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Optimal Blood
Pressure Control in
Intracerebral and
Subarachnoid
Hemorrhage
Stephan A. Mayer, MD
Assistant Professor of Neurology (in
Neurological Surgery), Columbia University
College of Physicians and Surgeons;
Director, Neurological Intensive Care Unit,
Columbia-Presbyterian Campus of New York
Presbyterian Hospital, Columbia University
Medical Center, New York, New York
Disclosures
Grant/Research Support:
Medivance, Inc., Novo Nordisk
Speakers Bureau/Consultant:
Astellas Pharma US, Inc., ESP Pharma,
Novo Nordisk
Stock/Shareholder:
Medivance, Inc., Radiant
Outline
• Physiology and pathophysiology
• Specific medications
• Specific conditions: blood pressure targets
Acute Hypertension −
Pathophysiology
Circulating and local factors acting on
endothelium and vascular smooth muscle
BP
=
Abrupt  BP
SVR
Abrupt  SVR
X
CO
(SV x HR)
SVR = systemic vascular resistance; CO = cardiac output; SV = stroke volume; HR = heart rate.
Oates JA, Brown NJ. In: Hardman JG, Limbird LE, eds. Goodman and Gilman’s Pharmacological Basis of
Therapeutics. 10th ed. New York, NY: McGraw-Hill; 1997:871-900.
Cerebral Autoregulation is Central
to Treatment of Hypertensive Crises
Cerebral Blood Flow
Patients with cerebral ischemia
lose their ability to autoregulate
Increasing risk of
hypertensive
encephalopathy
Autoregulatory failure
normotensive
chronic hypertensive
Increasing risk
of ischemia
50
100
150
200
250
MAP (mm Hg)
Adapted with permission from Varon J, Marik PE. Chest. 2000;118:214-227.
Columbia Stepwise
ICP Protocol
7
6
5
4
3
2
1
HYPOTHERMIA
PENTOBARBITAL
HYPERVENTILATION
OSMOTHERAPY
CPP OPTIMIZATION
SEDATION
SURGICAL DECOMPRESSION
ICP/CPP Management
75
Maximum
Dilatation
Zone of Normal
Autoregulation
Maximum
Constriction
50
50
25
25
0
0
0
25
50
75
100
125
Cerebral Perfusion Pressure (mm Hg)
ICP = intracranial pressure; CPP = cerebral perfusion pressure.
150
ICP (mm Hg)
Cerebral Blood Flow
(mL/100 g/min)
Passive
Collapse
ICP/CPP Management
Cerebral Blood Flow
(mL/100 g/min)
Passive
Collapse
Vasodilatory
Cascade Zone
Autoregulation
Breakthrough
Zone
Zone of Normal
Autoregulation
50
50
25
25
0
0
0
25
50
75
GOAL
100
125
Cerebral Perfusion Pressure (mm Hg)
ICP = intracranial pressure; CPP = cerebral perfusion pressure.
150
ICP (mm Hg)
75
Antihypertensive Agents Used
in Hypertensive Crisis
• Clonidine
• Nicardipine
• Diazoxide
• Nifedipine
• Enalaprilat
• Nitroglycerin
• Esmolol
• Nitroprusside
• Fenoldopam
• Phentolamine
• Hydralazine
• Trimethaphan
• Labetalol
Antihypertensive Agents Used
in Hypertensive Crisis
• Clonidine
• Nicardipine
• Diazoxide
• Nifedipine
• Enalaprilat
• Nitroglycerin
• Esmolol
• Nitroprusside
• Fenoldopam
• Phentolamine
• Hydralazine
• Trimethaphan
• Labetalol
Nicardipine vs
Adrenergic Blockers
Nicardipine
(Cardene IV)
Esmolol
(Brevibloc)
Labetalol
Administration
Continuous
infusion*
Bolus,
Continuous
infusion
Bolus,
Continuous
infusion
Onset + Offset
Rapid
Rapid
Slower
0
Decreased
Decreased
HR1
Minimal increase
Decreased
Decreased
SVR
Decreased
0
Decreased
Cardiac output1
Increased
Decreased
+/-
Positive
Positive
Positive
Advanced aortic
stenosis
Bradycardia
Heart block >1°
CHF
Bronchospasm
COPD
Bradycardia
Heart block >1°
CHF
Bronchospasm
COPD
Drug
Contractility
Myocardial O2
balance2
Contraindications
Hypertension in
Intracerebral Hemorrhage
• Up to 80% of patients with
intracerebral hemorrhage are
hypertensive on presentation
• Blood pressure spontaneously falls
over next several days
• Management is controversial
Britton M, et al. Stroke. 1986;17:861-864.
Carlberg B, et al. Stroke. 1993; 24:1372-1375.
Early Hematoma Growth
2.5 hrs
post-symptom onset
6.5 hrs
post-symptom
Occurs in ~35% of patients scanned <3 hours of onset,
but not predicted by hypertension
Reasons to Treat Hypertension
• Hypertension may predispose to
•
•
•
•
hematoma enlargement
Hypertension may promote edema
surrounding the hematoma
Hypertension is associated with
poor outcome
Patients whose MAP can be
controlled have a better outcome
End organ damage
Tuhrim S, et al. Ann Neurol. 1991;29:658-663.
Dandapani BK, et al. Stroke. 1995;26:21-24.
Reasons NOT to Treat
Hypertension
• Chronically hypertensive patients require
higher perfusion pressure due to shift of
autoregulatory curve
• Lowering blood pressure may promote
ischemia surrounding the hematoma
• ICP may be elevated and lowering blood
pressure reduces what could be marginal CPP
• Blood pressure and CPP reduction may induce
vasodilation and ICP plateau waves
Peri-clot Flow, Metabolism,
and OEF
CBF
CMRO2
OEF
Treatment of Hypertension in Acute
Intracerebral Hemorrhage (1999)
Recommendations
• Maintain MAP <130 mm Hg if history of
hypertension
– IV labetalol
– IV nicardipine
• Immediately post-craniotomy, keep
MAP <110 mm Hg
• If monitored, keep CPP (MAP-ICP) >70 mm Hg
CPP = cerebral perfusion pressure; MAP = mean arterial pressure; ICP = intracranial pressure.
Broderick JP, et al. Stroke. 1999;30:905-915.
Global Cerebral Edema in
Acute Subarachnoid Hemorrhage
The Columbia University
Subarachnoid
Hemorrhage
Outcomes
Project
SAH Day 0
• Develops in 20% of SAH
patients
• Predicted by LOC at onset
• Delayed edema associated
with Triple-H Therapy!
• Associated with increased
mortality, disability, and
cognitive impairment
SAH Day 18
Claassen J, et al. Stroke. 2002;33:1225-1232.
Kreiter KT, et al. Stroke. 2002;33:200-208.
Effect of Acute Physiologic
Derangements on Outcome
after Subarachnoid Hemorrhage
• SAH-PDS was
independently
associated with
3-month death or
severe disability
Score
Frequency
AA gradient >125 mm Hg
3
43%
HCO3 <20 mMol/L
2
21%
Glucose >180 mg/dL
2
31%
MAP <70 or >130 mm Hg
1
20%
Score range
0-8
100 –
% severely disabled
% dead
80 –
60 –
• Adjusted OR 1.3,
95% CI, 1.1−1.6
40 –
20 –
0–
0
SAH-PDS
N in each category
89
1
2
3
4
5
6
7
8
30
33
48
28
33
33
6
21
Claassen J, et al. Crit Care Med. 2004;32:832-838.
Effect of Acute Physiologic
Derangements on Outcome
after Subarachnoid Hemorrhage
Score
Frequency
AA gradient >125 mm Hg
3
43%
HCO3 <20 mMol/L
2
21%
Glucose >180 mg/dL
2
31%
MAP <70 or >130 mm Hg
1
20%
Score range
0−8
Claassen J, et al. Crit Care Med. 2004;32:832-838.
Rebleeding and Vasospasm
after SAH
Percent Probability
4–
3–
Symptomatic
Vasospasm
2–
Re-bleeding
1–
0–
0
I
1
I
2
I
3
I
4
I
5
I
6
I
7
I
8
I
9
I
10
I
11
I
12
Days after Subarachnoid Hemorrhage
The daily percentage probability for the development of symptomatic
vasospasm or re-bleeding after subarachnoid hemorrhage.
Day 0 denotes onset of subarachnoid hemorrhage.
Re-bleeding after
Subarachnoid Hemorrhage

• 585 patients
• Risk factors
– larger aneurysms
– poor clinical grade
– not BP
• 78% re-bled <72 hrs
after index bleed
• Associated with fivefold increased risk of
death at 3 months
Pr edict ed Rebleedin g Risk
• 6.7% re-bled

0.50
0.40

0.30



0.10











IV

V



0.20

V
IV






III


















II

I


III

II
I

0.00
10
20
30
40
Aneurysm Size (mm)
Naidech AM, et al. Arch Neurol. 2004 (in press).
Prevention of Re-bleeding in
Subarachnoid Hemorrhage
• Antihypertensive treatment to prevent re-bleeding
is controversial
• In the 1994 AHA Guidelines, antihypertensive
therapy alone is not recommended, but may be
combined with bed rest and/or anti-fibrinolytic agent
• Many centers control SBP ≤160 mm Hg until
aneurysm is secured
–IV nicardipine
–IV labetalol
Mayer SA, Merritt’s Textbook of Neurology, 10th Ed, Page 256.
Mayberg MR, et al. Circulation. 1994;90:2592-2605.
Left MCA Vasospasm
Fluid Management Protocol for
Symptomatic Vasospasm at
Columbia University Medical Center
• NS @ 100-150 mL/hr
• Place PAC
• 5% albumin 250 mL Q2H PRN PADP ≤14 mm Hg
• SBP 180−220 mm Hg
– Phenylephrine
– Norepinephrine
• Cardiac Index >4.0 L/min/m2
– Dobutamine
– Milrinone
• Transfuse HCT >30%
Neurocritical Care Society
www.neurocriticalcare.org
Management of
Blood Pressure in
Acute Ischemic Stroke
Mark J. Alberts, MD
Professor of Neurology,
Northwestern University Medical School;
Director, Stroke Program,
Northwestern Memorial Hospital,
Chicago, Illinois
Outline
• Natural history of HTN in AIS
• Physiology and pathophysiology
• Clinical observational studies
• Treatment studies
• Guidelines
• Medical therapies
• Clinical implications
Elevated Blood Pressure with
Acute Ischemic Stroke
• Very common ─ seen in up to 85% of patients
• Seen regardless of prior history
of hypertension
• Typically falls somewhat after first 24 hours
– Some studies report spontaneous fall within 6–8
hours of stroke onset
• May be a marker for pre-existing, but
undiagnosed, hypertension in some patients
Pathogenesis of Hypertension
with Ischemic Stroke
Several theories have been advanced
1. Sympathetic reaction
2. Hypoxic response
3. Exacerbation of underlying hypertension
4. Reaction to increased ICP ─ typically seen
after 2–3 days
Cerebral Autoregulation and
Cerebral Ischemia
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
50
100
150
200
250
MAP (mm Hg)
Adapted with permission from Varon J, Marik PE. Chest. 2000;118:214-227.
Rationale for Not Treating
Hypertension in Acute Ischemic Stroke
• Defective autoregulation
• Chronic hypertension shifts autoregulatory curve
• Vulnerable ischemic penumbra
• Unclear if patient taking their medications
– Restarting in acute setting could cause significant decline
in BP
• Clinical experience--make stroke symptoms worse!
Effect of Blood Pressure During the
Acute Period of Ischemic Stroke Outcome
(A Tertiary Analysis of the GAIN International Trial)
• Enrolled 1,455 patients with
acute ischemic stroke
• Blood pressure treatment was at
discretion of principal investigator
• Evaluated outcomes
Aslanyan S, et al. Stroke. 2003;34:2420-2425.
Acute Blood Pressure
Changes in GAIN
140 -
mm Hg
120 -
100 -
80 -
I
10
I
20
I
30
I
40
I
50
I
60
I
70
I
80
I
90
Hours
Aslanyan S, et al. Stroke. 2003;34:2420-2425.
Blood Pressure Changes
and Outcomes
Statistically Significant Associations Between
Primary Outcomes and Blood Pressure Variables
30% Increase From Baseline MAP
Outcome
Time
Mortality, HR
Barthel Index (dead or 0-55 vs
60-90 vs ≥95)
NIHSS score (dead or ≥2)
Rankin Scale score (dead or ≥2)
P
OR (95% Cl)*
P
3 mo
>.05
1.16 (1.06-1.27)
>.01
7d
>.05
>.05
1mo
2.01 (1.16-3.49)
.01
3 mo
2.39 (1.42-4.03)
>.01
>.05
>.05
>.05
7d
1.12 (1.03-1.23)
1.14 (1.01-1.28)
.01
1 mo
2.74 (1.11-6.73)
.03
3 mo
2.87 (1.33-6.20)
.01
>.05
1 mo
3.03 (1.30-7.02)
.01
>.05
>.05
>.05
3 mo
*Per additional 10 mm Hg
OR (95% Cl)
Weighted Average MAP
.03
Aslanyan S, et al. Stroke. 2003;34:2420-2425.
Blood Pressure Decrease During the Acute
Phase of Ischemic Stroke is Associated with
Brain Injury and Poor Stroke Outcome
• 304 patients with acute ischemic
hemispheric stroke
• 67 treated with blood pressure meds in ED
(no guidelines)
• 31 treated with blood pressure meds in
Stroke Unit (per guidelines)
Castillo J, et al. Stroke. 2004;35:520-526.
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0–
A
n = 18 n = 29
n = 39
n = 78
n = 49 n = 87
< 120 121 -140 141 -160 161 -180 181 -200 > 200
Early neurological deterioration %
Early neurological deterioration %
Outcome by
Admission Blood Pressure
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0–
B
n = 38
< 70
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0–
C
n = 18 n = 29
n = 39
n = 78
n = 49 n = 87
< 120 121 -140 141 -160 161 -180 181 -200 > 200
Systolic BP on admission (mm Hg)
n = 48
81 -90
n = 43
n = 30 n = 102
91 -100 101 -110 > 110
Diastolic BP on admission (mm Hg)
Post neurological outcome %
Post neurological outcome %
Systolic BP on admission (mm Hg)
n = 39
71 -80
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0–
D
n = 38
< 70
n = 39
71 -80
n = 48
81 -90
n = 43
n = 30 n = 102
91 -100 101 -110 > 110
Diastolic BP on admission (mm Hg)
Castillo J, et al. Stroke. 2004;35:520-526.
Effect of BP Changes on
Outcome
• Every 10 mm drop in BP < 180 mm Hg
was associated with a 25% increase in
poor outcome
• Every 10 mm increase in BP > 180 mm Hg
was associated with a 40% increase in
poor outcome
• Mean infarct volumes increased at either
extreme
The ACCESS Study
Evaluation of Acute Candesartan Cilexetil Therapy
in Stroke Survivors
• 342 patients with acute ischemic stroke
• Randomized
• Treated with candesartan 8–16 mg/day
for hypertension
• Trial stopped early due to efficacy results
Schrader J, et al. Stroke. 2003;34:1699-1703.
ACCESS Study Plan
Study Design
Candesartan*
Cerebral Ischemia
Hypertension
Candesartan*
for Hypertension
Placebo
No Antihyper Treatment
Normotension (n = 2)
Hospitalized
Day 1
Outpatient
Day 7
1 Yr
* 4-16mg according to blood pressure levels, combination therapy if necessary.
Schrader J, et al. Stroke. 2003;34:1699-1703.
Blood Pressure in ACCESS
Blood Pressure Over Time (Days)
mmHg 250
200
150
100
X
X
X
X
X
X
X
X
X
X
X
X
X
Candesartan systolic
Placebo systolic
Candesartan diastolic
Placebo diastolic
50
0
Schrader J, et al. Stroke. 2003;34:1699-1703.
ACCESS Outcomes
% Patients with Outcome
20
18
16
Candesartan
Placebo
18.7
14
12
10
9.8
8
6
7.2
4
2
2.9
0
Mortality
Vascular Events
Schrader J, et al. Stroke. 2003;34:1699-1703.
ACCESS Results
Cumulative Event Rate
.3
Cumulative
Event Rate
.2
Group
.1
Placebo
Placebo-censored
Candesartan
Candesartan-censored
0.0
0
100
200
300
400
Days Under Observation
Log rank test P = .0261
Schrader J, et al. Stroke. 2003;34:1699-1703.
Guidelines for Treating
Elevated Blood Pressure in
Acute Ischemic Stroke
• Treatment NOT recommended in most cases,
unless blood pressure is ≥220/≥120
– exceptions include hypertensive encephalopathy, aortic
dissection, MI, etc.
• Treatment to keep blood pressure <185/<110 in
patients who receive thrombolytic therapy (up to
24 hrs after Rx also)
• Use similar parameters for patients who require IV
heparin therapy (limited data)
Current Guidelines
• Moderately elevated blood pressure
(SBP >220 mm Hg/DBP 121–140 mm Hg)
– Labetalol 10-20 mg IV; repeat up to 300 mg
– Nicardipine 5 mg/hr IV
• Severe hypertension (DBP >140 mm Hg)
– Nitroprusside 0.5 mcg/kg/min IV
• Thrombolytic patients
– Labetalol or nitroglycerin paste PRETREATMENT
– Labetalol, nicardipine, nitroprusside DURING/AFTER Rx
– Labetalol drip 2-8 mg/min
Adams H, et al. Stroke. 2005;36:916-923.
HTN and Lytic Therapy
• Important to keep BP under control with
lytic therapy
• 24 hours post-lytic therapy is key time
• Failure to control BP is associated with
increased risk of hemorrhagic
complications
Preferred Agents
• Mild reductions needed
– Labetalol
– Nitroglycerin paste
– IV enalaprilat
– Diuretic
• More significant reductions needed
– IV nicardipine
– Sedation
– Remember to treat ICP
83
Theoretical Advantages of Dihydropyridine CCBs in
Acute Ischemia or Hemorrhagic Stroke
• May be neuroprotective in areas of sublethal
brain ischemia (penumbra)1-4
• Nicardipine IV allows rapid onset of effect and
accurate titration6
•
No significant increase in ICP
• Few if any cerebral, cardiac, pulmonary, allergic
or renal side effects6
1.
2.
3.
4.
5.
6.
Flamm ES, et al. J Neurosurg. 1998;68:393-400.
Allen GS, et al. N Engl J Med. 1983;308:619-624.
Petruk KC, et al. J Neurosurg. 1988;68:505-517.
Sabbatini M, et al. Clin Exp Hypertens. 2002;24:727-740.
Flamm ES. Am Heart J. 1989;117:236-242.
Cardene IV [package insert].
Refractory HTN in Ischemic
Stroke
• Rule out other medical problems
– Pain, infection, agitation, hypoxia
• Evaluate for increased ICP
– Brainstem/cerebellar strokes
– Herniation syndrome
Our Approach
• Stop most blood pressure medications
– Unclear if patients actually taking them
– Half the doses of any ß-blockers and clonidine
• Monitor blood pressure closely
• Administer IV fluids
– Patients often NPO and dehydrated on admission
• May begin gentle blood pressure meds around
discharge
– No large vessel stenosis
• Communicate with PCP on treatment plan
Conclusions
1. Hypertension after acute ischemic
stroke is common
2. Extremes of blood pressure are likely
deleterious in many cases
3. Gradual blood pressure adjustments
are generally recommended
4. Use antihypertensive agents that are
well tolerated and easy to titrate
Considerations for Blood
Pressure Control in
Aortic Aneurysm Surgery
Louis M. Guzzi, MD, FCCM
Section Chief, Critical Care Medicine,
Florida Hospital, Orlando, Florida;
Associate Professor of Anesthesiology,
Florida State University, Tallahassee,
Florida
Disclosures
• Speaker/Honoraria
ESP Pharma
GlaxoSmithKline
Pfizer Labs
Wyeth
Abdominal Aortic Aneurysm
• 13th leading cause of death in the U.S.
• Most common in men >65 years
• AAA causes 1.3% of all deaths among men
aged 65−85 years in developed countries
• Most abdominal aneurysms are
asymptomatic until rupture
Kniemeyer HW, et al. Eur J Vasc Endovasc Surg. 2000;19:190-196;
Gillum RF. J Clin Epidemiol. 1995;48:1289-1298; Sakalihasan N, et al. Lancet. 2005;365:1577-1589.
Abdominal Aortic Aneurysm −
Epidemiology
• Incidence has increased in the past
two decades
–
–
–
–
Smoking
Aging population
Introduction of screening programs
Improved diagnostic tools
• Prevalence in men > women
– Men between 1.3%−8.9%
– Women between 1.0%−2.2%
Lederle FA, et al. Arch Intern Med. 2000;160:1425-1430; Lindholt JS, et al. Euro J Vasc Endovasc Surg. 2000;20:369-373;
Lederle FA, et al J Vasc Surg. 2001;34:122-126; Singh K, et al. Am J Epidemiol. 2001;154:236-244;
Vardulaki KA, et al. Br J Surg. 2000;87:195-200; Sakalihasan N, et al. Lancet. 2005;365:1577-1589.
Abdominal Aortic Aneurysm −
Diagnosis
• Aneurysm = a permanent and irreversible localized
dilatation of a vessel
• Conventionally diagnosed if the aortic diameter is 30 mm
or more
• Dilatation affects the 3 layers of the vascular tunic
– Otherwise the dilation is called pseudoaneurysm
• Most are fusiform affecting the whole circumference of
the artery
• Aneurysms that only include part of the artery
circumference are termed saccular
Sakalihasan N, et al. Lancet. 2005;365:1577-1589.
Abdominal Aortic Aneurysm −
Diagnosis
• Usually asymptomatic
• Diagnosed incidentally during clinical exam
• Ultrasonography is the simplest and cheapest
diagnostic procedure
• CT scans helpful to determine surgical
treatment ─ endovascular or open surgery
• MRI
Sakalihasan N, et al. Lancet. 2005;365:1577-1589.
Abdominal Aortic Aneurysm −
Rupture
• Most aneurysms discovered
by screening are of small size
and do not need immediate
surgical repair
• In general, the risk of rupture
increases as the diameter of
the aneurysm enlarges
• Mortality rate for patients with
ruptured AAA is 65%−85%
• Approximately half of deaths
attributed to rupture occur
before the patient reaches the
surgical room
Lederle FA, et al. N Engl J Med. 2002;346:1437-1444; N Engl J Med. 2002;346:1445-1452;
Ashton HA, et al. Lancet. 2002;360:1531-1539; Sakalihasan N, et al. Lancet. 2005;365:1577-1589.
Proposed Management
of an Asymptomatic
Abdominal Aortic Aneurysm
Asymptomatic Abdominal Aortic Aneurysm
<4.5 cm
Follow-up
Ultrasonography
every 6 months
4.5–5.0 cm
Follow-up
Ultrasonography
every 3 months
or 6 months
5.0–5.5 cm
Surgery
Follow-up
Open or
Ultrasonography
endovascular
every 3 months
Repair if:
or 6 months
• Female patients
• Familial cases
• “Proved rapid
growth
• Positive PET scan
• High serum markers
(such as MMP-9)
>5.5 cm
Surgery
Open or
endovascular
Adapted from: Sakalihasan N, et al. Lancet. 2005;365:1577-1589.
Surgical Treatment of
Abdominal Aortic Aneurysm
Is endovascular repair preferable to open repair?
Open Surgical Treatment vs Endovascular Repair
• Advantages
• Advantages
– Used for >50 yrs
– Rate of failure 0.3%
• Disadvantages
– High rate of complications
– Long recovery
– Reduced rates of operative
morbidity and mortality
– Shorter initial hospital stay
– Shorter recovery time
• Disadvantages
– Rupture of AAA
– Late complications?
– Cost
Lederle FA. N Engl J Med. 2004;351:1677-1679; Sakalihasan N, et al. Lancet. 2005;365:1577-1589.
Major Outcomes in DREAM
Outcome
Open
Repair
(%)
Endovascular
Repair
(%)
Relative Risk
(95% CI)
Operative mortality
4.6
1.2
3.9
(0.9−32.9)
Operative mortality
and severe
complications
9.8
4.7
2.1
(0.9−5.4)
Operative mortality
and moderate or
severe
complications
23.6
18.1
1.3
(0.9−2.0)
Prinssen M, et al. N Engl J Med. 2004;351:1607-1618.
Hypertension
Management During
Abdominal Aortic
Aneurysm Surgery
Characteristics of
Perioperative Hypertension
• May last 2−12 hours
• Requires rapid intervention
• Systemic vasoconstriction often associated with
intravascular hypovolemia
• Mechanisms related to:
– Vasoconstriction and tachycardia secondary to
increased circulating catecholamines
– Vasoconstriction secondary to activation of the RAAS
Mansoor GA, Frishman WH. Heart Dis. 2002;4:358-371.
Goal of Therapy for
Perioperative Hypertension
• Prevent postoperative hypertension (POH)
which is a significant risk factor for1,2
– Myocardial ischemia and heart failure
• ↑ Left ventricular (LV) afterload leads to ↑ MVO2
– Cerebrovascular events
• Intracerebral hemorrhage
• Postcraniotomy hypertension [SBP >160 mm Hg OR
DBP >90 mm Hg] correlates with intracerebral bleeding3
– Bleeding at suture sites
1. Oparil S, et al. Am J Hypertens. 1999;12:653-666.
2. Neely C. In: Goldmann D, et al, eds. Perioperative Medicine. New York, NY: McGraw-Hill; 1994:531-542.
3. Basali A, et al. Anesthesiology. 2000;93:48–54.
Properties of an Ideal
Antihypertensive Agent
•
•
•
•
•
•
•
•
•
Treats underlying pathophysiology
Rapid onset of action
Predictable dose response
Titratable to desired BP
Minimal dosage adjustments
Minimal adverse effects
No increase in intracranial pressure (ICP)
Preserves glomerular filtration and renal blood flow
Acceptable cost to benefit ratio
Oparil S, et al. Am J Hypertens. 1999;12:653-664.
Levy JH. Anesthesiol Clin North Am. 1999;17:567-579.
Acute Antihypertensive
Treatment During Anesthesia
• Anesthesia may alter pharmacokinetics of
antihypertensive agents1
• Bolus dosing1,2
–
Shorter preparation time
–
Decreases time to effect
–
Shorter exposure to medications may reduce
postoperative monitoring and critical care
1. Cheung AT, et al. Anesth Analg. 1999;89:1116-1123.
2. Cheung D, et al. Am Heart J. 1990:119:438-442.
Differential Diagnosis for POH
• Blood pressure
measurement error
– Non-invasive
• Cuff size
• Cuff placement
– Intra-arterial
• Transducer at level
of heart
• Calibrate to accurate
zero
• Pain
• Full bladder
• Hypothermia
– Vasoconstrictive response
• Hyperthermia
• Hypermetabolic state
• Hypoxia
• Hypercarbia
Bessman, ES. Invasive Monitoring, Pacing Techniques, and Automatic and Implantable Defibrillators.
In: Tintinalli, J, Emergency Medicine: A Comprehensive Study Guide, 5th ed. McGraw-Hill, 2000;403.
Acute Hypertension:
Treatment Options
Circulating and local factors acting on
endothelium and vascular smooth muscle
BP
Abrupt  BP
Treatment
Options
=
SVR
X
CO
Abrupt  SVR
(SV x HR)
ACE inhibitors
α-blockers
Calcium-channel blockers
Dopamine agonists
Nitrovasodilators
β-blockers
Treatment Options −
Sodium Nitroprusside
• Potent venous/arterial vasodilator
• Immediate onset, 1- to 2-minute duration
• May cause nausea, vomiting, muscle twitching, sweating,
•
•
•
•
•
thiocyanate and cyanide poisoning
May  ICP
Requires special delivery system
Usually requires direct artery pressure monitoring
Causes significant venous pooling - watch in dehydrated
patients
Abrupt cessation may cause coronary steal in patients
with coronary artery disease
The 6th Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2416.
Treatment Options
Nitroglycerin
• Vasodilator
• Onset, 2–5 minutes
• Duration, 3–5 minutes
• May cause headache, vomiting, methemoglobinemia
• Tolerance with prolonged use
• Special considerations
– Acute left ventricular failure
– Coronary ischemia
• IV form requires special delivery system
• May decrease CBF
The 6th Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2416.
Nitrovasodilators
Nitroprusside vs Nitroglycerin
Drug
Nitroprusside
Nitroglycerin
Rapid onset of peak effect
++++
+++
Afterload reduction
++++
+
Preload reduction
++
++++
Coronary steal reported
+
0
Coronary dilation – large vessel
+
++++
Coronary dilation – small vessel
+/-
+/-
Tachycardia
++
++
Potential for symptomatic
hypotension
++
+++
Ease of administration
++
+++
++++
0
Cyanide toxicity
Pepine CJ. Clin Ther. 1988;10:316-325.
Treatment Options −
- and -adrenergic Blockers
Drug
Onset of
Action
Duration of
Action
Adverse
Events
Special
Considerations
Labetalol
5–10 min
3–6 hours
Heart block
Orthostatic
hypotension
Most hypertensive
emergencies
except acute heart
failure
Hypotension
Nausea
Aortic dissection
Perioperative
Esmolol
1–2 min
10–20 min
The 6th Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2416.
-blocker Treatment Option −
Esmolol
• Advantages
– Treats tachycardia and hypertension
– Short duration of effect
– Preserves myocardial O2 supply
• Disadvantages
– Bradycardia
– Depresses myocardial contractility
– Reactive airway disease
– Continuous monitoring of BP/HR required
Oparil S, et al. Am J Hypertension. 1999;12:653-664.
Combined - and -blocker
Treatment Option − Labetalol
• Properties
– No reduction in cerebral, renal, or coronary blood flow
– Intermediate time to onset
– Moderate effect/not easily titrated
– May exacerbate reactive airway disease
– Less potential for bradycardia
– Can depress cardiac contractility
– Ratio of α- to β- blockade, 1:7
Hoffman BB. In: Hardman JG, Limbird LE, eds. Goodman and Gilman’s Pharmacological
Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill;1997:215-268.
Le Bret F, et al. J Cardiothorac Vasc Anesth. 1992;6:433-437.
Treatment Options −
Calcium-channel Blockers (CCBs)
Drug
Onset of
Action
Duration
of Action
Adverse
Events
Special
Considerations
Nicardipine
~2.7 min
15–30 min;
may
exceed 4
hours
Tachycardia
Most hypertensive
emergencies
Headache
Flushing
Local phlebitis
The 6th Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2416.
Cardene IV prescribing information [package insert]. PDL BioPharma Inc. 2006
IV Dihydropyridine CCB −
Nicardipine
• Only IV dihydropyridine CCB available in U.S.
• Arterial vasodilator1
• Produces significant decreases in SVR2-5
• More selective for vascular smooth muscle than
cardiac muscle1
• No AV nodal depression
• Minimal myocardial depression
• Cerebral and coronary vasodilator
• No significant increase in ICP6
1. Clarke B, et al. Br J Pharmacol. 1983;79:333P; 2. Lambert CR, et al. Am J Cardiol. 1987;60:471-476; 3. Silke B, et al. Br J
Clin Pharmacol. 1985;20:169S-176S; 4. Lambert CR, et al. Am J Cardiol. 1985;55:652-656; 5. Visser CA, et al. Postgrad
Med J. 1984;60:17-20; 6. Nishiyama T, et al. Can J Anaesth. 2000;47:1196-1201.
Change in MAP (mm Hg)
Plasma Nicardipine Concentration (ng/mL)
Nicardipine − Pharmacokinetics of
IV Bolus Administration
150
100
10
0
-10
-20
-30
-40
-50
50
120 140
Nicardipine concentration (ng/mL)
0
20
40
60
80
100
Group 1: 0.25 mg
Group 2: 0.5 mg
Group 3: 1.0 mg
Group 4: 2.0 mg
0
0
0.5
1.0
1.5
2.0
2.5
Time after Drug Administration (hrs)
3.0
3.5
Adapted from Cheung AT, et al. Anesth Analg. 1999;89:1116-1123.
Calcium Channel Blockers
Nicardipine
Diltiazem
Verapamil
(dihydropyridine)
(benzothiazepine)
(phenylalkylamine)
Peripheral
Vasodilation1
+++++
+++
+++
Coronary
Vasodilation2
+++++
+++
++++
Suppression
of SA Node2
+
+++++
+++++
Suppression
of AV Node2
0
++++
+++++
Suppression
of Cardiac
Contractility2
0
++
++++
The relative effects are ranked from no effect (0) to most prominent (+++++).
1. Frishman WH, et al. Med Clin North Am. 1988;72:523-547.
2. Adapted from Goodman and Gilman’s: The Pharmacologic Basis of Therapeutics. 9th ed. 2001.
Nicardipine vs Nitroprusside
Drug
Nicardipine
Nitroprusside
Rapid onset of peak effect
++++
++++
Afterload reduction
++++
++++
Preload reduction
0
++
Coronary steal reported
0
+
Coronary dilation – large vessel
+++
+
Coronary dilation – small vessel
+++
+/-
Tachycardia
+
++
Potential for symptomatic
hypotension
+
++
++++
++
0
++++
Ease of administration
Cyanide toxicity
Summary
• Optimal management of blood pressure
must consider the disease process and the
patient’s history
• Predictability of response is essential
• Patients best treated with titratable IV
antihypertensive agents
• The majority of complications are from
overaggressive lowering of blood pressure