Statement INDIAN PEDIATRICS 103 VOLUME 44 __ FEBRUARY 17, 2007 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 Evaluation and Management of Hypertension 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]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 Writing Committee Arvind Bagga Rupesh Jain M. Vijayakumar Madhuri Kanitkar Uma Ali
Transcript
Statement
INDIAN PEDIATRICS 103 VOLUME 44__FEBRUARY 17, 2007
Systemic hypertension is an importantcondition in childhood, with estimated populationprevalence of 1-2% in the developed countries(1).Nutritional surveys, in the USA show a significantsecular increase in systolic and diastolic bloodpressures(1). The causes for increase in bloodpressure are attributed to obesity, change indietary habits, decreased physical activity andincreasing stress. Similar data is lacking fromIndia; small surveys in school children suggest aprevalence ranging from 2-5%(2).
Hypertension is classified as essential(primary) or secondary to, e.g., a renalparenchymal, renovascular or an endocrinedisorder. Most children with sustained, severe orsymptomatic hypertension have an underlyingetiology, and are at risk for acute and chroniccomplications. Screening studies suggest thatessential hypertension is also important during latechildhood and adolescence. There is increasingevidence that essential hypertension tracks intoadulthood, resulting in considerable cardio-vascular morbidity(3).
In view of concerns regarding hypertension inchildhood and its long-term consequences, a
Evaluation and Management ofHypertension
From the Indian Pediatric Nephrology Group, IndianAcademy of Pediatrics, Mumbai, India.
Correspondence to: Dr. Arvind Bagga, Department ofPediatrics, All India Institute of Medical Sciences,Ansari Nagar, New Delhi 110 029, India.E-mail: [email protected]
Consensus Meeting of Experts of the IndianPediatric Nephrology Group was held inBangalore on 25 November 2005 in order to:
1. Recommend criteria for screening and defininghypertension in children;
2. Outline the evaluation of children detected tohave hypertension; and
3. Suggest an approach to treatment.
Definitions and Staging of Hypertension
Tables I and II show normative data on bloodpressure values, based on age and heightpercentiles, derived from a large multiethniccohort of children in USA(4). The Expert Groupendorses the guidelines on definition ofhypertension proposed in the Fourth US TaskForce Report on Hypertension(4), which are inbroad conformity with the Seventh Joint NationalCommission Report for adults(5). Assessment ofboth systolic and diastolic pressures is importantand interpreted in relation to age and height relatednormative data. If percentiles of systolic anddiastolic pressures are different, the higherpercentile is used for defining and staginghypertension. Normative data from the SecondReport should be used for defining hypertension ininfancy(6).
• Pre-hypertension is defined as systolic ordiastolic blood pressure between the 90th and95th percentile. Adolescents having bloodpressure >120/80 mm Hg, but below the 95thpercentile are also included in this category.
• Hypertension is defined as systolic or diastolicblood pressure exceeding the 95th percentilefor age, gender and height, on at least threeseparate occasions, 1-3 weeks apart.
Since the severity of hypertension influences itsmanagement, it should be staged as below.
• Stage 1 hypertension: Systolic or diastolicblood pressure values exceeding the 95th
Writing CommitteeArvind BaggaRupesh JainM. VijayakumarMadhuri KanitkarUma Ali
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percentile and up to 5 mm above the 99thpercentile. Blood pressures in this range shouldbe rechecked at least twice in the next 1-3weeks, or sooner if symptomatic, before thepatient is diagnosed to have sustainedhypertension.
• Stage 2 hypertension: Systolic or diastolicblood pressure values 5 mm or more above the99th percentile. The presence of stage 2hypertension should be confirmed on a repeatmeasurement, at the same visit. These patientsrequire further evaluation within one week orimmediately if they are symptomatic.
Figures 1 and 2 provide charts for screeningand staging of hypertension in boys and girlsrespectively. These have been prepared, by theExpert Group, using data from Tables I and II at the50th percentile for the height for age. For example,in a 5-year-old girl with height at the 50thpercentile, systolic blood pressure between 110and 122 mm Hg and diastolic pressure between 72and 84 mm Hg represent stage 1 hypertension.Blood pressure values exceeding 122/84 mm Hgrepresent stage 2 hypertension (Fig. 2). Bloodpressure values are typically 3-5 mm lower orhigher in subjects with height at the 10th or 95thpercentile respectively.
While the screening charts are useful for rapidevaluation, detailed tables in Tables I-II should beconsulted before initiating therapy.
White coat hypertension
Some children may show blood pressurehigher than the 95th percentile in clinic or hospitalsetting, while it is below 90th percentile in familiarenvironments(7). These patients do not needpharmacological treatment, but require bloodpressure monitoring over the next 12 months,since a proportion is at risk of sustained essentialhypertension.
Screening for hypertension
The awareness that essential hypertension hasits origin in childhood has resulted in increasedemphasis on screening. The Group recommendsannual measurement of blood pressure in all
children more than 3-year-old, who are seen inclinics or hospital settings. Blood pressure shouldalso be measured in at-risk younger children with:(i) history of prematurity, very low birth weightor interventions in NICU; (ii) congenital heartdisease; (iii) recurrent urinary tract infections,known renal or urological diseases, hematuria orproteinuria; (iv) family history of congenital renaldisorders; (v) malignancy, post organ transplant;(vi) conditions associated with hypertension,e.g., neurofibromatosis, tuberous sclerosis andambiguous genitalia. Blood pressure should bemeasured in patients who present with featuresof kidney or heart disease, seizures, alteredsensorium and headache or visual complaints.
Accurate techniques for measurement of bloodpressure are necessary for its diagnosis, stagingand follow up(8).
Measurement devices
Mercury sphygmomanometer: Normative valuesfor blood pressure are based on sphygmo-manometry, which continues to be the preferredmethod for blood pressure estimation. While it isrecommended that blood pressure devices becalibrated and validated regularly, this process iscumbersome(9). Physicians should be aware thatmercury is a major environmental pollutant andthat accidental mercury spills must be managedappropriately. (For guidelines, refer to USEnvironment Protection Agency; www.epa.gov).
Oscillometric devices: These devices areincreasingly used in infants (in whom auscultationis difficult) and in intensive care settings whenfrequent blood pressure measurements areneeded. However, neither are most oscillometricdevices validated for children, nor are therenormative data based on these readings(10).Blood pressure values on oscillometry, whichexceed the 90th percentile must therefore beconfirmed by sphygmomanometry.
Aneroid and other devices: These instruments,based on spring-based technology require frequentcalibration and validation. The use of aneroiddevices and wrist or finger band oscillometry forblood pressure measurements is discouraged.
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STATEMENT
80
90
100
110
120
130
140
150
160
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age (yr)
mm
Hg
90th percentile 95th percentile 99th percentile + 5 mm
Systolic blood pressure.
40
50
60
70
80
90
100
110
120
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age (yr)
mm
Hg
Diastolic blood pressure.
Ambulatory blood pressure monitoring (ABPM):Continuous recordings over 12- or 24-hr arebelieved to reflect true blood pressures accurately,are more reproducible and correlate with targetorgan damage. A lack of availability of theseinstruments and normative standards has limitedthe utility of ABPM for the diagnosis ofhypertension in children(4).
Sphygmomanometry
Blood pressure is recorded once the child hasrested for 5-10 minutes. The measurement is doneeither in sitting or supine position, the latterpreferred for younger children. The right arm isused for consistency and for comparison withstandard tables; the cubital fossa should be at heart
Fig. 1. Blood pressure levels for boys at 50th percentile for height. Chart depicting90th (closed diamonds), 95th (open circles) and 99th + 5 mm (closedtriangles) percentile values for (a) systolic and (b) diastolic blood pressures,representing cut off values for the diagnosis of pre-hypertension, stage I andstage II hypertension respectively in boys (based on reference 4).
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80
90
100
110
120
130
140
150
160
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age (yr)
mm
Hg
90th percentile 95th percentile 99th percentile + 5 mm
Systolic blood pressure.
Diastolic blood pressure.
40
50
60
70
80
90
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120
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age (yr)
mm
Hg
level and the observer's eye at the level of themercury column. Choosing the correct cuff size iscrucial since a small cuff might overestimate thereadings and vice versa (Table III). The width ofthe cuff bladder should be 40% of the armcircumference midway between the olecranon and
the acromion and its length 80-100% of the armcircumference. If an appropriate cuff size is notavailable, the next larger size is used(4).
With the stethoscope on the brachial artery, themercury column is lowered slowly (2 mm persecond). Systolic blood pressure is the point when
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, representingcut off values for the diagnosis of pre-hypertension, stage I and stage IIhypertension respectively in girls (based on reference 4).
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STATEMENT
Korotkoff sounds are first heard (K1) anddisappearance of sounds (K5) is the diastolicpressure. If Korotkoff sounds persist, the measure-ment is repeated with less pressure on thestethoscope head. If the sounds persist at lowintensity, then K4 (muffling of sounds) is recordedas the diastolic pressure. Blood pressurerecordings should be expressed to the nearest2 mm Hg. A high reading should be confirmedafter the child has rested for 5 minutes and theaverage of 2-3 readings is taken as the value forthat occasion.
Transient hypertension
Hypertension may be transient in certainconditions, e.g., acute glomerulonephritis, acuteintermittent porphyria, Guillain Barre syndrome,raised intracranial pressure, corticosteroidadministration, anxiety and hyperthyroidism.Therapy for hypertension may be required in somecases. Persistence of elevated blood pressuresrequires detailed evaluation.
Sustained hypertension
Sustained hypertension in children is oftensecondary to an underlying renal disease (TableIV); approximately 60-70% patients have renalparenchymal disorders and 5-25% has reno-vascular disease(11,12). Coarctation of aorta is animportant cause during infancy. In recent years,essential hypertension has become an importanthealth concern. Patients with essential hyper-tension are usually postpubertal and over-weight;they typically show stage 1 hypertension and haveno evidence of target organ damage.
Clinical features and complications
Most patients with pre-hypertension and hyper-tension are asymptomatic or have non-specificsymptoms(13). Infants may show irritability,failure to thrive, vomiting, feeding problems,seizures or respiratory distress(4). The occurrenceof epistaxis is rare.
Acute complications (hypertensive crises)
Patients with stage 2 hypertension are at risk forhypertensive crises, which are classified asemergencies or urgencies, based on the respectivepresence or absence of acute end organ damage(e.g., hypertensive encephalopathy, intracerebralbleeding, acute left ventricular failure and renalfailure). The occurrence of these complications isrelated to the rate of rise and duration ofhypertension, rather than absolute blood pressurevalues(14,15).
Hypertensive encephalopathy is characterizedby lethargy, dullness, headache, seizures andvisual disturbances including blindness. Cerebralinfarction, hemorrhage and facial nerve palsy mayoccur(11). Neuroimaging shows features of whitematter degeneration in the parieto-occipital area(posterior leukoencephalopathy), which arereversible with treatment(14). Examination of theretina might shows hemorrhages, exudates orpapilledema. Acute left ventricular failure isanother life-threatening complication of severehypertension.
While hypertensive emergencies requirereduction of blood pressure within hours, the same
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can be achieved over 2-3 days in patients withhypertensive urgencies.
Chronic complications (target organ damage)
Sustained hypertension results in changes ineyes (hypertensive retinopathy), heart (increasedleft ventricular mass, diastolic dysfunction),kidneys (albuminuria), brain and blood vessels(increased initimal and medial thickness). There isevidence that these changes are common, evenin patients with long standing stage 1 hyper-tension(4,16).
Evaluation
Careful history and physical examinationprovide clues to the underlying etiology (Table V).History is taken for dietary habits, abdominaltrauma, physical activity, and symptoms related to
renal, cardiac or thyroid disorders. Infants areassessed for history of oligohydraminos andinvasive procedures in NICU (e.g., umbilicalartery catheterization). Family history is taken forhypertension, diabetes, dyslipidemia, obesity,premature cardiovascular or cerebrovasculardisease and renal disorders.
The patient’s height and weight are measuredand body mass index (BMI) calculated. Patientswho are overweight or obese are at risk for essentialhypertension. The peripheral pulses should bepalpated, and blood pressure measured in botharms and at least one lower limb; pressure in thelower limbs normally exceeds that in the upperextremities by 10-20 mm Hg(4).
Investigations
Secondary hypertension must be considered in
TABLE V–Clinical Features Indicating Underlying Diagnosis
Underlying Featurecause
Renal parenchymal, Facial puffiness, edema, abdominal pain, dysuria, hematuria, frequency, polyuria;urological history of urinary tract infections; abdominal mass
Renovascular, Asymmetric pulses, abdominal/neck bruit, weak femoral artery pulses, café au lait spots,coarctation of aorta neurofibromatosis
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
every child or adolescent who presents withelevated blood pressures. Since the majority ofpatients with secondary hypertension has a renal orrenovascular etiology, screening tests aredesigned to evaluate for these conditions (TableVI). All patients with hypertension should also bescreened for target organ damage.
The extent of evaluation depends on thepatient’s age, severity and duration of hyper-tension, presence of target organ damage andfamily history. Prepubertal patients, and those withstage 2 hypertension, features of end organdamage or underlying disorders are evaluated indetail. An obese adolescent with stage 1 systolic
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STATEMENT
hypertension, baseline tachycardia, family historyof hypertension, and normal history and physicalexamination needs no more than the basicevaluation (Table VI).
Based on clinical features and initial evaluation,a cause for hypertension is suggested in mostinstances. Confirmation of the diagnosis requiresspecific investigations tailored to specific needs(Table VII). Occasionally, the cause for hyper-tension may not be found despite detailedevaluation. Judicious use of radionuclide andbiochemical investigations, conducted incollaboration with a pediatric nephrologist, isrecommended in such cases.
Management
It is useful to distinguish essentialfrom secondary hypertension. While the initialmanagement for patients with essential hyper-tension comprises of life style modifications (seebelow), most patients with sustained secondaryhypertension require treatment with anti-hypertensive agents(4).
Pre-hypertension
Patients are primarily managed by lifestylemodifications (see below) and revaluated 6months later. The parents of these children areinformed and advised regarding careful follow up.Medications are not required unless the patient hascomorbid conditions (e.g., chronic kidney disease,
diabetes mellitus or dyslipidemia) or evidence oftarget organ damage.
Essential hypertension
Patients with essential hypertension are initiallymanaged with lifestyle modifications. Pharmaco-logical therapy is initiated if there is (i) a comorbidcondition (chronic kidney disease, diabetesmellitus or dyslipidemia), (ii) target organ damageor (iii) failure of blood pressure to decline belowthe 95th percentile, despite lifestyle modifications,for 6 months.
Lifestyle modifications
Lifestyle changes are recommended forall children with hypertension; interventionsbased on daily routines are likely to be moresuccessful.
Weight reduction
Achievement of ideal body weight isimportant, since reduction of weight reducessensitivity of blood pressure to salt and attenuatescardiovascular risk factors, e.g., dyslipidemiaand insulin resistance. Reduction of BMI by10% is reported to lead to 8-12 mm Hg fall insystemic blood pressure(4). Weight reductionshould be achieved by regular physical activityand diet modification. Prevention of excessweight gain limits future increases in bloodpressure.
TABLE VII–Additional Diagnostic Tests for Sustained Hypertension
Renovascular hypertension Doppler flow studies, captopril renographyAngiography (MR, spiral CT, digital subtraction or conventional)Renal vein renin activity
Coarctation of aorta Echocardiography, angiography
Endocrine causes Thyroxine, thyroid stimulating hormonePlasma renin activity, aldosteronePlasma and urinary cortisolPlasma and urine catecholamines; MIBG scan, CT/MR imaging
ANA antinuclear antibody, ANCA antineutrophil cytoplasmic antibody, anti-dsDNA, anti-double stranded DNAantibody, DMSA demercaptosuccinic acid, MIBG meta-iodobenzyl guanidine.
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Increased physical activity
Children are encouraged to be active not onlyfor weight control but for their well being. Whilethey often find defined physical exercises (aero-bics, tread mills) boring, they are likely to continueactivities incorporated into their routines, e.g.,walking or cycling to school, playing with friendsoutdoors and swimming. The Group supports therecommendations of 30-60 minutes or more ofphysical activity every day that is developmen-tally appropriate, enjoyable and involving avariety of activities(17). Adolescent girls in ourcountry should be specifically targeted, since theyspend considerably less time than boys in outdoorsport.
Participation in competitive sports is avoided inpatients with stage 2 hypertension or target organdamage, until blood pressure is controlled satis-factorily. Strength training (isometric) exercises(e.g., weight lifting, gymnastics, karate and judo)should be avoided.
Dietary changes
Direct evidence on the benefits of dietarychanges from rigorous, well-controlled trials inchildren and adolescents is sparse. Accordingly,the effect of diet on blood pressure in children isextrapolated chiefly from studies on adults.
Recommendations for daily sodium intake inchildren range between 1-1.5 g (45-65 mEqsodium, 2.6-3.8 g salt). Dietary sodium restrictionis associated with small reductions in bloodpressure in children(4,19). A ‘no added saltdiet’ is a satisfactory approach to restrict salt intake.Intake of food products high in sodium (processedand canned foods, items prepared in fast foodshops including pizzas, pickles and salted potatochips) should be avoided. Increased potassiumintake, through vegetables and fruits, is associatedwith modest reduction of systolic and diastolicblood pressure in adults with essential hyper-tension(19). Potassium intake should however berestricted in children with chronic kidney diseasewith glomerular filtration rate (GFR) below 30 mL/min/1.73 m2, adrenal insufficiency, severe heartfailure, or those receiving treatment withangiotensin converting enzyme inhibitors (ACEI),
non-steroidal anti-inflammmatory agents andpotassium sparing diuretics. Despite suggestionsthat foods rich in calcium, magnesium, folic acidand fiber are useful in reducing blood pressure,there is limited evidence in this regard.
An increased intake of fresh vegetables andfruits, whole grains and non-fat dairy isrecommended. These foods are low in sodium andsaturated fat and rich in minerals (potassium,calcium, magnesium) and fiber. The Groupendorses the dietary recommendations of the IAPConsensus Committee on Obesity(20). The dailyfood composition is considered a 'thali', where half(50%) is vegetables, salads and fruits, a quarter(25%) is cereals (rice and/or chapattis), and theremainder is protein based (legumes, milk, egg,animal protein). The intake of fried foods, snacksand sweet dishes should be limited.
Secondary hypertension
Patients with sustained secondary hyper-tension require therapy with antihypertensiveagents. Physicians should be aware of the risk ofhypertensive emergencies in children with stage 2hypertension. The need to adhere to healthy eatinghabits 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 despite6-months’ of lifestyle modifications, and (v) pre-hypertension or stage 1 hypertension withcomorbid conditions (diabetes, chronic kidneydisease or dyslipidemia).
Principles of treatment
The goal for treatment is reduction of bloodpressure to levels <95th percentile, unlesscomorbid conditions or target-organ damageis present, when it should be lowered to <90thpercentile.
Commonly used medications in childreninclude ACEI, calcium channel blockers(CCB), vasodilators, β blockers and thiazide
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STATEMENT
TABLE VIII–Oral Antihypertensive Medications
diuretics (Table VIII).
Therapy is initiated with one agent, at anappropriate dose and the dose is increaseduntil the desired blood pressure is achieved. Ifthe highest dose is not effective or if there areside effects, a drug from a different class isadded or substituted.
Medications with a longer duration of action(once, twice daily dosing) are preferred forbetter compliance and less side effects.
Dose adjustment of antihypertensive medica-tions need not be made more frequently thanevery 2-3 days.
An approach to the treatment of hypertension is
A g en ts D o se ; fre q u en cy C o m m en ts A n g io te n sin con v er tin g en zy m e in h ib ito rs , a n g io ten s in re cep to r b lo c kers C a p to p r il 0 .3 - 6 m g /k g /d ay ; tid E n a la p ril 0 .1 - 0 .6 m g /k g /d a y ; q d L is ino p r il 0 .0 6 - 0 .6 m g /k g /d a y ;
q d R a m ip ril 6 m g/m 2; q d Irb esa rtan 4 -5 m g /k g /d ay L o sar ta n 0 .7 - 1 .4 m g /k g /d a y ; q d
U se ca u tio us ly if G F R < 3 0 m l/m in /1 .7 3 m 2; a vo id in re na l a rte ry s te no sis U se sm a lle r d o ses in n eo n a tes M o n ito r se ru m p o tassiu m , c re a tin ine reg u la r ly S id e e ffe c ts : h yp e rk a le m ia , im p a ired ren a l fun c tio n s; ane m ia , ne u tro p en ia , d ry co u g h in fre q ue n t
C a lc iu m c h a n n e l b lo ckers A m lo d ep ine 0 .0 5 - 0 .5 m g /k g /d a y ;
q d -b id N ife d ip in e (e x ten d ed re le ase )
0 .2 5 - 3 m g/k g /d a y ; q d -b id
Is ra d ip in e 0 .1 5 - 0 .8 m g /k g /d a y ; tid
E x ten d ed re lease n ife d ep ine m u st b e sw a llo w ed w ho le S id e e ffe c ts : H ead a c he , flush ing , d iz z iness , ta ch y ca rd ia ; a t h ig h er d o ses : lo w er ex tre m ity ed e m a , e ry th em a
B eta -b lo ck ers A te no lo l 0 .5 - 2 m g /k g /d ay ; q d -
b id M eto p ro lo l 1 - 6 m g/k g /d ay ; b id P ro p an o lo l 1 - 4 m g/k g /d ay ; tid L a b e ta lo l 1 - 4 0 m g/k g /d a y ; b id -
tid
A te no lo l: d ec rease d o se b y 5 0 % a t G F R < 5 0 m l/m in /1 .7 3 m 2; g ive o n a lte rn a te d ay s a t G F R < 1 0 m l/m in /1 .7 3 m 2
S leep d is tu rb anc e s w ith p ro p ran o lo l, m e to p ro lo l; h yp erlip id e m ia A vo id in as th m a , hea rt fa ilu re ; b lu n t sym p to m s o f h y p o glyce m ia
C e n tra l a lp h a a g o n ist C lo nid in e 5 - 2 5 µg /k g /d a y ; tid -q id A b ru p t ce ssa tio n m a y cau se reb o un d
h yp erte ns io n ; se d a tio n P er ip h era l a lp h a a n ta g o n ist P ra zo sin 0 .0 5 - 0 .5 m g /k g /d a y ;
b id -tid M a y cau se ‘firs t d o se ’ h yp o te ns io n , syn co p e
V a so d ila to rs H yd ra laz in e 1 - 8 m g/k g /d ay ; q id M in o xid il 0 .1 - 1 m g /k g /d ay ; q d -
b id
F o r h yp er te n sio n re frac to ry to o the r d ru gs S id e e ffe c ts : h ea d ach e , p a lp ita tio n , flu id re ten tio n , co n g est iv e h ea r t fa ilu re ; p e rica rd ia l e ffu s io n s , h yp er tr ich o sis w ith m ino x id il
D iu re tic s F ruse m id e 0 .5 - 6 m g /k g /d ay ; q d -
b id S p iro n o lac to ne * 1 - 3 m g/k g /d ay ; q d -b id M eto la zo ne 0 .2 - 0 .4 m g /k g /d a y ; q d H yd ro ch lo ro th iaz id e 1 - 3 m g/k g /d ay ; q d A m ilo r id e * 0 .4 - 0 .6 m g /k g /d a y ; q d
M o n ito r e lec tro ly te s, flu id sta tu s p e rio d ica lly T h ia z id es : d ys lip id e m ia , h yp e rg lyce m ia , h yp eru rice m ia , h yp o ka le m ia , h yp o m a g ne se m ia L o o p d iu re tic s : m e tab o lic a lka lo s is , h yp o ka le m ia , h yp erca lc iu ria *U se c a u tio u sly w ith A C E I , an g io te ns in rec ep to r b lo ck ers
q d o nc e d a ily ; b id tw ice d a ily ; t id th r ic e d a ily ; q id fo ur tim e s d a ily
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Nifedipine and amlodipine are effective CCBfor children. The availability of long actingpreparations permits once or twice daily dosing.Sustained release preparations of nifedipineshould be swallowed whole, and not crushed orchewed. Captopril, chiefly used in young infants,requires dosing every 6-8 hr. Beyond infancy,enalapril (1-2 daily doses) is preferred. NewerACEI (lisinopril, ramipril) require once dailydosing and have fewer side effects. Angiotensinreceptor blockers used in children includelosartan, valsartan and irbesartan. Cardioselectiveβ-blockers (atenolol, metoprolol) are effectiveagents, requiring once or twice daily dosing andhave few side effects. The use of propranolol islimited in view of the need for multiple daily dosesand side effects. Labetalol, a α- and β-blocker, isuseful in patients refractory to other medications.
Combinations minimize the side effects byallowing administration of lower dosage ofdifferent agents. With combination therapy,
consideration must be given to combining drugswith complementary mechanism of action, e.g.,ACEI (or angiotensin receptor blocker) with aCCB or thiazide diuretic, or vasodilator withdiuretic or β blocker (Fig. 3). While combinationsof ACEI and angiotensin receptor blocker havebeen proposed for adults, similar experience islimited in children(21). Long term combination ofthiazides with β-blockers may be associated withan increased incidence of glucose intolerance(22).
Specific recommendations
The choice of medication also dependson the cause of hypertension and associatedcomplications.
Essential hypertension: While there is no con-sensus on the appropriate initial therapy, thechoices are between CCB and ACEI. Therapy withβ-blockers is recommended in patients whocannot tolerate ACEI or CCB(22).
Acute glomerulonephritis: Hypertension in post-infectious glomerulonephritis is of short durationand associated with salt and water retention. Fluidand sodium restriction and judicious use of loopdiuretics are useful in patients with circulatorycongestion, hypertension and edema. Severehypertension with or without encephalopathy is anemergency and usually responds to treatment withCCB and furosemide. Occasionally treatment witha β-blocker or ACEI may be necessary.
Chronic kidney disease: The target blood pressurein these patients is <90th percentile. For patientswith chronic kidney disease stage I-III (GFR >30mL/min/1.73 m2) therapy should be initiated withACEI, since these agents also reduce proteinuriaand retard progression of renal damage(23).Monitoring of serum potassium and creatinine isnecessary, initially at 7-14 days and then every 1-3months. The dose of ACEI (or angiotensin receptorblockers) is reduced if serum creatinine exceeds30-35% from the baseline or there is hyperkalemia.Treatment with ACEI should be avoided inpatients with advanced chronic kidney disease(stage IV-V; GFR <30 mL/min/1.73 m2). Therapyin these cases is initiated with either a CCB orβ-blocker.
Guidelines for managing hypertension in
Fig. 3. Therapy is initiated with a calcium channel blocker(CCB), angiotensin converting enzyme inhibitor(ACEI) or β adrenergic blocker. If two drugs arerequired, the ACEI (or β-blocker) should becombined with a CCB. Unsatisfactory control ofblood pressure requires the use of additional agents.
↓
↓
INDIAN PEDIATRICS 117 VOLUME 44__FEBRUARY 17, 2007
STATEMENT
patients with chronic kidney disease also include:
Sodium intake is restricted to between 1-1.5 g(45-65 mEq sodium, 2.6-3.8 g salt).
Co-administration of diuretics helps inreducing sodium and volume overload.Thiazides (hydrochlorothiazide, chlorthali-done) are satisfactory, but not effective at GFR<30 mL/min/1.73 m2.
Additional medications include α-blockers(prazosin, labetalol), centrally acting agents(clonidine) or vasodilators (hydralazine,minoxidil).
The dosage of some medications (e.g.,atenolol) need modification in renalimpairment (Table VIII).
Renovascular disease: In patients with highprobability or confirmed renovascular disease,therapy should be initiated with a CCB or/and aβ-blocker. Additional agents include prazosin,labetalol, clonidine, hydralazine and/or minoxi-dil. While therapy with ACEI or angiotensinreceptor blockers is avoided in patients withsuspected or confirmed bilateral renovasculardisease, these agents might be used cautiously inthose with unilateral renovascular hypertension.
Complications of hypertension
ACEI are the preferred initial agents in subjectswith ventricular dysfunction. Additional therapymay be given with loop or thiazide diuretics, βblockers and aldosterone antagonists. ACEI orangiotensin receptor blockers are recommendedfor patients with associated proteinuria.
Drug step-down
Overweight children with uncomplicatedessential hypertension, who successfully loseweight, are best candidates for “step-down”treatment. This approach attempts a gradualreduction of the medication after 8-12 months ofsatisfactory blood pressure control. Patients mustmaintain a healthy lifestyle and blood pressureshould be checked regularly (q 3 months) aftercessation of therapy. Step down of drug therapymight also be possible in patients in whom a
specific intervention has ameliorated the under-lying cause for hypertension, e.g., followingresection of pheochromocytoma or balloondilatation for renovascular disease.
Monitoring
Patients and their families should receivecounseling for cardiovascular risk factors anddyslipidemia, and continued emphasis on lifestylemodifications. Blood pressure is monitored every3 months. Screening for end organ damage andrenal dysfunction (proteinuria, serum creatinine)and surveillance for side effects of drugs isrequired annually.
Hypertensive emergencies
Patients with stage 2 hypertension may presentwith acute, life threatening target organ damageinvolving central nervous system (encephalo-pathy, seizures), heart (pulmonary edema) orkidneys (acute renal failure). These patients needhospitalization for monitoring and supportivecare. Blood pressure levels are usually 5-15 mmabove the 99th percentile, and should be reducedto safe levels. Rapid reduction of blood pressuremight, however, compromise blood flow andresult in ischemic complications in the brain,retina, spinal cord and kidneys. Blood pressurereduction, therefore, must be regulated inorder to prevent end organ damage to theseorgans(24).
The difference between the observed anddesired (95th percentile) blood pressure isestimated; 25-30% of the desired reduction shouldoccur in the first 3-4 hr, another 25-30% in the next24 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, labetaloland nicardipine) (Table IX). Therapy with enteralantihypertensive drugs should be instituted within6-12 hr of parenteral therapy, and the lattergradually withdrawn over the next 12-24 hr.
Sodium nitroprusside is the agent with thelongest track record, readily available and the leastexpensive of all parenteral drugs. This agent canbe used in most hospital settings, provided there is
STATEMENT
INDIAN PEDIATRICS 118 VOLUME 44__FEBRUARY 17, 2007
TA
BL
E I
X –
Man
agem
ent
of H
yper
tens
ive
Em
erge
ncie
s
Drug
s Do
se
Com
men
ts
Sodi
um
nitro
prus
side
IV in
fusio
n: 0
.3-8
µg/
kg/m
in (i
n 5%
dext
rose
)
Prot
ect i
nfus
ate f
rom
ligh
t
Ons
et o
f act
ion
at 3
0 se
cond
s; pe
aks 2
min
; disa
ppea
rs w
ithin
3 m
in o
f sto
ppag
e
Med
icati
on fo
r >48
hr a
t dos
e of >
3 µg
/kg/
min
ute
mig
ht ca
use c
yani
de to
xici
ty (d
izzi
ness
, con
fusio
n,
seiz
ures
, jaw
stiff
ness
and
lacti
c aci
dosis
), w
hich
is tr
eate
d w
ith am
yl n
itrat
e, so
dium
nitr
ate a
nd
hem
odia
lysis
IV in
fusio
n of
sodi
um th
iosu
lfate
(one
-tent
h do
se o
f nitr
opru
ssid
e) o
r hyd
roxy
coba
lam
in p
reve
nts t
oxici
ty
Nitr
ogly
cerin
e IV
infu
sion:
1-3
µg/
kg/m
in, i
ncre
ase
1 µg
/kg/
min
q 3
0 m
in
Ons
et o
f act
ion
at 2
-5 m
in; d
urat
ion
5-10
min
afte
r disc
ontin
uatio
n
Alte
rnati
ve to
nitr
opru
ssid
e (es
peci
ally
in ad
ults
with
coro
nary
arte
ry d
iseas
e)
Met
hem
oglo
bine
mia
, hea
dach
e, ta
chyc
ardi
a may
occ
ur; t
achy
phyl
axis
on p
rolo
nged
use
Labe
talo
l IV
infu
sion:
0.2
5-3
mg/
kg/h
r; or
bolu
s: 0.
2-1
mg/
kg/d
ose;
may
repe
at
q 5-
10 m
in to
max
imum
40
mg
Ons
et o
f act
ion
with
in 5
-10
min
; dur
atio
n 3-
6 hr
Orth
osta
tic h
ypot
ensio
n, ab
dom
inal
pai
n, d
iarrh
ea m
ay o
ccur
Avo
id in
pat
ient
s with
asth
ma,
hear
t fai
lure
or h
eart
bloc
k
Nife
dipi
ne
PO: 0
.25
mg/
kg
Unp
redi
ctab
le an
d of
ten u
ncon
trolle
d fa
ll of
blo
od p
ress
ure;
mig
ht b
e use
d if
no ac
cess
to p
aren
tera
l age
nts
Nic
ardi
pine
IV
infu
sion:
0.5
-5 µ
g/kg
/min
;
max
imum
5 m
g/hr
May
caus
e ref
lex ta
chyc
ardi
a, in
crea
se cy
closp
orin
e lev
els
Avo
id in
hea
d tra
uma,
intra
cran
ial h
emor
rhag
e
Phen
tola
min
e IV
bol
us: 0
.1-0
.2 m
g/kg
(max
imum
5
mg)
; rep
eat 2
-4 h
r
Use
d fo
r phe
ochr
omoc
ytom
a; ad
min
ister
1-2
hr p
rior t
o su
rger
y
May
caus
e ref
lex ta
chyc
ardi
a
INDIAN PEDIATRICS 119 VOLUME 44__FEBRUARY 17, 2007
STATEMENT
facility for monitoring of blood pressure. Initiallyinfused at a rate of 0.3-0.8 mg/kg per minute, thedose may be increased in increments of 0.1-0.2 mg/kg per minute, every 15 minutes, if the desiredreduction is not achieved. Blood pressure ismeasured at least every 15 minutes; pupillaryreflexes, visual acuity and level of consciousnessare also monitored. Two IV lines should bemaintained, one for drug infusion and the other forsaline infusion (if the blood pressure were to fallprecipitously). Loss of pupillary reflex to light is anearly indicator of retinal vascular ischemia,requiring immediate infusion of normal saline.Patients receiving nitroprusside at dosesexceeding 2-3 mg/kg per minute for longer than48 hr are at risk of cyanide toxicity, and even earlierif there is hepatic or renal dysfunction.
Experts have discouraged the use of immediaterelease sublingual or oral nifedipine forhypertensive emergencies in adults, since suddenreduction of blood pressure might lead toarrhythmias, syncope, cerebrovascular accidentsand myocardial infarction. These complicationsare rarely reported in children, and nifedipinehas been used safely and effectively, bypediatricians, for hypertensive emergencies(25).The risks of side effects due to sudden fall of bloodpressure are limited, particularly if the dose ofnifedipine is between 0.1-0.25 mg/kg(26).Physicians should however be aware that theresponse to short acting nifedipine might beinconsistent and unpredictable (requiring morethan one dose) or uncontrolled (sudden fall ofblood pressure).
Volume depletion is common in patients withsevere hypertension and IV administration of loopdiuretic together with a potent anti-hypertensiveagent might lead to a precipitous drop in bloodpressure. Diuretics should therefore be avoidedunless specifically indicated for volume over-load as occurs in glomerulonephritis coexistingpulmonary edema.
Hypertensive urgencies
Hypertensive urgencies differ from emer-gencies in having no evidence of acute targetorgan damage. Patients have stage 2 hypertension
and less dramatic symptoms (e.g., headache and/or vomiting), but are at risk for progression tohypertensive emergencies. Controlled reductionof blood pressure, using oral medications, overseveral hours is desirable. Effective oral agentsinclude nifedipine, clonidine and labetalol.
The onset of action of nifedipine (0.25 mg/kg,maximum 10 mg) administered orally is within5-10 min, peaks at 30-60 min and lasts for 2-6 hr.While children show reflex tachycardia, theoccurrence of serious complications with the use oforal nifedipine in this situation is rare. Oraladministration of clonidine (0.05-0.1 mg) is alsoeffective, although the onset of action (30-60 min)and peak effect (2-4 hr) is delayed. Sedation andorthostatic 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 prolongedduration of action (4-8 hr). Despite overall efficacyof the above agents, a predictable reduction ofblood pressure is often not possible. Patients withhypertensive urgencies should be observedclosely, since use of IV medications might berequired.
Neonatal hypertension
The management of hypertension in neonateswas not separately addressed by the Expert Group.Blood pressure in neonates is determined by birthweight and gestational age. Renovascular (renalartery or venous thrombosis) and renalparenchymal disorders are important causes ofhypertension. Newborns with severe hyper-tension are managed with continuous IV infusionof nitroprusside or labetalol. Effective oral agentsinclude CCB, hydralazine and minoxidil; ACEIshould be administered at lower doses.
Conclusions
The above guidelines represent a consensusview based on evidence and opinion of experts ofthe Indian Pediatric Nephrology Group. Measure-ment of blood pressure is an important componentof pediatric physical examination that enablesscreening for hypertension. Elevated bloodpressure in children may be a sign of anunderlying disease or represent early onset
STATEMENT
INDIAN PEDIATRICS 120 VOLUME 44__FEBRUARY 17, 2007
essential hypertension. Pediatricians should beaware of the principles of early detection,evaluation and management of such patients.Children with hypertension need long term followup, counseling and treatment, which should beachieved by their primary pediatricians incollaboration with pediatric nephrologists.
REFERENCES
1. Munter P, He J, Cutler JA, Wildman RP, WheltonBK. Trends in blood pressure among children andadolescents. JAMA 2004; 291: 2107-2113.
2. Mohan B, Kumar N, Aslam N, Rangbulla A,Kumbkarni S, Sood NK, et al. Prevalence ofsustained hypertension and obesity in urban andrural school going children in Ludhiana. IndianHeart J 2004; 56: 310-314.
3. Lane DA, Gill P. Ethnicity and tracking bloodpressure in children. J Human Hypertension 2004;18: 223-228.
4. National High Blood Pressure Education ProgramWorking Group. The Fourth report on the diagnosis,evaluation and treatment of high blood pressure inchildren and adolescents. Pediatrics 2004; 114(suppl): 555-576.
5. National Heart, Lung and Blood Institute JointNational Committee on Prevention, Detection,Evaluation and Treatment of High Blood Pressure.The Seventh Report of the Joint NationalCommittee on prevention, detection, evaluationand treatment of high blood pressure: The JNC 7report. JAMA 2003; 289: 2560-2572.
6. Report of the Second Task Force on Blood PressureControl in Children 1987. National Heart, Lung andBlood Institute, Bethesda, Maryland. Pediatrics1987; 79: 1-25
7. Stabouli S, Kotsis V, Toumanidis S, Papamichael C,Constantopoulos A, Zakopoulos N. White-coat andmasked hypertension in children: association withtarget-organ damage. Pediatr Nephrol 2005; 20:1151-1155.
8. Pickering TG. Principles and techniques of bloodpressure measurement. Cardiol Clin 2002; 20: 207-223.
9. Working Group on Blood Pressure Monitoring ofthe European Society of Hypertension. Internationalprotocol for validation of blood pressure measuringdevices in adults. Blood Pressure Monit 2002; 7:3-17.
10. Butani L, Morgenstern BZ. Are pitfalls of
oscillometric blood pressure measurementspreventable in children? Pediatr Nephrol 2003; 18:313-318.
11. Srivastava RN, Bagga A. Hypertension. In:Srivastava RN, Bagga A. Pediatric Nephrology, 4thed. New Delhi: Jaypee Brothers, 2005, p. 292-315.
12. Hari P, Bagga A, Srivastava RN. Hypertension inchildren. Indian Pediatr 2000; 37: 268-274.
13. Croix B, Feig DI. Childhood hypertension is not asilent disease. Pediatr Nephrol 2006; 21: 527-532.
14. Vaughan CJ, Delanty N. Hypertensive emergencies.Lancet 2000; 356: 411-417.
15. Linakis J. The assessment and management ofhypertensive emergencies and urgencies inchildren. Pediatr Emergency Care 2005, 21: 391-396.
16. Flynn JT, Alderman MH. Characteristics of childrenwith primary hypertension seen at a referral center.Pediatr Nephrol 2005; 20: 961-966.
17. Council on Sports Medicine and Fitness andCouncil on School Health. Active healthy living:prevention of childhood obesity through increasedphysical activity. Pediatrics 2006; 117: 1834-1842.
18. American Academy of Pediatrics Committee onSports Medicine and Fitness. Athletic participationby children and adolescents who have systemichypertension. Pediatrics 1997; 99: 637-638.
19. Appel LJ, Brands MW, Daniels SR, Karanja N,Elmer PJ, Sacks FM. Dietary approaches to preventand treat hypertension. A scientific statement fromthe American Heart Association. Hypertension2006; 47: 296-308.
20. Bhave S, Bavdekar A, Otiv M, IAP National TaskForce for childhood prevention of adult diseases:Childhood obesity. Indian Pediatr 2004; 41: 559-575.
21. Yang Y, Ohta K, Shimizu M, Nakai A, Kasahara Y,Yachie A., et al. Treatment with low-dose angio-tensin-converting enzyme inhibitor (ACEI) plusangiotensin II receptor blocker (ARB) in pediatricpatients with IgA nephropathy. Clin Nephrol 2005;64: 35-40.
23. Hogg RJ, Furth S, Lemley KV, Portman R., SchwartzGJ, Coresh J, et al. National Kidney Foundation’sKidney Disease Outcomes Quality Initiative clinicalpractice guidelines for chronic kidney disease inchildren and adolescents: Evaluation, classificationand stratification. Pediatrics 2003; 111: 1416-1421.
INDIAN PEDIATRICS 121 VOLUME 44__FEBRUARY 17, 2007
STATEMENT
24. Fenves AZ, Ram CV. Drug treatment of hyper-tensive urgencies and emergencies. Semin Nephrol2005; 25: 272-280.
25. Calvetta A, Martino S, von Vigier RO, Schmidtko J,Fossali E, Bianchetti MG. What goes up mustimmediately come down! Which indication forshort-acting nifedipine in children with arterialhypertension? Pediatr Nephrol 2003; 18: 1-2.
26. Yiu V, Orrbine E, Rosychuk RJ, MacLaine P,Goodyer P, Girardin C, et al. The safety and use ofshort-acting nifedipine in hospitalized hypertensivechildren. Pediatr Nephrol 2004; 19: 644-650.
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, NewDelhi
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 TrustHospital, 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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