The Journal of Emergency Medicine, Vol. 19, No. 4, pp.

339 –346, 2000

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Clinical
Communications

STROKE PRECIPITATED BY MODERATE BLOOD PRESSURE REDUCTION

Glenn M. Fischberg,
Reprint Address: Mark Fisher,
MD, Edward Lozano, MD, Kumar Rajamani, MD, Sebastian Ameriso, MD, and
Mark J. Fisher, MD
University of Southern California, Los Angeles, California
MD, Department of Neurology, University of California Irvine Medical Center, 101 The City Drive South,
Building 55, Room 121, Orange, CA 92868

e Abstract—Rapid lowering of blood pressure can precip-
itate or worsen ischemic strokes. This usually has been
observed in the setting of profoundly lowered pressure and
hypotension. We report on six patients in whom ischemic
neurologic injury ensued or worsened after moderate re-
duction of blood pressure by pharmacological treatment.
The 6 patients suffered new or worsened ischemic neuro-
logic deficits after receiving oral or intravenous antihyper-
tensive medications, mostly after relatively small doses.
Mean arterial blood pressure in these patients was de-
creased by 25 ⴞ 7.7%, or 37 ⴞ 16 mm Hg (mean ⴞ SD)
without resultant hypotension. These cases emphasize the
potential hazards of moderate blood pressure reduction by
antihypertensive medications in the setting of an acute
ischemic stroke or transient ischemic attack (TIA), as well
as rapidly treated hypertension even in those who have not
yet manifested ischemic symptoms. © 2000 Elsevier Sci-
ence Inc.
e Keywords—Hypertension; ischemic stroke; TIA; treat-
ment; complications
INTRODUCTION
The role of hypertension as a risk factor for stroke is well
recognized (1). Nevertheless, the treatment of hyperten-
sion in the setting of acute brain ischemia remains con-
troversial (2). We report six patients who had initiation
or worsening of neurologic deficits after moderate blood
pressure reduction caused by the administration of anti-
hypertensive medication. All six patients were evaluated
by members of the Stroke Service of the Los Angeles
County–University of Southern California Medical Cen-
ter between 1995 and 1998.
CASE 1
A 60-year-old, right-handed woman was admitted for
uncontrolled diabetes and a diabetic ulcer on the left leg.
Nine years prior, she had suffered an ischemic stroke
causing left hemiparesis, from which she had recovered
fully. She also had hypertension and hypercholesterol-
emia. She was receiving enalapril, isosorbide, and aspirin
in addition to insulin. She had a right carotid endarter-
ectomy 1 year before admission. Her blood pressure was
180/90 mm Hg. Neurologic examination revealed evi-
dence of a mild peripheral neuropathy. Brachial pressure
was monitored every 8 h by automated equipment. On
the third day after admission, she complained of nausea
and vertigo. Blood pressure was noted to be 220/120 mm
Hg. After 10 mg of oral nifedipine, her blood pressure
remained 220/110 mm Hg, and nausea and vertigo per-
sisted. Two hours after the first dose, she received an-
other 10 mg of nifedipine sublingually. Ten minutes
later, she developed left-sided weakness and became
lethargic, while her blood pressure was 168/86 mm Hg.
She then exhibited left gaze-evoked nystagmus, mild
weakness in the left upper and left lower extremities, and
mild left upper extremity dysmetria. Magnetic resonance
imaging (MRI) of the brain the next day revealed an old

RECEIVED: 9 April 1999; FINAL SUBMISSION RECEIVED: 6 June 2000;

ACCEPTED: 21 June 2000
339
340
infarct in the right parieto-occipital region and a 3 mm
lesion in the superior pons on the right. Intracranial
magnetic resonance angiography (MRA) revealed no
flow in the right carotid artery, stenosis of the left middle
cerebral artery, an absent right vertebral artery signal,
and stenosis in the left distal vertebral artery. She im-
proved fully in 5 days and was subsequently discharged
home.
CASE 2
A 64-year-old, right-handed woman with diabetes was
seen in the Emergency Department (ED) for mild head-
aches, lightheadedness, and a vague feeling of unsteadi-
ness. She was found to have a brachial blood pressure of
180/110 mm Hg, was given a prescription for meclizine
and felodipine, and was discharged from the ED at 10:30
a.m. At approximately 5:30 p.m., she took the first dose
of 10 mg of felodipine, and went to sleep. She awoke at
7:00 a.m. with slurred speech and profound left-sided
weakness, and was unable to walk. Re-evaluation in the
ED revealed a blood pressure of 152/88 mm Hg. Neu-
rologic examination revealed left-sided facial and ex-
tremity weakness, diminished perception of pain in the
left arm and leg, and mild dysphagia. A computed to-
mography (CT) scan demonstrated a 5-mm right para-
median pontine infarct. Duplex ultrasonography and
echocardiography were normal. Untreated systolic blood
pressure in the hospital, monitored every 4 to 8 h by a
brachial cuff and automated equipment, ranged from 173
to 193 mm Hg, and diastolic pressure ranged from 83 to
111 mm Hg. Her symptoms improved modestly before
discharge after 1 week.
CASE 3
A 58-year-old, right-handed man presented to the ED
after sudden generalized headache, dizziness, blurred
vision, dysarthria, right arm weakness, and gait diffi-
culty. All symptoms resolved eight hours before admis-
sion. He had had four similar episodes during the prior
week. Each episode resolved spontaneously within 30
min. His past medical history was significant for hyper-
tension, diabetes mellitus, and alcohol abuse. His blood
pressure by brachial cuff was 190/120 mm Hg. General
physical and neurologic examinations were normal. He
received 10 mg of nifedipine orally. His blood pressure
30 min later was 128/80 mm Hg. A previous check at 15
min was at an intermediate level. Examination at this
time revealed global aphasia, conjugate gaze deviation to
the left, a right homonymous hemianopsia, a supranu-
clear facial palsy on the right, moderate right-sided hemi-
G. M. Fischberg et al.
paresis and right-sided neglect. MRI revealed an infarct
involving the left occipital lobe, thalamus, and posterior
limb of the internal capsule. Duplex ultrasound showed
bilateral non-flow restrictive internal carotid artery ste-
noses, and normal antegrade vertebral flow bilaterally.
Electrocardiography showed a normal sinus rhythm with
occasional premature supraventricular complexes. Echo-
cardiography revealed mild left ventricular dysfunction
and hypertrophy. Routine laboratory investigations were
all within normal limits, with the exception of a positive
urine culture. After 7 days, he was transferred to a
nursing care facility with residual aphasia and right-sided
hemiparesis.
CASE 4
A 49-year-old, right-handed man was admitted 4 h after
an episode of right hemiparesis, right hemiparesthesias,
and dysarthria that had lasted for 20 min. His past med-
ical history was significant for hypertension, obesity, and
recent onset of headaches. On examination, his blood
pressure by brachial cuff was 174/114 mm Hg. Neuro-
logic examination was entirely normal. He was treated
with 10 mg of labetalol HCl intravenously (i.v.). His
blood pressure fell to 154/88 mm Hg after 5 min. Ten
minutes after receiving the drug, he developed right-
sided weakness. He had right facial weakness, marked
dysarthria, and a Babinski sign on the right. Laboratory
analyses showed serum cholesterol of 275 mg/dL and
serum glucose of 235 mg/dL. MRI revealed an infarct in
the left putamen and internal capsule. Carotid ultrasound
was normal. Seven days after hospitalization, the patient
had improved moderately and was discharged to a reha-
bilitation center.
CASE 5
A 60-year-old, right-handed man presented to the ED
with complaints of malaise. His blood pressure by bra-
chial cuff was found to be 170/100 mm Hg, but the
physical examination was otherwise normal. He was
given 10 mg of nifedipine sublingually, and his blood
pressure fell to 152/98 mm Hg when checked after 10
min. He was discharged. As he walked out of the hospital
he experienced weakness on the left side and unsteadi-
ness of his gait. After 3 h, he was brought to the hospital
for re-evaluation. His blood pressure was 120/88 mm
Hg. Neurologic examination revealed left-sided ataxia
and moderate left hemiparesis with a left Babinski sign.
MRI showed an infarct in the right side of the pons.
MRA of the intracranial vessels revealed irregularity of
the basilar artery suggestive of stenosis, but other vessels
Acute Stroke and Blood Pressure 341

Table 1. Patient Summaries

Patient Age Neurological Baseline Antihypertensive Post-treatment % MAP

No. (yrs) Presentation BP Drugs BP Change* Outcome

1 60 Nausea and vertigo 220/120 Nifedipine (sublingual) 168/86 26% stroke

Lightheadedness
2 63 and headache 180/110 Felodipine (oral) 160/80 18% stroke
3 58 Resolved TIA 190/120 Nifedipine (oral) 128/80 33% stroke
4 49 Resolved TIA 174/114 Labetalol (intravenous) 154/88 18% stroke
5 60 Asymptomatic 170/100 Nifedipine (sublingual) 120/88 20% stroke
6 30 Asymptomatic 280/120 Triamterene/HCTZ, 160/85 36% bilateral
Nifedipine, captopril, retinal
hydralazine (all oral) infarctions

*Mean MAP fall of 25 ⫾ 7.7%.

BP, blood pressure; MAP, mean artrial pressure; TIA, transient ischemic attack.

were normal. Two days later, he developed worsening of DISCUSSION

weakness on the left side, and he was given heparin i.v.
Periodic pressure monitoring by brachial cuff did not
demonstrate dramatic changes. The next day, however,
he complained of severe epigastric pain and was found to
have acute pancreatitis. He subsequently developed cir-
culatory failure and died.
CASE 6
A 30-year old woman presented to the ED with com-
plaints of abdominal pain. Her past medical history in-
cluded only severe systemic hypertension, and she had
run out of her medications 2 weeks prior. Her blood
pressure by brachial cuff and auscultation at the time was
280/120 mm Hg. Pharmacy records confirmed her latest
medication regimen. All her usual medications were then
reinitiated orally at the same time, as usually taken,
including triamterene/hydrochlorothiazide, nifedipine,
captopril and hydralazine. Two hours later, she had pro-
found visual loss. Her blood pressure was then checked
again, and was 160/85 mm Hg. Neurologic examination
revealed intact cognition. Vision was greatly impaired in
both eyes. She was unable to read, had generally im-
paired light perception, and was able to distinguish some
gross movements with each eye in different fields of
vision. Funduscopic examinations showed narrowed ar-
terioles, indistinct disc margins, and later, cotton wool
exudates. The remainder of the neurologic examination
was within normal limits. A non-contrast CT scan of the
brain did not reveal any lesions. Carotid and renal artery
ultrasound studies were within normal limits. Collagen-
vascular screens were negative. During her hospital
course, she had partial recovery of vision, beginning later
the same day, and no further neurologic symptoms. For-
mal ophthalmologic consultation confirmed bilateral ret-
inal ischemic insults.
We report the cases of two patients with transient isch-
emic attacks (TIAs), two patients with mild ischemic or
nonspecific symptoms, and two patients asymptomatic
for cerebrovascular disease; all had ischemic neurovas-
cular events precipitated or exacerbated after use of
antihypertensive medication (Table 1). Some patients in
similar situations as these may require and benefit from
some pressure reduction, and it cannot be stated with
certainty that hypertensive treatment precipitated these
observed events; however, the temporal nature of the
events is striking. It has been frequently noted that some
patients have deterioration of neurologic status in con-
junction with decrease in blood pressure. In fact, induc-
tion of hypertension in such patients can in selected cases
improve clinical outcome (3). Blood pressure was ele-
vated in all patients, and the fall in pressure after medi-
cation was generally moderate: 37 ⫾ 16 mm Hg in mean
arterial pressure (MAP) without hypotension. Previous
reports have highlighted the adverse effects of antihy-
pertensive treatment, including myocardial and cerebral
ischemia (4 – 6) (Table 2). In most of those reported, the
fall in mean arterial pressure was severe. Some individ-
uals within these series demonstrated more moderate
pressure reduction as presented herein. Some of those
patients had symptoms of hypotension and shock (5).
The patients presented here had generally more moderate
decreases in blood pressure, and were neither hypoten-
sive nor had global cerebral or systemic symptoms of
hypotension. This series also differs by including pa-
tients with resolved TIAs.
These randomly accrued cases emphasize the impor-
tance of cautious treatment of hypertension, particularly
for patients with evidence of cerebrovascular insuffi-
ciency and in those with an established history of hyper-
tension. Not all patients, even with ongoing ischemic
symptoms, have such a reaction to blood pressure treat-
342 G. M. Fischberg et al.

Table 2. Published Series of Acute Stroke in the Setting of Blood Pressure Treatment

Number Decline in MAP (mmHg)

Author (year) of Patients Mean (⫾SD) Initial Neurological Condition

1) Graham (1975)23 2 81 ⫾ 9 asymptomatic

2) Jackson et al. (1976)24 6 45 ⫾ 25 asymptomatic
3) Kumar et al. (1979)25 1 200 headache, dizziness
4) Ledingham et al. (1979)26 10 92 ⫾ 23 asymptomatic
5) Britton (1980)5 6 141 ⫾ 43 mild ischemic strokes
6) Nobile-Orasio et al. (1981)27 2 Unknown asymptomatic
7) Lavin (1986)6 2 75 ⫾ 35 mild ischemic strokes
8) Schwartz et al. (1990)28 2* 69 ⫾ 8 mild ischemic stroke
9) Present series (2000) 6 37 ⫾ 16 mild ischemic symptoms, TIA, asymptomatic

*Two events in the same patient separated by 9 months.

MAP, mean artial pressure;TIA, transient ischemic attack.

ment. The MRA for Case 1 revealed multifocal intracra-
nial large-vessel stenoses. Case 3 had repeated TIAs
suggesting underlying large-vessel disease. Tandem
small vessel compromise with an occluded right verte-
bral artery and left vertebral artery stenosis may have
contributed to the stroke in this case. Cases 2 and 4 were
consistent with primary small-vessel infarctions. Case 5
demonstrated evidence of mild-to-moderate atheroscle-
rotic disease in the basilar artery by an MRA with an
infarct territory suggesting occlusion of a small penetrat-
ing branch stemming from the diseased large vessel.
Case 6 involved bilateral retinal infarctions in a young
woman who had been on hypertensive treatment, and
was tolerating a normotensive status only 2 weeks prior.
Thus, infarction in this case likely involved the largely
reversible constrictive arterial changes that develop
within the first several weeks of sustained hypertension.
In normal subjects, cerebral autoregulation ensures a
constant cerebral blood flow within a wide range of
perfusion pressure, generally with a lower range of 50 to
60 mm Hg and an upper range of 150 to 160 mm Hg.
Cerebral blood flow is kept constant by arteriolar con-
striction during increases in blood pressure, and by reflex
vasodilatation with a reduction in blood pressure (7). In
hypertensive individuals, the lower limit of autoregula-
tion is often elevated, and has been demonstrated to be as
high as 130 mm Hg (8,9). Irreversible structural changes
with chronic hypertension include smooth muscle hyper-
plasia and medial necrosis, followed by endothelial ad-
herence of monocytes and penetration by plasma com-
ponents (10,11). Reversible changes, which develop
within weeks of induced hypertension in experimental
models, include sodium and water retention in the vessel
walls, as well as muscular hypertrophy. Reversion of
fluid retention and muscular hypertrophy in these vessels
with gradual blood pressure reduction should allow a
complete return to normotensive status without adverse
events.
Patients with cerebrovascular disease have impaired
autoregulation of cerebral blood flow, and are at an
increased risk of cerebral ischemia even with a slight fall
in blood pressure (12). Meyer et al. found that dysauto-
regulation of cerebral blood flow following stroke is
more marked in hypertensive patients than in normoten-
sive individuals (13). Hypoxia, hypercarbia, and low pH
may all contribute to induced vasodilatation in ischemic
regions. Vasodilatory compensation may be limited by
proximal vessel obstruction. Experimental primate stud-
ies of middle cerebral artery ischemia have demonstrated
profound alterations in cerebral blood flow with changes
in mean arterial pressure (14). Autoregulatory alterations
often extend beyond presumed ischemic regions (15).
Single positron emission computed tomography studies
have demonstrated that worsening or failure of recovery
of perfusion in stroke patients may be adversely affected
by minor MAP changes (16). Two patients (Cases 1 and
2) in this series had symptoms suggesting ongoing cere-
bral ischemia at the time of treatment, which may have
been subject to such autoregulatory limitations.
Two patients (Cases 3 and 4) had TIAs with no
symptoms at the initiation of anti-hypertensive treatment.
Such patients may demonstrate impaired autoregulation
and abnormal cerebral vasomotor reactivity both during
and after a transient ischemic attack, but will likely revert
to normal within a few days (15–18). Cerebral blood
flow in the interim remains particularly vulnerable to
rapid changes in blood pressure. Also, despite TIA
symptoms dissipating within 24 h, brain imaging may
show a permanent defect in 28 to 30% of patients,
demonstrating that persisting ischemia and infarction
may occur despite symptom resolution (19,20).
Even for patients without known cerebrovascular dis-
ease, as in Cases 5 and 6, rapid reduction of blood
pressure may have adverse effects. In normotensive and
hypertensive individuals, a drop in mean arterial pressure
of approximately 25% can result in reduced cerebral
Acute Stroke and Blood Pressure
blood flow (9). With long-standing hypertension, this
may begin at MAPs as high as 130 mm Hg. High
autoregulatory limits may not correct with long-term
hypertension treatment (9). Hence, those already on
medication may have baseline pressures closer to their
lowest tolerated limits, and may at times be subject to
altered perfusion with more modest pressure changes.
Patient 6 likely represented a case of reversible changes
in the retinal arterial walls as described above. More
gradual reinstitution of her medications, instead of re-
ceiving them all simultaneously, might have resulted in
no complications.
Without underlying vasculopathy, initial perfusion
reduction usually would not be expected to cause
symptoms. Ischemia caused solely by more profound
hypotension or global hypoperfusion is often antici-
pated in borderzone regions, which may involve cor-
tical or subcortical internal borderzone areas (21).
Borderzone infarctions result from ischemia in regions
subserved by terminal branches of separate larger vas-
cular territories. Ischemia is seen at the junction be-
tween two major vascular territories. Borderzone in-
farction did not occur in the cases presented here. In
previously asymptomatic patients, including Case 5
with a pontine lacune and the majority in Table 2,
most of the precipitated infarcts were not of this
pattern. Small vessel lacunes and larger arterial terri-
tory infarcts in these cases emphasize that underlying
asymptomatic small vessel disease or large vessel
stenoses further reduce the threshold for focal perfu-
sion deficits. The result is that previously asymptom-
atic patients may present with ischemic deficits at or
before the first 25% drop in pressure, which may occur
even at hypertensive levels.
In 1997, the National Institute of Neurologic Disor-
ders and Stroke (NINDS) formulated consensus guide-
lines for initial blood pressure treatment in acute strokes
(29). Treatment of systolic blood pressures of 185 to 220
mm Hg or diastolic pressures of 105 to 120 mm Hg is
deferred, in the absence of other clear needs for imme-
diately lowered pressure. Spontaneous falls of 30 mm Hg
systolic and 10 mm Hg diastolic pressure have been
described within the first 90 min of evaluation of acute
stroke patients (22). Trends should be checked with
readings 10 to 20 min apart before initiating therapy. For
those who have received thrombolytics, pressure is gen-
erally checked every 15 min for the first 2 h, then every
30 min for the next 6 h, and every 2 h for the remainder
of a 24-h period, to ensure that hypertension does not
increase hemorrhagic risk.
In hypertensive crises, manifestations are not solely a
function of the degree of pressure elevation, but also the
rapidity of change and the baseline pressure for an indi-
vidual. Accelerated hypertension often includes retino-
343
pathic findings, including hemorrhages, and segmental
arterial narrowing. Malignant hypertension includes pap-
illedema as a rule. Other symptoms may include malaise,
headache, and renal dysfunction. Diastolic pressure is
often 120 mm Hg or greater. Hypertensive urgencies
involve elevated blood pressure without evidence of end
organ damage. Common hypertensive urgencies requiring
address include malignant hypertension, severe hyperten-
sion perioperatively, and hypertension with intractable
nosebleeding, with sympathomimetic drug overdoses, in
renal transplant patients, in those with coronary artery
disease, and in association with burns. These patients
usually can be managed with reduction of blood pressure
over many hours, or even over days, and often may be
treated with oral agents.
Hypertensive emergencies display signs of end organ
damage, including encephalopathy, acute left ventricular
failure, myocardial infarction, acute aortic dissection,
eclampsia, acute or worsening renal failure, acute sub-
arachnoid hemorrhage, and microangiopathic hemo-
lytic anemia. Such patients should have pressure low-
ered within a few hours at most when identified.
Parenteral medications that afford close control and
reliable responses are recommended. Pressure should
be checked by the time of expected effect, and re-
checking for a continued downward trend before the
time of possible maximal effect, or steady state,
should be performed before deciding to continue or
change the current dosing regimen. For nitroglycerin,
onset of action may be 2 to 5 min, with a steady state
at 30 min. For parenteral hydralazine, effect may be
seen initially in 10 to 30 min, but it may increase up to
80 min. For oral hydralazine, peaks may be seen at 1
to 2 h. Tailored monitoring is important, particularly
in those with possibly compromised vascular beds. In
stroke patients, worsening neurologic function below a
particular blood pressure threshold should be sought
for possible tapering of medication, or even pressure
augmentation.
Certain situations may lend themselves toward or
away from particular medications. In patients with cog-
nitive dysfunction, central-acting clonidine, or methyl-
dopa may cloud the neurologic examination and should
be avoided. If clonidine is stopped abruptly, it may cause
a marked withdrawal syndrome of increased pressure,
nausea, sweating, nervousness, and headache. With aor-
tic dissection, medications that may cause tachycardia,
such as hydralazine, diazoxide, and the calcium channel
blockers nifedipine and nicardipine should be avoided.
They may create a more hyperdynamic state that can
aggravate dissection. Trimethaphan, a ganglion blocking
agent, is advisable due to a negative inotropic effect and
a blunted pulsatility. Prolonged use of this drug may
result in tachyphylaxis because of intravascular volume
344
expansion, which may be abated by diuretics. Labetalol
or esmolol are also options. Preload and afterload reduc-
tion with nitroprusside or angiotensin-converting en-
zyme (ACE) inhibitors may be of benefit. Nitroprusside
is particularly useful to reduce pulmonary edema, as is
nicardipine. Nitroglycerine is also appropriate with car-
diac ischemia. Phentolamine, an alpha blocking agent, or
labetalol, with alpha and ␤-blocking effects, would be a
situation-specific approach to a catacholamine crisis. A
beta blocker used alone in this case can aggravate pe-
ripheral vascular constriction due to an unopposed alpha
effect. Beta blockers can exacerbate congestive heart
failure, asthma, or chronic bronchitis; however, esmolol
is fairly ␤-1 specific with little bronchial effect. Raised
intracranial pressure may be worsened by indiscriminate
vasodilatating agents, including nitroprusside, nicardi-
pine, and nifedipine, which may increase cerebral blood
volume. They also may steal blood from marginally
perfused regions in cerebral ischemia by shunting to
normal regions with a greater vasodilatatory reserve.
Labetalol and ACE inhibitors do not have an adverse
effect on cerebral blood flow or volume. In patients with
renal artery stenosis, ACE inhibitors can be detrimental
to kidney function. Enalapril may work well acutely, but
substantial response may not occur in a third of patients,
more so in the black population, and escalating doses do
not reliably produce an escalating response. In eclamptic
and pre-eclamptic patients, hydralazine has been used
commonly; this medication does not have an adverse
effect on uteroplacental blood flow (30). Labetalol also
has been used successfully in pregnancy (31). Diazoxide
may create a more precipitous fall in blood pressure, may
produce fetal hyperglycemia, and may interfere with
labor by causing uterine muscle relaxation. Nitroprusside
has demonstrated evidence of fetal cyanide toxicity in
animals (32).
The use of calcium channel blockers, particularly
nifedipine, has been widespread in the past 20 years. Its
use sublingually does not hasten absorption, but swal-
lowing a bitten or broken capsule can accelerate efficacy,
which generally begins within 5 to 10 min. Peak effects
are seen generally in 30 – 60 min, and the duration is
approximately 6 h. Nifedipine has gained substantial
attention for adverse events associated with its institu-
tion, including unexpected hypotension, angina, isch-
emic electrocardiographic (EKG) changes, pulmonary
edema, renal failure, and ischemic cerebral events
(33,34). Underlying use of other antihypertensive
agents and volume depletetion may facilitate unex-
pected hypotension. A review of 63 patients receiving
oral nifedipine for hypertensive crises revealed aver-
age drops in MAP of 25.1% (35–38). Forty-one of
those received 10 mg, and 22 received 20 mg. One
study in a black population demonstrated an average
G. M. Fischberg et al.
drop of 36% with only 10 mg (38). In a series of
moderately hypertensive elderly patients (mean age 73
years), only 5 mg of sublingual nifedipine reduced
MAP by 35% (39). This reflects substantially greater
concentrations in older patients. In this group, 11% of
the 55 patients with left ventricular hypertrophy, and
one of 38 patients without, showed ischemic EKG
changes. This is in conjunction with an increase in
heart rate, which is commonly seen. Reflex tachycar-
dia may occur. Nifedipine has a relatively greater
negative inotropic effect than other possible calcium
channel blockers. With peripheral vasodilatation, this
may lead to circulatory collapse in patients with prom-
inent aortic valve stenosis. Oral captopril, labetalol,
and clonidine may work equally well acutely; how-
ever, these also require caution, as already discussed,
in particular populations.
Extended-release nifedipine provides a more gradual
reduction. Patients should be observed for complications
until the 6-h plasma peak. Bioavailability is approxi-
mately 86% that of the immediate-release form, with
reduced peak effect. In one of the previously cited series,
20 mg produced nearly the same reduction of approxi-
mately 30% as 10 mg of the immediate-release prepara-
tion, with a peak effect at a mean of 283 min versus 100
min, respectively (38).
Other commonly used calcium channel blockers are
nicardipine and verapamil. Nicardipine offers a rapid
5 to 15 min onset of action, and lasts only 30 to 40
min, allowing fairly well-controlled titration. Short
duration makes it useful for often transient postoper-
ative hypertension. Recommended infusion rates are
usually from 5 to 15 mg/hr. As with nifedipine, the
degree of pressure reduction is somewhat proportional
to the baseline level. Reflex tachycardia may also
occur. The increase in heart rate and decrease in
peripheral vascular resistance are not accompanied by
a significant negative inotropic effect; cardiac output
tends to be increased. This profile of action may be
beneficial in those with congestive heart failure. Cor-
onary vessels tend to dilatate more than peripheral
arteries, but increased heart rate may still lead to
ischemia on occasion.
Intravenous verapamil is less likely to cause a large,
precipitous drop in pressure than nifedipine or nicardi-
pine. A general guideline for use is a 5 to 10 mg IV bolus
followed by an infusion of 3 to 25 mg/hr. Onset of action
is generally from 1 to 5 min, with a duration of 30 to 60
min. Particular concerns include sinus or atrioventricular
nodal depression. This may be most detrimental to those
with any degree of underlying heart block. The PR
interval may be prolonged in up to 30% of those treated
at doses necessary for hypertensive crises (40). Calcium
channel blockers, but verapamil to a greater degree than
Acute Stroke and Blood Pressure
the others noted, may increase digoxin levels, by even
greater than 50% (41). Conduction abnormalities with a
negative inotropic effect can exacerbate pulmonary or
peripheral vascular congestion.
When dealing with hypertensive crises, and particu-
larly in the setting of acute or known underlying
cerebrovascular disorders, several precautions are nec-
essary. If long-acting medications are used, unexpect-
edly large and potentially damaging declines in pres-
sure may result with difficult timely reversal. Initial
pressure may be misleading; repeated readings to
screen for a downward trend are desirable before
initiating treatment. The minimal initial blood pres-
sure control required should be undertaken to ensure
tolerance in patients with TIAs and ongoing evidence
of cerebral ischemia. Hypertension treatment, and re-
institution of therapy, should be commenced cau-
tiously and gradually to avoid precipitating ischemic
neurologic deficits in hypertensive patients with or
without a history of cerebrovascular symptoms.
Acknowledgments—This work was supported by NIH Grant NS
31945.
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