HYPERTENSIONIN CHILDREN

Maria E. de Ferris, MD, MPH, PhD

Associate Professor

UNC Medical School

HTN in Children

• Task Force on Blood Pressure Control in Children– 1977– 1987– Revised in 1996 and 2004

• Epidemiological-based data– >70,000 children used to define standards– Categorized by Gender/Age/Height

Definitions

• Normal– <90th percentile

• High-normal– 90-95th percentile

• Hypertension– >95th percentile on three consecutive measurements

– This presumes 5% prevalence of hypertension in pediatric population

**Tables in Harriet Lane**

Daniels J Peds 1996: 125:208; Harshfield AJH 2002 15:525

BP Racial Differences

• AA children have higher readings than other races but not clinically relevant (in girls their stage of maturation is different)

• Not different when controlled for their height and skin folding

• AA have sympathetic tone, dopamine Hydrolyase, glucose, renin & heart rate

periph. resistance, insulin & Na intol

Genetic/Environmental Factors

• Familial prevalence

• dietary Na, K, Ca

• Unlike adults, children do not respond to dietary changes

• Among adolescents, females respond better to Na diet

Mutner2004 JAMA 291(17):2007; Williams 1992 AJPH 82:358

Weight and BP

• A direct relationship has been found between weight and BP at as early as 5 years of age

• This is more prominent at the second decade of life

• Between 13-17% of adolescents are obese and in more recent studies up to 30%

Prevalence of Hypertension

• About 25% of the adult population in the US has HTN

• In children 90% is secondary HTN

• In adults 90% is essential HTN

• Direct relationship exists between weight and BP

Accurate Measurement• Use Right arm• Sphygmomanometer device

– Oscillometric in < 3yo – Auscultative method with manual sphygmomanometer

• Cuff size– Too small = falsely high– Too large = falsely low– Width of cuff = 2/3 shoulderelbow

• Inflate cuff 20-30 mm Hg above the point at which the radial pulse disappears.

• Korotkoff Sounds– Now use 5th phase for all aged infants/children

CV Effects of HTN

• It accelerates Coronary artery disease

• Risk factor for CVA, heart and renal failure

• Direct correlation of LV measurement and HTN

Ambulatory Blood Pressure Measurement

• 24 hr. ABPM is used in many centers for adults and now children BP monitoring

• Better than a ‘snap shot’ or single measurement

• Detects circadian rhythms

• Different in Txp patients “non-dippers”

Etiology of Pediatric HTN

• Spurious- inappropriate cuff, apprehension

• Renal- renal parenchymal dz, acute GN, renal artery stenosis, renal vein thrombosis, pyelonephritis, HSP, HUS, stones, polycystic kidney dz

• Cardiovascular- coarctation of the aorta, PDA, AV fistula

• Endocrine- Hyperthyroidism, CAH, Cushing syn, Pheochromocytoma, Conn syndrome

Etiology of Pediatric HTN (2)

• CNS- ICP, Guillain-Barre,

• Drugs- Sympathomimetics, steroids, cocaine & licorice

• Neoplasm- Wilms Tumor, neuroblastoma

• Collagen vascular/autoimmune• Immobilization/Traction• Malignant Hyperthermia

Diff Dx. Of HTN: Newborn

• Renal Artery Stenosis or Thrombosis

• Renal Vein Thrombosis

• Congential Anomalies

• Coarctation of the Aorta

• BPD, PDA less common IVH

Dif. Dx. of HTN: Infancy

• Coarctation of the aorta

• Renovascular disease

• Renal parenchymal disease

Dif. Dx. Of HTN: 1-6 years

• Renal Parenchymal disease

• Renovascular disease

• Coarctation of the Aorta

• Endocrine causes (less common)

• Essential HTN (less common)

Dif. Dx. of HTN: 6-12 years

• Renal Parenchymal disease

• Renovascular disease

• Coarctation of the Aorta

• Endocrine causes (less common)

• Essential HTN (less common)

• Iatrogenic (less common)

Dif. Dx. of HTN: 12-18 years

• Essential HTN

• Iatrogenic

• Renal Parenchymal disease

• Renovascular disease (less common)

• Coarctation of the Aorta (less common)

• Endocrine causes (less common)

Causes of Pediatric HTN• Neonates

– Renal, renal, renal!• Renal artery thrombosis• Renal artery stenosis• Congenital renal malformations

– Coarctation of the aorta– BPD

• Infants to 10 y.o.a.– Renal, renal, renal!

• Renal artery stenosis• Renal parenchymal disease

– Coarctation

• 11y.o.a to adolescence – Renal parenchymal disease– Primary (essential) hypertension (on the rise!)

Hypertensive Crises

• Hypertensive Emergency:• BP greater than 99th percentile with evidence of end

organ damage– Encephalopathy, Infarction, Cerebral hemorrhage,

Myocardial ischemia

• Hypertensive Urgency:• BP greater than 99th percentile without evidence of

end organ damage

Evaluation of HTN: History

• NB period (UAC, BPD), growth pattern, use of medications (cold, contraceptives)

• Urological or renal disorders

• Endocrine (sweat, wt. loss, palpitations, fevers, muscle cramps & weakness

• Family Hx

Evaluation of HTN: PE

• Fundoscopy (papilledema, hemorrhage)• Thyroid exam• Evidence of heart failure (gallop, hepatomegaly,

edema), check 4 extremity BP & Femoral pulses• Abdominal exam (masses, bruit)• GU exam (virilization)• Neurologic exam (including visual acuity)

Evaluation of HTN: PE (2)

• Neurofibromas, café-au-lait spots, tuberous sclerosis, moon fascies, buffalo hump, hirsutism, rashes

• Enlarged kidneys, abdominal masses

• Chromosomal abnormalities (Turner, Williams, Von Hippel-Lindau)

Diagnostic Evaluation

• Urinalysis (protein, blood)

• Electrolytes• BUN/Cr• CBC• EKG• Renal US

Consider:• TSH• Head CT• Echocardiogram• Renin level• Urine VMA, HVA• Urine drug screen

Evidence of End Organ Damage

• Headache• Vision changes• Altered mental status

(lethargy)

• Vomiting• Epistaxis

• Papilledema• Retinal hemorrhages• Cranial nerve palsy• Paralysis• Left Vent. H • Heart failure

HTN Evaluation Phase 1

• CBC, UA, Urine C&S (PRN)

• SMAC 12, lipid panel

• Renal US

• Heart Echocardiogram

HTN Evaluation Phase 2

• Renal Scan (with ACE inhibitor?)

• Urine cathecolamines

• Plasma and urinary steroids

HTN Evaluation Phase 3

• Renal Artery Imaging or renal vein sampling

• Caval sampling for cathecolamines

• Scan of adrenals

Goals of BP control

• Do NOT decrease BP to normal levels because of hypo-perfusion

• Aim of treatment should be 25-30% reduction (may need to decrease further if still symptomatic)

• The goal is to achieve BP levels bellow the 95th

(at the 50th) percentile for age and to prevent long term effects

• Lower BP slower in patients with chronic rather than acute hypertension (look at EKG/ECHO)

Management

• Rule out hypertension secondary to elevated intracranial pressure before lowering BP

• Lowering BP too fast can cause hypotension, poor cerebral perfusion causing permanent neurologic damage including vision loss, myocardial ischemia, renal hypoperfusion and ATN

• Non-pharmacological means: diet, exercise

HTN Rx: Diuretics

• HCTZ - Decreases morbi/mortality

• They do not work well if GFR < 30 ml/min

• Most effective in combination w/other agents even at low doses

• Caution: DM2, gout & cardiac arrhythmias

• Used more for adult care

HTN Rx: -Blockers

• Selective -Blockers (prazosin, terazosin) block post-synaptic receptors, relax vascular smooth muscles and vascular resistance

• Better at bedtime

• Side effects: BP (syncope w/1st dose), exacerbates incontinence

-Blockers are used in:

• DM• Lipid abnormalities• Symptomatic benign

prostate hypertrophy

• Non-selective HTN -Blockers (phentolamine and phenoxybenzamine) are used in pheochromocytoma

Direct-Acting Vasodilators

• Hydralazine & Minoxidil produce direct arterial vasodilation

• Reflex tachycardia & fluid retention

• May induce lupus-like syndrome (+ANA)

• Nitroprusside for emergencies but check thyocyanide levels in 3 days

Hydralazine

• Vasodilator, arteriole

• Dose: 0.1-0.5 mg/kg/dose IV, may be repeated two times if no response, otherwise q 4-6hrs

• Onset: 5-20 min

• Half life: 2-6 hrs

• Disadvantages: SLE-like syndrome, reflex tachycardia, flushing, worsens angina

• DIAZOXIDE is similar in profile

Clonidine• Centrally acting α2 agonist

– Reduces cardiac output and peripheral resistance

• Dose: 1-2.5mcg/kg/dose PO q 6 hrs

• Onset: rapid (minutes)

• Half life: up to 12 hrs

• Advantages: Emergency Rx, ease of administration (PO) and can transition to long term therapy

• Disadvantages: side effects (sedation, dry mouth, dizziness, postural hypotension), rebound hypertension after abrupt withdrawal in chronic use

Nitroprusside

• Vasodilator, venous and arterial• Dose: 0.5-8 mcg/kg/min

• Onset: instantaneous

• Half life: 10 min, thiocyanate 3-7 days

• Advantages: Instantaneous onset and able to be titrated quickly

• Disadvantages: Decreases preload and afterload and causes reflex tachycardia, photo degradation (cover in foil), metabolized to cyanide then thiocyanate (renally excreted and can cause nausea, vomiting, hallucinations, metabolic acidosis)

-Blockers

• Decrease cardiac contractility, renin release and central sympathetic outflow

• Good choice with CAHD, atrial fib, SVT, migraine, hyperthyroidism and pro-op HTN

• Shown to morbi/mortality• Depression, sleep disturbance, impotence and

exercise tolerance (less severe w/ -1 selective blockers

-Blockers Should be avoided in:

• Asthma • COPD • 2nd and 3rd. degree

heart block • Sick sinus syndrome

• Moderate LV dysfunction

• IDDM• Peripheral Vascular

Disease

Labetolol• Combined β and α blocker (approx 10-15% α)

– Reduces cardiac output, some peripheral vasodilatation

• Dose: 0.2-1mg/kg IV bolus or 0.25-3mg/kg/hr drip

• Onset: 5-10 min

• Half life: 5 hrs

• Advantages: used in renal disease, can be given in frequent boluses, no adverse effect on ICP or hypoxic VQ mismatch.

• Disadvantages: not as potent as nicardipine & nitroprusside, not well studied in children, contra-indicated in asthma and decreased left ventricular function.

Ca-Channel Blockers

• Inhibit the movement of Ca ions from plasma into the cell through voltage-dependent Ca Channels, leading to vasodilation and low BP

• Verapamil and diltiazem peripheral resistance w/significant inotropic effects, slowing AV conductionCHF in LVH

Ca-Channel Blockers:

• Short acting not used in Chronic Rx

• Sublingual nifedipine may cause MI

• Good choice for elderly, AA & angina pats

• Avoid in WPW Syndrome

Nicardipine

• Calcium channel blocker

• Dose: 1-5 mcg/kg/min, bolus 0.03mg/kg

• Onset: rapid (1-2 min)

• Half life: 40 min

• Advantages: fairly even drop of BP, hypotension unusual, reversible with Ca++

• Disadvantages: may increase ICP

Nifedipine

• Class II Calcium Channel Blocker

• Arguably the most studied drug for pediatric hypertension– 1995 moratorium placed on sublingual fast-

acting use in adults– Hypotension-related myocardial ischemia

• Not FDA approved for hypertension

Nifedipine• Calcium Channel Blocker

– Peripheral arteriolar dilation

• Dose: 0.25-0.5mg/kg q 4-6 hrs po/SL

• Onset: 5-10 min, peak 30-60 min

• Half life: 3-4 hrs

• Advantages: can improve GFR and renal plasma flow, ease of administration, rapid onset, very effective (even in long-standing or severe hypertension)

• Disadvantages: unpredictable drop in blood pressure, reflex tachycardia & cardiac output, metabolized by cytochrome P450 system

ACE-Inhibitors

• Inhibit angiotensin converting enzyme (AI to AII does not take place)

• Appropriate first line of Rx for DM, heart failure, low ejection Fx and post-MI

• Diuretics can enhance action

ACE-Inhibitors

• NEVER USE IN PREGNANT WOMEN

• Never used if bil. renal artery stenosis

• Cough 5-20% (related to bradykinin level)

• Caution with renal impairment

• May be used in Txp patients

Angiotensin-II Receptor Antagonists

• Similar effects as an ACE inhibitor

• Less cough as they do not bradykinin

• Some cases of angioneurotic edema reported

HTN Complications

• Retinal Involvement

• I and II changes (arteriolar narrowing, A-V nicking & copper wiring) = Chronic HTN

• III and IV (rupture of vessels. Hgs. And exudates, optic disk edema) = accelerated or malignant HTN.

• May resolve w/BP control

Coronary Artery Disease

• HTN increases hemodynamics

• Regression of LVH improves CHF

• HTN leads to CAD due to LVH

• Rx of HTN alone does not resolve it

Hypertension

Hyperlipidemia

Physicalinactivity

CARDIOVASCULAR RISK INKIDNEY PATIENTS

Smoking

Diabetes

Homocysteinemia

Periodontaldisease

Renal Involvement

• HTN is the cause of renal failure in 33% of patients

• Renal involvement is more frequent in AA or the elderly

Cerebrovascular Involvement

• The main Cx. Of HTN is thrombotic rather than hemorrhagic

• Endothelial damage, abnl. Levels of hemostatic factors and abnormal blood flow is seen in HTN

UNC HTN Trials

• Ramipril: Ages 6-16 Outpatient

• Olmesartan: Ages 1-16 Outpatient

• IV Nicardipine: Ages 2-16 GCRC Study

• Barbara Gordon and John Bryson: Nurse coordinators

• CALL US!

Sources

• 4th Report on HTN: http://pediatrics.aappublications.org/cgi/content/full/114/2/S2/555

• Sinaiko. Hypertension in Children. NEJM 1996; 335(26)1968-73.

• Temple, Nahata. Treatment of Pediatric Hypertension. Pharmacotherapy 2000; 20(2)140-50.

• Groshong. Hypertensive Crisis in Children. Pediatric Annals 1996; 25(7)368-76.

• www.nhlbi.nih.gov

Other Sources• Egger, Deming, Hamada, Perkin, Sahney. Evaluation of the safety of short-acting

nifedipine in children with hypertension. Pediatr Nephrol (2002)17:35-40.• Blaszak, Savage, Ellis. The use of short-acting nifedipine in pediatric patients with

hypertension. J Peds 2001; 139(1)34-37.• Flynn, Mottes, Brophy, Kershaw, Smoyer, Bunchman. Intravenous nicardipine for

treatment of severe hypertension in children. J Peds 2001;139(1)38-41.• Michael, Groshong, Tobias. Nicardipine for hypertensive emergencies in children

with renal disease. Pediatri Nephrol (1998)12:40-42.• Varon, Marik. The Diagnosis and Management of Hypertensive Crises. Chest

2000; 118(1) 214-27.• Calhoun, Oparil. Treatment of Hypertensive Crisis. NEJM. 1990;323:1177-1183• Deal, Barratt, Dillon. Management of Hypertensive Emergencies. Arch Dis Child.

1992;667:1089-1092