Transcript Perioperative Hypertension, When does it matter by

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Sukh Brar MD FRCPC
Royal Columbian Hospital
October 26th, 2013
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Definitions
Prevalence
Pathophysiology
Preoperative
Intraoperative
Postoperative
Treatment
Outcomes
Summary
*
*Seventh Joint National Committee on the
Detection, Evaluation and Treatment of High
Blood Pressure (JNC VII) [2003]
*British Hypertension Society Guidelines [1999]
*World Hypertension Society/International
Society of Hypertension (WHO/ISH) guidelines
*Differ w.r.t inclusion of target organ damage
and the limit for initiating treatment
Acute and Chronic Hypertension:
Clinical Context
Chronic
Hypertension
Hypertension
Emergencies
Acute
Hypertension
Syndromes
Classification of Severe Hypertension
*Uncomplicated Stage 3 HTN
*Hypertensive Crises
*Urgencies
*Emergencies
JNC VI. Arch Intern Med 1997;157:2413-2448
Hypertensive Urgencies:
Defined by Effects or Setting
Hypertension with
 Progressive target organ damage
Hypertensive Emergencies:
Defined by Effects
Severe HTN with acute end organ
damage:







Central nervous system
Myocardial ischemia or heart failure
Renal damage
Active hemorrhage
Eclampsia
Microangiopathic hemolytic anemia
Aortic dissection
Hypertensive Emergencies:
Hypertensive Emergencies:
*Acute Hypertension
Acute Hypertension
Hypertensive
Urgency
Hypertensive
Emergency
Perioperative
Hypertension
Severe HTN
WITHOUT acute
end-organ damage
Severe HTN
(BP >180/120 mm Hg)
WITH end-organ
damage
HTN* occurring prior
to, during, or following
surgical procedures
Requires BP control
over several
days-weeks
Requires immediate,
aggressive BP control
Requires immediate
BP control
* Poorly defined
*
*Hypertension occuring in the pre-operative,
intra-operative or post-operative period.
*Importance:
*Increased risk of cardiovascular events
*Increased post-operative morbidity and mortality
*Association with end-organ damage
Percent of Population
Prevalence of HTN by Age
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
0.0
83.8
HTN Risk > 115/75
73.9
63.6
49.1
69.5
55.4
37.5 37.4
23.2
11.2
18.3
6.4
20-34
35-44
45-54
Men
NHANES: 1999-2004. Source: NCHS and NHLBI.
55-64
Women
65-74
75+
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* Physiology Perioperative Hypertension
* Hyperadrenergic response to surgery
* Increase SVR, decrease preload
* Rapid intravascular volume shifts
* Renin angiotensin activation
* Adrenergic stimulation (cardiac & neural)
* Serotonergic overproduction
* Baroreceptor denervation
* Altered cardiac reflexes
* Inadequate anesthesia
* Cross clamp
Marik P. Chest. 2007;131:1949-1962.
SVR;
Humoral
vasoconstrictors
Mechanical stress
Endothelial injury
Permeability
Coagulation
Fibrinoid necrosis
* Remodeling
Normal
Large Arteries (hypertrophic) in PPH
Outward
Hypertrophic
remodeling
Inward
Eutrophic
remodeling
Small Arteries (eutrophic) in diastolic HTN
Courtesy of Schiffrin EL.
Courtesy of Schiffrin EL.
Pathogenic Role of Mechanical Forces
Oscillatory Shear Stress*
Occurs sites prone to lesion formation
Carotid bulb
Prox. Coronaries
Distal aorta
High Shear  Atheroprotective
Low Shear  Atherogenic
*Wide PP  Augments Oscillatory Shear
Pressure/Stretch
Elevated Stretch with Hypertension
Pro-Inflammatory / Atherogenic
The Endothelium Modulates Vascular Tone
O
NO
X
Endogenous
vasodilators
PGI2
Courtesy of JJ Ferguson III, MD.
O2  -
Catecholamines
AT-II
TxA2
Endogenous
vasoconstrictors
Endothelium
Aldosterone
ADH (vasopressin)
Proposed Vascular Pathophysiology
of Hypertensive Urgency
CAMs
NO
Endogenous
vasodilators
(-)
PGI2
(+)
O2  -
Catecholamines
AT-II
Endogenous
TxA2
vasoconstrictors
ET1
Aldosterone
ADH (vasopressin)
Acute ↑ BP triggers ↑ cellular adhesion molecular expression
Vaughan CJ, Delanty N. Lancet. 2000;356:411-7.
Courtesy of JJ Ferguson III, MD.
Proposed Vascular Pathophysiology
of Hypertensive Emergency
TxA2, PAI-1, TF
• Overwhelmed control of vascular tone leads to coagulation cascade activation
• Loss of endothelial activity coupled with coagulation and platelets promotes DIC
Vaughan CJ, Delanty N. Lancet. 2000;356:411-7.
Courtesy of JJ Ferguson III, MD.
* Pathophysiology of Acute Hypertensive
Syndromes
↑BP
Mechanical
stress on the
vessel wall
Further release of
humoral
vasoconstrictors
Fibrinoid necrosis of
small blood vessels
Release of Local
humoral
vasoconstrictors
Augments HTN
Pressure
natriuresis
Endothelial
damage
Volume
depletion
RAAS
activation
Activation of the
clotting cascade
Major physiologic
derangements
Vasopressin
endothelin
catecholamines
Courtesy of JJ Ferguson III, MD.
Sympathetic Nervous System Regulation of Blood Pressure
CNS
Adrenal
Gland
Baroreceptor
Reflexes
Adrenergic
Catecholamines
Tone
Veins
Capacitance
Arteries
Resistance
Afterload
Preload
Heart
Cardiac Output
Volume/Pressure
Renin/Angiotensin
Blood Pressure
Kidney
Renin-Angiotensin-Aldosterone Regulation of Blood Pressure
Renin
Substrate
Angiotensin I
Angiotensin II
Renin
Aldosterone
Kidney
Sodium &
Water
Reabsorption
Adrenal Cortex
Vasoconstriction
Blood Pressure
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*CVS effects:
*Increased
BP→ ↑ afterload & myocardial oxygen
demand → myocardial oxygen supply and demand
imbalance.
*Chronic ↑ BP → myocardial hypertrophy → myocardial
oxygen supply and demand imbalance
*Hypertrophied
myocardium → decreased compliance
→ abnormal diastolic filling
*Effects of Perioperative Hypertension
*CNS effects:
*Increased risk of stroke
*Impaired cerebral autoregulation
*Especially important in neurosurgical patients
*Effects on renal function
*Effective control of BP prevents renal dysfunction
*Intraoperative urine output monitoring for assessment
perioperative renal function
of
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* Patients with well-controlled HTN preoperatively less
likely to experience intraoperative BP lability & postop
complications
* Recent UpToDate Meta-Analysis suggests that in
patients with hypertension, elective surgery does not
need to be delayed as long as the blood pressure is
below 170/110 mmHg.
* Patients taking chronic antihypertensive meds should
CONTINUE taking meds until time of Sx.
UpToDate June 27, 2013: Perioperative management of hypertension
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Comfere T et al. Anesth and Analg 2005; 100: 636-44
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Kihara et al. Anesth Analg 2003; 96: 890-5
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Prys-Roberts C et al. BJA 1971; 43: 122-137
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* 17,638 consecutive day surgery patients
* Hypertension and intraoperative adverse events
* Any event
* Cardiovascular events
* Hypertension
* Arrhythmia
* Hypotension
* Bradycardia
* Tachycardia
OR 2.2 (1.4-3.6)
OR 2.5 (1.5-4.2)
174 (76%)
21 (9.2%)
14 (6.1%)
13 (5.7%)
7 (3.1%)
Cheung F et al. BJA 1999; 83: 262-70
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* Acute BP elevations > 20% considered
hypertensive emergency
* Chronic Htive patients more likely to be labile
* Result in increased risk of postop mortality &
renal failure, especially during CV procedures
* Htive events more commonly during carotids >
abdominal aorta > peripheral vascular >
intraperitoneal > intrathoracic surgeries.
* If known LV dysfunction +/- CAD, increased risk
of myocardial ischemia or CHF.
Perioperative hypertension: Diagnosis and Treatment. Varon 2011 NJCC
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* More common in preop Htive patients & vascular Sx
* SBP > 190 mmHg and/or DBP > 100 mmHg on 2 consecutive
readings post surgical intervention
* Occur in first 20 minutes of postop period
* Resolution can require up to 3 hours
* If left untreated, increases risk cv ischemia, AMI, CVA &
bleeding
Perioperative hypertension: Diagnosis and Treatment. Varon 2011 NJCC
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ER/CC
OR
PACU
Myocardial Ischemia
Vascular clamping
(afterload)
Pain
Hypercarbia/
Hypoxemia
Reduced organ
perfusion
-Renal
-Cerebral
Hyperdynamic
Myocardium
Anxiety
Distended
Bladder
Malignant
Hyperthermia
Hypervolemia
Diastolic Dysfunction
Vasoconstriction
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*Preoperative hypertension
*Withdrawal of antihypertensive medications
*Pain
*Emergence Delirium/Agitation
*Hypoxia
*Hypercarbia
*Hypothermia
*Hypervolemia
*Type of Surgery
*
*Hypertensive crises
*Hypertensive encephalopathy
*Acute ICP elevation
*Acute Aortic Dissection
*Acute pulmonary edema with LVF
*Acute MI/Unstable Angina
*Eclampsia
*Acute Renal Failure
*Pheochromocytoma crisis
Treatment Guidelines*
 Hypertensive Emergencies
Initiate treatment immediately
 Hypertensive Urgencies
Reduce BP within a few hours
 Non-urgent Stage 3 Hypertension
Reduce BP within one week
*JNC VI. Arch Intern Med 1997;157:2413-2448
*
Reduce MAP by 20-25%
or
Reduce MAP to 110-120 mmHg
(whichever is higher)
Achieve target BP within 2-4 hours
* Goals for an Ideal Antihypertensive Agent in
Setting of Cardiac Surgery
Desirable Properties for Intravenous Agent
*Rapid onset of action
*Predictable dose response
*Titratable to desired BP
*Highly vascular selective
*Maintain stroke volume and cardiac output
*Rapidly reversible
*Low risk of overshoot hypotension
*Low risk of adverse reactions
Levy JH. Anesthesiol Clin North Am. 1988;17:587-678.
Oparil S et al. Am J Hypertens. 1999;12:653-664.
* Therapeutic Approaches to Arterial
Vasodilation: Armamentarium
Treatment Options
* ACE inhibition
* Alpha-1 adrenergic blockade
* Calcium channel blockade
* Dopamine-1 stimulation
* Ganglionic blockade
* Cyclic nucleotide stimulation
* PDE inhibition
* Potassium channel modulation
Levy JH: The ideal agent for perioperative hypertension. Acta Anaesth Scand 1993; 37(S):20-25.
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*
*
* 3rd generation dihydropyridine CCB
H
* Approved for HTive crisis & when need tight BP control
* Ultra-short-acting, selective arteriolar vasodilator
* Half life of 1 minute!!!
* BP lowering effects seen within 2-3 minutes of infusion
*
* Rapidly metabolized by red blood cell esterases
* Metabolism not affected by renal or hepatic function
* Stroke volume and CO usually increase
* Increases coronary blood flow
* Protects against ischemia/reperfusion injury
*
* 2nd generation dihydropyridine CCB
* High vascular and cerebral/coronary vasodilation
* Onset of action 5-15 min & duration 4-6 hours
* Reduces cardiac & cerebral ischemia
*
* Dosage independent of weight  initial infusion of 5
mg/hr  increase by 2.5 mg/hr q5min to max 15 mg/h
* Proven highly effective for postop HTN.
* BP control typically within 10-15 min & few changes
* Increases CO & CBF & improves CV02 supply vs demand
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* Potent venodilator & only affects arterial tone and high
doses
* In volume depleted patients, NTG may cause severe
hypotension & reflex tachycardia
* Reduces BP by reducing preload and CO
* Increases severity of hyperadrenergic state found in APH.
* High doses may cause methemoglobinemia
* Low doses may support IV antihypertensive therapy in APH
pts with ACS, RHF or pulmonary edema
*
* Arterial and venous vasodilator, decreases both afterload
and preload.
* Very potent agent, with an onset of action of seconds,
duration 1-2 minutes and a T1/2 of 3-4 minutes.
* Concerns with cyanide toxicity! (44% cyanide by weight)
* In patients with CAD, a significant reduction in regional
blood flow (coronary steal) can occur.
*
* Can reduce renal blood flow and renal function
* Decreases cerebral blood flow & increases ICP
* Data suggests that SNP in excess of 4 mcg/kg/min for
as little as 2-3 hours may lead to cyanide toxicity.
* ONLY use when other IV antihypertensive agents are
unavailable, or in specific clinical circumstances with
normal renal and hepatic function. (< 2 mcg/kg/min).
*
* Direct arteriolar vasodilator having little or no effect on
venous circulation.
* Known to increase circulating catecholamines!
* Rapid onset (within 5-15 min)
* Decrease in BP can last up to 12 hours
* Can be difficult to titrate BP responses
* Recent meta-analysis in OB = increased complications!
*
* Unique among IV BP agents in mediating vasodilation by
acting on peripheral dopamine-1 receptors.
* 10 times more potent than dopamine!
Mediates renal
arterial vasodilation & promotes natriuresis and diuresis.
* Onset of action is within 5 minutes & max response within
15 minutes.
* Duration of action is 30-60 minutes & no rebound HTN
when stopped.
*
* Quickly metabolized by conjugation in liver
* After starting at 0.1 mcg/kg/min, titrate q 15min
* Infusion range of 0.03 – 0.3 mcg/kg/min controls BP
* Particularly benificial in pts. With impaired renal
function.
* HTive crisis + Renal Dysfunction = 1st or 2nd choice agent!
*
* Combined selective alpha-1 and nonselective betaadrenergic receptor blocker
* Alpha- to beta-blocking ratio of 1:7.
* Metabolized by the liver to inactive molecule
* BP lowering effect begins within 2-5 minutes after
administration
* Peak at 5-15 minutes & lasts 2-4 hours.
*
* Heart rate either maintained or slightly reduced
* Labetolol maintains CO & decreases SVR w/o reducing peripheral
blood flow (maintains cerebral, renal and coronary blood flow)
* Loading dose of 20mg & repeated incremental doses of 20-80mg
given at 10 minute intervals to reduce BP
* After initial loading dose, using infusion at 1-2 mg/min &
titrating until hypotensive effect quite effective.
* Found to be safe and effective with response rate of 85 – 100%
*
* Particularly useful in severe postop HTN with tachycardia
* Ultra-short-acting cardioselective, beta-adrenergic blocking
agent.
* Onset of action within 60 seconds, duration of action 10-20
minutes.
* Metabolism of esmolol through rapid hydrolysis of ester linkages
by red blood cell esterases
* Not dependent on renal or hepatic function.
*
* Ideal beta-adrenergic blocker in postoperative patients
who are at risk for CAD
* Available for both IV use as bolus & infusion
* Suitable agent in situations where CO, HR, BP increased
* Typically given as 0.5 – 1.0 mg/kg loading dose over 1
minute & infusion at 50 mcg/kg/min & increasing up to
300 mcg/kg/min as necessary.
*
* RAAS hyperactive during/after major surgery & likely
important mediator of microvascular ischemic injury
* Antagonism of RAAS with ACEI may afford protection against
cerebrovascular and renal adverse outcomes
* 1.25mg over 5 minutes every 6 hours titrated by increments
of 1.25mg at 12-24 hours to a maximum of 5mg every 6 hours.
* Onset of action 15 minutes, peak effect in 1 hour and
duration of action is 6 hours.
*
* In context of hypertensive emergencies, IV long-acting
ACEI such as enalaprilat NOT recommended due to
unpredictable antihypertensive effects.
* Can use preemptively in patients undergoing craniotomy
for control of HTN during emergence.
* Can combine with esmolol, labetolol or nicardipine to
improve postoperative BP control.
►
1500 pts, 21 hospitals, 79% therapy in ED
►
Median age 58, Women 49%, AA 58%
►
Initial BP 201/110
►
90% HTN, 33% kidney history , 17% drug
abuse
Reason for Admission
HTN
Neuro
ACS
CHF
100.0%
Time to Initiation of 96.7%
IV Therapy
100%
87.4%
90%
80%
72.4%
70%
60%
50%
45.3%
40%
30%
20%
10%
0%
Within 1
Hour
Granger et al. SCCM February 2008
Within 3
Hours
Within 6
Hours
Within 12
Hours
Within 24
Hours
►
1500 pts, 21 hospitals, 79% therapy in ED
►
Median age 58, Women 49%, AA 58%
►
Initial BP 201/110
Reason for Admission
HTN
Neuro
ACS
CHF
►
90% HTN, 33% kidney history , 17% drug
abuse
50
40
Time to Initiation of IV Therapy
40.1
40.2
30
20
10
6.5
10.4
8.4
0
New Endorgan
Damage*
Granger et al. SCCM February 2008
In-hospital
Death*
Admit to
90-day Death*
90-day
Readmission
90-day
Readmission
Due to HTN
Systolic BP Control Over 24 Hours by First
IV Antihypertensive
Change from qualifying (%)
0
Enalapril*
Hydralazine*
Labetolol*
Metoprolol*
Nitroglycerin*
Nicardapine*
Nipride*
-10
-20
-30
-40
0
2
4
Regardless of 1st antihypertensive
50-75% of pts required > one agent
Granger et al. SCCM February 2008
6
8
10
12
14
16
Time since IV initiation (h)
18
20
22
n=982
*Median
24
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“There are known knowns; there are
things we know that we know.
There are known unknowns; that is to say,
there are things that we now know we
don't know.
But there are also unknown unknowns –
there are things we do not know we don't
know.”
Former United States Secretary of Defense, Donald Rumsfeld – February 2002
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*Each 10mmHg INCREASE PP
* 11% increase stroke
* 16% increase death
* 12% increase in recurrent MI
*Each 10mmHg RISE MAP = 20% increase stroke!
Hypertension,1999;34:375-80
* Systolic BP Control Over 24 Hours
SBP
135 – 145 mmHg
Upper
Lower
65 - 75 mmHg
0
6
12
Time (hours)
18
24
Excursions in Perioperative BP
Control Related to Increased 30-day Mortality
Odds
Ratio
95% CI
[Lower Limit,
Upper Limit]
I mm Hg x 60 min
1.20
[1.06, 1.27]
2 mm Hg x 60 min
1.43
[1.13, 1.61]
3 mm Hg x 60 min
1.71
[1.20, 2.05]
4 mm Hg x 60 min
2.05
[1.27, 2.61]
5 mm Hg x 60 min
2.46
[1.35, 3.31]
40
Data on file, The Medicines Company.
41
42
43
44
Perioperative BP Lability Predicts Mortality in
Patients Undergoing Cardiac Surgery
►
►
Analysis of DUKE
Heart Center
database in pts
undergoing CT
surgery
● N =5238
● 3.1M BP
evaluations
AUC (95135mmHg)
predictive of 30day mortality
Aronson S et al. SCCM 2008. Poster #557.
P=0.0139
OR =1.02 per 100 mm Hg x min
95% CI [1.004-1.037]
Mean Duration of Excursions
Minutes SBP > 135 or < 95mmHg per incident
Samples (n=7187)
DUKE patient population
Development & validation
datasets
P-Value < 0.0001, O.R.-1.068 (1.036-1.102)
Cardiac Surgery Patients –
Inadequate BP Control
Increased risk of 30-day
death, CVA, MI and renal dysfunction vs patients with tight BP control
The worse the control, the poorer the outcomes.
SCA 2008
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* 1. Imperative to urgently treat BP >180/110 perioperatively when associated
with end organ impairment or damage.
* 2. Can proceed with elective surgery when BP < 170/110 and minimal
comorbidities without increased postop morbidity/mortality. Continue talking
majority of anti-HTN meds preop.
* 3. Pathophysiology of HTN involves interactions with many organ systems
including brain, heart, kidneys, adrenals and endothelium. Periop HTN leads to
increased CVS, CNS, Renal and other end organ damage and increased
morbidity
* 4.
Chronic HTN patients much more labile throughout periop period with
potential for hypoperfusion if too aggressively treated.
* 5.
Postop HTN >190/100 occurs within 20 minutes & may require several hours
to resolve. Many agents can be used with significant risks of excessive relative
hypotension.
*
* 6. Quickly identify underlying mechanism of hypertension and treat.
* 7. Reduce MAP 20-25% or MAP <110-120 mmHg in HTive urgency/emergency w/i 2-4
hours.
* 8. Clevidipine, Esmolol are ideal short acting titratable agents.
Labetolol is highly
effective including as an infusion and fenoldopam is useful if coexisiting renal disease.
* 9.
Majority of APH patients require 2-3 drugs and 2-4 hours to obtain adequate control.
Potential for significant hypotension at 4-8 hour mark with many agents.
* 10.
ECLIPSE trial suggests that more stringent targets of SBP 75 – 145 mmHg can reduce
30 day mortality. Time spent outside this range incrementally increases risks of death,
CVA, MI and renal dysfunction.
* 11.
Interdisciplinary rounds in the PACU facilitates improved quaility of care, reduces
variation in care and may improve outcomes.
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*3.
*4.
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*6.
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*8.
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Definitions
Prevalence
Pathophysiology
Preoperative
Intraoperative
Postoperative
Treatment
Outcomes
Summary
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1. Intraoperative Blood Pressure. Charlson et al., Ann Surgery 1990. Vol 212 (5): 567-580.
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3. The Relationship between Acute Pressure Derangements & Comprehensive Vascular Protection in the Setting of CT
Surgery. Aronson S. Dept. of Anesthesiology DUHS.
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4. Perioperative Hypertension: Diagnosis and Treatment. Soto-Ruiz KM et al. NJCC Vol 15 (3) June 2011.
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7. Perioperative Management of Hypertension. Kaplan et al. UpToDate Jun 27, 2013.
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10. ACC/AHA 2007 Guidelines on Perioperative Cardiac Evaluation and Care for Noncardiac Surgery… Circulation
2007: 116: e418-e500.
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11. Hypertension in the Inpatient Setting: Mechanisms and Pharmacologic Management. PPT.
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14. Esmolol Reduces Perioperative Ischemia in Noncardiac Surgery: A Meta-analysis of Randomized Controlled
Studies. Landoni G et al. Journal of Cardiothoracic and Vascular Anesthesia, Vol 24, No. 2 (April 2010): 219-229.
2. Risks of General Anesthesia and Elective Operation in the Hypertensive Patient. Goldman L and Caldera DL.
Anesthesiology 50: 285-292, 1979.
5. Should Peri-Operative Hypertension Lead to Postponing Surgery. Howell, S. University of Leeds.
6. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC – 7). US Dept. of HHS May 2003.
8. Treatment of Specific Hypertensive Emergencies. Kaplan et al. UpToDate Feb 6, 2012.
9. The ECLIPSE Trials: Comparative Studies of Clevidipine to Nitroglycerin, Sodium Nitroprusside, and Nicardipine for
Acute Hypertension Treatment in Cardiac Surgery Patients. IARS. Vol 107 (4), October 2008.
12. Perioperative Management of Hypertension. Costas Tsioufis. Department of Cardiology, University of Athens. PPT
13. Perioperative Blood Pressure Variability in the Treated Hypertensive Patients. Kiyohara et al. Clinical and
Experimental Hypertension, 2013: 35 (4): 291-294.
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15. Hypertension Crisis. Papadopoulos et al. Blood Pressure. 2010; 19: 328-336.
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18. Clevidipine: A New Intravenous Option for the Management of Acute Hypertension. Ndefo et al. Am J Health-Syst. Pharm.
2010; 65: 351-60.
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19. Peri-operative hypertension and Acute hypertensive crises. Dr. Kunal Karamchandani. PPT
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21. Interdisciplinary Rounds in the Postanesthetic Care Unit. Hoke N and Falk S. Anesthesiology Clin 30 (2012) 427-431.
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23. Perioperative Hypertensive Crises: Newer Concepts. Fontes ML & Varon J. International Anesthesiology Clinics 2012Volume
50, Number 2, 40-58.
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24. Assessment and Nursing Management of Hypertension in the Perioperative Period. Nunnelee JD & Spaner SD. Journal of
PeriAnesthetia Nursing Vol 15; No 3 (June); 2000: pp. 163-168.
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25. Perioperative hypertension: A review of current and emerging therapeutic agents. Marik PE & Varon J. Journal of Clinical
Anesthesia (2009) 21, 220-229.
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26. Management of Perioperative Hypertensive Urgencies With Parenteral Medications. Ahuja K. Charap MH. Journal of
Hospital Medicine 2010; 5: E11-E16.
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27. Strategies for Managing Perioperative Hypertension. Desai RG et al.Current Hypertension Reports 2009; 11: 173-177.
16. Studying the Treatment of Acute hyperTension (STAT) Registry. Granger et al. Am Heart J 2009; 158: 599-606.
17. Improved Perioperative Blood Pressure Control Leads to Reduced Hospital Costs. Getsios et al. Expert Opin. Pharmacother.
(2013) 14(10): 1285-1293.
20. Hemodynamic Control and Clinical Outcomes in the Perioperative Setting. Aronson S and Varon J. Journal of
Cardiothoracic and Vascular Anesthesia, Vol. 25, No 3 (June), 2011: pp. 509-525.
22. Hemodynamic and Related Challenges: Monitoring and Regulation in the Postoperative Period. Plante A et al.
Anesthesiology Clin 30 (2012) 527-554.
28. Perioperative Hypertension: Defining At-Risk Patients and Their Management. Lien SF & Bisognano JD. Curr Hypertens Rep
(2012) 14; 432-441.