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dehavenon2021
dehavenon2021
dehavenon2021
46
1 Department of Neurology, University of Utah, Salt Lake City, Utah Address for correspondence Adam de Havenon, MD, Department of
2 Department of Neurology, Yale University, New Haven, Connecticut Neurology, University of Utah, 175 N. Medical Dr, Salt Lake City, UT
3 Department of Neurology, University of Washington, Valley Medical 84132 (e-mail: adam.dehavenon@hsc.utah.edu).
Center, Seattle, Washington
4 Department of Radiology, University of Utah, Salt Lake City, Utah
5 Department of Neurology, New York University, New York, New York
6 Department of Neurosurgery, University of Virginia, Charlottesville,
Virginia
7 Department of Neurosurgery, University of Utah, Salt Lake City, Utah
8 Department of Neurology, Vanderbilt University Medical Center,
Historically, the effect of blood pressure (BP) on stroke out- flow, and consequent infarct progression.2 This could be
come has been shown to have a U-shaped curve, with extremes particularly important in penumbral territory where a pres-
in BP associated with worse outcomes.1 Provision of adequate sure-passive system exists in which arteries and arterioles
cerebral perfusion in acute ischemic stroke (AIS) patients with maximally dilate in response to tissue ischemia and no longer
large vessel occlusion (LVO) represents a critical aspect of exhibit the capacity for pressure autoregulation. In this
patient care in both the peri- and intraprocedural settings as manner, cerebral blood flow could be directly dependent on
it relates to endovascular thrombectomy (EVT). Intuitively, systemic BP.3 However, hypertension could be damaging to the
reductions in systemic BP before revascularization may result stroke and penumbra by promoting edema, cytotoxic media-
in a cerebral perfusion decrement, compromised collateral tors, and hemorrhagic conversion.4–6
published online Issue Theme Acute Stroke; Guest © 2021. Thieme. All rights reserved. DOI https://doi.org/
January 20, 2021 Editors: Navdeep Sangha, MD, and Koto Thieme Medical Publishers, Inc., 10.1055/s-0040-1722721.
Ishida, MD 333 Seventh Avenue, 18th Floor, ISSN 0271-8235.
New York, NY 10001, USA
Blood Pressure Management for Acute Ischemic Stroke Havenon et al. 47
Table 1 American Heart Association guidelines for bral collateral failure.6,11–13 Interventional trials to alter BP
perithrombectomy blood pressure8 prior to EVT or IV tPA are few, but there are ample data on BP
reduction in the hours and days after stroke onset using a
Clinical Blood Class of Level of variety of antihypertensive medications. The Prehospital
scenario pressure recommendation evidence
Transdermal Glyceryl Trinitrate in Patients with Ultra-acute
goal
presumed stroke (RIGHT-2) failed to show benefit in the
Pre-EVT, 185/110 IIa B-NR
hyperacute window.14 The Controlling Hypertension and
no tPA
Hypotension Immediately Post Stroke (CHHIPS) and Evalua-
Pre-EVT, <180/105 I B-R
tion of Acute Candesartan Cilexetil Therapy in Stroke Survi-
post-tPA
administration vors (ACCESS) reported a mortality benefit, but no functional
benefit of BP lowering during the acute phase of stroke.4,15
Peri-EVT, 180/105 IIa B-NR
no tPA BEST, a trial evaluating β-blockers in AIS, showed increased
mortality in patients randomized to early β-blocker use.16
Pre-EVT, <180/105 I B-R
post-tPA SCAST, a randomized study lowering BP in AIS patients using
administration candesartan, suggested a higher risk of poor outcome in the
Post-EVT, 180/105 IIa B-NR treatment group.17 Accordingly, a Cochrane review of 26 trials
no tPA concluded that there is “insufficient evidence that lowering BP
and TICI 0–2a during the acute phase of stroke improves functional out-
Post-EVT, <180/105 IIb B-NR come.”18 Recently, the ENCHANTED (Enhanced Control of
post-tPA
higher BP, Rordorf et al concluded that patients with “large anesthesia induction, and (3) vasodilation caused by use of
extracranial or intracerebral vessel stenosis or occlusion” seem anesthetic gases resulting in a steal phenomenon, whereby
to have the most benefit from induced BP.28 Hillis et al induced cerebral blood flow is shunted to healthy brain tissue from the
higher BP in a small number of patients with perfusion– penumbra. However, randomized trials have failed to show a
diffusion mismatch and reported a “strong, statistically signif- difference in outcomes of patients treated with general anes-
icant association between improved function and improved thetics versus conscious sedation.40,41 One key factor that
perfusion.”29 In Hillis et al’s study, intravenous phenylephrine putatively explains the better outcomes with general anesthesia
was titrated to achieve a 10 to 20% increase in mean arterial in observational studies versus in clinical trials may be the
pressure over 1 to 8 hours, and this target was maintained for prompt treatment of hypotensive episodes for anesthetized
at least 24 hours. Each patient in the intervention group patients in clinical trials.42
showed some degree of improvement on the NIHSS and a Recent publications have studied the impact of hypotension
cognitive battery after the treatment target was reached. On on patient outcomes after EVT, independent of anesthetic
day 3, the NIHSS score had improved by 4.2 1.0 in the choice. By strictly analyzing their experience with patients
intervention group and by 1.2 3.0 in the control group. Based who underwent EVT under general anesthesia, Löwhagen
on these and other studies,30–32 induced hypertension may be Hendén et al were able to control for the confounding effect
a reasonable approach to the prethrombectomy LVO patient, of anesthesia type, and noted that intraprocedural mean BP
especially if there is a prolonged period between medical care reductions of >40% from baseline were predictive of poor
access and endovascular recanalization, such as in “hub and outcome.43 Similarly, Whalin et al studied patients who were
spoke” stroke systems of care.33 treated via conscious sedation and showed that for every
recanalization (TICI 0–2a). Similarly, Goyal et al examined alization.53 Similar results were seen in a secondary analysis
patients with LVOs following successful EVT.46 Patients who of Mistry et al’s cohort of patients receiving EVT, where
died at 3 months from onset had higher maximum SBP levels elevated postprocedural BPV was associated with worse
compared with those who did not (184 24 mm Hg vs. 90-day functional outcome. It remains unclear whether
167 21 mm Hg; p < 0.001), whereas patients who were func- increased BPV in the post-EVT period is the direct cause of
tionally independent at 3 months had a lower maximum SBP poor outcome or whether increased BPV is an epiphenome-
level (163 20 mm Hg vs. 179 23 mm Hg; p < 0.001). Inter- non of infarct growth or other physiologic stressors.
estingly, BP management was not associated with the develop-
ment of symptomatic intracerebral hemorrhages (sICH),
Discussion
although the overall rates of sICH were relatively low (6.5%).
Anadani et al also identified BP following EVT as a determinant Randomized controlled trial data are lacking to guide man-
of outcomes at 3 months.47 In their analysis of patients under- agement of peri-EVT BP, but it has been common practice to
going EVT for LVO, a lower average SBP was associated with allow permissive hypertension to recruit collaterals in the
improved functional outcomes (modified Rankin’s scale: 0–2) setting of vessel occlusion and then reduce BP following
at 3 months. Interestingly, maximum SBP following EVT was recanalization.54–57 Eventually, guidelines were released
not associated with improved outcomes. advocating for SBP 180/105 mm Hg for the first 24 hours
Conversely, the SIESTA investigators did not identify after treatment in patients undergoing EVT.7 Concurrently,
changes in postprocedural BP to be associated with neuro- evidence emerged that lowering BP, at least post-EVT, could
logical improvement or long-term functional outcome in a provide some benefit.46,58,59 With the conceptual progress
post hoc analysis.42 However, there were some distinct
otherwise proves less easily titratable and often causes brady- For the pre-EVT period, one research topic that has partic-
cardia.71 Nearly all high-quality data guiding management of ular appeal is induced hypertension. Under normal circum-
LVO patients involve only anterior circulation occlusions. Fur- stances, the cerebral vasculature has the intrinsic ability to
ther data are needed for posterior circulation patients, which, maintain relatively constant cerebral blood flow despite
for instance, accounted for 18% of thrombectomy cases in the changes in systemic BP, a mechanism known as cerebral
cohort of Goyal et al.46 Finally, patients with tandem disease or autoregulation.73 This mechanism ensures that the cerebral
underlying stenosis are now more commonly undergoing blood flow matches the brain’s metabolic demands and
angioplasty and stent placement of both extra- and intracranial protects it from hypo- or hyperperfusion. After large-vessel
disease in conjunction with EVT. These patients merit addi- intracranial occlusion, the downstream perfusion pressure in
tional consideration for reperfusion syndrome in addition to BP that vessel will be reduced below the lower autoregulatory
control guidelines driven by EVT data.72 limit. Exhaustion of compensatory vasodilatory capacity and
the loss of intrinsic autoregulatory function in the ischemic
tissue leads to pressure passivity.74,75 This means that changes
Future Research Directions
in systemic BP are directly transmitted to the brain, and by
Future research should focus on optimizing not only biomarker increasing BP, a corresponding increase in cerebral blood flow
outcomes such as infarct volume but also functional outcomes to the ischemic tissue occurs.
of EVT-treated patients. Data-driven and actionable BP targets Animal experiments have shown that even a short interval of
need to be generated in the pre-, peri-, and post-EVT period. induced hypertension effectively augments cerebral blood flow
Large observational studies with sophisticated data-science in LVO via an abrupt opening of collapsed collateral vessels.76
Fig. 1 A patient with a left middle cerebral artery occlusion stroke (seen on diffusion weighted imaging [DWI]). The top row shows magnetic resonance
imaging perfusion with a mean arterial pressure (MAP) of 83 mm Hg and the bottom row shows the same patient 10 minutes later after an intravenous
phenylephrine infusion was started, raising MAP to 112 mm Hg. After blood pressure augmentation, there is noticeable improvement in the MRI perfusion
characteristics, with reduction in hypoperfused tissue (mean transit time, MTT) and improvement in cerebral blood flow (CBF).
to the level of a hypertensive emergency should be avoided volumes and worse functional outcome. Stroke 2019;50(07):
because it can induce end-organ dysfunction including myo- 1797–1804
cardial infarction, renal impairment, and hemorrhagic stroke,79 3 Vitt JR, Trillanes M, Hemphill JC III. Management of blood pressure
during and after recanalization therapy for acute ischemic stroke.
but the induction of mild hypertension for a short duration
Front Neurol 2019;10:138
appears relatively safe based on preliminary data. Four nonran- 4 Potter JF, Robinson TG, Ford GA, et al. Controlling hypertension
domized studies using IV vasopressors with treatment duration and hypotension immediately post-stroke (CHHIPS): a random-
between 3 and 7 days had only one major adverse event, a sICH ised, placebo-controlled, double-blind pilot trial. Lancet Neurol
in a patient who was concurrently therapeutically anticoagu- 2009;8(01):48–56
5 Hubert GJ, Muller-Barna P, Haberl RL. Unsolved Issues in the
lated with IV heparin.28,31,80,81 However, despite compelling
Management of High Blood Pressure in Acute Ischemic Stroke. Int
conceptual reasons and pilot data, we will need rigorous clinical
J Hypertens [online serial]. 2013 2013. Accessed October 23, 2013
trial evidence to support BP augmentation as a potential neuro- at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655558/
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7 Powers WJ, Rabinstein AA, Ackerson T, et al;American Heart
support studies that would use calcium channel blockers or
Association Stroke Council. 2018 Guidelines for the early man-
nitric oxide donors as opposed to β-blockers or angiotensin- agement of patients with acute ischemic stroke: a guideline for
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