E SPECIAL ARTICLE

Blood Pressure and the Brain: How Low Can You Go?
John C. Drummond, MD

There are occasionally intraoperative circumstances in which reduction of mean arterial pres-
sure (MAP) to levels well below those that occur in nonanesthetized adults is necessary or
unavoidable. In these situations, clinicians are inevitably concerned about the limits of the tol-
erance of the brain for hypotension. Reference to the phenomenon of cerebral blood flow auto-
regulation is frequently made in discussions of safe MAP limits. However, in several respects,
prevalent conceptions about cerebral blood flow autoregulation may be incomplete or inaccu-
rate. The principal theses offered by this review are: (1) that the average lower limit of cerebral
blood flow autoregulation in normotensive adult humans is not less than a MAP of 70 mm Hg;
(2) that there is considerable intersubject variability in both the lower limit of cerebral blood flow
autoregulation and the efficiency of cerebral blood flow autoregulation; (3) that there is a sub-
stantial blood flow reserve that buffers the normal central nervous system against critical blood
flow reduction in the face of hypotension; (4) that there are several common clinical phenomena
that have the potential to compromise that buffer, and that should be taken into account in
decision making about minimum acceptable MAPs; and (5) that the average threshold for the
onset of central nervous system ischemic symptoms is probably a MAP of 40–50 mm Hg at the
level of the circle of Willis in a normotensive adult in a vertical posture and 45–55 mm Hg in
a supine subject. However, these MAPs should probably only be approached deliberately when
the exigencies of the surgical situation absolutely require it. (Anesth Analg 2019;128:759–71)

T
here are occasionally intraoperative circumstances
in which reduction of mean arterial pressure (MAP)
to levels well below those that occur in nonanesthe-
tized adultsa is necessary or unavoidable. In these situa-
tions, clinicians are inevitably concerned about the limits of
the tolerance of the central nervous system (CNS) for MAP
reduction. Simply put, what are the thresholds at which
the risk of ischemic injury becomes substantial in adult
humans? That is the question that this submission attempts
to address. The question invites answers expressed as
numeric thresholds. However, it should be understood at
the outset that any numeric values that are offered represent
population averages. There are large SDs on most biologi-
cal responses, and pushing physiology on the basis of aver-
ages will almost certainly lead practitioners occasionally to
discover individual outliers who are less tolerant of hypo-
tension. There is a second variable, “time,” in the injury/
no injury equation. Inevitably, there are MAPs that will be
tolerated when hypotension is brief but that will not be tol-
erated when it is sustained. In the “MAP × time = sufficient
to cause injury” equation, MAP and time will inevitably
be inversely proportional, and the threshold values will be
impossible to predict for individual patients.
Any discussion of the tolerance of the CNS to relative
hypotension will inevitably give emphasis to the topic of CNS
blood flow autoregulation. Cerebral blood flow autoregula-
tion refers to the capacity of the CNS to maintain blood flow
levels relatively constant across a range of MAPs, assuming
that other elements of physiology are held constant. Figure 1
includes a typical cerebral blood flow autoregulation “curve”
(the solid line) depicting the relationship between MAP and
cerebral blood flow. There is a central plateau bounded by
inflection points representing the lower and upper limits of
cerebral blood flow autoregulation, below and above which,
respectively, the cerebral circulation is pressure passive, with
cerebral blood flow varying pari passu with MAP. In Figure 1,
the lower limit of cerebral blood flow autoregulation and the
upper limit of cerebral blood flow autoregulation are repre-
sented as a value in the low 70s and 150 mm Hg, respectively.
The parameter on the x-axis of cerebral blood flow autoregu-
lation curves is sometimes cerebral perfusion pressure, rather
than MAP. Cerebral perfusion pressure is calculated as MAP
– intracranial pressure (ICP). Cerebral perfusion pressure is
used less often because a measure of ICP measures is often
unavailable. Normal ICP is 5–10 mm Hg. A MAP of 70 mm
Hg can be viewed as equivalent to a cerebral perfusion pres-
sure of 60–65 mm Hg. The details of the physiological mecha-
nisms of cerebral blood flow autoregulation are not critical
to this review. While other processes may be involved,1 cere-
bral blood flow autoregulation is probably largely myogenic
(ie, a function of local vascular smooth muscle response to
changing intraluminal pressure in vessels between the distal
carotid and vertebrobasilar arteries and pial arteries down to
diameters in the vicinity of 100–200 μm).2

From the Department of Anesthesiology, the University of California San
Diego, La Jolla, California; and Anesthesia Service, VA Medical Center, San
Diego, California.
Accepted for publication December 18, 2018.
Funding: None.
The author declares no conflicts of interest.
Reprints will not be available from the author.
Address correspondence to John C. Drummond, MD, VA San Diego Health-
care System, 3350 La Jolla Village Dr, MC 125, Room 5289, San Diego, CA
92161. Address e-mail to jdrummond@ucsd.edu.
Copyright © 2019 International Anesthesia Research Society
MISUNDERSTANDINGS ABOUT AUTOREGULATION
There appear to be several aspects of the cerebral blood flow
autoregulation phenomenon that may not be fully appreci-
ated by all clinicians. Chief among them are: (1) that the aver-
age lower limit of cerebral blood flow autoregulation (ie, that
MAP below which cerebral blood flow is pressure passive
and MAP and cerebral blood flow vary linearly), resides at
a MAP significantly greater than the widely advertised value
This review addresses adult physiology and will not attempt to explain the
a

DOI: 10.1213/ANE.0000000000004034 many variations that may apply to pediatric subjects.

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 EE Special Article
Figure 2. This figure is probably the origin of the classical depiction
of cerebral blood flow autoregulation. The implication of a lower limit
of cerebral blood flow autoregulation of 50 mm Hg (vertical arrow)
is apparent. The subject groups that anchor the left-hand end of the
curve (circle) had signs of central nervous system ischemia at a
mean arterial pressure of 38 ± 11 mm Hg, making it unlikely that the
lower limit of cerebral blood flow autoregulation for the population
was actually 50 mm Hg. Adapted with permission from Physiological
Reviews: Lassen NA. Cerebral blood flow and oxygen consumption
in man. Physiol Rev. 1959;39:183–238.5 CBF indicates cerebral
blood flow.
of 50 mm Hg; and (2) that the effectiveness of cerebral blood
flow autoregulation varies enormously from individual to
individual. While an autoregulatory plateau, as depicted in
Figure 1, is readily demonstrable in some normal subjects, in
others it is less evident.3 One consequence of this variability
is that cerebral blood flow autoregulation represents a much
more effective buffer against the injurious potential of hypo-
tension in some individuals than in others.
1. The lower limit of autoregulation: There is probably
considerable misunderstanding about the numeri-
cal value of the average adult lower limit of cere-
bral blood flow autoregulation. While diagrams
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Figure 1. Cerebral blood flow autoregu-
lation curves depicting the relationship
between mean arterial pressure (MAP)
and cerebral blood flow. The solid
curve is the classical representation,
with a relatively broad plateau phase.
The solid vertical arrow indicates an
average lower limit of autoregulation
for normotensive adult humans of
approximately 70 mm Hg. The 2 dot-
ted line curves represent the variations
that occur within a normal population,
with some subjects having effectively
shorter plateaus and some have very
little autoregulatory capacity. CBF indi-
cates cerebral blood flow.
that have appeared for many years in standard text-
books have commonly depicted the adult human
lower limit of cerebral blood flow autoregulation as
approximately 50 mm Hg, the actual average lower
limit of cerebral blood flow autoregulation for a non-
anesthetized adult is unlikely to be anything less
than an average MAP value in the low 70s, with con-
siderable variation among individuals. Nonetheless,
50 mm Hg has been widely cited for decades as the
human lower limit of cerebral blood flow autoregu-
lation (and this author certainly on the list of those
who have promulgated that misinformation4). While
that value may apply in several small animal spe-
cies, it most definitely is not applicable to humans.
The widely quoted “50” is probably derivative of a
figure (Figure 2) that appeared in a review of cere-
bral physiology by Lassen,5 published in 1959. The
figure displayed a composite of the then available
data on a graph of MAP versus global cerebral blood
flow. The hand-drawn curve through the various
points on that graph certainly appears to indicate
a lower limit of cerebral blood flow autoregulation
of approximately 50 mm Hg. The left-hand end of
that curve is anchored by data from an investiga-
tion by Finnerty et al.6 In that study, blood pressure
was lowered in nonanesthetized subjects suffi-
ciently to produce symptoms of cerebral ischemia,
and the data points that anchor the left-hand end of
Lassen’s curve, identified as “1” and “2” and circled
in Figure 2 are cerebral blood flow values recorded
at the ischemic symptom MAP threshold. The origin
of those data points is not specified by Lassen.5 In
Finnerty et al’s6 total population of 37 subjects, some
of whom had untreated hypertension, symptoms
occurred at an average MAP of 48 mm Hg and were
associated with a roughly 40% reduction in global
cerebral blood flow. My extraction of Finnerty et al’s6
data for 12 normotensive subjects (baseline MAP
91 ± 10, range 75–103 mm Hg and average age 46 ±
13 years) indicates a MAP ischemia threshold of 38
ANESTHESIA & ANALGESIA
 Blood Pressure and the Brain

Table. Data for the Lower Limit of Cerebral Blood Flow Autoregulation Obtained in Adult Human Subjects
Mean Lower Limit of Cerebral Blood
Flow Autoregulation (mm Hg)
Authors Hypotensive Technique Cerebral Blood Flow Method (Range, SD, or CI)
Morris et al17 Hexamethonium Kety-Schmidt technique, using nitrous oxide as the tracer >62 (54–78)
McCall18a Hydralazine Veratrum viride Kety-Schmidt technique, using nitrous oxide as the tracer <64 (33–80)
<57 (40–72)
Moyer et al9 Hexamethonium Pendiomide Kety-Schmidt technique, using nitrous oxide as the tracer >62 (53–80)
Trimethaphan >61 (54–72)
>57 (44–75)
Strandgaard10 Trimethaphan/tilt 1/arterial-jugular venous oxygen content difference 73 ± 9
Waldemar et al12 Lower body negative pressure/ Single proton emission computed tomography and, 1/ 79 (57–101)
trimethaphan ± captopril arterial-jugular venous oxygen content difference
Larsen et al13 Lower body negative pressure/ Single proton emission computed tomography and, 1/ 79 (53–113)
labetalol or trimethaphan arterial-jugular venous oxygen content difference
Cerebral blood flow velocity (middle cerebral artery) 91 (41–108)
Olsen et al14 Lower body negative pressure/ Single proton emission computed tomography and, 1/ 88 (76–101)
labetalol arterial-jugular venous oxygen content difference
Olsen et al15 Lower body negative pressure/ 1/arterial-jugular venous oxygen content difference 73 (60–100)
labetalol 1/arterial-transcranial near infra-red spectroscopy 79 (73–101)
saturation difference
Joshi et al16b Spontaneous variation on Mean velocity index (Δcerebral blood flow 66 (43–90)
cardiopulmonary bypass velocity/ΔMAP)
Data are presented as mean values with ranges, SDs (±), or CIs. The constancy of cerebral metabolic rate was assumed, and the fraction 1/arterial-jugular
venous oxygen content difference is used to determine relative cerebral blood flow; single proton emission computed tomography was used where indicated to
calibrate relative cerebral blood flow values; near-infrared spectroscopy was used to determine regional cerebral oxygen saturation. The constancy of cerebral
metabolic rate was assumed, and the fraction 1/arterial-transcranial near infra-red spectroscopy saturation difference was used to determine relative cerebral
blood flow; < indicates that the lower limit of cerebral blood flow autoregulation was not identified, but that cerebral blood flow was unchanged from the control
value at the MAP indicated; > indicates that the lower limit of cerebral blood flow autoregulation was not identified, but that cerebral blood flow was less than the
control cerebral blood flow value at the MAP indicated.
Abbreviation: MAP, mean arterial pressure.
a
Subjects were pregnant women near term (see text).
b
Subjects were receiving general anesthesia (see text). All others were nonanesthetized.

± 11 mm Hg, with a cerebral blood flow reduction
of 35%. Whichever of Finnerty et al’s6 patients are
represented on the Lassen5 figure, it seems unlikely
that the lower limit of cerebral blood flow autoregu-
lation is actually the value suggested by his graph.
The lower limit of cerebral blood flow autoregula-
tion is likely to be substantially greater than the
MAP at which symptoms and a 35%–40% reduction
of cerebral blood flow are observed. Furthermore, in
several other investigations, the average threshold
for the onset of ischemic symptoms was determined
to occur at MAPs that support the improbability of
an average lower limit of cerebral blood flow auto-
regulation of 50 mm Hg in adult humans: Morris
et al,8 62 mm Hg; Moyer et al,9 “approaching”
55 mm Hg; Strandgaard,10 43 mm Hg; and Njemanze7
(vide infra), 49 mm Hgb. Nonetheless, the apparent
impact of the Lassen5 publication has been remark-
ably durable. One continues to see reference, in nom-
inally rigorously reviewed forums, to a lower limit
of cerebral blood flow autoregulation of 50 mm Hg.11
The Table presents the results of the available studies per-
formed in neurologically normal adult humans which
yielded either specific determinations of the lower limit of
cerebral blood flow autoregulation10,12–16 or data that pro-
vide insight into the MAP range above or below where
it must reside.9,17,18 All of the studies, except that of Joshi
b
Njemanze7 used a blood pressure cuff on the arm. I have applied a correction
for the hydrostatic gradient, assuming a 12-inch vertical difference between
the arm and the external auditory canal.
et al,16 entailed static determinations (ie, they used a measure
of cerebral blood flow or some variable that can reasonably
be expected to vary in a linear relationship with cerebral
blood flow, during sustained periods of stable MAP). The
data collectively indicate that average lower limit of cerebral
blood flow autoregulation for a nonanesthetized adult can-
not be less than a MAP in the low 70s. Two of the entries are
superficially inconsistent with that conclusion. The study
by McCall16 used hydralazine or veratrum viride to induce
hypotension in pregnant women late in the third trimester.
The effects of late pregnancy on the cerebral circulation are
not well characterized; and hydralazine is known to be a
cerebral vasodilator. The effect of veratrum viride is obscure.
The report by Joshi et al16 offers the lowest estimated average
human lower limit of cerebral blood flow autoregulation (66
mm Hg, CI, 43–90) and deserves detailed comment, in large
part because it is the only entry in the Table that involves anes-
thetized subjects. First, for at least for 2 reasons, the observed
mean lower limit of cerebral blood flow autoregulation of
66 mm Hg is not inconsistent with the conclusion offered
above that average adult lower limit of cerebral blood flow
autoregulation is not less than a MAP in the low 70s. That
investigation was performed in patients on cardiopulmonary
bypass (CPB). The experimental conditions were such that a
given MAP would be likely to achieve a better than typical
cerebral perfusion pressure (cerebral perfusion pressure =
MAP − ICP). Under the conditions of the study, the patients
probably had very low ICPs. The combination of depressed
cerebral metabolic rate (isoflurane 0.5%–1.0%, 33°C) and very
low venous pressures because of gravity drainage of the right
heart drainage on CPB was likely to render ICP as low as it is

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 EE Special Article
in any physiological circumstance. Second, the authors iden-
tified impaired cerebral blood flow autoregulation on the
basis of a dynamic cerebral blood flow autoregulation index
derived from %Δcerebral blood flow velocity/%ΔMAP,
using 0.4 as the threshold value to define impaired cerebral
blood flow autoregulation. As acknowledged by the authors,
the choice of threshold was arbitrary. Had they selected the
lower threshold values (eg, 0.3) used by others (see Table 1
in the review by Rivera-Lara et al19), their calculated lower
limit of cerebral blood flow autoregulation would have been
a MAP >70 mm Hg.
It is notable that the report by Joshi et al16 represents the
only published determination of the lower limit of cerebral
blood flow autoregulation in anesthetized, neurologically
normal adult humans. It is possible that the use of vasodilat-
ing anesthetic agents and/or the blunting by anesthetic agents
of the sympathetic response to hypotension might result in
lower limit of cerebral blood flow autoregulation values than
those that are presented for the nonanesthetized subjects in
the Table. However, it appears unreasonable to this reviewer
to entrust the well-being of our patients to speculation of
that nature. Pending additional data, it seems appropriate to
assume that the average lower limit of cerebral blood flow
autoregulation in adult humans is not <70 mm Hg.
2. The intersubject variability of autoregulation: The
Table also provides the ranges, SDs, or CIs associ-
ated with the observed average lower limit of cerebral
blood flow autoregulations. The intersubject variabil-
ity is remarkable. From those data, it might reasonably
be concluded that at least some of the normal subjects
included in these studies probably did not have cere-
bral blood flow autoregulation plateaus within the
range of MAPs that are likely to occur during general
anesthesia. In fact, in an investigation by Lucas et al3
that examined variation in cerebral blood flow veloc-
ity with MAP (though it did not attempt to calculate a
lower limit of cerebral blood flow autoregulation), no
apparent autoregulatory plateau was evident in any
of 11 normal subjects.
The typical “one-size-fits-all” diagrammatic representations
of cerebral blood flow autoregulation that have appeared
widely in standard texts are likely to be misleading in sev-
eral respects. First, some misrepresent (underestimate) the
average lower limit of cerebral blood flow autoregulation.
Second, in some subjects, the plateau is considerably nar-
rower than the 80–100 mm Hg width often suggested.20
Third, the absolutely horizontal representation of the cere-
bral blood flow autoregulation plateau is likely to be inac-
curate. When a cerebral blood flow autoregulation plateau
exists, it probably has a slightly positive slope.1 Cerebral
blood flow autoregulation diagrams would be more repre-
sentative of normal physiology if they were presented as a
family of curves (Figure 1) to emphasize the interindividual
variability of cerebral blood flow autoregulation.
ADDITIONAL COMMENTS ABOUT
AUTOREGULATION
Before discussing the clinical implications of the forego-
ing, there are 2 additional topics of relevance to clinicians
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attempting to understand the literature on cerebral blood
flow autoregulation: (1) the use of term “impaired auto-
regulation”; and (2) the influence of cardiac output (CO) on
cerebral blood flow autoregulation.
1. Impaired autoregulation: One often hears or reads
that such and such “impairs autoregulation.” With
some frequency, those using that phrase fail to spec-
ify whether they are referring to the cerebral blood
flow autoregulation response to increasing blood
pressure or decreasing blood pressure (or both). It
is the latter, decreasing blood pressure, that is likely
to be of greater clinical importance. An impaired
response to increasing blood pressure will result
in sustained vascular engorgement in the event of
hypertension. Isoflurane, for instance, impairs the
response to increasing blood pressure more so than
sevoflurane,21,22 but this is infrequently likely to be a
matter of intraoperative consequence. Furthermore,
a rapid change in blood pressure will result in a tran-
sient (ie, 3–4 minutes) alteration in cerebral blood
flow even when cerebral blood flow autoregulation
is intact. Impairment of the response to decreasing
blood pressure, and therefore a reduced ability to
maintain cerebral blood flow in the event of hypo-
tension, is of greater concern. However, even agents
that render the cerebral circulation pressure passive
(eg, some volatile agents and blood pressure–low-
ering drugs), and, therefore by definition, “impair
autoregulation,” may not actually be deleterious to
the maintenance of perfusion. Whether or not they
differ in their effects on cerebral blood flow autoregu-
lation, there is nothing to choose between isoflurane
and sevoflurane in terms of cerebral blood flow dur-
ing hypotension. While isoflurane and sevoflurane
do not actually cause an increase in cerebral blood
flow during blood pressure reduction, both cause a
state of relative luxury perfusion during hypoten-
sion.23,24 Furthermore, the vasodilation caused by
some agents that impair autoregulation may actu-
ally result in a greater cerebral blood flow at a given
MAP. Pharmacologically impaired autoregulation
does not always represent a bogeyman that must be
dreaded and avoided.
2. The influence of CO on autoregulation: While the
widely reproduced diagrams of cerebral blood flow
autoregulation depicting cerebral blood flow as a
function of MAP (or cerebral perfusion pressure) do
not acknowledge CO as a relevant variable, there is,
in fact, considerable evidence that, in at least some
circumstances, it is.25–33 Ogoh et al29 reported a linear
relationship between CO and middle cerebral artery
mean blood velocity at rest and during exercise that
was independent of Paco2. Ide et al25 observed that
the increase in cerebral blood flow velocity that nor-
mally occurs during intense exercise was attenuated
by beta blockade. Because beta blockade had no
effect on cerebral blood flow velocity during minimal
exercise, they surmised that the effect was the result
of limitation of CO. The same authors reported that
patients with atrial fibrillation also had a reduced
ANESTHESIA & ANALGESIA
 Blood Pressure and the Brain
ability to increase cerebral perfusion during exercise,
which they attributed to their impaired ability to
increase the CO.26,31 A study by Kim et al27 revealed
that increases in CO without changes in MAP
increased cerebral blood flow in the setting of cere-
bral vasospasm after subarachnoid hemorrhage. The
relationship is not evident in the face of all pathol-
ogy, and the mechanisms are uncertain. However,
sympathetic innervation of the cerebral vessels may
be involved. The sympathetic response to a decrease
in blood pressure has been shown to contribute to
the reduction of cerebral blood flow that occurs dur-
ing hypotension.34 This is thought to be mediated, at
least in part, via adrenergic innervation of extracra-
nial and proximal intracranial arteries,35,36 because
cerebral blood flow reduction is attenuated by block-
ing or extirpating the cervical sympathetic chain.34
Whatever the mechanism, clinicians who seek to
maintain CNS blood flow by support of MAP should
probably be mindful of the possibility that increas-
ing MAP at the expense of CO may not achieve the
desired CNS blood flow augmentation.
WHY SO LITTLE HARM?
If the 2 “misunderstandings” that have just been asserted
are, in fact, prevalent, clinicians who have seen a great
many patients with sustained MAPs <70 mm Hg, might
well ask, “Why has there not been a greater incidence of
cerebral injury?” There are 2 principal reasons: (1) The CNS
blood flow reserve; and (2) the predominant use of horizon-
tal positions for the performance of surgery.
1. The CNS blood flow reserve: The healthy human
nervous system lives in a state of luxury perfusion.
Resting CNS flow considerably exceeds the mini-
mum required to deliver adequate energy-yielding
substrates. Herein, the difference between resting
CNS flow and the flow at which the earliest symp-
toms of CNS ischemia occur will be referred to the as
the “CNS blood flow reserve.” Some clinicians may
not be aware of the CNS blood flow reserve and may
therefore not be sensitive to situations in which the
reserve may not be present and in which patients
are therefore likely to be more vulnerable to hypo-
tension than would be the case in the face of nor-
mal physiology. The brain can tolerate a reduction
of the baseline cerebral blood flow of approximately
35%–40% before the onset of ischemic symptom-
atology.6,7 Note that even the ischemic symptom
threshold is highly unlikely to be the threshold for
injury unless the reduced blood flow is very sus-
tained. The investigation by Finnerty et al,6 which
observed symptoms at an average cerebral blood
flow reduction of 40%, has been mentioned above.
Njemanze,7 using a tilt table, studied cerebral blood
flow velocity changes in patients susceptible to pos-
tural hypotension. His observations in 40 patients 56
± 18 years of age were that ischemic symptomatol-
ogy began with average cerebral blood flow velocity
reductions from baseline of 35%, and that syncope
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ensued at average reductions of 50%. Probably of
greater interest to clinicians are the MAPs at which
those symptom thresholds occurred. For Finnerty et
al’s6 entire 37-subject group, which included some
untreated hypertensives, symptoms occurred at an
average MAP of 48 mm Hg. For his normotensive
subjects, the average was 38 mm Hg.6 In the study
by Njemanze,7 blood pressure was measured with a
blood pressure cuff applied to the arm.7 By assuming
a vertical distance from midcuff to the external audi-
tory canal of 12 inches, I estimate that the MAP at the
symptom threshold was 40 mm Hg. In an additional
investigation, Strandgaard10 identified a MAP of 43
± 8 mm Hg as the threshold for cerebral ischemic
symptoms in normotensive subjects in whom blood
pressure was reduced with trimethaphan. Cerebral
blood flow was not measured at the time of symp-
tom onset. A reasonable summary of the available
literature is that the first signs of insufficient oxy-
gen delivery to the brain will occur in normotensive
adult subjects at MAPs between 40 and 50 mm Hg at
the level of the circle of Willis. Note that these num-
bers are MAPs and not cerebral perfusion pressures,
and should be assumed to apply only when ICP is
normal (ie, relatively low).
The CNS blood flow reserve serves as a critical buffer
against the adverse effects of hypotension and is the prin-
cipal reason why blood pressures well below resting nor-
mal levels are so frequently well tolerated in the operating
room environment. However, it is my perception that this
CNS blood flow reserve phenomenon is not emphasized in
the training received by anesthesiologists, and that at least
some clinicians are minimally aware of the phenomenon.
As a result, some clinicians may fail to recognize situations
in which the normal CNS blood flow reserve has already
been compromised, rendering individual patients relatively
more vulnerable to hypotension. There are at least 5 situ-
ations (discussed later in the section, “Compromise of the
CNS Blood Flow Reserve”) in which this may occur: (1)
recent central nervous injury; (2) raised local tissue pres-
sure; (3) chronic hypertension; (4) loss or absence of collat-
eral blood flow pathways; and (5) vertical hydrostatic blood
pressure gradients between the heart and the brain.
2. Horizontal surgical positions: In any fluid column
that is directed upward by an ejecting force, the
pressure within that column diminishes in propor-
tion to the height above the source. If a garden hose
is pointed upward, the water rises until the weight
of the vertical column produces a pressure equal
to that at the nozzle. This same reduction in pres-
sure occurs in a vertically oriented arterial system.
The magnitude of the effect, based on the density of
blood, is such that for every inch (2.54 cm) of verti-
cal displacement, pressure within the column can
be expected to decrease by 2 mm Hg. If the MAP
of the blood exiting the aortic valve is 95 mm Hg,
by the time it has traveled roughly 12 inches verti-
cally to the level of the circle of Willis, the pressure
will be 95 − (12 × 2 = 24) = 71 mm Hg. This leads to
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 EE Special Article
the second explanation (the first is the CNS blood
flow reserve, vide supra) for the apparent toler-
ance of the human brain to the relative hypoten-
sion that is so common during general anesthesia.
In a patient anesthetized with the head at the level
of the heart, an intraoperative MAP of 70 mm Hg
is “normal” in terms of cerebral perfusion pres-
sure. (In the horizontal position, ICP is inevitably
greater than in the vertical position. Therefore,
at a constant MAP at the circle of Willis, cerebral
perfusion pressure will actually be slightly lower
in the horizontal position.) This arithmetic means
that the first 20%–25% reduction in MAP as mea-
sured by a blood pressure cuff on the arm is literally
“free” in terms of its effects on cerebral perfusion
pressure. At a MAP of 70 mm Hg in a horizontal
position, cerebral perfusion pressure is very little
different from that which occurs in the sitting or
standing positions. This explains the absence of
intraoperative cerebral harm, which, in turn, has
probably contributed to the relatively casual pre-
vailing attitudes about relative hypotension intra-
operatively. This bit of physiological naivety has
been reinforced by investigations purporting to
demonstrate the absence of adverse cerebral effects
of “hypotension,” using a MAP of 70 mm Hg as
the definition of hypotension.37 It also is probably
part of the explanation for why the superficially
logical relationship between the incidence of stroke
and intraoperative hypotension has not been con-
spicuous across many investigations.38–40 CPB has
been the context in which the stroke–hypotension
relationship has been examined most extensively.
However, there are 2 limitations with that litera-
ture. The first is the problem that any conclusion
derived from the high stroke-risk patients common
in the context of CPB may not be broadly relevant.
Second, and more significant, is the difficulty that
the studies comparing MAP ranges during CPB
present contradictory conclusions.40 Two recently
published studies highlight that difficulty. The ret-
rospective investigation by Sun et al41 reported an
association between stroke and intraoperative MAP
of <64 mm Hg. However, a randomized, prospec-
tive investigation by Vedel et al42 comparing MAPs
of 40–50 vs 70–80 mm Hg reported no differences in
stroke rate (with any trends leaning in favor of the
lower MAP). Whatever the causative role of hypo-
tension in the occurrence of stroke, it has been theo-
rized that hypotension may be more important as
an aggravator of thromboembolic strokes that have
occurred independently by reducing clearance of
microemboli or perfusion in boundary zones.43–45
COMPROMISE OF THE CNS BLOOD FLOW
RESERVE
At least 5 circumstances can result in a reduction of the
blood flow reserve that normally serves so well to buf-
fer the healthy human CNS against the adverse effects of
hypotension.
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1. CNS injury: Autoregulation is a physiologically frag-
ile phenomenon. Many CNS injury states,46 but most
particularly, subarachnoid hemorrhage47 and trau-
matic brain injury,48 and probably spinal cord injury
and stroke,49 have the potential to impair the cere-
bral blood flow autoregulation response to hypoten-
sion and to render blood flow pressure passive in
response to blood pressure reduction. In addition,
acute traumatic brain injury and subarachnoid hem-
orrhage commonly result in resting cerebral blood
flow values that are approximately 50% of those seen
in normal subjects. These 2 phenomena, impaired
cerebral blood flow autoregulation and reduction
in resting CNS blood flow, are well demonstrated
in the setting of human traumatic brain injury and
subarachnoid hemorrhage.50,51 They are less well
demonstrated for spinal cord, but the physiology of
the spinal cord is a “microcosm of the brain,”52 and
it is reasonable to assume, pending information to
the contrary, that impaired autoregulation and low
baseline flow occur there as well. The implications
are presented graphically in Figure 3, in which the
line of pressure passivity is drawn through a CNS
blood flow value that is approximately half of nor-
mal. Reduction of MAP in a normal subject to 50
mm Hg might encroach significantly but not criti-
cally on the CNS blood flow reserve, but the same
blood pressure reduction occurring in the face of
recent CNS injury might reduce flows to injurious
levels.53–55 The duration of this impaired autoregula-
tion/low flow state is known to be at least 72 h and
sometimes considerably longer after traumatic brain
injury.48,56 It has been shown to persist for 7 days in
animal models of spinal cord injury, and the current
clinical recommendation is for 7 days of MAP sup-
port.57,58 The assumption that at least 7 days of MAP
support is appropriate in all acute CNS injury situa-
tions appears prudent.
2. Raised local tissue pressure: Anything that exerts
direct local pressure on the CNS and thereby raises
local tissue pressure reduces the net perfusion pres-
sure achieved by a given MAP. While discussions of
acceptable intraoperative blood pressures frequently
focus on MAP, it is really perfusion pressure that
is the important variable. Perfusion pressure is the
difference between MAP and venous pressure or
local tissue pressure, whichever is greater. In many
instances, venous pressure and local tissue pres-
sure are unknown. However, in many normal cir-
cumstances, those pressures are relatively low, and,
as a result, MAP becomes a reasonable surrogate
for perfusion pressure. However, when local tissue
pressures are raised, MAP may substantially under-
estimate perfusion pressure. This consideration is
already familiar in some contexts. The importance
of taking ICP into consideration in determining cere-
bral perfusion pressure is well established, but there
are other circumstances in which this local pressure
phenomenon is relevant, including cervical spinal
stenosis, any situation in which CNS tissue is under
ANESTHESIA & ANALGESIA
 Blood Pressure and the Brain
pressure from a surgical retractor, and perhaps in
the circumstances of raised intraocular pressure dur-
ing prone surgery. To conceptualize this difference
clearly, it may be helpful to distinguish between
perfusion pressure, as calculated by the difference
between MAP and venous pressure, and “transmu-
ral pressure,” calculated as the difference between
intraluminal vascular and local tissue pressures.
When pressure is applied locally to CNS tissue, the
determinant of flow through the local capillaries is
transmural pressure (ie, the pressure differential
between the vessel lumen and the local extravascu-
lar pressure). One encounters only infrequent use of
that term, probably because a measure of that local
tissue pressure is frequently not available. Figure 4
is an attempt to indicate the qualitative importance
of transmural pressure. In that figure, flow through
a capillary bed that is under local pressure will be
determined not by the perfusion pressure as calcu-
lated by the difference between arterial and venous
pressure, but rather by the transmural pressure.
While the morbidity that is actually associated with
this local pressure phenomenon is very difficult to
discern in the published literature, this author’s
anecdotal experience is that underappreciation of
this phenomenon has most certainly led on many
occasions to morbidity in the context of cervical spi-
nal stenosis.
3. Hypertension: It has been demonstrated in both ani-
mals and humans that chronic hypertension results
in “right shifting” of the cerebral blood flow autoreg-
ulation curve.10 Both the lower limit of cerebral blood
flow autoregulation and the upper limit of cerebral
blood flow autoregulation are shifted to greater
MAP values than occur in normotensive subjects.59
The teleological explanation for this phenomenon is
that to reduce vessel distension and the risk of rup-
ture, mother nature thickens the intima and media
of cerebral vessels. The downside of this protective
mechanism is that these vessels dilate less readily,
which results in the right shifting. Important for the
clinician is Strandgaard’s10 observation that, in his
subjects, there was a good correlation between rest-
ing MAP and both the lower limit of cerebral blood
flow autoregulation and the MAP at which ischemic
symptoms first occurred. While it is frequently said
that treating hypertension “resets” (ie, left shifts), the
autoregulatory curve, to my knowledge, it is only the
investigation by Strandgaard10 that provides human
data to support that assertion. Among his study
groups were: (1) “well-controlled” hypertensive
subjects (n = 9); and (2) normotensive subjects (n =
10). Their baseline MAPs were, respectively, 116 ± 18
and 98 ± 10 mm Hg; and their lower limit of cerebral
blood flow autoregulations were 96 ± 17 and 73 ± 9
mm Hg. The relatively constant difference between
the baseline and lower limit of cerebral blood flow
autoregulation MAPs in the 2 groups suggests that
the hypertensive subjects, all of whom had been
treated for from 1 to 8 years after an average intake
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MAP of 148 ± 12 mm Hg had, in fact, left-shifted in
proportion to the MAP reduction that had occurred
with treatment (from 149 to 116 mm Hg). However,
the time course of this left shifting is unknown. In a
separate group of 4 severely hypertensive patients,
studied before and after 8–12 months of antihyper-
tensive treatment, only 1 demonstrated apparent
left shifting of the cerebral blood flow autoregula-
tion curve. This leads to the uncomfortable clinical
implication that what resetting occurs may not be
accomplished quickly. In addition, there are no data
to indicate whether the antihypertensive agent that
is used is relevant to the extent or time course of
resetting.
4. Collateral blood supply: Part of the explanation for
the tolerance of the CNS for relative hypotension is
generous collateralization. Blood has more than 1
way of reaching most parts of the CNS; but as a result
of vascular disease, congenital variation, and iatro-
genesis (surgery), collateralization may vary from
individual to individual, making some vascular beds
almost unpredictably more vulnerable to hypoten-
sion. This variation may be particularly relevant in 3
vascular distributions: (a) The circle of Willis; (b) the
anterior spinal artery; and (c) the optic nerve.
a. The Circle of Willis. Standard anatomic diagrams
(Figure 5) suggest that blood has at least 2 alterna-
tive pathways for arriving at any of the 3 principal
cerebral arteries. However, postmortem examina-
tion studies have revealed that only approximately
50% of normal subjects have a complete circle of
Willis,60 that up to 25% of adults do not have func-
tional posterior communicating arteries,61 that
3%–5% of adults do not have an anterior com-
municating artery62,63; and that approximately 7%
of adults have 1 carotid artery distribution, more
often the left, that is isolated (ie, without collat-
eral communication via an anterior or a posterior
communicating artery). There is additional collat-
eralization potential via leptomeningeal vessels
and/or the ophthalmic artery; but these, too, are
variable. This author has encountered instances in
which those congenital variations appear to have
made individual patients unpredictably more
vulnerable to hypotensive insults.64,65
b. The anterior spinal artery. The arterial supply to
the anterior spinal artery system is very variable,
with the number of feeding vessels varying sub-
stantially among subjects. The most constant of
these is the arteria radicularis magna, also known
as the artery of Adamkiewicz. The arteria radicu-
laris magna typically enters the spinal canal via
an intervertebral foramen between the T8 and L1
vertebral bodies, usually on the left side. The arte-
ria radicularis magna then makes a “hairpin” turn
in a caudal direction as it joins the anterior spinal
artery.66 It serves to deliver blood principally to the
conus medullaris. In some individuals, the blood
delivery of the arteria radicularis magna to the
conus medullaris is supplemented by arteries that
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 EE Special Article

travel cephalad with the roots of the cauda equina. to produce a lesion in the axial center of the nerve,
These vessels typically originate from the internal which would, in turn, be expected to cause the cen-
iliac artery.66 The arteria radicularis magna proba- tral visual deficit that is, in fact, most common with
bly delivers very little cephalad flow in the anterior posterior ischemic optic neuropathy.72 Furthermore,
spinal artery in most subjects and the diameter of posterior ischemic optic neuropathy occurring in
the anterior spinal artery cephalad to the junction other surgical situations (gastrointestinal bleeding
with the arteria radicularis magna is typically very and radical neck dissection) has yielded pathologic
narrow.66 In some individuals, the anterior spinal specimens in which the location of the lesion is con-
artery is discontinuous at this level.67 This means sistent with Baig et al’s74 hypothesis.75,76 I should
that the majority of the blood supply to the spinal hasten to mention that while this author believes
cord at and above approximately the T10 vertebral that posterior ischemic optic neuropathy is often
level is descending caudally from the upper por- a boundary zone ischemia phenomenon to which
tions of the anterior spinal artery. In some indi- relative hypotension may contribute, that opinion
viduals, there is, as a result, a boundary zone, or is not confirmed by the existing literature. In par-
“watershed,”c territory in the mid-thoracic and ticular, the American Society of Anesthesiologists’
low thoracic spinal cord region.66 These vascular Advisory on Post Operative Visual Loss states spe-
variations have the potential to make some indi- cifically “that the use of deliberate hypotensive tech-
viduals unpredictably more vulnerable to spinal niques during spine surgery has not been shown to
cord ischemia in the event of hypotension or the be associated with the development of perioperative
loss of or sacrifice of intercostal or intervertebral visual loss.”77
feeding vessels. The author has encountered an
instance in which it appeared that induced hypo-
tension resulted in infarction of the conus medul-
laris and the upper portions of the cauda equina.68
c. The optic nerve. Two regions of the optic nerve are
variably and potentially precariously collateralized.
The first is the optic disk. The blood supply to the
optic disk comes via the posterior ciliary arteries,
which are noncollateralized end arteries that are
variable in number.69 Well before the phenomenon
of postoperative visual loss after spine surgery
brought ischemic optic neuropathy to prominence,
anterior ischemic optic neuropathy was well known
to ophthalmologists. Anterior ischemic optic neu-
ropathy presents most often as partial or “altitu- Figure 3. Cerebral blood flow autoregulation in acute injury states.
dinal” visual loss, typically in patients with optic In acute injury states, most notably traumatic brain injury and sub-
discs with specific anatomic characteristics (small arachnoid hemorrhage, cerebral blood flow is frequently reduced to
levels approximately half of normal, and autoregulation is impaired
disk, small cup-to-disk ratio, “crowded” disk) and (ie, the mean arterial pressure [MAP]/cerebral blood flow relation-
with risk factors for vascular disease, and especially ship is pressure passive [dotted line]). MAPs that might be tolerated
in patients in whom nocturnal hypotension, often in normal subjects may reduce cerebral blood flow to critically low
in association with new treatment of hypertension, levels (vertical arrow). CBF indicates cerebral blood flow.
has occurred.69–71 Posterior ischemic optic neuropa-
thy was much less familiar before the phenomenon
of blindness after prolonged prone surgery.72 The
precise location of the pathology of posterior isch-
emic optic neuropathy occurring after spine surgery
is not well characterized73 because (fortunately)
patients are rarely submitted to postmortem exami-
nation after spine surgery. However, Baig et al74 has
proposed that there is a region of relatively sparse
collateralization in the midportion of the optic nerve
(ie, midway between the globe and the optic canal),
where the nerve is usually supplied entirely by cen-
tripetal arterioles arising from the pia on the surface
of the nerve, and that this is where the insult of poste-
rior ischemic optic neuropathy occurs. Insufficiency
of this blood supply pathway would be expected Figure 4. Perfusion pressure and transmural pressure. See text
(“Raised Local Tissue Pressure”) for discussion. The magnetic reso-
c
The common term “watershed” will hereafter be avoided because the nance image on the right is from a patient with severe cervical spinal
metaphor is not apt. Water flows away from a watershed. Boundary zone stenosis. + indicates raised local tissue pressure; MAP, mean arte-
is preferred. rial pressure; VP, venous pressure.

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 Blood Pressure and the Brain
Figure 5. Common variations in the anatomy of
the circle of Willis expressed as percentage prev-
alence (%) in disease-free adults. See text for dis-
cussion. ACA indicates anterior cerebral artery;
AComm, anterior communicating artery; MCA,
middle cerebral artery; PCA, posterior cerebral
artery; Pcomm, posterior communicating artery.
Acute Focal Cerebral Ischemia
The management of the patient with acute focal cerebral isch-
emia (stroke) merits mention in the context of a discussion
of collateral blood flow. It is almost entirely in the setting of
neurovascular interventions (thrombectomy, thrombolysis)
after acute stroke that anesthesiologists provide general anes-
thesia for individuals known to have recently experienced a
focal stroke. In that situation, it is generally understood that
perfusion of the potentially salvageable tissue at the periph-
ery of a stroke, the so-called penumbra, is dependent on col-
lateral perfusion, sometimes across boundary zone territories
between cerebral artery distributions, and that this type of
perfusion requires the maintenance of high-normal MAPs.
Few anesthesia providers need to be instructed that main-
tenance of blood pressure in this situation is important.78
However, focal ischemic lesions (strokes) occasionally occur
spontaneously during anesthesia.38,79 It seems likely, albeit
unproven, that the effects of such insults will be aggravated
that by relative hypotension during general anesthesia.45 This
possibility provides another incentive not to induce or permit
degrees of hypotension that are not specifically necessary for
the conduct of the surgical procedure, especially in patients
at risk for stroke.80
5. Vertical hydrostatic gradients: Intraoperative patient
positions in which the head is substantially above the
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heart result in vertical hydrostatic gradients. It is this
author’s conclusion that such gradients have impor-
tant physiologic implications and that blood pres-
sure should be obtained or arithmetically corrected
to the cranial level.81 The lack of adverse effects on
the brain of a 25% reduction from a typical awake
MAP in the common horizontal surgical positions
has contributed to the casual attitude toward blood
pressure reductions of this order. However, bringing
this same attitude to situations in which the surgi-
cal position results in the head being substantially
above the heart has resulted, in this author’s opin-
ion, in a significant incidence of neurological injury.82
Since before the time that the term “neuroanesthe-
sia” achieved currency, it has been an article of faith
among neuroanesthetists that blood pressure during
sitting neurosurgical procedures be transduced and
maintained at the level of the external auditory canal.
However, when the beach chair position was intro-
duced into orthopedics, somehow the laws of phys-
ics were perceived to be different when the surgical
objectives were bones rather than brains. Figure 6
attempts to depict the issues. If a MAP that is widely
deemed to be acceptable in a supine orientation (eg,
65 mm Hg, as measured by a blood pressure cuff
on the arm is accepted during beach chair position
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 EE Special Article
surgery), the MAP at the external auditory canal is
approximately 41 mm Hg. Normotensive individu-
als in a head-up posture should tolerate a MAP of
41, although some will have presyncopal symp-
tomatology. However, perfusion would probably
be sufficient in most subjects to prevent neurologic
injury unless this level of hypoperfusion was very
sustained. However, if it was necessary to place the
blood pressure cuff on the calf, the vertical gradient
becomes larger. In the beach chair position configu-
rations used in this author’s institution, the incre-
ment to the gradient is only 6 inches. But, a MAP of
65 at the calf therefore results a calculated MAP at
the external auditory canal of 29 mm Hg. This has
the potential to be much more rapidly injurious.
There has not been universal agreement that making
allowance for this hydrostatic difference is necessary or
important. It has been argued that, because an equivalent
reduction in venous pressure, to negative values, occurs
simultaneously with the reduction in arterial pressure, the
arterial to venous blood pressure difference is unchanged
by the head-up position and that cerebral perfusion pres-
sure is therefore unaltered. This “closed-loop” or “siphon”
model of the cerebral circulation holds that as long as per-
fusion pressure is adequate somewhere in a vertically ori-
ented circulatory loop, it will be adequate everywhere in
that loop. This author has argued that this rationale is spe-
cious because it assumes siphon-like function of the cerebral
function.81 Those who have used siphons will appreciate
that they function only with rigid tubing. Too much of the
cerebral vasculature amounts to nonrigid tubing to entrust
our patients’ well-being to the unproven and improbable
closed loop model.
THE BOTTOM LINE
Practitioners frequently want to know, “How low can you
go?” The very question is unappealing because it implies
an element of brinkmanship that is not the modus operandi
of anesthesiologists. However, surgical circumstances may
occasionally justify induced hypotension and the matter of
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acceptable minimum pressures becomes relevant. Therefore,
I offer the following speculation, which is based largely on
ischemic symptom thresholds in nonanesthetized adults
and not on outcome data. In a head-up position, when ICP
is low, MAPs of 40–50 mm Hg at the level of the circle of
Willis should be tolerated by most healthy, normotensive
patients who are free of vascular disease. In the supine posi-
tion, when ICP is likely to be somewhat higher, minimum
pressures of 45–55 mm Hg should be tolerated. In the beach
chair position, assuming a 12-inch vertical gradient between
the midpoint of a blood pressure cuff on the arm and the
external auditory canal, a minimum cuff MAP of 65–70
should result in circle of Willis MAPs of 40–45 mm Hg. In
the event of the use of a blood pressure cuff on the calf, I
suggest minimum MAPs of 80–85 mm Hg. This recommen-
dation entails slightly more than the 12 mm Hg allowance
appropriate to the additional 6 inches of gradient attendant
on the use of a calf cuff because distal lower extremity blood
pressures can be greater than those recorded in the arm.83
In beach chair position surgery, great care should be taken
to assure that there is no compression of the jugular veins,
which would increase ICP and reduce the net cerebral per-
fusion pressure achieved by any given MAP.84
All of the foregoing recommendations constitute
extremes that should never be routine and should only be
approached when surgical circumstances provide a signifi-
cant incentive for reduced blood pressure. Periods of hypo-
tension should be kept as brief as possible. Intermittent
hypotension, in response to varying surgical needs, will
be preferable to sustained hypotension. Monitoring of the
nervous system has the potential to widen the latitudes.
The combination of somatosensory and motor evoked
potentials will provide substantial assurance that there is
not significant ischemia of the brain and spinal cord. There
is increasing interest in the use of near-infrared spectros-
copy devices to monitor brain oxygenation in anesthetized
patients. However, this author is of the opinion that because
of the hyperfocal nature of the brain region monitored,
because of performance variation among the clinically
available devices, and because of the problem of extracra-
nial contamination, the false negative potential is too great
Figure 6. Hydrostatic gradients in the sitting posi-
tion. Mean arterial pressures (MAPs) at the level
of the external auditory canal (as a marker of the
level the circle of Willis) have been calculated on
the basis of the density of blood and estimated
vertical distances between the external auditory
canal and the center of blood pressure cuffs on
the arm and on the lower leg, 12 inches and 18
inches, respectively. A 1-inch vertical displace-
ment results in a calculated reduction in intraar-
terial pressure of 2 mm Hg. The blood pressures
at the right-hand side of the panel represent a
normotensive awake state. The remaining calcu-
lations assume intraoperative blood pressure cuff
MAPs of 65 mm Hg.
ANESTHESIA & ANALGESIA
 Blood Pressure and the Brain
for a “normal” near-infrared spectroscopy signal to give
complete assurance as to the well-being of the brain.
In summary, the principal theses offered by this review are:
(1) that the average lower limit of cerebral blood flow auto-
regulation in normotensive adult humans is not <70 mm Hg;
(2) that there is considerable intersubject variability in both
the lower limit of cerebral blood flow autoregulation and the
efficiency of cerebral blood flow autoregulation; (3) that there
is as substantial blood flow reserve that buffers the normal
CNS against critical blood flow reduction in the face of hypo-
tension; (4) that there are several common clinical phenomena
that have the potential to compromise that buffer; and (5) that
the average threshold for the onset of CNS ischemic symp-
toms is probably a MAP of 40–50 mm Hg at the level of the
circle of Willis in a normotensive adult in a vertical posture
and 45–55 mm Hg in a supine subject. These latter pressures
should probably only be approached deliberately when the
exigencies of the surgical situation absolutely require it. E
DISCLOSURES
Name: John C. Drummond, MD.
Contribution: This author conceived of and wrote the manuscript.
This manuscript was handled by: Gregory J. Crosby, MD.
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