Journal of Clinical Anesthesia 88 (2023) 111125

Contents lists available at ScienceDirect

Journal of Clinical Anesthesia

journal homepage: www.elsevier.com/locate/jclinane

Original Contribution

A long duration of intraoperative hypotension is associated with

postoperative delirium occurrence following thoracic and orthopedic
surgery in elderly
Wen Duan, M.D a, 1, Cheng-Mao Zhou, M.D, Ph.D a, 1, Jin-Jin Yang, M.D a, Yue Zhang, M.D a,
Ze-Ping Li, M.D a, Da-Qing Ma, M.D, Ph.D b, Jian-Jun Yang, M.D, Ph.D a, *
a
Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
b
Division of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster
Hospital, London, UK

H I G H L I G H T S

• There is equivocal evidence on the association between intraoperative hypotension and POD.
• A cumulative duration of intraoperative hypotension (MAP ≤65 mmHg) for ≥ 5 mins increased the occurrence of POD.
• Timely correcting intraoperative hypotension may decrease the occurrence of POD in elderly.

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Postoperative delirium (POD) is a common surgical complication associated with increased
Intraoperative hypotension morbidity and mortality in elderly. Although the underlying mechanisms remain elusive, perioperative risk
Postoperative delirium factors were reported to be closely related to its development. This study was designed to investigate the as­
Anesthesia
sociation between the duration of intraoperative hypotension and POD incidence following thoracic and or­
Elderly
thopedic surgery in elderly.
Method: The perioperative data from 605 elderly undergoing thoracic and orthopedic surgery from January 2021
to July 2022 were analyzed. The primary exposure was a cumulative duration of mean arterial pressure (MAP) ≤
65 mmHg. The primary end-point was the POD incidence assessed with confusion assessment method (CAM) or
CAM-ICU for three days after surgery. Restricted cubic spline (RCS) was conducted to examine the continuous
relationship between the duration of intraoperative hypotension and POD incidence adjusted with patients’
demographics and surgery related factors. Then the duration of intraoperative hypotension was categorized into
three groups: no hypotension, short (< 5 mins) or long duration (≥ 5 mins) of hypotension for further analysis.
Result: The incidence of POD was 14.7% (89 cases out of 605) within three days after surgery. The duration of
hypotension presented a non-linear and “inverted L-shaped” effect on POD development. Compared to no hy­
potension, long duration (adjusted OR 3.93; 95% CI: 2.07–7.45; P < 0.001) rather than short duration of MAP
≤65 mmHg (adjusted OR 1.18; 95% CI: 0.56–2.50; P = 0.671) was closely related to the POD incidence.
Conclusion: Intraoperative hypotension (MAP ≤65 mmHg) for ≥5 mins was associated with an increased inci­
dence of POD after thoracic and orthopedic surgery in elderly.

* Corresponding author at: Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 East
Jianshe Road, Zhengzhou, Henan 450052, China.
E-mail address: yjyangjj@zzu.edu.cn (J.-J. Yang).
1
These authors contributed equally.

https://doi.org/10.1016/j.jclinane.2023.111125
Received 27 December 2022; Received in revised form 7 April 2023; Accepted 12 April 2023
Available online 19 April 2023
0952-8180/© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
W. Duan et al.
1. Introduction
Postoperative delirium (POD) is an acute-onset neurological
complication following surgery and is characterized as attention
disturbance, conscious alteration and cognitive dysfunction. It
commonly occurs in elderly 24 and 72 h after surgery, with an incidence
rate of up to 50% [1–4]. POD results in prolonged hospital stay,
increased readmissions and even high mortality [2,5]. In recent years,
awareness of its impact, risk factors and prevention have been increased
dramatically [2,6].
Intraoperative hypotension frequently occurs during surgery, which
potentially decreases oxygen or blood flow supply to vital organs and
causes heart, kidney and brain injuries [7]. There is equivocal evidence
of the association between intraoperative hypotension and POD [8–12].
Although, it was suggested that intraoperative hypotension may reduce
cerebral perfusion, subsequently disturbing brain homeostasis and even
causing brain injury and then subsequently lead to POD development
[13–17]. The brain has a certain reserve capacity responding to ischemia
and hypoxia challenge in young people or adults [18,19]. This capacity
is reduced in elderly under general anesthesia due to their weaker
arterial elasticity and other comorbidities [20–23]. A certain period
hypotension during surgery may damage patients’ brains and result in
neurological complications, including POD [24,25]. Therefore, we hy­
pothesized that intraoperative hypotension might lead to the occurrence
of POD and investigated the association between intraoperative hypo­
tension and POD incidence in elderly after thoracic and orthopedic
surgery.
2. Materials and methods
2.1. Data source
This retrospective observational cohort study was approved by the
Ethics Review Committee of the First Affiliated Hospital of Zhengzhou
University (2022-KY-1358), and informed consent was waived. Data
from 605 elderly who underwent thoracic or orthopedic surgery at the
First Affiliated Hospital of Zhengzhou University, Henan, China, from
January 2021 to July 2022, were collected from institutional electronic
medical records and anesthesia information systems (DocareV5.0).
2.2. Study population
The inclusion criteria were as follows: (1) elderly (aged ≥60 years)
who had thoracic surgery or orthopedic surgery under general anes­
thesia; (2) invasive blood pressure monitoring data available during the
operation. Exclusion criteria: (1) lack of preoperative Mini-Mental State
Examination (MMSE) score; (2) preoperative cognitive dysfunction: a
preoperative MMSE score of <17 in illiterate patients, <20 in patients
with primary school education, and <24 in patients with a secondary
school education or above [26]; (3) history of mental disorders: such as
depressive disorder, general anxiety disorder, and schizophrenia; (4)
duration of anesthesia <1 h; (5) delirium data unavailable; (6) intra­
operative blood pressure recording duration lost >5% of total anesthesia
time.
2.3. Data collection
Invasive pressure was measured through a radial artery catheter
before or immediately after induction and automatically recorded every
minute. Intraoperative blood pressure data was exported from anes­
thesia information system (DocareV5.0, Su zhou medicalsystem tech­
nology, Su Zhou in China) to Excel. Blood pressure recordings
containing artifacts were removed (see the online supplement) for
further analysis as reported previously [27]. The cumulative duration of
hypotension was recorded as the sum of the duration of MAP ≤65 mmHg
during whole surgery.
2
Journal of Clinical Anesthesia 88 (2023) 111125
Patients’ demographics and intraoperative parameters were
collected; they were age, sex, body mass index (BMI), comorbidities
(hypertension, diabetes mellitus, coronary heart disease, stroke, and
chronic lung disease), the Charlson comorbidity index [28], smoking,
drinking, preoperative MMSE score, ASA physical status, baseline MAP,
pre-induction MAP, surgical specialty (thoracic surgery and orthopedic
surgery), duration of anesthesia, blood loss and blood transfusion.
2.4. Outcome
POD was assessed by the postoperative follow-up team during three
days after surgery using CAM or CAM-ICU [29,30]. Assessments were
performed twice per day before 10:00 h and after 17:00 h for post­
operative three days. POD was diagnosed once patients were delirious at
least one occasion assessed either with CAM or CAM-ICU during the
study period.
2.5. Statistical analysis
The Kolmogorov-Smirnov test was used to assess normal distribution
of continuous variables. For baseline characteristics analysis, the Chi-
square test or Fisher’s exact test for categorical variables were used.
The Mann-Whitney U test was used to compare none normally distrib­
uted variables. Multivariable logistic regression was used to identify the
association between intraoperative hypotension and POD which was
adjusted with pre-defined potential confounding variables that may
have clinical significance.
To identify and visualize the continuous relationship of the duration
of hypotension with the risk of POD, we performed RCS analysis with
three knots set as the 10th, 50th, and 90th percentiles. In the RCS, we
treated 0 min of MAP ≤65 mmHg as the reference, with adjustments of
the aforementioned covariates. Then, accordingly, the duration of
intraoperative hypotension was categorized into three groups for further
analysis: no hypotension, short (< 5 mins) or long duration (≥ 5 mins) of
hypotension. The association between short or long duration of intra­
operative hypotension and POD relative to no hypotension as the
reference group was determined.
Subgroup analyses were performed to determine whether the asso­
ciation between intraoperative hypotension and POD was also related to
the surgical procedure, a history of arterial hypertension, and long
duration of surgery (≥ 3 h). For effect modifiers analyses, interaction
terms were assessed using the Wald test for the linear combination of
interaction coefficients.
With exploratory intent, we conducted the following post-hoc anal­
ysis: 1) investigating the association between intraoperative hypoten­
sion at different time intervals and POD; 2) assessing the duration and
severity of intraoperative hypotension with a time-weighted average
(TWA) of MAP ≤65 mmHg [31] and an increased risk of POD; and 3)
exploring the duration of intraoperative hypotension in relation to the
major postoperative complications during hospitalization after surgery.
Data were analyzed with R 4.0 and SPSS 26.0. A P value < 0.05 (two-
sided) was considered to be statistically significant.
3. Results
A total of 605 elderly who had thoracic or orthopedic surgeries under
general anesthesia at the First Affiliated Hospital of Zhengzhou Uni­
versity from January 2021 to July 2022 and met the inclusion and
exclusion criteria were included (Fig. 1). In our cohort, the incidence of
POD was 14.7% (n = 89/605). The baseline characteristics and surgery-
related data are summarized in Table 1. The patients with POD were
older, had a lower preoperative MMSE score, a longer duration of MAP
≤65 mmHg, and a higher probability of intraoperative blood
transfusion.
The inverted L-shaped RCS curve indicated that patients with a
longer duration of MAP ≤65 mmHg had an increased risk of POD with
W. Duan et al.
Fig. 1. Study flow chart.
MMSE: Mini-Mental State Examination.
some non-linearity (P < 0.001), after adjustment with the confounding
variables. The risk of POD was increased rapidly with <5 mins duration
of hypotension and tended to stabilize and at the high risk with >5 mins
of hypotension (Fig. 2).
A total of 186 (30.7%) and 217 (35.9%) patients experienced short
and long durations of a MAP ≤65 mmHg, respectively. Short duration of
hypotension (< 5 mins) was not associated with POD (adjusted OR 1.18;
95% CI: 0.56–2.50, P = 0.671), while long duration of hypotension (≥ 5
mins) increased the risk of POD (adjusted OR 3.93; 95% CI: 2.07–7.45, P
< 0.001, Table 2).
The association of hypotension duration and POD is not related to the
history of hypertension, duration of surgery and surgical types (P for
interactions = 0.520, 0.722, and 0.417, respectively; Table 3).
Exploratory analysis showed that a duration of hypotension of <4
mins or 4–5 min did not increase the incidence of POD, whereas 5–6 min
and >5 mins were significantly associated with an increased incidence
of POD (Supplementary Fig. 1). We analyzed the continuous relationship
between TWA of MAP ≤65 mmHg and POD and found that a linear
relationship was significant [OR: 1.59 (1.03–2.44); P = 0.035] (Sup­
plementary Table 1) but the nonlinear relationship was not significant
(P = 0.959). More cases of acute kidney injury (AKI), acute myocardial
injury (AMI), stroke, shock, ICU admission and death were found in
patients with a long duration of intraoperative hypotension during
hospitalization after surgery (Supplementary Fig. 2). None of these
complications occurred in patients without intraoperative hypotension
except for one patient admitted to the ICU.
4. Discussion
This study found a non-linear and “inverted L-shaped” association
between intraoperative hypotension and POD occurrence, with >5 mins
duration of hypotension associated with an increased risk of POD.
Intraoperative hypotension also increased other complications, such as
organ ischemic injuries. These findings suggest that timely preventing
intraoperative hypotension may decrease POD incidence and other
complications.
Ushio et al. [32] demonstrated that a long cumulative duration of
intraoperative hypotension with a MAP <75 mmHg increased the risk of
3
Journal of Clinical Anesthesia 88 (2023) 111125
POD in adult patients after cardiopulmonary bypass. Maheshwari et al.
[31] found that the intraoperative TWA of MAP <65 mmHg increased
the risks of POD in patients admitted to ICU after surgery. In contrast,
Hirsch et al. [10] reported that increased intraoperative blood pressure
fluctuation rather than the duration of intraoperative hypotension was
associated with POD in elderly after noncardiac surgery. This discrep­
ancy might be attributed to the relatively small sample size and less
study power [10]. We for the first time found that the duration of hy­
potension resulted in POD occurrence in a non-linear manner. Although
the non-linear effect of hypotension on AKI and myocardial injury was
documented after noncardiac surgery [33].
Our study indicated that the brain may tolerate the intraoperative
hypotension followed by cerebral hypoperfusion for 5 mins without
increasing the risk of POD and the following reasons may support this.
First, the compensatory mechanisms may buffer the cerebral nervous
system (CNS) against the decreased cerebral blood flow [34–37]. Sec­
ond, reserved glycogen can maintain neuronal survival for 3–5 min
under complete cerebral ischemia [38]. Third, the CNS in healthy
humans can tolerate a reduction of the baseline of the cerebral blood
flow by 35% to 40% before the onset of ischemic symptoms [39,40].
Finally, general anesthesia decreases the cerebral metabolic rate, which
may prolong the tolerance time of the brain to ischemic injury [41].
However, when the above compensatory mechanisms are compromised,
hypotension lasted for >5 min, as shown in our study, followed by ce­
rebral hypoperfusion, which led to POD development. However, the
tolerance time for injury of the brain may be shortened at even a lower
blood pressure. Recently, Wachtendorf et al. [12] reported that the
hypotension (MAP <55 mmHg) duration of both <3 and ≥ 3 mins all
increased the occurrence of POD in certain adult patients undergoing
noncardiac surgery.
The decrease in cerebral blood flow may make neuronal cells more
vulnerable to ischemic injury or may cause ischemia-reperfusion injury
after blood flow restored. Subsequently, POD occurrence was due to
neuronal injuries which was considered to be possible mechanisms
[17,42]. It has also been reported that intraoperative oxidative stress
was enhanced after ischemia-reperfusion and was independently related
to the development of neuronal injury and POD [43,44]. Taylor et al.
reported that neuronal injurious marker and high cerebrospinal fluid
W. Duan et al. Journal of Clinical Anesthesia 88 (2023) 111125

Table 1
Patients characteristics and distribution of variables. Data are presented as
median [IQR] or n (%).
No delirium Delirium P-value

n = (516) n = (89)

Characteristics
Age, yr, median [IQR] 68 [65–71.5] 70 [66.5–74] 0.003
Sex: male, n(%) 247 (47.9%) 50 (56.2%) 0.147
BMI, kg/m2, median [IQR] 24.3 24.5 0.907
[22.05–26.7] [21.9–27.25]
Comorbidities
Hypertension, n(%) 222 (43.0%) 39 (43.8%) 0.908
Diabetes mellitus, n(%) 78 (15.1%) 18 (20.2%) 0.223
Coronary heart disease, n(%) 91 (17.6%) 17 (19.1%) 0.739
Stroke, n(%) 87 (16.9%) 17 (19.1%) 0.605
Chronic lung disease, n(%) 36 (7.0%) 10 (11.2%) 0.161
Smoking, n(%) 109 (21.1%) 24 (27.0%) 0.219
Drinking, n(%) 56 (10.9%) 10 (11.2%) 0.815
Charlson comorbidity index, 2 [1–3] 3 [1–4] 0.014
median [IQR]
MMSE, median [IQR] 25 [22–27] 23 [20–26] <0.001
ASA physical status 0.023
I, n(%) 16 (3.1%) 2 (2.2%)
II, n(%) 335 (64.9%) 46 (51.7%)
III, n(%) 163 (31.5%) 39 (43.8%)
IV, n(%) 2 (0.4%) 2 (2.2%)
Baseline MAP, mmHg, median 93 [89–100] 93 [88–98] 0.417
[IQR] Fig. 2. Nonlinear association of duration of MAP ≤65 mmHg with risk of POD
adjusted for with for age, sex, BMI, drinking, hypotension, stroke, chronic lung
disease, MMSE, Charlson comorbidity index, anesthesia time, blood loss, and
Intraoperative factors
Pre-induction MAP, mmHg, 108 [99–116.5] 106 [96–116.5] 0.501
blood transfusion.
median [IQR]
Surgical specialty 0.999
Thoracic surgery, n(%) 281 (54.5%) 49 (65.1%) Table 2
Orthopedic surgery, n(%) 235 (45.5%) 40 (44.9%) Univariable and multivariable logistic regression analysis for prediction of
Minutes for MAP ≤65 mmHg, 2 [0–7] 5 [2− 13] <0.001 postoperative delirium after non-cardiac surgery.
min, median [IQR]
TWA of MAP ≤65 mmHg, mmHg 0.03 0.09 <0.001 Variables Univariate analysis Multivariable analysis
[0.00–0.16] [0.02–0.26] OR (95%CI) P-value OR (95%CI) P-value
Anesthesia time, h, median [IQR] 3.08 3.33 0.164
[2.42–4.12] [2.44–5.06] MAP ≤65 mmHg
Blood loss, L, median [IQR] 0.10 0.15 0.163 0 min
[0.05–0.20] [0.10–0.30] <5mins 1.34 0.428 1.18 0.671
Blood transfusion, n(%) 26 (2.3%) 12 (13.5%) 0.002 (0.65–2.73) (0.56–2.50)
≥5mins 4.34 <0.001 3.93 <0.001
IQR = inter-quartile range; BMI: body mass index; ASA: American society of (2.36–7.96) (2.07–7.45)
anesthesiologists; MMSE: Mini-Mental State Examination; TWA: time-weighted Age 1.06 0.006 1.04 0.138
average. (1.02–1.11) (0.99–1.09)
Male, sex 0.72 0.149 0.54 0.032
(0.46–1.13) (0.31–0.95)
lactate, which are sensitive to tissue oxygen deficiency, were associated BMI 1.01 0.717 1.05 0.210
with POD incidence [45]. Furthermore, deep anesthesia, which is often (0.95–1.08) (0.98–1.12)
accompanied by intraoperative hypotension, was considered to induce Drinking 1.04 0.915 1.26 0.583
(0.51–2.12) (0.56–2.85)
neuronal injury and increase POD incidence [46–48]. The above
Hypertension 1.03 0.889 0.99 0.978
assumption may also be supported by other postoperative complications (0.66–1.63) (0.58–1.70)
found in this study. Indeed, the other postoperative complications, such Stroke 1.16 0.605 0.90 0.768
as AKI, AMI, and stroke, frequently occurred in the long hypotension (0.65–2.07) (0.46–1.77)
patients than those who had short duration of hypotension or no Chronic lung disease 1.69 0.166 1.15 0.764
(0.81–3.54) (0.47–2.80)
hypotension.
MMSE 0.86 <0.001 0.83 <0.001
It is worth pointing out that this is a retrospective, single-center and (0.80–0.92) (0.77–0.90)
observational study and only patients undergoing thoracic and ortho­ Charlson comorbidity 1.24 0.002 1.20 0.033
pedic surgery were included. Thus, the generality of our patient popu­ index (1.08–1.42) (1.01–1.41)
Anesthesia time 1.14 0.052 0.98 0.789
lation is questionable. There were also considerable patients who were
(1.00–1.31) (0.83–1.15)
excluded into data analysis due to lack of clarity and unavailable data Blood loss 2.43 0.032 1.59 0.388
including those patients without MMSE data in the records. Whether the (1.01–5.48) (0.55–4.59)
duration and severity of intraoperative hypotension on complications Blood transfusion 2.94 0.004 1.71 0.242
including delirium following surgery were under- or over-estimated is (1.42–6.06) (0.70–4.19)
unknown. Lastly, there is a very high occurrence of delirious patients CI: confidence interval; OR: odds ratio; BMI: body mass index; MMSE: Mini-
who had hypotension lasted for from 5 to 6 min with an extreme OR Mental State Examination.
value (Supplement Fig. S1). This is likely co-incident but relatively small
sample size is also a possible reason. On the other hand, there are many
confounding factors in clinical settings which may cause disproportional
dataset. Nevertheless, this did not affect the conclusions.

4
W. Duan et al. Journal of Clinical Anesthesia 88 (2023) 111125

Table 3 Appendix A. Supplementary data

Subgroup analyses in patients with three categories of MAP ≤65 mmHg.
Multivariable logistic model was adjusted with for age, MMSE, Charlson co­ Supplementary data to this article can be found online at https://doi.
morbidity index, anesthesia time, blood loss and blood transfusion. org/10.1016/j.jclinane.2023.111125.
Analysis Total Adjusted OR (95% CI) P for
(incident interaction References
%)

<5 mins ≥5mins [1] Inouye SK, Westendorp RG, Saczynski JS, et al. Delirium in elderly people. Lancet
2014;383:911–22. https://doi.org/10.1016/S0140-6736(13)60688-1.
History of arterial 0.520 [2] Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction,
hypertension and management. Br J Anaesth 2020;125:492–504. https://doi.org/10.1016/j.
No history of 344 1.64 6.06 bja.2020.06.063.
arterial (14.5%) (0.30–5.12); (2.20–16.69) [3] Mattison MLP. Delirium. Ann Intern Med 2020;173. https://doi.org/10.7326/
hypertension AITC202010060. ITC49–ITC64.
History of 261 1.02 2.87 [4] Wilson JE, Mart MF, Cunningham C, Shehabi Y, Girard TD, MacLullich AMJ, et al.
arterial (18.8%) (0.36–2.88); (1.19–6.92) Delirium. Nat Rev Dis Primers 2020;6:90. https://doi.org/10.1038/s41572-020-
hypertension 00223-4.
[5] Murthy S, Hepner DL, Cooper Z, Bader AM, Neuman MD. Controversies in
Duration of 0.722
anaesthesia for noncardiac surgery in older adults. Br J Anaesth 2015;115:ii15–25.
surgery
https://doi.org/10.1093/bja/aev396.
Short duration 273 1.13 4.22 [6] Fong TG, Inouye SK. The inter-relationship between delirium and dementia: the
of surgery (<3 (13.2%) (0.40–3.23) (1.70–10.51) importance of delirium prevention. Nat Rev Neurol 2022;18:579–96. https://doi.
h) org/10.1038/s41582-022-00698-7.
Long duration of 332 1.48 4.24 [7] Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative
surgery (≥3 h) (16.0%) (0.51–4.31) (1.72–10.44) hypotension and the risk of postoperative adverse outcomes: a systematic review.
Surgical procedure 0.464 Br J Anaesth 2018;121:706–21. https://doi.org/10.1016/j.bja.2018.04.036.
Thoracic 330 1.42 6.93 [8] van Zuylen ML, Gribnau A, Admiraal M, Ten Hoope W, Veelo DP, Hollmann MW,
surgery (14.8%) (0.41–4.92) (2.48–19.32) et al. The role of intraoperative hypotension on the development of postoperative
Orthopedic 275 1.07 2.60 cognitive dysfunction: a systematic review. J Clin Anesth 2021;72:110310. https://
surgery (14.5%) (0.42–2.76) (1.11–6.42) doi.org/10.1016/j.jclinane.2021.110310.
[9] Wesselink EM, Abawi M, Kooistra NHM, Kappen TH, Agostoni P, Emmelot-Vonk M,
MMSE: Mini-Mental State Examination. et al. Intraoperative hypotension and delirium among older adults undergoing
transcatheter aortic valve replacement. J Am Geriatr Soc 2021;69:3177–85.
https://doi.org/10.1111/jgs.17361.
5. Conclusion [10] Hirsch J, DePalma G, Tsai TT, Sands LP, Leung JM. Impact of intraoperative
hypotension and blood pressure fluctuations on early postoperative delirium after
non-cardiac surgery. Br J Anaesth 2015;115:418–26. https://doi.org/10.1093/bja/
Our study showed that >5 mins of intraoperative hypotension aeu458.
increased the occurrence of postoperative delirium after thoracic and [11] Wesselink EM, Kappen TH, van Klei WA, Dieleman JM, van Dijk D, Slooter AJ.
orthopedic surgery in the elderly, suggesting that a timely correcting Intraoperative hypotension and delirium after on-pump cardiac surgery. Br J
Anaesth 2015;115:427–33. https://doi.org/10.1093/bja/aev256.
intraoperative hypotension may decrease the risk of POD.
[12] Wachtendorf LJ, Azimaraghi O, Santer P, Linhardt FC, Blank M, Suleiman A, et al.
Association between intraoperative arterial hypotension and postoperative
Data sharing statement delirium after noncardiac surgery: a retrospective multicenter cohort study. Anesth
Analg 2022;134:822–33. https://doi.org/10.1213/ANE.0000000000005739.
[13] Brown CH, Neufeld KJ, Tian J, Probert J, Laflam A, Max L, et al. Effect of targeting
All data generated or analyzed during this study were included in the mean arterial pressure during cardiopulmonary bypass by monitoring cerebral
published article. Further inquiries about the datasets can be directed to autoregulation on postsurgical delirium among older patients: a nested randomized
the corresponding author on reasonable request. clinical trial. JAMA Surg 2019;154:819–26. https://doi.org/10.1001/
jamasurg.2019.1163.
[14] Smith PJ, Blumenthal JA, Hoffman BM, Rivelli SK, Palmer SM, Davis RD, et al.
Funding Reduced cerebral perfusion pressure during lung transplant surgery is associated
with risk, duration, and severity of postoperative delirium. Ann Am Thorac Soc
2016;13:180–7. https://doi.org/10.1513/AnnalsATS.201507-454OC.
This work was supported by the National Natural Science Foundation [15] Pappa M, Theodosiadis N, Tsounis A, Sarafis P. Pathogenesis and treatment of post-
of China (81971020, 82171189). operative cognitive dysfunction. Electron Physician 2017;9:3768–75. https://doi.
org/10.19082/3768.
[16] Chaix I, Manquat E, Liu N, Casadio MC, Ludes PO, Tantot A, et al. Impact of
CRediT authorship contribution statement hypotension on cerebral perfusion during general anesthesia induction: a
prospective observational study in adults. Acta Anaesthesiol Scand 2020;64:
Wen Duan: Conceptualization, Investigation, Methodology, Data 592–601. https://doi.org/10.1111/aas.13537.
[17] Hori D, Ono M, Rappold TE, Conte JV, Shah AS, Cameron DE, et al. Hypotension
curation, Methodology, Writing – original draft. Cheng-Mao Zhou:
after cardiac operations based on autoregulation monitoring leads to brain cellular
Formal analysis, Methodology, Writing - review & editing. Jin-Jin injury. Ann Thorac Surg 2015;100:487–93. https://doi.org/10.1016/j.
Yang: Data curation, Methodology, Visualization. Yue Zhang: Data athoracsur.2015.03.036.
curation, Software. Ze-Ping Li: Software,Formal analysis. Da-Qing Ma: [18] Sforza M, Bianchini E, Alivernini D, Salvetti M, Pontieri FE, Sette G. The impact of
cerebral vasomotor reactivity on cerebrovascular diseases and cognitive
Formal analysis, Writing - review & editing. Jian-Jun Yang: Formal impairment. J Neural Transm (Vienna) 2022;129:1321–30. https://doi.org/
analysis, Methodology, Project administration, Writing - review & 10.1007/s00702-022-02546-w.
editing. [19] Claassen JAHR, Thijssen DHJ, Panerai RB, Faraci FM. Regulation of cerebral blood
flow in humans: physiology and clinical implications of autoregulation. Physiol
Rev 2021;101:1487–559. https://doi.org/10.1152/physrev.00022.2020.
Declaration of Competing Interest [20] Eames PJ, Blake MJ, Panerai RB, Potter JF. Cerebral autoregulation indices are
unimpaired by hypertension in middle aged and older people. Am J Hypertens
2003;16:746–53. https://doi.org/10.1016/s0895-7061(03)00947-6.
The authors report no conflicts of interest. [21] Immink RV, van den Born BJ, van Montfrans GA, Koopmans RP, Karemaker JM,
van Lieshout JJ. Impaired cerebral autoregulation in patients with malignant
Acknowledgements hypertension. Circulation 2004;110:2241–5. https://doi.org/10.1161/01.
CIR.0000144472.08647.40.
[22] Sun Z. Aging, arterial stiffness, and hypertension. Hypertension 2015;65:252–6.
None. https://doi.org/10.1161/HYPERTENSIONAHA.114.03617.
[23] Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW. Dynamic and static
cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia.

5
W. Duan et al.
Anesthesiology 1995;83:66–76. https://doi.org/10.1097/00000542-199507000-
00008.
[24] NeuroVISION Investigators. Perioperative covert stroke in patients undergoing
non-cardiac surgery (NeuroVISION): a prospective cohort study. Lancet 2019;394:
1022–9. https://doi.org/10.1016/S0140-6736(19)31795-7.
[25] Sun LY, Chung AM, Farkouh ME, van Diepen S, Weinberger J, Bourke M, et al.
Defining an intraoperative hypotension threshold in association with stroke in
cardiac surgery. Anesthesiology 2018;129:440–7. https://doi.org/10.1097/
ALN.0000000000002298.
[26] Li H, Jia J, Yang Z. Mini-mental state examination in elderly chinese: a population-
based normative study. J Alzheimers Dis 2016;53:487–96. https://doi.org/
10.3233/JAD-160119.
[27] Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, et al.
Relationship between intraoperative hypotension, defined by either reduction from
baseline or absolute thresholds, and acute kidney and myocardial injury after
noncardiac surgery: a retrospective cohort analysis. Anesthesiology 2017;126:
47–65. https://doi.org/10.1097/ALN.0000000000001432.
[28] Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying
prognostic comorbidity in longitudinal studies: development and validation.
J Chronic Dis 1987;40:373–83. https://doi.org/10.1016/0021-9681(87)90171-8.
[29] Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying
confusion: the confusion assessment method. A new method for detection of
delirium. Ann Intern Med 1990;113:941–8. https://doi.org/10.7326/0003-4819-
113-12-941.
[30] Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, et al. Delirium in
mechanically ventilated patients: validity and reliability of the confusion
assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286:
2703–10. https://doi.org/10.1001/jama.286.21.2703.
[31] Maheshwari K, Ahuja S, Khanna AK, Mao G, Perez-Protto S, Farag E, et al.
Association between perioperative hypotension and delirium in postoperative
critically ill patients: a retrospective cohort analysis. Anesth Analg 2020;130:
636–43. https://doi.org/10.1213/ANE.0000000000004517.
[32] Ushio M, Egi M, Fujimoto D, Obata N, Mizobuchi S. Timing, threshold, and
duration of intraoperative hypotension in cardiac surgery: their associations with
postoperative delirium. J Cardiothorac Vasc Anesth 2022;36:4062–9. https://doi.
org/10.1053/j.jvca.2022.06.013.
[33] Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, et al.
Relationship between intraoperative hypotension, defined by either reduction from
baseline or absolute thresholds, and acute kidney and myocardial injury after
noncardiac surgery: a retrospective cohort analysis. Anesthesiology 2017;126:
47–65. https://doi.org/10.1097/ALN.0000000000001432.
[34] Liebeskind DS. Collateral circulation. Stroke 2003;34:2279–84. https://doi.org/
10.1161/01.STR.0000086465.41263.06.
[35] Liu P, De Vis JB, Lu H. Cerebrovascular reactivity (CVR) MRI with CO2 challenge: a
technical review. NeuroImage 2019;187:104–15. https://doi.org/10.1016/j.
neuroimage.2018.03.047.
Journal of Clinical Anesthesia 88 (2023) 111125
[36] Li S, Hafeez A, Noorulla F, Geng X, Shao G, Ren C, et al. Preconditioning in
neuroprotection: from hypoxia to ischemia. Prog Neurobiol 2017;157:79–91.
https://doi.org/10.1016/j.pneurobio.2017.01.001.
[37] Tzeng YC, Ainslie PN. Blood pressure regulation IX: cerebral autoregulation under
blood pressure challenges. Eur J Appl Physiol 2014;114:545–59. https://doi.org/
10.1007/s00421-013-2667-y.
[38] Turner DA, Adamson DC. Neuronal-astrocyte metabolic interactions:
understanding the transition into abnormal astrocytoma metabolism.
J Neuropathol Exp Neurol 2011;70:167–76. https://doi.org/10.1097/
NEN.0b013e31820e1152.
[39] Njemanze PC. Critical limits of pressure-flow relation in the human brain. Stroke
1992;23:1743–7. https://doi.org/10.1161/01.str.23.12.1743.
[40] Finnerty FA, Witkin L, Fazekas JF. Cerebral hemodynamics during cerebral
ischemia induced by acute hypotension. J Clin Invest 1954;33:1227–32. https://
doi.org/10.1172/JCI102997.
[41] Vimala S, Arulvelan A, Chandy Vilanilam G. Comparison of the effects of propofol
and sevoflurane induced burst suppression on cerebral blood flow and
oxygenation: a prospective. Randomised Double-Blinded Study World Neurosurg
2020;135:e427–34. https://doi.org/10.1016/j.wneu.2019.12.015.
[42] Casey CP, Lindroth H, Mohanty R, Farahbakhsh Z, Ballweg T, Twadell S, et al.
Postoperative delirium is associated with increased plasma neurofilament light.
Brain 2020;143:47–54. https://doi.org/10.1093/brain/awz354.
[43] Lopez MG, Hughes CG, DeMatteo A, O’Neal JB, McNeil JB, Shotwell MS, et al.
Intraoperative oxidative damage and delirium after cardiac surgery.
Anesthesiology 2020;132:551–61. https://doi.org/10.1097/
ALN.0000000000003016.
[44] Lopez MG, Pandharipande P, Morse J, Shotwell MS, Milne GL, Pretorius M, et al.
Intraoperative cerebral oxygenation, oxidative injury, and delirium following
cardiac surgery. Free Radic Biol Med 2017;103:192–8. https://doi.org/10.1016/j.
freeradbiomed.2016.12.039.
[45] Taylor J, Parker M, Casey CP, Tanabe S, Kunkel D, Rivera C, et al. Postoperative
delirium and changes in the blood-brain barrier, neuroinflammation, and
cerebrospinal fluid lactate: a prospective cohort study. Br J Anaesth 2022;129:
219–30. https://doi.org/10.1016/j.bja.2022.01.005.
[46] Evered LA, Chan MTV, Han R, Chu MHM, Cheng BP, Scott DA, et al. Anaesthetic
depth and delirium after major surgery: a randomised clinical trial. Br J Anaesth
2021;127:704–12. https://doi.org/10.1016/j.bja.2021.07.021.
[47] Berndt N, Kovács R, Schoknecht K, Rösner J, Reiffurth C, Maechler M, et al. Low
neuronal metabolism during isoflurane-induced burst suppression is related to
synaptic inhibition while neurovascular coupling and mitochondrial function
remain intact. J Cereb Blood Flow Metab 2021;41:2640–55. https://doi.org/
10.1177/0271678X211010353.
[48] Fang PP, Shang ZX, Xu J, Hu J, Zhang SC, Fan YG, et al. Contribution of
intraoperative electroencephalogram suppression to frailty-associated
postoperative delirium: mediation analysis of a prospective surgical cohort. Br J
Anaesth 2022. https://doi.org/10.1016/j.bja.2022.11.002. S0007-0912: 00634-1.