Treatment of Acute Hypertension in Neuroemergencies

Treatment of Acute Hypertension in Neuroemergencies


>>DR. SUNG: Hello. My name is Gene Sung. I’m the director of Neurocritical Care and
Stroke at the University of Southern California. Today we’ll be talking about the treatment
of acute hypertension in neuro emergencies. As we all know the new mantra is ‘Time is
Brain, especially in acute ischemic stroke. So the longer you have ischemia, the more
neuronal damage there is. Per minute almost two million neurons are
lost, which leads to almost three weeks of increased aging. In an hour about 120 million neurons are lost,
over three and a half years of accelerated aging. And in a typical stroke about 1.2 billion
neurons are lost, which leads to maybe 36 years of accelerated aging. Blood pressure management is a key component
for patients being considered for tPA therapy. Door-to-tPA treatment in less than 60 minutes
is the standard of care. Gently bring blood pressure to less than 185
over 110 mmHg to qualify for tPA therapy. Maintain blood pressure at less than or equal
to 180 over 105 mmHg after tPA is administered. Controlled blood pressure lowering during
acute stroke can best be achieved with intravenous antihypertensive therapies. A single optimal medication to lower the blood
pressure in all patients with acute stroke has not been determined and an individualized
approach is best. Treating emergent elevated blood pressure
is a major consideration for improved rapid triage and management of patients. As many as 10% of otherwise eligible patients
do not receive tPA because of acute hypertension. Acute treatment of hypertension has not been
shown to improve stroke outcomes. The Stroke Expert Panel emphasized the importance
of timely management of emergent blood pressure prior to tPA administration. For stroke centered guidelines the joint commission
is recommending that the door-to-MD time should be less than 10 minutes. The door-to-neurological expertise should
be less than 15 minutes. The door-to-CT scan should be less than 25
minutes. The door-to-CT interpretation should be less
than 45 minutes. And the door-to-drug or delivery of tPA should
be less than 60 minutes. Large retrospective studies in the AIS focus
on minimizing blood pressure variability. Blood pressure variability was associated
with hemorrhagic transformation after acute ischemic stroke independent of thrombolysis. And the systolic blood pressure variability
was associated with symptomatic intracerebral hemorrhage and death in thrombolysis treated
acute ischemic stroke patients. Blood pressure variability in the subacute
phase of ischemic stroke was associated with poor three-month outcomes. IV treatment of acute hypertension is a vital
consideration in neuro emergencies. In acute ischemic stroke management of hypertension
is key in the timing of thrombolysis therapy. In acute intracerebral hemorrhage high systolic
blood pressure is associated with hematoma expansion. And in aneurysmal subarachnoid hemorrhage
rebleeding may be associated with systolic blood pressure greater than 160 mmHg. As we know, the body is actually pretty good
at taking care of itself. And in this is certainly the case in cerebral
autoregulation. So with very low blood pressures we can have
ischemia in the brain. For very high blood pressures you can hypertensive
encephalopathy. But the brain, through cerebral autoregulation,
control cerebral blood flow over a fairly large range of mean arterial pressure, as
you can see in the red line for the normotensive patients in a normal patient. This curve is altered for patients with chronic
hypertension, as you can–see in the blue line, but still a fairly regulated autoregulation
and delivery of cerebral blood flow. In the case of ischemia this autoregulation
is lost, and cerebral blood flow becomes linearly dependent on mean arterial pressure. In the case of hemorrhage the cerebral autoregulation
is lost, and the cerebral blood flow changes linearly with mean arterial pressure. So control of blood pressure is critical for
these patients. The indications for ready-to-use Cardene I.V.
or nicardipine hydrochloride. Cardene I.V. is a premixed injection is indicated
for the short-term treatment of hypertension when oral therapy is not feasible or not desirable. For a prolonged control of blood pressure
transfer patients to oral medication as soon as their clinical condition permits. Cardene I.V. or nicardipine is contraindicated
in patients with advanced aortic stenosis. Hypotension and reflex tachycardia may potentially
occur during treatment with Cardene. Therefore close monitoring of blood pressure
and heart rate is required. If unacceptable hypotension or tachycardia
occurs the infusion should be discontinued. Slow titration of Cardene is recommended in
patients with heart failure or significant left ventricular dysfunction, particularly
in combination with a beta-blocker. Close monitoring of a response to Cardene
I.V. is advised in patients with angina, heart failure, impaired hepatic function, or renal
impairment. To reduce a possibility of venous thrombosis,
phlebitis, local irritation, and extravasation, administer Cardene I.V. through large peripheral
veins or central veins rather than arteries or small peripheral veins. If Cardene I.V. is administered in a peripheral
vein, to minimize the risk of venous irritation change the site of infusion every twelve hours. The most common adverse reactions are headache,
nausea or vomiting, hypotension, and tachycardia. Key considerations for choosing an antihypertensive
agent in acute stroke. Perhaps one of the most desired characteristics
of any agent is rapid onset of action. So in the case of acute ischemic stroke, uh,
where considering reperfusion therapies and some blood pressure goals must be managed
quickly to consider reperfusion therapies. As we just said, time is brain. The longer you’re having ischemia and not
able to deliver reperfusion therapies more permanent injury is occurring. In the cases of intracerebral hemorrhage and
aneurysmal subarachnoid hemorrhage we’re concerned about rebleeding, the longer you have high
blood pressure the longer and greater the chance of having rebleeding from either the
initial intracerebral hemorrhage or from the aneurysm rupture. So rapid onset of action is critical. Rapid offset of action is also desirable. If the blood pressure falls too rapidly then
we want to stop the continued hypotension. Cardene I.V. has a 50% offset of action in
about 30 minutes. And plasma concentrations decline triexponentially
with a rapid early distribution phase. Minimal preparation required is also desirable. This goes along with the rapid onset of action,
having something available, uh, on hand that can be safely administered. Cardene I.V. is premixed and ready to use. Predictable dose response requiring few dose
adjustments. So knowing what you’re going to be getting
with different agents is critical. This formulation of Cardene I.V. allows for
rapid or gradual titration and effect on blood pressure significantly correlated with plasma
concentrations. No invasive blood pressure monitoring required
is desired because this also helps with rapid onset of action. If you don’t have to place different invasive
monitors and wait for calibration for accurate blood pressure readings you can start your
medications early and quicker. For Cardene I.V. close monitoring of blood
pressure and heart rate by means appropriate to the clinical setting does not require necessarily
invasive blood pressure monitoring. Cardene I.V. is not indicated for the treatment
or prevention of acute ischemic stroke in intracerebral hemorrhage or acute subarachnoid
hemorrhage. Safety and administration. A slow titration of Cardene I.V. is recommended
in patients with heart failure or significant left ventricular dysfunction, particularly
in combination with a beta-blocker. So as we know, blood pressure is comprised
of the cardiac output times the systemic vascular resistance. And cardiac output is comprised of the stroke
volume times a heart rate. Different antihypertensive drugs have different
mechanisms of action at different components, uh, of this equation. Nicardipine is a selective calcium channel
blocker, which works specifically at the systemic vascular resistance. The ready-to-use benefits. So this is the only available FDA-approved
premixed formulation of nicardipine hydrochloride. Immediately available for rapid intervention. Guaranteed stability for 24 months under appropriate
storage conditions. Admixed generic nicardipine hydrochloride
I.V. is stable for only 24 hours under appropriate storage conditions. Minimizes medication admixture errors. Can be stored at point of care. The Joint Commission, American Society of
Health-System Pharmacists, and the Institute for Safe Medication Practices recommend the
use of ready-to-use medications. Ready-to-use bags save time and labor. And again, remember, Cardene I.V. is contraindicated
in patients with advanced aortic stenosis. Blood pressure reduction in acute ischemic
stroke, intracerebral hemorrhage and subarachnoid hemorrhage in the emergency department. In a prospective pseudo-randomized study of
patients who presented in the ED with primary acute ischemic stroke, intracerebral hemorrhage
or subarachnoid hemorrhage receiving Cardene I.V. for 24 hours Cardene was administered
at 5 mg/hr and increased every 15 minutes by 2.5 mg/hr until the target systolic blood
pressure was reached or a maximum of 15 mg/hr was achieved. Blood pressure goals were defined using current
consensus recommendations. Vital signs, blood pressure, and heart rate
were taken every 15 minutes until goal blood pressure was achieved. As you can see, the ready-to-use nicardipine
delivered a smooth, predictable blood pressure control. So, again, of the 26 patients treated the
average initial systolic blood pressure was 215 mmHg. 89% of patients achieved their respective
systolic blood pressure goals within 60 minutes. Less than one dose adjustment was needed to
reach blood pressure goal. There was one incidence of hypotension. No rescue therapy was required. So the gradual titration of Cardene was used. Cardene, again, is not indicated for treatment
or prevention of acute ischemic stroke, intracerebral hemorrhage, or aneurysmal subarachnoid hemorrhage. There are guidelines from the American Heart
Association and American Stroke Association for the management of aneurysmal subarachnoid
hemorrhage, which indicate again that blood pressure should be controlled with a titratable
agent to balance a risk of stroke, hypertension related rebleeding, and the maintenance of
cerebral perfusion pressure. And in their guideline nicardipine may give
smoother blood pressure control than labetalol and sodium nitroprusside, although data showing
different clinical outcomes are lacking. The magnitude of blood pressure control to
reduce the risk of rebleeding has not been established. But a decrease in systolic blood pressure
to less than 160 mmHg is reasonable. Patients otherwise eligible for acute reperfusion
therapy, uh, except that blood pressure is greater than 185 over 110 mmHg consider labetalol
pushes of 10 to 20 mg I.V. over one to two minutes which you can repeat once, or nicardipine
5 mg/hr I.V. titrate up to 2.5 mg every 5 to 15 minutes, maximum dose of 15 mg/hr when
desired blood pressure is reached. Adjust to maintain the proper blood pressure
limits. So in acute ischemic stroke patients who are
not potential candidates for acute reperfusion therapy consideration should be given to lowering
blood pressure if systolic blood pressure is greater than 220 mmHg or diastolic blood
pressure is greater than 120 mmHg, or as indicated for other concomitant medical conditions that
would benefit from blood pressure reduction such as myocardial ischemia, aortic dissection,
or heart failure. I was a part of the ATACH trial. This was the Antihypertensive Treatment of
Acute Cerebral Hemorrhage trial in the ED. This was an open-label, dose-escalation, multicenter,
prospective study of patients with intracerebral hemorrhage with elevated systolic blood pressure
greater than or equal to 170 mmHg, presenting to the ED within six hours of symptom onset. Controlling blood pressure in these patients
was so controversial that the methodology of this study had to be done in different
tiers. So patients are enrolled in three tiers of
systolic blood pressure treatment goals. The first tier was lowering the blood pressure
to 170 to 200 mmHg. If there were no safety concerns then tier
two was initiated for a different set of patients to lower the blood pressure to 140 mmHg to
170 mmHg. After evaluation and if there were no safety
concerns in these patient the next tier was initiated for the next group of patients,
which was to lower blood pressure to 110 to 140 mmHg. Cardene I.V. was initiated at 5 mg/hr, then
increased by 2.5 mg/hr every 15 minutes as needed, up to a maximum of 15 mg/hr. As we can see there were 60 patients treated
in three systolic blood pressure target-range tiers. The median initial systolic blood pressure
was 212 mmHg. 90% of patients achieved their respective
systolic blood pressure goals within all tiers. And what we found was that blood pressure
control was quick and maintained well for the next 24 hours after the trial was initiated. What the guidelines state, the American Heart
Association and American Stroke Association guidelines for the management of spontaneous
intracerebral hemorrhage. And in their statement they mention the INTERACT
study, which was the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage, which
provided an important proof of concept for early blood pressure lowering in patients
with intracerebral hemorrhage. But the data are insufficient to recommend
a definitive policy. And they also refer to the ATACH trial which
confirms the feasibility and safety of the early rapid blood pressure lowering in an
intracerebral hemorrhage. This study used a four-tiered, dose escalation
of intravenous nicardipine-based blood pressure lowering in 80 patients with intracerebral
hemorrhage. Hypotension and reflex tachycardia may potentially
occur during treatment with Cardene I.V. Therefore close monitoring of blood pressure
and heart rate is required. If unacceptable hypotension or tachycardia
occurs the infusion should be discontinued. Case study: reduction of blood pressure in
acute ischemic stroke. The patient history and presentation. 78-year-old female with difficulty speaking,
complaining of weakness on the right side, brought to the emergency department by a family
approximately four hours after onset of symptoms. History of hypertension and type two diabetes. Medications: metoprolol and metformin. Clinical findings. The physical exam: blood pressure is 205 over
115 with a mean arterial pressure of 145. Heart rate is 88. Respiratory rate is 18. She’s afebrile. Her neurological examination: her speech is
slurred and difficult to understand. She is awake and alert. Her pupils are equal, round, and reactive
to light and accommodation. Right hemiparesis. Her NIH stroke scale is 12. Diagnostic and lab results: hemoglobin is
8.1; potassium is 4.6; glucose is slightly elevated at 150, BUN of 22; CPK is 85. Troponins are not elevated. The clinical findings, the echocardiogram
showed a sever LVH with mild enlargement of the left atrium, a grade four diastolic dysfunction,
and normal sinus rhythm, no left atrial thrombus, no PFO, chest x-ray was normal. The imaging showed the evidence of a prior
stroke but no intracerebral hemorrhage. And the cerebral angiogram revealed occlusions
involving two distal branches of the superior and inferior divisions of left MCA. So this is a little bit unusual in having
two separate occlusion, uh, in distal branches of the MCA. It could be that a larger thrombus approximately
broke up to cause this, or perhaps there was a cardioembolic phenomenon. The diagnosis: an acute ischemic stroke and
hypertensive emergency. How would you treat this patient? So the treatment plan. So there should be consideration of some kind
of reperfusion therapy. To achieve that you need to lower the systolic
blood pressure to less than 185 and the diastolic blood pressure to less than 110 consistent
with AHA/ASA guidelines to reduce the risk of intracerebral hemorrhage. In this circumstance intra-arterial thrombolysis
was initiated via microcatheter placed in the right MCA. The AHA/ASI guidelines recommendations regarding
intra-arterial fibrinolysis are this may be beneficial for treatment of carefully selected
patients with major ischemic strokes of less than six hours duration caused by occlusions
of the MCA who are not otherwise candidates for I.V. tPA. The optimal dose of intra-arterial rtPA is
not well established. And tPA does not have FDA approval for intra-arterial
use. Cardene I.V. was administered by infusion
and initiated at a dose of 5 mg/hr to reduce blood pressure due to the risk of intracerebral
hemorrhage. Cardene was titrated in increments of 2.5
mg/hr to a maximum of 15 mg/hr to achieve systolic blood pressure less than 185 and
diastolic blood pressure less than 110 to enable thrombolysis according to AHA/ASA guidelines. Blood pressure was maintained less than 185
over 110 through 15 hours after initiation. Metoprolol was held. Sliding scale for insulin was used. I.V. eptifibatide was administered following
the procedure. At my institution we may have treated the
patient a little bit differently. Uh, we still might have considered intravenous
tPA, uh, though this would be a high-risk situation. Uh, or other mechanical embolectomy is a possibility
as well. Following thrombolysis and acute hypertension
treatment CT scan at 24 hours reveals a small infarction without any intracerebral hemorrhage. And, as you can see, the small infarction
is on the right-hand CT scan with the two small arrows. So the efficacy of blood pressure lowering
with Cardene, uh, lowered patient’s blood pressure from 205 over 115 to target of less
than 185 over 110. And maintained smooth blood pressure control
without significant adverse events. And you can see on the graph that the blood
pressure was maintained within range for at least the 15 hours that it was monitored. Case study in the reduction of blood pressure
in an acute intracerebral hemorrhage. The patient history and presentation: a 48-year-old
male found unresponsive at home by family, brought to a hospital by ambulance. Family members relate a history of hypertension,
renal impairment, hypercholesterolemia, and ischemic heart disease with heart failure. His prescription bottles brought with him
contain lisinopril, clonidine, atorvastatin, and bumetanide. Clinical findings. The physical examination: blood pressure is
240 over 160 mmHg with a MAP of 187 mmHg. Heart rate is 140. Respiratory rate is 24, and he’s afebrile. His neurological examination: his pupils are
equal round and reactive to light and accommodation. He’s unarousable, neck is supple. His withdrawal to painful stimuli shows decreased
movement in the right arm and leg. Diagnostic and laboratory results: cardiac
auscultation, prominent S2 is heard, no aortic murmur, S3 easily heard. His electrocardiogram shows a sinus tachycardia,
a left bundle branch block, a LV strain pattern in lateral chest leads. Chest x-ray shows cardiomegaly with pulmonary
edema. Echocardiogram: no valvular disease, left
ventricular ejection fraction is 30%. Serum chemistry: potassium is 5.1, creatinine
is 2.1, troponins are within normal limits, BNP is elevated. The head CT shows a large intracerebral hemorrhage
in the left temporal lobe. Diagnosis. So this acute intracerebral hemorrhage in
the left temporal lobe. It is also a hypertensive emergency because
of the elevated blood pressure and neurological findings. Exacerbation of cardiac failure and renal
impairment. So how would you treat this patient? The patient seemed to be in respiratory distress,
so elective intubation to control the airway was first order of business. As well as initiating treatment with Cardene
I.V., premixed injection of 5 mg/hr with upward titration of 2.5 mg/hr as needed to achieve
a MAP of 130 to potentially lower the risk of rebleeding. Neurosurgical consultation for potential evacuation
of hematoma and/or insertion of a ICP monitor. Cardene I.V. was administered by infusion
and dose titrated to achieve systolic blood pressure of 160 mmHg with frequent monitoring
of heart rate. The patient was prepped for ventriculostomy,
which is performed within four hours of hospital administration, and the increased ICP was
treated with hyperventilation, although that’s only a temporizing measure for short term. And after 21 hours of therapy with Cardene
I.V. oral antihypertensive medications were begun via NG tube, and Cardene I.V. dose was
titrated downward and discontinued at hour 48. Ventriculostomy was removed on day three of
hospitalization. On day ten the patient was transferred to
an acute care rehab facility with continuation of all oral medications. The efficacy of blood pressure lowering with
Cardene. It reduced the admission systolic blood pressure
of 240 mmHg to 160 mmHg within two and a half hours of infusion initiation, allowing placement
of the ventriculostomy because the elevated blood pressure could potentially lead to a
increased risk of hemorrhage with that procedure. Successfully controlled blood pressure for
21 hours. Then as oral antihypertensives were initiated
Cardene was gradually down titrated and discontinued at 48 hours with no significant adverse events
reported. Slow titration of Cardene is recommended in
patients with heart failure or significant left ventricular dysfunction, particularly
in combination with a beta-blocker. Case study: Reduction of blood pressure in
subarachnoid hemorrhage. The patient history and presentation: a 47-year-old
male with a history of poorly controlled hypertension brought to hospital by ambulance. Family members say he’s said, I have the worst
headache of my life, and then he vomited. He became increasingly sleepy and unresponsive. They called 911. The family states the patient is a smoker
and is noncompliant with his blood pressure medications lisinopril and torsemide. The clinical findings, the physical examination:
blood pressure is elevated at 205 over 115 with a MAP of 145. The heart rate is 78, respiratory rate twelve,
afebrile. The neurological examination: pupils are equally
round and reactive to light, confused, unable to follow commands, no definitive evidence
of focal neurologic deficits, nuchal rigidity is present. The diagnostic and laboratory results: there’s
a cardiac auscultation, a prominent S2 but no aortic murmur. Serum chemistry and hematology unremarkable. EKG shows a sinus rhythm and LVH by voltage. Head CT reveals subarachnoid hemorrhage present
in midline with hydrocephalus. Cerebral angiogram shows a large ruptured
aneurysm of the left ACA and an unruptured aneurysm of the left MCA. Subarachnoid hemorrhage secondary to ruptured
left ACA aneurysm. It’s a Hunt and Hess grade three. Incidental unruptured aneurysm at the left
MCA. This is a hypertensive emergency. How would you treat this patient? Treatment plan. Elective intubation to control airway. Even though the patient is not currently in
respiratory distress because of future treatments a mechanical ventilation is probably going
to be needed. Uh, initiate treatment with Cardene I.V. premixed
injection at 5 mg/hr with upward titration at 2.5 mg/hr as needed to lower the MAP to
less than 90 mmHg. Although, uh, at my institution and others,
uh, some will follow the systolic blood pressure, uh, most importantly to lower the chances
of a rerupture. Perform endovascular coiling of the ACA aneurysm
to prevent rebleeding, and continue the use of Cardene I.V. during surgery and post-operative
period. Insert a ICP monitor and treat hydrocephalus
with ventriculostomy. In some institutions, perhaps, depending on
the amount of hydrocephalus seen, uh, this will be done even before the aneurysm is coiled. Safety information. So hypotension and reflex tachycardia may
potentially occur during treatment with Cardene I.V. Therefore close monitoring of blood pressure
and heart rate is required. If unacceptable hypotension of tachycardia
occurs the infusion should be discontinued. The hospital course. Nicardipine was administered by infusion over
the next nine days to control the mean arterial pressure with a target of less than 100 mmHg. The patient was extubated on day three postoperatively
when neurological findings improved. Oral antihypertensive treatment was begun
on day five, and dosage of Cardene was discontinued on day ten. Ventriculostomy was removed on day seven after
ICP returned normal. And coiling of the unruptured left MCA aneurysm
was scheduled. Cardene is contraindicated in patients with
advanced aortic stenosis. The most common adverse reactions are headache,
nausea and vomiting, hypotension, tachycardia. The results, again the efficacy of blood pressure
lowering with Cardene I.V. It successfully reduced patient’s mean arterial
pressure from 145 to less than 90 to allow coiling of the ruptured ACA aneurysm and with
appropriate titration maintained smooth predictable mean arterial pressure control for nine days
postoperatively. The dosage and administration. For rapid titration initiate at 5 mg/hr. And if necessary you may increase by 2.5 mg/hr
to a maximum dose of 15 mg/hr. Titrate every five minutes –adjust infusion
rate as needed to maintain the desired response. For a gradual titration initiate the 5 mg/hr,
and if necessary you may increase by 2.5 mg/hr to a maximum dose of 15 mg/hr. Titrate every 15 minutes and adjust infusion
rate as needed to maintain the desired response. Hypotension and reflex tachycardia may potentially
occur during treatment with Cardene I.V., nicardipine hydrochloride, therefore close
monitoring of blood pressure and heart rate is required. If unacceptable hypotension or tachycardia
occurs the infusion should be discontinued. So ready-to-use Cardene I.V., nicardipine
hydrochloride, dosage and administration. The dosage and administration of Cardene I.V.,
nicardipine hydrochloride. So there are two different concentrations
of premixed bags. One is 40 mg and 200 cc, and the other is
20 mg, 200 cc. To treat the appropriate dose you have a different
infusion rates for the different concentrations as seen in the charts. Summary. The timely and tight control hypertension
is critical in neuro emergencies. Proven study rapid precise blood pressure
control, onset of effect within minutes. IV dosing delivers predictable steady results,
increases cardiac output. Coronary steal has not been observed. Not associated with bradycardia or rebound
hypertension. Premixed and ready means that this is immediately
available for rapid intervention, minimizes the medication admixture errors, and the Joint
Commission, American Society of Health-System Pharmacists, and the Institute for Safe Medication
Practices recommend the use of ready-to-use medications. Cardene I.V. is contraindicated in patients
with advance aortic stenosis. This is the end of the presentation. Thank you very much for your attention. And have a good day.

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