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Albuterol Delivery Via Metered Dose Inhaler in A Spontaneously Breathing Pediatric Tracheostomy Model.
Albuterol Delivery Via Metered Dose Inhaler in A Spontaneously Breathing Pediatric Tracheostomy Model.
Summary. Rationale: Little data are available regarding efficiency of drug delivery devices
and techniques despite their widespread use in spontaneously breathing tracheostomized
patients. We compared patient dose achieved with different devices, inhalation techniques,
tracheostomy tube sizes and breathing patterns using a spontaneously breathing tracheostom-
ized pediatric model. Methods: A tracheostomy model was connected in series to a breathing
simulator with a filter interposed (patient dose). Breathing patterns of a 16-month-old and a 6-
and 12-year-old child with tracheostomy with internal diameters (mm) of 3.5, 4.5, and 5.5 were
used. Albuterol HFAp MDI was used. Aerotrach Plus, MediBag, Aerochamber MV, Aerocham-
ber Mini, and inline adapter with 6-inch tubing were tested. The latter 3 devices were also
tested with assisted technique. Albuterol was analyzed via spectrophotometry. Results: Aero-
trach Plus outperformed almost all devices tested. Aerochamber MV with unassisted technique
was the second best and the adapter was the worst. Comparison of efficiency between best
and worst performer ranged from 3- to 17.2-fold. The 16-month-old breathing pattern and the
3.5 mm tracheostomy tube had the lowest patient dose. The use of assisted technique de-
creased patient dose by 18–67% for the 4.5 and 5.5 mm but not for 3.5 mm tracheostomy
tubes. A median of 7.4% of the nominal dose was deposited in the tracheostomy tubes. Con-
clusions: Aerotrach Plus and the adapter were the most and least efficient devices respectively.
Tracheostomy size and breathing pattern affected drug delivery. The use of assisted technique
reduced aerosol delivery. Pediatr Pulmonol. 2013; 48:1026–1034. ß 2012 Wiley Periodicals, Inc.
Key words: tracheostomy; metered dose inhaler; spacer; delivery device; children.
1
Department of Pediatrics, Pulmonology Section, University of Arkansas pediatric pulmonary fellow at University of Arkansas for Medical Scien-
for Medical Sciences, Little Rock, Arkansas. ces at the time the study was performed.
2
Pediatric Aerosol Research Laboratory, Arkansas Children’s Hospital Partial data were presented in abstract format at 2010 American Thoracic
Research Institute, Little Rock, Arkansas. Society Meeting by Dr. Chavez.
3
McClane Children’s Hospital at Scott and White, Temple, Texas. *Correspondence to: Ariel Berlinski, MD, Associate Professor, Depart-
ment of Pediatrics, Pulmonary Medicine, University of Arkansas for
Conflict of interest: Dr. Berlinski served as Principal Investigator in clini- Medical Sciences, 1 Children’s Way, Slot 512-17, Little Rock, AR
cal trials sponsored by Johnson & Johnson, MPEX Pharmaceutical, 72202. E-mail: berlinskiariel@uams.edu
Gilead, Philips and was recipient of an unrestricted educational grant
from S&T Technologies. None of their products are discussed in this Received 19 July 2012; Accepted 3 October 2012.
manuscript. Alma Chavez have no conflict of interest do declare.
DOI 10.1002/ppul.22715
The study was performed at the Pediatric Aerosol Research Laboratory Published online 5 November 2012 in Wiley Online Library
(Arkansas Children’s Hospital Research Institute). Dr. Chavez was a (wileyonlinelibrary.com).
Different delivery devices including pressurized metered with internal diameter (ID)/external diameters of 3.5/
dose inhalers (pMDI), nebulizers and dry powder 5 mm, 4.5/6.3 mm, and 5.5/7.6 mm were used.
inhalers have been adapted to deliver inhaled medica-
tions through tracheostomies.4–13 Few in vitro studies Breathing Patterns
using adult models have provided some insight into the
complexity of aerosol delivery through tracheosto- Three different breathing patterns corresponding to a
mies.14–16 These studies, mainly involving nebulizers, 16-month-old (Vt ¼ 80 ml, RR ¼ 30 bpm, I:E ¼ 1:3),
reported that interface, tracheostomy size, type of add-on 6 years old (Vt ¼ 155 ml, RR ¼ 25 bpm, I:E ¼ 1:2)
device and its configuration, use of assisted technique and 12 years old (Vt ¼ 310 ml, RR ¼ 20 bpm,
and presence of bias flow significantly affected drug de- I:E ¼ 1:2) were used.
livery. However these studies used models that by design
could have overestimated drug delivery. In addition, Devices and Delivery Technique
making extrapolations from adult data it is not accurate
Devices were operated with either unassisted or
because children use smaller size artificial airways and
assisted technique. The latter involves the use of
have smaller tidal volumes (Vts).17,18 Some animal data
a resuscitation bag as a means to increase the Vt.
comparing device/delivery techniques are available.19
The following devices were tested with unassisted
Despite the widespread use of pMDIs in spontane-
technique: Aerotrach Plus; Aerochamber Mini,
ously breathing tracheostomized patients little data are
Aerochamber MV (all 3 from Monaghan Medical,
available regarding the efficiency of different delivery
Plattsburgh, NY), and an inline adapter (RTC
devices.2 There is an imperative need to have data to
22-D, Instrumentation Industries, Inc., Bethel Park,
support different strategies when delivering aerosols to
PA) with a 6-in. corrugated tubing (110 ml) inter-
spontaneously breathing pediatric patients. In this in
posed between the tracheostomy and the adapter
vitro study we compared the amount of drug reaching
the carina (patient dose) of a spontaneously breathing
tracheostomized pediatric model using different deliv-
ery devices and techniques, different breathing patterns
and tracheostomies of different sizes.
We hypothesize: (1) that different devices will deliver
different patient doses; (2) that the addition of assisted
breaths will increase patient dose; (3) that increasing
tracheostomy size will increase patient dose; and (4)
that breathing patterns of younger children will deter-
mine smaller patient dose.
Tracheostomy Tubes
Three different sizes of uncuffed tracheostomies Fig. 1. Spontaneously breathing tracheostomized pediatric
(Tracoe, Boston Medical Products, Westborough, MA) model.
Pediatric Pulmonology
1028 Berlinski and Chavez
Fig. 3. Devices used with assisted technique. Top row: Aerochamber MV and Aerochamber
Mini. Bottom row: MediBag and inline adapter with 6-in. extension. All devices except Medi-
Bag are connected to a self-inflating resuscitation bag.
Pediatric Pulmonology
Aerosol Delivery via Pediatric Tracheostomy 1029
Tracheostomy
size (ID) Breathing Most Least
(mm) pattern efficient efficient Difference1
Tracheostomy Size
For devices using the unassisted technique patient
dose achieved with the 4.5 mm tracheostomy tube was
similar to that obtained with a 5.5 mm tracheostomy
tube for all breathing patterns with the exception of
Aerochamber MV/12-year-old breathing pattern (Fig. 4
and Table 2). The patient dose achieved by the 3.5 mm
tracheostomy tube was lower than the others for all
breathing patterns (Fig. 4 and Table 2).
In general devices using the assisted technique
showed no differences in patient dose among different
tracheostomy tube sizes (Fig. 4 and Table 2). The
Medibag/6-year-old breathing pattern scenario had
a similar pattern than the unassisted devices
(4.5 mm ¼ 5.5 mm > 3.5 mm). Other scenarios (Med-
iBag and Aerochamber Mini with assisted technique/
12-year-old breathing pattern) showed the following
Pediatric Pulmonology
Aerosol Delivery via Pediatric Tracheostomy 1031
TABLE 2— P Values for Comparison of Patient Dose Among Tracheostomy Tubes of Different Sizes
16 mo 3.5 vs. 4.5 <0.0001 <0.0001 0.014 0.0008 0.02 0.025 0.19 0.0002
3.5 vs. 5.5 <0.0001 <0.0001 0.012 — 0.46 0.19 0.19 —
4.5 vs. 5.5 0.35 0.28 0.99 — 0.12 0.002 0.19 —
6 yo 3.5 vs. 4.5 <0.0001 0.0005 <0.0001 0.022 0.0001 0.13 0.15 0.97
3.5 vs. 5.5 0.0001 0.002 <0.0001 — <0.0001 0.13 0.15 —
4.5 vs. 5.5 0.72 0.41 0.85 — 0.96 0.13 0.15 —
12 yo 3.5 vs. 4.5 0.005 <0.0001 <0.0001 0.036 0.6 0.097 0.08 0.07
3.5 vs. 5.5 0.0005 0.0005 <0.0001 — 0.09 0.097 0.79 —
4.5 vs. 5.5 0.17 0.0028 0.85 — 0.022 0.097 0.033 —
BP, breathing pattern; ATþ, Aerotrach Plus; A MV, Aerochamber MV; A Mini, Aerochamber Mini; AD, inline adapter; MB, MediBag.
Bold font represents statistically significant differences.
P values obtained with ANOVA for repeated measures followed by Tukey test when multiple comparison was required.
behavior: 3.5 mm ¼ 4.5 mm and 3.5 mm ¼ 5.5 mm unassisted technique Aerochamber MV (compared to
with 5.5 mm > 4.5 mm. The 16-month-old breathing 6 years old breathing pattern P ¼ 0.11, P ¼ 0.054, and
pattern showed responses in different directions. P ¼ 0.99, respectively. The 6-year breathing led to
The MediBag showed that 4.5 mm > 3.5 mm, and higher patient doses than for the 16-month-old breath-
3.5 mm ¼ 5.5 mm with 4.5 mm ¼ 5.5 mm; and ing pattern for all tested devices except MediBag, Aero-
Aerochamber MV with assisted technique showed that chamber Mini with assisted and unassisted technique,
4.5 mm > 3.5 mm ¼ 5.5 mm, while the inline adapter and inline adapter with assisted technique (P ¼ 0.97,
with assisted technique showed a higher patient dose P ¼ 0.16, P ¼ 0.99, P ¼ 0.06, respectively).
for the 3.5 mm than for the 4.5 mm.
Drug Deposited in the Tracheostomy Tube
Breathing Pattern
A median amount of 7.4% was deposited in the tra-
The older child breathing pattern had the highest pa- cheostomy tube. When data were pooled and analyzed
tient dose for all tested devices with the tracheostomy by tracheostomy tube size no differences were found
5.5 mm except for the Aerotrach Plus and (5.2 5.6%, 6.2 4.4%, and 8.9 3.5% for 3.5, 4.5,
Aerochamber MV with assisted breathing (P ¼ 0.44 and 5.5 mm, respectively; P ¼ 0.15). No differences
and P ¼ 0.99 when compared to the 6-year-old breath- were found when data were pooled for breathing pat-
ing pattern). The latter pattern led to higher patient terns either (6.7 5%, 7.1 4%, 8.1 5% for the
doses than for the 16-month-old breathing for all tested 16-month-old, 6 years old, and 12 years old, respective-
devices. ly, P ¼ 0.61). When data were pooled and analyzed by
The older child breathing pattern had a higher patient device the inline adapter (0.7 0.6%) had the lowest
dose than the youngest breathing pattern for all tested amount of drug deposited in the tracheostomy tube ex-
devices with the tracheostomy 4.5 mm except for the cept for Aerochamber MV with unassisted technique
Aerotrach Plus (P ¼ 0.072). The older breathing pat- (5.8 3.9%, P ¼ 0.11) and inline adapter with assisted
tern had similar patient dose than the 6-year-old breath- technique (3.1 2.2%, P ¼ 0.96). The Aerochamber
ing pattern except for Aerochamber MV with MV with assisted technique (10.1 6%, P ¼ 0.0006)
unassisted and assisted technique and inline adapter had the highest amount followed by Aerochamber Mini
with assisted technique (P < 0.0001, P ¼ 0.0034, and with assisted technique (9.3 1.6%, P ¼ 0.002), Aero-
P ¼ 0.01, respectively). The 6 years breathing pattern chamber Mini with unassisted technique (7.5 2.5%,
led to higher patient doses than for the 16-month-old P ¼ 0.03), Aerotrach Plus (7.4 5.5%, P ¼ 0.03), and
breathing for all tested devices except for Aerochamber Medibag (6.7 3.5%, P ¼ 0.01).
MV with assisted technique and inline adapter
with assisted technique (P ¼ 0.14, and P ¼ 0.65,
DISCUSSION
respectively).
The older child breathing pattern had the highest pa- Little data are available regarding efficiency of drug
tient dose for all tested devices with the tracheostomy delivery devices and techniques despite their wide-
3.5 mm except for inline adapter with assisted and spread use in spontaneously breathing tracheostomized
Pediatric Pulmonology
1032 Berlinski and Chavez
2
patients. In this study we compared patient dose Assisted Delivery
achieved with different devices, inhalation techniques,
We found that the use of assisted technique signifi-
tracheostomy tube sizes, and breathing patterns using a
cantly decreased drug delivery thus rejecting our second
spontaneously breathing tracheostomized pediatric
hypothesis. Piccuito et al.14 in an adult type tracheoto-
model. We found that a valved holding chamber made
my model found that the addition of flow and humidity
of anti-static material that does not require removal of
decreased drug delivery when using pMDIs. One
pMDI canister from the plastic actuator and the inline
could speculate that the presence of additional flow
adapter were the most and least efficient devices respec-
was responsible for the decrease in drug delivery. How-
tively. We also found that tracheostomy size and breath-
ever, one cannot ignore the data showing that in me-
ing pattern affected drug delivery. Finally, the use of
chanically ventilated patients the presence of humidity
assisted technique was found to reduce aerosol delivery.
decreases drug delivery by 50%.27 O’Callaghan et al.19
in an animal study found that the use of assisted tech-
Delivery Device nique decreased drug delivery to the lungs by 30%.
In their study they used radiolabeled beclomethasone
We found that a valved holding chamber made of a
delivered to spontaneously breathing tracheostomized
non-electrostatic material was the most efficient deliv-
(ID ¼ 3 mm) rabbits. These data are in agreement with
ery device. That device was the only one that did not
our findings. Conversely, Cole et al.28 and Diblasi
require removal the canister from the plastic booth.
et al.29 found in a neonatal model that the assisted tech-
Also, the device has an inspiratory valve placed proxi-
nique enhanced drug delivery. There are several impor-
mal to the tracheostomy. We think that these three ele-
tant differences between theirs and our setups. The
ments are responsible for the superior performance of
stroke volume used was not reported in one study and
the device. These data are in agreement with those of
was 250–500 ml in the other. They used very small Vts
Dubus et al.,22 who compared albuterol delivery via
(8–11.6 ml and 6–60 ml, respectively) and used smaller
pMDI in spontaneously breathing rabbits intubated with
ETTs (2.5 mm, and 2–4 mm, respectively). In addition
an ETT with an ID ¼ 3 mm. They found that the
tracheostomies are shorter than ETTs and length of the
valved holding chamber made of non-electrostatic ma-
tube has been previously inversely correlated with drug
terial was the most efficient one. Our data are also in
output.15,30 Interestingly, Ari et al.15 in an adult type
agreement with in vitro studies using spontaneously
tracheostomy model using a jet nebulizer found that
breathing models without artificial airways.23 We also
drug delivery was significantly enhanced with the use
found that the adapter was the worse delivery device.
of assisted technique. We speculate that the difference
These data are in agreement with previously published
with our study is due to the different nature of drug
data involving pMDIs delivering drugs in a ventilator
delivery device (pMDI vs. nebulizer) and the use of an
circuit.24 In our study a large spacer was the second
adult type model that had a tight connection between
most effective device delivering more drug than the
the tracheostomy tube and the filter. The former is sup-
small volume/shorter device made of anti-static materi-
ported by our own data when using nebulizers with the
al. We speculate that the larger length allowed for more
same tracheostomy model.31 Our model allowed for
deceleration of particles therefore decreasing extra-pul-
expiration of drug that remained in the airways that did
monary deposition.25,26 Piccuito et al. in an in vitro
not deposit while the one from Ari et al. did not.
study using an adult scenario (Vt ¼ 400 ml, RR ¼ 20,
I:E ¼ 1:2) compared albuterol delivery of a nebulizer
Tracheostomy Size
and a pMDI. They used a cuffed tracheostomy tube
with ID of 8 mm and a filter placed at the end of the We found that the influence of tracheostomy size on
tube. The authors used a spacer (Aerovent, Monaghan drug delivery is affected by the use of assisted tech-
Medical, Plattsburgh, NY) with pMDI under four differ- nique. The latter eliminated most size differences by
ent configurations: high flow heated humidity with making the systems less efficient. Patient dose was
either t-piece or tracheostomy mask and no additional similar between the 4.5 and 5.5 mm tracheostomy
flow with t-piece and one-way valve placed either distal tube and higher than the 3.5 mm. Our results partially
or proximal to the spacer. The latter was found to be confirm our third hypothesis. Our data are in
the most efficient one. These data are in agreement agreement with data from other studies that evaluated
with ours showing that different devices/configurations the effect of ETT characteristics on drug delivery.19,32
significantly affect drug delivery thus confirming our More recently, Pitance et al.16 using an in vitro
first hypothesis. adult tracheostomy model (Vt ¼ 440 ml, RR ¼ 20,
Practitioners need to be aware of the several-fold dif- I:E ¼ 1:2) found that a reduction of ID led to a reduc-
ference in efficiency found in this and other studies to tion of delivered drug when using different configura-
avoid either under-dosing or overdosing their patients. tions of a nebulizer.
Pediatric Pulmonology
Aerosol Delivery via Pediatric Tracheostomy 1033
Pediatric Pulmonology
1034 Berlinski and Chavez
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cheobronchial airways: effect of growth-rate assumptions. Inhal kane-beclomethasone versus chlorofluorocarbon-beclomethasone
Toxicol 2006;18:803–808. delivery in neonatal models. Arch Dis Child Fetal Neonatal Ed
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Pediatric Pulmonology