Download Using Nicardipine in the Stroke Unit

Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
Using IV Nicardipine for Blood Pressure
Treatment in a Stroke Unit Setting
Mark J. Alberts, MD
Professor of Neurology
Northwestern University
Deborah Bergman, NP
Senior Nurse
Northwestern Stroke Center
Northwestern Memorial Hospital
Chicago, IL
Hypertensive Crisis:
Emergency vs Urgency
•
•
Hypertensive emergency1,2
– Evidence of end-organ damage
• Kidney
• Retina
• Heart
• Brain
– About 500,000 cases annually in US due to high prevalence
of HTN
Hypertensive urgency1,2
– No evidence of end-organ damage
– BP reduction over several hours to days
– Usually treated with oral antihypertensives
1. Mansoor GA, Frishman WH. Heart Dis. 2002;4:358-371.
2. Varon J, Marik PE. Chest. 2000;118:214-227.
End-Organ Damage Characterizes
Hypertensive Emergencies
Brain
Hypertensive encephalopathy
Stroke
Retina
Hemorrhages
Exudates
Papilledema
Cardiovascular System
Unstable angina
Acute heart failure
Acute myocardial infarction
Acute aortic dissection
Dissecting aortic aneurysm
Kidney
Hematuria
Proteinuria
Decreasing renal function
Adapted from Varon J, Marik PE. Chest. 2000;118:214-227.
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Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
Pathophysiologic Principles at
Work in the Hypertensive Milieu
Acute Hypertension―Pathophysiology
Circulating and local factors acting on
endothelium and vascular smooth muscle
BP
=
SVR
Abrupt ↑ BP
X
Abrupt ↑ SVR
CO
(SV x HR)
SVR = systemic vascular resistance; CO = cardiac output; SV = stroke volume; HR = heart rate.
Adapted from Hoffman BB. In: Brunton LL, et al, eds. Goodman & Gilman’s The Pharmacological Basis of
Therapeutics. 11th ed. New York, NY: The McGraw-Hill Companies Inc; 2006:845-868.
Cerebral Autoregulation Is Central to
Treatment of Hypertensive Crises
Patients with chronic hypertension
autoregulate cerebral blood flow
around higher set points
Cerebral Blood Flow
Patients with cerebral ischemia
lose their ability to autoregulate
Increasing risk of
hypertensive
encephalopathy
Ischemia
Normotensive
Chronic hypertensive
Increasing risk
of ischemia
0
50
100
150
200
250
MAP (mm Hg)
Adapted with permission from Varon J, Marik PE. Chest. 2000;118:214-227.
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Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
Hypertension Can Drive Elevated
Intracranial Pressure
75
Vasodilatory
Maximum
Cascade
Zone
Dilatation
Autoregulation
Maximum
Breakthrough
Zone
Constriction
Zone of Normal
Autoregulation
50
50
25
25
0
0
0
25
50
75
100
125
150
Intracranial Pressure (mm Hg)
Cerebral Blood Flow
(mL/100 g/min)
Passive
Collapse
Cerebral Perfusion Pressure (mm Hg)
Courtesy of Stephan A. Mayer, MD.
Vascular Smooth Muscle Contraction Is
Calcium Dependent
Ca++
↓↓↓
↓↓↓
Calcium influx into vascular
smooth muscle
may occur via opening of
L-type calcium channels
Ca++ plus
calmodulin
↓
Myosin kinase
↓↓↓
Release of intracellular stores
may also be a source of Ca++
Actin-myosin interaction
→ Contraction
↓
Ca++
Adapted with permission from Frishman WH, et al. Curr Probl Cardiol. 1987;12:285-346.
BP Goals in Ischemic Stroke
• Usually no need to treat unless BP > 220 or >
120 mm Hg
• TPA patients have different parameters
– 180-185 systolic; 105-110 diastolic
• Do not want a sudden drop
• New guidelines suggest that it is OK to begin
BP medications after 24 hours
– Rule out a high-grade proximal stenosis
– Typically begin with oral agents if BP >
160/>100
Class 1 C recommendations
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Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
Predictors of Outcome
●
Hematoma volume
●
GCS
●
Intraventricular
hemorrhage
●
Age
●
ICH location (deep)
●
Increased cerebral edema
(midline shift, herniation)
Manno EM, et al. Mayo Clin Proc. 2005;80:420-433; Garibi J, et al. Br J
Neurosurg. 2002;16:355-361; Flaherty ML, et al. Neurology. 2006;
66:1182-1186.
Hematoma Expansion
• 72% have some hematoma expansion over the first 24 hours
• 38% have significant (>33%) expansion over 24 hours
• In 26% of these cases, the enlargement is within 1 hour
Davis SM, et al. Neurology. 2006;66:1175-1181;
Brott T, et al. Stroke. 1997;28:1-5.
Approaches to Prevent or Reduce ICH
Expansion
• Controlling blood pressure
– Under study
• Using recombinant factor 7 (all patients)
– 1 positive and 1 negative study
– Clear biologic effect; unclear benefit
• Correct coagulopathy immediately
– Factor 7; PCC (prothrombin concentrate complex);
transfuse platelets
• If all fail--consider emergency surgery
• Prognosis poor without intervention
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Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
AHA Suggested Recommended Guidelines
for Treating Elevated BP in Spontaneous ICH
(2007)
SBP and MAP Levels
(mm Hg)
Treatment
SBP >200
or
MAP >150
Consider aggressive reduction of BP with
continuous IV infusion, with frequent BP
monitoring every 5 min
SBP >180
or
MAP > 130
and evidence or suspicion
of elevated ICP
Consider monitoring ICP and reducing BP
using intermittent or continuous IV
medications to keep CPP >60–80 mm Hg
SBP >180
or
MAP >130
and no evidence or suspicion
of elevated ICP
Consider a modest reduction of BP (eg,
MAP of 110 mm Hg or target BP of 160/90
mm Hg) using intermittent or continuous IV
medications to control BP, and clinically
reexamine the patient every 15 min
AHA = American Heart Association; CPP = cerebral perfusion pressure; ICH = intracerebral hemorrhage; MAP = mean arterial
pressure, SBP = systolic blood pressure.
Broderick J et al. Stroke. 2007;38:2001-2023.
Understanding Cerebral Hemodynamics
• CPP = MABP – ICP
• If an agent reduces MABP but does not
decrease ICP, then CPP will fall in some
cases
• If MABP falls and ICP rises, CPP can fall
dramatically
• Depends on ability of cerebral
autoregulation to compensate
IV Medications That May Be Considered for
Control of Elevated BP in Patients With ICH
(2007 AHA Guidelines)
Drug
Labetalol
Nicardipine
IV Bolus Dose
5–20 mg q 15 min
Continuous
Infusion Rate
2 mg/min
(max. 300 mg/d)
NA
5–15 mg/h
Esmolol
250 µg/kg IVP
loading dose
25–300 µg · kg−1 · min−1
Enalapril
1.25–5 mg IVP q 6 h*
NA
Hydralazine
5–20 mg IVP q 30 min
1.5–5 µg · kg−1 · min−1
Nipride
NA
0.1–10 µg · kg−1 · min−1
Nitroglycerin
NA
20–400 µg/min
AHA = American Heart Association; ICH = intracerebral hemorrhage; IVP = intravenous push; NA = not applicable.
*Because of the risk of precipitous blood pressure lowering, the enalapril first test dose should be 0.625 mg.
Broderick J et al. Stroke. 2007;38:2001-2023.
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Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
AHA/ASA guideline: BP management
in acute hemorrhagic stroke
SBP >200 mm Hg or MAP >150 mm Hg
• Consider aggressive ↓BP with continuous IV infusion
– Monitor BP q5 min
SBP >180 mm Hg or MAP >130 mm Hg; ↑ICP evident or suspected
• Monitor ICP
Administer intermittent or continuous IV antihypertensive treatment
to keep cerebral perfusion pressure 60-80 mm Hg
SBP >180 mm Hg or MAP >130 mm Hg and no ↑ICP
• Administer intermittent or continuous IV antihypertensive treatment
to achieve modest ↓BP (eg, target BP 160/90 mm Hg or MAP 110 mm Hg)
– Reexamine patient q15 min
These are all Class IIb level C recommendations
ICP = intracranial pressure
Broderick J et al. Stroke. 2007;38:2001-23.
Nicardipine
•
Selective arteriolar vasodilator1,2
•
Calcium ion channel inhibitor2
•
Onset of action: 5-10 minutes3
•
Duration: 15-30 minutes; may exceed 4 hours3
•
Adverse effects: tachycardia, headache, flushing, and local phlebitis3
•
Special indications/contraindications
– No significant effect on ICP4
– Appropriate in most hypertensive emergencies except acute
heart failure1-3
– Use with caution in coronary ischemia3
•
Only IV CCB indicated for short-term treatment of HTN2; maintains or
increases cardiac output2; as effective as sodium nitroprusside with fewer
dose adjustments5; not associated with coronary steal2
1. Rose JC, et al. Neurocrit Care. 2004;1:287-299. 2. Cardene I.V. (nicardipine hydrochloride). Prescribing information. Fremont,
Calif: PDL BioPharma Inc; 2006. 3.The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure. US Dept of HHS; NIH publication No. 04-5230; 2004:55. 4. Nishiyama T, et al. Can J
Anesth. 2000;47:1196-1201. 5. Neutel JM, et al. Am J Hypertens. 1994;7:623-628.
Use of IV Nicardipine in a Stroke Unit for
Acute Blood Pressure Control
• Many patients require acute BP control but
are otherwise stable
• They often do not need all of the services
of an NICU
• Can these patients be treated safely in a
Stroke Unit setting?
• We performed a prospective open-label
study to answer this question
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Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
Inclusion Criteria
• Enrolled patients with:
– Ischemic stroke
– ICH
– SAH
– CVT
– Hypertensive urgency, crisis
– Pre or post IV TPA therapy
• Who required BP control with an IV agent
Exclusion Criteria
• Need for ICU care due to unstable vital
signs or other conditions (intubation)
• Contraindications to IV Nicardipine therapy
• Need for arterial catheters
Treatment Paradigm
• Trained Stroke Unit nurses on the use of IV
Nicardipine
• Used non-invasive blood pressure monitoring
and multi-channel telemetry
• Began IV Nicardipine at dose of 5 mg/hr
• Titrated as needed to achieve desired BP
– Goal determined by treating physician
PRIMARY ENDPOINT: Achievement of desired
blood pressure
SAFETY ENDPOINT: 1) symptomatic
hypotension, 2) transfer to NICU due to inability
to control BP, 3) other complication due to
nicardipine infusion
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Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
Study Population
•
•
•
•
•
12 patients enrolled to date (plan = 20)
6 male/ 6 female
Age range 41 - 85 yrs
Disease: 5 ICH 4 Ischemic 3 HTN Urg
Location: 9-NICU 2-ED 1-MICU
Results
•
•
•
•
•
•
# dose adjustments: 1-15
Treatment time: 1 – 64 hours
% who achieved target BP: 100%
% with symptomatic hypotension: 0%
% requiring ICU transfer: 0%
% with side effects: 0%
Conclusions
• Blood pressure control is possible using IV
Nicardipine in a Stroke Unit type setting for
patients with a variety of cerebrovascular
disorders
• There were no serious hypotensive events
or other serious side effects
• Most patients could be controlled with a
modest number of dose adjustments
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Using Nicardipine in the Stroke Unit: Improving Patient Flow
Mark J. Alberts, MD
Limitations
• These were selected patients in a specific
stroke unit setting
• Nurses had special training and back-up of
experienced nurses
• Study is ongoing with a relatively small
number of patients
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