Transcript HYPERTENSION - University of North Carolina at Chapel Hill

HYPERTENSION
IN 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**
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
Daniels J Peds 1996: 125:208;
Harshfield AJH 2002 15:525
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
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%
Mutner2004 JAMA 291(17):2007;
Williams 1992 AJPH 82:358
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 shoulderelbow
• 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)
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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
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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
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Renal Parenchymal disease
Renovascular disease
Coarctation of the Aorta
Endocrine causes (less common)
Essential HTN (less common)
Dif. Dx. of HTN: 6-12 years
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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
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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
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Consider:
TSH
Head CT
Echocardiogram
Renin level
Urine VMA, HVA
Urine drug screen
Evidence of End Organ Damage
• Headache
• Papilledema
• Vision changes
• Retinal hemorrhages
• Altered mental status • Cranial nerve palsy
(lethargy)
• Paralysis
• Vomiting
• Left Vent. H
• Epistaxis
• Heart failure
HTN Evaluation Phase 1
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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
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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
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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 voltagedependent Ca Channels, leading to
vasodilation and low BP
• Verapamil and diltiazem  peripheral
resistance w/significant inotropic effects,
slowing AV conductionCHF in LVH
Ca-Channel Blockers:
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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 fastacting use in adults
– Hypotension-related myocardial ischemia
• Not FDA approved for hypertension
Nifedipine
• Calcium Channel Blocker
– Peripheral arteriolar dilation
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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
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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
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HTN increases hemodynamics
Regression of LVH improves CHF
HTN leads to CAD due to LVH
Rx of HTN alone does not resolve it
Smoking
Diabetes
Hypertension
Physical
inactivity
Hyperlipidemia
Periodontal
disease
Homocysteinemia
CARDIOVASCULAR RISK IN
KIDNEY PATIENTS
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
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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/con
tent/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)14050.
• 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