Epinephrine administration via a laryngeal mask airway: what is the optimal dose?

Abstract

Background. The aim of this animal study was to clarify the effects of laryngeal mask airway (LMA)-administrated epinephrine and to assess the optimal dose.Methods. Thirty pigs were anesthetized and intubated with a cuffed tracheal tube (TT) and an LMA. Then they were assigned to one of five groups. The control group received distilled water 10 mL via the TT; the TT group received epinephrine 50 μg/kg via the TT; and the other three groups received two, four or six times the TT dose of epinephrine via the LMA. Heart rate (HR) and arterial pressure were monitored before and after drug administration for 15 minutes.Results. After epinephrine administration, the LMA-6 and TT groups had elevated systolic, diastolic and mean arterial pressures at 1 min and there was no significant difference between the two groups. In the TT group, these parameters peaked at 2 min then declined rapidly. In the LMA-6 group, they increased more slowly, and then maintained a plateau. The control, LMA-2 and LMA-4 groups failed to display significant persistent (>2 min) hemodynamic changes.Conclusions. We could not identify an optimal LMA-administrated epinephrine dose. The TT route is suitable when a high peak drug effect is required and the LMA route may be preferable if a persistent plateau effect is desired. Effective LMA administration of drugs may require larger doses than those given via TT.

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Epinephrine administration
via a laryngeal mask airway:
what is the optimal dose?
ABSTRACT
Background. The aim of this animal study was to clarify the effects of laryngeal mask airway (LMA)-administrated epineph-
rine and to assess the optimal dose.
Methods. Thirty pigs were anesthetized and intubated with a cuffed tracheal tube (TT) and an LMA. Then they were assigned
to one of five groups. The control group received distilled water 10 mL via the TT; the TT group received epinephrine 50 ?g/
kg via the TT; and the other three groups received two, four or six times the TT dose of epinephrine via the LMA. Heart rate
(HR) and arterial pressure were monitored before and after drug administration for 15 minutes.
Results. After epinephrine administration, the LMA-6 and TT groups had elevated systolic, diastolic and mean arterial pres-
sures at 1 min and there was no significant difference between the two groups. In the TT group, these parameters peaked
at 2 min then declined rapidly. In the LMA-6 group, they increased more slowly, and then maintained a plateau. The control,
LMA-2 and LMA-4 groups failed to display significant persistent (>2 min) hemodynamic changes.
Conclusions. We could not identify an optimal LMA-administrated epinephrine dose. The TT route is suitable when a high
peak drug effect is required and the LMA route may be preferable if a persistent plateau effect is desired. Effective LMA
administration of drugs may require larger doses than those given via TT.
KUO-TAI CHEN ( ? ) •
HUNG-JUNG LIN
Emergency Department
Chi-Mei Medical Center
901 Chung-Hwa Road, Yung Kang
Tainan 710, Taiwan
Phone: 886-6-2812811 ext. 57196
Fax: 886-6-2816161
E-mail: 890502@mail.chimei.org.tw
CHIN-KUN LIAO •
NING-PING FOO
Department of Emergency Medicine
Chi-Mei Medical Center, Liouying
HUNG-JUNG LIN
Department of Biotechnology, Southern
Tainan University of Technology
CHIN-CHAN LIN
Department of Medical Research
Chi-Mei Medical Center
HOW-RAN GUO
Department of Environmental and
Occupational Health and Department
of Environmental and
Occupational Medicine, Medical
College,National Cheng Kung University
KUO-TAI CHEN
School of Medicine, Taipei Medical University
CHIN-KUN LIAO • HUNG-JUNG LIN • NING-PING FOO •
CHIN-CHAN LIN • HOW-RAN GUO • KUO-TAI CHEN
ORIGINAL
SIGNA VITAE 2010; 5(2): 25 - 28
Keywords: airway, drug delivery,
epinephrine, laryngeal mask airway
(LMA), tracheal tube
Introduction
Laryngeal mask airways (LMA) are
widely used in anaesthesia and resus-
citation. (1,2) They are easy to use and
require minimal training, which makes
them an excellent alternative airway
device for personnel who are not famil-
iar with airway management. (3-5)
Health care workers have been giv-
ing drugs through airway devices for
decades. (6) Among these devices, the
tracheal tube (TT) is most commonly
used. However, considerable training
is required to acquire and maintain the

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skill of tracheal intubation. (7) Our previ-
ous studies revealed that using a cath-
eter inserted through an LMA into the
trachea to deliver drugs is as effective
as using the TT route. (8,9) However,
the ease of passing a catheter and
documenting its correct position are
still under investigation. (10,11)
Trevisanuto et al. and Spain et al.
reported that delivering surfactant and
bronchodilator via an LMA is effective
in treating neonatal respiratory distress
syndrome and bronchospasm, respec-
tively. (12,13) Our previous studies
showed that LMA-administered epine-
phrine was well absorbed through the
mucosa of the airway but that, com-
pared with the TT route, the same dose
produced a lower plasma level. (8,9)
The optimal LMA-administered dose
of epinephrine is unknown. We there-
fore gave increasing doses of LMA-
administered epinephrine to identify a
dose equipotent to a standard TT dose
and to clarify the characteristics of drug
absorption via this route.
Materials and Methods
The Animal Care and Users Committee
of the Chi-Mei Medical Center approved
the study and the animals were cared
for in accordance with national and
institutional guidelines.
Thirty domestic Yorkshire pigs, nine
males and 23 females, weighing 16.5–
27 kg were anesthetized with intrave-
nous pentothal 30 mg/kg and randomly
assigned to one of five groups:
Control Group: 10 mL of distilled water
via the TT.
TT Group: epinephrine 50 ?g/kg via
the TT.
LMA-2 Group: epinephrine 100 ?g/kg
via the LMA (twice the TT group dose).
LMA-4 Group: epinephrine 200 ?g/kg
via the LMA (four times the TT group
dose).
LMA-6 Group: epinephrine 300 ?g/kg
via the LMA (six times the TT group
dose).
All doses of epinephrine were diluted
to a total volume of 10 mL with dis-
tilled water. The animals were intubated
with a cuffed TT (internal diameter 5
mm) and size 3 LMA (LMA-ClassTM,
Laryngeal Mask Company, Henley on
Thames, UK) (figure 1). We used a
fibre-optic bronchoscope to confirm
the position of the TT and to ensure that
the opening of the larynx faced directly
towards the lower aperture of the LMA.
The animals were ventilated via the TT
with a respiratory rate of 15 breath/min,
tidal volume 20 mL/kg and FiO2 1.0. All
animals were attached to a three-lead
ECG monitor and given an infusion of
0.9% normal saline solution at 20 mL/h
throughout the experiment. A carotid
or femoral catheter was inserted for
continuous heart rate (HR) and arte-
rial blood pressure (BP) monitoring. An
intravenous flush of heparin 3000 IU
was given to avoid intra-catheter clot
formation.
To achieve steady state conditions, a
20-min stabilization period followed the
completion of the above procedures.
We recorded baseline HR and BP. Sub-
sequently, we deflated the cuff of the TT
in the LMA-2, LMA-4 and LMA-6 groups
to facilitate spraying epinephrine into
the trachea through the LMA. In the
control and TT groups, epinephrine and
distilled water were delivered via the TT
and in the other groups via the LMA.
Drug administration was followed by
five forceful artificial respirations using
an Ambu Bag. The cuff of the TT was
re-inflated after epinephrine adminis-
tration in the LMA groups. HR and BP
were recorded continuously for 15 min
following medication delivery. At the
end of the experiment, the animals were
killed by injection of potassium chloride
solution 10 mEq. The methods of medi-
cation administration are presented in
figure 1; all other procedures are illus-
trated in figure 2.
All experimental results are presented
as medians unless otherwise noted
(table 1).
The differences in HR and BP between
the five groups were compared using
the Kruskal-Wallis followed by Mann-
Whitney U tests. The intra-animal chang-
es in hemodynamic variables were inves-
tigated using the Wilcoxon signed rank
test. All statistical tests were performed
at a two-tailed significance level of 0.05.
Table 1. Biometric data.
Group Control TTLMA-2 LMA-4LMA-6
Number of animals
(M/F)
6 (2/4)6 (2/4) 6 (3/3)6 (1/5)6 (1/5)
Weight
(kg, mean±SD)
21.6±3.5 21.1±3.0 22.9±3.1 21.2±2.3 21.6±2.2
LMA, laryngeal mask airway; TT, tracheal tube.
Figure 1. In the control and TT gro-
ups, epinephrine was given via the TT
(upper picture). In the LMA-2, LMA-4
and LMA-6 groups, epinephrine was
given via the LMA (lower picture).
LMA, laryngeal mask airway; TT, tra-
cheal tube.
AP, arterial pressure; HR, heart rate;
LMA, laryngeal mask airway; TT, tra-
cheal tube.
Figure 2. Timeline for the experimen-
tal protocol. *Inflate and deflate TT
cuff in the LMA-2, LMA-4 and LMA-6
groups.

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Results
There were no significant differences in
biometric data between the five groups
(table 1). The hemodynamic changes
following epinephrine administration via
the TT or LMA are illustrated in figures
3-6.
The LMA-6 and TT groups had an
increase in systolic arterial pressure
(SAP) at 1 min post-injection (p=0.028,
both groups). The response lasted for
11 min and 8 min, respectively. The
TT group had the highest peak SAP,
at 2 min post-injection. However, the
increase in SAP lasted longer in the
LMA-6 group. There was no signifi-
cant difference between the two groups
(p=0.605).
Both the LMA-6 and TT groups had
significant elevations in diastolic arterial
pressure (DAP) 1–7 min and in mean
arterial pressure (MAP) 1–8 min post-
injection, respectively. Similarly, the TT
group reached the highest peak DAP
and MAP at 2 min after epinephrine
administration. There was no signifi-
cant difference between the groups
(p=0.629 in DAP and p=0.642 in MAP).
The HR increased in the TT group at 0.5
min and in the LMA-6 group at 1 min
post-injection (p=0.028 and p=0.046,
respectively). The effect persisted for
15 min in both groups. The TT group
had the highest HR at 2 min. There was
a significant difference between the two
groups (p=0.01).
The control, LMA- and LMA-4 groups
failed to display significant persistent
(>2 min) hemodynamic changes after
epinephrine administration.
Discussion
We tested increasing doses of LMA-
administrated epinephrine and com-
pared the effect with the standard tra-
cheal route. After epinephrine adminis-
tration, both the LMA-6 and TT groups
had significant elevations in SAP,
DAP, and MAP. Though there were
no statistically significant differences
between these two groups, the pattern
of hemodynamic changes were dis-
tinct. In the TT group, the hemodynam-
ic parameters peaked promptly after
epinephrine administration, and then
declined rapidly. The peak levels were
higher than in the other groups. Those
in the LMA-6 group increased more
slowly and reached a plateau later. The
differences in response presumably
reflect different speeds of drug absorp-
tion, which are themselves the result
of differences in the available area for
absorption. With the LMA route, drug
absorption occurs partly through the
laryngeal mucosa and partly through
the broncho-alveolar mucosa. With the
TT route, all drug absorption is through
the broncho-alveolar mucosa.
Niemann et al. reported that epine-
phrine given at standard doses via a
tracheal tube during cardiac arrest and
cardiopulmonary resuscitation (CPR)
was of no benefit. (14) European
Resuscitation Council CPR guidelines
recommend epinephrine delivery via
tracheal tube only as the last resort.
(15) The onset and the peak pharma-
cological effect of the LMA-6 group
were slower and lower than in the TT
group, and cardiac arrest is likely to
further decrease drug effects. There-
fore, unless higher than six times the
tracheal dose is given, it is impractical
to administer epinephrine via the LMA
in resuscitation scenarios.
Trevisanuto et al. successfully treated
neonatal respiratory distress syndrome
by LMA-administered surfactant in
eight preterm infants. (12) The LMA
route avoided the potential risks of tra-
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LMA, laryngeal mask airway; TT, tra-
cheal tube.
Figure 3. Systolic arterial pressure
(SAP) changes following epinephrine
administration.
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LMA, laryngeal mask airway; TT, tra-
cheal tube.
Figure 4. Diastolic arterial pressure
(DAP) changes following epinephri-
ne administration.
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LMA, laryngeal mask airway; TT, tra-
cheal tube.
Figure 5. Mean arterial pressure
(MAP) changes following epinephri-
ne administration.
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LMA, laryngeal mask airway; TT, tra-
cheal tube.
Figure 6. Heart rate (HR) changes
following epinephrine administra-
tion.

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cheal intubation, such as upper airway
damage, infection, bradycardia and
potentially catastrophic tracheal mal-
positioning. For certain drugs where a
steady plateau effect instead of a high
peak level is desired, the LMA is still an
alternative route for drug delivery. How-
ever, given the smaller area of drug
absorption for the LMA route, doses
higher than those recommended for
tracheal administration are likely to be
required.
There were a number of limitations to
our study. First, the LMA fitted loosely
in the pig larynx and leakage of epine-
phrine solution may have occurred,
compromising interpretation of the
drug effect. In addition, there was a TT
in the trachea: although we deflated
the cuff to reduce occlusion, the TT
would have impeded dispersion of
epinephrine into the broncho-alveolar
area and may have led to an under-
estimate of the effects of LMA-admin-
istered epinephrine. Moreover, drug
delivery via different airway devices
involves different degrees of experi-
mental stress, which may have led
to variable changes of heart rate and
arterial pressure.
Conclusions
In comparison with standard tracheal
route, LMA administration of six times
the standard tracheal dose of epine-
phrine achieved statistically equivalent
hemodynamic changes. The effects
achieved via the tracheal route peaked
sooner but swiftly declined; those of
LMA route rose more slowly and were
maintained at a plateau. We could
not identify an optimal LMA-adminis-
tered epinephrine dose. Doses larger
than those recommended for trache-
al administration may be needed for
drugs given via the LMA.
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