Basic, Clinical and Systems Neuroscience

E   Original Clinical Research Report

Association Between Cerebral Desaturation and

Postoperative Delirium in Thoracotomy With One-Lung
Ventilation: A Prospective Cohort Study
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Fan Cui, MD,* Wei Zhao, MD,† Dong-Liang Mu, MD,* Xu Zhao, MD,‡§ Xue-Ying Li, MS,∥
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Dong-Xin Wang, MD, PhD,* Hui-Qun Jia, MD,† Feng Dai, PhD,¶ and Lingzhong Meng, MD§

BACKGROUND: The association between cerebral desaturation and postoperative delirium in

thoracotomy with one-lung ventilation (OLV) has not been specifically studied.
METHODS: A prospective observational study performed in thoracic surgical patients. Cerebral
tissue oxygen saturation (Scto2) was monitored on the left and right foreheads using a near-
infrared spectroscopy oximeter. Baseline Scto2 was measured with patients awake and breathing
room air. The minimum Scto2 was the lowest measurement at any time during surgery. Cerebral
desaturation and hypersaturation were an episode of Scto2 below and above a given threshold
for ≥15 seconds during surgery, respectively. The thresholds based on relative changes by
referring to the baseline measurement were <80%, <85%, <90%, <95%, and <100% baseline
for desaturation and >105%, >110%, >115%, and >120% baseline for hypersaturation. The
thresholds based on absolute values were <50%, <55%, <60%, <65%, and <70% for desatura-
tion and >75%, >80%, >85%, and >90% for hypersaturation. The given area under the threshold
(AUT)/area above the threshold (AAT) was analyzed. Delirium was assessed until postoperative
day 5. The primary analysis was the association between the minimum Scto2 and delirium using
multivariable logistic regression controlled for confounders (age, OLV time, use of midazolam,
occurrence of hypotension, and severity of pain). The secondary analysis was the association
between cerebral desaturation/hypersaturation and delirium, and between the AUT/AAT and
delirium using multivariable logistic regression controlled for the same confounders. Multiple
testing was corrected using the Holm-Bonferroni method. We additionally monitored somatic
tissue oxygen saturation on the forearm and upper thigh.
RESULTS: Delirium occurred in 35 (20%) of 175 patients (65 ± 6 years old). The minimum left
or right Scto2 was not associated with delirium. Cerebral desaturation defined by <90% baseline
for left Scto2 (odds ratio [OR], 5.82; 95% confidence interval [CI], 2.12-19.2; corrected P =.008)
and <85% baseline for right Scto2 (OR, 4.27; 95% CI, 1.77-11.0; corrected P =.01) was asso-
ciated with an increased risk of delirium. Cerebral desaturation defined by other thresholds,
cerebral hypersaturation, the AUT/AAT, and somatic desaturation and hypersaturation were all
not associated with delirium.
CONCLUSIONS: Cerebral desaturation defined by <90% baseline for left Scto2 and <85% base-
line for right Scto2, but not the minimum Scto2, may be associated with an increased risk of
postthoracotomy delirium. The validity of these thresholds needs to be tested by randomized
controlled trials. (Anesth Analg 2021;133:176–86)

KEY POINTS
• Question: Are cerebral desaturation and postthoracotomy delirium associated?
• Findings: Cerebral desaturation, defined by <90% baseline for left cerebral tissue oxygen
saturation (Scto2) or <85% baseline for right Scto2, was associated with delirium based on mul-
tivariable logistic regression controlled for confounders and corrected for multiple testing.
• Meaning: Cerebral desaturation may be responsible for postthoracotomy delirium in some
patients.

From the *Department of Anesthesiology and Critical Care, Peking
University First Hospital, Beijing, China; †Department of Anesthesiology,
The Fourth Hospital of Hebei Medical University, Shijiazhuang, China;
‡Department of Anesthesiology, Second Xiangya Hospital, Central South
University, Changsha, China; §Department of Anesthesiology, Yale
University School of Medicine, New Haven, Connecticut; ∥Department
of Biostatistics, Peking University First Hospital, Beijing, China; and
¶Department of Biostatistics, Yale University School of Public Health, New
Haven, Connecticut.
Accepted for publication January 28, 2021.
Funding: This trial was supported by the National Key R&D Program of
China (no. 2018YFC2001800) and Project of Health Commission of Hebei
Province (no. 20190709). The sponsors had no role in designing or conduct-
ing the study; collecting, managing, analyzing, or interpreting the data; or
preparing and approving the manuscript.
DOI: 10.1213/ANE.0000000000005489
Conflicts of Interest: See Disclosures at the end of the article.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of
this article on the journal’s website (www.anesthesia-analgesia.org).
F. Cui and W. Zhao contributed equally.
This study is registered at the Chinese Clinical Trial Registry (http://www.
chictr.org.cn) (no.: ChiCTR-ROC-17012627).
Reprints will not be available from the authors.
Address correspondence to Dong-Liang Mu, MD, Department of
Anesthesiology and Critical Care, Peking University First Hospital, Xishiku
St No. 8, Beijing 100034, China. Address e-mail to mudongliang@icloud.com;
Lingzhong Meng, MD, PhD, Department of Anesthesiology, Yale University
School of Medicine, 333 Cedar St, TMP 3, PO Box 208051, New Haven, CT
06520. Address e-mail to lingzhong.meng@yale.edu.
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 E  Original Clinical Research Report

GLOSSARY
AAT = area above the threshold; ASA = American Society of Anesthesiologists; AUT = area under
the threshold; BIS = bispectral index; BMI = body mass index; CAM = Confusion Assessment
Method; CI = confidence interval; COPD = chronic obstructive pulmonary disease; GA = general
anesthesia; ICU = intensive care unit; IQR = interquartile range; LOH = length of hospital stay;
MoCA = Montreal cognitive assessment; OLV = one-lung ventilation; OR = odds ratio; POD = post-
operative delirium; Scto2 = cerebral tissue oxygen saturation; SD = standard deviation; Ssto2 =
somatic tissue oxygen saturation
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P
ostoperative delirium (POD) is an acute fluc-
tuating brain dysfunction characterized by
inattention, disorganized thinking, and altered
levels of consciousness.1 POD is associated with vari-
ous adverse outcomes including prolonged mechani-
cal ventilation, prolonged intensive care unit (ICU)
stay and length of hospitalization, increased health
care cost, and higher mortality.1–3 Risks of POD vary
among different surgeries. The reported incidence of
delirium ranges from 7% to 23% in patients having
thoracotomy.2,3
Cerebral hypoxia is a potential risk factor for
delirium.1,4 Cerebral oximetry based on near-infrared
spectroscopy enables continuous and noninvasive
measurement of cerebral tissue oxygen saturation
(Scto2).5 In essence, Scto2 assesses the balance between
cerebral tissue oxygen consumption and supply in the
superficial brain tissue bed illuminated by near-infra-
red lights. In thoracic surgical patients undergoing
one-lung ventilation (OLV), the incidence of cerebral
desaturation, defined as a decrease in Scto2 of more
than 15% from the baseline level, can be as high as
70%–100%.6,7 However, the relationship between
cerebral desaturation and POD in thoracic surgical
patients has not been reported.
Furthermore, it is important to understand how
the severity of cerebral desaturation and POD is
related and if there is an Scto2 threshold below which
the risk of delirium is increased.5,8 The previously
used thresholds were relative changes (<75%, <80%,
and <85% baseline) and absolute values (<50% and
<60%).9–14 These thresholds originated from 2 studies.
One study reported that the Scto2 ratio between the
measurement obtained at the end of the hypothermic
cardiopulmonary bypass and the baseline measure-
ment was <70% (relative change) in 3 patients who
had neurologic deficits15; the other study implied
that Scto2 should be maintained above 50% (abso-
lute value) based on the data of 2 patients who had
significant changes in somatosensory-evoked poten-
tial during carotid endarterectomy.16 Therefore, these
thresholds, although already widely cited, are rather
empirical and not specifically based on its relation-
ship with POD. A few randomized controlled trials
tested the effectiveness of Scto2-guided care for POD
reduction using these thresholds in cardiac surgical
patients9–14; however, the pooled data did not show
a favorable effect (relative risk, 0.67; 95% confidence
interval [CI], 0.41-1.08).17 One of the limitations
among these studies may be related to the threshold
used to guide patient care. It is worth noting that none
of these randomized studies were based on thoracic
surgical patients.
In this study, we hypothesized that cerebral desat-
uration is associated with postthoracotomy delirium.
Our primary aims were as follows: (1) to investigate
the association between the minimum Scto2 and POD
and (2) to investigate the association between cerebral
desaturation defined by a given threshold and POD,
and between the area under the threshold (AUT)/area
above the threshold (AAT) that was given and POD.
METHODS
This prospective observational cohort study was
approved by the Clinical Research Review Board
of Peking University First Hospital (no. 2017-1378),
registered in the Chinese Clinical Trial Registry (no.
ChiCTR-ROC-17012627), and conducted at Peking
University First Hospital and The Fourth Hospital
of Hebei Medical University from September 2017
to October 2018. Written informed consent for study
participation was obtained from all patients or their
legal representatives.
Participants
Adult patients who were ≥55 years old and scheduled
to undergo a 2-hour-or-longer elective thoracotomy
with OLV were eligible. The exclusion criteria were
any of the following: (1) refusal to participate; (2)
emergent, urgent, or trauma surgery; (3) poor hearing
or vision impeding delirium assessment; (4) language
barrier impeding delirium assessment; (5) history of
schizophrenia; (6) dementia; and (7) American Society
of Anesthesiologists physical status >III.
Anesthesia and Perioperative Care
In the operating room, all patients were monitored
using pulse oximetry, electrocardiography, and non-
invasive blood pressure. All patients received general
anesthesia, with or without an epidural or paraver-
tebral block at the discretion of the attending anes-
thesiologist. Anesthesia induction was accomplished
using a bolus of propofol (2–4 mg/kg) and continu-
ous infusion of sufentanil (site-effect concentration,

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 Cerebral Desaturation and Postoperative Delirium
0.2–0.5 ng/mL). Anesthesia was maintained using
propofol (4–10 mg/kg/h) and sufentanil (site-effect
concentration, 0.2–0.5 ng/mL) continuous infusion.
Bispectral index (BIS) monitor was used to maintain
the BIS value between 40 and 60. All patients were
endotracheally intubated and mechanically venti-
lated with a tidal volume of 6–8 mL/kg. Pulse oxygen
saturation was maintained at 92% or higher. End-
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tidal carbon dioxide partial pressure was maintained
at 35–45 mm Hg. The systolic blood pressure was
maintained above 80% of the baseline level. The naso-
pharyngeal temperature was maintained at 36–37 °C.
Postoperative pain was managed using patient-con-
trolled intravenous analgesia programmed to deliver
a background infusion of sufentanil at 1.25 µg/h and
a 2.5-µg bolus with a lockout interval of 8 minutes for
breakthrough pain. The goal of analgesia was to keep
the pain score at 3 or lower, assessed using an 11-point
numeric rating scale (where 0 and 10 indicate no pain
and the worst pain, respectively). For pains with a
score ≥4, extra sufentanil, 5–10 µg per dose, was given
if the patient was in the postanesthesia care unit; alter-
natively, flurbiprofen, 50–100 mg per dose, was given
if the patient was in a regular hospital room.
Tissue Oxygen Saturation Monitoring
Tissue oxygen saturation was monitored using the
FORE-SIGHT ELITE tissue oximeter (CASMED,
Branford, CT; now acquired by Edwards Lifesciences,
Irvine, CA). We monitored 4 tissue beds, including
the left forehead, right forehead, forearm over the
brachioradialis muscle, and upper thigh over the
quadriceps. The oximetry sensors were placed on
the arm and leg that were positioned on the upper
side in a laterally positioned patient. The modern
tissue oximeter enables the monitoring of different
tissue beds.18,19 Oxygen saturation of different tis-
sue beds may not always correlate with each other19
and likely have different associations with patient
outcomes.20–22 We named the measurement derived
from the probes placed on the forehead as Scto2 and
the measurement derived from the probes placed
on the arm and leg as somatic tissue oxygen satu-
ration (Ssto2). While the primary aim of this study
was to investigate the association between Scto2
and delirium, we also investigated the association
between Ssto2 and delirium. We compared the anal-
ysis based on Scto2 monitoring with the analysis
based on Ssto2 monitoring, because the difference
between these 2 sets of analysis would inform if
tissue oximeter is trustworthy based on the follow-
ing rationale: we would see an association between
Scto2 and delirium, not between Ssto2 and delirium,
if delirium as a brain dysfunction is related to inad-
equate cerebral, not somatic, oxygen supply (one of
our hypotheses).
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The baseline measurement was obtained in all
patients before anesthesia induction, with patients
resting and breathing room air. Tissue oxygen satura-
tion was continuously monitored throughout surgery.
The screen of tissue oximeter was covered with an
opaque bag to blind anesthesia providers to the moni-
toring. Dedicated research personnel checked tissue
oximeter every 10 minutes to ensure proper function.
The data, generated by tissue oximeter every 2 sec-
onds, were extracted from the monitor at the end of
surgery.
The Minimum Scto2
The minimum Scto2 was the lowest measurement at
any time during surgery. One of our primary aims
was to investigate the association between the mini-
mum Scto2 and delirium.
Tissue Desaturation/Hypersaturation
The other primary aim of our study was to investi-
gate the association between cerebral desaturation
and delirium. Cerebral desaturation was an episode
of left or right Scto2 lower than a given threshold
for 15 consecutive seconds or longer during surgery.
The duration of 15 seconds was empirical due to the
lack of evidence attesting to its validity. The thresh-
olds used to define cerebral desaturation were <80%,
<85%, <90%, <95%, and <100% baseline, that is, the
relative changes by referring to the baseline measure-
ment, and <50%, <55%, <60%, <65%, and <70%, that
is, simply the absolute values.
We also investigated the association between cere-
bral hypersaturation and delirium, as it was sug-
gested by a previous study that cerebral hyperoxia
may be associated with delirium in cardiac surgical
patients.23 Cerebral hypersaturation was an episode
of left or right Scto2 higher than a given threshold
for 15 consecutive seconds or longer during surgery.
The thresholds used to define cerebral hypersatura-
tion were >105%, >110%, >115%, and >120% baseline,
that is, the relative changes by referring to the base-
line measurement, and >75%, >80%, >85%, and >90%,
that is, simply the absolute values.
We additionally investigated the association
between somatic desaturation and delirium, and
between somatic hypersaturation and delirium based
on the reasoning specified above. The definitions
of somatic desaturation and hypersaturation were
similar to the definitions of cerebral desaturation
and hypersaturation. The thresholds used to define
somatic desaturation and hypersaturation were simi-
lar to the thresholds used to define cerebral counter-
parts except the following: the absolute values used
to define somatic desaturation were <55%, <60%,
<65%, <70%, and <75%, and the absolute values
used to define somatic hypersaturation were >80%,
ANESTHESIA & ANALGESIA
 E  Original Clinical Research Report
>85%, >90%, and >95%. This difference was based on
the observation that Ssto2 measurement tends to be
higher than Scto2 measurement.20,21
AUT and AAT
The effect of tissue desaturation or hypersaturation
might depend on both the magnitude and time of the
adverse changes.21,24 Therefore, we additionally inves-
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tigated the association between each of AUT and AAT
and delirium. AUT or AAT (min × %) was the prod-
uct of the difference, between the actual measure-
ment and the threshold, accumulated throughout the
duration when the actual measurement surpassed the
threshold.21,24
Postoperative Delirium
POD was defined as any episode of delirious symp-
tom within postoperative 5 days.25 Delirium was
assessed twice daily, between 06:00–08:00 and 18:00–
20:00, using the Chinese version of the Confusion
Assessment Method (CAM) in nonintubated patients
and the CAM-ICU in intubated patients.26–28 The
research personnel who were responsible for delirium
assessment participated in a 4-hour training session
with the following agenda: (1) an introduction to the
symptoms, diagnosis, and treatment of delirium, (2) a
lecture on how to use CAM and CAM-ICU for delir-
ium assessments, and (3) a simulation training course
with a quiz at the end of training. All trainees were
required to answer all quiz questions correctly.26,28
Research personnel who were responsible for out-
come assessment were not allowed to access patient
data collected during surgery.
Statistical Analysis
Continuous variables following a normal distribu-
tion were presented as mean and standard devia-
tion (SD); otherwise, they were presented as median
and interquartile range. Histograms and Q-Q plots
were used to assess the normality of distribution.
Categorical variables were presented as frequencies
and percentages.
The association between the minimum Scto2 and
delirium was analyzed using multivariable logistic
regression controlled for confounders. The confound-
ers were based on the known risk factors (ie, age, OLV
time, use of midazolam, occurrence of hypotension,
and severity of pain).29
The associations between tissue desaturation and
delirium, and between tissue hypersaturation and
delirium were analyzed using multivariable logis-
tic regression controlled for the same confounders
as above. For different tissue beds monitored (ie,
left Scto2, right Scto2, arm Ssto2, and leg Ssto2), we
analyzed 2 different types of thresholds (ie, relative
changes versus absolute values), and for each type
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of threshold, up to 9 different tests were performed.
To control the type I error at 5%, the P values were
corrected using the Holm-Bonferroni method per the
number of tests performed for each tissue bed and for
each type of threshold.
The association between AUT/AAT and delirium
was analyzed using multivariable logistic regression
controlled for the same confounders as above. Multiple
testing was corrected using the same method as above.
We additionally used restricted cubic splines with 3
knots to visualize the shape of the association between
the odds of delirium and the size of AUT/AAT.30
All statistical analyses were performed using
the SPSS statistical package version 14.0 (SPSS
Inc, Chicago, IL) and R version 3.5.3 packages (R
Foundation for Statistical Computing, Vienna,
Austria). The significance level for each general
hypothesis was 0.05.
Sample Size Calculation
The incidence of delirium after thoracotomy was
approximately 10% in our institution.31 A previous
study showed that the minimum Scto2 was 49% and
55% in delirious and nondelirious cardiac surgical
patients, respectively.32,33 For a statistical significance of
0.05, power of 0.8, and SD of 7%, we needed 166 patients
to detect a statistically significant between-group dif-
ference of 6% in the minimum Scto2. We planned to
enroll 175 patients, considering a 5% dropout rate.
RESULTS
Patient Characteristics and Perioperative Data
Of the 207 patients screened, 175 (65 ± 6 years old)
participated in the formal study (Figure 1). Delirium
occurred in 35 (20%) of these 175 patients. The demo-
graphic characteristics and perioperative data are
summarized in Table 1.
Association Between the Minimum Scto2 and
Delirium
The minimum Scto2 measured on the right forehead
was 58.9% ± 8.1%, which was not significantly asso-
ciated with delirium (odds ratio [OR], 0.96; 95% CI,
0.92-1.01; P =.08) after controlling for confounders
including age, OLV time, use of midazolam, occur-
rence of hypotension, and severity of pain on postop-
erative day 1 (Table 2). The minimum Scto2 measured
on the left forehead was 59.9% ± 8.5%, which was also
not significantly associated with delirium after con-
trolling for the same confounders (OR, 0.98; 95% CI,
0.94-1.03; P =.46).
Association Between Tissue Desaturation and
Delirium
The incidences of delirium in patients who sur-
passed and did not surpass a given threshold are
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 Cerebral Desaturation and Postoperative Delirium
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Figure 1. Flowchart of the study.
presented in Table 3 for relative change-based thresh-
olds and Table 4 for absolute value-based thresholds.
Cerebral desaturation defined by <90% baseline
for left Scto2 (OR, 5.82; 95% CI, 2.12-19.2; corrected
P =.008) and by <85% baseline for right Scto2 (OR,
4.27; 95% CI, 1.77-11.0; corrected P =.01) was asso-
ciated with an increased risk of delirium based on
multivariable logistic regression controlled for the
same confounders as above and corrected for mul-
tiple testing (Table 3). Cerebral desaturation defined
by other relative change-based thresholds (Table 3)
and by absolute value-based thresholds (Table 4) was
not associated with delirium. Somatic desaturation
defined by relative change-based thresholds (Table 3)
and by absolute value-based thresholds (Table 4) was
not associated with delirium.
Association Between Tissue Hypersaturation
and Delirium
Cerebral hypersaturation defined by relative change-
based thresholds (Table 3) and by absolute value-
based thresholds (Table 4) was not associated with
delirium based on multivariable logistic regression
controlled for the same confounders and corrected for
multiple testing as above. Somatic hypersaturation
defined by relative change-based thresholds (Table 3)
and by absolute value-based thresholds (Table 4) was
also not associated with delirium.
Association Between AUT/AAT and Delirium
No AUT/AAT calculated per either a relative change-
based threshold or an absolute value-based threshold,
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based on either Scto2 data or Ssto2 data, was associ-
ated with delirium (Supplemental Digital Content,
Table, http://links.lww.com/AA/D428). The asso-
ciations between the odds of delirium and the size of
AUT calculated per the threshold of <90% baseline are
presented in Figure 2.
DISCUSSION
Delirium occurred in 20% of patients after thoracot-
omy with OLV. The minimum intraoperative Scto2
was not associated with postthoracotomy delirium.
However, cerebral desaturation, defined as either
left Scto2 <90% baseline or right Scto2 <85% base-
line lasting for 15 consecutive seconds or longer,
was associated with an increased risk of delirium.
No AUTs/AATs calculated per thresholds based
on either relative changes or absolute values were
associated with delirium. The results of our study
suggest that it may be reasonable to use <90% base-
line for both left and right Scto2 as the threshold of
cerebral desaturation in thoracic surgical patients.
Although it was the threshold <85% baseline, not
<90% baseline, for right Scto2 that was associated
with delirium in our study, we opted for <90% base-
line for both right and left Scto2 as the threshold for
cerebral desaturation definition to be consistent.
Moreover, overestimation (ie, using right Scto2 <90%
baseline to diagnose cerebral desaturation) may be
more desirable than underestimation (ie, using right
Scto2 <85% baseline to diagnose cerebral desatura-
tion), because the former is less likely to miss a con-
cerning cerebral desaturation.
ANESTHESIA & ANALGESIA
 E  Original Clinical Research Report

Table 1. Patient Characteristics and Perioperative Table 1. Continued

Data Patients
Patients Variable (n = 175)
Variable (n = 175) Intraoperative tissue oxygen saturation and
Age, mean ± SD, y 64.5 ± 6.4 hypotension
Female, n (%) 84 (48.0) Left minimum Scto2, mean ± SD, %c 59.9 ± 8.5
BMI, mean ± SD, kg/m2 25 ± 3 Right minimum Scto2, mean ± SD, %d 58.9 ± 8.1
Smoking, n (%)a 30 (17.1) Forearm minimum Ssto2, mean ± SD, % 58.8 ± 14.4
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Education level, n (%) Thigh minimum Ssto2, mean ± SD, % 61.0 ± 13.3
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Illiterate 15 (8.6) Hypotension, n (%)e 68 (38.9)

Elementary school 44 (25.1) Severity of postoperative pain, median [IQR], scoref
Middle school 34 (19.4) First day 4 [3–5]
High school 52 (29.7) Second day 3 [3–5]
College and above 30 (17.1) Third day 3 [2–4]
ASA physical status, n (%)
Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass
I 1 (0.6) index; COPD, chronic obstructive pulmonary disease; GA, general anesthesia;
II 136 (77.7) IQR, interquartile range; LOH, length of hospital stay; MoCA, Montreal Cog-
III 38 (21.7) nitive Assessment; OLV, one-lung ventilation; Scto2, cerebral tissue oxygen
Comorbidity, n (%) saturation; SD, standard deviation; Ssto2, somatic tissue oxygen saturation.
Stroke 12 (6.9) a
Patients were categorized as a smoker if the smoking index (smoking index
Coronary artery disease 20 (11.4) = cigarettes per day × years of tobacco use) was <400.
Hypertension 72 (41.1)
b
The data of tissue oxygen saturation were missing in 1 patient who did not
develop postthoracotomy delirium.
Arrythmia 12 (6.9) c
One delirious patient and 2 nondelirious patients were excluded due to miss-
COPD 4 (2.3) ing data.
Asthma 2 (1.1) d
Three delirious patients and 1 nondelirious patient were excluded due to
Diabetes 30 (17.1) missing data.
Hyperlipidemia 3 (1.7) e
Hypotension was defined as systolic blood pressure <90 mm Hg or 70% of
Baseline MoCA score and tissue oxygen the baseline value that required treatments.
saturationb, mean ± SD
f
The severity of pain during movement was assessed using a numeric rating
MoCA, score 25.0 ± 4.0 scale, ie, an 11-point score scale with 0 indicating no pain and 10 indicating
worst pain.
Left Scto2, % 70.4 ± 5.6
Right Scto2, % 69.3 ± 5.5
Forearm Ssto2, % 77.0 ± 7.2
Thigh Scto2, % 75.1 ± 8.0 Table 2. Association Between the Minimum
Surgery side, n (%) Cerebral Tissue Oxygen Saturation and
Left lung 74 (42.3) Postthoracotomy Delirium
Right lung 101 (57.7) Variablea OR (95% CI) P value
Surgery type, n (%) Minimum Scto2 measured on the right 0.96 (0.92-1.01) .08
Lobectomy 173 (98.9) forehead (per % increase)b
Pneumonectomy 2 (1.1) Age (per year increase) 0.99 (0.92-1.06) .72
Anesthesia type, n (%) One-lung ventilation time (per hour increase) 1.29 (1.00-1.70) .06
GA only 140 (80.0) Use of midazolam (yes versus no) 2.11 (0.89-4.96) .09
GA + epidural anesthesia 11 (6.3) Occurrence of hypotension (yes versus no) 2.19 (0.96-5.10) .06
GA + paravertebral block 24 (13.7) Severity of pain on postoperative day 1 1.36 (1.02-1.82) .03
Time-related variables (per score increase)
Anesthesia time, mean ± SD, h 4.2 ± 1.7
Surgery time, mean ± SD, h 3.3 ± 1.6 Abbreviations: CI, confidence interval; OR, odds ratio; Scto2, cerebral tissue
oxygen saturation.
Duration of OLV, mean ± SD, h 3.0 ± 1.5 a
The confounders included in this multivariable logistic regression are age,
LOH, median [IQR], d 6 [5–8] one-lung ventilation time, use of midazolam, occurrence of hypotension, and
Intraoperative drugs, input, and output severity of pain on postoperative day 1.
Propofol, median [IQR], mg 527 [120–1070] b
When using the minimum Scto2 measured on the left forehead in multivari-
Sufentanil, median [IQR], μg 30 [24–59] able logistic regression, the OR is 0.98 (95% CI, 0.94-1.03; P = .46).
Etomidate, n (%) 88 (50.3)
Nitrous oxide, n (%) 52 (29.7) value), <55% (absolute value), and <80% baseline (rela-
Midazolam, n (%) 52 (29.7)
Estimated blood loss, median [IQR], mL 50 [30–100] tive change), and AUT of <60% (absolute value) and
Urine output, median [IQR], mL 350 [250–500] <55% (absolute value). These variables had a between-
Crystalloid input, median [IQR], mL 1100 [1000–1600] group difference when based on postoperative, but not
(Continued) intraoperative, Scto2 data. They additionally showed
an association between postoperative absolute Scto2
A recent prospective cohort study investigated the decrease (the only Scto2 variable analyzed) and delir-
association between cerebral desaturation and POD in ium using multivariable logistic regression. Because
96 cardiac surgical patients.34 The authors investigated only 3 thresholds were investigated, this study could
the differences in various Scto2 measurements between not determine the association of other potential thresh-
the patients with and without delirium. These vari- olds with delirium. In comparison, our study was
ables were baseline Scto2, lowest Scto2, absolute and performed in thoracic surgical patients, explored mul-
relative Scto2 decrease, desaturation <60% (absolute tiple thresholds, and, most importantly, investigated

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 Cerebral Desaturation and Postoperative Delirium

Table 3. Incidence of Relative Change-Based Tissue Desaturation and Hypersaturation and Their
Associations With Postthoracotomy Delirium
Threshold Threshold not
surpassed surpassed Multivariable logistic regressiona
Corrected
Threshold Delirious/total patient no. (%)b OR (95% CI)c P value P valued
Left Scto2
<80% baseline 12/41 (29.3) 22/131 (16.8) 1.90 (0.76-4.61) .16 .80
<85% baseline 20/73 (27.4) 14/99 (14.1) 2.30 (0.99-5.49) .06 .42
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<90% baseline 29/107 (27.1) 5/65 (7.7) 5.82 (2.12-19.2) .001 .008
<95% baseline 32/143 (22.4) 2/29 (6.9) 4.03 (1.05-26.7) .08 .48
<100% baseline 34/167 (20.4) 0/5 (0.0) – – –
>105% baseline 33/168 (19.6) 1/4 (25.0) 0.32 (0.03-7.32) .37 >.99
>110% baseline 32/160 (20.0) 2/12 (16.7) 1.22 (0.26-8.95) .82 >.99
>115% baseline 28/141 (19.9) 6/31 (19.4) 0.85 (0.30-2.71) .78 >.99
>120% baseline 22/110 (20.0) 12/62 (19.4) 1.01 (0.44-2.43) .97 >.99
Right Scto2
<80% baseline 12/39 (30.8) 20/132 (15.2) 2.83 (1.14-6.99) .02 .12
<85% baseline 20/69 (29.0) 12/102 (11.8) 4.27 (1.77-11.0) .002 .01
<90% baseline 24/100 (24.0) 8/71 (11.3) 2.67 (1.08-7.19) .04 .20
<95% baseline 29/142 (20.4) 3/29 (10.3) 2.36 (0.69-11.1) .21 .63
<100% baseline 32/165 (19.4) 0/6 (0.0) – – –
>105% baseline 32/166 (19.3) 0/5 (0.0) – – –
>110% baseline 30/156 (19.2) 2/15 (13.3) 1.35 (0.31-9.56) .72 >.99
>115% baseline 28/144 (19.4) 4/27 (14.8) 1.03 (0.34-3.64) .99 >.99
>120% baseline 19/119 (16.0) 13/52 (25.0) 0.47 (0.20-1.12) .09 .36
Forearm Ssto2
<80% baseline 18/82 (22.0) 17/92 (18.5) 1.32 (0.59-2.97) .50 >.99
<85% baseline 21/114 (18.4) 14/60 (23.3) 0.71 (0.31-1.66) .43 >.99
<90% baseline 27/140 (19.3) 8/34 (23.5) 0.78 (0.31-2.13) .61 >.99
<95% baseline 33/167 (19.8) 2/7 (28.6) 0.71 (0.12-5.78) .72 >.99
<100% baseline 34/173 (19.7) 1/1 (100.0) – – –
>105% baseline 26/138 (18.8) 9/36 (25.0) 0.63 (0.25-1.65) .33 >.99
>110% baseline 11/91 (12.1) 24/83 (28.9) 0.30 (0.12-0.70) .007 .056
>115% baseline 7/61 (11.5) 28/113 (24.8) 0.33 (0.11-0.83) .03 .21
>120% baseline 3/35 (8.6) 32/139 (23.0) 0.34 (0.08-1.10) .11 .66
Thigh Ssto2
<80% baseline 9/60 (15.0) 26/114 (22.8) 0.50 (0.19-1.18) .13 .96
<85% baseline 20/88 (22.7) 15/86 (17.4) 1.39 (0.62-3.17) .43 >.99
<90% baseline 24/118 (20.3) 11/56 (19.6) 1.04 (0.45-2.53) .93 >.99
<95% baseline 29/154 (18.8) 6/20 (30.0) 0.40 (0.12-1.36) .13 .96
<100% baseline 34/172 (19.8) 1/2 (50.0) 0.07 (0.00-2.14) .09 .81
>105% baseline 34/163 (20.9) 1/11 (9.1) 2.64 (0.44-51.1) .38 >.99
>110% baseline 30/130 (23.1) 5/44 (11.4) 2.32 (0.86-7.43) .12 .96
>115% baseline 24/103 (23.3) 11/71 (15.5) 1.74 (0.77-4.17) .19 .96
>120% baseline 19/73 (26.0) 16/101 (15.8) 1.73 (0.77-3.93) .18 .96
Values in bold were considered statistically significant.
Abbreviations: –, not assessable; CI, confidence interval; OR, odds ratio; Scto2, cerebral tissue oxygen saturation; Ssto2, somatic tissue oxygen saturation.
a
The confounding factors included in multivariable analysis are age, one-lung ventilation time, use of midazolam, occurrence of hypotension, and severity of pain
on postoperative day 1.
b
The denominator is the number of patients who surpassed or did not surpass the threshold, while the numerator is the number of patients with delirium. Due
to missing data, 1 delirious patient and 2 nondelirious patients were excluded in left Scto2 analysis and 3 delirious patients and 1 nondelirious patient were
excluded in right Scto2 analysis.
c
The OR is the odds of delirium when desaturation or hypersaturation occurs over the odds of delirium when desaturation or hypersaturation does not occur.
OR >1 suggests desaturation or hypersaturation is associated with an increased risk of delirium, whereas OR <1 suggests desaturation or hypersaturation is
associated with a decreased risk of delirium.
d
The P values were corrected for multiple testing using the Holm-Bonferroni method for each tissue bed.

the association between tissue oxygen saturation and
delirium using multivariable logistic regression exclu-
sively, that is an analysis from exposure to outcome,
not backward. A backward analysis is from outcome to
exposure, that is, investigating the difference in expo-
sure between the patients with different outcomes.
In clinical practice, the minimum Scto2 is a retro-
spective diagnosis and varies among patients; there-
fore, this parameter is not practical in acute care when
an adverse change needs to be reversed timely. The cal-
culation of AUT/AAT is dependent on a prespecified
threshold; therefore, it is essentially a threshold-based
management if using AUT/AAT to guide patient care.
Moreover, the calculation of AUT/AAT requires the
knowledge of time when a potentially adverse change
might have already occurred for a while; therefore, it
is also a retrospective approach in this regard and very
practical in acute care. In contrast, using threshold,

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Table 4. Incidence of Absolute Value-Based Tissue Desaturation and Hypersaturation and Their Asso-
ciations With Delirium
Threshold surpassed Threshold not surpassed Multivariable logistic regressiona
Corrected
Threshold Delirious/total patient no. (%)b OR (95% CI)c P value P valued
Left Scto2
<50% 5/20 (25.0) 29/152 (19.1) 1.20 (0.33-3.73) .77 >.99
<55% 10/35 (28.6) 24/137 (17.5) 1.53 (0.56-3.89) .39 >.99
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<60% 16/73 (21.9) 18/99 (18.2) 1.19 (0.51-2.75) .68 >.99

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<65% 27/122 (22.1) 7/50 (14.0) 1.74 (0.69-4.83) .26 >.99

<70% 33/157 (21.0) 1/15 (6.7) 2.93 (0.49-56.4) .33 >.99
>75% 33/165 (20.0) 1/7 (14.3) 1.77 (0.24-37.4) .63 >.99
>80% 31/144 (21.5) 3/28 (10.7) 3.30 (0.93-16.1) .09 .72
>85% 28/118 (23.7) 6/54 (11.1) 2.74 (1.03-8.41) .06 .54
>90% 10/47 (21.3) 24/125 (19.2) 1.15 (0.45-2.78) .76 >.99
Right Scto2
<50% 5/17 (29.4) 27/154 (17.5) 1.88 (0.50-6.20) .31 >.99
<55% 8/32 (25.0) 24/139 (17.3) 1.55 (0.54-4.15) .39 >.99
<60% 22/83 (26.5) 10/88 (11.4) 2.90 (1.21-7.41) .02 .16
<65% 29/137 (21.2) 3/34 (8.8) 2.31 (0.68-10.9) .22 >.99
<70% 31/161 (19.3) 1/10 (10) 1.36 (0.21-26.5) .78 >.99
>75% 32/163 (19.6) 0/8 (0.0) – – –
>80% 27/141 (19.1) 5/30 (16.7) 1.12 (0.38-3.81) .85 >.99
>85% 18/110 (16.4) 14/61 (23.0) 0.63 (0.27-1.51) .30 >.99
>90% 9/49 (18.4) 23/122 (18.9) 0.99 (0.38-2.43) .98 >.99
Forearm Ssto2
<55% 5/43 (11.6) 30/131 (22.9) 0.55 (0.17-1.52) .28 >.99
<60% 14/74 (18.9) 21/100 (21.0) 1.08 (0.46-2.46) .86 >.99
<65% 18/96 (18.8) 17/78 (21.8) 0.83 (0.37-1.85) .64 >.99
<70% 24/133 (18.0) 11/41 (26.8) 0.57 (0.24-1.40) .21 >.99
<75% 31/165 (18.8) 4/9 (44.4) 0.27 (0.06-1.23) .08 .72
>80% 32/165 (19.4) 3/9 (33.3) 0.42 (0.09-2.32) .28 >.99
>85% 23/114 (20.2) 12/60 (20.0) 0.71 (0.29-1.73) .44 >.99
>90% 5/40 (12.5) 30/134 (22.4) 0.43 (0.13-1.21) .13 >.99
>95% 1/8 (12.5) 34/166 (20.5) 0.47 (0.02-3.03) .50 >.99
Thigh Ssto2
<55% 5/39 (12.8) 30/135 (22.2) 0.50 (0.15-1.41) .22 >.99
<60% 12/60 (20.0) 23/114 (20.2) 0.78 (0.32-1.79) .57 >.99
<65% 18/92 (19.6) 17/82 (20.7) 0.81 (0.36-1.82) .62 >.99
<70% 26/128 (20.3) 9/46 (19.6) 1.11 (0.46-2.86) .83 >.99
<75% 34/160 (21.3) 1/14 (7.1) 4.37 (0.77-82.9) .17 >.99
>80% 35/159 (22.0) 0/15 (0.0) – – –
>85% 32/149 (21.5) 3/25 (12.0) 2.19 (0.61-10.8) .27 >.99
>90% 16/78 (20.5) 19/96 (19.8) 0.92 (0.41-2.07) .85 >.99
>95% 5/25 (20.0) 30/149 (20.1) 0.77 (0.22-2.24) .65 >.99
Abbreviations: –, not assessable; CI, confidence interval; OR, odds ratio; Scto2, cerebral tissue oxygen saturation; Ssto2, somatic tissue oxygen saturation.
a
The confounding factors included in multivariable analysis are age, one-lung ventilation time, use of midazolam, occurrence of hypotension, and severity of pain
on postoperative day 1.
b
The denominator is the number of patients who surpassed or did not surpass the threshold, whereas the numerator is the number of patients with delirium.
Due to missing data, 1 delirious patient and 2 nondelirious patients were excluded in left Scto2 analysis, and 3 delirious patients and 1 nondelirious patient
were excluded in right Scto2 analysis.
c
The OR is the odds of delirium when desaturation or hypersaturation occurs over the odds of delirium when desaturation or hypersaturation does not occur.
OR >1 suggests desaturation or hypersaturation is associated with an increased risk of delirium, whereas OR <1 suggests desaturation or hypersaturation is
associated with a decreased risk of delirium.
d
The P values were corrected for multiple testing using the Holm-Bonferroni method for each tissue bed.

that is, a prespecified value, to guide patient care is
practical, because it can be standardized across differ-
ent patients and is a diagnosis that can be made instan-
taneously when an adverse change takes place.
Our study suggests that cerebral desaturation and
postthoracotomy delirium are associated; however,
a more important question is how to define cerebral
desaturation. We showed that the thresholds based
on relative changes are more robustly associated with
delirium than the thresholds based on absolute val-
ues. This finding is in accordance with the fact that,
due to the inherent technological limitations, the cur-
rent continuous wave-based tissue oximeters, as in
our study, are recommended to be used as a trend-
of-change monitor, instead of a monitor that provides
absolute measurements.5,35 Moreover, different pro-
prietary tissue oximeters, likely due to their different
designs and algorithms, may provide different read-
ings when their probes are placed at the same location,
at the same time, and in the same patient. Using rela-
tive changes by referring to the baseline values may
minimize or overcome the potential differences in

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 Cerebral Desaturation and Postoperative Delirium

A B
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C D

Figure 2. Association between area under the threshold and the odds ratio of delirium. The area was calculated per the threshold of <90%
baseline for left cerebral tissue oxygen saturation (A), right cerebral tissue oxygen saturation (B), forearm somatic tissue oxygen saturation
(C), and thigh somatic tissue oxygen saturation (D). CI indicates confidence interval.

measurements among different oximeters. Moreover,
using relative change as threshold makes the stan-
dardization across different patients and monitors
possible.
Our study showed that the incidence of cerebral
desaturation is a matter of definition. When using a
<90% baseline to define cerebral desaturation, 61%
(107 of 174) and 57% (100 of 174) of our patients had
left and right cerebral desaturation during thora-
cotomy, respectively. In contrast, when using a <80%
baseline, 24% (41 of 174) and 22% (39 of 174) of our
patients had left and right cerebral desaturation,
respectively. These findings imply that it is important
to determine properly the threshold to maximize the
potential benefits.
Our study singled out <90% baseline for cere-
bral desaturation definition, which is different from
the currently widely used threshold of <80% base-
line. This discrepancy highlights the complexity and
importance of threshold determination.
It is tempting, based on our results, to speculate
whether or not maintaining left and right Scto2 ≥90% base-
line may lead to a lower incidence of postthoracotomy
delirium. Caution must be practiced, however, because
of the difference between association and causation, that
is, they may or may not fall together. The cause-effect
relation needs to be tested by randomized controlled
trials in which head-to-head comparisons between the
Scto2-guided care and usual care are performed.
Our study did not find an association between Ssto2
and delirium. This may be primarily attributable to
the fact that delirium is a brain, not a muscle, dysfunc-
tion. The differential associations of Scto2 versus Ssto2
with POD corroborate a relationship between cerebral
desaturation and brain dysfunction.
Our study has limitations. First, the sample of our
study is very modest, which may not be adequate for
precise OR estimation, as suggested by the wide CI of
our study. Second, we might have not thoroughly and
adequately adjusted for potential confounders in our
study. Third, as a cohort study, it revealed an associa-
tive, not causative, relation between cerebral desatu-
ration and delirium. Fourth, as an observational study,
it does not answer the question of how to intervene
when cerebral desaturation occurs. Fifth, we only tar-
geted delirium; therefore, we do not know the asso-
ciation between cerebral desaturation and outcomes
that are not in the form of delirium. Sixth, different
tissue oximeters have been approved by the Food and
Drug Administration for patient use; therefore, we do
not know if our findings can be generalized to differ-
ent tissue oximeters. Seventh, we do not know if our
findings can be generalized to other patient popula-
tions or not. Eighth, our original power analysis was
based on the difference in exposure (ie, the minimum
Scto2) between the patients with different outcomes
(ie, with or without delirium). We did not calculate
our sample size from exposure to outcome. This was

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 E  Original Clinical Research Report
due to the fact that when we designed the study in
2017, there were no data associating intraoperative
cerebral desaturation with postthoracotomy delirium.
Therefore, our study should be regarded as explor-
atory and a call for further research in this area.
CONCLUSIONS
Delirium occurred in 20% of patients after thoracot-
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omy with OLV. The minimum Scto2 was not asso-
ciated with postthoracotomy delirium. Cerebral
desaturation defined by left Scto2 <90% baseline or
right Scto2 <85% baseline lasting for 15 seconds or
longer was associated with an increased risk of POD.
Our findings’ generalizability in other patient popula-
tions remains to be determined. Whether clinical care
aiming to maintain left and right Scto2 above 90%
baseline reduces postthoracotomy delirium deserves
randomized controlled studies. E
ACKNOWLEDGMENTS
The authors thank Prof Xin-Yu Sun (Department of
Psychiatrics, Peking University Sixth Hospital, Beijing,
China) for her help with neurocognition assessment,
Dr Xi-Chun Yang (Department of Anesthesiology
and Critical Care, Peking University First Hospital,
Beijing, China) for her help with the data analysis, and
Drs Zhi-Jiao Wang and Jing-Pu Shi (Department of
Anesthesiology, The Fourth Hospital of Hebei Medical
University, Shijiazhuang, China) for their help with the
data collection.
DISCLOSURES
Name: Fan Cui, MD.
Contribution: This author helped in data acquisition, data
analysis, and manuscript drafting.
Conflicts of Interest: None.
Name: Wei Zhao, MD.
Contribution: This author helped in data acquisition, data
analysis, and critical revision of the manuscript for important
intellectual content.
Conflicts of Interest: None.
Name: Dong-Liang Mu, MD.
Contribution: This author helped in concept and design, data
analysis, data interpretation, manuscript drafting, critical revi-
sion of the manuscript for important intellectual content, and
supervision.
Conflicts of Interest: None.
Name: Xu Zhao, MD.
Contribution: This author helped in data analysis, data inter-
pretation, and critical revision of the manuscript for important
intellectual content.
Conflicts of Interest: None.
Name: Xue-Ying Li, MS.
Contribution: This author helped in data analysis, data inter-
pretation, and critical revision of the manuscript for important
intellectual content.
Conflicts of Interest: None.
Name: Dong-Xin Wang, MD, PhD.
Contribution: This author helped in concept and design,
administrative or material support, and critical revision of the
manuscript for important intellectual content.
July 2021 • Volume 133 • Number 1
Copyright © 2021 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Conflicts of Interest: None.
Name: Hui-Qun Jia, MD.
Contribution: This author helped in data acquisition and criti-
cal revision of the manuscript for important intellectual content.
Conflicts of Interest: None.
Name: Feng Dai, PhD.
Contribution: This author helped in data analysis, data inter-
pretation, and critical revision of the manuscript for important
intellectual content.
Conflicts of Interest: None.
Name: Lingzhong Meng, MD.
Contribution: This author helped in concept and design, man-
uscript drafting, critical revision of the manuscript for impor-
tant intellectual content, technical or material support, and
supervision.
Conflicts of Interest: L. Meng was a consultant to CASMED
(now acquired by Edwards Lifesciences, Irvine, CA).
This manuscript was handled by: Gregory J. Crosby, MD.
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