Defining an Intraoperative Hypotension Threshold in

Association with Stroke in Cardiac Surgery

Louise Y. Sun, M.D., S.M., Amy M. Chung, M.D., M.Sc., Michael E. Farkouh, M.D., M.Sc.,
Sean van Diepen, M.D., M.Sc., Jesse Weinberger, M.D., Michael Bourke, M.D., Marc Ruel, M.D., M.P.H.

ABSTRACT

Background: Stroke is a leading cause of morbidity, mortality, and disability in patients undergoing cardiac surgery. Iden-
tifying modifiable perioperative stroke risk factors may lead to improved patient outcomes. The association between the
severity and duration of intraoperative hypotension and postoperative stroke in patients undergoing cardiac surgery was
evaluated.
Methods: A retrospective cohort study was conducted of adult patients who underwent cardiac surgery requiring cardiopul-
monary bypass at a tertiary center between November 1, 2009, and March 31, 2015. The primary outcome was postoperative
ischemic stroke. Intraoperative hypotension was defined as the number of minutes spent within mean arterial pressure bands
of less than 55, 55 to 64, and 65 to 74 mmHg before, during, and after cardiopulmonary bypass. The association between
stroke and hypotension was examined by using logistic regression with propensity score adjustment.
Results: Among the 7,457 patients included in this analysis, 111 (1.5%) had a confirmed postoperative diagnosis of stroke.
Stroke was strongly associated with sustained mean arterial pressure of less than 64 mmHg during cardiopulmonary bypass
(adjusted odds ratio 1.13; 95% CI, 1.05 to 1.21 for every 10 min of mean arterial pressure between 55 and 64 mmHg;
adjusted odds ratio 1.16; 95% CI, 1.08 to 1.23 for every 10 min of mean arterial pressure less than 55 mmHg). Other fac-
tors that were independently associated with stroke were older age, hypertension, combined coronary artery bypass graft/
valve surgery, emergent operative status, prolonged cardiopulmonary bypass duration, and postoperative new-onset atrial
fibrillation.
Conclusions: Hypotension is a potentially modifiable risk factor for perioperative stroke. The study’s findings suggest that
mean arterial pressure may be an important intraoperative therapeutic hemodynamic target to reduce the incidence of stroke
in patients undergoing cardiopulmonary bypass. (Anesthesiology 2018; 129:440-7)

S TROKE and cognitive impairment are the second lead-

ing cause of postoperative morbidity, mortality, and
long-term disability.1 Strokes complicate 1.3 to 2.2% of
What We Already Know about This Topic
• Ischemic stroke after cardiac surgery is a devastating
complication affecting approximately 2% of patients
coronary artery bypass graft (CABG) surgeries2–4 and up to
• The relationship between hypotension occurring before,
8.7% of other major cardiac procedures.5 during, and after cardiopulmonary bypass and stroke remains
The lack of a clear understanding of the pathophysiol- unclear
ogy of postoperative stroke led to the lack of evidence-based
What This Article Tells Us That Is New
strategies to reduce the incidence of this complication. The
traditional putative mechanism for perioperative cerebral • Mean arterial pressure less than 65 mmHg for 10 or more
min during cardiopulmonary bypass is associated with an
ischemia is thromboembolism.1 The unique physiologic increased risk of stroke
vasomotor changes associated with cardiopulmonary bypass • Even mild relative hypotension, defined as a less than 10%
(CPB) suggest that hypotensive or distributive events may decrease from preinduction baseline during bypass, was also
associated with an increased risk of stroke
compound or even surpass embolic events in explaining
strokes after cardiac surgery; however, this hypothesis has
not been well studied. Additionally, there are no mean arte- during select phases of surgery such as the average MAP
rial pressure (MAP) maintenance guidelines for patients on CPB6 and lack of minute-to-minute blood pressure
undergoing CPB, and the associations between hypotension variations throughout the surgical procedure. Optimal
thresholds, duration, and stroke remain unclear. Previous blood pressure thresholds for stroke prevention have been
analyses have been limited by blood pressure measurements described as MAP within 30% of baseline in a noncardiac,
This article is featured in “This Month in Anesthesiology,” page 1A. This article has a visual abstract available in the online version.
Submitted for publication August 7, 2017. Accepted for publication May 8, 2018. From the Division of Cardiac Anesthesiology (L.Y.S.,
A.M.C., M.B.) and the Division of Cardiac Surgery (M.R.), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; the School of Epi-
demiology and Public Health (L.Y.S.), University of Ottawa, Ottawa, Ontario, Canada; Cardiovascular Research Program, Institute for Clini-
cal Evaluative Sciences, Ottawa, Ontario, Canada (L.Y.S.); Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
(M.E.F.); the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada (M.E.F.); the Department of Critical Care
and Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada (S.v.D.); and the Department of Neurology, The Icahn School
of Medicine at Mount Sinai, New York, New York ( J.W.).
Copyright © 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. Anesthesiology 2018; 129:440-7

Anesthesiology, V 129 • No 3 440 September 2018

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<zdoi;10.1097/ALN.0000000000002298>
 PERIOPERATIVE MEDICINE
nonneurologic surgery cohort, and ranges from systolic pres-
sure of greater than 90 mmHg at any point,7 MAP of greater
than 66 mmHg,8 and between 80 and 100 mmHg during
CPB in the context of cardiac surgery.9
This study aims to evaluate the association between the
severity and duration of intraoperative hypotension and
postoperative stroke. We hypothesize that hypotension dur-
ing and after CPB is associated with the risk of postoperative
stroke.
Materials and Methods
Design and Selection Criteria
The Research Ethics Board at the University of Ottawa Heart
Institute (Ottawa, Ontario, Canada) approved this protocol
and waived the need for individual patient informed con-
sent. We conducted a retrospective cohort study of 7,457
consecutive adult patients who underwent cardiac surgery
requiring CPB at the University of Ottawa Heart Institute
between November 1, 2009, and March 31, 2015. The Uni-
versity of Ottawa Heart Institute is a high-volume, univer-
sity-based tertiary care center that performs a full scope of
cardiac procedures. Patients undergoing off-pump proce-
dures were excluded because we aimed to study the associa-
tion of hypotension and stroke during the distinct periods
before, during, and after CPB. In addition, thoracic aortic
surgeries, cardiac transplantation, and ventricular assist
devices were excluded.
This study adhered to the Strengthening the Reporting
of Observational Studies in Epidemiology guidelines. The
primary outcome and the statistical analysis plan were made
before accessing the data.
Data Sources
We performed a retrospective analysis of prospectively col-
lected data from the University of Ottawa Heart Institute
perioperative database, which is a multimodular database
managed by a multidisciplinary committee and which
undergoes regular, scheduled quality assurance audits. This
database contains patient demographics, comorbidities,
intraoperative management and hemodynamics, postopera-
tive interventions, and in-hospital outcomes.10
All intraoperative invasive blood pressure measurements
were recorded automatically every 15 s in an electronic
patient record (CompuRecord, Philips Medical Systems,
The Netherlands), with any artifacts removed by using an
automated algorithm as previously described.11 Specifically,
because there were up to four recorded MAP values per min-
ute, the median of these values was selected for the analysis.
Time periods corresponding to absent (no MAP readings) or
aberrant MAP values (an isolated MAP value that differed
more than 50% from both preceding and subsequent values)
were deleted. This approach effectively removed artifacts in
invasive MAP values related to manipulation of the arterial
line including blood sampling, clamping, flushing, and zero-
ing.11 In the event when arterial tracings were dampened,
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femoral or direct aortic pressure monitoring was provided
by the surgeon via a three-way stopcock, connected to the
original arterial line transducer. The new arterial record-
ings automatically replaced the dampened MAP recordings
in the electronic record. MAP readings were analyzed from
the onset of end-tidal carbon dioxide (i.e., induction) until
the last end-tidal carbon dioxide reading (i.e., the conclu-
sion of anesthesia and transfer of patient from the operating
room to the intensive care unit).11 We routinely place arterial
lines before induction at our institution with the exception
of critical emergencies such as aortic rupture, which were
excluded from this analysis. Intraoperative hemodynamic
data was processed by using R (version 3.2.1; https://cran.r-
project.org/bin/windows/base/old/3.2.1/; accessed on June
1, 2015).
Outcome and Exposures
The primary outcome was in-hospital postoperative isch-
emic stroke during the index surgical admission, defined
as new focal or global neurologic deficit of cerebrovascular
origin lasting 24 h or longer that was not present before sur-
gery. Potential strokes were identified in the perioperative
database by a trained data abstractor. Such cases were then
confirmed as strokes by clinician members of the study team
(L.Y.S., A.M.C.) after reviewing the physician notes, con-
sults, and postoperative brain computed tomography and
magnetic resonance imaging studies.
Three definitions were used a priori to define intraop-
erative hypotension, namely, the number of minutes spent
within MAP bands of less than 55, 55 to 64, and 65 to
74 mmHg before, during, and after CPB. During CPB,
MAP is driven by the pump flow and systemic vascular
resistance. Although MAP before CPB and MAP after CPB
are both driven by systemic vascular resistance and intrinsic
cardiac function, the post-CPB pulsatile flow and systemic
vascular resistance are also influenced by factors such as CPB
duration, degree of myocardial preservation, and air embo-
lism. We therefore separated the periods before, during, and
after CPB in our analyses due to their physiologic distinct-
ness. The selected MAP thresholds were based on thresholds
shown to be associated with harm in recent studies of hypo-
tension during noncardiac surgery.11–13
Statistical Analysis
Continuous variables were analyzed by using analysis of vari-
ance and presented as mean (SD). Categorical variables were
analyzed by using chi-square test and presented as number
(proportion).
Association of Hypotension and Stroke. The possible asso-
ciation between hypotension and stroke was examined by
using logistic regression with propensity score adjustment
based on the theoretical framework proposed by Rosenbaum
and Ruben14 to estimate the average treatment effect among
treated. Propensity scores were derived for each of the pre-
defined MAP bands (i.e., MAP levels of less than 55, 55 to

64, and 65 to 74) to represent the likelihood of an intra-
operative hypotensive event lasting for 1 min or longer. The
propensity of each threshold of hypotension was calculated
by using a nonparsimonius multivariable logistic regression
model based on biologically plausible risk factors of hypo-
tension (age, sex, body surface area, left ventricular ejection
fraction less than 35%, hypertension, heart failure, peripheral
vascular disease, atrial fibrillation, pulmonary hypertension,
active endocarditis, recent myocardial infarction, previous
stroke, transient ischemic attack, carotid disease, diabetes,
renal insufficiency, dialysis dependence, surgery type, opera-
tive priority, preoperative cardiogenic shock or cardiac arrest,
CPB duration, lowest hematocrit on CPB, intraoperative
blood transfusion, and intraoperative tranexamic acid dose
of 5g or more). Because current knowledge of hypoten-
sion risk factors is limited, these covariates were derived in
consultation with the main components of the Society of
Thoracic Surgeons15 and EuroScore II16 risk scores. Each of
the propensity-adjusted models consisted of four continu-
ous variables: the propensity score corresponding to one of
the predefined MAP thresholds and three covariates repre-
senting the total duration of hypotension below that MAP
threshold before, during, and after CPB, respectively. The
propensity score models had moderate discriminating abili-
ties (c-statistics ranging from 0.66 to 0.75). The covariates
and their definitions are provided in appendix 1.
Other Stroke Risk Factors. We identified other stroke risk
factors through a nonparsimonious multivariable logistic
regression model with variables that were selected a priori
based on perioperative stroke literature,1,5,17 the key com-
ponents of the Society of Thoracic Surgeons score,15 and the
EuroScore II.16 These risk factors were age, sex, history of
transient ischemic attack, stroke, or carotid stenosis; hyper-
tension, diabetes, reoperative procedure, CPB duration,
postoperative atrial fibrillation, mixed CABG and valve/
other procedure and thoracic aortic surgery, as compared to
CABG-only or single-valve procedures.5 We tested for the
presence of any interaction between MAP levels before, dur-
ing, and after CPB of less than 55 mmHg and each of these
covariates using multiplicative interaction terms.
Sensitivity Analyses. Several sensitivity analyses were per-
formed post hoc. First, we examined the association of longest
hypotensive episode durations before, during, and after CPB
with stroke as a means for assessing consecutive hypotensive
minutes. Although we address the association between con-
secutive minutes of hypotension and stroke via a sensitiv-
ity analysis of longest hypotensive episodes, more rigorous
analyses of the time-varying patterns of hypotensive episodes
contributing to a total cumulative hypotensive duration
were beyond the scope of this study. Second, as the pre- and
post-CPB periods had in common the pulsatile flow that
was driven by intrinsic cardiac function, we repeated the
above-described propensity-adjusted analyses by combining
the total durations of hypotension pre- and post-CPB into a
single variable. Thus, two distinct variables, one representing
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Hypotension and Stroke in Cardiac Surgery
the combined pre- and post-CPB hypotension duration and
the other representing hypotension duration on CPB, were
studied. Third, we combined the total durations of hypo-
tension throughout the entire case into a single variable to
examine the impact of the cumulative duration of hypo-
tension on stroke. Fourth, we determined the association
of stroke with relative hypotension thresholds. The relative
thresholds examined were decreases in MAP of less than
10%, 10 to 20%, and 20 to 30% from the preinduction
value. The preinduction MAP was defined as the mean of
three consecutive MAP measurements immediately before
induction of anesthesia and 3 min before the first appearance
of continuous expired carbon dioxide registration.7
We used the odds ratio (95% CI) to describe the measure
of association. We defined a minimum clinically meaning-
ful effect as more than 1.05 per 10 min of hypotension, and
more than 1.5 for other covariates. In this primarily explor-
atory study, we did not correct for multiple testing. Statistical
analyses were conducted using SAS 9.4 (SAS Institute, USA),
with statistical significance defined by a two-tailed P < 0.05.
Missing Data
Main outcome and exposure variables were complete for
all included subjects. Left ventricular ejection fraction was
imputed using the group mean for 112 (1.5%) of patients.
Weight was imputed with the group mean for 15 patients.
The proportion of absent and artifactual MAP values
removed was less than 1% of the total. No other data were
missing.
Results
Among the 7,457 patients included in this analysis, 111
(1.4%) had a confirmed postoperative diagnosis of stroke.
The absolute risk of stroke was 0.7% (n = 22) in isolated
CABG, 1.2% (n = 23) in valve-only, and 2.8% (n = 66)
in combined CABG/valve. Table  1 summarizes the demo-
graphic and perioperative characteristics of patients with
and without strokes. Stroke patients were more frequently
older and female; had preexisting hypertension, carotid or
cerebrovascular disease, renal insufficiency, active endocar-
ditis, or preoperative cardiogenic shock; underwent surger-
ies that were reoperative, emergent, or more complex (i.e.,
combined CABG/valve); had longer CPB durations, lowest
CPB hematocrit less than 0.22, or new-onset atrial fibril-
lation postoperatively. Pre-CPB MAP less than 55 mmHg
modified the effect of new-onset postoperative atrial fibrilla-
tion on stroke (interaction P = 0.05).
Table 2 demonstrates the average total and longest episode
durations of hypotension exposure before, during, and after
CPB. Compared to nonstroke patients, stroke patients were
more likely to have had MAP less than 55 pre-CPB and MAP
less than 64 during and after CPB. The absolute risk of stroke
increased with decreasing MAP thresholds, such that those
who were exposed to longer than the average duration of MAP
less than 55 had the highest risk of stroke. Table 3 illustrates the
 PERIOPERATIVE MEDICINE

Table 1.  Characteristics of Patients with and without Postoperative Strokes

Variable Stroke (n = 111) No Stroke (n = 7,346) P Value

Demographic
 Mean age (SD), yr 69 ± 15 65 ± 12 0.01
 Female sex, n (%) 44 (40) 2,059 (28) 0.007
Medical history, n (%)
 Hypertension 93 (84) 5,253 (72) 0.004
 LVEF < 35% 10 (9) 898 (12) 0.30
 Heart failure 41 (37) 2,379 (32) 0.31
 Carotid disease, TIA, or stroke 33 (30) 1,364 (19) 0.003
 Diabetes on medications 31 (28) 1,952 (27) 0.75
 GFR < 50  ml · min–1 · 1.73 m–2 38 (34) 1,207 (16) < 0.001
 Dialysis 3 (3) 146 (2) 0.59
 Reoperative procedure 11 (10) 686 (9) 0.84
 Emergent surgery 24 (22) 675 (9) < 0.001
 Preoperative shock 12 (11) 345 (5) 0.003
 Active endocarditis 8 (7) 176 (2) 0.001
 Type of surgery, n (%)
 CABG only 22 (20) 3,144 (43) < 0.001
 Valve only 23 (21) 1,869 (25)
 Combined CABG/valve 66 (59) 2,333 (32)
Intraoperative
 Mean bypass duration (SD), min 149 ± 79 107 ± 52 < 0.001
 Lowest hematocrit < 0.22, n (%) 20 (18) 601 (8) < 0.001
Postoperative
 New-onset atrial fibrillation 45 (41) 761 (10) < 0.001

CABG = coronary artery bypass grafting; GFR = glomerular filtration rate calculated using the Cockcroft–Gault formula; LVEF = left ventricular ejection
fraction; TIA = transient ischemic attack.

Table 2.  Mean Durations of Total and Longest Episodes of Hypotension before, during, and after Cardiopulmonary Bypass and Their
Corresponding Stroke Risk

Total Hypotension Duration (min) Longest Episode Duration (min)

Absolute Absolute
Stroke, mean No Stroke, Risk,* n Stroke, mean No Stroke, Risk,* n
Timing MAP (mmHg) (SD) mean (SD) (%) P Value (SD) mean (SD) (%) P Value

Pre-CPB < 55 5.4 ± 9.9 3.3 ± 7.1 28 (2.1%) 0.03 3.0 ± 5.7 1.9 ± 3.6 24 (2.2%) 0.05
55–64 14.1 ± 15.2 12.2 ± 14.4 39 (1.6%) 0.17 5.5 ± 6.5 4.4 ± 7.2 35 (2.2%) 0.13
65–74 22.9 ± 21.1 26.1 ± 20.4 47 (1.2%) 0.11 11.6 ± 15.1 11.1 ± 12.5 39 (1.7%) 0.69
CPB < 55 21.4 ± 35.5 9.5 ± 15.4 32 (3.8%) < 0.001 8.6 ± 15.9 3.9 ± 7.7 26 (4.4%) 0.003
55–64 27.6 ± 27.2 25.5 ± 21.9 40 (2.1%) 0.002 15.3 ± 20.7 10.5 ± 14.8 36 (2.4%) 0.02
65–74 34.4 ± 34.9 23.9 ± 22.1 45 (1.6%) 0.43 26.5 ± 37.0 20.8 ± 22.2 34 (1.6%) 0.11
Post-CPB < 55 9.2 ± 20.0 3.8 ± 11.1 25 (3.1%) 0.006 3.5 ± 7.3 1.9 ± 4.5 26 (3.1%) 0.02
55–64 23.5 ± 27.3 16.0 ± 18.6 38 (2.2%) 0.004 9.7 ± 12.6 6.9 ± 10.3 38 (2.7%) 0.02
65–74 27.4 ± 25.4 26.6 ± 21.0 46 (1.5%) 0.73 20.6 ± 25.2 15.9 ± 16.7 39 (2.0%) 0.05

*In patients who had a hypotensive episode that was longer than the mean hypotension duration suffered by stroke patients.
CPB = cardiopulmonary bypass; MAP = mean arterial pressure.

association between stroke and various thresholds of hypoten-
sion before, during, and after CPB. Stroke was associated with
longer durations of hypotension during CPB. Specifically, in
the analysis using total hypotension duration, every additional
10 min of CPB MAP less than 55 was associated with a 16%
increased odds of stroke (adjusted odds ratio 1.16; 95% CI,
1.08 to 1.23), and every additional 10 min of MAP between
55 and 64 was associated with a 13% increased odds of stroke
(adjusted odds ratio 1.13; 95% CI, 1.05 to 1.21).
In addition to intraoperative hypotension, other inde-
pendent predictors of stroke risk included older age,
hypertension, combined CABG/valve surgery, emergent
operative status, prolonged CPB duration, and postopera-
tive new-onset atrial fibrillation (table  4). This multivari-
able model had excellent discriminative ability (c-statistic
0.81). Post hoc, we determined that we achieved 92% power
at a 0.05 significance level to detect an odds ratio of 1.5 for
risk factors with a prevalence of 20% or greater and 73%
power to detect an odds ratio of 1.5 for risk factors with

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 Hypotension and Stroke in Cardiac Surgery

Table 3.  Propensity-adjusted Odds Ratios of Stroke across Different Thresholds and Durations of Intraoperative Hypotension

Adjusted OR (95% CI) per 10 min of Hypotension

Timing MAP (mmHg) Total Hypotension Duration P Value Longest Episode Duration P Value

Pre-CPB < 55 0.98 (0.80–1.21) 0.86 1.25 (0.86–1.83) 0.24

55–64 0.99 (0.87–1.13) 0.84 1.04 (0.86–1.27) 0.68
65–74 0.92 (0.83–1.03) 0.16 0.95 (0.81–1.10) 0.48
CPB < 55 1.16 (1.08–1.23)*† < 0.001 1.16 (1.02–1.31)*† 0.02
55–64 1.13 (1.05–1.21)*† 0.001 1.10 (1.01–1.21)*† 0.03
65–74 1.05 (0.96–1.14) 0.28 1.08 (1.01–1.16)*† 0.03
Post-CPB < 55 1.08 (0.99–1.19) 0.18 1.04 (0.82–1.35) 0.76
55–64 1.08 (0.99–1.17) 0.07 1.08 (0.97–1.21) 0.21
65–74 1.02 (0.93–1.12) 0.70 1.08 (0.99–1.18) 0.07

*Clinically meaningful association. †Statistically significant association.

CPB = cardiopulmonary bypass; MAP = mean arterial pressure; OR = odds ratio.

Table 4.  Multivariable Predictors of Stroke Sensitivity Analyses

The association between hypotension and stroke remained
Adjusted OR
Predictor (95% CI) P Value
robust in sensitivity analyses where the longest hypotension
episodes were considered in place of total duration (table 3).
Demographic In addition to similar increases in the odds of stroke in the
 Age (per 10 yr) 1.33 (1.07–1.65)* 0.01
lower MAP bands, every additional 10 min of CPB MAP
 Female sex 1.40 (0.92–2.13) 0.11
between 65 and 74 was associated with an 8% increased odds
Medical history
 Hypertension 2.27 (1.23–4.19)*† 0.009 of stroke (adjusted odds ratio 1.08; 95% CI, 1.01 to 1.16).
 LVEF < 35% 1.85 (0.86–4.00) 0.12 Table  5 illustrates the association between stroke and
 Heart failure 0.66 (0.42–1.04) 0.08 total hypotension duration throughout the entire surgical
 Carotid disease, TIA, or stroke 1.44 (0.90–2.30) 0.13 case (i.e., before, during, and after CPB) and combined pre-
 Diabetes on medications 1.01 (0.64–1.58) 0.98 and post-CPB hypotension durations. In both of these sen-
 GFR < 50  ml · min–1 · 1.73 m–2 0.85 (0.53–1.39) 0.52 sitivity analyses, more than 10 min of MAP less than 64 was
 Dialysis 0.66 (0.18–2.41) 0.53 associated with stroke. In the sensitivity analysis that exam-
 Reoperative procedure 0.71 (0.35–1.43) 0.33
ined relative MAP thresholds (table 6), small decreases (less
 Emergent surgery 2.04 (1.09–3.83)*† 0.03
 Preoperative shock 1.44 (0.63–3.29) 0.39
than 10%) in MAP pre-CPB appeared protective, whereas
 Active endocarditis 1.56 (0.55–4.43) 0.41 any MAP thresholds below the preinduction value during
 Type of surgery CPB were associated with stroke.
  CABG only Reference 0.005
  Valve only 1.62 (0.84–3.14) Discussion
  Combined CABG/valve 2.82 (1.64–4.86)*†
Intraoperative Our findings suggest that intraoperative blood pressure may
 Bypass duration (per 10  min) 1.04 (1.01–1.06)* 0.003 be a modifiable risk factor for stroke after cardiac surgery. We
 MAP < 55 mmHg (per 10  min) identified critical MAP thresholds and durations for postop-
 Pre-CPB 0.98 (0.78–1.23) 0.83 erative ischemic stroke to be MAP less than 64 mmHg for
 During CPB 1.11 (1.03–1.20)*† 0.008 more than 10 min during CPB. This finding is important
 Post-CPB 1.07 (0.98–1.18) 0.14 because stroke is associated with mortality, quality of life, and
 Lowest hematocrit < 0.22 1.14 (0.64–2.02) 0.65
healthcare cost.
Postoperative
The present study is novel in its exploration of the asso-
 New-onset atrial fibrillation 4.42 (2.90–6.74)*† < 0.001
ciation between hypotension and stroke throughout all
*Statistically significant association. †Clinically significant association. phases of cardiac surgery on a minute-to-minute basis. One
CABG = coronary artery bypass graft; CPB = cardiopulmonary bypass;
GFR = glomerular filtration rate calculated using the Cockcroft–Gault for-
novel aspect of this study is the continuous high-fidelity
mula; LVEF = left ventricular ejection fraction; MAP = mean arterial pres- intraoperative recording of invasive blood pressure mea-
sure; OR = odds ratio; TIA = transient ischemic attack.
surements for each physiologically distinct stage of surgery.
Published studies evaluating the association between hypo-
a prevalence of 10% or greater. On testing multiplicative tension in cardiac surgery and stroke were not performed
interaction terms, we found that the effect of pre-CPB MAP in contemporary surgical populations, were descriptive in
less than 55 on stroke was amplified by complex surgery nature, and/or did not explore minute-to-minute blood
(combined CABG and valve) and new-onset postoperative pressure thresholds throughout the intraoperative period.
atrial fibrillation. Our findings are nonetheless consistent with previous

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 PERIOPERATIVE MEDICINE

Table 5.  Propensity-adjusted Odds Ratios of Stroke across Different Thresholds of Combined Durations of Hypotension

Combined Hypotension Duration before, Combined Hypotension Duration before

during, and after CPB and after CPB

MAP (mmHg) per 10 min of Hypotension Adjusted OR (95% CI) per 10 min P Value Adjusted OR (95% CI) per 10 min P Value

< 55 1.09 (1.05–1.12)*† < 0.001 1.09 (1.04–1.15)*† 0.001

55–64 1.08 (1.04–1.12)*† < 0.001 1.08 (1.03–1.14)*† 0.002
65–74 1.00 (0.97–1.04) 0.92 0.99 (0.94–1.04) 0.66

*Clinically meaningful association. †Statistically significant association.

CPB = cardiopulmonary bypass; MAP = mean arterial pressure; OR = odds ratio.

Table 6.  Propensity-adjusted Odds Ratios of Stroke across Different Relative Thresholds and Durations of Intraoperative
Hypotension

Timing Relative Drop per 10 min of Hypotension Adjusted OR (95% CI) per 10 min of Hypotension P Value

Pre-CPB < 10% 0.94 (0.89–1.00) 0.04

10–20% 0.91 (0.79–1.04) 0.18
20–30% 0.97 (0.86–1.10) 0.65
CPB < 10% 1.07 (1.03–1.11)*† 0.001
10–20% 1.15 (1.03–1.29)*† 0.02
20–30% 1.16 (1.00–1.30)*† 0.05
Post-CPB < 10% 0.92 (0.77–1.06) 0.50
10–20% 0.87 (0.74–1.02) 0.08
20–30% 0.98 (0.87–1.10) 0.74

*Clinically significant association. †Statistically significant association.

CPB = cardiopulmonary bypass; OR = odds ratio.

reports. In a randomized control study of 248 patients
undergoing CABG and valve surgery in the early 1990s, the
high-MAP group (CPB MAP target of 80 to 100 mmHg)
had a lower incidence of strokes (2.4% vs. 7.2%) and mor-
tality (1.6% vs. 4.0%) at 6 months, compared to the con-
trol group whose CPB MAP target was 50 to 60 mmHg.8
Two historical cohort studies of CABG patients demon-
strated that intraoperative hypotension defined as a systolic
blood pressure less than 90 mmHg for more than 30 min or
intraoperative systolic blood pressure less than 40 mmHg
for more than 5 min were each associated with an up to
fourfold higher risk of stroke.18,19 In addition, in patients
with established cardiac surgery-related strokes, those with
at least 10-mmHg decrease in MAP from preoperative value
had four times the odds of bilateral watershed infarcts.6
During cardiac surgery, hypotension occurs as a result
of decreased venous return from cardiac manipulation,
arrhythmias, reduced ventricular function, and/or decreased
systemic vascular resistance.20 Despite the importance of
maintaining systemic perfusion pressure,4,13 no guidelines
provide perfusion pressure targets or define what duration
of hypotension can be harmful. The range of cerebral auto-
regulation is thought to be between MAP of 50 and 150
mmHg.21,22 In practice, common CPB MAP targets vary
between 50 and 70 mmHg.23 The determination of an
optimal CPB perfusion pressure is often based on the per-
ceived lower limit of autoregulation. Early studies suggested
50 to 55 mmHg to be acceptable in healthy young volunteers
and animal models.21 Subsequently, a MAP of no less than
70 mmHg has been suggested in normotensive, nonanes-
thetized adults,24–26 and a MAP of no less than 66 mmHg
has been suggested in anesthetized elderly patients during
CPB.7 Despite decreased cerebral metabolic demand under
general anesthesia, the commonly accepted CPB MAP target
of 50 mmHg is likely inappropriate in elderly patients with a
rightward cerebral autoregulatory shift.27,28
Neurologic complications are a cause of major morbidity
and mortality after cardiac surgery. Although the pathogenesis
of stroke is multifaceted, current evidence points to patient-
related risk factors as a more important contributor than sur-
gical technique, such as the use of cardiopulmonary bypass.29
We identified independent stroke risk factors after adjustment
for intraoperative hypotension. Our finding of older age,18,29–36
preexisting hypertension,1,37,38 combined valvular and CABG
surgery,5,39–41 and prolonged CPB duration41 are consistent
with multiple previous reports. Most importantly, in addition
to defining critical thresholds of hypotension as a modifiable
stroke risk factor, we also confirmed CPB duration and postop-
erative atrial fibrillation37,38 as strong and potentially modifiable
risk factors. Of note, MAP less than 55 mmHg pre-CPB ampli-
fied the effect of new-onset postoperative atrial fibrillation on
the development of stroke. Careful perioperative planning may
mitigate the effects of nonmodifiable stroke risk factors such as
age and complex surgery, but careful perfusion pressure man-
agement during CPB and employing preventative measures
against postoperative atrial fibrillation are potential therapeutic
strategies to reduce postoperative stroke that merit evaluation in
a prospective multicenter trial.

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Limitations and Strengths
Our study has several limitations. First, there are limitations
that are inherent of its retrospective and observational design.
Our study demonstrates a strong association between stroke
and hypotension. However, further studies are needed to
demonstrate whether stroke results directly from hypotension
or also indirectly through low cardiac output, hypovolemia,
and vasopressor use. Second, we are limited in our ability
to collect certain data elements that may be related to the
occurrence of hypotension, such as precise end-tidal concen-
trations of volatile anesthetics and maintenance medications.
Nonetheless, this study is novel in its attempt to define hypo-
tension on a minute-to-minute basis during physiologically
distinct periods of cardiac surgery (i.e., before, during, and
after CPB) and therefore provides important insight for blood
pressure management throughout the surgical period. Third,
our findings are to be interpreted in the context of multiple
testing. Furthermore, although we address the association
between consecutive minutes of hypotension and stroke via
a sensitivity analysis of longest hypotensive episodes, more
rigorous analyses of the time-varying patterns of hypoten-
sive episodes contributing to a total cumulative hypotensive
duration were beyond the scope of this study. However, our
refined MAP artifact removal algorithm allowed for reliable
definition of hypotensive episodes. Fourth, the present study
is single center in nature. Further studies are needed to con-
firm the generalizability of our findings.
Conclusions
In conclusion, we observed an increased risk of perioperative
stroke when intraoperative MAP fell below 64 mmHg for
more than 10 min during CPB. Our findings suggest that
intraoperative MAP may be a modifiable hemodynamic
therapeutic target for stroke prevention in patients under-
going cardiac surgery and provide a rationale for prospec-
tive studies of hemodynamic goal-directed therapies in these
patients.
Research Support
Supported in part by the Research Funds of the Division of
Cardiac Anesthesiology of the University of Ottawa Heart In-
stitute, Ottawa, Ontario, Canada. Dr. Chung was supported by
the Heart and Stroke Foundation (Ontario, Canada) Hannah
Pherril Scholarship.
Competing Interests
Dr. Farkouh receives research support from Amgen
(­Mississauga, Ontario, Canada). The other authors declare
no competing interests.
Correspondence
Address correspondence to Dr. Sun: Room H2410, 40
Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada. lsun@
ottawaheart.ca. This article may be accessed for personal
use at no charge through the Journal Web site, www.
anesthesiology.org.
Anesthesiology 2018; 129:440-7 446 Sun et al.
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Hypotension and Stroke in Cardiac Surgery
Appendix 1. Covariates and Their
Definitions
All covariate information is prospectively collected in our
institutional perioperative database. These data are provided
by attending anesthesiologists on the day of surgery, undergo
weekly audits, and are of research quality.10
Stroke Postoperative ischemic stroke, defined as
new focal or global neurologic deficit of
cerebrovascular origin lasting ≥ 24 h that
was not present before surgery and was
nonhemorrhagic in nature
Intraoperative Defined as duration (min) of MAP < 55, 65,
­hypotension and 75 mmHg before, during, and after
cardiopulmonary bypass
Small body ­ Body surface area < 1.7 m2
surface area
Rent myocardial Most recent myocardial infarction within 30
infarction days of surgery
0 - None
1 - Non-Q wave or transmural infarction
Heart failure Documented history of heart failure
Carotid disease Unilateral or bilateral occlusion in the inter-
nal carotid artery of ≥ 50% or previous
history of carotid endarterectomy
Diabetes on Diabetes mellitus treated with oral hypogly-
­medications cemic and/or insulin
Emergent surgery Surgery that must take place within 24 h of
acute hospital admission
Preoperative Requirement for inotropic support with
shock evidence of end organ hypoperfusion or
dysfunction or intraaortic balloon pump in
situ before surgery
Active endocarditis Endocarditis that is currently being treated
with antibiotics
Intraoperative Number of packed red blood cells,
transfusion expressed as a continuous variable
New-onset atrial New postoperative atrial fibrillation that was
fibrillation not present preoperatively
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