Malignant Hypertension

Severe hypertension (usually greater than 180/120 mmHg) with acute microvascular injury: retinal haemorrhages and exudates, with or without papilloedema, and often thrombotic microangiopathy, acute kidney injury or encephalopathy.

• Mechanism: pressure induced endothelial injury, fibrinoid necrosis of arterioles, activation of renin and angiotensin, and pressure natriuresis with volume depletion, which further drives the hypertension.
• Historically most untreated patients died within a year. With treatment, 5-year survival exceeds 75%. Renal failure is the main long term consequence.
• A secondary cause is found in a substantial minority, especially in young patients.

• Headache, visual blurring, nausea, confusion, seizures, chest pain, dyspnoea, oliguria, weight loss, polyuria and nocturia.
• Fundoscopy: flame haemorrhages, cotton wool spots, hard exudates, papilloedema.
• Signs of end organ damage: pulmonary oedema, reduced urine output, focal neurology.
• Differential diagnosis: hypertensive urgency without organ injury, hypertensive encephalopathy, acute stroke, aortic dissection, eclampsia, phaeochromocytoma crisis, stimulant intoxication, scleroderma renal crisis.
• Complications: acute kidney injury and end stage kidney disease, heart failure, stroke, intracerebral haemorrhage, visual loss, thrombotic microangiopathy.

• Repeat BP in both arms; fundoscopy by an experienced examiner.
• ECG (left ventricular hypertrophy, ischaemia), chest X-ray, troponin if chest pain.
• Urinalysis (protein, red cells, casts), urea, creatinine, electrolytes (hypokalaemia suggests aldosterone excess or renovascular disease), full blood count and blood film (fragmented red cells), lactate dehydrogenase, haptoglobin, bilirubin.
• Pregnancy test in women of childbearing age; urine drug screen where stimulant use is suspected.
• Renal ultrasound; echocardiography; CT or MRI of brain if neurological signs.
• Secondary cause workup: plasma renin and aldosterone, plasma or urine metanephrines, cortisol testing, renal artery imaging, urine and serology for glomerulonephritis and scleroderma.

• Admit to monitored care. Aim to reduce mean arterial pressure by no more than 20 to 25% in the first hours, then to about 160/100 mmHg over 2 to 6 hours, then to normal over 24 to 48 hours. Excessive early falls risk cerebral, coronary and renal ischaemia. Exceptions: aortic dissection needs systolic BP less than 120 mmHg within 20 minutes; in pre-eclampsia, bring BP to less than 160/110 mmHg promptly, then control gradually.
• Preferred IV agents:
  • Labetalol 20 mg IV bolus, then 20 to 80 mg every 10 minutes (maximum 300 mg), or infusion 0.5 to 2 mg/min. Avoid in asthma, bradycardia, heart block, acute heart failure.
  • Nicardipine 5 mg/h increased by 2.5 mg/h every 5 to 15 minutes to a maximum of 15 mg/h.
  • Glyceryl trinitrate 5 to 100 micrograms/min for pulmonary oedema or ischaemia.
  • Furosemide 40 to 80 mg IV for volume overload (avoid in volume depletion).
  • Phentolamine 5 mg IV for catecholamine excess.
  • Sodium nitroprusside 0.25 to 10 micrograms/kg/min only when other agents fail, for the shortest possible time (less than 24 to 48 hours), with cyanide and thiocyanate monitoring, particularly in renal impairment.
  • Hydralazine 5 to 10 mg slow IV every 20 to 30 minutes in pregnancy, though response is unpredictable.
• Avoid sublingual nifedipine because of abrupt, uncontrolled falls in pressure.
• Oral transition (once BP is controlled, or in settings without IV agents): amlodipine 5 to 10 mg daily, nifedipine retard 10 to 20 mg twice daily, labetalol 100 to 400 mg twice daily. Then add ramipril 2.5 to 10 mg daily or an ARB once renal artery stenosis and volume depletion are excluded or monitored, and a thiazide like diuretic (chlorthalidone 12.5 to 25 mg daily). Add spironolactone 25 to 50 mg daily for resistant disease.
• Thrombotic microangiopathy: lower the pressure first; if haemolysis and thrombocytopenia persist, consider plasma exchange only after other causes are excluded.
• Acute kidney injury: dialysis for refractory hyperkalaemia, acidosis, or fluid overload. Renal recovery can take weeks to months, so delay judging dialysis dependence.
• Treat the underlying cause when found: adrenalectomy for adenoma, angioplasty for fibromuscular dysplasia, immunosuppression for glomerulonephritis, and for scleroderma renal crisis captopril 6.25 to 12.5 mg increased to 50 mg three times daily.
• Special groups: pregnancy (labetalol, nifedipine, hydralazine; deliver if refractory); children (specialist care, lower dosing); elderly (slower reduction).
• Follow up: review weekly until BP is stable, then monthly for 3 months; check creatinine and potassium after every ACE inhibitor change; repeat fundoscopy at 1 to 3 months; screen for non-adherence and secondary hypertension.