Treatment of Hypertension in the Emergency Setting: CARDENE® I.V.

Treatment of Hypertension in the Emergency Setting: CARDENE® I.V.


>>DR.CANNON: Hello, I’m Chad Cannon. I’m a practicing emergency medicine physician
at the University of Kansas Hospital in Kansas City, Kansas. And I’m also the research director and vice
chairman of the department. And thank you for joining us today. And we’re going to be talking about the treatment
of hypertension in the emergency department setting. Hypertensive emergency and urgency are still
the least understood and worst treated acute medical problems. In a particular study by Zampaglione out of
Turin, Italy, he looked at 14,200 patients that were presented to the emergency department. Around 449 of these patients were diagnosed
with a hypertensive crisis. Of these hypertensive crises around a quarter
of these were actually hypertensive emergencies. And three-quarters approximately were hypertensive
urgencies. Hypertensive crisis is an umbrella term that
encompasses both hypertensive emergencies and urgencies. Better terms would be to use the terms specifically
hypertensive emergency, which is an elevated blood pressure greater than 180/120 with evidence
of impending or progressive target organ damage. A hypertensive urgency is an elevated blood
pressure without any evidence of acute end organ damage. The pathophysiology of a hypertensive emergency
is common among all the different types of hypertensive emergencies. The final common pathway is an abrupt increase
in blood pressure that leads to endothelial damage, an increase in local vasoconstrictors
which causes a loss of autoregulation, which causes this end organ damage. And this leads to further an increase in circulating
vasoconstrictors which is a vicious cycle. There are numerous causes of hypertensive
emergencies. In the brain we can have hypertensive encephalopathy,
ischemic stroke, and a cerebral hemorrhage. In the kidney we can have damage that causes
acute glomerulonephritis. In the endocrine system we have patients that
have elevated hormones that lead to pheochromocytoma. In the heart, examples of a hypertensive emergency
would include aortic dissection, acute left ventricular failure, myocardial infarction. And then there’s also drug-induced hypertension
that can be caused by cocaine, amphetamines, and other sympathomimetics. All these types of hypertensive emergencies
however do share that final common, um, pathophysiology of an abrupt increase in systemic vascular
resistance which leads to the elevated blood pressure. Looking at patients who present with hypertensive
emergencies and urgencies, these patients don’t always come in with evidence of end
organ damage that has been objectively determined, so we have to rely on symptoms that would
suggest end organ damage. And the most common symptoms when a patient
is presented to the emergency department that end up being hypertensive emergencies include
chest pain, dyspnea, neurological deficit. Common signs and symptoms of a hypertensive
urgency include headache, nosebleed, and psychomotor agitation. And, as you can see, patients who present
with faintness or who are weak or dizzy they often end up being classified as a hypertensive
emergency or a hypertensive urgency. And that’s why these patients are often so
difficult for the emergency physician to treat. In the workup of a patient who we are evaluating
for hypertensive emergencies and urgencies it’s important to take a careful history including
the symptoms, their past medical history, the medications that the patient takes, if
the patients actually had any illicit substances. When the patient presents to the emergency
department we want to obtain a blood pressure in both arms; we want to complete a focused
examination, including the cardio and vascular exam, neurological exam, and, if possible,
an examination of the optic fundi. Laboratory tests that we often obtain include
a CBC, a BUN and creatinine, electrolytes, cardiac markers such as troponin and BNP. It’s important to obtain an electrocardiogram,
a chest X-ray, a urinalyses, and, depending on the situation, we often have to obtain
neuroimaging such as a brain CAT scan or MRI, a CT of the chest, or ultrasound examinations. Looking at the estimated incidence of the
different types of hypertensive emergencies, we can see here that the brain is the most
common with acute ischemic strokes, hypertensive encephalopathy, and intracerebral and subarachnoid
hemorrhages. Many patients also have acute heart failure
and acute coronary syndrome. Aortic dissection is a rare but very disastrous
example of a hypertensive emergency. And other types of hypertensive emergency
such as eclampsia, retinal hemorrhage, and micro or angiopathic hemolytic anemia are
much more rare. This particular slide has to do with the important
concept of autoregulation. A normotensive patient is represented by the
red curve. As you can see, these patients are able to
control their cerebral blood flow over a wide range of blood pressures. A chronic hypertensive patient has that same
curve but you can see it’s shifted to the right. So they are also able to autoregulate to maintain
blood flow but at a higher range of pressures. But a patient who has had an insult and has
end organ damage and loss of autoregulation, they’re represented by the gray straight line. So small changes in blood pressure lead to
big changes of blood flow. This is very important in why we need to be
careful in managing these patients, in bringing down their blood pressure gradually so we
don’t cause worsening insult. This is similar to what we just saw on the
prior slide. The important point is that precise control
is critical in treating a patient with a hypertensive emergency. And a precipitous blood pressure reduction
may actually be dangerous. The indication for ready-to-use Cardene I.V.,
nicardipine hydrochloride, is for the short-term treatment of hypertension when oral therapy
is not feasible or not desirable. For prolonged control of blood pressure transfer
patients to oral medication as soon as their clinical condition permits. Some important safety information about ready-to-use
Cardene I.V. is displayed on this slide. Cardene I.V. is contraindicated in patients
with advanced aortic stenosis. 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
should occur the infusion should be discontinued. 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. Close monitoring of a response to Cardene
I.V., nicardipine hydrochloride, is advised in patients with angina, heart failure, impaired
hepatic function, or renal impairment. To reduce the 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 that all
occur greater than 3% are headache, nausea and vomiting, hypotension, and tachycardia. Please see full prescribing information. Some key considerations for choosing an antihypertensive
agent in hypertensive emergencies include the following desired characteristics: having
a rapid onset of action, having a rapid offset of action, requiring minimal preparation,
having a predictable dose response requiring few dose adjustments, being well tolerated,
and having little potential for adverse effects, and also not requiring any invasive blood-pressure
monitoring. These are all characteristics that Cardene
displays. Cardene I.V. causes arterialor-specific vasodilatation,
which decreases systemic vascular resistance. And this, in turn, decreases blood pressure. Other I.V. antihypertensive agents work on
other aspects of the blood pressure equation displayed here. Moving on to a study known as a STAT registry. This study was a U.S.-based, multi-center,
observational study looking at the routine management and practices of over 1,500 patients
with acute severe hypertension treated in the emergency department and the ICU setting. Severe hypertension was defined as greater
or than equal to one blood pressure measurement greater than a180 mmHg systolic blood pressure
and/or 110 mmHg diastolic blood pressure. Patients with subarachnoid hemorrhage were
included if they had a blood pressure measurement greater than 140 mmHg and/or a diastolic blood
pressure greater than 90 mmHg. Patients were excluded if they had received
a hypertensive therapy in the perioperative setting or during the peripartum period, or
if they had received therapy 24 hours after hospitalization or if they were treated with
comfort-care measures only. Looking at the number of I.V. antihypertensive
used based on initial therapy you can see that many patients required one, two, or three
or more different drugs to be used to control their blood pressure. Nicardipine patients had the highest rate
of success as used as a single agent. Important safety information includes that
the most common adverse reactions greater than 3% are headache, nausea, vomiting, hypotension,
and tachycardia. Another study in the emergency department
looking at treating acute hypertension was fortunate to be involved with was a multicenter
study looking at patients who presented to the emergency department with systolic blood
pressures greater than or equal to 180 mmHg on two separate readings ten minutes apart. In this study, Cardene I.V. was administered
at 5 mg an hour and increased every five minutes by 2.5 mg an hour until the target blood pressure,
which was defined by the treating physician, was achieved. A hundred and ten patients were treated with
Cardene I.V. These patients had a median initial systolic
blood pressure of 212 millimeter mercury. At study completion the systolic blood pressure
had dropped to 163 mmHg. And, as you can see, 92% of these patients
reached their target blood pressure within 30 minutes. Cardene I.V. is not indicated for treatment
or prevention of acute ischemic stroke, intracranial hemorrhage, or subarachnoid hemorrhage. And Cardene I.V. is contraindicated in patients
with advanced aortic stenosis. A subgroup analysis of this same study was
also performed in patients with renal disease; 52 patients were enrolled, and these patients
had creatinine clearances less than 75 mm a minute. The mean baseline systolic blood pressure
in these patients was 218. And by 15 minutes the median systolic blood
pressure had dropped by 40, 92% of these patients reached their target blood pressure within
30 minutes. No serious adverse events were reported. Cardene I.V. should be titrated gradually
in patients with renal impairment as decreased systemic clearance are observed in these patients. Another prospective study of patients who
presented to the emergency department with acute ischemic stroke, intracerebral hemorrhage,
or subarachnoid hemorrhage was performed. In this study, Cardene I.V. was administered
at 5 milligrams an hour and increased every 15 minutes by two-and-a-half milligrams an
hour until the target systolic blood pressure range was achieved. Blood pressure goals were defined using current
consensus recommendations. Blood pressure and heart rate were taken every
15 minutes until the blood pressure was achieved. Twenty-six patients with neurological emergencies
were treated. The initial systolic blood pressure was 215
millimeter mercury. Eighty-nine percent of these patients achieved
their respective blood pressure goal with 60 minutes. And this smooth reduction of blood pressure
was maintained over 24 hours. There was only one incidence of hypotension. No rescue therapy was required. Cardene I.V. is not indicated for the treatment
or prevention of acute ischemic stroke, intracerebral hemorrhage, or a subarachnoid hemorrhage. Moving on to the ATACH trial, which stands
for Antihypertensive Treatment of Acute Cerebral Hemorrhage trial, in the emergency department. This was an open-label, dose-escalation, multicenter
perspective study of patients with intracerebral hemorrhage with elevated systolic blood pressure
greater than 170 mmHg who presented to the emergency department within six hours of symptom
onset. Patients were enrolled in three tiers of systolic
blood pressure treatment goals. Tier one was 170 to 200. Tier two, 140 to 170. And tier three was more aggressive at 110
to 140. Cardene I.V. was initiated at 5 milligrams
an hour and then increased by two-and-a-half milligrams an hour every 15 minutes as needed
up to a maximum of 15 milligrams an hour. As you can see in this graph, rapid blood
pressure reduction in patients with intracerebral hemorrhage was achieved. And this was maintained over 24 hours. Over 60 patients were treated in these three
different systolic blood pressure tiers. The mean initial systolic blood pressure was
212, and 90% of these patients achieved their respective systolic blood pressure goal within
two hours in all tiers. Gradual titration of Cardene I.V. was used. Cardene I.V. is not indicated for the treatment
or prevention of the intracerebral hemorrhage. Now let’s look at some case studies. First case study will be on hypertensive emergency
with acute intracerebral hemorrhage. The following case study demonstrates how
Cardene I.V. (nicardipine hydrochloride) could be used in the short-term treatment of hypertension
when the practitioner determines that oral antihypertensive therapy is not feasible or
desirable. Patient symptoms will vary, and individual
clinical evaluation should be done to determine the best course of therapy. This was a 48-year-old male who was found
unresponsive at home by family. He’s brought into the hospital by EMS. Family members related a history of hypertension,
renal disease, high cholesterol, prior ischemic heart disease with heart failure. His prescription bottles were brought by EMS,
and these included lisinopril, clonidine, Lipitor, and Bumex. On physical examination the patient’s blood
pressure was 240 over 160, heart rate was 140. The patient was breathing 24 times a minute. The patient was afebrile. On neurological examination the patient’s
pupils were equally reactive to light and accommodation. The patient was unarousable. The neck was supple. When the patient was subjected to painful
stimuli there was no movement in the right arm or leg. Physical exam of the heart showed a prominent
S2, no aortic murmur, and an S3 gallop was easily heard. The EKG showed sinus tachycardia, a left bundle
branch block, and a left ventricular strain pattern in the lateral chest leads. Chest X-ray showed a enlarged heart with pulmonary
edema. Serum chemistries showed a potassium of 5.1,
a creatinine of 2.1, the troponin in was within normal limits, but the BNP was elevated. The head CT was obtained which showed a large
intracerebral hemorrhage in the left temporal lobe. An echocardiogram was later obtained and showed
no valvular disease but a left of ventricular ejection fraction of 30%. Our diagnosis was acute intracerebral hemorrhage
of the left temporal lobe. And this was a true hypertensive emergency. This patient also had an exacerbation of cardiac
failure, and the patient displayed renal impairment. How would you treat this patient? The treatment plan included an elective intubation
to control the airway. Cardene I.V. was initiated at 5 mg an hour
with an upward titration at two-and-a-half milligrams an hour to achieve a mean arterial
pressure of 130 mmHg. Neurosurgery consultation was obtained for
a potential evacuation of the hematoma and possible insertion of an intracerebral pressure
monitor. And as a reminder, important safety information:
Cardene I.V. (nicardipine hydrochloride) is contraindicated in patients with advanced
aortic stenosis. During this patient’s hospital, course Cardene
I.V. was administered by an infusion, and the dose was titrated to achieve a systolic
blood pressure goal of 160. The patient was prepped for ventriculostomy
which was performed early in the course of arrival. The increased intracranial pressure was treated
with hyperventilation. And after nearly a day of therapy with Cardene
I.V. oral antihypertensive medications were started via the nasogastric tube. And the Cardene I.V. dose was titrated downward
and discontinued by 48 hours. The patient’s 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. When this patient presented to the emergency
department the systolic blood pressure was 240, and as you can see in the graph the blood
pressure was decreased to 160 mmHg target over a two-and-a-half-hour infusion. This allowed safe placement of the ventriculostomy. Additional safety information is the following;
Hypotension and reflex tachycardia may potentially occur during the 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. Our next case study focuses on acute ischemic
stroke with hypertension. This was a 78-year-old female who presented
with difficulty speaking and complaining of weakness on the right side. The patient was brought to the emergency department
by family approximately four hours after symptom onset. The patient did have a history of high blood
pressure and type II diabetes. Her medications included metoprolol and metformin. On exam the patient had a blood pressure of
205 over 115, a heart rate of 88, breathing 18 times a minute, and the patient was afebrile. On neurological exam the patient displayed
slurred speech and was difficult to understand. She was awake and alert. Her pupils were equal reactive to light and
accommodation, and she displayed a right hemiparesis. Her NIH stroke scale was twelve. The patient’s laboratory values showed a hemoglobin
of 8.1, potassium and glucose were relatively normal. The patients troponin was not elevated. Chest X-ray was normal. In a CT and in a subsequent MRI showed evidence
of a prior lacunar infarct but no intracerebral hemorrhage. A cerebral angiogram revealed occlusions involved
two distal branches of the superior and inferior divisions of the left middle cerebral artery. Our diagnosis was an acute ischemic stroke
and a hypertensive emergency. How would you treat this patient? Our treatment plan included lowering the systolic
blood pressure to less than 185 and the diastolic blood pressure to less than 110, which is
consistent with the American Heart Association and American Stroke Association guidelines
to reduce the risk of intracerebral hemorrhage. Intra-arterial thrombolysis was performed
via microcatheter in the right middle cerebral artery. And the patient also was administered I.V. Integrilin to prevent reocclusion following
the procedure. Cardene I.V. was administered by an infusion
and initiated at a dose of 5 milligrams an hour to reduce blood pressure due to the risk
of intracerebral hemorrhage. It was titrated by increments of two-and-a-half
milligrams an hour to reach the AHA/ASA target blood pressure, less than 185 over 110 mmHg. This patient’s home metoprolol was held. Sliding scale insulin was used. And I.V. Integrilin was administered following the
procedure. And as a reminder the most common adverse
reactions greater than 3% are headache, nausea, vomiting, hypotension, and tachycardia. With administration of Cardene I.V. the patient’s
initial blood pressure of 205 over 115 was decreased to a target less than 185 over 110. This was achieved in a smooth manner without
significant adverse events. Now let’s look at opportunities for efficiencies
and compliance with guidelines. Potential reasons for admixed generic nicardipine
wastage include that once the admixture occurs nicardipine expires in 24 hours. If nicardipine is discontinued for a patient,
the admixed bags may be discarded. Ready-to-use medications save time. These ready-to-use bags save pharmacy time
and labor. They can be stored at the point of care, which
improves efficiency. They’re immediately available for rapid intervention. Ready-to-use medications also support guidelines. Ready-to-use medications minimize admixture
errors. The Joint Commission, the American Society
of Healthsystem Pharmacies, and the Institute For The Safe Medication Practices recommend
the use of ready-to-use medications. Cardene I.V. has guaranteed stability for
24 months under the appropriate storage conditions. Admixed generic nicardipine is stable for
only 24 hours. Ready-to-use Cardene I.V. is sterile and available
in these two formulations. Ready-to-use, premixed medications comply
with guidelines. These medications are dispensed in the most
ready-to-administer forms commercially available. And a system must be in place to safely provide
these medications to meet patient needs even when the pharmacy is closed. When making purchasing decisions, one should
look beyond acquisition cost, and they need to consider drug availability. In 2012 there were over 117 drug shortages,
84 involving sterile injectable drugs. And many of these drugs were short in the
emergency department. Drug shortages may be costly for the overall
hospital system in terms of not only increased costs but also the time spent dealing with
these shortage issues and, most importantly, the potential adverse effect on patient care. Cardene I.V. is recommended or included in
the following management guidelines: the 2010 AHA/ASA management of spontaneous intracerebral
hemorrhage, the 2012 guideline for the management of aneurysmal subarachnoid hemorrhage, and
the 2013 guidelines for early management of patients with acute ischemic stroke. Ready-to-use Cardene I.V. can be used for
rapid titration of blood pressure or gradual titration. For rapid titration it should be initiated
at 5 milligrams an hour and titrated by 2.5 milligrams an hour every five minutes. For gradual titration Cardene I.V. should
be initiated at 5 milligrams an hour, titrated by 2.5 milligrams an hour every 15 minutes
to a maximum dose of 15 milligrams an hour. Following achievement of the blood pressure
goal, decrease the infusion rate to 3 milligrams an hour. Ready-to-use Cardene I.V. is available in
two different preparations, 40 milligrams in 200 milliliters and 20 milligrams in 200
milliliters. In summary, ready-to-use Cardene I.V. provides
rapid and precise blood pressure control. I.V. dosing delivers predictable study results. It increases cardiac output, but coronary
steal has not been observed. Cardene I.V. is not associated with bradycardia
or rebound hypertension. Cardene I.V. is immediately available for
rapid intervention. It minimizes medication admixture errors. The Joint Commission, the American Society
of Healthsystem Pharmacists, and the Institute for Safe Medication Practices recommend the
use of ready-to-use medication. Once again, Cardene I.V. (nicardipine hydrochloride)
is contraindicated in patients with advanced aortic stenosis. This concludes the presentation. Thank you for joining me today.

Leave a Reply

Your email address will not be published. Required fields are marked *