CRITICAL CARE AND TRAUMA
SECTION EDITOR
JUKKA TAKALA
The Effects of Different Mouth-to-Mouth Ventilation
Tidal Volumes on Gas Exchange During Simulated
Rescue Breathing
Angelika Stallinger, MD*, Volker Wenzel, MD*, Stephan Oroszy, MD*, Viktoria D. Mayr,
Ahamed H. Idris, MD, Karl H. Lindner, MD*, and Christoph Hormann, MD*
*Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens-University, Innsbruck, Austria; and
Department of Emergency Medicine, University of Florida College of Medicine, Gainesville, Florida
The American Heart Association recommends tidal vol-
umes of 700 to 1000 mL during mouth-to-mouth ventila-
tion, but smaller tidal volumes of 500 mL may be of ad-
vantage to decrease the likelihood of stomach inflation.
Because mouth-to-mouth ventilation gas contains only
17% oxygen, but 4% carbon dioxide, it is unknown
whether 500-mL tidal volumes given during rescue
breathing may result in insufficient oxygenation and in-
adequate carbon dioxide elimination. In a university hos-
pital research laboratory, 20 fully conscious volunteer
health care professionals were randomly assigned to
breathe tidal volumes of 500 or 1000 mL of mouth-to-
mouth ventilation gas (17% oxygen, 4% carbon dioxide,
79% nitrogen), or room air control (21% oxygen, 79% ni-
trogen) for 5 min. Arterial blood gases were taken imme-
diately before, and after breathing 5 min of the experimen-
tal gas composition. When comparing 500 versus 1000 mL
of mouth-to-mouth ventilation tidal volumes with 500 mL
W
hen ventilating a tracheally unintubated pa-
tient, the distribution of gas between lungs
and stomach depends on the lower esopha-
geal sphincter pressure, respiratory mechanics [respi-
ratory system compliance and degree of airway ob-
struction (1)], and the technique of the rescuer
performing basic life support (inspiratory flow rate,
peak airway pressure, and tidal volume) (2). Stomach
inflation is a complex problem that may cause regur-
gitation, aspiration, pneumonia, and possibly, death
(3). Stomach inflation may also increase intragastric
This project was supported, in part, by the Austrain Science
Foundation Grant P14169-MED, Vienna, Austria, the Founders
Grant of the Society of Critical Care Medicine, Anaheim, CA, and
departmental funds.
Accepted for publication July 17, 2001.
Address correspondence to Dr. Angelika Stallinger, and reprint
requests to Dr. Karl H. Lindner, Leopold-Franzens-University,
Department of Anesthesiology and Critical Care Medicine, Anich-
strasse 35, 6020 Innsbruck, Austria. Address e-mail to Angelika.
Stallinger@uibk.ac.at.
2001 by the International Anesthesia Research Society
0003-2999/01
MD*,
of room air, 500 mL of mouth-to-mouth ventilation tidal
volume resulted in significantly (P 0.05) lower mean
sem arterial oxygen partial pressure (70 1 versus 85 2
versus 92 3 mm Hg, respectively), and lower oxygen
saturation (94 0.4 versus 97 0.2 versus 98 0.2%), but
increased arterial carbon dioxide partial pressure (46 1
versus 40 1 versus 39 1 mm Hg, respectively). Sixteen
of 20 volunteers had to be excluded from the experiment
with 500 mL of mouth-to-mouth ventilation gas after
about 3 min instead of after 5 minutes as planned because
of severe nervousness, sweating, and air hunger. We con-
clude that during simulated mouth-to-mouth ventilation,
only large (approximately 1000 mL), but not small (ap-
proximately 500 mL) tidal volumes were able to maintain
both sufficient oxygenation and adequate carbon dioxide
elimination.
(Anesth Analg 2001;93:12659)
pressure, push up the diaphragm, restrict lung move-
ments, and thereby decrease the respiratory system
compliance (4). Decreased respiratory system compli-
ance may force even more gas into the stomach,
thereby inducing a vicious respiratory cycle with each
tidal volume of increasing stomach inflation, and de-
creasing lung ventilation (5). A few studies showed
that by providing reasonable ventilation while avoid-
ing significant stomach inflation (6), a tidal volume of
500 mL instead of 800 1200 mL may be a good com-
promise when ventilating a tracheally unintubated
patient. Studies performed in both bench (7) and clin-
ical (8) settings during respiratory arrest and cardio-
pulmonary resuscitation (CPR) (9) have confirmed the
beneficial effects of small (approximately 500 mL/
approximately 7.5 mL/kg) instead of large (800 to
1200 mL/approximately 15 mL/kg) tidal volumes as
long as oxygen supplementation is used (Fio2 0.4).
Small tidal volumes of approximately 500 mL con-
taining room air (21% oxygen) were not sufficient to
Anesth Analg 2001;93:12659 1265
1266 CRITICAL CARE AND TRAUMA STALLINGER ET AL.
TIDAL VOLUMES AND RESCUE BREATHING
maintain adequate oxygenation and carbon dioxide
elimination in anesthetized, paralyzed, supine adults
(10), suggesting that mouth-to-mouth ventilation gas,
which contains only approximately 17% oxygen, but
approximately 4% carbon dioxide (11), may not be
safe and effective for basic life support ventilation. If
this were the case, large tidal volumes during mouth-
to-mouth ventilation would be needed, although the
risk of stomach ventilation would be increased. Ac-
cordingly, the purpose of the present study was to
assess the effects of small (approximately 500 mL)
versus large (approximately 1000 mL) tidal volumes
with 17% oxygen and 4% carbon dioxide on gas ex-
change during simulated mouth-to-mouth ventilation.
Our hypothesis was that there would be no difference
in study endpoints between groups.
Methods
The experimental protocol of this study was approved
by the IRB of the Leopold-Franzens University, Inns-
bruck, Austria. Health care professionals (physicians
and medical students) volunteered as participants in
this study, and provided written informed consent.
Before the actual experiment, the volunteers were al-
lowed to familiarize themselves with the experimental
setup consisting of an anesthesia machine, noseclip,
and arterial blood gas sampling kit. Namely, the
breathing circuit and pneumotachometer of this anes-
thesia machine (Fabius; Drager, Lubeck, Germany)
were explained in detail to ensure proper compliance
with the experimental protocol. The nitrous oxide out-
let of this anesthesia machine was connected to a
custom-made bottle of gas containing mouth-to-
mouth ventilation gas (17% oxygen, 4% carbon diox-
ide, 79% nitrogen) (11); room air connections were not
replaced. Because this anesthesia machine is fresh-gas
independent, the simulated mouth-to-mouth ventila-
tion gas could be readily adjusted with the regular
oxygen controls of fresh gas flow. Thus, volunteers
could breath through a mouthpiece connected via an
airway filter with the regular ventilator tubing using
either simulated mouth-to-mouth ventilation gas or
room air to be set randomly by the investigators. We
removed the absorption chalk of the anesthesia ma-
chine to ensure that exhaled carbon dioxide was not
eliminated out of the breathing circuit. Furthermore,
fresh gas flow was adjusted at 12 L/min, which is at or
above the entitled minute ventilation of 6 L/min and
12 L/min, respectively.
The volunteers were placed on an operation table in
the supine position, and the experimental setup and
protocol were explained in detail. Namely, the venti-
lation rate was prescribed at 12/min, tidal volume at
500 or 1000 mL, and a noseclip was used to prevent
inhaling room air through the nose during the exper-
iment, and to ensure that all expired air was being
ANESTH ANALG
2001;93:12659
measured. A subsequent test run ensured that all vol-
unteers were willing and able to breathe tidal volumes
and had respiration rates as prescribed by the exper-
imental protocol. The volunteers were then random-
ized to breathe for 5 min either 500 mL of room air
(21% oxygen, 79% nitrogen), or 500 mL or 1000 mL of
simulated mouth-to-mouth ventilation gas (17% oxy-
gen, 4% carbon dioxide, 79% nitrogen), respectively.
Both the volunteers and the data recording investiga-
tor were blinded during the experiment to the venti-
lation gas being used. During the experiment, one
investigator monitored and coached the volunteers to
remain with their breathing pattern within the exper-
imental protocol, while another investigator recorded
ventilation variables. While breathing the experimen-
tal tidal volume of the gas mixtures, exhaled tidal
volume, end-tidal carbon dioxide, and respiratory rate
were measured with the pneumotachometer of the
anesthesia machine; blood pressure, oxygen satura-
tion, and heart rate were measured with a patient
monitor (AS 3 Compact; Datex Ohmeda, Helsinki,
Finland). Arterial blood gas samples were taken after
5 min of every ventilation attempt, respectively, before
the experiment was terminated and were analyzed
with a blood gas analyzer (Rapidlab 860; Chiron Di-
agnostics, East Walpol, MA). If oxygen saturation de-
creased below 90%, the experiment was concluded
immediately, and 100% oxygen was given. Also, each
volunteer was allowed to stop the experiment by
themselves at any time point if adverse effects, such as
severe nausea or sweating, air hunger, or dizziness,
were felt; management was then performed as above.
All values were expressed as mean sem. Compar-
isons were made with one-factor and repeated mea-
sure analysis of variance, and with Newman-Keuls
multiple comparison procedure. Was set at 0.05 for
statistical significance.
Results
Twenty volunteer participants (7 women [35%], 13
men [65%]; age range 22 to 38 yr; none had underlying
cardiac or respiratory disease) were enrolled in this
study. Comparing 500 mL versus 1000 mL of mouth-
to-mouth ventilation gas versus 500 mL of room air
tidal volumes, there was a significant (P 0.05) de-
crease of mean sem oxygen saturation and arterial
oxygen partial pressure values, and significant in-
crease of arterial carbon dioxide partial pressure when
breathing 500 mL of mouth-to-mouth ventilation tidal
volume (Table 1, Fig. 1). In the 500-mL mouth-to-
mouth ventilation gas group, 16 of 20 volunteers (80%)
discontinued the trial after about 3 min because of
severe nervousness, dizziness, sweating, or air hunger
instead of after 5 min as planned. In contrast, 20 of 20
ANESTH ANALG CRITICAL CARE AND TRAUMA STALLINGER ET AL. 1267
2001;93:12659 TIDAL VOLUMES AND RESCUE BREATHING

Table 1. Effects of Different Tidal Volumes During Simulated Rescue Breathing with Room Air and Mouth-to-Mouth
Ventilation Gas on Arterial Blood Gas Variables and Respiratory Variables
Mouth-to-mouth ventilation
Room air (17% O2, 4% CO2, 79% N2)
(21% O2, 79% N2)
Tidal volume 500 mL 1000 mL 500 mL
Sao2 (%) 98 0.2 97 0.2* 94 0.4
Pao2 (mm Hg) 92 3 85 2* 71 2
Pao2 (kPa) 12.3 0.4 11.3 0.3* 9.5 0.3
Paco2 (mm Hg) 39 1 41 1* 46 1
Paco2 (kPa) 5.2 0.1 5.5 0.1* 6.1 0.1
pH 7.43 0.01 7.39 0.01* 7.37 0.01
Exhaled VE (L/min) 6.8 1 11.6 1.6 6.7 1
Exhaled VT (mL) 567 83 967 133 558 83
All values are given in mean standard error of the mean.
Sao2 arterial oxygen saturation, Pao2 arterial oxygen partial pressure, Paco2 arterial carbon dioxide partial pressure, VE minute ventilation, VT
tidal volume.
* P 0.05 500 mL of room air versus 1000 mL of mouth-to-mouth ventilation; P 0.05 500 mL of room air versus 500 mL of mouth-to-mouth ventilation;
P 0.05 1000 mL versus 500 mL of mouth-to-mouth ventilation.

and finally, termination of experimental gas breathing

Figure 1. Pao2 and Paco2 while breathing 500 mL of room air versus
500 or 1000 mL of mouth-to-mouth ventilation gas.
volunteers in both the 1000-mL mouth-to-mouth ven-
tilation and 500-mL room air groups successfully com-
pleted the 5-min study period, respectively. When
compared with 500 mL of room air, both 500 and
1000 mL of mouth-to-mouth ventilation tidal volumes
had significantly higher arterial carbon dioxide partial
pressure and end-tidal carbon dioxide, and signifi-
cantly lower oxygen saturation, arterial oxygen partial
pressure, and pH values (Table 1). No differences
were observed in blood pressure or heart rate
throughout the experiment.
Discussion
In this model of simulated mouth-to-mouth ventila-
tion (11), tidal volumes of 1000 mL, but not 500 mL,
resulted in adequate oxygenation and carbon dioxide
elimination when compared with a tidal volume of
500 mL containing room air. Moreover, breathing
500 mL of mouth-to-mouth ventilation gas resulted in
severe air hunger, sweating, tachycardia, nervousness,
in 16 of 20 volunteers after about 3 minutes, instead of
after 5 minutes as planned. Interestingly, no correla-
tion could be found between tidal volume require-
ments and either body weight, or body mass index.
Measuring respiratory variables such as tidal vol-
umes or even gas mixtures in a clinical investigation of
basic life support ventilation is extremely difficult.
Also, performing mouth-to-mouth ventilation reflects
a hypoxic and hypercarbic gas mixture; this is the only
circumstance in medicine of continuously administer-
ing a ventilation gas of which each component may
result in life-threatening cardiocirculatory collapse
(12). Accordingly, this experiment was not deemed
ethical to perform in fully anesthetized patients by the
IRB of our institution. Although the present data were
obtained in fully conscious healthy, spontaneously
breathing supine adults, the question arises whether
information derived from this experiment can be ex-
trapolated to the cardiopulmonary arrest setting as
well. During low rates of blood flow similar to those
rates found in shock and CPR, alterations in minute
ventilation significantly influenced end-tidal carbon
dioxide and both arterial and mixed venous satura-
tion, pH, and carbon dioxide (13). In fact, when using
an Fio2 of 0.4, at a flow of 12% of baseline cardiac
output, arterial oxygen partial pressure was main-
tained at 96 mm Hg despite the fact that ventila-
tion was at 50% of the control minute ventilation.
Although that study (13) suggests that ventilation-
perfusion conditions with normal cardiac output ver-
sus normal minute ventilation compared with
decreased cardiac output versus decreased minute
ventilation may be actually comparable, the mecha-
nisms involved, such as changes in cardiac output,
and/or increases in pulmonary shunt attributed to
hypercapnia, are most likely more complex (14).
1268 CRITICAL CARE AND TRAUMA STALLINGER ET AL.
TIDAL VOLUMES AND RESCUE BREATHING
Systemic oxygen use during CPR becomes flow de-
pendent; thus, if systemic perfusion is approximately
15% of normal, there may be less need for supplemen-
tal oxygen. However, marked increases in the pulmo-
nary venous admixture may require higher inspired
oxygen tension to overcome increases in the alveolar-
arterial oxygen gradient (15). Accordingly, it is un-
known whether this may indicate that 500-mL tidal
volumes of mouth-to-mouth ventilation gas may be
sufficient for oxygenation and carbon dioxide elimi-
nation during low-flow states such as during CPR,
and thus further investigation may be warranted and
our results may only apply to a beating heart.
The clinical importance of our results may be more
important than anticipated. For example, whereas our
healthy volunteers were enrolled into the study with
normal oxygenation and carbon dioxide levels, a car-
diac arrest victim is usually fully deoxygenated, indi-
cating that the oxygen binding effects of hemoglobin
are in the steep part of the rightward-shifted curve
because of hypercapnia. Accordingly, an approxi-
mately 10% change in oxygen saturation at approxi-
mately 97%, such as in our volunteers, may indicate
significantly less changes in oxygen partial pressure
than at approximately 50% oxygen saturation in car-
diac arrest patients. Also, carbon dioxide increases
cardiac afterload and pulmonary vascular resistance,
both of which are not beneficial during cardiac
resuscitation.
During recent conferences intended to update the
CPR guidelines, an effort was made to simplify the
recommendations as much as possible (16). For exam-
ple, it would be highly desirable to recommend a
single tidal volume regardless of the ventilation de-
vice and/or technique being used. Several clinical and
laboratory studies confirmed that small (approxi-
mately 500 mL/7.5 mL/kg) instead of large (approx-
imately 800 1200 mL/15 mL/kg) tidal volumes with
an Fio2 0.4 during basic life support ventilation pro-
vide reasonable oxygenation and carbon dioxide elim-
ination while significantly decreasing the risk of stom-
ach ventilation (6 9). The present study adds
important knowledge to the aforementioned guide-
linessuggesting not to recommend 500-mL, but
1000-mL tidal volumes during mouth-to-mouth ven-
tilation because of the apparent risk of further deteri-
orating the degree of both hypoxia and hypercarbia in
an apneic patient. Accordingly, although the trade-off
to achieve less stomach inflation with 500-mL tidal
volumes with oxygen is readily available during bag-
valve-mask ventilation, this strategy with mouth-to-
mouth ventilation gas and 500-mL tidal volumes
would be obtained, according to our data, most likely
with hypoxia and hypercarbia. Our observation is in
full agreement with the pioneer work of Safar (17)
ANESTH ANALG
2001;93:12659
who demonstrated excellent efficacy of mouth-to-
mouth ventilation in anesthetized and paralyzed vol-
unteer adults, but showed that tidal volumes were
consistently larger than 1000 mL.
The mechanism of gas exchange in our study may
be partially explained by extrapolating experience of
apneic ventilation. For example, during apneic venti-
lation for brain-death diagnosis, the patients lungs are
filled with 100% oxygen, while the endotracheal tube
is subsequently disconnected from the ventilator, but
connected to an oxygen reservoir. Thus, if a patient
with brain death does not breath, arterial carbon di-
oxide usually increases at a rate of approximately 2.5
to 4 mm Hg/minute (18). This is comparable to our
volunteers, in whom breathing mouth-to-mouth ven-
tilation gas caused an increase of arterial carbon diox-
ide of approximately 2 mm Hg/minute. Interestingly,
these two maneuvers with apnea and endogenous
carbon dioxide production versus spontaneous venti-
lation with endogenous carbon dioxide production
and additional exogenous carbon dioxide inhalation
resulted in comparable arterial carbon dioxide. Be-
cause arterial oxygen levels of approximately 70 mm
Hg in our volunteers were nonhypoxic, an arterial
carbon dioxide level of approximately 46 mm Hg may
suggest that increased carbon dioxide levels induced
an air hunger, nervousness, sweating, tachycardia,
and subsequent discontinuation of the experiment by
most volunteers. However, this would be in disagree-
ment with an experiment in which conscious volun-
teers breathing 100% oxygen with an approximate
arterial oxygen level of 450 mm Hg were able to hold
their breath for approximately 14 minutes, while eas-
ily tolerating arterial carbon dioxide levels of approx-
imately 91 mm Hg (19). Accordingly, if arterial oxygen
is not 400 mm Hg as during apneic ventilation, but
only approximately 70 mm Hg, and further decreasing
as in our volunteers, increasing arterial carbon dioxide
levels may not be well tolerated, which may be the
most likely explanation of our observation. This is in
full agreement with a historic experiment performed
in 1908 demonstrating excellent efficacy of apneic ven-
tilation for 1 to 2 hours in dogs with 100% oxygen, but
not with room air (20).
Some limitations of the present model need to be
noted. First, our fully conscious volunteers were spon-
taneously breathing, which does not simulate positive
pressure ventilation such as during mouth-to-mouth
ventilation. Thus, although we did not measure pul-
monary ventilation/perfusion ratios, our volunteers
most likely had less dead space ventilation, and a
better ventilation/perfusion distribution than a pa-
tient receiving mouth-to-mouth ventilation. Accord-
ingly, had we performed the present study in anesthe-
tized patients, the differences would have likely been
even greater. Interestingly, the 4 of 20 volunteers who
ANESTH ANALG
2001;93:12659
were able to breathe the small mouth-to-mouth ven-
tilation tidal volumes for 5 minutes were either smok-
ers or those who reported episodes of sleep apnea,
suggesting a better tolerance for increased levels of
arterial carbon dioxide. Finally, our volunteers had
normal cardiac output; accordingly, our results may
have been different in patients with severely de-
creased cardiac output such as during CPR or shock.
In conclusion, during simulated mouth-to-mouth
ventilation, only large (approximately 1000 mL), but
not small (approximately 500 mL) tidal volumes were
able to maintain both sufficient oxygenation and ade-
quate carbon dioxide elimination.
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