CME

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

N CME

icholas, a 10-year-old boy with a history of inter mit tent a sthma 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

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

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

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HYPERTENSION

ILLUSTRATION:JOEL AND SHARON HARRIS/ARTICUL ATE GRAPHICS:

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.

Accreditation cme2 is accredited by the ACCME to provide continuing medical education for physicians. Credit Designation cme2 designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Target audience: Pediatricians and primary care physicians To earn CME credit for this activity Participants 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.

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 >>p.48

Disclosures Editors 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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The authors have nothing to disclose with regard to affiliations with, or financial interest in, any organization that may have an interest in any part of this article. Resolution of conflict of interest cme 2 has implemented a process to resolve conflicts of interest for each continuing medical education activity, to help ensure content validity, independence, fair balance, and that the content is aligned with the interest of the public. Conflicts, if any, are resolved through a peer review process. 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.

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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.

Figure 1 Choose the appropriate size cuff

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 inflate 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) measurements? While t here 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.

IMAGE:JOEL AND SHARON HARRIS/ARTICUL ATE GRAPHICS

CME

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HYPERTENSION

Table 1 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

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 • Coarctation of the aorta • 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

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

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CME 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) Medications – Steroids – Decongestants/cold preparations – Oral contraceptive pills – NSAIDs – Stimulant medications (eg, dexedrine, methylphenidate) – Beta-adrenergic agonists (eg, theophylline) – Erythropoietin – Cyclosporine/tacrolimus – Tricyclic antidepressants – Recent 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

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 flow 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

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HYPERTENSION

Table 3 Physical examination findings suggestive of definable hypertension Findings* Vital signs

• •

Possible etiology

Tachycardia Decreased lower extermity pulses; drop in BP from upper to lower extremities

• •

Hyperthyroidism, pheochromocytoma, neuroblastoma, primary hypertension Coarctation of the aorta

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

Moon facies Elfin facies Webbed neck Thyromegaly

•

Pallor, flushing, diaphoresis Acne, hirsutism, striae Café-au-lait spots Adenoma sebaceum Malar rash Acanthrosis nigricans

•

Widly spaced nipples Heart murmur Friction rub

•

•

•

Apical heave Mass Epigastric/flank bruit Palpable kidneys

Genitalia

•

Ambiguous/virilization

•

Adrenal hyperplasia

Extremities

•

Joint swelling Muscle weakness

•

Systemic lupus erythematosus, collagen vascular disease Hyperaldosteronism, Liddle syndrome

• •

Head and neck

• • • •

Skin

• • • • • •

Chest

• • •

Abdomen

• • •

•

• •

• • •

• • • • •

• •

• • •

•

Cushing syndrome Williams syndrome Turner syndrome Hyperthyroidism Pheochromocytoma Cushing syndrome, anabolic steroid abuse Neurofibromatosis Tuberous sclerosis Systemic lupus erythematosus Type 2 diabetes Turner syndrome Coarctation of the aorta Systemic lupus erythematosus (pericarditis), collagen vascular disease, end-stage renal disease with uremia LVH/chronic hypertension Wilms tumor, neuroblastoma, pheochromocytoma Renal artery stenosis Polysystic kidney disease, hydronephrosis, multicystic dysplastic kidney, mass (see above)

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.

• Plasma a nd uri ne catechola mi nes to ident if y catecholamine-mediated hypertension (ie, pheochromocytoma)

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. >>p.52

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CME

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 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;342:1378 2. 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

IMAGE: GET T Y IMAGES/MEDIOIMAGES/PHOTODISC

The link between OSA and hypertension

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HYPERTENSION

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 4to 8-year-olds and 1.5 grams/day for children 9 years and older.1

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 prehypertension 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 endorgan 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 Point chosen shou ld be a i med at treating the underlying etiology, Taken with particular attention being paid to co-morbid conditions Weight loss by such as diabetes, asthma, and itself can migraines. decrease blood Af ter a f u l l eva luation to determine etiology is completed pressure, and (and any interventions are underother associated taken to treat the underlying disease process), initial antihyperCV risk factors tensive therapy for a child who should also continues to be hypertensive be expected should include either a calcium channel blocker (CCB) or an to regress or angiotensin converting enzyme improve with (ACE) inhibitor, unless there is a compelling reason to use an agent weight loss. 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 hy pertension may particularly benefit from ACE inhibitors or angiotensin-

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CME Table 5 Pharmacologic interventions for pediatric hypertension Drug class

Examples

Diuretics

• • • •

Hydrochlorothiazide Metalozone Furosemide Torasemide

Comments

Hypokalemia, hypercholesterolemia, hyperglycemia Rare side effects: • Blood dyscrasias, photosensitivity, pancreatitis

•

•

•

•

Betablockers

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

•

Calcium channel blockers (CCBs)

Verapamil, diltiazem Dihydropyridines (Felodipine, Isradipine, Nicardipine, Nifedipine) Available in pediatric labeling:* • Amlodipine

•

Conduction defects, decreased contractility, gingival hyperplasia, flushing, headache, peripheral edema

•

Angiotensinconverting enzyme inhibitors†

Captopril Ramipril Available in pediatric labeling:* • Benazepril* • Enalapril* • Fosinopril • Lisinopril*

Cough, rash, loss of taste, hyperkalemia Rare side effects: • Leukopenia, anemia, angioedema

Available in pediatric labeling:* • Losartan* • Valsartan* • Irbesartan (label states was ineffective in children)

•

Angiotensin receptor blockers†

Alphaand betablockers

• •

Hyperkalemia Gynecomastia

•

Potassiumsparing diuretics

•

Spironolactone Amiloride

Major side effects

• •

• •

• •

• •

• •

Labetalol Carvedilol

•

• • •

•

•

• • •

Hyperkalemia, cough (less frequent than with ACE inhibitors), angioedema

• • •

•

Postural hypotension, Beta-blocking side effects

• • • •

Direct vasodilators

Central alpha antagonists

• •

• •

Hydralazine Minoxidil

Methyldopa Clonidine

•

•

Headaches, tachycardia, lupuslike syndrome (hydralazine), fluid retention, hirsutism (minoxidil)

•

Hepatic and “auto-immune” disorders (methyldopa), sedation, dry mouth, “withdrawal” (clonidine)

•

•

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) 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 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

Generally well tolerated Consider for children active in sports

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) 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) 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 Hydralazine: Long-term use not effective secondary to tolerance, edema Minoxidil reserved for refractory cases in conjunction with other medications (particularly diuretics) 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).

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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, Point patient lifestyle, and comorbid conditions. Taken Once therapy is initiated, close moniACE inhibitors and toring for desired effect, ARBs can lead to presence of side effects hyperkalemia and and compliance is vitally important. There are renal failure in certain no specific, published individuals. Therefore, guidelines regarding frequency of monitoring lab tests should be a nd fol low-up a f ter undertaken one to two initiation of therapy, weeks after starting but in the beginning it would be reasonable to either one of these measure a child’s blood medications to look pressure at least weekly and arrange for followfor evidence of these up every three months. conditions. 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 measurement 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. >>p.56

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CME

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, 2008 2. Fixler DE, Laird WP, Fitzgerald V, et al: Hypertension screening in schools: results of the Dallas study. Pediatrics 1979;63:32 3. 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;114:664 4. Sorof JM, Lai D, Turner J, et al: Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004;113:475 5. Sorof J, Daniels S: Obesity hypertension in children: a problem of epidemic proportions. Hypertension 2002;40:441 6. 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;45:142 7. 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, 2008 8. 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, 2008 9. Bartosh SM, Aronson AJ: Childhood hypertension: An update on etiology, diagnosis, and treatment. Pediatr Clin North Am 1999;46:235 10. Flynn JT: Evaluation and management of hypertension in childhood. Prog Pediatr Cardiol 2001;12:177 11. Sinaiko AR: Hypertension in children. N Engl J Med 1996;335: 1968 12. 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%20 hypertension&source=preview&selectedTitle=1~150&anchor=14#14. Accessed Oct. 17, 2008 13. 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;116:1488 14. Muntner P, He J, Cutler JA, et al: Trends in blood pressure among children and adolescents. JAMA 2004;291:2107 15. 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;148:195 16. 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;338:1650 18. 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;336:1117 19. Flynn JT: Hypertension in adolescents. Adolesc Med Clin 2005;16:11 20. 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;35:439 21. 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;18:585 22. Srinivasan SR, Myers L, Berenson GS: Changes in metabolic syndrome variables since childhood in prehypertensive and hypertensive subjects: the Bogalusa Heart Study. Hypertension 2006;48:33 23. Rocchini AP, Katch V, Anderson J, et al: Blood pressure in obese adolescents: effect of weight loss. Pediatrics 1988;82:16 24 . 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;106:143 25. Textor SC, Townsend RR: Hypertension. NephSAP 2008;7:63 26. Rocchini AP, Katch V, Kveselis D, et al: Insulin and renal sodium retention in obese adolescents. Hypertension 1989;14:367 27. Goodfriend TL, Calhoun DA: Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension 2004;43:518 28. 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;67:163 29. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, et al: Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci USA 2003;100:14211 30. Flynn JT: Pediatric hypertension: recent trends and accomplishments, future challenges. Am J Hypertens 2008;21:605 31. Mathew B, Patel SB, Reams GP, et al: Obesity-hypertension: emerging concepts in pathophysiology and treatment. Am J Med Sci 2007;334:2331 32. 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

IMAGE: GET T Y IMAGES/SIEDE PREIS/KEITH BROFSK Y

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. ◽

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