Outline

• Hypertension in Children
  • signs and symptoms
  • causes
  • management
• Hypertensive Emergencies
  • Definitions
  • Malignant Hypertension
  • Pathophysiology Diagram
  • Clinical Presentation
  • Management
  • Antihypertensive Medications
• References

CASE: 12 year old white male presented to Peds Renal Clinic with BP 170-190's/130-150's and complaints of headache 2-3x/week and vision changes. He was diagnosed with hypertension of unknown etiology 2 years ago, but was lost to follow up and never treated. He also c/o easy fatigueability yet still participated in sports. Family history significant for: maternal hypertension age 28 being treated with beta-blockers and ACE inhibitors; Mx GM with CAD age 50 and Graves; Mx great aunt and aunt with Graves. Exam unremarkable except for obesity (>95%) and BP 191/152. ? blurred disc margin in one exam. Work-up negative except for very high TSH level 243 (Normal 0-5) and mildly low thyroxine 0.52 (Normal 0.8-1.8). ECHO with LVH, good function.

He was initially treated with a Nipride drip to bring BP down by 25% in the first 24 hours, then changed to Atenolol and started on Synthroid. This was changed to Vasotec due to excessive beta blockade. BP well controlled with the 2 drugs.

Discussion

HYPERTENSION IN CHILDREN

Signs and Symptoms:

• Failure to thrive
• Nausea/Vomiting
• Lethargy
• Irritability
• Headache
• Visual problems
• Cardiac failure
• Seizures
• Stroke
• Facial palsy

Causes of HTN in neonates and infants

• Renal artery thrombosis
• Coarctation of aorta
• Congenital renal structure or parenchymal disease
• Renal artery stenosis
• BPD
• Abdominal surgery
• ECMO

Causes of HTN in children and adolescents

1-10 years of age	10 years-adolescence
Renal disease Coarctation Renal artery stenosis Hypercalcemia Neurofibromatosis Neurogenic tumors Pheochromocytoma Mineralocorticoid excess Hyperthyroidism Transient after urology surgery Immobilization Sleep-apnea associated Essential (rare)	Renal disease Essential hypertension Diagnoses as listed to the left

Management of crises:

• Same general principles as in adults (see remainder of outline)
• Sodium nitroprusside best drug used for most difficult cases
• Diazoxide, nifedipine, captopril and labetolol have been used safely and effectively

HYPERTENSIVE EMERGENCIES

DEFINITIONS:

Hypertensive emergency: rapid decompensation of vital organ function secondary to an inappropriately elevated BP. Requires lowering of BP within 1 hour to decrease morbidity. Absolute level of BP is less important than the deterioration of vital organ function. Examples: hypertensive encephalopathy, intracranial hemorrhage, left ventricle failure and pulmonary edema, acute MI and unstable angina, adrenergic crisis, dissecting aortic aneurysm and eclampsia.

Hypertensive urgency: BP should be lowered over several hours. Examples: uncomplicated malignant hypertension, acute renal failure, perioperative hypertension, HTN a/w burns and severe hypertension a/w coronary artery disease.

Malignant hypertension: presence of Keith-Wagner grade IV retinal changes (papilledema)

Accelerated hypertension: presence of grade III retinopathy (hemorrhages, cotton wool spots, hard exudates. Accelerated and malignant usually grouped together as malignant hypertension.

MALIGNANT HYPERTENSION

• Incidence: occurs in 1% of hypertensive population
  • males>females by 2:1 occurring in infants to elderly
  • decreasing incidence in Caucasian population, but still high in Black and Indian-Asian
• Etiology: can develop de novo or accompany essential or secondary hypertension
  • Essential HTN (most common)
  • Renal parenchymal etiology
    • Glomerulonephritis
    • Tubulointerstitial nephritis
    • Systemic (sclerosis, HUS/TTP, DM, SLE, vasculitis)
    • Congenital (renal aplasia)
  • Renovascular
    • Atheroma
    • Fibromuscular dysplasia
    • Takayasu's arteritis
    • Acute occlusion
    • Polyarteritis nodosa
  • Endocrine
    • Pheochromocytoma
    • Conn's
    • Cushing's
  • Drugs (cocaine, amphetamine, clonidine withdrawal, MAOI interaction, Epo ,CSA)
  • Tumor-related (renal cell CA, Wilm's, lymphoma)
  • Coarctation
  • Pre-eclampsia/Eclampsia
• Pathophysiology
  • Most important factor leading to malignant HTN is severe, rapid elevation of BP. Rapidity of onset suggests a triggering factor superimposed on pre-existing HTN followed by a positive feedback loop leading to higher BP and further activation of the precipitating factors.

Clinical Presentation

Blood pressure: 150-290/100-180

Optic Fundi: grade III-IV are hallmarks of malignant hypertension

• can present with impairment of vision ranging from blurring to blindness
• loss of autoregulation of retinal vessels due to hypertension, resulting in development of areas of narrowing and dilatation in the vessels
• Retinal hemorrhages due to necrosis of capillary and precap arteriolar walls
• Hard exudates due to endothelial damage leading to leakage and deposition of plasma proteins in posterior retina. In the macular region, this may form a radiating pattern called the macula star
• Soft exudates due to ischemic infarct of the nerve fibers
• Papilledema due to swelling of the optic disc with obliteration of the cup. Early signs include overfilling of veins, loss of venous pulsations, hyperemia of the nerve head, and blurring of disc margins.
• With treatment of hypertension, retinal lesions can be reversed and vision often returns to normal.

Heart: 11% present with heart failure

• malignant HTN can cause acute heart failure and lead to pulmonary edema from pressure overload.
• LVH found in 75% at presentation
• can also present with ischemic heart disease, angina, MI, aortic dissection

Neuro: often present with headache and dizziness

• True hypertensive encephalopathy uncommon
• consists of headache, nausea, vomiting, blurred vision, impaired cognitive function, generalized seizures or cortical blindness
  • *critical precipitating factor is suddenness and rapidity of rise of BP, resulting in loss of autoregulation of cerebral vessels leading to cerebral vasodilation, hyperperfusion, breakdown of blood-brain barrier, plasma exudation and focal cerebral edema.
• as BP is lowered, fluid extravasation decreases and cerebral autoregulation returns. In chronic hypertensives, autoregulation takes time to re-establish, therefore need longer time to decrease BP and avoid precipitating cerebral ischemia.

Kidneys: non-nephrotic range proteinuria frequently seen. Increased creatinine levels seen in 31%. Urinalysis reflects any underlying renal disease.

FEN/Heme:

• hypokalemic metabolic alkalosis due to volume depletion and secondary
• hyperaldosteronism
• plasma renin activity and aldosterone increased in most. With therapy, renin decreases rapidly, but aldosterone remain elevated for months
• microangiopathic hemolytic anemia (fragments, thrombocytopenia, elevated FDP and fibrinogen).

General: weakness, malaise, fatigue and weight loss.

Management

GOAL: decrease BP, stabilize and reverse damage to target organs

• initial assessment focuses on signs of CV, neuro, renal and ocular damage
• identify stroke, MI and aortic dissection
• baseline labs: CBC with smear, lytes, BUN/Cr, UA, CXR and ECG Renal U/S with Doppler, CT/MRI if warranted
• careful monitoring of BP, fluid balance, lytes and renal function
• malignant HTN with organ failure or other emergencies: reduce BP rapidly
• uncomplicated malignant HTN or urgencies: reduce BP no > 20% or to target DBP 100-110 in 24 hour period
• chronic HTN: slow decrease in BP, no >20-25% decrease in 24 hour period

*blindness, paralysis, coma and death have been reported in adults and children as a result of inappropriately aggressive therapy

• volume depletion is common and may lead to excess hypotension with therapy
• avoid diuretics unless volume overloaded
• once stable, check for secondary causes of HTN
• introduce oral agents once BP is controlled
• avoid drugs that cause reflex sympathetic activity in myocardial ischemia and aortic dissection
• avoid drugs with CNS side effects in hypertensive encephalopathy (clonidine, methyldopa)

Antihypertensive Medications

Drugs	Mechanism of Action	Use/Contraindication	Side Effects
Nitroprusside	decreases arterial and sympathetic venous tone by donating NO	almost universal use in aortic dissection use with beta blocker	-causes reflex stimulation -can increaseICP -thiocyanate tox -decrease in P02
Nitroglycerine	decreases afterload myo 02 consumption	use with myocardial ischemia to improve coronary perfusion	-cause hypotension reflex tachy with volume depletion -tolerance with prolonged use
Labetolol	alpha and beta blocker decreases PVR without reflex stimulation of CO	contraindicated with bradycardia, heart block, heart failure, bronchospasm paradox HTN in pheo, therefore, need alpha block 1st
Beta blockers - propanolol - esmolol	short acting beta-1	dissecting aneurysm adjunctive therapy to decrease heart rate in HTN a /w MI, unstable angina, thyrotoxicosis	avoid in cocaine-induced due to paradox rise in BP thrombophlebitis and necrosis with IV infiltration
Diazoxide	arterial vasodilator	rarely used due to profound drops in BP reflex sympathetic activation and sodium retention
Trimethaphan camsylate	ganglionic blocker dilates both resistant and capacitant vessels	Largely supplanted by nipride due to S/E Does not increase ICP or cause reflex tachy like nipride. Good alternative for aortic dissection	blurred vision, dry mouth, bowel and bladder paresis, anhidrosis, histamine release and severe orthostatic hypo
Alpha blockers (nonselective) phentolamine phenoxybenzamine	longer acting	less freq used due to efficacy of nipride use for excess catecholamine states: pheo, cocaine and and amphetamine overdose, MAOI crisis
ACE inhibitors captopril enalaprilat		either can be used in hypertensive urgencies and drugs of choice  for scleroderma renal crisis -contraindicated in pregnancy
Hydralazine	direct vasodilator	used primarily in eclampsia may cause rapid fall in BP and reflex tachy contra in dissection and ischemia
Minoxidil	vasodilator	useful in malignant HTN a/w renal failure
Calcium Channel Blockers	cause vasodilation	Short acting nifedipine not recommended for hypertensive emergencies Verapamil safe in postinfarction HTN; also okay with aortic dissection when beta blockers are contraindicated (Verapamil is contraindicated in small children/infants) Nicardipine can be used in postoperative HTN, but not a drug of choice for hypertensive crises
Clonidine	central acting alpha 2 adrenergic agonist		Can cause somnolence and confusion
Fenoldopam	D1 agonist--vasodilator	useful for pts with renal impairment no rebound HTN after stopping	HA/nausea/flushing/tachy/increases IOP

References: (click on links to see abstracts through Pub-Med)

• Brogden RN and Markham A: Fenoldopam (Review). Drugs 54(4) 634-650, 1997.
• Kitiyakara C and Guzman NJ: Malignant Hypertension and Hypertensive Emergencies. J of Amer Soc of Neph. 133-142, 1998.
• Murphy C: Hypertensive Emergencies. Emergency Med Clinics.13 (4) 973-1003, 1995.
• Ram CVS: Immediate Management of Severe Hypertension. Cardiology Clinics. 13(4) 579-591, 1995.
• Saito I, Ito K and Saruta T: Hypothyroidism as a Cause of Hypertension. Hypertension 5(1) 112-115, 1983.
• Sinaiko AR and Wells TG: Childhood Hypertension. Hypertension. 1853-1865. Raven Press, 1990.

Written by Connie Saqueton, MD June 30, 1998, edited for the web and placed on the server 7/6/98

Last updated July 6, 1998 at 1040 CDT

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