manejo de la crisis hipertensiva - colegio de médicos de la crisis hipertensiva 2… · disminuir...

Manejo de la Emergencia Hipertensiva

JONATHAN POVEDA MD

HSJD/CLINICA BIBILICA

2014

OBJETIVOS

1. Diagnosticar y tratar en forma precoz y oportuna la

descompensación hipertensiva arterial.

2. Investigar, diagnosticar y tratar la causa que origina la crisis

hipertensiva.

3. Identificar, evitar y tratar los daños irreversibles de órganos

blancos.

4. Establecer los lineamientos en el diagnóstico y tratamiento del

paciente con crisis hipertensiva.

5. Disminuir la morbilidad y mortalidad en la crisis Hipertensiva.

Chronic

hypertension

Hypertensive

emergencies

Acute

vascular

reactivity

Courtesy of S Aronson, MD.

Acute and chronic hypertension: Clinical

context

Sympathetic overactivation drives acute

hypertension

Calhoun DA, Oparil S. N Engl J Med. 1990;323:1177-83.

Cheung AT. J Card Surg. 2006;21(suppl):S8-14.

Weitz HH. Med Clin North Am. 2001;85:1151-69.

Sympathetic overactivation

Acute hypertension

Arteriosclerosis Chronic hypertension

Important triggers include clonidine withdrawal, cocaine abuse,

certain surgical settings

Perioperative ISH associated with

postoperative adverse events

Event rate (%) Odds ratio

No ISH

(n = 1457)

ISH

(n = 612)

Renal failure/insufficiency 6.7 8.8 1.3 (0.9-1.9)

Stroke 6.3 10.1 1.7 (1.2-2.3)

LV dysfunction 29.1 34.3 1.3 (1.0-1.6)

Renal failure/insufficiency,

stroke, LV dysfunction, death

33.2 40.9 1.4 (1.1-1.7)

Aronson S et al. Anesth Analg. 2002;94:1079-84.

N = 2069 scheduled for CABG

ISH = isolated systolic hypertension

Acute hypertension:

Subgroups and settings

Acute hypertension

Hypertensive

urgency

Hypertensive

emergency

Perioperative

hypertension

Operating room

Postanesthesia care Emergency

department

Intensive care

unit

JNC 7 definitions

Hypertensive emergency BP >180/120 (240/120) mm Hg

complicated by evidence of

impending or progressive end-organ

damage

Hypertensive urgency Severe elevation in BP without

progressive end-organ damage

Chobanian AV et al. Hypertension. 2003;42:1206-52

-Hypertensin Primer 2008 AHA

.

Hypertensive urgencies/emergencies:

Patients and organ systems at risk

Cardiopulmonary

• ADHF • ACS • Acute pulmonary edema • Acute aortic syndromes Neurovascular • Hypertensive encephalopathy • Stroke

Ocular

• Papilloedema

Renal

• Acute renal dysfunction

Calhoun DA, Oparil S. N Engl J Med. 1990;323:1177-83.

Marik PE, Varon J. Chest. 2007;131:1949-62.

ACS = acute coronary syndrome

ADHF = acute decompensated heart failure

1% of hypertensives (1990 data). Contemporary prevalence may be lower


Prevalence of organ system complications

Incidence (%)

CNS

Cerebral infarction 24.5

Hypertensive encephalopathy 16.3

Intracerebral/subarachnoid hemorrhage 4.5

CV

Pulmonary edema 22.5

Acute congestive heart failure 14.3

ACS 12.0

Eclampsia 4.5

Aortic dissection 2.0

N = 449 presenting to Emergency Department with hypertensive

urgency/emergency

Zampaglione B et al. Hypertension. 1996;27:144-7.

N Engl J Med 2005;353:2788-96.


Most common presenting symptoms

Urgencies

• Headache (22%)

• Epistaxis (17%)

• Faintness and psychomotor

agitation (10%)

Emergencies

• Chest pain (27%)

• Dyspnea (22%)

• Neurological deficit (21%)

Zampaglione B et al. Hypertension. 1996;27:144-7.

Perioperative hypertension:

Scope of the problem

• Generally acknowledged to be common but little data available on

exact prevalence in contemporary surgical practice

• Markers of increased risk for perioperative ↑BP include:

– History of hypertension

– Type of surgery

• Cardiac

• Carotid

• Peripheral vascular

• Abdominal aortic

• Intraperitoneal/intrathoracic

• Pheochromocytoma tumor

Skarvan K. Curr Opin Anaesthesiol. 1998;11:29-35.

Weitz HH. Med Clin North Am. 2001;85:1151-69.

Erstad BL, Barletta JF. Ann Pharmacother. 2000;34:66-79.

Pathophysiology overview

Sustained neurohormonal activation and vasoconstriction leads to

• Endothelial decompensation

• Altered vascular structure

Vicious cycle of homeostatic failure begins, leading to

• Loss of cerebral and local autoregulation

• Organ system ischemia and dysfunction

• Myocardial infarction

Pathophysiology of hypertension

INAPPROPRIATELY HIGH

SYMPATHETIC OUTFLOW

Increased large

arterial stiffness

Inappropriately high

cardiac output

Abnormal venoconstriction

and high venous return

INAPPROPRIATELY HIGH

RENIN RELEASE

ABNORMAL RENAL

SALT/WATER HANDLING

Increased

systemic

resistance

NO

PGI2

Catecholamines

AT-II

ADH (vasopressin)

Aldosterone

TxA2

ET1

Endogenous

vasoconstrictors

The endothelium modulates vascular tone

Courtesy of JJ Ferguson III, MD.

Endogenous

vasodilators

Proposed vascular pathophysiology

of hypertensive urgency

Vaughan CJ, Delanty N. Lancet. 2000;356:411-7.


Acute ↑ BP triggers ↑ cellular adhesion molecular expression

NO

PGI2

Catecholamines

AT-II

ADH (vasopressin) Aldosterone

TxA2

ET1 ( - ) ( + )

CAMs

Endogenous

vasodilators

Endogenous

vasoconstrictors

• Overwhelmed control of vascular tone leads to coagulation cascade activation • Loss of endothelial activity coupled with coagulation and platelets promotes DIC

Proposed vascular pathophysiology

of hypertensive emergency

Vaughan CJ, Delanty N. Lancet. 2000;356:411-7.


TxA2

LANCET 2001;356: 413

Endothelial shear stress

Chatzizisis YS et al. J Am Coll Cardiol. 2007;49:2379-93.

ESS = endothelial shear stress

Proportional to the product of blood

viscosity (μ) and spatial gradient of

blood velocity at the wall (dv/dy).

Endothelial mechanoreceptors sense

changes

in shear stress


Shear stress rapidly activates endothelial

signal transduction and gene expression

Chien S et al. Hypertension. 1998;31[part 2]:162-9.

Maximum activation

Signal Transduction

Basal activity

Ras ERK

JNK

0 30 60 min

Ac

tiva

tio

n

Maximum

activation

Gene Expression

Basal activity

C-fos mRNA MCP-1 mRNA

0 60 120 min

Ac

tiva

tio

n

180 240

Definition and example of pulsatile, low, and

oscillatory ESS


Cross-section

Blood

flow

Pulsatile ESS

(15-70 dyne/cm2) - Direction: Unidirectional

- Magnitude: Physiologic time-average

Low and oscillatory ESS

(<10-12 dyne/cm2) - Direction: Bidirectional (oscillatory)

- Magnitude: Low time-average

Spontaneous Rupture and

Thrombus Formation

Distal Microembolization

2

5


Implications of low and high shear stress

Effects of high

shear stress

Endothelial dysfunction

Vascular injury

Thrombosis

Neurohumoral activation

Atherosclerosis

Plaque rupture

Effects of low

shear stress

Perioperative triggers

of adverse physiologic states

• Surgical trauma

• Anesthesia/analgesia

• Intubation/extubation

• Pain

• Hypothermia

• Bleeding/anemia

• Fasting

• Transfusion

Devereaux PJ et al. CMAJ. 2005;173:627-34.

Inflammatory

Hypercoagulable

Stress

Hypoxia

Physiologic state

Proposed mechanisms of perioperative MI

Devereaux PJ et al. CMAJ. 2005;173:627-34.

Inflammation Hypercoagulable

state Stress Hypoxia

↑TNF-α

↑IL-1

↑IL-6

↑CRP

↑PAI-1

↑Factor VIII

↑Platelet reactivity

↑Antithrombin III

↑Catecholamine and

cortisol levels

↓Oxygen delivery

Plaque fissuring

Coronary artery

shear stress

Plaque fissuring

↑BP

↑HR

↑FFAs

↑Relative insulin

deficiency

↑Oxygen demand

Myocardial

ischemia

Acute coronary

thrombosis

Perioperative myocardial infarction

Summary: The pathophysiology of acute

hypertensive syndromes

Mechanical

stress on the

vessel wall ↑BP

Release of humoral

vasoconstrictors

↑BP

Endothelial

damage

Activation of the

clotting cascade

Further release of

humoral

vasoconstrictors

Fibrinoid necrosis

of small blood

vessels

Pressure

natriuresis

Volume

depletion

RAAS activation

Vasopressin

endothelin

catecholamines Major physiologic

derangements


Pathophysiology of acute hypertensive

syndromes: A vicious cycle


Vascular

injury

Tissue

ischemia

Vasoconstrictor release

Profile of an ideal parenteral antihypertensive

• Treats underlying pathophysiology

• Rapid onset of action

• Predictable dose response

• Minimal dosage adjustments

• Highly selective

• No increase in intracranial pressure

• Rapidly reversible

• Low risk of overshoot hypotension or adverse reaction

• Easy conversion to oral agents

• Acceptable cost-benefit ratio

Levy JH. Anesthesiol Clin North Am. 1999;17:567-79.

Oparil S et al. Am J Hypertens. 1999;12:653-64.

Sodium nitroprusside: Profile

• Arterial and venodilator

– ↓Preload and afterload

• Onset: Immediate

• Duration of action: 1-2 min

• Adverse effects

– Nausea, vomiting, muscle twitching, sweating, thiocyanate and

cyanide intoxication, coronary steal, maldistribution of blood flow

• Light sensitive: requires special delivery system

Chobanian AV et al. Hypertension. 2003;42:1206-52.

Aggarwal M, Khan IA. Cardiol Clin. 2006;24:135-146.

Esmolol: Profile

• Blocks β1 receptors of heart and vasculature

– ↓Heart rate, cardiac output, and stroke volume

• Onset: 1-2 min

• Duration of action: 10-30 minutes

• Adverse effects:

– Hypotension, nausea, asthma, 1st degree heart block, HF


Aggarwal M, Khan IA. Cardiol Clin. 2006;24:135-146.

Fenoldopam: Profile

• Selective dopamine-1 receptor agonist

– ↓Peripheral vascular resistance

– ↑Renal blood flow, natriuresis, and diuresis

• Onset: <5 min

• Duration of action: 30 min


– Tachycardia, headache, nausea, flushing


Oparil S et al. Am J Hypertens. 1999;12:653-664.

Labetalol: Profile

• α1- and β1-receptor blocker

– ↓Peripheral vascular resistance (α1 blockade)

– No reflex tachycardia (β1 blockade)

– Maintains coronary, cerebral, and renal blood flow

• Onset: 5-15 min

• Duration of action: 4-6 hours


– Vomiting, scalp tingling, bronchoconstriction, dizziness, nausea,

heart block, orthostatic hypotension


Marik P, Varon J. Chest. 2007;131:1949-62.

Nicardipine: Profile

• 2nd generation dihydropyridine calcium channel blocker

– Coronary and cerebral arterial vasodilation

– No negative inotropic or dromotropic effects

– ↓Systemic vascular resistance

• Onset: 5-15 min

• Duration of action: 15-30 mins


– Tachycardia, headache, flushing, local phlebitis


Levy JH. Tex Heart Inst J. 2005;32:467-71.

0

20

40

60

80

100

120

140

160

180

200

3:00 4:00 5:00 6:00 7:00 8:00 9:00

Time

mm

Hg

10 15 8

SBP MAP DBP Target SBP Target

MAP Range

BP reduction with IV nicardipine

Courtesy of WF Peacock, MD

Nicardipine vs SNP for perioperative

hypertension

Time to

response

(min)

# Dose changes

Adverse

events

Cardiac

patients

Noncardiac

patients

Nicardipine 14.1 ± 1*

(n = 51)

1.5 ± 0.2†

(n = 18)

1.6 ± 0.1‡

(n = 33)

7%

(5/71)

SNP 30.4 ± 3.5

(n = 51)

5.1 ± 1.4

(n = 15)

4.6 ± 0.6

(n = 36)

18%

(12/68)

*P = 0.0029 vs SNP, †P ≤ 0.05 vs SNP ‡Significant treatment differences

in 2/5 centers (P < 0.05)

Halpern NA et al. Crit Care Med. 1992;20:1637-43.

N = 139 following cardiac or noncardiac surgery

End

Fenoldopam vs SNP in acute hypertension:

Similar hemodynamic effects

Panacek EA et al. Acad Emerg Med. 1995;2:959-65.

N = 153 evaluable patients; acute end-organ damage not a study requirement

*P < 0.05 FNP vs SNP

Fenoldopam (FNP) SNP

0.5

Blood

pressure

(mm Hg)

1.0 2.0

Maintenance time (hours)

4.0 6.0 Baseline Start 70

90

110

100

150

200

250

* *

Heart rate

(bpm)

Fenoldopam vs dopamine: Similar effects

on perioperative renal function

0

5

10

15

20

25

30

35

40

45

Patients

(%)Fenoldopam

Dopamine

Cr elevation

≥25%

Cr elevation

≥50%

Renal replacement

therapy

Bove T et al.

Circulation. 2005;111:3230-5.

N = 80 cardiac surgery patients at high risk for perioperative renal

dysfunction*

*Continuous Improvement in Cardiac Surgery Program score >10

Calcium channel blockers in acute

hypertension


1st generation: Nifedipine

2nd generation: Nicardipine

3rd generation: Clevidipine

Clevidipine: Pharmacokinetic overview

• Dihydropyridine calcium channel blocker (CCB)

• T½ ≈ 1 min

• Selective arteriolar dilation

↓Systemic vascular resistance

↓Afterload

↑Stroke volume

↑Cardiac output

• No venous dilation

– No effect on cardiac filling pressure

• No effect on HR

Nordlander M et al. Cardiovasc Drug Rev. 2004;22:227-50.

Clevidipine: Principles of use

• Linear relationship between dosage and arterial blood

concentrations

– Relationship maintained for dose rates up to 7 nmol/kg per min

• Rapid clearance following infusion discontinuation

– BP returns to baseline within 10 min

Ericsson H et al. Anesthesiology. 2000;92:993-1001.

Hypertensive

Urgencies/Emergencies:

Guidelines

Hypertensive emergencies: JNC 7 consensus

recommendations*

• Admit to ICU

• Administer short-acting parenteral antihypertensive with close

monitoring

↓BP by ≤25% within 1 hour

↓BP to 160/100-110 mm Hg over next 2-6 hours

↓BP to 130/85 mm Hg over next 24-48 hours

Chobanian AV et al. Hypertension. 2003;42:1206-52. *Expert opinion

Hypertensive urgencies: JNC 7 consensus

recommendations*

• Some patients may benefit from short-acting oral antihypertensive

treatments

– However, in one recent study, resting for 60 min was associated

with ↓BP of >20% in 1/3 of patients

– In addition, no evidence that failure to ↓BP in emergency

department is associated with ↑short-term risk

• Adjust or reinstitute antihypertensive regimen

to gradually ↓BP over next few days


Duarte M et al. Presented at ASH. 2006.

*Expert opinion

JNC 7: Treatment of acute hypertension in

preeclampsia

Dosing Precautions

Hydralazine 5 mg IV bolus, then 10 mg

q20-30 min to max 25 mg;

Repeat in several hr

Labetalol

(second-line)

20 mg IV bolus, then

40 mg 10 min later, 80 mg

q10 min for 2 additional

doses to max 220 mg

Nifedipine

(controversial)

10 mg po, repeat q20 min

to max 30 mg

Precipitous ↓BP when

using with MgSO4

SNP

(rarely-when others fail)

0.25 µg/kg per min to max

5 µg/kg per min

Cyanide poisoning may

occur if used >4 hr


Consider if childbirth is imminent

BP management in acute aortic syndrome

Goal: Decrease aortic wall stress by rapidly ↓BP and ↓HR

IV β-blockers and SNP or oral ACEI

IV CCBs if β-blockers contraindicated

All patients should also be evaluated to determine if surgical management

is necessary

Nienaber CA, Eagle KA. Circulation. 2003;108:772-8.


Circulation 2005;112;3802-3813

N Engl J Med 2008;358:494-501.

Circulation 2005;111;816-828

Vaughan C. Lancet 2000; 356: 41197

N Engl J Med, Vol. 344, No. 19, 2001

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

Broderick J et al. Stroke. 2007;38:2001-23.

ICP = intracranial pressure

AHA/ASA guideline: BP management

in acute ischemic stroke

SBP >185 mm Hg

or

DBP >110 mm Hg Nitropaste 1-2 in

Nicardipine infusion 5 mg/hr

and uptitrate by 2.5 mg/hr

q5-10 min

When desired BP attained,

reduce to 3 mg/hr

Candidates for rtPA or other acute reperfusion intervention

Adams HP Jr et al. Stroke. 2007;38:1655-711.

If BP not

controlled,

consider

SNP

or

or

Labetalol 10-20 mg IV

over 1-2 min

May repeat once

Circulation 2007;116;1504-1514

N Engl J Med 2007;356:706-13.

Circulation 2006;113;1361-1376

Perioperative hypertension:

No consensus on degree of BP control

• No formal guidelines on definitions, treatment strategies, and BP

goals

• General strategy is to maintain MAP ±20% of baseline

• Treatment threshold in clinical studies varies:

– MAP: 90-110 mm Hg

– SBP: 110-175 mm Hg

– DBP: 95-110 mm Hg

Cheung AT. J Card Surg. 2006;21(suppl):S8-14.

Vuylsteke A et al. J Cardiothorac Vasc Anesth. 2000;14:269-73.

Management of

Hypertensive

Emergencies

New paradigm in treatment of acute

hypertension

Acute vascular injury has chronic sequelae

Prevention of exaggerated BP variation (too high/too low) is desirable

Courtesy of JL Izzo Jr, MD.

SBP too high

• Cardiac overload

• Vascular damage

SBP too low

• Thrombosis?

• Organ dysfunction

Follow-up care in hypertensive emergencies

• Goal: Transition to oral therapy as soon as patient can tolerate

therapy

• Monitor carefully: Abrupt switch may result in ↑BP

• Most patients may be discharged on oral medication within 24-72

hours

• Clinical setting offers an opportunity to improve BP control and

medication adherence

Vidt DG. In: Hypertension Primer. In press.

MUCHAS GRACIAS

[email protected]