Hypertension In Children
 

Hypertension In Children

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The prevalence of hypertension in children is reported to be 1–3%. In recent years, the prevalence of hypertension ...

The prevalence of hypertension in children is reported to be 1–3%. In recent years, the prevalence of hypertension
in school-aged children appears to be increasing, perhaps as a result of the increased prevalence of obesity (Sorof JM,
Lai D, Turner J, Poffenbarger T, Portman PJ. Overweight, ethnicity and the prevalence of hypertension in school-aged
children. Pediatrics . The majority of these children have mild hypertension, most often primary.
However, secondary causes of hypertension such as renal parenchymal diseases and renovascular disorders still
remain the leading cause of paediatric hypertension, particularly in children < 12 years of age. Regardless of its
cause, the significant elevation of blood pressure can lead to acute organ dysfunction, and hypertensive child almost
always warrants a diagnostic evaluation.

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Hypertension In Children Hypertension In Children Document Transcript

  • Hypertension In Children
  • Apollo Medicine 2011 December Review Article Volume 8, Number 4; pp. 248–260 © 2011, Indraprastha Medical Corporation Ltd Hypertension in children NilamThaker* *Consultant Paediatric Nephrologist, 86/3, H Colony, Near Nehrunagar Circle, Ambawadi, Ahmedabad, Gujarat, India. ABSTRACT The prevalence of hypertension in children is reported to be 1–3%. In recent years, the prevalence of hypertension in school-aged children appears to be increasing, perhaps as a result of the increased prevalence of obesity (Sorof JM, Lai D, Turner J, Poffenbarger T, Portman PJ. Overweight, ethnicity and the prevalence of hypertension in school-aged children. Pediatrics 2004;113:475–82.). The majority of these children have mild hypertension, most often primary. However, secondary causes of hypertension such as renal parenchymal diseases and renovascular disorders still remain the leading cause of paediatric hypertension, particularly in children <12 years of age. Regardless of its cause, the significant elevation of blood pressure can lead to acute organ dysfunction, and hypertensive child almost always warrants a diagnostic evaluation. Keywords: Antihypertensive therapy, children, essential hypertension, hypertension, hypertensive crisis, secondary hypertension Correspondence: Dr. Nilam Thaker, E-mail: nilamht@yahoo.co.in doi: 10.1016/S0976-0016(11)60001-X DEFINITIONS AND STAGING OF HYPERTENSION • Pre-hypertension is defined as systolic or diastolic blood pressure (BP) between 90th and 95th percentiles. Adoles- cents having BP >120/80mmHg, but below the 95th per- centile are also included in this category. • Hypertension is defined as systolic or diastolic BP exceed- ing the 95th percentile for age, gender, and height, on at least 3 separate occasions, 1–3 weeks apart. Since the severity of hypertension influences its man- agement, it is staged as below: • Stage 1 hypertension: Systolic or diastolic BP values exceeding the 95th percentile and up to 5mmHg above the 99th percentile. • Stage 2 hypertension: Systolic or diastolic BP values 5mmHg or more above the 99th percentile. Two facts regarding levels and distribution of BP in children and adolescence are well accepted; BP increases steadily during growth and maturation, and adolescence is a fast growth period during which body mass and BP change rapidly. For these reasons, reference BP values specific to gender, age, and height have been introduced for children and adolescents by the Task Force group which is sponsored by the National Heart, Lung and Blood Institute.1 Assessment of both systolic and diastolic pressures are important and interpreted in relation to age- and height-related normative data derived from fourth task group report (Tables 1 and 2).2 Normative data from the Second Report of Task Force should be used for defining hypertension in infancy (Figure 1).3 White Coat Hypertension and Masked Hypertension In patients with white coat hypertension (WCH), BP is >95th percentile in clinic or hospital setting, while it is below 90th percentile in familiar environments. Opposite phenomenon is called masked hypertension (MH) where BP is normal in hospital, but high at home.4 Both are easily diagnosed by ambulatory BP monitoring. Children with WCH and MH require regular follow-up as they are at risk of sustained hypertension. Screening for Hypertension Blood pressure should be measured in all children >3 years old presented to healthcare setting.5 Blood pressure should also
  • Hypertension in children Review Article 249 © 2011, Indraprastha Medical Corporation Ltd be measured in at-risk younger children with: (i) History of prematurity, very low birth weight, or interventions in neo- natal intensive care unit (NICU); (ii) congenital heart dis- ease; (iii) recurrent urinary tract infections, known renal or urological diseases, hematuria or proteinuria; (iv) family history of congenital renal disorders; (v) malignancy; (vi) postorgan transplant; and (vii) conditions associated with hypertension, e.g., neurofibromatosis, tuberous sclerosis, and ambiguous genitalia. ETIOLOGY Primary or Essential Hypertension Patients are usually obese and postpubertal children. They typically show stage 1 hypertension and have no evidence of target organ damage. Secondary Hypertension Up to 60–70% of incidence occurs due to renal parenchymal disease, 5–20% due to renovascular causes and remaining due to other causes (Table 3). CLINICAL FEATURES AND CONSEQUENCES Most patients with pre-hypertension and hypertension are asymptomatic or have nonspecific symptoms.6 Headache, nausea, vomiting, and weight loss may be present. Severe hypertension may present with sensorial impairment, visual disturbances, focal neurological deficits, seizures, and heart failure. Infants may show irritability, failure to thrive, vomiting, feeding problems, seizures, or respiratory distress. In the newborn period, hypertension manifest with features mim- icking sepsis, intracranial hemorrhage, or cardiorespiratory distress. Therefore, accurate BP recording must be carried out in all sick neonates. If sustained hypertension remains untreated, it may give rise to damage to various organs (Table 4). Although it is generally agreed that early essential hyper- tension poses little immediate risk to most children, it carries the potential for future end-organ damage. In children, the accurate identification of hypertension at the earliest possi- ble age would, therefore, give healthcare providers the opportunity to initiate preventive measures, thereby reducing the chance of developing end-organ damage and its concom- itant morbidity and mortality.7 EVALUATION OF HYPERTENSION Careful history and physical examination provide clues to the underlying etiology (Tables 5 and 6). INVESTIGATIONS The extent to which investigations are required depends on the persistence and severity of hypertension. However, all patients with hypertension should undergo baseline investi- gations (Table 7). Obese and adolescent children should be screened for associated co-morbidity. Based on clinical features and baseline investigations, a cause for hypertension is suggested in most instances. Confirmation of the diagnosis requires specific investiga- tions tailored to specific needs (Table 8). MANAGEMENT It is useful to distinguish essential from secondary hyperten- sion. While the initial management for patients with essential hypertension comprises lifestyle modifications, most patients with sustained secondary hypertension require treatment with antihypertensive agents.2 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 co-morbid 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. Pharmacological therapy is initiated if there is (i) a co-morbid condition (chronic kidney disease, diabetes mellitus, or dyslipidemia), (ii) target organ
  • 250 Apollo Medicine 2011 December; Vol. 8, No. 4 Thaker © 2011, Indraprastha Medical Corporation Ltd Table1Bloodpressurelevelsforboysbyageandheightpercentile.5 Age (yr) BP (percentile) SystolicBP(mmHg)DiastolicBP(mmHg) HeightpercentileHeightpercentile 5th10th25th50th75th90th95th5th10th25th50th75th90th95th 150th8081838587888934353637383939 90th9495979910010210349505152535354 95th989910110310410610654545556575858 99th10510610811011211311461626364656666 250th8485878890929239404142434444 90th979910010210410510654555657585859 95th10110210410610810911059596061626363 99th10911011111311511711766676869707171 350th8687899193949544444546474848 90th10010110310510710810959596061626363 95th10410510710911011211363636465666767 99th11111211411611811912071717273747575 450th8889919395969747484950515152 90th10210310510710911011162636465666667 95th10610710911111211411566676869707171 99th11311411611812012112274757677787879 550th9091939596989850515253545555 90th10410510610811011111265666768696970 95th10810911011211411511669707172737474 99th11511611812012112312377787980818182 650th91929496989910053535455565757 90th10510610811011111311368686970717272 95th10911011211411511711772727374757676 99th11611711912112312412580808182838484 750th929495979910010155555657585959 90th10610710911111311411570707172737474 95th11011111311511711811974747576777878 99th11711812012212412512682828384858686 850th9495979910010210256575859606061 90th10710911011211411511671727273747576 95th11111211411611811912075767778797980 99th11912012212312512712783848586878788
  • Hypertension in children Review Article 251 © 2011, Indraprastha Medical Corporation Ltd 950th95969810010210310457585960616162 90th10911011211411511711872737475767677 95th11311411611811912112176777879808181 99th12012112312512712812984858687888889 1050th979810010210310510658596061616263 90th11111211411511710911973737475767778 95th11511611711912112212377787980818182 99th12212312512712813013085868688888990 1150th9910010210410510710759596061626363 90th11311411511711912012174747576777878 95th11711811912112312412578787980818282 99th12412512712913013213286868788899090 1250th10110210410610810911059606162636364 90th11511611812012112312374757576777879 95th11912012212312512712778798081828283 99th12612712913113313413586878889909091 1350th10410510610811011111260606162636464 90th11711812012212412512675757677787979 95th12112212412612812913079798081828383 99th12813013113313513613787878889909191 1450th10610710911111311411560616263646565 90th12012112312512612812875767778797980 95th12412512712813013213280808182838484 99th13113213413613813914087878990919292 1550th10911011211311511711761626364656666 90th12212412512712913013176777879808081 95th12612712913113313413581818283848585 99th13413513613814014214288899091929393 1650th11111211411611811912063636465666767 90th12512612813013113313478787980818282 95th12913013213413513713782838384858687 99th13613713914114314414590909192939494 1750th11411511611812012112265666667686970 90th12712813013213413513680808182838484 95th13113213413613813914084858687878889 99th13914014114314514614792939394959697 BP:bloodpressure.
  • 252 Apollo Medicine 2011 December; Vol. 8, No. 4 Thaker © 2011, Indraprastha Medical Corporation Ltd Table2Bloodpressurelevelsforgirlsbyageandheightpercentile.5 Age (yr) BP (percentile) SystolicBP(mmHg)DiastolicBP(mmHg) HeightpercentileHeightpercentile 5th10th25th50th75th90th95th5th10th25th50th75th90th95th 150th8384858688899038393940414142 90th97979810010110210352535354555556 95th10010110210410510610756575758595960 99th10810810911111211311464646565666767 250th8585878889919143444445464647 90th989910010110310410557585859606161 95th10210310410510710810961626263646565 99th10911011111211411511669697070717272 350th8687888991929347484849505051 90th10010010210310410610661626263646465 95th10410410510710810911065666667686869 99th11111111311411511611773737474757676 450th8888909192949450505152525354 90th10110210310410610710864646566676768 95th10510610710811011111268686970717172 99th11211311411511711811976767677787979 550th8990919394959652535354555556 90th10310310510610710910966676768696970 95th10710710811011111211370717172737374 99th11411411611711812012078787979808181 650th9192939496979854545556565758 90th10410510610810911011168686970707172 95th10810911011111311411572727374747576 99th11511611711912012112280808081828383 750th9393959697999955565657585859 90th10610710810911111211369707071727273 95th11011111211311511611673747475767677 99th11711811912012212312481818282838484 850th959596989910010157575758596060 90th10810911011111311411471717172737474 95th11211211411511611811875757576777878 99th11912012112212312512582828383848586
  • Hypertension in children Review Article 253 © 2011, Indraprastha Medical Corporation Ltd 950th96979810010110210358585859606161 90th11011011211311411611672727273747575 95th11411411511711811912076767677787979 99th12112112312412512712783838484858687 1050th989910010210310410559595960616262 90th11211211411511611811873737374757676 95th11611611711912012112277777778798080 99th12312312512612712912984848586868788 1150th10010110210310510610760606061626363 90th11411411611711811912074747475767777 95th11811811912112212312478787879808181 99th12512512612812913013185858687878889 1250th10210310410510710810961616162636464 90th11611611711912012112275757576777878 95th11912012112312412512679797980818282 99th12712712813013113213386868788888990 1350th10410510610710911011062626263646565 90th11711811912112212312476767677787979 95th12112212312412612712880808081828383 99th12812913013213313413587878889899091 1450th10610610710911011111263636364656666 90th11912012112212412512577777778798080 95th12312312512612712912981818182838484 99th13013113213313513913688888990909192 1550th10710810911011111311364646465666767 90th12012112212312512612778787879808181 95th12412512612712913013182828283848585 99th13113213313413613713889899091919293 1650th10810811011111211411464646566666768 90th12112212312412612712878787980818182 95th12512612712813013113282828384858586 99th13213313413513713813990909091929393 1750th10810911011111311411564656566676768 90th12212212312512612712878797980818182 95th12512612712913013113282838384858586 99th13313313413613713813990909191929393 BP:bloodpressure.
  • 254 Apollo Medicine 2011 December; Vol. 8, No. 4 Thaker © 2011, Indraprastha Medical Corporation Ltd Table 3 Etiology of hypertension. Renal parenchymal Renovascular Endocrine Neurological Cardiovascular Drug-induced Monogenic (+ve F/H, low K, low renin) Acute and chronic GN ARF/CRF Reflux nephropathy Obstructive uropathy HUS Polycystic kidney Hereditary nephritis (Alport’s) Vasculitis (lupus, HSP, polyarteritis) Renal artery stenosis Renal vessel thrombosis Aorto-arteritis Cushing syndrome Pheochromocytoma CAH Hyperaldosteronism Hyperthyroidism Hyperparathyroidism Increased ICT Guillain–Barré syndrome Coarctation of aorta PDA Corticosteroids Cyclosporin Tacrolimus Erythropoietin Glucocorticoid- remediated aldosteronism Apparent mineralocorticoid excess Liddle’s syndrome Gordon’s syndrome GN: glomerulonephritis; ARF: acute renal failure; CRF: chronic renal failure; HUS: hemolytic-uremic syndrome; HSP: Henoch Schönlein purpura; CAH: congenital adrenal hyperplasia; ICT: intracranial tension; PDA: patent ductus arteriosus. B SystolicBP 115 110 105 100 95 90 85 80 75 70 65 0 1 2 3 4 5 6 Months 95th 80th 75th 70th 7 8 9 10 11 12 75 70 65 60 55 50 45 DiastolicBP 0 1 2 3 4 5 6 Months 95th 90th 75th 50th 7 8 9 10 11 12 75 70 65 60 55 50 45 DiastolicBP 0 1 2 3 4 5 6 Months 95th 90th 75th 50th 7 8 9 10 11 12 115 110 105 100 95 90 85 80 SystolicBP 75 70 65 0 1 2 3 4 5 6 Months 95th 90th 75th 50th 7 8 9 10 11 12 A 87 68 51 4 101 65 59 4 106 63 63 5 106 63 66 5 106 63 68 6 105 65 70 7 105 66 72 8 105 67 73 9 105 68 74 9 105 68 76 10 105 69 77 10 105 69 78 11 105 69 80 11 90th percentile Systolic BP (mmHg) Diastolic BP (mmHg) Height (cm) Weight (Kg) 76 68 54 4 98 65 55 4 101 64 56 4 104 64 58 5 105 65 61 5 106 65 63 6 106 66 66 7 106 66 68 8 106 66 70 9 106 67 72 9 106 67 74 10 105 67 75 10 105 67 77 11 90th percentile Systolic BP (mmHg) Diastolic BP (mmHg) Height (cm) Weight (Kg) Figure 1 Age-specific percentiles for blood pressure in boys (A) and girls (B) from birth to 12 months of age. Reprinted from the Second Report of Task Force on Blood Pressure Control in Children.3 BP: blood pressure.
  • Hypertension in children Review Article 255 © 2011, Indraprastha Medical Corporation Ltd Table 6 Physical examination. General examination Systemic examination Blood Pallor, edema, rashes, Palpable kidney, renal pressure pigmentation joint bruit, hepatomegaly, in all four swelling, rickets (bony signs of heart failure, limbs, deformity), obesity, short neurologic deficit peripheral stature, ambiguous pulsation genitalia/virilization Table 7 Baseline investigations. Evaluation for cause Co-morbidity Target organ damage CBC FBS Heart: ECG, ECHO Urea/creatinine Lipid profile Brain: MRI Electrolytes, blood gas Uric acid Eyes: Fundus Urine routine, C/S Kidneys: Proteinuria Renal USG CBC: complete blood count; USG: ultrasonography; FBS: fasting blood sugar; ECG: electrocardiogram; ECHO: echocardiography; MRI: mag- netic resonance imaging; C/S: culture and sensitivity. damage, or (iii) failure of BP to decline below the 95th per- centile, despite lifestyle modifications for 6 months. NonpharmacologicTreatment This includes lifestyle modification in the form of: • weight reduction in obese, • increased physical activity. At least 30–60 min or more of physical activity every day that is developmentally appropriate, enjoyable and involv- ing a variety of activities,8 • dietary changes in the form of salt restriction. Recom- mendations for daily sodium intake in children range between 1 and 1.5g. PharmacologicTreatment 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 co-morbid conditions (diabetes, chronic kidney disease or dyslipidemia). Aim ofTreatment • Reduction of BP to levels <95th percentile. • Blood pressure <90th percentile when co-morbid condi- tions or target-organ damage is present. Angiotensin Converting Enzyme Inhibitors Angiotensin converting enzyme inhibitors (ACEi) (capto- pril, enalapril, etc.) directly block the formation of angi- otensin II (AT-II), and at the same time increase bradykinin level. The net results are reduced vasoconstriction, reduced sodium and water retention, and increased vasodilatation (through bradykinin). Table 4 Target organ damage due to hypertension. Brain Heart Kidney Eyes Hypertensive encephalopathy Left ventricular hypertrophy Albuminuria Papilloedema Intracerebral bleed Left ventricular failure Chronic kidney disease Hypertensive retinopathy Table 5 History. Symptoms of HTN Symptoms of underlying cause F/H Neonatal history Headache, vomiting, visual disturbance convulsion, altered sensorium Renal: Polyuria, nocturnal eneuresis, UTI, hematuria, edema Endocrine: Muscle weakness, sweating, flushing Systemic: Joint pain, rash, fever, weight loss Drugs: Steroids, CNI, EPO Hypertension, diabetes, obesity, renal diseases Umbilical catheterization, neonatal asphyxia, episodes of severe hypotension, history of oligohydraminos Infants: Irritability, failure to thrive HTN: hypertension; UTI: urinary tract infection; CNI: calcineurin inhibitor; EPO: erythropoietin; F/H: family history.
  • 256 Apollo Medicine 2011 December; Vol. 8, No. 4 Thaker © 2011, Indraprastha Medical Corporation Ltd Angiotensin Receptor Blockers Angiotensin receptor blockers (ARBs) (losartan, irbesartan) competitively inhibit AT-II receptor and thereby decrease peripheral vascular resistance (PVR). They have no action on bradykinin production or metabolism (Figure 2). Antihypertensive Drugs and their Mechanism of Action Blood pressure is a product of the cardiac output (CO) and PVR. BP=CO×PVR, CO=Heart rate×Stroke volume. where, BP: blood pressure; CO: cardiac output; PVR: peri- pheral vascular resistance Various antihypertensive drugs (Table 9) decrease the BP by decreasing either of the CO or of the PVR or both: • Angiotensin converting enzyme inhibitors, ACEi (captopril, enalapril, etc.). • Angiotensin receptor blocker (losartan, irbesartan). • Calcium channel blocker (CCB) (nifedipine, amlodipine, etc.). They inhibit the influx of calcium into arterial smooth muscle cells and cause dilatation of peripheral arterioles. Thereby, they decrease BP by decreasing PVR. • Sympathoplegic drugs: – Centrally acting adrenergic drugs, e.g., clonidine. Angiotensinogen Renin Kallikrein Kininogen ACE (Kininase-II) BradykininAngiotensin-I ↑ BP ↓ BP Angiotension-II Vasoconstriction Aldosterone secretion Inactive products ↑ PVR ↑ Na+ and H2 O retension Vasodilation ↓ PVR ↑ Prostaglandin synthesis Figure 2 Renin–angiotensin system. ACE: angiotensin converting enzyme; PVR: peripheral vascular resistance; BP: blood pressure. Table 8 Additional diagnostic tests. Glomerulonephritis Reflux nephropathy Renovascular Endocrine Coarctation of aorta Serum C3, C4, ASO, MCU, DMSA Doppler renal vessel Plasma and urine cortisol, ECHO, angiography ANA, dsDNA, Captopril renography urine catecholamine ANCA MR angiography Thyroid hormones, parathormone Renal biopsy Digital subtraction Plasma renin activity, angiography aldosterone level CT/MR imaging, MIBG scan ASO: antistreptolysin-O; MCU: micturating cysto-urethrogram; DMSA: dimercaptosuccinic acid; ANA: antinuclear antibody; dsDNA: double-stranded deoxyribonucleic acid; ANCA: anti-neutrophil cytoplasmic antibody; CT: computerized tomography; MR: magnetic resonance; MIBG: metaiodobenzyl- guanidine; ECHO: echocardiography.
  • Hypertension in children Review Article 257 © 2011, Indraprastha Medical Corporation Ltd Clonidine is a centrally acting (presynaptic) α2-agonist. It prevents neurotransmitter release, decreases sympa- thetic tone, and thereby decreases BP. – Drugs acting on peripheral nervous system: ❍ β-blocker (propranolol, atenolol, etc.) They decrease BP by decreasing the CO through action on β1-receptor. Labetalol is both α- and β-blocker. It decreases BP by decreasing both CO and PVR. ❍ α-blocker (prazosin, phentolamine, etc.). Prazosin is α1-blocker while phentolamine is α1- and α2-blocker.They decrease the BP by decreasing PVR. • Vasodilators (hydralazine, sodium nitroprusside, diazox- ide, minoxidil). They relax the smooth muscle of arterioles (and/or veins), decrease PVR and BP. • Diuretics (loop diuretic, thiazide). By causing natriuresis, they decrease total blood volume and CO. Table 9 Oral antihypertensive agent.7 Agents Dose; frequency Comments Angiotensin converting enzyme inhibitors, angiotensin receptor blockers Captopril 0.3–6mg/Kg/day; tid Use cautiously if GFR <30mL/min/1.73m2 ; 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 0.1–0.6mg/Kg/day; qd Lisinopril 0.06–0.6mg/Kg/day; qd Ramipril 6mg/m2 ; qd Irbesartan 4–5mg/Kg/day Losartan 0.7–1.4mg/Kg/day; qd Calcium channel blockers Amlodipine 0.05–0.5mg/Kg/day; qd–bid Extended release nifedipine must be swallowed whole Side-effects: Headache, flushing, dizziness, tachycardia; at higher doses: Lower extremity edema, erythema Nifedipine (extended release) 0.25–3mg/Kg/day; qd–bid Isradipine 0.15–0.8mg/Kg/day; tid Beta-blockers Atenolol 0.5–2mg/Kg/day; qd–bid Atenolol: Decrease dose by 50% at GFR <50mL/min/1.73m2 ; give on alternate days at GFR <10mL/min/1.73m2 Sleep disturbances with propranolol, metoprolol; hyperlipidemia Avoid in asthma, heart failure; blunt symptoms of hypoglycemia Metoprolol 1–6mg/Kg/day; bid Propranolol 1–4mg/Kg/day; tid Labetalol 1–4mg/Kg/day; bid–tid Central α-agonist Clonidine 5–25mg/Kg/day; tid–qid Abrupt cessation may cause rebound hypertension; sedation Peripheral α-antagonist Prazosin 0.05–0.5mg/Kg/day; bid–tid May cause ‘first-dose’ hypotension, syncope Vasodilators Hydralazine 1–8mg/Kg/day; qid For hypertension refractory to other drugs Side-effects: Headache, palpitation, fluid retention, congestive heart failure; pericardial effusions, hypertrichosis with minoxidil Minoxidil 0.1–1mg/Kg/day; qd–bid Diuretics Frusemide 0.5–6mg/Kg/day; qd–bid Monitor electrolytes, fluid status periodically Thiazides: Dyslipidemia, hyperglycemia, hyperuricemia, hypokalemia, hypomagnesemia Loop diuretics: Metabolic alkalosis, hypokalemia, hypercalciuria *Spironolactone 1–3mg/Kg/day; qd–bid Metolazone 0.2–0.4mg/Kg/day; qd Hydrochlorothiazide 1–3mg/Kg/day; qd *Amiloride 0.4–0.6mg/Kg/day; qd *Use cautiously with ACEi, angiotensin receptor blockers GFR: glomerular filtration rate; ACEi: angiotensin converting enzyme inhibitor; qd: once daily; bid: twice daily; tid: thrice daily; qid: four times daily.
  • 258 Apollo Medicine 2011 December; Vol. 8, No. 4 Thaker © 2011, Indraprastha Medical Corporation Ltd Principles ofTreatment (Figure 3) • Therapy is initiated with one agent. • Dose is increased until desired BP achieved. If highest dose is not effective or side-effects, drug from different group added. • Drug with longer duration of action is preferred for better compliance. Length ofTherapy The appropriate duration of treatment for a child or adoles- cent is unknown. Some patients require lifelong therapy; others may experience improvement or even resolution of hypertension. For these reasons, if BP is under excellent con- trol and no organ system damage is present, medications can be tapered and discontinued under careful observation if the underlying cause is corrected (i.e., renovascular hypertension, drug-induced hypertension, adrenal tumors).9 Blood pressure should be monitored carefully on follow-up, since a signifi- cant proportion of patients become hypertensive in the future. Specific Recommendations Acute Glomerulonephritis Hypertension is of short duration and occurs due to sodium and water retention. Therefore, loop diuretics are preferred and CCB and ACEi can be added if required. Chronic Glomerulonephritis Chronic kidney disease stages I–III (glomerular filtration rate [GFR]>30mL/min/1.73m2 ) therapy should be initiated with ACEi, since these agents also reduce proteinuria and retard the progression of renal damage.10 Treatment with ACEi should be avoided in patients with advanced chronic kidney disease (stages IV–V; GFR <30mL/min/1.73m2 ) because of the risk of hyperkalemia. Therapy in these cases is initiated with either a CCB or a β-blocker. Renovascular Disease Therapy should be initiated with a CCB and/or β-blocker.Addi- tional agents include prazosin, labetalol, clonidine, hydrala- zine, and/or minoxidil.Therapy withACEi orARB is avoided in patients with suspected or confirmed bilateral renovascular disease, because of the risk of precipitation of renal failure. Hypertensive Crisis Acute elevation of BP to level likely to cause end-organ damage: • Hypertensive emergency: Severe hypertension with imme- diate and ongoing target organ damage. • Hypertensive urgency: No target organ damage. Blood pressure homeostasis is governed by the interaction of multiple forces involving the cardiovascular system and kidney, and modulated by neural and humoral mechanisms. Tissue perfusion in the kidney, brain, and heart is main- tained over a wide spectrum of BP fluctuations by humoral and myogenic mechanisms, resulting in the autoregulation of blood flow in various organs. End-organ damage from severe hypertension occurs when BP rises above the ranges of autoregulation.11,12 Hypertensive crisis is predominantly angiotensin-dependent with high vascular reactivity, elevated levels of norepinephrine and vasopressin, and decreased levels of vasodilating hormones such as kininogens, kinins, and prostacyclins. Severe hypertension induces changes in the renal arte- rioles that lead to endothelial damage, platelet and fibrin deposition, and thromboxane release. This cascades into vasoconstriction, ischemia, myointimal proliferation, and decompensation of autoregulatory mechanisms resulting in hypoperfusion to the heart, kidney, and brain. A microangi- opathic hemolytic anemia and intravascular coagulation develop that mimic thrombotic thrombocytopenic purpura.13 This sequence of events leads to proliferative endarteritis and fibrinoid necrosis of the arterial wall. Hypertensive crisis can result in hypertensive encepha- lopathy from the cerebral hyperperfusion, endothelial dys- function, microvascular injury, and cerebral edema. This in turn can be manifested as posterior reversible encephalopa- thy (PRES) in imaging studies (Figure 4).14 Changes are noted in the posterior cerebral cortex and can be considered to occur from vasogenic edema. Start with CCB or ACEi or β-blocker Combination therapy (either) • ACEi + CCB • ACEi + thiazide diuretic • β-blocker + CCB Combine ACEi + CCB + prazosin/β-blocker/thiazide Additional agents Clonidine, labetalol, hydralazine, minoxidil Blood pressure >95th percentile Blood pressure >95th percentile Figure 3 Approach to treatment. CCB: calcium channel blocker; ACEi: angiotensin converting enzyme inhibitor.
  • Hypertension in children Review Article 259 © 2011, Indraprastha Medical Corporation Ltd Management of Hypertensive Emergency Blood pressure reduction is done as follows: • The difference between the observed and desired (95th percentile) BP is estimated: – 25–30% of the desired reduction in the first 3–4h. – 25–30% in the next 24h. – Desired level over the next 2 days. • Agents of choice include short-acting, intravenous (i.v.) preparations that are titrated to response (sodium nitro- prusside, labetalol, and nicardipine) (Table 10). Therapy with enteral antihypertensive drugs should be instituted within 6–12h of parenteral therapy, and the latter gradu- ally withdrawn over the next 12–24h. Intravenous Nicardipine • Dihydropyridine CCB. • Reduces PVR. • It does not have a negative inotropic effect and can be used in the presence of bronchospasm and in patients with hepatic and renal failure. • Its half-life is 10–15min and the onset of action is within 15min. • Side-effects: Tachycardia and flushing. Sodium Nitroprusside • Rapid onset of action and reduces pre-load and after- load; consequently, it is beneficial in congestive heart failure induced by hypertensive crisis. • Initially infused at a rate of 0.3–0.8μg/Kg/min, the dose may be increased in increments of 0.1–0.2mg/Kg/min, every 15min, if the desired reduction is not achieved. Blood pressure is measured at least every 15 min. • Use of the drug for >24–48h can lead to an accumula- tion of thiocyanate, especially in the presence of renal and hepatic insufficiency. Thiocyanate poisoning can Table 10 Drugs used for hypertensive emergency. Drugs Class Route Dose Side-effects Nicardipine Calcium channel blocker i.v. 1–3μg/Kg/min Headache, increased intracranial pressure Sodium nitroprusside Vasodilator i.v. 0.5–8μg/Kg/min Nausea, muscle twitching, headache, cyanide toxicity with decreased renal function Labetalol α- and β-blocker i.v. infusion Bolus 0.5–3mg/Kg/h 0.2–1mg/Kg/dose Nausea, bradycardia. Avoid in asthma, congestive heart failure, hyperkalemia Hydralazine Vasodilator i.v. 0.1–0.5 mg/Kg/ dose every 4–6h Tachycardia, palpitation, flushing, headache Phentolamine α-blocker i.v. 0.1–0.2mg/Kg/dose Used in pheochromocytoma. May cause orthostatic hypotension, tachycardia i.v.: intravenous. A B Figure 4 Magnetic resonance imaging. (A) Fluid-attenuated inversion recovery and (B) T2-weighted images. Bilateral, relatively sym- metrical high-intensity areas are depicted in the white and gray matter of the occipital region.
  • 260 Apollo Medicine 2011 December; Vol. 8, No. 4 Thaker © 2011, Indraprastha Medical Corporation Ltd cause methemoglobinemia, metabolic acidosis, altered mental status and seizures. Labetalol • α- and β-sympathetic reduces PVR. • It has a relatively long half-life (3–5 h), and this should be taken into account when titrating the dose of the drug. • It should not be used in patients with bronchospastic dis- ease or congestive cardiac failure as it has a negative ino- tropic effect. It should also be used with caution in children with diabetes. • Labetalol has the potential to worsen hyperkalemia, and this has to be considered in children with impaired kid- ney function. • This drug can be given as an i.v. bolus, which can be advantageous when an infusion cannot be started quickly. Management of Hypertensive Urgency No target damage but are at risk of progression to hyperten- sive emergencies if not treated. Control BP with oral medication gradually over 2–3 days. Effective oral medications are CCB, clonidine, labeta- lol and minoxidil (Table 11). Finally, education, anticipatory guidance, early detection, accurate diagnosis, and effective therapy may help improve the long-term outcomes of children and adolescents with hypertension. REFERENCES 1. Report of the Task Force on Blood Pressure Control in Children. National Heart, Lung and Blood Institute. Pediatrics 1977;59:797–820. 2. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114(Suppl 2):1–22. 3. Report of the Second Task Force on Blood Pressure Control in Children 1987. National Heart, Lung and Blood Institute, Bethesda, Maryland. Pediatrics 1987;79:1–25. 4. Stabouli S, Kotsis V, Toumanidis S, Papamichael C, Constantopoulos A, Zakopoulos N. White-coat and masked hypertension in children: association with target-organ damage. Pediatr Nephrol 2005;20:1151–5. 5. Srivastava RN, Gulati A. Hypertension. In: Pediatric Nephrology 5th ed. Srivastava RN, Bagga A, eds. New Delhi: Jaypee Brothers 2011:337–59. 6. Bagga A, Kanitkar M, Ali U, et al. Evaluation and manage- ment of hypertension. Indian Pediatr 2007;44:103–21. 7. Lurbe E, Alcon JJ, Redon J. Epidemiology and consequences of childhood hypertension. Comprehen Pediatr Nephrol 2008;41:637–42. 8. Council on Sports Medicine and Fitness and Council on School Health. Active healthy living: prevention of childhood obesity through increased physical activity. Pediatrics 2006; 117:1834–42. 9. Gulati S. Childhood hypertension. Ind Pediatr 2006;43: 326–33. 10. Hogg RJ, Furth S, Lemley KV, et al. National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative clin- ical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification and stratification. Pediatrics 2003;111:1416–21. 11. Chandar J, Zilleruelo G. Hypertensive crisis in children. Pediatr Nephrol 2011;26:597–603. 12. Roman RJ. Autoregulation of blood flow. In: Hypertension Primer: The Essentials of High Blood Pressure 3rd ed. Izzo JL, Black HR, eds. Council for High Blood Pressure Research, American Heart Association/Lippincott-Williams & Wilkins, Philadelphia 2003:114–7. 13. Zhang B, Xing C, Yu X, Sun B, Zhao X, Qian J. Renal thrombotic microangiopathies induced by severe hypertension. Hypertens Res 2008;31:479–83. 14. Kwon S, Koo J, Lee S. Clinical spectrum of reversible posterior encephalopathy syndrome. Pediatr Neurol 2001;24:361–4. Table 11 Drugs used for hypertensive urgency. Drugs Class Route Dose Side-effects Isradipine Calcium channel blocker Oral 0.05–0.1mg/Kg/dose, maximum 5mg/dose Tachycardia, headache Clonidine Central α-agonist Oral 5–25μg/Kg/day tds Sedation, rebound hypertension Minoxidil Vasodilator Oral 0.1–2mg/Kg/day bd Hypertricosis, pericardial effusion Labetalol α- and β-blockers Oral 1–3mg/Kg/day bd Bradycardia
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