Treatment of Hypertensive Crisis

Hypertensive Crisis

systolic blood pressure (SBP) level ≥180 mmHg and/or a diastolic blood pressure (DBP) level ≥ 120 mmHg with or without acute target organ damage (TOD).

Hypertensive Urgency

• It is defined as elevation BP greater than 180/120 mm Hg, without signs of Target Organ Damage (TOD).
• Presenting symptoms include headache, shortness of breath, anxiety, and epistaxis.

Hypertensive Emergency

• It is defined as elevation of BP greater than 180/120 mm Hg in presence of signs of TOD

• Global burden – 24% & 21% of male & females with HTN (SBP>=140 OR DBP>=90).

India – Prevalence of HTN is 25% in urban & 10% in rural people in India of which 20.6% are men & 20.9% women.

Causes

• Non-adherence to anti-hypertensive medication
• Renovascular Disease
• Pheochromocytoma
• Hyperaldosteronism
• Drug Induced hypertension
• Eclampsia/pre-eclampsia
• Vasculitis

Diagnosis

• History – Hypertension, Medications, Substance abuse, Comorbid conditions
• BP – Both arms, Supine & Standing (Aortic dissection)
• Cardiac – ECG, Cardiac Enzymes, 2D-echo, X-ray
• Renal – Serum Creatinine & BUN, Liver Enzymes

Management

• Not addressed in recent JNC-8
• Current recommendations based on
  • JNC-7 guidelines
  • ACC/AHA 2017

Normalisation of BP is usually not recommended

• Sudden fall in BP may cause acute hypoperfusion of vital organs & results in myocardial ischemia, hemiplegia, or  acute renal failure.

Hypertensive Urgency

• Remember: Start Low, Go Slow
• Fully titrate before adding second med
• Titrate to effect (or side effect)
• Treatment with an oral, short-acting agent such as Captopril, Labetalol
• Increasing dose, Use of combination

Goal of Therapy: Hypertensive Emergency

• <1hr à Reduce Systolic Blood Pressure(SBP) ≤ 25%
  • 2-6hr à if stable, reduce to 160/100–110 mmHg
  • 24-48hr à Well tolerated & stable toward normal BP

Pharmacotherapy

1. Vasodilators
   1. Sodium nitroprusside
   1. Nitro-glycerine
   1. Nifedipine
   1. Nicardipine
   1. Clevidipine
   1. Fenoldopam
   1. Hydralazine
   1. Enalaprilat
2. Adrenergic inhibitors
   1. Labetalol
   1. Esmolol
   1. Phentolamine

Sodium Nitroprusside – MOA – Preload & afterload

• Arteriolar & venous dilation, cerebral vasodilation
• DOSE- 0.3–0.5 mcg/kg/min IV infusion, max – 10 mcg/kg/min

Ultra short acting -1-2min, t ½ 3-4 minutes

• Adverse Effect/Precaution-
• Cyanide & thiocyanate toxicity prolonged infusion,      
• Thiosulfate – to prevent cyanide toxicity
• Bottle is covered with an opaque wrapping
• Continuous BP monitoring
• Use à Aortic dissection,  Acute LVF

Nitroglycerin

• MOA- Greater preload reduction than afterload, Decreases coronary vasospasm
• DOSE- 5-100mcg/min, Titrate up 10mcg every 5 mins

Onset 2-5min, Half life – 4min

• Adverse Effect/Precaution- Headache, Tachycardia, Tolerance, Continuous BP monitoring

C/I- Head trauma/Cerebral haemorrhage, with PDE-5 inhibitors

• Uses – Acute HF,  Acute coronary syndrome.

Oral/Sublingual Nifedipine

• MOA- Peripheral & coronary arteriolar dilator, Potential hypotension and/or reflex cardiac stimulation

Sudden uncontrolled & severe reductions in BP,  may precipitate  cerebral, renal & myocardial ischemic events

• “Inappropriate physician habits in prescribing nifedipine capsules in hospitalized patients”
• Cardiorenal Advisory Committee of FDA has concluded  “that practice of administering SL/oral nifedipine abandoned because this is not safe nor efficacious¹

Nicardipine

• MOA- L-type Ca⁺⁺ channel blocker – selective Arterial vasodilator, Cerebral & Coronary vasodilatation
• DOSE- Start 5mg/hr IV infusion, titrate every 15min to max 15mg/hr

Duration of action 15-30min,

Adverse Effect/Précaution- Worsen/cause HF,  Reflex tachycardia

• Uses – Ideal for CNS emergencies, Renal Disease

Clevidipine

• MOA- 3^rd gen (L-type) CCB, arterial vasodilator FDA approval (2008), Injectable emulsion
• DOSE- Start 1-2mg/hr with rapid titration to max 32mg/hr

Ultra short t1/2 – 1 min, Duration of action 5-15min, PPB -99.9%

• Adverse Effect/Precaution- Atrial fibrillation, C/I – Allergies (soy & egg products), Defective lipid metabolism
• Uses – All HTN emergencies (Safe in Renal & Hepatic dysfunction)

Fenoldopam

• MOA- Peripheral  Dopamine-1  agonist(DA1). 10 –fold more potent renal vasodilator than Dopamine
• DOSE- 01-0.3mcg/kg/min infusion, Max infusion rate – 1.6mcg/kg/min (Titratable, Predictable & Stable)
• Adverse Effect/Precaution- Tachycardia, Headache, Hypokalemia. Caution with glaucoma.
• Advantages- All HE, Renal insufficiency patients  Strokes (combination with Nicardipine)

Hydralazine

• MOA- Direct arteriolar dilator, opening high conductance Ca2+-activated K+ channels

Delayed onset, Unpredictable hypotensive effect

• DOSE- Dose: 10-20 mg I V, repeated in 30 mins, 10-40mg IM. Not titratable
• Adverse Effect/Precaution- TACHYCARDIA,  Drug-induced Lupus syndrome

Aggravation of angina, Sodium & water retention

• Advantages- Eclampsia

Enalaprilat

• MOA- Active component of Enalapril,  ACE inhibitor
• DOSE- 1.25-5mg IV every 6hr. Difficult to titrate
• Adverse Effect/Precaution- Excessive fall in BP, C/I- Acute MI, Renal Disease,  Pregnancy, Volume depletion
• Use – Acute LVF , Expensive

Esmolol

• MOA- Cardio selective β Blocker
• DOSE- Loading dose 500mcg/kg over 1 min, Infusion of 50-300mcg/kg/min
• Adverse Effect/Precautions- Bradycardia

C/I- 1^st degree heart block, COPD, CKD

• Uses- Aortic Dissection, Cardioprotective in CVS emergencies

Labetalol

• MOA- Selective α1 and non-selective β blocker (1:7)

Maintains cardiac output, Cerebral, renal, coronary blood flow, Reduces SVR

• DOSE- 20-80mg IV Bolus every 10min, or infusion of 2mg/min to max of 300mg.
• Adverse Effect/Precautions- Exacerbate CHF, C/I – COPD, Heart Block, decompensated HF
• uses- PIH, Pheochromocytoma

Phentolamine

• MOA- α adrenergic blocker
• DOSE- Bolus 5-20mg IV every 5min,
• Adverse Effect/Precaution- Tachycardia, flushing, Postural Hypotension

C/I- use with PDE-5 inhibitors, Renal Impairment

• Advantages- Pheochromocytoma, Cocaine associated HPT crisis

Management of Hypertensive Emergency with TOD

Pulmonary Edema (LVF)

• Nitroglycerin 5 mcg/min.
• Sodium Nitroprusside (reduces preload) -0.3 to 0.5 mcg/kg/min
• IV Diuretic (reduces preload & afterload)- 40mg IV
• Morphine – Vasodilator & Sympatholytic
• Clevidipine infusion 1–2 mg/h, max 32 mg/h.
• Low EF à Avoid beta blockers/Negative inotropes

Acute Myocardial Infarction

• Reduce MAP by 20 -25% of baseline
• Nitrates should be given till symptoms subside or until DBP<100
• Drug of choice: Nitroglycerine 5 mcg/min, Labetalol (or Esmolol), Nicardipine – 5 mg/h
• Avoid Hydralazine – Increase myocardial O₂ demand

Acute Aortic Dissection

• OK to aggressively reduce BP (<120/80)
• Reducing the shear stress on aortic wall
• Aim of treatment to reduce SBP as rapidly as possible down to 100-110 mmHg & to control tachycardia
• 1^st Esmolol then Nitroprusside
• Hydralazine is C/I

Ischemic Stroke

• Blood Pressure -Systolic > 185 or diastolic > 110 mm Hg
• Labetalol 10 to 20 mg IV over 1 to 2 min may repeat x 1                     or
• Nicardipine infusion, 5 mg/h, titrate up by 0.25 mg/h to max dose 15 mg/h
• Desired blood pressure obtained, reduce to 3 mg/h
• If BP not controlled or diastolic BP >140 mm Hg, consider IV sodium nitroprusside

Sympathetic crises

• PATHOLOGY- Pheochromocytoma, Monoamine oxidase inhibitor + tyramine, Cocaine/amphetamines overdose.
• GOAL- Reduce MAP by ~25% over several hours
• DOC- Phentolamine: 5-15mg IV bolus or drip 5-10mcg/kg/min

Beta-blocker- Labetalol (control tachycardia)

Benzodiazepines – Helpful in cocaine/amphetamine overdose

Pre-eclampsia and Eclampsia

• PATHOLOGY- Systemic arterial vasoconstriction (Including Placental)
• Defined as SBP = 140/90 mmHg or greater, OR a 20 mmHg rise in SBP or 10 mmHg rise in DBP from baseline
• Restlessness & hyper-reflexia , seizures, proteinuria
• GOAL- Delivery of the fetus and placenta
• DOC- MgSO4: 4-6gm over 15 minutes IV, drip 1-2gm/hr
• Hydralazine: 5-10mg IV, drip 5-10mg/hr
• Labetalol: 20mg IV, repeat prn q 10 mins, drip 1-2mg/min

Intracerebral Hemorrhage

Rise in BP due to increased ICP & irritation of ANS

• GOAL- Treatment based on clinical/radiographic evidence

Raised ICP – MAP<130 (1st 24hrs)

No raised ICP – MAP<110

To prevent re-bleeding & reduce edema.

BP >180/105 mmHg , benefit from gradual 20-25% reduction in BP

• DOC- IV Nicardipine 2mg bolus, then 4-15mg/hr (treat SAH )

Nimodipine PO 60mg q 4hr (to reverse vasospasm)