Pediatric Hypertension - Welcome — UNC School of …€¦ · Initial work-up for pediatric hypertension A diagnostic work-up should be conducted to rule out secondary causes of

CMECME

A review of proper screening, diagnosis, evaluation, and treatment

CMECME

Pediatric Hypertension

CMECME

EDUCATIONAL OBJECTIVES

• Identify children and adolescents for whom

hypertension screening is appropriate

• Implement an initial workup for pediatric

hypertension

• Develop treatment plans for children with

essential or secondary hypertension

Nicholas, a 10-year-old boy with a history of

intermit tent asthma and at tention def icit

hyperactivity disorder, is seeing you for the first

time for a well child visit. He has no complaints and

his mom has no specific questions or concerns. On

review of symptoms, Nicholas reports that he has some

chest pain when he has an asthma exacerbation. Current

medications include methylphenidate once daily and an

albuterol metered-dose inhaler as needed. His family history

reveals hypertension (HTN) in his father and paternal

grandfather, and diabetes mellitus in his paternal grandfather.

His mother and 12-year-old sister are healthy with no chronic

medical problems. On physical exam, his anthropometrics

and vital signs are as follows:

Height: 140 cm (50%)

Weight: 45 kg (95%)

Body mass index (BMI): 23 (>95%)

Temperature 37 °C

Heart rate: 85 bpm

Blood pressure (BP): 124/82 mm Hg by automated cuff

Physical exam is normal

46 www.contemporarypediatrics.com Vol. 25, No. 11

cntped1108_046.pgs 11.04.2008 12:44 ADVANSTAR_PDF/X-1a blackyellowmagentacyan

TAMMY BRADY, MD, GEORGE K. SIBERRY, MD, MPH, AND BARRY SOLOMON, MD, MPH

You reference the BP tables published in the Fourth

Report by the National High Blood Pressure Education

Program Working Group on High Blood Pressure in Children

and Adolescents,1 and discover that the BP norms for

a child of this age, gender, and height percentile are as

follows:

50%: 102/61

90%: 116/76

95%: 120/80

99%: 127/88

This clinical scenario of a child found to have an

elevated initial blood pressure is not uncommon. Pediatric

hypertension, previously reported to affect only 0.3% to

1.2% of children in the 1970s and 1980s,2,3 now affects

up to 5% of all children.4 One possible explanation for

this increase may be the current growing population

of obese children.5 The prevalence of hypertension in

children increases with increasing BMI percentile,4 placing

obese children at three-times higher risk of becoming

hypertensive when compared to non-obese children.5

Regardless of the cause for this increase, a child with

hypertension can be a dilemma for many primary care

providers. It is essential for providers to understand when

to screen for hypertension, how to conduct an initial

work-up, how to manage these patients, and when to

refer them to a subspecialist.

Which children should get their blood pressure checked?

Current recommendations state that all children 3 years of

age and older should have their blood pressure measured

at all health care encounters, including both well child

care and acute care or sick visits. Certain children younger

than 3 with comorbid conditions should also have their BP

measured at each visit. This population includes children

under 3 with1:

History of prematurity

History of low birth weight or neonatal intensive

care unit (NICU) stay

Presence of congenital heart disease, kidney disease,

or genitourinary abnormality

Family history of congenital kidney disease

Recurrent urinary tract infection (UTI), hematuria,

proteinuria

Transplant of solid organ or bone marrow

Malignancy

Taking medications known to increase blood

pressure (steroids, decongestants, nonsteroidal

anti-inflammatory drugs [NSAIDs], beta-adrenergic

agonists)

Presence of systemic illness associated with hypertension

(neurofibromatosis, tuberous sclerosis)

Evidence of increased intracranial pressure

•

•

•

•

•

•

•

•

•

•

DisclosuresEditors Toby Hindin, Jeannette Mallozzi, Jeff Ryan, and John Merriman disclose that they do not have any financial relationships with any manufacturer in this area of medicine.

Manuscript reviewers disclose that they do not have any financial relationships with any manufacturer in this area of medicine.

DR. BRADY is an assistant professor of pediatric nephrology at Johns Hopkins University School of Medicine.

DR. SIBERRY is an assistant professor of pediatrics in the divisions of general pediatric and adolescent medicine and pediatric infectious diseases at Johns Hopkins Hospital.

DR. SOLOMON is an assistant professor of pediatrics in the division of general pediatrics and adolescent medicine at Johns Hopkins Hospital, and medical director of the Harriet Lane Clinic at the Johns Hopkins School of Medicine.

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Target audience: Pediatricians and primary care physicians

To earn CME credit for this activityParticipants should study the article and log on to www.contemporarypediatrics.com, and click on the “Earn CME Credit” button on the left-hand side. Participants must pass a post-test and complete an online evaluation of the CME activity. After passing the post-test and completing the online evaluation, a CME certificate will be e-mailed to them. The release date for this activity is November 1, 2008. The expiration date is November 1, 2009.

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Unapproved/off-label use discussion

Faculty may discuss information about pharmaceutical agents, devices, or diagnostic products that are outside of FDA-approved labeling. This information is intended solely for CME and is not intended to promote off-label use of these medications. If you have questions, contact the medical affairs department of the manufacturer for the most recent prescribing information. Faculty are required to disclose any off-label discussion.

HYPERTENSIONIL

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>>p.48

NOVEMBER 2008 CONTEMPORARY PEDIATRICS 47


CMECME

How should blood pressure be measured in children?The proper technique for BP measurement via manual

auscultation is as follows1:

1. Ensure that the child has been resting for a minimum

of five minutes prior to measurement. The child should

be sitting with back supported, both feet on the floor and

right cubital fossa supported at heart level.

2. Choose the appropriate cuff size:

The cuff width should cover ~70% of the distance

between the acromion (bony extremity of the

shoulder girdle) and the olecranon (tip of the elbow).

(Figure 1)The cuff bladder length should be 80 to 100% of the

arm circumference, and the width should be at least

40% of the arm circumference at the midpoint of the

acromion-olecranon distance.

The importance of choosing the proper cuff size

should not be underestimated. Cuff sizes differ among

manufacturers (ie, all “child size” cuffs are not made

with the same dimensions), and choosing the wrong

cuff size can lead to either obtaining a falsely elevated

or underestimated BP reading (seen with a cuff that is

too small or too large, respectively).

3. Apply the cuff to the child’s bare arm.

4. Locate the radial pulse, inflate the sphygmomanometer

to 60 mm Hg and then slowly inf late in increments

•

•

of 10 mm Hg until the pulse disappears. The value at

which the pulse disappears plus 30 mm Hg is peak

inflation.

5. Deflate; wait 30 seconds.

6. Place the stethoscope over the brachial artery pulse (2

cm above the cubital fossa).

7. Inflate to the peak inflation level and then deflate at

2 to 3 mm Hg/second to a level 10 mm Hg lower than

the level of last Korotkoff ’s sound (K5).

8. Systolic blood pressure (SBP) is onset of two or more

consecutive tapping sounds (K1). Diastolic blood

pressure (DBP) is disappearance of Korotkoff ’s sounds

(K5); a bell can be used to best hear softer Korotkoff ’s

sounds.

If sounds can be heard down to 0 mm Hg, repeat

using less pressure.

If still present, use K4 as DBP (muffling of sounds).

But what about automated (oscillometric) measure-

ments? While there is a place for automated BP

measurements in a busy pediatric practice, the preferred

method is by manual auscultation. There are several reasons

for this preference.

One reason is that the normative blood pressure

tables used in the diagnosis of hypertension are based

on auscultatory—not oscillometric—BP values. Another

factor is that oscillometric machines (ie, “Dynamap”)

do not directly measure BP. Rather these machines

estimate the SBP and DBP based on the point of maximal

oscillation (mean intra-arterial pressure) during deflation

using algorithms that vary from one device to another.6

Additionally, oscillometric machines accommodate to the

previous reading by automatically inflating to 30 mm Hg

above the expected (ie, previous) SBP reading.

In order to optimally use these machines, providers should

discard the first reading, repeat the BP two more times one

minute apart, and then use the average of these two readings.

If a child’s BP is elevated based on this method (an elevated

BP is defined as a systolic or diastolic BP measurement

greater than or equal to the 90th percentile for that child’s

age, gender, and height percentile or a SBP of 120 mm Hg

and/or DBP of 80 mm Hg at any age), a BP should then be

measured by manual auscultation. If the BP continues to be

elevated as defined above, the BP should be repeated twice

manually at the same office visit, and an average SBP and DBP

should be used.

•

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Figure 1 Choose the appropriate size cuff



HYPERTENSION

Because of the inherent limitations to automated BP

readings, public blood pressure machines should be used

with caution when including them in your evaluation and

/or management of pediatric hypertension. Automated cuffs

need to be calibrated at regular intervals, and there is often

no readily available record of scheduled maintenance of

these public machines. Also, there is often only one cuff

size available, leading to false BP readings as described

above.7,8

Back to your patient

You repeat Nicholas’ BP by manual auscultation and obtain

a reading of 126/84 mm Hg; one minute later it’s 116/84 mm

Hg, giving him an average BP of 121/84. Again, referencing

the Fourth Report BP tables, you discover that Nicholas’

manual BP is between 120/80 and 132/93 (the 95th percentile

and 99th percentile plus 5 mm Hg for his age, gender and

height percentile). As he is asymptomatic (no complaints

of nausea, vomiting, epistaxis, blurry vision, or diplopia),

you have him come back weekly on two more occasions.

Manual BPs at these visits confirm he has sustained BPs

greater than or equal to the 95th percentile, and less than

the 99th percentile plus 5 mm Hg. You diagnose him with

Stage 1 Hypertension and initiate a work-up as outlined

by the Fourth Report*:

SBP or DBP percentile

When to recheck blood pressure?

Normal <90th Next health care visit

Prehypertension 90th to <95th

or

= 120/80 and

<90th percentile

Six months

Stage 1

hypertension

95th to

[99th + 5 mm Hg]

One to two weeks or

sooner if symptomatic;

if it continues to be

elevated on two or more

occasions, refer within

one month

Stage 2

hypertension

>99th + 5 mm Hg Evaluate or refer within

one week, or immediately

if symptomatic

*Adapted from the Fourth Report1

Initial work-up for pediatric hypertensionA diagnostic work-up should be conducted to rule out

secondary causes of hypertension for any child with a

confirmed diagnosis of prehypertension with comorbid

conditions (ie, African-American race, obesity, kidney

disease, insulin resistance or diabetes mellitus, history

of umbilical lines or recurrent urinary tract infections,

family history of HTN).

While primary (or “essential”) HTN is on the rise

in children, it should still be considered a diagnosis of

exclusion. Secondary hypertension is more common in

children than in adults, and is more likely the younger the

child and the higher the blood pressure at presentation.1,11

Similarly, the likely etiologies will vary by age of the child

(Table 1).

Table 1

Initial work-up for pediatric hypertension(in order of prevalence)9,10

Age range:

First year of life Secondary (99%)

Coarctation of the aorta

Renovascular*

Renal parenchymal disease

Miscellaneous causes†

Neoplasia (4%)

Endocrine (1%)

•

•

•

•

•

•

1 to 12 years Secondary (70% to 85%)

Renal parenchymal disease


Reflux nephropathy

Renovascular

Endocrine

Neoplasia

Miscellaneous

Primary (Essential) (15% to 30%)

•

•

•

•

•

•

•

12 to 18 years Primary (Essential) (85% to 95%)

Secondary (5% to 15%)

Same causes as 1- to

12-year-olds

•

*Renal artery/vein thrombosis, renal artery stenosis.†Bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH).

>>p.50



CMECME

When evaluating a child with HTN, one should start with

a focused history and physical (Tables 2 and 3). For all children with diagnosed hypertension, the initial

evaluation should include:

Basic metabolic panel (electrolytes, blood urea nitrogen

[BUN], creatinine), urinalysis and urine culture to

exclude renal disease and chronic pyelonephritis

Complete blood count to exclude anemia, which would

be consistent with chronic renal disease

Fasting lipids and glucose to identify lipid and/or

metabolic abnormalities

Thyroid function tests to exclude thyroid disease

Renal ultrasound with Doppler examination of the

renal vasculature to ensure the patient has two kidneys

of appropriate size, without cysts or other structural/

congenital anomalies, and to evaluate f low in both

organs

Echocardiogram to exclude cardiac etiology and evaluate

for evidence of left ventricular hypertrophy indicating

end-organ damage from long-standing hypertension

Retinal exam to evaluate for the presence of retinal

vascular changes; hypertensive retinopathy is another

form of end-organ damage

Additional evaluation for some children will include:

Drug screen for children or adolescents with a history

suggestive of using illicit drugs or substances that might

cause hypertension

Polysomnography for children with a history of

loud snoring or daytime somnolence, suggestive of

obstructive sleep apnea (see Obstructive sleep apnea

and hypertension on page 74)

Further evaluation for children under age 10 with Stage

1 HTN, or any child with Stage 2 HTN (generally done

by a specialist) is outlined as follows:

Ambulatory blood pressure monitoring to identify

children with white coat hypertension, and/or get more

information on blood pressure pattern and average

daily blood pressure

Plasma renin to identify low renin states, which would

suggest mineralocorticoid disease

Renovascular imaging to identify renovascular disease

(ie, renal artery stenosis). Some examples of imaging

include an magnetic resonance angiography, 3D

computed tomography, angiography (gold standard;

can simultaneously diagnose and treat renal artery

stenosis)

Plasma and urine steroid levels to identify steroid

mediated hypertension

•

•

•

•

•

•

•

•

•

•

•

•

•

Table 2

Important history and physical elements for hypertension evaluation

History

Symptoms suggestive of endocrine etiology (ie, weight loss,

sweating, flushing, fever, palpitations, muscle cramps, weakness, or

constipation)

History of prematurity, neonatal course, UAC/UVC lines

History of UTIs

Symptoms of obstructive sleep apnea (ie, difficulty falling asleep,

multiple nighttime awakenings, snoring, daytime somnolence)

MedicationsSteroidsDecongestants/cold preparations Oral contraceptive pillsNSAIDsStimulant medications (eg, dexedrine, methylphenidate)Beta-adrenergic agonists (eg, theophylline)ErythropoietinCyclosporine/tacrolimusTricyclic antidepressantsRecent abrupt discontinuation of antihypertensives

Nutritional supplements

Family history of HTN, early cardiovascular (CV) or cerebrovascular

events, end-stage renal disease (ESRD)

Diet (caffeine, salt intake)

Smoking/drinking/illicit drugs (eg, tobacco, ethanol, amphetamines,

cocaine, phencyclidine, MDMA [ecstasy])

Physical activity

•

•

•

•

•

–

–

–

–

–

–

–

–

–

–

•

•

•

•

•

Physical exam

Four extremity pulses and BPs

Moon facies, truncal obesity, buffalo hump

Retinopathy

Enlarged tonsils

Thyromegaly

Skin lesions (café au lait spots, neurofibromas, adenoma sebaceum,

striae, hirsutism, butterfly rash, palpable purpura)

Evidence of BPD, congestive heart failure

Abdominal mass, abdominal bruits

Edema

Pregnancy

•

•

•

•

•

•

•

•

•

•



HYPERTENSION

Plasma and urine catecholamines to ident i f y

catecholamine-mediated hypertension (ie, pheo-

chromocytoma)

Your patient’s evaluation

Nicholas’ initial work-up is negative: he has normal electrolytes,

renal function, hemoglobin, thyroid function and lipid profile.

• Renal ultrasound reveals two normal-sized kidneys with normal

arterial and venous flow. Echocardiogram demonstrates normal

left ventricular mass, and his ophthalmology evaluation ruled

out hypertensive retinopathy. You diagnose him with primary

hypertension and recommend lifestyle modifications as he

continues to be asymptomatic, and does not have evidence of

end-organ damage.

Table 3

Physical examination findings suggestive of definable hypertension

Findings* Possible etiology

Vital signs Tachycardia

Decreased lower extermity pulses;

drop in BP from upper to lower

extremities

•

•

Hyperthyroidism, pheochromocytoma, neuroblastoma, primary hypertension


•

•

Eyes Retinal changes• Severe hypertension, most likely to be associated with secondary hypertension•

Ear, nose, and throat Adenotonsillar hypertrophy• Suggests association with sleep disordered breathing (sleep apnea), snoring•

Height/weight Growth retardation

Obesity (high BMI)

Truncal obesity

•

•

•

Chronic renal failure

Primary hypertension

Cushing syndrome, insulin resistance syndrome

•

•

•

Head and neck Moon facies

Elfin facies

Webbed neck

Thyromegaly

•

•

•

•

Cushing syndrome

Williams syndrome

Turner syndrome

Hyperthyroidism

•

•

•

•

Skin Pallor, flushing, diaphoresis

Acne, hirsutism, striae

Café-au-lait spots

Adenoma sebaceum

Malar rash

Acanthrosis nigricans

•

•

•

•

•

•

Pheochromocytoma

Cushing syndrome, anabolic steroid abuse

Neurofibromatosis

Tuberous sclerosis

Systemic lupus erythematosus

Type 2 diabetes

•

•

•

•

•

•

Chest Widly spaced nipples

Heart murmur

Friction rub

•

•

•

Turner syndrome


Systemic lupus erythematosus (pericarditis), collagen vascular disease,

end-stage renal disease with uremia

•

•

•

Abdomen Apical heave

Mass

Epigastric/flank bruit

Palpable kidneys

•

•

•

•

LVH/chronic hypertension

Wilms tumor, neuroblastoma, pheochromocytoma

Renal artery stenosis

Polysystic kidney disease, hydronephrosis, multicystic dysplastic kidney, mass

(see above)

•

•

•

•

Genitalia Ambiguous/virilization• Adrenal hyperplasia•

Extremities Joint swelling

Muscle weakness

•

•

Systemic lupus erythematosus, collagen vascular disease

Hyperaldosteronism, Liddle syndrome

•

•

Adapted from Flynn JT: Prog Pediatr Cardiol 2001;12:177*Findings listed are examples of physical findings and do not represent all possible physical findings.

>>p.52



CMECME

Primary hypertension

Once a comprehensive work-up looking for secondary

causes of hypertension has been completed and found

to be negative, a diagnosis of primary (or “essential”)

hypertension can be made. This diagnosis, while still

considered to be a diagnosis of exclusion, is more frequently

found in post-pubertal and African American children, and

in children with BP on the lower end of the hypertensive

spectrum (ie, just above the 95th percentile). It is also more

frequently found in children with a positive family history

of HTN, and in those who are overweight or obese.12

The role of obesity in this diagnosis should not be

overlooked. The number of children with primary

hypertension is on the rise concomitant with the rise in

childhood obesity.4,5,13,14 Several studies have demonstrated

the increased risk of hypertension that exists among obese

children. For example, for each one unit increase in BMI

z-score, children 8 to 17 years of age have been shown to

have twice the risk of having a BP greater than the 95th

percentile.13 Even children as young as 2 to 5 years of age

are not immune to these effects of obesity and overweight;

their SBP and DBP have also been shown to increase with

increasing BMI.15

Obesity and hypertension both separately and together put

children at increased cardiovascular risk.16 Obese children

are more likely to have clustering of cardiovascular risk

factors in addition to hypertension, such as hyperlipidemia,

insulin resistance, type 2 diabetes mellitus and left

ventricular hypertrophy.5 Autopsy studies of children reveal

that even early in life there is evidence of coronary artery

pathology, associated with BMI, dyslipidemia, and systolic

and diastolic BP.17

The link between OSA and hypertension

The mechanism by which obstructive sleep apnea (OSA) leads to hypertension is still

not well understood. One study has found a linear relationship between the severity

of OSA symptoms, and the incidence of newly diagnosed HTN, independent of body

mass, age, gender, or baseline BP and cigarette and alcohol consumption.1

It is likely that the hypoxemia and hypercapnea experienced by individuals with

OSA leads to an increase in sympathetic nervous system activity, which then leads to

an increase in peripheral vascular resistance. Hypoxia has been shown to increase

levels of endothelin-1, a known potent and long-acting vasoconstrictor, as well as

other circulating vasoconstrictors.

Because appropriate treatment of OSA has been shown to decrease daytime and

nighttime mean systolic and diastolic blood pressures by up to 10 mm Hg,2 screening

for OSA should be included in a clinician’s work-up of a child with hypertension.

Reference

1. Peppard PE, Young T, Palta M, et al: Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342:13782. Becker HF, Jerrentrup A, Ploch T, et al: Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003;107:68

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HYPERTENSION

Additionally, obesity and hypertension in childhood places

these children at higher risk for obesity and hypertension

as adults,20 with increased risk for CV morbidity and

mortality.21 Blood pressure tracking from childhood to

adulthood is much more likely to occur with increasing

BMI.22 Because of this BP tracking from childhood to

adulthood, lifestyle changes should be emphasized for all

hypertensive children, but should also particularly be aimed

at obese children with primary hypertension.

Management of pediatric hypertension

Who gets treated?

Once a child is diagnosed with HTN and is appropriately

staged and evaluated, treatment should be initiated and

aimed at the underlying etiology. Children with pre-

hypertension or asymptomatic, Stage 1 Primary HTN who

do not have evidence of end-organ damage or diabetes,

should be “prescribed” lifestyle modifications (Table 4)

and be re-evaluated in six months. Children with persistent

hypertension after six months—despite attempts at lifestyle

modification—should be started on an anti-hypertensive

medication. Similarly, any child with symptomatic HTN,

Stage 2 HTN, secondary HTN, diabetes or evidence of end-

organ damage should be started on an anti-hypertensive

medication.

Even after deciding to treat with an anti-hypertensive,

nonpharmacologic lifestyle interventions should continue to

be emphasized at each visit, particularly in overweight or

obese children. It has been shown that weight loss by itself

can decrease blood pressure,23 and other associated CV

risk factors should also be expected to regress or improve

with weight loss.24 Additionally, increased physical activity

and fitness has been shown to be associated with lower

childhood BP and a reduced risk of HTN 16 to 50 years

later.25 Obese children are also more likely to be salt sensitive,

and thus more likely to respond to dietary restriction of

sodium, and improved intake of potassium. The insulin

resistance often seen in obese children leads to salt and

water retention,26 and preliminary studies have indicated

that adipocytes may secrete factors leading to increased

serum aldosterone, which then leads to increased renal

sodium reabsorption.27-29

Often implementing these changes for all family

members is necessary before any appreciable benefit can

be achieved.

How should I treat?

There are multiple medications available to treat hypertension

in children, for which pediatric dosing is now available

(Table 5). The particular agent

chosen shou ld be a imed at

treating the underlying etiology,

with particular attention being

paid to co-morbid conditions

such as diabetes, asthma, and

migraines.

Af ter a fu l l eva luation to

determine etiology is completed

(and any interventions are under-

taken to treat the underlying

disease process), initial antihyper-

tensive therapy for a child who

continues to be hypertensive

should include either a calcium

channel blocker (CCB) or an

angiotensin converting enzyme

(ACE) inhibitor, unless there is a

compelling reason to use an agent

from another class. Both CCBs and

ACE inhibitors are generally well tolerated with a minimal

side effect profile, and can be dosed once daily.

Obese children with primary hypertension may

particularly benefit from ACE inhibitors or angiotensin-

Weight loss by

itself can

decrease blood

pressure, and

other associated

CV risk factors

should also

be expected

to regress or

improve with

weight loss.

Point

Taken

Table 4

Non-pharmacologic interventions1

Aerobic exercise: 30 to 45 minutes “most days” of the week

Limit sedentary activities to less than two hours per day

Weight reduction if overweight

Increased intake of fresh vegetables, fruits, and low-fat dairy (the

Dietary Approaches to Stop Hypertension (DASH) Study eating

plan)18

Salt restriction*

Adequate intake of potassium and calcium (both shown to have

antihypertensive effects)19

Cessation of smoking

•

•

•

•

•

•

•

*Can start with recommending “no added salt” with ultimate goal of achieving the current recommendation of 1.2 grams/day total for 4- to 8-year-olds and 1.5 grams/day for children 9 years and older.1



CMECME

Table 5

Pharmacologic interventions for pediatric hypertension

Drug class

Examples Major side effects Comments

Diuretics Hydrochlorothiazide

Metalozone

Furosemide

Torasemide

•

•

•

•

Hypokalemia, hypercholesterolemia,

hyperglycemia

Rare side effects:

Blood dyscrasias, photosensitivity,

pancreatitis

•

•

Would avoid in children active in sports because of risk of

dehydration and/or electrolyte disturbances

Electrolytes should be monitored one week after initiation and

periodically thereafter

Most useful as adjunctive therapy (particularly with calcium

channel blocker, direct vasodilators)

•

•

•

Potassium-

sparing

diuretics

Spironolactone

Amiloride

•

•

Hyperkalemia

Gynecomastia

•

•

Would avoid in children active in sports because of risk of

dehydration and/or electrolyte disturbances

Electrolytes should be monitored one week after initiation and

periodically thereafter

•

•

Beta-

blockers

Atenolol

Timolol

Pindolol

Bisoprolol

Propranolol

Available in pediatric labeling:*

Metoprolol

•

•

•

•

•

Serious side effects:

Bronchospasm, congestive heart

failure, masking of insulin-induced

hypoglycemia, depression

Less serious:

Poor peripheral circulation, insomnia,

fatigue, decreased exercise tolerance,

hypertriglyceridemia

•

•

Preferred for hypertensive children who suffer from migraine

headaches

Non-cardioselective agents are contraindicated in asthma and in

children with heart failure; avoid in diabetics

May decrease athletic performance

Maximum dose may be limited by heart rate

•

•

•

•

Calcium

channel

blockers

(CCBs)

Verapamil, diltiazem

Dihydropyridines

(Felodipine, Isradipine,

Nicardipine, Nifedipine)


Amlodipine

•

•

•

Conduction defects, decreased

contractility, gingival hyperplasia,

flushing, headache, peripheral edema

• Generally well tolerated

Consider for children active in sports

•

•

Angiotensin-

converting

enzyme

inhibitors†

Captopril

Ramipril


Benazepril*

Enalapril*

Fosinopril

Lisinopril*

•

•

•

•

•

•

Cough, rash, loss of taste,

hyperkalemia

Rare side effects:

Leukopenia, anemia, angioedema

•

•

Contraindicated in pregnancy and in children with hyperkalemia

and/or bilateral renal artery stenosis (can cause flash pulmonary

edema)*

Preferred medication for hypertensive diabetics or hypertensive

patients with microalbuminuria or proteinuria

Should consider for obese children with primary hypertension

Need to monitor for hyperkalemia and renal failure one week after

starting, with each dose increase, and periodically (every six to

12 mos after that)

•

•

•

•

Angiotensin

receptor

blockers†


Losartan*

Valsartan*

Irbesartan (label states was

ineffective in children)

•

•

•

Hyperkalemia, cough (less frequent

than with ACE inhibitors), angioedema

• Contraindicated in pregnancy*

Preferred medication for hypertensive diabetics or hypertensive

patients with microalbuminuria, proteinuria

Need to monitor for hyperkalemia and renal failure one week after

starting, with each dose increase and periodically (every six to 12

mos after that)

•

•

•

Alpha-

and

beta-

blockers

Labetalol

Carvedilol

•

•

Postural hypotension, Beta-blocking

side effects

• Preferred medication for hypertensive children who suffer from

migraine headaches

Contraindicated in asthma and in children with heart failure; avoid

in diabetics

May decrease athletic performance

Maximum dose may be limited by heart rate

•

•

•

•

Direct

vasodilators

Hydralazine

Minoxidil

•

•

Headaches, tachycardia, lupus-

like syndrome (hydralazine), fluid

retention, hirsutism (minoxidil)

• Hydralazine: Long-term use not effective secondary to tolerance,

edema

Minoxidil reserved for refractory cases in conjunction with other

medications (particularly diuretics)

•

•

Central

alpha

antagonists

Methyldopa

Clonidine

•

•

Hepatic and “auto-immune” disorders

(methyldopa), sedation, dry mouth,

“withdrawal” (clonidine)

• Abrupt discontinuation can lead to severe rebound HTN•

*These agents have pediatric labeling that includes instructions for extemporaneous suspension preparation.30 † The choice of ACE inhibitor or ARB can be based on the formulation available (only certain members of each class can be compounded into a suspension), and on tolerability (newer formulations of ACE inhibitor reportedly have less cough and angioedema associated with them; some patients are hyperkalemic with one class and not the other).



HYPERTENSION

receptor blockers (ARBs) therapy as the likely mechanism

for HTN in this group is increased sodium retention and

sympathetic nervous system (SNS) activation. Moreover,

these agents may have beneficial effects on diabetes

and dyslipidemia. Because diuretics can worsen insulin

resistance and dyslipidemia, as well as increase SNS and

renin activity, they should be avoided in obese children

with hypertension. Also, beta blockers should be avoided

in this group as they can lead to weight gain, increased

triglycerides, and decreased high-density lipoprotein

cholesterol concentrations.31,32

A word of caution: ACE inhibitors and ARBs can lead

to hyperkalemia and renal failure in certain individuals.

Therefore, lab tests should be undertaken one to two weeks

after starting either one of these medications to look for

evidence of these conditions. Additionally, flash pulmonary

edema can occur if bilateral renal artery stenosis is present,

so it would be wise to delay prescribing an ACE inhibitor or

ARB until after obtaining a renal ultrasound with Doppler

examination of the renal vessels. Lastly, as ACE inhibitors

and ARBs can also be highly teratogenic, contraception

should be discussed with females of childbearing age when

considering these classes of medications.

Once a medication is chosen, the lowest dose should

be started, with the dose increased in a step-wise fashion

to achieve normotension and regression of end-organ

damage, if present. Once the patient reaches the maximum

recommended dose of a medication, or experiences side

effects that limit reaching the maximium recommended

dose, an additional medication is initiated in the same

manner.

The goal for both non-pharmacologic and pharmacologic

therapy is to achieve BPs less than the 95th percentile

for most children, or less than the 90th percentile for

children with chronic kidney disease, diabetes, or evidence

of end-organ damage. This should be done in a manner

to maximize BP response while minimizing side effects

and maximizing probability of patient compliance. Side

effects can be minimized by prescribing the least amount of

drug necessary to effectively reduce BP. Higher degrees of

medication compliance can be achieved by being mindful of

medication side effects,

patient lifestyle, and

comorbid conditions.

Once therapy is in-

it iated, close moni-

toring for desired effect,

presence of side effects

and compliance is vitally

important. There are

no specific, published

guidelines regarding

frequency of monitoring

and fol low-up af ter

initiation of therapy,

but in the beginning it

would be reasonable to

measure a child’s blood

pressure at least weekly

and arrange for follow-

up every three months.

Weekly BP monitoring

can occur in a clinic

setting (via a nursing visit), a school setting (where the

school nurse measures manual BPs and faxes the readings

to the physician), or in a home setting either with a

properly calibrated, automated cuff or by manual measure-

ment done by a properly trained family member. As previously

mentioned, public BP cuffs are not appropriate for this monitoring

as they are likely to be inaccurate.

Once the child has achieved target BP’s on a medication

regimen, clinic follow-up can be spaced to every six months.

ACE inhibitors and

ARBs can lead to

hyperkalemia and

renal failure in certain

individuals. Therefore,

lab tests should be

undertaken one to two

weeks after starting

either one of these

medications to look

for evidence of these

conditions.

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CMECME

When to refer?

Depending on provider comfort level, the diagnosis, initial

work-up and treatment can be provided in the primary care

setting, or can be handled by a specialist with expertise in

pediatric hypertension. Ongoing collaboration and frequent

communication between specialists and primary care

providers is essential for successful patient management.

Once presented with refractory hypertension or with a

child very likely to have secondary hypertension, referral

to a specialist should be made for further work-up and

treatment. ◽

References

1. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics 2004;114:555. Available at http://pediatrics.aappublications.org/cgi/reprint/114/2/S2/555. Accessed Oct. 17, 20082. Fixler DE, Laird WP, Fitzgerald V, et al: Hypertension screening in schools: results of the Dallas study. Pediatrics 1979;63:323. Sinaiko AR, Gomez-Marin O, Prineas RJ: Prevalence of “significant” hypertension in junior high school-aged children: The children and adolescent blood pressure program. J Pediatr 1989;114:6644. Sorof JM, Lai D, Turner J, et al: Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004;113:4755. Sorof J, Daniels S: Obesity hypertension in children: a problem of epidemic proportions. Hypertension 2002;40:4416. Pickering TG, Hall JE, Appel LJ, et al: Recommendations for blood pressure measurement in humans and experimental animals: Part 1: Blood pressure measurement in humans: A statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension 2005;45:1427. Get the most out of home blood pressure monitoring. Mayo Foundation for Medical Education and Research, 2008. Available at: www.mayoclinic.com/health/high-blood-pressure/HI00016. Accessed Oct. 5, 20088. Free blood pressure machines: Are they accurate? Mayo Foundation for Medical Education and Research, 2008. Available at: www.mayoclinic.com/health/blood-pressure/AN00567. Accessed Oct. 17, 20089. Bartosh SM, Aronson AJ: Childhood hypertension: An update on etiology, diagnosis, and treatment. Pediatr Clin North Am 1999;46:23510. Flynn JT: Evaluation and management of hypertension in childhood. Prog Pediatr Cardiol 2001;12:17711. Sinaiko AR: Hypertension in children. N Engl J Med 1996;335:196812. Epidemiology, risk factors, and etiology of hypertension in children and adolescents. UpToDate, 2008. Available at: www.utdol.com/online/content/topic.do?topicKey=pedineph/19132&linkTitle=Essential%20hypertension&source=preview&selectedTitle=1~150&anchor=14#14. Accessed Oct. 17, 200813. Din-Dzietham R, Liu Y, Bielo MV, et al: High blood pressure trends in children and adolescents in national surveys, 1963 to 2002. Circulation 2007;116:148814. Muntner P, He J, Cutler JA, et al: Trends in blood pressure among children and adolescents. JAMA 2004;291:210715. Falkner B, Gidding SS, Ramirez-Garnica G, et al: The relationship of body mass index and blood pressure in primary care pediatric patients. J Pediatr 2006;148:19516. Barlow SE, Dietz WH: Obesity evaluation and treatment: Expert Committee recommendations. The Maternal and Child Health Bureau, Health Resources and

Services Administration and the Department of Health and Human Services. Pediatrics 1998;102:E29.17. Berenson GS, Srinivasan SR, Bao W, et al: Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: The Bogalusa Heart Study. N Engl J Med 1998;338:165018. Appel LJ, Moore TJ, Obarzanek E, et al: A clinical trial of the effects of dietary patterns on blood pressure: DASH Collaborative Research Group. N Engl J Med 1997;336:111719. Flynn JT: Hypertension in adolescents. Adolesc Med Clin 2005;16:1120. Lughetti L, De Simone M, Verrotti A, et al: Thirty-year persistence of obesity after presentation to a pediatric obesity clinic. Ann Hum Biol 2008;35:43921. DiPietro L, Mossberg HO, Stunkard AJ: A 40-year history of overweight children in Stockholm: life-time overweight, morbidity, and mortality. Int J Obes Relat Metab Disord 1994;18:58522. Srinivasan SR, Myers L, Berenson GS: Changes in metabolic syndrome variables since childhood in prehypertensive and hypertensive subjects: the Bogalusa Heart Study. Hypertension 2006;48:3323. Rocchini AP, Katch V, Anderson J, et al: Blood pressure in obese adolescents: effect of weight loss. Pediatrics 1988;82:1624 . Williams CL, Hayman LL, Daniels SR, et al: Cardiovascular health in childhood: A statement for health professionals from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 2002;106:14325. Textor SC, Townsend RR: Hypertension. NephSAP 2008;7:6326. Rocchini AP, Katch V, Kveselis D, et al: Insulin and renal sodium retention in obese adolescents. Hypertension 1989;14:36727. Goodfriend TL, Calhoun DA: Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension 2004;43:51828. Goodfriend TL, Ball DL, Gardner HW: An oxidized derivative of linoleic acid affects aldosterone secretion by adrenal cells in vitro. Prostaglandins Leukot Essent Fatty Acids 2002;67:16329. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, et al: Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci USA 2003;100:1421130. Flynn JT: Pediatric hypertension: recent trends and accomplishments, future challenges. Am J Hypertens 2008;21:60531. Mathew B, Patel SB, Reams GP, et al: Obesity-hypertension: emerging concepts in pathophysiology and treatment. Am J Med Sci 2007;334:233132. Sharma AM, Pischon T, Engeli S, et al: Choice of drug treatment for obesity-related hypertension: where is the evidence? J Hypertens 2001;19:667

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