Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 2330–2338

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Journal of Cardiothoracic and Vascular Anesthesia

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Review Article

Hypoxia During One-Lung

Ventilation—A Review and Update
Javier H. Campos, MDn,1, Andrew Feider, MD†
n
Department of Anesthesia, University of Iowa Health Care, Iowa City, IA
†
Division of Cardiothoracic Anesthesia, Department of Anesthesia, University of Iowa Health Care,
Iowa City, IA

Keywords: hypoxia; one-lung ventilation; cerebral desaturation; thoracic surgery; extracorporeal membrane oxygenation

ONE-LUNG VENTILATION (OLV) often is required to
facilitate surgical exposure in the thoracic surgical patient with
the use of a double-lumen endotracheal tubes (DLT) or a
bronchial blocker.1 During OLV, an obligatory intrapulmonary
shunt may produce hypoxemia because of collapse of the
nondependent lung and increased atelectatic areas in the
dependent lung.2 This hypoxemic event will activate hypoxic
pulmonary vasoconstriction (HPV), which leads to contraction
of vascular smooth muscle in the pulmonary circulation in
response to a low regional partial pressure of alveolar oxygen,
thus decreasing the shunt by redirecting pulmonary blood flow
to the well-oxygenated and dependent lung.3
This review focuses on the factors that predict hypoxemia
during OLV: physiology of OLV, the response to hypoxemia
in healthy and anesthetized subjects, ventilatory modalities to
improve oxygenation and treat hypoxemia, the cerebral
desaturation episodes during OLV, and the use of extracorpor-
eal membrane oxygenation (ECMO).
Hypoxemia during thoracic surgery is defined as a decrease
in oxygen saturation (SaPO2) measured by pulse oximetry of
less than 85% to 90%; usually such episodes last a few minutes
during OLV. It also may be defined as an arterial oxygen
tension (PaO2) of less than 60 mmHg when the patient is being
ventilated at an inspired oxygen fraction (FIO2) of 1.0%.4
The incidence of hypoxemia during OLV is currently less
than 4% in part because of the use of flexible fiberoptic
1 reported a difference of 110 mmHg (280 v 170 mmHg)
Address reprint requests to Prof. Javier H. Campos, Department of
Anesthesia, University of Iowa Health Care, 200 Hawkins Drive, Iowa City,
IA 52242.
E-mail address: javier-campos@uiowa.edu (J.H. Campos).
bronchoscopy to achieve optimal position of lung isolation
devices. It is also attributable to the introduction of newer,
volatile anesthetics that cause less inhibition of HPV in a dose-
dependent manner and less venous admixture during OLV.5–7
Individuals with coexisting cardiovascular, cerebrovascular,
or pulmonary disease are undoubtedly at greater risk for
circulatory compromise caused by hypoxemia.8 Oxygen deliv-
ery to the myocardium may already be marginal in patients
with coronary artery disease. Decreases in the arterial oxygen
content will lead to additional myocardial stress. The decrease
in oxygen delivery can result in depressed myocardial func-
tion, and this can be seen during hypoxia and OLV. The
sympathetic nervous system is activated by systemic hypoxia9
resulting in increases in heart rate, pulmonary vascular
resistance, and systemic vascular resistance.
Factors That May Predict Patients Who Will Develop
Hypoxemia During OLV
A number of factors may predict which patients are most
likely to develop hypoxemia during OLV.10 Previous studies
have shown that significant predictors of decreased intraopera-
tive PaO2 are the following:

Side of the surgery: right-sided surgery (right lung collapse)
and left-sided ventilation.11 In one study12 the authors
in PaO2 when right and left lungs were ventilated with a
FIO2 of 1.0% during OLV. Because the right lung is
approximately 10% larger than the left lung, there is better

http://dx.doi.org/10.1053/j.jvca.2017.12.026
1053-0770/& 2018 Elsevier Inc. All rights reserved.
 J.H. Campos, A. Feider / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 2330–2338
oxygenation during left thoracotomy than during right
thoracotomy.

Pulmonary function test (the percentage of forced expira-
tory volume in one second [FEV1]): An inverse correlation
exists between the FEV1 and the PaO2. Patients with
chronic obstructive pulmonary disease (COPD) develop
auto positive end-expiratory pressure (PEEP). The corre-
sponding air trapping, which occurs at the end of the
expiration, appears to reduce atelectasis and preserve
oxygenation. The air trapped in the nonventilated lung also
tends to delay the onset of desaturation and hypoxemia.13

Low intraoperative PaO2, decreased values of PaO2 intrao-
peratively during two-lung ventilation in a lateral decubitus
position while the patient is receiving FIO2 1.0%.

Perfusion of the lungs: Lung perfusion studies12 have
demonstrated that the nonventilated and collapsed lung is
more impaired in patients presenting for pneumectomy or
lobectomy than in patients who present with solitary lung
nodes and undergo video-assisted thoracoscopic surgery. A
possible explanation is that large central tumors (ie, those
requiring pneumonectomy) have less perfusion to the
nondependent lung and more perfusion to the dependent
and ventilated lung; therefore, oxygenation is better main-
tained. In contrast, patients with small tumors (ie, solitary
nodes) have more perfusion to the nondependent lung
during OLV; these patients have a tendency to experience
transient episodes of hypoxemia intraoperatively.

Body mass index (BMI) plays an important role because it
affects ventilation and oxygenation. In one study14 patients
with a BMI greater than 30 kg/m2 who required OLV
during thoracic surgery developed more episodes of intrao-
perative and postoperative hypoxemia compared with non-
obese patients.

Previous lobectomy on the contralateral side: Patients with
previous lobectomy requiring a subsequent contralateral
lobectomy are known to develop hypoxemia during total
lung collapse if up to 25% of the lung function has been
affected by the previous lobectomy.15

Position of the patient during surgery: Gravity is a major
determinant of shunt fraction and perfusion.16 The vast
majority of thoracic procedures are performed with
the patient in a lateral position with few exemptions
(ie, bilateral lung transplant done in supine position).
Previous studies17 have shown that the PaO2 was signifi-
cantly higher during OLV in patients operated in the lateral
position compared with the supine position. During OLV in
a lateral decubitus position, gravity augments the redis-
tribution of perfusion to the ventilated or dependent lung,
improving and maintaining ventilation perfusion (V/Q)
matching. Table 1 lists the factors that increase the risk of
hypoxemia during OLV.
Physiology and Hypoxemia During OLV
When OLV is initiated, the nondependent lung becomes
atelectatic. Alveolar O2 decreases and hypoxemia sets in.
During OLV, a shunt-like effect may arise from continued
2331
Table 1
Factors That Potentially Increase the Risk of Hypoxemia During OLV

Right-sided thoracic surgery (right-lung collapse) and left-sided ventilation

High percentage of ventilation or perfusion to the operative lung on
preoperative V/Q scan

Normal preoperative spirometry (FEV1 or FVC)

Low PaO2 during two-lung ventilation in the lateral decubitus position

Morbidly obese patient BMI 430 kg/m2 during OLV

Previous lobectomy and contralateral lung collapse surgery
Abbreviations: BMI, body mass index; FEV1, forced expiratory volume in
1 second; FVC, forced vital capacity; OLV, one-lung ventilation; PaO2,
arterial oxygen tension.
perfusion of the nonventilated lung and inadequate expansion
of the ventilated or dependent lung while the patient is
receiving a high inspired O2 fraction (FIO2 ¼ 1.0%) or from
hemodynamic changes related to the anesthetic management
and position during thoracic surgery. Hypoxemia during OLV
is caused by venous admixture through shunts and areas of
low V/Q gas exchanging units.18 On the basis of animal
studies, the maximal HPV response during OLV decreases
blood flow to the nondependent lung by 50%.19 During the
course of OLV, the estimated venous admixture is usually
20% to 25% of total cardiac output.3 Therefore, patients who
are well oxygenated during two-lung ventilation will have a
PaO2 of approximately 350 to 400 mmHg and when converted
to OLV will have a PaO2 of approximately 150 to 200 mmHg
while receiving FIO2 1.0%.
With a patient in a lateral decubitus position when both
lungs are being ventilated, the proportion of the pulmonary
blood flow is distributed as follows: The dependent (non-
operative) lung receives approximately 60% of the pulmonary
blood flow (more perfusion), whereas the nondependent lung
(operative lung) receives 40% of the total pulmonary blood
flow. When OLV is instituted, the nondependent lung becomes
atelectatic. Because the alveolar O2 decreases, there is a
response to HPV in which increased pulmonary vascular
resistances diverts blood flow toward the dependent lung.
This is a biphasic reaction with an early response that usually
starts within seconds and reaches a peak between 20 to 30
minutes during OLV, followed by a delayed response during
the next 2 hours when the maximal vasoconstrictor response is
achieved. Throughout this time the PaO2 will gradually
increase. However, during repeated episodes of OLV and
re-expansion of the nondependent lung, the HPV reflex
appears to be augmented. During these subsequent periods
of OLV, oxygenation is thought to improve because the
blood flow in the reinflated lung has not returned to baseline
before the subsequent hypoxic challenge. In addition, OLV
induces a proinflammatory response, including cytokine
release and leukocyte recruitment on the ventilated lung.20
Also, a proinflammatory response has been reported on the
atelectatic and nonventilated lung.21 This proinflammatory
response has contributed to an increase of postoperative
pulmonary complications. Figure 1 displays the physiology
of OLV.
2332 J.H. Campos, A. Feider / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 2330–2338
Fig 1. (A) The redistribution of pulmonary blood flow in the lateral decubitus
position while both lungs are being ventilated. (B) The atelectatic nonventi-
lated lung along with the percentage of HPV response. In addition, the
ventilated lung presents some atelectatic areas at the base of the lung during
general anesthesia. HPV, hypoxic pulmonary vasoconstriction; PBF, pulmon-
ary blood flow; PVR, pulmonary vascular resistance; Qs/Qt, shunt fraction.
(Reproduced with permission from Campos.2
HPV is an auto regulatory reflex mechanism that reduces
pulmonary blood flow through the nondependent lung by 40%
to 50% and diverts part of the blood flow to the dependent
lung.Factors that will modify the HPV response during OLV
include hypotension, hypocapnia, hypothermia, the presence
and severity of COPD, and to minimal degree the use of
vasodilators, and vasoconstrictors, and anesthetic agents.
The Response to Hypoxia in Healthy Subjects and Levels of
Tolerance: It’s Feasible to Extrapolate This Concept to the
Anesthetized Patient Under OLV
In healthy individuals with normal cardiopulmonary func-
tion, hypoxia itself can be tolerated. Studies on hypoxia8 in
healthy subjects have reported that, in a 1-hour study, subjects
have been exposed to a total of 15 minutes of hypoxia at
SaPO2 o80% in an awake state.
To define hypoxia in healthy subjects, one must first define
what is an acceptable PaO2 level and/or SaPO2 value. An
interesting report on arterial blood gases and oxygen content in
climbers on Mount Everest showed that of 9 subjects ranging
in age from 22 to 48 years, 4 of them reached the summit
(altitude 8,848 m) without oxygen. The lowest arterial PaO2 in
1 of the subjects was 19 mmHg with a PaCO2 of 15.7 mmHg,
and the subject’s hemoglobin concentration was 18.7 g/dL.22
In a review article, Bickler et al8 stated in their conclusion that
“brief and profound hypoxia (SaPO2 50 70%) for 10  30
minutes in healthy humans is well tolerated and not
accompanied by systemic acidosis or circulatory impairment.”
Thus, it is not uncommon to observe transient episodes of
desaturation (SaPO2 o 90%) during OLV in anesthetized
healthy subjects. It would be difficult to do a study of a lower
threshold in this patient population; however, combining the
studies by Bickler et al8 and Grocott et al,22 the threshold for
lower saturation SaPO2 o 90% should be considered assum-
ing that subjects have no comorbid disease and their hemo-
globin concentration is 4 16 g/dL. Perhaps a range of SaPO2
between 85% and 90% will be tolerated in this patient
population under anesthesia during OLV. A lower threshold
for SaPO2 requires further investigation.
Effects of Cerebral Desaturation During OLV
The effects of hypoxia during OLV can be detrimental in
patients with previous history of cerebrovascular disease.
Profound, hypoxia (ie, o 65% SaPO2) may produce transient
changes in neurocognitive function. Acute profound hypoxia
exposure in laboratory settings produces transient cognitive
effects similar to reversible changes during altitude exposure
and the persistent changes seen after traumatic injury. Recently
there have been reports on the measurement of cerebral
oxygen saturation (SctO2) in the thoracic surgical patient.23,24
There are 2 monitors that measure SctO2. These devices have
been used in patients undergoing OLV with mixed results. In a
study involving thoracic surgical patients undergoing OLV,25
a cerebral oximetry monitor was used in 50 patients and
reported a decrease in SctO2 in 14 patients (28%) and a
decline in postoperative cognitive dysfunction evaluated by
mini-mental state examination. Another study24 involving
40 patients undergoing OLV, SctO2 monitor detected cerebral
desaturation in 28 patients, and the minimum SctO2 during
OLV was lower than the baseline value. Also, the percentage
change from baseline SctO2 was significantly negatively
correlated with preoperative respiratory function. One study23
showed that an absolute value of SctO2 of 80% was recorded
while patients were awake. During OLV the value decreased
to an average of 63% and after extubation rose to 71%. What
was interesting in this study was the lack of correlation with
SpO2 and PaO2 (no systemic hypoxic events).
Another study26 showed that cerebral oxygen desaturation
was decreased in all 18 patients studied during OLV, and no
correlation was found between cerebral desaturation and
cardiac output or other hemodynamic variables. Overall,
although measuring SctO2 value is interesting technology,
further studies are needed to demonstrate the changes in SctO2
during OLV and their association with hypoxemic events
measured by SaPO2. The scientific evidence at the present time
has limited value.
Management of Hypoxia During OLV
As previously reported,2 if hypoxemia occurs during OLV,
any nonurgent surgical procedure must be stopped, FIO2
should be increased to 1.0%, and two-lung ventilation
restored. After hypoxemia is treated and corrected then OLV
 J.H. Campos, A. Feider / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 2330–2338
Fig 2. Strategies used during the management of hypoxia and one-lung
ventilation (OLV). FIO2, inspired oxygen fraction; PaO2, arterial oxygen
tension; SaPO2, oxygen saturation.
is re-established (refer to Fig 2). Because malposition of the
lung isolation device is a common cause of hypoxemia,
the lung isolation device should be reassessed to ensure that
the DLT or bronchial blocker is in an optimal position. In
addition, all ventilated bronchial and segmental bronchi should
be inspected with the flexible fiberoptic bronchoscope to
ensure that the patient’s airway is clear of secretions.27
Maintaining adequate oxygenation during OLV requires a
high inspired oxygen concentration (FIO2 1.0%), however,
keeping a high FIO2 after the hypoxemic event has been
corrected may potentially cause an increased inflammatory
response and lung injury. An animal study (with rabbits)28
studying different concentrations of FIO2 during OLV (FIO2
0.6% v 1.0%) showed that the animals that received FIO2 0.6%
during OLV had less inflammatory response and less lung
injury; however, 3 of 10 animals developed hypoxemia
although a FIO2 of 0.6% provides adequate oxygenation in
the vast majority of the animals studied. Extrapolating the data
to humans, it appears that if a lower FIO2 (ie, 0.6%) can
maintain oxygenation during OLV then it is possible that
inflammatory response and less lung edema, thickening of the
alveolar wall, and lower acute injury will occur compared with
higher FIO2 1.0%. Further studies are needed to validate these
findings in the clinical setting.
Alveolar Recruitment Maneuvers During OLV
Lung recruitment is a ventilator maneuver aimed at rever-
sing atelectasis by means of brief, controlled increases in
airway pressure with expansion of the lungs. Clinical studies
involving thoracic surgical patients undergoing OLV have
2333
shown that applying alveolar recruitment maneuvers before
OLV or in the minute thereafter reduce atelectasis, improve
arterial oxygenation, and decreases pulmonary shunt and dead
space with adequate levels of PEEP. One study29 showed that
arterial oxygenation could be improved through recruitment of
both lungs before instituting OLV by giving 10 consecutive
breaths at a plateau pressure of 40 and incremental levels of
5 to 10 to a maximum of 20 cmH2O PEEP. Moreover, another
report30 showed that during OLV in the lateral decubitus
position, the application of a recruitment maneuver in the
dependent lung for 1 minute followed by continuous applica-
tion of PEEP 5 cmH2O effects improvement in arterial
oxygenation and respiratory mechanics. Another interesting
study31 demonstrated that the application of individualized
PEEP via a PEEP decrement trial resulted in an optimal static
compliance curve and also led to improved oxygenation,
ventilation, and lung mechanics compared with standard PEEP
on the dependent lung. In this study, the individualized PEEP
values in the study group were higher (an average of 10 7
2 cmH2O) compared with standard PEEP (of 5 cmH2O). The
advantage of using alveolar recruitment maneuvers prior to or
during OLV is the potential to eliminate the need for additional
therapeutic interventions such as continuous positive airway
pressure (CPAP). Table 2 displays the benefits of alveolar
recruitment maneuvers and individualized PEEP to improve
oxygenation and lung mechanics during OLV.
CPAP has been used to treat hypoxemia during OLV.32
CPAP is applied to the nondependent lung and improves
oxygenation by passive mechanisms (uptake of oxygen by the
alveoli with continuous oxygen administration). It is recom-
mended to start with 5 cmH2O CPAP. Another strategy to
maintain or improve oxygenation during hypoxemia and OLV
is the use of PEEP to the dependent lung. This is beneficial
because it restores functional residual capacity close to normal
values. This ventilatory maneuver will prevent atelectasis
when its value is titrated along the static compliance curve
of the flow/volume loop. The application of PEEP is related to
patient lung mechanics.33
The Role of Tidal Volume During OLV
Mechanical ventilation during thoracic surgery can lead to
clinically significant ventilator-induced lung injury. Large tidal
volumes (Vt) 4 8 mL/kg during OLV has been reported to
increase inflammatory response, injury to the lungs for
excessive ventilation, and increase postoperative pulmonary
complications. An alternative method to prevent or reduce
lung injury is to use low Vt (4-6 mL/kg) predicted body weight
(PBW) during OLV in order to reduce airway pressures. A
recent meta-analysis34 of randomized trials on low versus high
Vt during OLV in patients undergoing thoracic surgery
reported that use of low Vt was associated with preserved
gas exchange after OLV, a lower incidence of pulmonary
infiltration, and acute respiratory distress syndrome. However,
the incidence of postoperative pulmonary complications and
hospital length of stay were similar (high versus low Vt). It
appears that the use of low Vt during OLV is beneficial in
2334 J.H. Campos, A. Feider / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 2330–2338
Table 2
Benefits of Alveolar Recruitment Maneuvers and the Individualized PEEP to Improve Oxygenation and Lung Mechanics During OLV
Author No. Patients
Unzueta et al29 n ¼ 40
n ¼ 20 control group
(6 mL/kg Vt)
n ¼ 20 study group (ARS)
Cinnella et al30 n ¼ 13
Ferrando et al31 n ¼ 30
n ¼ 15 control group (5 cmH2O PEEP to
the dependent lung after ARS)
n ¼ 15 individual PEEP along with decrement
PEEP (average 10 7 2 cmH2O PEEP) to the
dependent lung after ARS
Abbreviations: ARS, alveolar recruitment strategies; OLV, one-lung ventilation; PEEP, positive end-expiratory pressure; Vt, tidal volume.
order to preserve oxygenation and decrease the injury to the
lung. The use of Vt of 4 to 6 mL/kg with 5 cmH2O while
trying to maintain a driving pressure o 25 cmH2O seems to be
reasonable initial ventilation parameters during OLV, and
adjustments can be made according to clinical condition.35
Further prospective, randomized studies are needed to demon-
strate the benefits of low Vt during OLV.
A different alternative to provide low Vt and maintain low
peak airway pressure is with the use of pressure-controlled
ventilation (PCV) during OLV. A study36 included patients
undergoing video thoracoscopic-assisted lobectomy to deter-
mine the benefits of PCV versus volume-controlled ventilation
(VCV). Two groups of patients were studied: 1 group received
PCV with low Vt (6 mL/kg PBW) and 5 cmH2O of PEEP
during OLV, and the other group received VCV on the
ventilated lung during OLV with the same Vt. The study
showed that the PCV mode was superior to VCV in main-
taining low peak airway pressure during OLV but no clinical
difference regarding intra- or postoperative oxygenation index;
also, the postoperative pulmonary complications were no
different in the groups studied. The advantages of PCV during
OLV include lower airway pressures, lower intrapulmonary
shunt leading to a reduced risk of ventilator induced lung
injury, and improvement on oxygenation. A meta-analysis37 of
6 randomized, controlled trials comparing PCV with VCV
during OLV reported that the PaO2/FIO2 ratio in the PCV
groups was higher than in the VCV groups. Also, it was
reported that the peak inspiratory pressure was significantly
lower in the PCV groups; however, no clinical difference was
found in PaCO2 or mean airway pressure. Overall this meta-
analysis showed that with PCV, peak inspiratory pressure was
significantly lower and improved on oxygenation; however,
the authors had no definitive recommendation. In contrast,
another meta-analysis38 comparing a protective ventilation
with low Vt (6 mL/kg PBW) versus conventional ventilation
during OLV, versus another comparative group with PCV
versus VCV, reported that protective ventilation with low Vt
was associated with reduced incidence of postoperative
End Point Outcome
Effects on oxygenation
PaO2 after 20 min of OLV

Alveolar recruitment (PEEP 5-20
Control group 182 7 79 mmHg
cmH2O for 10 breaths before and
Study group 251 7 69 mmHg
after OLV)
Effects on oxygenation during OLV After 1 min of ARS

ARS for 1 minute on the dependant
PaO2 pre 235 7 113 mmHg
lung plus 5 cmH2O PEEP
PaO2 post 351 7 120 mmHg
Effects on oxygenation and lung After OLV, arterial oxygenation
mechanics during OLV was higher in the study group

Control group 231 mmHg

Study group 306 mmHg
Static compliance increased in the study group
after ARS and PEEP adjustment
pulmonary complications compared with conventional ventila-
tion; however, PCV and VCV had similar results on the
incidence of pulmonary complications. Combining all these
studies, this topic remains controversial regarding the best
mode of ventilation during OLV.
Different Ventilatory Modalities to Preserve or Increase
Oxygenation During OLV
A different mode of ventilation to maintain or improve
oxygenation has been reported with the ventilation of the
operative lung via another ventilator connected to a limb of a
DLT connector of the nondependent and operative lung. One
study39 showed that the use of ipsilateral low-Vt high-
frequency ventilation with 1 to 2 mL/kg and a high frequency
of respiratory rate of 40 breaths/min showed that the PaO2/
FIO2 ratio was higher compared with another group of patients
who had conventional ventilation plus PEEP on the dependent
and ventilated lung. Also in this study, lung tissue was
biopsied during the surgery, and the group that received
conventional ventilation had more interstitial edema, alveolar
edema, and neutrophil infiltration compared with the ipsilateral
ventilation group.
Another similar study reported40 that a brief period of
intermittent positive pressure ventilation to the nondependent
lung with a fixed Vt of 70 mL and respiratory rate of 6/min is
effective in improving PaO2 and SaPO2 during OLV without
interfering with the surgery. In this study, the nondependent
(operative) lung was ventilated with PCV for 15 minutes after
initiation of OLV via an additional ventilator to ventilate the
operative lung. Although the results are promising, having to
set up an additional ventilator to maintain oxygenation can be
challenging at best.
An alternative method to treat hypoxemia during OLV for
thoracoscopic pulmonary lobectomy is the use of apneic
oxygen insufflation (AOI) to the nondependent lung. A recent
study41 showed that with application of 3 L of O2 via suction
catheter to the nonventilated side, the application of AOI on a
 J.H. Campos, A. Feider / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 2330–2338
limb of the DLT improved arterial oxygenation while surgery
was in progress. In the group of patients who received AOI the
incidence of hypoxemia during OLV in 45 patients studied
was 0%; in contrast, in the non-AOI group of 45 patients, it
was 18%. PaO2 values at 30 minutes during OLV for the AOI
group were a mean value of 170 mmHg versus 105 mmHg for
the non-AOI group without interference on the surgical field.
A different alternative to maintain oxygenation is with the
use of high-frequency jet ventilation (HFJV). A case report42
has shown that the use of HFJV through the lumen of the
Arndt blocker was able to treat hypoxemic events during OLV
when CPAP on the nondependent and operative lung failed to
improve oxygenation. The advantages of HFJV are that it uses
a very low tidal volume while maintaining adequate oxygena-
tion and that ventilation is maintained. In HFJV, PaCO2
gradually increasing hypercapnia can be prevented by increas-
ing the driving pressure.
Pharmacological Interventions Used During Hypoxia and
OLV
Several pharmacologic interventions to treat hypoxemia
during OLV have been reported. On a theoretical basis,
inhaled nitric oxide (iNO) should improve V/Q mismatch
during OLV by dilating pulmonary arteries to the ventilated
lung and improving blood flow to those segments. However,
one study43 showed that iNO had no benefit when adminis-
tered to the dependent lung during OLV. Routine use of iNO
to treat hypoxemia is not recommended.
Almitrine, a respiratory stimulant, is another drug that has
been investigated with mixed results. The effect of almitrine
on oxygenation is due to enhancement of HPV. In one study,
treatment with intravenous almitrine was shown to improve
hypoxemia.44 Another report45 found that almitrine combined
with iNO also improves oxygenation during OLV. At high
doses, almitrine increases mean pulmonary arterial pressures.
However, both of these studies used a total intravenous
anesthetic in order to prevent attenuation of HPV secondary
to the use of inhaled anesthetics. A subsequent study showed
that almitrine failed to improve oxygenation when an inhaled
anesthetic (sevoflurane) was used.46 Although almitrine is used
in Europe, this drug is not available in the United States and is
not FDA approved.
Another drug that has been used is dexmedetomidine, a
selective a2 adrenoceptor agonist. A study47 has shown that a
continuous infusion of dexmedetomidine during OLV with
sevoflurane anesthesia improved oxygenation and increased
the PaO2/FIO2 ratio during the intraoperative period. A
subsequent meta-analysis study reported that the use of
dexmedetomidine improved the oxygenation index (assess-
ment of intrapulmonary shunt and mean airway pressure) by
improving oxygenation and decreasing intrapulmonary shunt
fraction during OLV in patients receiving intravenous and or
inhalational agents.48 One potential explanation for the effects
of dexmedetomidine is that it reduces the required doses of
inhalational or intravenous anesthetics, thus reducing their
potential negative effects on HPV. Further studies are needed
2335
to validate the use of dexmedetomidine in patients undergoing
OLV.
Use of ECMO to Manage Oxygenation in Thoracic Surgery
Recently there have been an increasing number of case
reports on ECMO being used to manage oxygenation during
thoracic surgery where oxygenation cannot be maintained with
conventional techniques. There are 2 different methods in
which ECMO can be used in the thoracic surgical patient:
venovenous (VV) and venoarterial (VA). The advantage of
using ECMO includes the ability to maintain oxygenation and
carbon dioxide removal in cases where proper ventilation is
not feasible or sufficient due to patient-specific comorbidities
or anatomic derangements.
There are multiple reports and case series describing the use
of ECMO in patients with critical airway obstruction under-
going tracheal mass removal or stenting.49–51 In all of these
reports, elective initiation of ECMO (usually VV) prior to
induction of anesthesia or prior to start of the procedure led to
acceptable outcomes.
Figure 3A displays the different alternatives of cannulation
and use of ECMO. When cardiocirculatory support is needed,
VA ECMO is advantageous because it will oxygenate the blood
as well as support systemic blood pressure. However, VA
ECMO can have a major drawback if cardiac function is
improved but lung function remains poor. This may result in
Harlequin (or North-South) syndrome, which is a differential
hypoxemia between the upper and lower body during femoral
cannulation VA ECMO.52 In this situation, retrograde flow of
oxygenated blood from the femoral arterial cannula is competing
with antegrade flow from the heart, which pumps deoxygenated
blood due to poor lung function. A right radial arterial line is
necessary to monitor the PaO2 from the proximal aortic arch.
Extremely low values would correctly identify this syndrome.
There is a case report53 of severe emphysema, decompen-
sated respiratory failure, and cor pulmonale in a patient
undergoing lung volume reduction surgery. Prior to surgery,
femoral-femoral VA ECMO was initiated in order to preserve
oxygenation during OLV. Others have described VA ECMO
use in a patient undergoing esophagectomy after left pneumo-
nectomy or during segmentectomy for lung cancer in a patient
with previous pneumonectomy.54,55
VV ECMO is advantageous in maintaining oxygenation and
CO2 removal when cardiocirculatory support is not needed
(Fig 3B). A VV ECMO system that is rapidly gaining
popularity is the Avalon Elite (Maquet, Rastatt, Germany).
This is a single dual-lumen cannula inserted percutaneously
via the right internal jugular vein, and its distal tip sits in the
proximal inferior vena cava. Blood is aspirated through both
the superior vena cava and inferior vena cava. It is then
pumped through an oxygenator and into the second lumen of
the cannula, which exits into the right atrium, with blood flow
directed toward the tricuspid valve (Fig 3C).
A report of 2 cases56 described the use of the Avalon Elite
cannula in a patient with an existing left bronchopleural fistula
and thoracostomy who required a right thoracotomy for tumor
2336 J.H. Campos, A. Feider / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 2330–2338

Fig 3. (A) Peripheral VA ECMO uses a femoral drainage cannula advanced into the IVC and a femoral arterial reinjection cannula. (B) Femoral-jugular VV
ECMO uses a femoral drainage cannula in the IVC and a RIJ reinjection cannula in the RA. (C) Dual-lumen RIJ VV ECMO uses a single cannula inserted in the
RIJ and terminating in the proximal IVC. The reinjection port is located in the RA. ECMO, extracorporeal membrane oxygenation; IVC, inferior vena cava;
RA, right atrium; RIJ, right internal jugular vein; VA, venoarterial; VV, venovenous. (Adapted from Servier Medical Art: http://smart.servier.com.)

resection (left-lung ventilation and right-lung collapse).
ECMO was initiated prior to OLV to maintain oxygenation
during surgery. A case series of 9 patients,57 in whom VV
ECMO was used, reported that indications for ECMO included
severely impaired lung function, previous pulmonary resec-
tions including contralateral pneumonectomy, previous single-
lung transplantation, and extended carinal pneumonectomy.
Positive outcomes in these reports of anticipated VV ECMO
use are encouraging. As described in a case,58 hypoxemia may
develop even with adequate flow rates and may require
application of apneic oxygen delivery to the operative lung
in order to obtain an adequate systemic partial pressure of
oxygen. Table 3 shows indications of the use of ECMO to
manage oxygenation in thoracic surgical patients.
Future Research on Shunt Fraction and OLV
Conventional approach to estimate shunt fraction is
according to the Fick’s principle where arterial and mixed
Table 3
Indications for Use of ECMO to Improve Oxygenation During Thoracic
Surgery

Severe airway obstruction

Emergency loss of airway

Extended carinal pneumonectomy

Severe emphysema undergoing lung volume reduction surgery

Acute respiratory distress syndrome undergoing thoracotomy and
decortication

Tracheoesophageal fistula repair after previous pneumonectomy

Esophagectomy after previous pneumonectomy

Segmentectomy after previous contralateral pneumonectomy

Thoracotomy after previous single-lung transplantation

Thoracotomy with existing contralateral bronchopleural fistula

Salvage therapy for severe chest trauma
Abbreviation: ECMO, extracorporeal membrane oxygenation.
venous-blood samples are needed by an arterial line and a
pulmonary artery catheter. A different approach to estimate
shunt fraction can be done by measuring the velocity time
integral of the pulmonary venous flow pattern with transeso-
phageal echocardiography (TEE). The blood flow in the
nondependent (operative) lung is composed with intrapulmon-
ary shunt during OLV; the shunt fraction can be represented
by the ratio of blood flow volume in the nondependent lung to
the bilateral lung.
One preliminary study59 of the estimation of intrapulmonary
shunt in the nondependent lung with the use of TEE has been
reported. Fifteen patients under OLV were studied, echocar-
diography measurements included bilateral pulmonary vein
flows pathway, and cardiac outputs were measured. After
OLV, the velocity time integral of the upper pulmonary veins
increased significantly in the dependent lung and decreased
significantly in the nondependent lung (operative) lung. There
was also a significant linear correlation between shunt fraction
and PaO2; moreover, in their conclusion the authors suggested
that it is feasible to estimate intrapulmonary shunt fraction by
examining bilateral pulmonary vein flow in anesthetized
patients undergoing OLV with TEE. Further studies are
needed to validate these findings in a large-scale study to be
able to predict hypoxia with the use of TEE by measuring of
the pulmonary vein flows patterns.
Summary
Hypoxemia does not commonly occur during OLV. Antici-
pating the patients who will develop hypoxemia during OLV,
the use of alveolar recruitment maneuvers prior to or during
OLV will improve oxygenation. If hypoxemia occurs, one
should use fiberoptic bronchoscopy to confirm optimal
position of the lung isolation device. Unfortunately, there is
a disconnection between peripheral oxygen saturation and
cerebral saturation. Pharmacological interventions to correct
 J.H. Campos, A. Feider / Journal of Cardiothoracic and Vascular Anesthesia 32 (2018) 2330–2338
hypoxemia have a very limited value. In unique situations
when the airway is compromised or OLV is not possible or
sufficient in maintaining oxygenation, the use of ECMO is a
valuable option to maintain oxygenation.
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