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Statement

Indian Pediatrics 2007; 44:103-121

Evaluation and Management of Hypertension

 

Writing Committee

Arvind Bagga
Rupesh Jain
M. Vijayakumar
Madhuri Kanitkar
Uma Ali

 

From the Indian Pediatric Nephrology Group, Indian Academy of Pediatrics, Mumbai, India.

Correspondence to: Dr. Arvind Bagga, Department of Pediatrics, All India Institute of Medical Sciences,
Ansari Nagar, New Delhi 110 029, India. E-mail: [email protected]

 

Systemic hypertension is an important condition in childhood, with estimated population prevalence of 1-2% in the developed countries(1). Nutritional surveys, in the USA show a significant secular increase in systolic and diastolic blood pressures(1). The causes for increase in blood pressure are attributed to obesity, change in dietary habits, decreased physical activity and increasing stress. Similar data is lacking from India; small surveys in school children suggest a prevalence ranging from 2-5%(2).

Hypertension is classified as essential (primary) or secondary to, e.g., a renal parenchymal, renovascular or an endocrine disorder. Most children with sustained, severe or symptomatic hypertension have an underlying etiology, and are at risk for acute and chronic complications. Screening studies suggest that essential hypertension is also important during late childhood and adolescence. There is increasing evidence that essential hypertension tracks into adulthood, resulting in considerable cardio-vascular morbidity(3).

In view of concerns regarding hypertension in childhood and its long-term consequences, a Consensus Meeting of Experts of the Indian Pediatric Nephrology Group was held in Bangalore on 25 November 2005 in order to:

1. Recommend criteria for screening and defining hypertension in children;

2. Outline the evaluation of children detected to have hypertension; and

3. Suggest an approach to treatment.

Definitions and Staging of Hypertension

Tables I and II show normative data on blood pressure values, based on age and height percentiles, derived from a large multiethnic cohort of children in USA(4). The Expert Group endorses the guidelines on definition of hypertension proposed in the Fourth US Task Force Report on Hypertension(4), which are in broad conformity with the Seventh Joint National Commission Report for adults(5). Assessment of both systolic and diastolic pressures is important and interpreted in relation to age and height related normative data. If percentiles of systolic and diastolic pressures are different, the higher percentile is used for defining and staging hypertension. Normative data from the Second Report should be used for defining hypertension in infancy(6).

 
 
 

• Pre-hypertension is defined as systolic or diastolic blood pressure between the 90th and 95th percentile. Adolescents having blood pressure >120/80 mm Hg, but below the 95th percentile are also included in this category.

• Hypertension is defined as systolic or diastolic blood pressure exceeding the 95th percentile for age, gender and height, on at least three separate occasions, 1-3 weeks apart.

Since the severity of hypertension influences its management, it should be staged as below.

Stage 1 hypertension: Systolic or diastolic blood pressure values exceeding the 95th percentile and up to 5 mm above the 99th percentile. Blood pressures in this range should be rechecked at least twice in the next 1-3 weeks, or sooner if symptomatic, before the patient is diagnosed to have sustained hypertension.

Stage 2 hypertension: Systolic or diastolic blood pressure values 5 mm or more above the 99th percentile. The presence of stage 2 hypertension should be confirmed on a repeat measurement, at the same visit. These patients require further evaluation within one week or immediately if they are symptomatic.

Fig. 1. Blood pressure levels for boys at 50th percentile for height. Chart depicting 90th (closed diamonds), 95th (open circles) and 99th + 5 mm (closed triangles) percentile values for (a) systolic and (b) diastolic blood pressures, representing cut off values for the diagnosis of pre-hypertension, stage I and stage II hypertension respectively in boys (based on reference 4).

 

Figures 1 and 2 provide charts for screening and staging of hypertension in boys and girls respectively. These have been prepared, by the Expert Group, using data from Tables I and II at the 50th percentile for the height for age. For example, in a 5-year-old girl with height at the 50th percentile, systolic blood pressure between 110 and 122 mm Hg and diastolic pressure between 72 and 84 mm Hg represent stage 1 hypertension. Blood pressure values exceeding 122/84 mm Hg represent stage 2 hypertension (Fig. 2). Blood pressure values are typically 3-5 mm lower or higher in subjects with height at the 10th or 95th percentile respectively.

Fig. 2. Blood pressure levels for girls at 50th percentile for height. Chart depicting 90th (closed diamonds), 95th (open circles) and 99th + 5 mm (closed triangles) percentile values for (a) systolic and (b) diastolic blood pressures, representing cut off values for the diagnosis of pre-hypertension, stage I and stage II
hypertension respectively in girls (based on reference 4).

While the screening charts are useful for rapid evaluation, detailed tables in Tables I-II should be consulted before initiating therapy.

White coat hypertension

Some children may show blood pressure higher than the 95th percentile in clinic or hospital setting, while it is below 90th percentile in familiar environments(7). These patients do not need pharmacological treatment, but require blood pressure monitoring over the next 12 months, since a proportion is at risk of sustained essential hypertension.

Screening for hypertension

The awareness that essential hypertension has its origin in childhood has resulted in increased emphasis on screening. The Group recommends annual measurement of blood pressure in all children more than 3-year-old, who are seen in clinics or hospital settings. Blood pressure should also be measured in at-risk younger children with: (i) history of prematurity, very low birth weight or interventions in NICU; (ii) congenital heart disease; (iii) recurrent urinary tract infections, known renal or urological diseases, hematuria or proteinuria; (iv) family history of congenital renal disorders; (v) malignancy, post organ transplant; (vi) conditions associated with hypertension, e.g., neurofibromatosis, tuberous sclerosis and ambiguous genitalia. Blood pressure should be measured in patients who present with features of kidney or heart disease, seizures, altered sensorium and headache or visual complaints.

Accurate techniques for measurement of blood pressure are necessary for its diagnosis, staging and follow up(8).

Measurement devices

Mercury sphygmomanometer: Normative values for blood pressure are based on sphygmo-manometry, which continues to be the preferred method for blood pressure estimation. While it is recommended that blood pressure devices be calibrated and validated regularly, this process is cumbersome(9). Physicians should be aware that mercury is a major environmental pollutant and that accidental mercury spills must be managed appropriately. (For guidelines, refer to US Environment Protection Agency; www.epa.gov).

Oscillometric devices: These devices are increasingly used in infants (in whom auscultation is difficult) and in intensive care settings when frequent blood pressure measurements are needed. However, neither are most oscillometric devices validated for children, nor are there normative data based on these readings(10). Blood pressure values on oscillometry, which exceed the 90th percentile must therefore be confirmed by sphygmomanometry.

Aneroid and other devices: These instruments, based on spring-based technology require frequent calibration and validation. The use of aneroid devices and wrist or finger band oscillometry for blood pressure measurements is discouraged.

Ambulatory blood pressure monitoring (ABPM): Continuous recordings over 12- or 24-hr are believed to reflect true blood pressures accurately, are more reproducible and correlate with target organ damage. A lack of availability of these instruments and normative standards has limited the utility of ABPM for the diagnosis of hypertension in children(4).

Sphygmomanometry

Blood pressure is recorded once the child has rested for 5-10 minutes. The measurement is done either in sitting or supine position, the latter preferred for younger children. The right arm is used for consistency and for comparison with standard tables; the cubital fossa should be at heart level and the observer's eye at the level of the mercury column. Choosing the correct cuff size is crucial since a small cuff might overestimate the readings and vice versa (Table III). The width of the cuff bladder should be 40% of the arm circumference midway between the olecranon and the acromion and its length 80-100% of the arm circumference. If an appropriate cuff size is not available, the next larger size is used(4).

TABLE III
Dimensions for Blood Pressure Cuffs
Age Width (cm) Length (cm)
Newborn, infant 4 8
Child 9 18
Adolescent 10 24
Adult 13 30
Thigh 20 42

 

With the stethoscope on the brachial artery, the mercury column is lowered slowly (2 mm per second). Systolic blood pressure is the point when Korotkoff sounds are first heard (K1) and disappearance of sounds (K5) is the diastolic pressure. If Korotkoff sounds persist, the measure-ment is repeated with less pressure on the stethoscope head. If the sounds persist at low intensity, then K4 (muffling of sounds) is recorded as the diastolic pressure. Blood pressure recordings should be expressed to the nearest 2 mm Hg. A high reading should be confirmed after the child has rested for 5 minutes and the average of 2-3 readings is taken as the value for that occasion.

Transient hypertension

Hypertension may be transient in certain conditions, e.g., acute glomerulonephritis, acute intermittent porphyria, Guillain Barre syndrome, raised intracranial pressure, corticosteroid administration, anxiety and hyperthyroidism. Therapy for hypertension may be required in some cases. Persistence of elevated blood pressures requires detailed evaluation.

Sustained hypertension

Sustained hypertension in children is often secondary to an underlying renal disease (Table IV); approximately 60-70% patients have renal parenchymal disorders and 5-25% has reno-vascular disease(11,12). Coarctation of aorta is an important cause during infancy. In recent years, essential hypertension has become an important health concern. Patients with essential hyper-tension are usually postpubertal and over-weight; they typically show stage 1 hypertension and have no evidence of target organ damage.

TABLE IV

Causes of Persistent Hypertension
Renal parenchymal disease:  Chronic glomerulonephritis, reflux nephropathy, obstructive uropathy,
 polycystic kidney disease, renal dysplasia
Renovascular hypertension: Idiopathic aortoarteritis (Takayasu disease), renal artery stenosis, renal
artery thrombosis
Cardiovascular disease: Coarctation of aorta
Primary (essential) hypertension
*Endocrine: Pheochromocytoma, Cushing syndrome, congenital adrenal hyperplasia, primary
hyperaldosteronism, Liddle’s syndrome, syndrome of apparent mineralocorticoid excess,
glucocorticoid remediable aldosteronism, neuroblastoma
*Renal tumors: Wilms’ tumor, nephroblastoma

Clinical features and complications

Most patients with pre-hypertension and hypertension are asymptomatic or have non-specific symptoms(13). Infants may show irritability, failure to thrive, vomiting, feeding problems, seizures or respiratory distress(4). The occurrence of epistaxis is rare.

Acute complications (hypertensive crises)

Patients with stage 2 hypertension are at risk for hypertensive crises, which are classified as emergencies or urgencies, based on the respective presence or absence of acute end organ damage (e.g., hypertensive encephalopathy, intracerebral bleeding, acute left ventricular failure and renal failure). The occurrence of these complications is related to the rate of rise and duration of hypertension, rather than absolute blood pressure values(14,15).

Hypertensive encephalopathy is characterized by lethargy, dullness, headache, seizures and visual disturbances including blindness. Cerebral infarction, hemorrhage and facial nerve palsy may occur(11). Neuroimaging shows features of white matter degeneration in the parieto-occipital area (posterior leukoencephalopathy), which are reversible with treatment(14). Examination of the retina might shows hemorrhages, exudates or papilledema. Acute left ventricular failure is another life-threatening complication of severe hypertension.

While hypertensive emergencies require reduction of blood pressure within hours, the same can be achieved over 2-3 days in patients with hypertensive urgencies.

Chronic complications (target organ damage)

Sustained hypertension results in changes in eyes (hypertensive retinopathy), heart (increased left ventricular mass, diastolic dysfunction), kidneys (albuminuria), brain and blood vessels (increased initimal and medial thickness). There is evidence that these changes are common, even in patients with long standing stage 1 hyper-tension(4,16).

Evaluation

Careful history and physical examination provide clues to the underlying etiology (Table V). History is taken for dietary habits, abdominal trauma, physical activity, and symptoms related to renal, cardiac or thyroid disorders. Infants are assessed for history of oligohydraminos and invasive procedures in NICU (e.g., umbilical artery catheterization). Family history is taken for hypertension, diabetes, dyslipidemia, obesity, premature cardiovascular or cerebrovascular disease and renal disorders.

TABLE V

Clinical Features Indicating Underlying Diagnosis
Underlying cause

Feature

Renal parenchymal, Facial puffiness, edema, abdominal pain, dysuria, hematuria, frequency, polyuria; urological history of urinary tract infections; abdominal mass
Renovascular,
hypertension
Asymmetric pulses, abdominal/neck bruit, weak femoral artery pulses, café au lait spots, coarctation of aorta neurofibromatosis
Connective tissue disease Arthritis, arthralgias, unexplained fever, polymorphic rash
Endocrine Muscle weakness, cramps; episodic fever, pallor, sweating, flushing, tachycardia; polyuria, polydipsia, failure to thrive; abdominal mass; ambiguous genitalia/virilization

The patient’s height and weight are measured and body mass index (BMI) calculated. Patients who are overweight or obese are at risk for essential hypertension. The peripheral pulses should be palpated, and blood pressure measured in both arms and at least one lower limb; pressure in the lower limbs normally exceeds that in the upper extremities by 10-20 mm Hg(4).

Investigations

Secondary hypertension must be considered in every child or adolescent who presents with elevated blood pressures. Since the majority of patients with secondary hypertension has a renal or renovascular etiology, screening tests are designed to evaluate for these conditions (Table VI). All patients with hypertension should also be screened for target organ damage.

TABLE VI

Basic Diagnostic Work Up
Evaluation for cause
Hemogram
Blood urea, creatinine, electrolytes
Fasting lipids, glucose, uric acid
Urinalysis, culture
24-hr urinary protein or spot protein to creatinine ratio Chest X-ray
Renal ultrasonography
Screen for target organ damage
Retinal fundus examination
Urine: microalbumin, spot protein to creatinine ratio Chest X-ray, ECG, echocardiography

The extent of evaluation depends on the patient’s age, severity and duration of hypertension, presence of target organ damage and family history. Prepubertal patients, and those with stage 2 hypertension, features of end organ damage or underlying disorders are evaluated in detail. An obese adolescent with stage 1 systolic hypertension, baseline tachycardia, family history of hypertension, and normal history and physical examination needs no more than the basic evaluation (Table VI).

Based on clinical features and initial evaluation, a cause for hypertension is suggested in most instances. Confirmation of the diagnosis requires specific investigations tailored to specific needs (Table VII). Occasionally, the cause for hypertension may not be found despite detailed evaluation. Judicious use of radionuclide and biochemical investigations, conducted in collaboration with a pediatric nephrologist, is recommended in such cases.

TABLE VII
Additional Diagnostic Tests for Sustained Hypertension
Condition Diagnostic investigations
Glomerulonephritis Complement (C3), ANA, ANCA, anti-dsDNA, renal biopsy
Reflux nephropathy Micturating cystourethrogram, DMSA scintigraphy
Renovascular hypertension Doppler flow studies, captopril renography
  Angiography (MR, spiral CT, digital subtraction or conventional)
  Renal vein renin activity
Coarctation of aorta Echocardiography, angiography
Endocrine causes Thyroxine, thyroid stimulating hormone
  Plasma renin activity, aldosterone
  Plasma and urinary cortisol
  Plasma and urine catecholamines; MIBG scan, CT/MR imaging

Management

It is useful to distinguish essential from secondary hypertension. While the initial management for patients with essential hyper-tension comprises of life style modifications (see below), most patients with sustained secondary hypertension require treatment with anti-hypertensive agents(4).

Pre-hypertension

Patients are primarily managed by lifestyle modifications (see below) and revaluated 6 months later. The parents of these children are informed and advised regarding careful follow up. Medications are not required unless the patient has comorbid conditions (e.g., chronic kidney disease, diabetes mellitus or dyslipidemia) or evidence of target organ damage.

Essential hypertension

Patients with essential hypertension are initially managed with lifestyle modifications. Pharmaco-logical therapy is initiated if there is (i) a comorbid condition (chronic kidney disease, diabetes mellitus or dyslipidemia), (ii) target organ damage or (iii) failure of blood pressure to decline below the 95th percentile, despite lifestyle modifications, for 6 months.

Lifestyle modifications

Lifestyle changes are recommended for all children with hypertension; interventions based on daily routines are likely to be more successful.

Weight reduction

Achievement of ideal body weight is important, since reduction of weight reduces sensitivity of blood pressure to salt and attenuates cardiovascular risk factors, e.g., dyslipidemia and insulin resistance. Reduction of BMI by 10% is reported to lead to 8-12 mm Hg fall in systemic blood pressure(4). Weight reduction should be achieved by regular physical activity and diet modification. Prevention of excess weight gain limits future increases in blood pressure.

Increased physical activity

Children are encouraged to be active not only for weight control but for their well being. While they often find defined physical exercises (aerobics, tread mills) boring, they are likely to continue activities incorporated into their routines, e.g., walking or cycling to school, playing with friends outdoors and swimming. The Group supports the recommendations of 30-60 minutes or more of physical activity every day that is developmentally appropriate, enjoyable and involving a variety of activities(17). Adolescent girls in our country should be specifically targeted, since they spend considerably less time than boys in outdoor sport.

Participation in competitive sports is avoided in patients with stage 2 hypertension or target organ damage, until blood pressure is controlled satisfactorily. Strength training (isometric) exercises (e.g., weight lifting, gymnastics, karate and judo) should be avoided.

Dietary changes

Direct evidence on the benefits of dietary changes from rigorous, well-controlled trials in children and adolescents is sparse. Accordingly, the effect of diet on blood pressure in children is extrapolated chiefly from studies on adults.

Recommendations for daily sodium intake in children range between 1-1.5 g (45-65 mEq sodium, 2.6-3.8 g salt). Dietary sodium restriction is associated with small reductions in blood pressure in children(4,19). A ‘no added salt diet’ is a satisfactory approach to restrict salt intake. Intake of food products high in sodium (processed and canned foods, items prepared in fast food shops including pizzas, pickles and salted potato chips) should be avoided. Increased potassium intake, through vegetables and fruits, is associated with modest reduction of systolic and diastolic blood pressure in adults with essential hyper-tension(19). Potassium intake should however be restricted in children with chronic kidney disease with glomerular filtration rate (GFR) below 30 mL/min/1.73 m2, adrenal insufficiency, severe heart failure, or those receiving treatment with angiotensin converting enzyme inhibitors (ACEI), non-steroidal anti-inflammmatory agents and potassium sparing diuretics. Despite suggestions that foods rich in calcium, magnesium, folic acid and fiber are useful in reducing blood pressure, there is limited evidence in this regard.

An increased intake of fresh vegetables and fruits, whole grains and non-fat dairy is recommended. These foods are low in sodium and saturated fat and rich in minerals (potassium, calcium, magnesium) and fiber. The Group endorses the dietary recommendations of the IAP Consensus Committee on Obesity(20). The daily food composition is considered a 'thali', where half (50%) is vegetables, salads and fruits, a quarter (25%) is cereals (rice and/or chapattis), and the remainder is protein based (legumes, milk, egg, animal protein). The intake of fried foods, snacks and sweet dishes should be limited.

Secondary hypertension

Patients with sustained secondary hypertension require therapy with antihypertensive agents. Physicians should be aware of the risk of hypertensive emergencies in children with stage 2 hypertension. The need to adhere to healthy eating habits and lifestyle is emphasized.

Drug therapy

Drug therapy is indicated in patients with (i) acute or chronic complications of hypertension, including evidence of target organ damage, (ii) secondary hypertension, (iii) stage 2 hypertension, (iv) stage 1 hypertension that persists despite 6-months’ of lifestyle modifications, and (v) pre-hypertension or stage 1 hypertension with comorbid conditions (diabetes, chronic kidney disease or dyslipidemia).

Principles of treatment

► The goal for treatment is reduction of blood pressure to levels <95th percentile, unless comorbid conditions or target-organ damage is present, when it should be lowered to <90th percentile.

► Commonly used medications in children include ACEI, calcium channel blockers (CCB), vasodilators, b blockers and thiazide diuretics (Table VIII).

► Therapy is initiated with one agent, at an appropriate dose and the dose is increased until the desired blood pressure is achieved. If the highest dose is not effective or if there are side effects, a drug from a different class is added or substituted.

► Medications with a longer duration of action (once, twice daily dosing) are preferred for better compliance and less side effects.

► Dose adjustment of antihypertensive medications need not be made more frequently than every 2-3 days.

TABLE VIII Oral Antihypertensive Medications
 

Agents

Dose; frequency

Comments

Angiotensin converting enzyme inhibitors, angiotensin receptor blockers

Captopril

0.3 - 6 mg/kg/day; tid

Use cautiously if GFR <30 ml/min/1.73 m2; avoid in renal artery stenosis

Use smaller doses in neonates

Monitor serum potassium, creatinine regularly

Side effects: hyperkalemia, impaired renal functions; anemia, neutropenia, dry cough infrequent

Enalapril

0.1 - 0.6 mg/kg/day; qd

Lisinopril

0.06 - 0.6 mg/kg/day; qd

Ramipril  

6 mg/m2; qd

Irbesartan

4-5 mg/kg/day

Losartan

0.7 - 1.4 mg/kg/day; qd

Calcium channel blockers

Amlodepine

0.05 - 0.5 mg/kg/day; qd-bid

Extended release nifedepine must be swallowed whole

Side effects: Headache, flushing, dizziness, tachycardia; at higher doses: lower extremity edema, erythema

Nifedipine (extended release)

0.25 - 3 mg/kg/day; qd-bid

Isradipine

0.15 - 0.8 mg/kg/day; tid

Beta-blockers

Atenolol

0.5 - 2 mg/kg/day; qd-bid

Atenolol: decrease dose by 50% at GFR <50 ml/min/1.73 m2; give on alternate days at GFR <10 ml/min/1.73 m2

Sleep disturbances with propranolol, metoprolol; hyperlipidemia

Avoid in asthma, heart failure; blunt symptoms of hypoglycemia

Metoprolol

1 - 6 mg/kg/day; bid

Propanolol

1 - 4 mg/kg/day; tid

Labetalol

1 - 40 mg/kg/day; bid-tid

Central alpha agonist

Clonidine

5 - 25 mg/kg/day; tid-qid

Abrupt cessation may cause rebound hypertension; sedation

Peripheral alpha antagonist

Prazosin

0.05 - 0.5 mg/kg/day; bid-tid

May cause ‘first dose’ hypotension, syncope

Vasodilators

Hydralazine

1 - 8 mg/kg/day; qid

For hypertension refractory to other drugs

Side effects: headache, palpitation, fluid retention, congestive heart failure; pericardial effusions, hypertrichosis with minoxidil

Minoxidil

0.1 - 1 mg/kg/day; qd-bid

Diuretics

Frusemide

0.5 - 6 mg/kg/day; qd-bid

Monitor electrolytes, fluid status periodically

Thiazides: dyslipidemia, hyperglycemia, hyperuricemia, hypokalemia, hypomagnesemia

Loop diuretics: metabolic alkalosis, hypokalemia, hypercalciuria

*Use cautiously with ACEI, angiotensin receptor blockers

Spironolactone*

1 - 3 mg/kg/day; qd-bid

Metolazone

0.2 - 0.4 mg/kg/day; qd

Hydrochlorothiazide

1 - 3 mg/kg/day; qd

Amiloride*

0.4 - 0.6 mg/kg/day; qd

qd once daily; bid twice daily; tid thrice daily; qid four times daily

 

An approach to the treatment of hypertension is shown in Fig. 3.

 

Nifedipine and amlodipine are effective CCB for children. The availability of long acting preparations permits once or twice daily dosing. Sustained release preparations of nifedipine should be swallowed whole, and not crushed or chewed. Captopril, chiefly used in young infants, requires dosing every 6-8 hr. Beyond infancy, enalapril (1-2 daily doses) is preferred. Newer ACEI (lisinopril, ramipril) require once daily dosing and have fewer side effects. Angiotensin receptor blockers used in children include losartan, valsartan and irbesartan. Cardioselective b-blockers (atenolol, metoprolol) are effective agents, requiring once or twice daily dosing and have few side effects. The use of propranolol is limited in view of the need for multiple daily doses and side effects. Labetalol, a a- and b-blocker, is useful in patients refractory to other medications.

Combinations minimize the side effects by allowing administration of lower dosage of different agents. With combination therapy, consideration must be given to combining drugs with complementary mechanism of action, e.g., ACEI (or angiotensin receptor blocker) with a CCB or thiazide diuretic, or vasodilator with diuretic or b blocker (Fig. 3). While combinations of ACEI and angiotensin receptor blocker have been proposed for adults, similar experience is limited in children(21). Long term combination of thiazides with b-blockers may be associated with an increased incidence of glucose intolerance(22).

Specific recommendations

The choice of medication also depends on the cause of hypertension and associated complications.

Essential hypertension: While there is no consensus on the appropriate initial therapy, the choices are between CCB and ACEI. Therapy with b-blockers is recommended in patients who cannot tolerate ACEI or CCB(22).

Acute glomerulonephritis: Hypertension in post-infectious glomerulonephritis is of short duration and associated with salt and water retention. Fluid and sodium restriction and judicious use of loop diuretics are useful in patients with circulatory congestion, hypertension and edema. Severe hypertension with or without encephalopathy is an emergency and usually responds to treatment with CCB and furosemide. Occasionally treatment with a b-blocker or ACEI may be necessary.

Chronic kidney disease: The target blood pressure in these patients is <90th percentile. For patients with chronic kidney disease stage I-III (GFR >30 mL/min/1.73 m2) therapy should be initiated with ACEI, since these agents also reduce proteinuria and retard progression of renal damage(23). Monitoring of serum potassium and creatinine is necessary, initially at 7-14 days and then every 1-3 months. The dose of ACEI (or angiotensin receptor blockers) is reduced if serum creatinine exceeds 30-35% from the baseline or there is hyperkalemia. Treatment with ACEI should be avoided in patients with advanced chronic kidney disease (stage IV-V; GFR <30 mL/min/1.73 m2). Therapy in these cases is initiated with either a CCB or b-blocker.

Guidelines for managing hypertension in patients with chronic kidney disease also include:

w Sodium intake is restricted to between 1-1.5 g (45-65 mEq sodium, 2.6-3.8 g salt).

w Co-administration of diuretics helps in reducing sodium and volume overload. Thiazides (hydrochlorothiazide, chlorthalidone) are satisfactory, but not effective at GFR <30 mL/min/1.73 m2.

w Additional medications include a-blockers (prazosin, labetalol), centrally acting agents (clonidine) or vasodilators (hydralazine, minoxidil).

w The dosage of some medications (e.g., atenolol) need modification in renal impairment (Table VIII).

Renovascular disease: In patients with high probability or confirmed renovascular disease, therapy should be initiated with a CCB or/and a b-blocker. Additional agents include prazosin, labetalol, clonidine, hydralazine and/or minoxidil. While therapy with ACEI or angiotensin receptor blockers is avoided in patients with suspected or confirmed bilateral renovascular disease, these agents might be used cautiously in those with unilateral renovascular hypertension.

Complications of hypertension

ACEI are the preferred initial agents in subjects with ventricular dysfunction. Additional therapy may be given with loop or thiazide diuretics, b blockers and aldosterone antagonists. ACEI or angiotensin receptor blockers are recommended for patients with associated proteinuria.

Drug step-down

Overweight children with uncomplicated essential hypertension, who successfully lose weight, are best candidates for "step-down" treatment. This approach attempts a gradual reduction of the medication after 8-12 months of satisfactory blood pressure control. Patients must maintain a healthy lifestyle and blood pressure should be checked regularly (q 3 months) after cessation of therapy. Step down of drug therapy might also be possible in patients in whom a specific intervention has ameliorated the underlying cause for hypertension, e.g., following resection of pheochromocytoma or balloon dilatation for renovascular disease.

Monitoring

Patients and their families should receive counseling for cardiovascular risk factors and dyslipidemia, and continued emphasis on lifestyle modifications. Blood pressure is monitored every 3 months. Screening for end organ damage and renal dysfunction (proteinuria, serum creatinine) and surveillance for side effects of drugs is required annually.

Hypertensive emergencies

Patients with stage 2 hypertension may present with acute, life threatening target organ damage involving central nervous system (encephalopathy, seizures), heart (pulmonary edema) or kidneys (acute renal failure). These patients need hospitalization for monitoring and supportive care. Blood pressure levels are usually 5-15 mm above the 99th percentile, and should be reduced to safe levels. Rapid reduction of blood pressure might, however, compromise blood flow and result in ischemic complications in the brain, retina, spinal cord and kidneys. Blood pressure reduction, therefore, must be regulated in order to prevent end organ damage to these organs(24).

The difference between the observed and desired (95th percentile) blood pressure is estimated; 25-30% of the desired reduction should occur in the first 3-4 hr, another 25-30% in the next 24 hr, and then to the desired level over next 2 days. Agents of choice include short acting, intravenous (IV) preparations that are titrated to response (sodium nitroprusside, nitroglycerine, labetalol and nicardipine) (Table IX). Therapy with enteral antihypertensive drugs should be instituted within 6-12 hr of parenteral therapy, and the latter gradually withdrawn over the next 12-24 hr.

Sodium nitroprusside is the agent with the longest track record, readily available and the least expensive of all parenteral drugs. This agent can be used in most hospital settings, provided there is facility for monitoring of blood pressure. Initially infused at a rate of 0.3-0.8 mg/kg per minute, the dose may be increased in increments of 0.1-0.2 mg/kg per minute, every 15 minutes, if the desired reduction is not achieved. Blood pressure is measured at least every 15 minutes; pupillary reflexes, visual acuity and level of consciousness are also monitored. Two IV lines should be maintained, one for drug infusion and the other for saline infusion (if the blood pressure were to fall precipitously). Loss of pupillary reflex to light is an early indicator of retinal vascular ischemia, requiring immediate infusion of normal saline. Patients receiving nitroprusside at doses exceeding 2-3 mg/kg per minute for longer than 48 hr are at risk of cyanide toxicity, and even earlier if there is hepatic or renal dysfunction.

Experts have discouraged the use of immediate release sublingual or oral nifedipine for hypertensive emergencies in adults, since sudden reduction of blood pressure might lead to arrhythmias, syncope, cerebrovascular accidents and myocardial infarction. These complications are rarely reported in children, and nifedipine has been used safely and effectively, by pediatricians, for hypertensive emergencies(25). The risks of side effects due to sudden fall of blood pressure are limited, particularly if the dose of nifedipine is between 0.1-0.25 mg/kg(26). Physicians should however be aware that the response to short acting nifedipine might be inconsistent and unpredictable (requiring more than one dose) or uncontrolled (sudden fall of blood pressure).

Volume depletion is common in patients with severe hypertension and IV administration of loop diuretic together with a potent anti-hypertensive agent might lead to a precipitous drop in blood pressure. Diuretics should therefore be avoided unless specifically indicated for volume over- load as occurs in glomerulonephritis coexisting pulmonary edema.

Hypertensive urgencies

Hypertensive urgencies differ from emergencies in having no evidence of acute target organ damage. Patients have stage 2 hypertension and less dramatic symptoms (e.g., headache and/or vomiting), but are at risk for progression to hypertensive emergencies. Controlled reduction of blood pressure, using oral medications, over several hours is desirable. Effective oral agents include nifedipine, clonidine and labetalol.

The onset of action of nifedipine (0.25 mg/kg, maximum 10 mg) administered orally is within 5-10 min, peaks at 30-60 min and lasts for 2-6 hr. While children show reflex tachycardia, the occurrence of serious complications with the use of oral nifedipine in this situation is rare. Oral administration of clonidine (0.05-0.1 mg) is also effective, although the onset of action (30-60 min) and peak effect (2-4 hr) is delayed. Sedation and orthostatic hypotension occurs in many patients. Sublingual or oral administration of captopril (6.25-25 mg) also shows a rapid onset (10-30 min) and peak (1-2 hr), and relatively prolonged duration of action (4-8 hr). Despite overall efficacy of the above agents, a predictable reduction of blood pressure is often not possible. Patients with hypertensive urgencies should be observed closely, since use of IV medications might be required.

Neonatal hypertension

The management of hypertension in neonates was not separately addressed by the Expert Group. Blood pressure in neonates is determined by birth weight and gestational age. Renovascular (renal artery or venous thrombosis) and renal parenchymal disorders are important causes of hypertension. Newborns with severe hyper-tension are managed with continuous IV infusion of nitroprusside or labetalol. Effective oral agents include CCB, hydralazine and minoxidil; ACEI should be administered at lower doses.

Conclusions

The above guidelines represent a consensus view based on evidence and opinion of experts of the Indian Pediatric Nephrology Group. Measurement of blood pressure is an important component of pediatric physical examination that enables screening for hypertension. Elevated blood pressure in children may be a sign of an underlying disease or represent early onset essential hypertension. Pediatricians should be aware of the principles of early detection, evaluation and management of such patients. Children with hypertension need long term follow up, counseling and treatment, which should be achieved by their primary pediatricians in collaboration with pediatric nephrologists.

 

Participants of the Expert Group

Indira Agarwal, Christian Medical College Hospital, Vellore

Vinay Agarwal, Max Hospital, New Delhi

Uma Ali, Bai Jerbai Wadia Hospital for Children, Mumbai

Anand Alladi, Apollo Hospital, Bangalore

Arvind Bagga, All India Institute of Medical Sciences, New Delhi

Sushmita Banerjee, Calcutta Medical Research Institute, Kolkata

Sanjeev Gulati, Fortis Hospital, New Delhi

Pankaj Hari, All India Institute of Medical Sciences, New Delhi

Arpana Iyengar, St. John's Medical College, Bangalore

Rupesh Jain, Ekta Hospital for Children, Raipur

Madhuri Kanitkar, Armed Forces Medical College, Pune

Mukta Mantan, Chacha Nehru Hospital, Delhi

Kamini Mehta, Lilavati Hospital & Research Center, Mumbai

Kumud Mehta, Jaslok Hospital & Research Center, Mumbai

B.R. Nammalwar, Kanchi Kamakoti CHILDS Trust Hospital, Chennai

Amitav Pahari, Apollo Hospital, Kolkata

Saroj Patnaik, Air Force Hospital, Gorakhpur

Kishore Phadke, St. John's Medical College, Bangalore

N. Prahlad, Mehta Children's Hospital, Chennai

T.R. Premalatha, Bangalore Medical College, Bangalore

V.K. Sairam, Sri Ramchandra Medical College, Chennai

Jayati Sengupta, AMRI Hospital, Kolkata

Prabha Senguttuvan, Institute of Child health, Chennai

Mehul Shah, Apollo Hospital, Hyderabad

Jyoti Sharma, Bharti Vidyapeeth Medical College, Poona

R.N. Srivastava, Apollo Hospital, New Delhi

V. Tamilarasi, Christian Medical College, Vellore

A.S. Vasudev, Apollo Hospital, New Delhi

M. Vijayakumar, Mehta Children's Hospital, Chennai.


 

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