Progress Review

Stroke and Encephalopathy After Cardiac Surgery

An Update
Guy M. McKhann, MD; Maura A. Grega, RN, MSN; Louis M. Borowicz Jr, MS;
William A. Baumgartner, MD; Ola A. Selnes, PhD

Background and Purpose—As a result of advances in surgical, anesthetic, and medical management, cardiac surgery can
now be performed on older, sicker patients, some of whom have had prior cardiac interventions. As surgical mortality
has declined in recent years, attention has focused on the complications of stroke and encephalopathy after cardiac
surgery.
Summary of Review—Patients with preexisting cerebrovascular disease are at increased risk for these untoward
neurological outcomes, which are associated with longer lengths of hospital stay, higher costs, and greater mortality. The
mechanisms underlying these neurological events may include microemboli and hypoperfusion during surgery, and
postoperative atrial fibrillation. Predictive models, based on information available before surgery, allow identification
of these “high risk” patients.
Conclusion—Establishing the degree of functionally significant vascular disease of the brain before surgery should be an
essential part of the preoperative evaluation, particularly when modifications in surgical technique or novel
neuroprotective agents are being evaluated. (Stroke. 2006;37:562-571.)
Key Words: brain injuries 䡲 cardiovascular surgical procedures 䡲 cerebrovascular accident
䡲 coronary artery bypass 䡲 outcome assessment

T he most common cardiac surgical procedure per-

formed in the United States is coronary artery bypass
grafting (CABG). In the past 2 decades, there have been
significant changes in the population undergoing cardiac
surgery. Improvements in surgical procedures have made it
possible to operate successfully on older patients with
more comorbid disease. Conversely, this population is at
higher risk for age-related cerebrovascular disease, which
may predispose them to more severe neurological compli-
cations, including stroke and encephalopathy, during the
immediate postoperative period. This is exemplified in
Table 1, in which the risk factor profiles and outcomes for
patients at our hospital undergoing CABG in 1994 are
compared with those having surgery in 2004. We and
others have previously reviewed the neurocognitive com-
plications associated with CABG.1–3 Therefore, this review
focuses on 4 main questions regarding neurological prob-
lems associated with cardiac surgery: what are the out-
comes of patients having stroke or encephalopathy in the
postoperative period?; can we predict who is at highest
risk?; what are the underlying mechanisms?; and what
strategies are available to avoid injury to the brain includ-
ing possible future pharmacological interventions.
Neurological Outcomes in Cardiac
Surgical Patients
Stroke: Incidence
The reported incidence of stroke after cardiac surgery varies
depending on the procedure and whether the findings have
been obtained prospectively or retrospectively, such as from
chart review. For example, the stroke incidence with CABG
has been reported from 1.5%4 to 5.2%5 in prospective studies
as compared with 0.8% to 3.2% in retrospective studies.6,7
The incidence of encephalopathy and stroke in our prospec-
tive studies appears to be increasing, as shown in Table 1. We
believe that this increased incidence is because more “high
risk” patients currently undergo surgery at our institution than
10 years ago.
Chart reviews may not accurately identify the postopera-
tive timing during which strokes occur. Likosky et al found
that 42% of strokes were identified on postoperative day 1
and additional 20% by day 2,8 whereas other investigators,
relying solely on chart review, have suggested that the
majority of strokes occur several days after surgery.9 We
prospectively tracked the incidence (Table 2) and stroke
outcomes (Table 3) of CABG and all other types of cardiac
surgical procedures at our institution and found that the

Received July 29, 2005; final revision accepted October 12, 2005: accepted October 13, 2005.
From the Departments of Neurology (G.M.M, O.S.S.) and Surgery (W.A.B., M.A.G.), The Johns Hopkins University, School of Medicine; and The
Zanvyl Krieger Mind/Brain Institute (G.M.M., L.M.B.), The Johns Hopkins University, Baltimore, Md.
Correspondence and reprint requests to Dr Guy M. McKhann, 338 Krieger Hall, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD
21218. E-mail guy.mckhann@jhu.edu
© 2006 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000199032.78782.6c

562
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 McKhann et al Stroke and Encephalopathy After Cardiac Surgery 563

TABLE 1. The Johns Hopkins Hospital CABG Experience: TABLE 3. Impact of Stroke on Early Outcomes After
Comparison of Patients Having Isolated CABG in 1994 and 2004 Cardiac Surgery23
CABG in 1994, CABG in 2004, Stroke, No Stroke,
n⫽724 n⫽290 P Value Variable (n⫽214) (n⫽5757) P Value
Hypertension 502 (69%) 230 (80%) 0.001 Intensive care unit length of 7.3 3.6 ⬍0.0001
Past stroke 51 (7%) 22 (8%) 0.42 stay, d

Carotid bruit 107 (15%) 32 (12%) 0.09 Postoperative hospital length 25.2 9.7 ⬍0.0001
of stay, d
Diabetes mellitus 216 (30%) 107 (37%) 0.01
Total hospital charges $60 750 $30 705 ⬍0.0001
Age, y 64.1⫾10 64.1⫾10 0.89
Hospital mortality 41 (19%) 240 (4%) ⬍0.0001
Stroke risk category17
Low risk 323 (45%) 130 (45%)
Medium risk 315 (43%) 104 (36%) 0.008 Stroke: Outcomes and Predictors of
High risk 86 (12%) 54 (19%)
High-Risk Patients
Patients with postoperative stroke have significantly higher
Cardiopulmonary 108⫾35 105⫾30 0.20
bypass time, min
mortality rates. Bucerius found that those with stroke had a
6-fold higher mortality (22.2% versus 3.75%; P⫽⬍0.001).10
Outcomes
The investigators from the Northern New England Cardio-
Perioperative stroke 21 (2.9%) 13 (4.5%) 0.14
vascular Disease Study Group11 compared survival in those
Encephalopathy 56 (7.7%) 40 (13.8%) 0.003 with and without stroke after CABG and found that survival
Death 21 (2.9%) 5 (1.7%) 0.20 rates at 1 year were 83% versus 94.1%, at 5 years 58.7%
Postoperative length 8.7⫾9.6 9.2⫾9.7 0.44 versus 83.3% and at 10 years 26.9% versus 61.9%, respec-
of stay, d tively. These differences were significant and those diag-
nosed with stroke had a 3-fold greater risk of death during the
10-year follow-up. In addition, in our experience, more than
majority of strokes were detected shortly after surgery (Fig- half the patients with strokes require in-patient rehabilitation
ure). Importantly, the incidence of stroke is much higher in before returning home.
the setting of combined cardiac procedures (ⱖ2) and in more A number of investigators have developed preoperative
technically challenging operations, such as aortic aneurysm predictive models to determine those at higher risk for
repairs with the use of hypothermic circulatory arrest. Strokes stroke.12–16 In general, these models use factors associated
that were identified after 7 days were more likely to occur in with systemic vascular disease, such as hypertension, diabe-
either patients having valve surgery or those with ventricular tes, peripheral vascular disease, evidence of cerebrovascular
disease, and age. The important point of these risk models is
assist devices. The mechanism for the delayed occurrence of
that they take into account the additive effect of known risk
postoperative stroke is not clear. As discussed below, 1
factors and allows for a stroke probability to be estimated for
possible mechanism is atrial fibrillation.
individual patients. We have developed predictive models for
those patients who are at increased risk for perioperative
stroke. Our original model was reported in 19975 and then
TABLE 2. Incidence of Stroke by Cardiac Surgical Procedure revised in 200217 to account for the changing demographics
(Data From 2001–2004) of our surgical population (see Table 4). Notably, all the
Cardiac Surgical Stroke Percent of Strokes Identified in the components required for this model are available to the
Procedure Rate First 2 Days of Surgery physician and the patient before surgery, thus permitting
CABG 4.1% 84% discussion of projected surgical risks to patients and families.
Valve 3.1% 65%
CABG/Valve 7.9% 76%
CABG/Other 7.2% 80%
Aortic repair 8.7% 83%
Other 3.6% 59%
CABG indicates isolated CABG, isolated off-pump CABG, or isolated Redo
CABG; VALVE, includes any valve replacement, valve repair, Ross procedure,
annuloplasty, or valve ring in any valve position (eg, combined with a patent
foramen ovale, ventricular septal defect closure, or Maze procedure); CABG/
Valve, CABG plus any of the valve procedures listed above; CABG/Other, CABG
plus any of the following: patent foramen ovale, surgical ventricular recon-
struction, carotid endarterectomy, Maze procedure, ventricular assist device;
Aortic procedure, includes Aortic root replacement, or aortic valve replacement
composite (eg, combined with CABG); Other, includes ventricular assist device, Timing of when strokes occur in the postoperative period
pericardial window, pericardectomy, attempted surgeries, congenital repairs, (n⫽563). Postoperative day 0 includes time in the intensive care
transplants. unit on the day of surgery.

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564 Stroke February 2006
TABLE 4. Risk Model to Predict Stroke in Patients
Having CABG
Example: A 75-year-old patient with no history of previous stroke or
hypertension is at lower risk (P⫽0.04) than a 65-year-old who has reported a
previous stroke and has diagnosed hypertension (P⫽0.07).
As an example of how stroke probabilities can differ, we
compare 2 presurgical candidates (see Table 4). The identi-
fication of high-risk patients has both intraoperative and
postoperative implications that are discussed in the section on
protecting the brain.
Stroke: Diagnosis and Treatment
The presence of stroke in the postoperative period may be
signaled by the inability of the patient to emerge from
anesthesia (follow commands, move all extremities) in the
first 6 hours after the operation. Patients suspected of having
a stroke should be evaluated by a neurologist immediately
and brain imaging obtained. In our experience, brain MRI,
specifically diffusion-weighted imaging (DWI), is the most
sensitive and accurate neuroimaging technique in this patient
population.
DWI can now detect acute ischemic events related to
microemboli. This technique reveals significantly more le-
sions than conventional MRI (T2 and Flair) and is more likely
to demonstrate multiple lesions in a “watershed” pattern of
distribution.18 In a recent study of 35 consecutive candidates
for CABG, no DWI-positive lesions were found before
surgery.19 This low yield from preoperative imaging suggests
that studies using DWI may be able to rely solely on post-
operative imaging for the detection of new surgery-related
lesions. This study also found that most of the DWI lesions after
surgery were small, but 5 patients had multiple lesions. They
concluded that patients with preexisting MRI abnormalities were
more likely to develop new DWI-positive lesions after surgery.
Knipp et al evaluated 29 patients and found that 13 (45%) had
new lesions, but these were not associated with impaired
neuropsychological performance in their study.20 Newer appli-
cations of MRI have been introduced to assess, and predict,
eventual infarct size using either DWI21 or cerebral blood flow
heterogeneity by dynamic susceptibility contrast MRI.22 These
approaches have yet to be applied to postoperative stroke after
CABG, but might be useful in evaluating approaches to preven-
tive therapies.
If DWI is not feasible, because of the presence of metallic
implants or surgical metal (temporary epicardial pacing
wires), head computed tomography should be obtained. We
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have previously shown that patients who have a pattern of
watershed infarction on brain imaging have worse out-
comes.23 Thus, this may be the most appropriate population to
provide interventions that can decrease the penumbral area of
brain at risk. Recent studies indicate that stroke patients with
hypoperfused brain tissue can be identified by comparing the
mismatch between DWI and perfusion-weighted imaging.24
This postoperative population may benefit from being main-
tained at higher blood pressure levels.25
Encephalopathy: Incidence
In contrast to stroke, less attention has been paid to patients
with diffuse brain injury or encephalopathy after cardiac
surgery. Encephalopathy has been characterized in the liter-
ature using a variety of descriptors, including confusion,
delirium, seizures, coma, prolonged alteration in mental
status, combativeness, and agitation. The reported incidence
of postoperative encephalopathy varies widely from 8.4% to
32%.26,27 Some studies have used structured rating/testing
scales to define this outcome, whereas others have used
clinical documentation. In studies that have used a clinical
diagnosis,26 the incidence is reported as being lower than
those with structured interviews.28 –30 Irrespective of the
criteria used to define encephalopathy, patients with this
postoperative complication clearly have worse outcomes.
Encephalopathy: Outcomes and Predictors of
High-Risk Patients
Like stroke, encephalopathy is also associated with poor
in-hospital outcomes,17 with increased length of stay in the
hospital, and with higher mortality than in patients without
this complication. In our studies, the average length of stay
for patients without a complication is 8 days, compared with
14 days for those with encephalopathy, and in-hospital
mortality is 7.5% for patients with encephalopathy, which
is 3 times the rate of other postoperative patients without
this complication. In addition, a proportion of patients with
postoperative encephalopathy are not able to return home
after discharge from the acute care hospital but require
rehabilitation for assistance with activities of daily living. As
with stroke, predictive factors have been identified for en-
cephalopathy (see Table 5). The factors that appear important
are history of previous stroke, hypertension, diabetes, pres-
ence of carotid bruit, and age. Using these 5 risk factors,
individual probabilities can be identified before surgery.
Several studies have also identified severity of vascular
disease and previous cerebrovascular disease as important
factors.17,26,31,32
Encephalopathy: Diagnosis and Treatment
Because the clinical presentation of encephalopathy tends to
be more subtle in the postoperative period, many patients do
not get formally diagnosed. Symptoms generally present
following extubation, when patients are able to speak, but
encephalopathy should be suspected in patients who emerge
from anesthesia with persistent agitation or combativeness.
These patients can often be identified before extubation, and
in some situations, encephalopathy may delay their ability to
be removed from ventilatory support.
 McKhann et al Stroke and Encephalopathy After Cardiac Surgery 565

TABLE 5. Risk Model for Predicting Encephalopathy in CABG Patients

CVA indicates history of cerebrovascular accident; CB, presence of carotid bruit; HTN, history of hypertension; DM,
history of diabetes mellitus.
Example: a 64-year-old patient with a history of hypertension and diabetes mellitus has twice the risk of developing
encephalopathy (0.06) compared to a 64-year-old patient with no risk factors (0.03).

Although few studies of encephalopathy have included
imaging, it is believed that patients with encephalopathy also
have evidence of multiple embolic phenomena. Djaiani et al33
concluded that atheromatous disease of the ascending aorta
is a major contributor to brain injury as seen on diffusion-
weighted MRI after surgery. It is likely that patients with
postoperative coma, stroke, and encephalopathy represent a
continuum of conditions with a similar underlying mecha-
nism: showers of embolic material to the brain.34
Underlying Pathophysiology of Stroke
and Encephalopathy
Preexisting Cerebrovascular Disease
As discussed above, history of previous stroke, as well as
hypertension, diabetes, age, and presence of carotid bruit are
risk factors that predict which patients are at greatest risk for
neurological complications after cardiac surgery. Almost all
cardiac surgical candidates are known to have atherosclerotic
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disease (demonstrated by coronary angiogram). Evidence is
also growing that these patients have much more cerebrovas-
cular disease than was previously recognized. Therefore,
many patients have potentially compromised cerebrovascular
circulation even before they come to surgery.
In the United States, preoperative MRI has been difficult to
obtain because of the short time between hospital admission
and surgery.35 Thus, it has been difficult to demonstrate an
association between the degree of preexisting vascular dis-
ease and neurological outcomes. However, in a study from
Japan in which MRI scans were obtained before surgery in
421 CABG candidates,36 30% of patients had small brain
infarctions and 20% had multiple infarctions. Thus, one-half
of this sample had evidence of ischemic brain abnormalities
before surgery. In addition, these findings of the degree of
cerebrovascular disease on MRI were correlated with the
occurrence of both postoperative stroke and cognitive change.
In a study that included a combination of MRI and
magnetic resonance angiography, an even higher prevalence
566 Stroke February 2006
of cerebrovascular disease was found in 39 patients before
CABG, with existing cerebral infarction in 97%, internal
carotid artery disease in 25%, periventricular hyperintensities
in 87%, and external carotid artery disease in 41%.37 Thus, it
is important to know the status of the carotid arteries as well.
These authors suggest that those patients with evidence of
vascular disease on screening MRI should have further
follow-up, such as duplex ultrasonography, single-photon
emission– computed tomography, or angiography. In a study
comparing CABG patients with those undergoing spinal cord
stimulation, white matter disease was found in both groups
before surgery, but cerebral complications after surgery were
higher in the CABG patients who had preexisting white
matter lesions.38
The finding that candidates for CABG have varying
degrees of cerebrovascular disease should not be surprising.
Silent brain infarcts are common on MRI in neurologically
asymptomatic elderly subjects. In an MRI study of commu-
nity subjects, white matter brain abnormalities were found in
nearly one-third of those with a history of hypertension,
diabetes mellitus, peripheral vascular disease, and myocardial
infarction (similar to cardiac surgical patients).39 A possible
surrogate marker of preexisting cerebrovascular disease may
be poor performance on neuropsychological tests even before
surgery.40,41 In a sample of 311 patients with diagnosed
coronary artery disease, cognitive performance was signifi-
cantly lower at baseline testing when compared with control
subjects with no risk factors for cardiovascular disease.42 This
difference has not been observed in all aspects of cognition,
but in those areas affected by chronic cerebrovascular dis-
ease, including executive function, and psychomotor and
motor speed.43 This type of cognitive profile is comparable to
that seen in prospective studies of patients with MRI-defined
subcortical disease.44 In addition, a recent study involving
over 12 000 middle-aged individuals suggested that cognitive
test scores below demographic norms predicted subsequent
cardiovascular events independently of established cardiovas-
cular risk factors.45
Microemboli
Although macroembolization is less common during modern
cardiac surgery, microembolization remains a problem. The
extracorporeal circulatory pump system used during cardio-
pulmonary bypass creates a unique susceptibility to embolic
injury. The internal surface of the pump components and
pump tubing is lined with foreign material that creates an
interface which is predisposed to the formation of microem-
boli, even though patients are fully heparinized. While on the
cardiopulmonary bypass pump, the pulmonary circulation,
which acts as a natural filter between the venous system and
the arterial circulation, is removed. Microemboli may be
gaseous or particulate, such as thrombus and lipid. Aortic
atheromatous debris may be the most common source of
cerebral microembolism.46
There is an increased risk for cerebral microemboli during
the surgery.47 In addition, transesophageal echocardiography
and epiaortic scanning have indicated an association between
the degree of atheroma in the ascending aorta and new brain
ischemic lesions identified by imaging studies.33,47,48 Thus,
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the surgical technique was modified to decrease manipulation
of the aorta by use of a single aortic clamp instead of the more
conventional double clamping technique involving an aortic
clamp and a side-biting clamp. In the experience of a single
surgeon at our hospital, the single clamp technique was
associated with fewer strokes and less neurologic injury/
encephalopathy.49 Another approach is the use of intra-aortic
filters to capture particulate emboli. These filters do accom-
plish this goal.50 Further, in prospective controlled studies,
filters were associated with better neurologic outcomes in
high risk patients.51
Studies with transcranial doppler have documented that
embolic showers are particularly likely to occur during
cannulation and clamping/unclamping of the aorta.52 These
emboli vary in size and composition, and may consist of air
or solids. Recently, Abu-Omar compared CABG, off-pump
CAB, and open heart valve surgery patients using a newer
transcranial doppler ultrasound technique that purports to
distinguish between gaseous and particulate embolic material.53
The total numbers of emboli varied dramatically between
procedures: open heart procedures had the most, CABG next,
and off-pump had by far the least. Most emboli were gaseous,
but the percentages varied: those with open heart had 20%
particulate, CABG 24%, and off-pump 9% particulate.
Hypoperfusion
Although there is agreement that prolonged periods of hypo-
perfusion during cardiac surgery may place the patient at risk
for ischemic injury, it is less clear what degree and duration
of hypoperfusion can be tolerated intraoperatively. Older
patients and those with comorbid disease, such as hyperten-
sion and diabetes, may be at greater risk because of alter-
ations in the autoregulation of cerebral blood flow. The
optimal level of mean arterial pressure during cardiopulmo-
nary bypass is controversial because there are very few
studies with intraoperative blood pressure data to implicate
hypoperfusion as a risk factor for stroke and encephalopathy
outcomes. Murkin et al54showed that even though they were
able to demonstrate a 15% increase in cerebral blood flow
during surgery with pulsatile flow versus nonpulsatile flow, it
did not reduce the incidence of stroke. In one of the few
randomized trials, Gold et al assigned 124 patients to a low
mean arterial pressure group (50 to 60 mm Hg) and 124
patients to a high mean arterial pressure group (80 to
100 mm Hg) during cardiopulmonary bypass. Those in the
high pressure group had fewer combined cardiac and neuro-
logical complications (4.8% versus 13%) and fewer strokes
(2.4% versus 7.2%).55 Caplan and Hennerici have suggested
that decreased flow may result in reduced washout of micro-
embolic materials from the brain, and that the watershed areas
are particularly susceptible to this combination.56 This latter
hypothesis thus brings together two of the putative underlying
mechanisms for vascular damage during CABG, suggesting
that microembolism in the context of hypoperfusion may be
associated with greater risk of ischemic injury.
Atrial Fibrillation
It is widely accepted that atrial fibrillation is associated with
embolic stroke in the general population. Because atrial
 McKhann et al
fibrillation occurs at a high rate (30%) in the early cardiac
surgical postoperative period, attempts have been made to
develop models for predicting postoperative atrial fibrillation.
One model, based on data from the Multicenter Study of
Perioperative Ischemia Epidemiology II, involved 5436 pa-
tients from 70 hospitals and 17 countries.57 The authors found
that atrial fibrillation was associated with a greater incidence
of infections, renal dysfunction, and encephalopathy. It is also
important to determine the timing of neurological complica-
tions and the occurrence of atrial fibrillation. In a retrospec-
tive study, Lahtinen attributed 36% of postoperative strokes
to the development of atrial fibrillation. They were able to
show that, on average, there were 2.5 episodes of atrial
fibrillation before the stroke event.58 In our own studies of
DWI in high-risk patients who had a new postoperative DWI
lesion, 75% also had postoperative atrial fibrillation.
These and other studies highlight the importance of the
prevention of postoperative atrial fibrillation. Zimmer per-
formed a meta-analysis of prospective studies of prophylactic
treatment for patients undergoing cardiac surgery.59 Of 1783
patients reviewed, 1569 (88%) underwent CABG. A variety
of treatments were used, which included combinations of 1 or
more drugs (Amiodarone, Sotalol, Procainamide), and pacing
wires. Overall, there was a 50% decrease in the occurrence of
atrial fibrillation, with a 1-day decrease in hospital stay,
hospital costs, stroke, and mortality. A review by Crystal et
al60 also reported similar findings. Therefore, preventative
treatment strategies in the postoperative period need to be
maximized in this population of patients at risk.
Pathologic Findings in Cardiac
Surgical Patients
Several investigators have attempted to identify pathologic
changes in the brains of cardiac surgical patients who died in
the postoperative period. In autopsy studies, 1 group found
small capillary arterial dilations containing microemboli in
the brain; the material in these emboli is most likely lipid.61
The numbers of small capillary arterial dilations are associ-
ated with increasing time on the cardiopulmonary bypass
pump, particularly with heart valve surgery rather than
CABG. With increased survival time after surgery (in days),
both the number and the size of these emboli decreases.62
There are few other studies of the neuropathological
changes after CABG, and their interpretation is complicated
by the need to distinguish the pathological lesions resulting
from the CABG procedure from those of the underlying
pathology of vascular disease. Emmrich and colleagues
retrospectively examined the brains of 262 patients who came
to autopsy shortly after open heart surgery.63 The majority of
these patients survived less than a month after the surgery. Of
these patients, 48% had CABG and the remaining patients
had valve surgery, combined valve and CABG, or heart
transplantation. Forty percent of the CABG patients had large
infarcts, and 8% had microinfarcts. Brain hemorrhages were
seen in 35% of the CABG autopsy samples. An incidental
finding of Alzheimer’s type pathology was observed in 14%
of cases, the majority of which were mild abnormalities.
The underlying neuropathology of cerebrovascular disease
is complex and includes ischemic brain injury, with multi-
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Stroke and Encephalopathy After Cardiac Surgery 567
infarcts, small vessel disease, leukoariosis, and hippocampal
sclerosis.64 – 66 Increasingly, the underlying pathology is in-
ferred from imaging studies, primarily MRI. For example, a
recent study emphasized the correlation of microbleeds in
cerebral cortex, as detected by T2-weighted gradient-echo
MRI, and subsequent cognitive dysfunction, particularly on
executive function. There are no prospective studies, to our
knowledge, that correlate neurologic outcomes after CABG
with subsequent neuropathologic findings.67
Stroke After Other Cardiac Interventions
From the mid 1960’s through the mid 1980’s CABG was
essentially the only intervention for coronary artery disease,
but in the past 2 decades other procedures have become
available: percutaneous coronary intervention or PCI (angio-
plasty and stent placement) procedures, and an alternative
surgical procedure, off-pump coronary artery bypass surgery
(“off-pump surgery”). Typical of many cardiac surgery cen-
ters around the country, the number of CABG procedures in
our hospital declined by nearly 60% from 1994 to 2004
(Table 1). The reported stroke rate after PCI is markedly
lower (0.3%) than after CABG in several studies.68 Whether
this is because patient populations under study may have
different stroke risks is unclear.
With the introduction of off-pump CABG, it was widely
assumed that neurological complications in the immediate
postoperative period would be almost eliminated. This surgi-
cal procedure, in its early phases, boasted the advantages of
no aortic manipulation, no hypothermia, and no use of the
cardiopulmonary bypass pump. Theoretically, these differ-
ences from conventional CABG would be expected to result
in fewer microemboli entering the brain in off-pump versus
conventional CABG surgery.69,70 We say theoretically be-
cause a recent report indicated a similar rate of ischemic
lesions, as indicated by postoperative DWI, in off-pump as
opposed to on-pump CABG. This finding suggests that
factors other than the use of the cardiopulmonary bypass are
associated with postoperative ischemic lesions.71
With a stroke rate of only 2% to 5% in the CABG group,
it takes a study involving a large number of patients to
reliably establish the beneficial effects of an alternative
procedure, and most studies in the literature have sample
sizes too small to show statistical significance. Nevertheless,
a large study by Bucerius (n⫽16 184) found a difference in
the incidence of stroke between conventional CABG (3.9%)
and off pump group (2.5%),10 indicating that stroke risk was
reduced but not eliminated with this alternative procedure.
Further, in a study comparing high risk patients subjected to
off-pump CABG versus on-pump CABG, off-pump CABG
was associated with improved survival rate.72
This same group also compared these 2 surgical popula-
tions both in terms of the rate and timing of stroke and found
different distributions. On-pump surgery was associated with
early stroke (2 days), whereas off-pump was associated with
later stroke (4 days). These authors suggest that the mecha-
nisms of stroke might be different in the 2 groups.73
As described below, off-pump surgery can be done in
multiple ways that can affect the production of emboli.
MIDCAB surgery was initially done without aortic manipu-
568 Stroke February 2006

lation using laparoscopic instruments inserted into the tho- TABLE 6. Neuroprotective Strategies to be Used in
racic cavity via small, keyhole incisions. Off-pump surgery Cardiac Surgery
has since changed so that patients have a full sternotomy, and Time Issue Suggestions
in some cases partial occluding aortic clamps are used,
Before Identification of patients Alternative surgical procedures
whereas others use the “no touch” aortic technique in which
Surgery at high risk using (off-pump)
the coronary grafts are completed as grafts to an internal established “risk Use of PCI therapy
mammary artery. In an analysis of 7272 patients, Kapetanakis models” Use of carotid endarterectomy or
et al found that those with aortic manipulation were 1.8 times Identification of carotid stenting84
more likely to have had stroke than those without any aortic artery stenosis Alteration of surgical procedures,
manipulation.74 Similar conclusions have been reached by Preexisting eg, blood pressure management
other investigators.75,76 Thus, particularly for patients with a cerebrovascular disease Pretreatment with drug therapy
and ischemic lesions
diseased aorta, there may be a neurological benefit of off-
identified on imaging
pump CABG using the “no touch” aortic technique compared (MRI)
with conventional CABG procedures. Atrial fibrillation
Fewer emboli may not be the only advantage of off-pump
During Aortic atheroma Use of epiaortic/TEE ultrasound
surgery; there may also be less myocardial damage.77 How- Surgery Systemic hypoperfusion to identify ascending and arch
ever, the issue of stroke after on-pump versus off-pump Brain hyperthermia aortic disease
CABG must be considered in the context of the relative Hyperglycemia Modifications to surgical
merits of these two procedures by other criteria. A large body Microemboli procedure: minimize aortic
of literature on this controversial topic has recently been manipulation, use of single
reviewed in a Scientific Statement from the American Heart aortic cross clamp for proximal
grafts, no touch aortic technique,
Association.78 This group concluded that excellent outcomes
altered cannula placement
may be achieved with either procedure and that individual Use of higher blood pressures
outcomes may depend more on patient related variables than during CPB
on the choice of procedure. Increase hematocrit to 30%
Use of alpha-stat pH
Protecting the Brain During management (for adults)54
Cardiac Surgery Prevent rewarming
temperatures ⬎37°C85
Strategies for protecting the brain during cardiac surgery can
Prevent hyperglycemia by
be considered in 2 stages: avoiding injury to the brain, and having a structured glucose
preventing secondary ischemic damage/promoting recovery. management protocol
Much research in cardiac surgery has focused on the former. in place86,87
Table 6 summarizes these strategies and suggests ways to Use of arterial line filters
implement them. Avoid use of cardiotomy
Methods for preventing secondary ischemic damage and suction61
promoting recovery of brain tissue have proven much more After Prevention of atrial Early intervention on arrhythmias
challenging. Using a canine model of cardiopulmonary by- Surgery fibrillation Use of diffusion-weighted MRI
pass and hypothermic circulatory arrest, work in the labora- Diagnosis and Early blood pressure
identification of interventions to minimize
tory of 1 author (W.A.B.) has yielded several conclusions
ischemic brain lesions infarction size88
regarding the pathways of such ischemic brain damage during Brain perfusion Use of diffusion-weighted
cardiac surgery.79 They can be summarized in the following mismatch MRI/Perfusion-weighted imaging
way: glutamate excitotoxicity contributes to injury80; inhibi- Early blood pressure
tion of glutamate excitotoxicity reduces injury81– 83; hypother- interventions to minimize
mic circulatory arrest induces nitric oxide; and nerve injury is infarction size
reduced by inhibition of neuronal nitric oxide synthase.
Unfortunately, these therapeutic leads from animal experi- majority of patients. Nonetheless, a subset of patients with
ments have yet to yield an effective pharmacological neuro- preexisting risk factors for cerebrovascular disease are at high
protective agent that can be safely used in patients undergo- risk for stroke or encephalopathy. In addition, before surgery,
ing cardiac surgery. Indeed, similar problems have plagued very little is known about the status of not only the vascula-
neurologists who treat stroke patients in the general popula- ture of the brain but also the existence of previous underlying
tion. As newer agents are contemplated, however, we think cerebrovascular disease. We suggest that neurologists have a
that patients undergoing cardiac surgery provide a unique role in assisting their colleagues in cardiology and cardiac
clinical opportunity for evaluating such agents. Patients at surgery to identify those at risk for adverse neurological
high risk for stroke and encephalopathy can be identified outcomes. In addition, they need to be involved in evaluating
before surgery; these selected populations can then be ran- patients after surgery for change in neurological condition,
domized prospectively and controlled studies implemented. both by examination and interpretation of imaging studies.
Most important, neurologists should be involved in the design
Conclusion and interpretation of studies comparing different intervention
From a neurological standpoint, cardiac surgery as currently techniques, modification of existing procedures, and trials of
practiced is a safe and effective procedure for the great neuroprotective agents.
Downloaded from http://stroke.ahajournals.org/ by guest on September 7, 2015
 McKhann et al
Acknowledgments
This work was supported by grants number NS 35610 and AG 05146
from the National Institutes of Health, the Johns Hopkins Medical
Institutions GCRC grant RR 00052, and from the Dana Foundation.
We thank the staff and participants in our studies. We offer special
thanks to Pamela Talalay, Maryanne Martin, and Scott Zeger for
their important contributions. We also acknowledge our participating
cardiac surgeons and cardiologists.
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A. Selnes

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