20.9%20; (L) 9.3%20; (M) 10.9%16.1%20; (N) 1.9%7.8%22; and (O) 9.2%
26.9%22, 43.3%25, and 6.6%17.1%27.
 Table 1. In vitro Studies on Aerosol Drug Delivery Through Tracheostomy Using a Model of a Spontaneously Breathing Adult
Study reference
(year) Experimental setup Drug and dosage Study variables Results
20
Piccuito et al. Sideways connection Albuterol sulfate 1. Aerosol devices: Jet nebulizer There was no significant difference between jet
(2005) Vt: 400 mL (2.5 mg/4 mL) for and pMDI nebulizer and pMDI delivery efficiency, but the jet
RR: 20 bpm nebulizer 2. Interfaces: For nebulizer: nebulizer delivered more drug.
I:E ratio: 1:2 Albuterol pMDI:CFC T-Piece and tracheostomy mask Using the jet nebulizer, aerosol deposition obtained
400 lg (100 lg/puff) For pMDI: Valved T-piece with a from the T-piece (382 lg) was greater than the
1-way valve placed proximal or tracheostomy mask (322 lg).
distal of the spacer. The addition of 30 L/min flow as heated (107 lg for
3. External gas flow T-piece and 130.2 lg for mask), heated/humid
4. TT size 8 mm ID (75.2 lg for T-piece and 36.2 lg for mask), or dry
flow aerosol (124.8 for T-piece and 86.6 lg for
mask) reduced drug delivery.
pMDI with a valved T-piece using a 1-way valve in
the proximal position (83.8 lg) was more efficient
than when the valve is placed in distal position
(37.1 lg).
The addition of 30 L/min of heated humidity yielded a
lung dose of 64.4 and 43.7 lg for the T-piece and
mask, respectively.
Ari et al.21 Sideways connection Albuterol Sulfate 1. Airways: ETT and TT Aerosol delivery through ETT (226.3 lg with t-piece)

7
(2012) Vt: 450 mL (2.5 mg/3 mL) 2. Interfaces tracheostomy mask, was significantly less than TT (344.8 lg with t-
RR: 20 bpm and T-Piece piece and 173 lg with tracheostomy collar).
I:E ratio: 1:2 3. Delivery technique: unassisted Aerosol deposition with the tracheostomy mask was
Passive lung for vs. assisted breathing technique lower than the T-piece.
the assisted 4. TT and ETT size 8 mm ID The use of the assisted technique increased lung dose,
technique irrespective of type of artificial airway and interface
(1193.8 and 680.8 lg for TT and ETT, respective-
ly).
Pitance et al.23 Direct connection Amikacin 500 mg 1. TT size 10, 8.5, 8, and 6.5 mm ID Lung doses for TT ID 10, 8.5, 8, and 6.5 were as
(2013) Vt: 440 mL (125 mg/mL) 2. Inner Cannula 8.5 and follows: Vented = 59.2, 57, 55.4, and 45.9 lg
RR: 20 bpm 6.5 mm ID Vented+Spacer = 95.9, 75.5, 72.1, and 49.5 lg
I:E ratio: 1:2 3. Nebulizers vented, vented+ Unvented = 78.9, 65.4, 63.3, and 44.1 lg
Inspiratory spacer, and unvented Aerosol delivery increased with the larger ID of the
Pause: 10% tracheostomy tube size. There was no significant
difference between 8 mm ID and 8.5 mm ID on
aerosol delivery.
Removing the inner cannula increased aerosol
deposition up to 31%.
Delivery efficiency of unvented nebulizer with
corrugated tubing was greater than the vented
nebulizer used with or without spacer except for
the TT with ID 6.5 mm.
(continued)
 Table 1. (Continued)
Study reference
(year) Experimental setup Drug and dosage Study variables Results
26
Bugis et al. Sideways connection Albuterol sulfate 1. Interfaces: tracheostomy mask, The tracheostomy collar (175 lg) was more efficient
(2015) Vt: 400 mL (2.5 mg/3 mL) face mask, and wright mask than the face mask (87.5 lg) and the Wright mask
RR: 20 bpm 2. Fenestration open or closed (102.5 lg) when the fenestrations are open.
I:E ratio: 1:2 or 2:1 3. I:E ratio 1:2 and 2:1 Closing fenestration (235 lg) with the tracheostomy
4. TT size 8 mm ID (fenestrated) collar resulted in greater aerosol deposition com-
pared with open fenestration.
Aerosol deposition with 2:1 ratio increased with 1:2
ratio by 65.7%, 31.9%, 75.6%, and 74.3% for
tracheostomy collar open and close, wright open
and face mask open, respectively.
Ari et al.28 Sideways connection Albuterol sulfate 1. Aerosol devices: Jet and vibrating Aerosol delivery obtained from the jet nebulizer
(2016) Vt: 400 mL (2.5 mg/3 mL) mesh nebulizers (164.8 and 149.5 lg for room air and heat moisture

8
RR: 20 bpm 2. Humidifiers and ambient gas: exchanger (HME) conditions, respectively) was less
I:E ratio: 1:2 heated humidifiers, unheated than the mesh nebulizer (441.8 and 425 lg for room
humidifiers, heat-moisture ex- air and HME conditions, respectively).
changers, and room air. The addition of 40 L/min flow resulted in a reduction
3. Exhalation: active of lung dose for jet nebulizer (62.2% and 43.9% for
(heated/humidified) and heated and unheated gas, respectively), and
passive (dry) exhalation vibrating mesh nebulizer (82.5% and 73.1% for
4. TT size 8 mm ID heated and unheated gas, respectively).
Delivery efficiency of nebulizers was the greatest in
room air and the lowest when heated humidifiers
with higher flows were used.
The use of a model that had exhaled humidity resulted
in a significant reduction in lung dose for the
vibrating mesh nebulizer with HME (14.1%), and
jet nebulizer with external heated humidity (43.8%)
but was not different for the other tested conditions.
Vt, tidal volume; RR, respiratory rate; I:E, inspiratory:expiratory; TT, tracheostomy tube; ETT, endotracheal tube; pMDI, pressurized metered dose inhaler; ID, internal diameter.
 Table 2. In Vitro Studies on Aerosol Drug Delivery Through Tracheostomy Using a Model of a Spontaneously Breathing Child
Study reference
(year) Experimental setup Drug and dosage Study variables Results
Berlinski24 Direct connection Albuterol sulfate 1. TT Size: 3.5 and 5.5 mm ID Lung doses for the breath-enhanced, breath-actuated, and
(2013) 16 month-old: Vt: 80 mL (2.5 mg/3 mL) 2. Breathing patterns: 16-month-old and 12- continuous output jet nebulizer alone, with extension and
RR: 30 bpm year-old children with extension and assisted technique were as follows:
I:E ratio: 1:3 3. Nebulizers: Breath-enhanced, 16 month/3.5ID: 41, 3.8, 24.8, 39.3, and 61.5 lg
12-year-old: Vt: 310 mL breath-actuated, and continuous output jet 16 month/5.5 ID: 92.3, 14.5, 27.3, 33, and 69.3 lg.
RR: 20 bpm nebulizers. 12 years/3.5 ID: 65.8, 13.8, 35, 33.3, and 76 lg.
I:E ratio: 1:2 4. Interfaces T-piece, tracheostomy mask, T- 12 years/5.5 ID: 129.8, 52, 42.8, 57, and 70.8 lg.
piece with extension tube The size of TT, breathing pattern, the type of interface used, and
5. Delivery techniques unassisted delivery technique impact aerosol delivery. The size of TT
breathing vs. assisted breathing has a direct relationship with lower aerosol deposition.
The breathing pattern of a 12-year-old child with large tidal
volume increased aerosol deposition compared with the
breathing pattern of a 16-month-old.
Delivery efficiency of the breath-enhanced nebulizer (Pari LC
Plus) was greater than the continuous jet (Up-Draft-II)
and the breath-actuated (AeroEclipse) nebulizers.
The tracheostomy mask is less efficient than the T-piece.
Adding an extension tube to the T-piece improves aerosol
deposition.
Tracheal dose was high for the breath-enhanced (range 177.5
262.8 lg), and for the continuous output jet nebulizer with

9
extension tube and the assisted technique (range
128213.3 lg).
Berlinski et al.22 Direct connection ProAir HFA 900 lg 1. TT Size: 3.5 mm ID, 4.5 mm ID and Lung doses (average of all TTs) for the 16 months, 6 and 12
(2013) 16 month-old: Vt: 80 mL (90 lg/puff) 5.5 mm ID years old were as follows: Aerochamber MV: 219.5, 262.6,
RR: 30 bpm 2. Breathing patterns: 16-month-old and 6- and 331.3 lg
I:E ratio: 1:3 and 12-year-old children Aerotrach: 384.7, 444.3, and 452.7 lg.
6-years old: Vt: 155 mL 3. Delivery technique: unassisted Aerochamber Mini: 113.9, 155.2, and 195 lg.
RR: 25 bpm breathing vs. assisted breathing Adapter: 39.3, 61.3, and 70.4 lg.
I:E ratio: 1:2 4. Interfaces Aerotrach Plus, Changing TT ID from 4.5 to 3.5 mm decreased lung dose, but
12-years-old: Vt:310 mL Aerochamber Mini, Aerochamber MV, changing from 5.5 to 4.5 mm does not.
RR: 20 bpm Medibag and inline adapter with six Breathing patterns of children impacted the amount of drug
I:E ratio: 1:2 in corrugated tubing delivered to children. The younger the child, the less aerosol
was delivered to the lungs. No difference was found on aerosol
deposition between 6 year-old and 12 year-old children.
Assisted technique reduced aerosol drug delivery generated by
pMDI/spacer/VHC by 40%60%.
Inline adapter was the least efficient interface, whereas aerosol
delivery obtained from the Aerotrach Plus was greater than
the rest of the interfaces in this study.
Alhamad et al.25 Direct connection for Albuterol sulfate 1.TT size 4.5 mm ID Aerosol delivery with the jet nebulizer (147 lg) was less than
(2015) unassisted and sideways (2.5 mg/3 mL) for 2. Devices: Jet nebulizer, vibrating mesh that with the mesh nebulizer (494.3 lg) and pMDI/spacer
connection for assisted nebulizer nebulizer, and pMDI/Aerochamber MV (203.7 lg).
2 years-old: Vt: 150 mL Ventolin HFA 360 lg 3. Delivery technique: unassisted vs. assisted There was no significant difference on aerosol drug delivery
RR: 25 bpm (90 lg/puff) for breathing technique. between unassisted and assisted breathing techniques.
I:E ratio: 1:2 pMDI
(continued)
 Table 2. (Continued)
Study reference
(year) Experimental setup Drug and dosage Study variables Results
27
Cooper et al. Direct connection Albuterol sulfate 1. TT Size: 3.5 and 4.5 mm ID Lung doses for different breathing profiles were as follows:
(2015) Infant: Vt: 50 mL (2.5 mg/3 mL) for 2. Devices: Jet nebulizer and pMDI Infant: 64.2, 28.2, and 114.4 lg for nebulizer, Aerotrach, and
RR: 30 bpm nebulizer 3. Interfaces: AeroTrach, AeroChamber Aerochamber Mini, respectively.
I:E ratio: 1:3 Ventolin HFA 900 lg Mini Child: 99, 74.3, and 158.3 lg for nebulizer, Aerotrach, and
Child: Vt: 155 mL (90 lg/puff) for 4. Breathing patterns: infant, children, and Aerochamber Mini, respectively.
RR: 25 bpm pMDI older children Older child: 93, 135, and 123.8 lg for nebulizer, Aerotrach, and
I:E ratio: 1:2 5. Delivery technique: unassisted vs. assisted Aerochamber Mini, respectively.
Older Child: Vt: 300 mL breathing technique The use of assisted technique in a 1224% increase with the
RR: 25 bpm 6. Delivery route: oronasal vs. TT nebulizer. However, it resulted in a 48% decrease with the
I:E ratio: 1:2 pMDI and infant breathing pattern but no change and 11% for
the child and older child breathing patterns, respectively.
Aerosol drug delivery was influenced by the aerosol device,
interface, breathing pattern, delivery techniques, and TT size
used in this study. While delivering nebulized albuterol with
face mask decreased lung dose compared with the
tracheostomy with the jet nebulizer, switching from facial to
tracheostomy route led to no change or increase in aerosol
deposition with the pMDI.
Berlinski et al.29 Direct connection Ventolin HFA 900 lg 1. TT Size: 4.5 mm ID Respimat/VHC (23.7, 233.1, and 175.9 lg for the infant, child,
(2016) Infant: Vt: 50 mL (90 lg/puff) for the 2. Devices: Respimat and pMDI and older child breathing pattern, respectively)
RR: 30 bpm pMDI and 3. Interfaces: Vortex VHC with adapter delivered a higher lung dose than pMDI/VHC (71.4, 214.8,

10
I:E ratio: 1:3 Combivent 4. Breathing patterns: infant, children, and and 314.1 lg. for the infant, child, and older child breathing
Child: Vt: 155 mL Respimat 1000 lg older children pattern, respectively).
RR: 25 bpm (100 lg of 5. Delivery technique: unassisted breathing Lung dose was higher for TT than oronasal delivery.
I:E ratio: 1:2 albuterol/actuation) technique
Older child: Vt: 300 mL 6. Delivery route: oronasal vs. TT
RR: 25 bpm
I:E ratio: 1:2
Wee et al.30 6 years-old: For Tobramycin nebulizer 1. TT Size and breathing pattern: 4.0 mm The breathing pattern had an effect on the DPI (91.9 and 102 lg
(2016) nebulizer Vt: 129 mL solution: 300 mg/ ID/6 year-old 5.5 mm ID/12 year-old for the 6- and 12 year-old model, respectively) but not on the
RR: 24 bpm 5 mL and TOBI 2. Devices: Pari LC Plus and Podhaler nebulizer therapy (69.5 and 75.2 lg for the 6- and 12 year-old
I:E ratio: 1:1.5 Podhaler 28 mg/ model, respectively).
For DPI Peak capsule The DPI was more efficient than the nebulizer.
inspiratory flow: Three capsules of the DPI deliver a similar amount of
60 L/min inhaled tobramycin than the nebulizer.
volume: 0.75 L
12-years-old: for nebulizer
Vt:234 mL
RR: 24 bpm
I:E ratio: 1:1.5
For DPI peak
inspiratory flow:
80 L/min inhaled
volume: 1.34 L
Vt, tidal volume; RR, respiratory rate; I:E, inspiratory:expiratory; TT, tracheostomy tube; DPI, dry powder inhalers; VHC, valved holding chamber.
AEROSOL DELIVERY THROUGH TRACHEOSTOMIES
Effect of cannula on aerosol delivery
The ID of the tracheostomy tube affects the amount of
drug delivered beyond its tip into the airways. This has been
shown in both pediatric and adult in vitro models. Pediatric
studies evaluating pMDI with VHCs, spacer, and adapters
reported a decrease in lung dose when decreasing the tra-
cheostomy ID from 4.5 to 3.5 mm but not when decreasing it
from 5.5 to 4.5 mm.(22,27) Other studies evaluating nebulized
therapy reported a decrease in lung dose when the trache-
ostomy ID was decreased from either 5.5 mm or 4.5 to
3.5 mm.(24,27)
Studies evaluating nebulized albuterol in adult models
reported a direct correlation between tracheostomy tube size
and lung dose and a 34% increase in lung dose when fen-
estrations of the tracheostomy tube were closed.(23,26) An
increase of similar magnitude was achieved by removing the
inner cannula.(23)
The amount of drug deposited in the tracheostomy tube
ranges from 2% to 16% of the nominal dose in adults as
opposed to 0.8%10% of the nominal dose in pediatrics.(2224)
A negative relationship between the ID of the tracheostomy
tube and the amount of drug lost in the cannula was reported in
adult models.(23)
No research has been found in the literature on the effect
of tube material and electrostatic charge on aerosol drug
delivery with tracheostomy.
In summary, there is a direct correlation between ID of a
tracheostomy tube and lung dose in pediatric and adult
models using pMDIs and nebulizers. Removing the inner
cannula and closing the fenestrations enhanced drug deliv-
ery during nebulization in different adult models. However,
removing the inner cannula takes away the 15 mm adapter
that connects to a T-piece, therefore forcing the use of a less
efficient tracheostomy mask. The effects of these actions are
the most likely to cancel each other out.
Effect of type of aerosol device on aerosol delivery
Nebulizers of different operating principles, pMDI with
different adapters, spacer and VHCs, soft mist inhalers with
VHC, and DPIs have been studied in different in vitro
models.(2030)
A study in an adult model showed that an unvented
nebulizer with corrugated tube was more efficient than a
standard unvented and vented nebulizer configuration.(23)
Another study in a pediatric model showed that the breath
enhanced was the most efficient followed by the continuous
output and the breath-actuated nebulizers.(24) They also
reported that the addition of corrugated tubing after the
nebulizer resulted in an increase in lung dose. The breath-
enhanced nebulizer and the continuous output jet nebulizer
with the extension and assisted technique delivered a large
amount of drug to the tracheal model before reaching the
filter placed at carinal level, thus potentially allowing tar-
geting of the large airways during tracheitis. Other studies in
pediatric and adult models showed that a vibrating mesh
nebulizer was more efficient than the continuous output jet
nebulizer.(25,28) Studies in adult models showed that the
addition of 3040 L/min of continuous flow of heated and
humidified air resulted in a decreased lung dose.(20,28)
Studies comparing lung dose obtained with albuterol
pMDI in pediatric models with direct connection showed
11
that VHCs made of nonelectrostatic material are the most
efficient add-on devices.(22,27,29) A study in an adult model
reported that the placement of a one-way valve in a spacer
resulted in a 2.3-fold increase in drug delivery when the
valve was moved from proximal to distal position to the
patient.(20) A study comparing a nebulizer solution and a
DPI tobramycin in pediatric in vitro models demonstrated
that the DPI was more efficient than the nebulized solution
(24% vs. 87% respectively).(30)
In summary, device selection and configuration signifi-
cantly affects drug delivery. The addition of a reservoir to
a continuous output jet nebulizer increases drug delivery.
Small-volume nonelectrostatic VHCs (Aerochamber Mini
and Aerotrach) are good alternatives for delivery of al-
buterol with pMDI in models of spontaneously breathing
tracheostomized children. The addition of continuous flow
hinders drug delivery in models of spontaneously breathing
tracheostomized adults.
Effect of MDI formulation on aerosol delivery
A study comparing albuterol delivered by an HFA pMDI
and Soft Mist Inhaler with a metallic VHC in a pediatric
model showed that the Soft Mist Inhaler delivered a higher
lung dose than the pMDI.(29) This is consistent with com-
parisons in spontaneously breathing adults.
Effect of use of assisted technique on aerosol delivery
The assisted technique consists of increasing the tidal
volume and flow with a resuscitation bag during inhalation
while the aerosol is being delivered (Fig. 6). The use of the
assisted technique is a highly prevalent practice; therefore, it
is important to evaluate its effect on aerosol delivery.(38)
Studies evaluating lung dose obtained with albuterol
nebulization reported different outcomes. Some showed
different degrees of increment in lung dose (1- to 3-fold)
when the assisted technique was used.(21,24,27) The differ-
ences could be attributed, in part, to the difference in the
in vitro models.(21,24,27) One of the studies also reported that
use of the assisted technique in every other breath delivered
a higher lung dose than assistance with every breath and also
increased tracheal delivery during aerosol therapy.(24)
Conversely, other studies using pediatric models reported no
increase in lung dose when the assisted technique was
used.(25,27)
Studies evaluating pMDI with VHC in pediatric models
(tracheostomy ID 3.5, 4.5, and 5.5 mm and tidal volume
ranging from 80 to 310 mL) reported that the use of the
assisted technique resulted in either a reduction or no change
in lung dose.(22,25,27)
In summary, the use of the assisted technique during
nebulization did not uniformly increase lung dose in pedi-
atric models but showed an increase in an adult model. The
use of the assisted technique increased tracheal dose, which
might have some application for delivery of inhaled anti-
biotics for the treatment of tracheobronchitis. The use of a
disposable bacterial filter placed right after the bag is re-
commended to prevent the aerosol from entering the bag and
from depositing on its valve system. However, the use of the
assisted technique with pMDI and spacer/VHC resulted in a
decrease or no change in lung dose in several pediatric
models. Based on these data, the use of this practice should
12
FIG. 6. Example of a resuscitation bag used with the assisted technique.
be discouraged in spontaneously breathing children or adults
with tracheostomy.
Effect of breathing pattern on aerosol delivery
Several studies in pediatric and adult in vitro models re-
ported that breathing patterns with increased inspiratory
time and larger tidal volumes resulted in a higher lung dose
during nebulizer therapy.(24,26,27) One study using a pedi-
atric model reported that this phenomenon plateaued at a
tidal volume of 155 mL.(27)
One study compared tobramycin delivery between a
breath-enhanced nebulizer (Pari LC Plus) with a nebu-
lizer solution (TOBI; Novartis Pharmaceuticals, East
Hanover, NJ), and a DPI (TOBI Podhaler; Novartis
Pharmaceuticals, East Hanover, NJ) using pediatric mod-
els.(30) The authors did not find any difference in drug
delivery for the nebulized formulation but reported an 11%
increase for the DPI with larger tidal volumes and peak
inspiratory flow.
The effect of different breathing patterns on aerosol de-
livery through tracheostomy with pMDI and soft mist inhal-
ers has been only studied in pediatric models. Several studies
reported that breathing patterns with larger tidal volumes
resulted in larger lung doses.(22,27,29) However, some studies
found that this effect plateaued at 155 mL.(27,29)
In summary, longer inspiratory times and larger tidal vol-
umes (up to a point) are associated with larger lung dose when
either nebulizers or soft mist inhalers/VHC are used. Studies
using pMDIs/VHC suggest that the use of tidal volumes larger
than the volume of the VHC might not offer an advantage.
Effect of interface on aerosol delivery
Studies using pediatric and adult in vitro models reported
that in general a T-piece is more efficient than a tracheostomy
mask during aerosol delivery via a nebulizer.(20,21,24,26,27)
Also, studies using pediatric and adult in vitro models
compared drug delivery via the oronasal route and tracheos-
tomy route and reported that the latter was more efficient.(26,27)
Table 3 provides descriptions, advantages, and disad-
vantages of each interface used for aerosol drug delivery to
spontaneously breathing patients with tracheostomy.
BERLINSKI ET AL.
In summary, a T-piece is a more efficient interface than
the tracheostomy mask for nebulization in pediatric (direct
connection) and adult (sideways connection) models. Tra-
cheostomy delivery is more efficient than oronasal delivery
in pediatric (direct connection) and adult (sideways con-
nection) models.
Effect of passing through tracheostomies on aerosol
characteristics
Several studies evaluated particle size, using impaction
techniques, of aerosols generated by nebulizers and pMDI
both before and after traveling through the tracheostomy
tubes.(24,27) One study evaluated tracheostomies with ID of
3.5 and 5.5 mm and reported that the mass median aerody-
namic diameter (MMAD) of the aerosol decreased for all
tested nebulizers but more for the tracheostomy with smaller
ID.(24) The MMAD decreased from 4.56 to 1.21.38 lm for
the continuous output jet nebulizer; from 3.47 to 1.26
1.58 lm for the breath-enhanced nebulizer; and from 3.43 to
1.221.77 lm for the breath-actuated nebulizer. Another
study reported particle size of albuterol HFA connected to
two different VHCs (Aerochamber Mini and Aerotrach)
both before and after passing through a tracheostomy tube
with an ID of 4.5 mm.(27) They found that the MMAD de-
creased from 2.142.15 to 1.651.74 lm.
In summary, the particle size of aerosols is reduced when
traveling through tracheostomies. The ID of the tracheos-
tomy and the formulation of the drug influence the intensity
of this phenomenon.
Airway Clearance and Secretion Management
In patients with a tracheostomy, the heating and filtering
function by the upper airways are either disturbed or by-
passed completely.(46) Moreover, hypersecretion and im-
paired mucociliary clearance is observed in patients with
limited capacity for active elimination of secretions.(47) In-
deed, cooling and drying of the mucosa slows the muco-
ciliary clearance, and it causes airway inflammation and
thickening of mucous secretions by dehydration.(5) Tra-
cheostomy is also regularly associated with underlying re-
spiratory diseases and smoking status, which themselves
impact clearance of the airway and secretions.(48)
 Table 3. Descriptions, Advantages, and Disadvantages of Each Interface Used for Aerosol Therapy
Interfaces Description
Tracheostomy A tracheostomy collar, also known as a
mask/collar tracheostomy mask, is a small mask with a
large hole that fits over the patients
tracheostomy site through an adjustable
elastic strap that is placed around the
patients neck to hold the mask in place.
T-piece/ T-piece, sometimes referred to as T-tube or
T-tube/briggs briggs adapter, is a T-shaped device that
adapter can be used in a direct and in a sideways
connection. In the direct connection, the
nebulizer is placed at the bottom, and one
end to the tracheostomy while the other
end of the T-piece is attached to a 6 inch
13
large bore tubing that acts as a reservoir.
During the sideways connection, the
bottom part connects to the tracheostomy
and the other two openings connect to a
high-flow gas system and a 6 inch large
bore tubing.
Manual The manual resuscitation bag is a hand-bag
resuscitation device that provides positive pressure
bag ventilation for patients with tracheostomy
who are not breathing or breathing
adequately.
Wright mask The wright mask is an interface that includes
a face mask and tracheostomy collar for
delivery of bland aerosol and oxygen
therapy.
Advantages
Simple and easy to use
Creates more stable setting that is less prone
to accidental removal of tracheostomy
tube.
Requires minimal equipment for the setup.
Creates a more comfortable setting for
patients with tracheostomy, as it does not
add extra weight on the tracheostomy tube.
Easy to use
Provided with most continuous output jet
nebulizers
Ability to assist the patients breathing with
prolonged inflation breaths.
Provides a closed system for aerosol drug
delivery.
Minimal aerosol loss during therapy.
Disadvantages
Is less efficient in aerosol drug delivery
Results in significant aerosol lost to the
environment.
Opens the lungs to direct germs.
Increases moisture at the stoma level.
Sideways connection
Significant aerosol wasted in the
atmosphere.
May cause accidental removal of
tracheostomy tube.
May damage stoma due to its weight and
patient movement.
Lower aerosol deposition if the high-flow
gas system is on.
Direct connection
Most efficient interface
Technically more difficult setup.
More time required to prepare the setup.
More parts needed for the setup.
User may need additional training and
practice to provide proper aerosol therapy
with a manual resuscitation bag.
Expensive and inefficient with pMDIs
Bulky
Delivers less aerosol than the face mask and
the tracheostomy collar alone
14
Table 4. Disinfection Methods Recommended
for Patients with Cystic Fibrosis
Step 1 Clean parts with dish detergent soap and water
(tap water that meets local public health standards
could be used)
Step 2 Use either a heat or a cold disinfection method
Heat methods Cold methodsa
Boiling water (5 minutes) Soak in 70% isopropyl
alcohol (5 minutes)
Microwave (submerged in water) Soak in 3% hydrogen
(5 minutes) peroxide (30 minutes)
Dishwasher if water temperature
is equal to or higher than
70C for 30 min
Electric steam sterilizer a
Rinse off the
disinfectant with
sterile water
Step 3 Air dry the nebulizer
parts before storage
Modified from Saiman et al.(52)
Coughing is the primary mechanism for maintaining
patent airways when there is mucociliary dysfunction. In
tracheostomized patients, acute or chronic ineffective air-
way clearance can be related to impaired respiratory muscle
function or ineffective cough. Glottis closure is a major
contributor to the efficiency of the cough and can be im-
paired due to the presence of a tracheostomy. The inspired
volume cannot be held in the lungs to increase the intra-
thoracic pressure. In the laryngectomy patient, absolute loss
of glottic function further adds to alteration of the cough and
straining mechanism.
The need for using airway clearance techniques in this
population is based on the impairment that the presence of
tracheostomy causes to the physiological mechanisms of
cough and mucociliary clearance. Manual and mechanical
techniques are available to aid these patients.
Another consideration on physiotherapy management
concerns the disinfection of the nebulizers. Nebulizers and
other respiratory devices can present a potential source of
cross-contamination in various scenarios.(4951) Inhalation
of aerosols generated from a contaminated nebulizer could
be a primary source of bacterial colonization of the respi-
ratory tract and particularly deleterious in patients when
pulmonary contamination is of major importance as it is for
tracheostomized patients. Specific guidelines to properly
disinfect respiratory equipment used by patients with cystic
fibrosis are available (Table 4).(52) These guidelines are
relevant due to the overlap in infectious agents that exist
between patients with cystic fibrosis and tracheostomized
patients.
Best Practice
Based on the review of the currently available published
literature and the expert opinion of the panel, the following
are considered the best practice for delivering aerosols to
spontaneously breathing tracheostomized patients:
1. Place the largest appropriate cannula in both pediatric
and adult patients due to the direct correlation between
ID of a tracheostomy tube and lung dose.
BERLINSKI ET AL.
2. Use a T-piece as the interface for aerosol delivery
through tracheostomies, when possible, as they are
consistently more efficient than trach masks.
3. Remove secretions from the cannula and clean the
inner cannula when present before administration of
aerosol. In a fenestrated tracheostomy tube, insert the
non-fenestrated inner cannula to close the fenestra-
tions, before inhalation.
4. Add a reservoir to continuous output jet nebulizers to
increase drug delivery.
5. Small-volume nonelectrostatic VHCs effectively de-
liver pMDI aerosols.
6. Avoid adding external gas flow during aerosol ad-
ministration, because it decreases lung delivery. Either
stop the high-flow humidity/system during the ad-
ministration of aerosols through the tracheostomy or
increase drug doses accordingly.
7. Avoid using the assisted technique with pMDI and
spacer/VHC, because it decreases lung delivery.
8. Consider using the assisted technique with nebulizers
when targeting the large airways (i.e., inhaled antibiotics).
9. Coach patients, when possible, to take deep and slow
breaths while receiving inhaled therapy.
10. For non-hospitalized patients, clean the respiratory
equipment in accordance with currently recommended
guidelines for patients with cystic fibrosis (Table 4).
Future Research
As evidenced by this workshop, many questions regard-
ing the best way to deliver aerosols to spontaneously
breathing tracheostomized patients remain unanswered.
Should patients with cuffed tracheostomy tubes inflate
their cuff during aerosol delivery to minimize air entrain-
ment from the upper airway?
What breathing pattern would favor either central or pe-
ripheral deposition?
Will nebulizers that produce aerosols with particle size in
the 0.51 lm range result in higher and more distal depo-
sition than nebulizers that produce aerosols with particle
size in the 35 lm?
Does a tracheostomy mask interface result in higher
stoma problems than the T-piece interface?
What role, if any, do respiratory tract biofilms play in
absorption and end-organ bioactivity of drugs, once me-
chanical delivery to the airways and alveoli is optimized?
More in vivo studies using the same devices that have
been used for in vitro studies are needed. These studies need
to involve both pediatric and adult subjects.
Limited pharmacokinetic data of lung delivery are
available. Future studies need to evaluate lung distribution
of aerosols given via tracheostomy during spontaneous
breathing and with the assisted technique.
Clinical studies evaluating the effectiveness of drugs used
in tracheostomized patients are warranted.
Finally, the degree of optimization of drug delivery
that is necessary to improve patient outcomes remains
unknown.
Acknowledgments
The authors are indebted to the ISAM that provided
partial financial support for the face-to-face meeting. This
AEROSOL DELIVERY THROUGH TRACHEOSTOMIES
workshop report has been reviewed and endorsed by the
ISAM Board. The authors acknowledge Ms. Phaedra Yount
(Arkansas Childrens Research Institute) for her help with
Figure 5.
Author Disclosure Statement
A.B. served as Principal Investigator in clinical trials
sponsored by Vertex, AbbVie, Allergan, Genentech, Jans-
sen, Gilead, Teva, Philips, Novartis, National Institutes of
Health, and Therapeutic Development Network. A.B. is a
Science Advisor to the International Pharmaceutical Aerosol
Consortium on Regulation and Science. A.A. declared a
relationship with Bayer Pharmaceuticals, Aerogen, and
ARC Medical. J.F. is currently Chief Scientific Officer for
Aerogen Pharma Corp. and had previously provided con-
sultancy services to Aerogen Ltd, Ansun, Dance Biopharm,
Quark Pharmaceutical, Bayer, and WHO. T.T. has provided
consultancy services to biotech companies, including Smiths
Medical and Baxter Healthcare. I.A. holds patents for
aerosol devices for infants and provided unpaid consulta-
tions to InspiRx. The remaining authors do not have any
conflict of interest.
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Received on September 16, 2016
in final form, November 29, 2016
Reviewed by:
Sunalene Devadason
Bruce Rubin
Address correspondence to:
Ariel Berlinski, MD
Department of Pediatrics
University of Arkansas for Medical Sciences
1 Childrens Way, Slot 512-17
Little Rock, AR 72202
E-mail: berlinskiariel@uams.edu