Hypertension in paediatrics, Renal Unit RHC

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Objectives

The following guideline has been developed and is regularly reviewed by clinicians within the Renal Unit at the Royal Hospital for Children.  These guidelines are based on current evidence and best practice relating to the investigation and management of hypertension in infants, children and adolescents (aged 1-17 years). A separate West of Scotland guideline exists for ‘Hypertension in neonatal patients’ and this should be referred to if necessary. These guidelines are intended for use by clinicians and nursing staff. For further discussion of this guideline, please contact a member of the nephrology team based within the Renal Unit (On call Consultant through switchboard, Renal Registrar on page 18282 or 84563 or via Renal Hotdesk 0141 452 4563).

Definition of hypertension

Blood pressure rises throughout childhood relative to age and height. As with height and weight there are specific percentiles for blood pressure measurement available for both sexes. Published values for blood pressure for both sexes are included in the appendices 1 & 2.

Definitions are as follows:

2016 European Society for Hypertension Guideline Classification of hypertension in children and adolescents2.

Category

0-15 years
SBP and/or DBP percentile

16 years and older
SBP and/or DBP percentile

Normal

<90th 

<130/85

High-normal

>90th to <95th 

130-139/85-89

Hypertension

>95th 

>140/90

Stage 1 hypertension

95th to 99th and 5mmHg

140-159/90-99

Stage 2 hypertension

>99th plus 5mmHg

160-179/100-109

 

Stage 2 hypertension may be associated with systemic features due to target-organ damage (e.g. left ventricular hypertrophy, renal impairment, retinopathy).

The European Society for Hypertension proposes a flow chart (see below) for hypertension based on percentile distribution of age sex and height for those age <16 years old. A consensus in the present guidelines is now presented for adolescent males and females aged 16 or older, where the definition of hypertension should no longer be based on the 95th percentile but on the absolute cut off used for adults2.

From the 2016 European Society for Hypertension guidelines for the management of high blood pressure in children and adolescents2.

Measurement of blood pressure

Previously the “gold standard” for blood pressure measurement was mercury sphygmomanometry, now banned due to the environmental toxicity of mercury. Blood pressure is most commonly measured using automated oscillometric devices. While convenient and widely used, if a raised blood pressure is suspected following use of an automated device auscultation using a validated manual device must be performed to confirm a suspected raised blood pressure. https://bihsoc.org/bp-monitors/for-specialist-use details devices validated by the British and Irish Hypertension Society.

An appropriate sized cuff must be used. The width of the cuff should cover at least 75% of the upper arm from the acromion to the olecranon, leaving sufficient space at the antecubital fossa to allow application of the bell of the stethoscope. The diastolic blood pressure is recorded when the sounds disappear (5th Korotkoff sound) for all ages. In some children Korotkoff sounds can be heard down to 0mmHg, which excludes diastolic hypertension. 

Measure the blood pressure with the child in a seated position and their arm gently supported, ideally after the child has been sitting quietly for 5 minutes (or lying supine for an infant). Confirm hypertension with an average of measurements on three separate days/visits. Measure height and plot on an appropriate gender-specific growth chart to establish the height percentile then refer to the blood pressure centile chart for the appropriate gender.

24 hour ambulatory blood pressure monitoring (ABPM) is increasingly recognized as useful in the diagnosis and management of hypertension. To confirm a diagnosis of hypertension in children > 6 years old consider performing 24 hour ABPM.

Indications for the use of ABPM in the diagnosis of hypertension include2:

  • Confirming hypertension before drug treatment
  • Avoid WCHT (reported in up to 50% of cases suspected on casual BP readings3)
  • Chronic kidney disease
  • Types 1 & 2 diabetes mellitus
  • Renal, liver or heart transplant
  • Severe obesity +/- Obstructive Sleep Apnoea (OSA).

Infants and younger children may require admission to hospital for blood pressure monitoring in order to confirm the diagnosis as reliable blood pressure recordings can be difficult to obtain in this age group. 

History

It is important to ask about the following:

  • Review of symptoms
  • Neonatal history
    • Prematurity
    • Umbilical catheterization
    • Bronchopulmonary dysplasia
    • Patent ductus arteriosus
  • Past history of renal disease and urinary tract infections
  • Congenital heart disease and cardiovascular risk factors
  • Family history
    • Primary hypertension
    • Systemic disease
    • Endocrine disorders
  • Drug history including steroids, oral contraceptives, illicit drugs, tobacco, alcohol
  • Diet including salt intake
  • Nausea and/or vomiting
  • Urinary symptoms including polyuria, oliguria/anuria and haematuria
  • Neurological symptoms
    •  Headaches
    • Visual disturbance
    • Behavioural change
    • Altered mental state
    • Drowsiness
    • Seizures
  • Cardiac symptoms
    • Chest pain
    • Palpitations
    • Oedema (periorbital and peripheral)
    • Dyspnoea
  • Weight faltering or weight loss
Examination
  • Signs of heart failure
    • Tachycardia
    • Gallop rhythm
    •  Hepatomegaly
    • Raised jugular venous pressure
  • Absent of weak femoral pulses potentially indicative of coartaction of the aorta - if this is detected then measure four limb blood pressure
  • Neurological deficit
    •  Weakness
    • Hypotonia or hypertonia
    • Hyper-reflexia and clonus
    • Upgoing plantars
    • Cranial nerve deficits
  • Papilloedema and/or retinal haemorrhages
  • Organomegaly and/or abdominal masses
  • Evidence of thyroid disease including goitre and eye signs
  • Carotid, abdominal and/or femoral bruits
  • Obesity and Cushingoid features
Causes of hypertension

Most significant hypertension in children below age 10 years is secondary to an underlying cause. Primary (essential) hypertension is a diagnosis increasingly recognized in older children, aged over 10 years, associated with a family history of hypertension and/or being overweight. 

Primary (essential) hypertension

Obesity

Family history of hypertension or cardiovascular disease

Secondary hypertension in 
neonates and infants

 

 

 

 

 

 

 

 

Renal causes

  • Renal hypodysplasia
  • Uropathy
  • Acute kidney injury
  • Cystic kidney disease
  • Renovascular
    • Renal artery thrombosis
    • Renal artery stenosis
    • Renal vein thrombosis

Cardiovascular causes

  • Coarctation of the aorta
  • Patent ductus arteriosus +/- Indometacin

Respiratory

  • Chronic lung disease/BPD
  • Pneumothorax

Neurological

  • Seizure
  • Intracranial hypertension

Iatrogenic

  • ECMO
  • Medications

Secondary hypertension in children and adolescents

 

 

 

 

 

 

Renal causes

  • Renal parenchymal disease
  • Renal artery stenosis
  • Acute post-streptococcal glomerulonephritis
  • Membranoproliferative glomerulonephritis
  • Diffuse proliferative glomerulonephritis
  • Lupus nephritis
  • IgA nephropathy
  • Haemolytic uraemic syndrome
  • Nephrotic syndrome
  • Reflux nephropathy
  • Polycystic kidney disease
  • Wilms’ tumour

Cardiac causes

  • Coarctation of the aorta

Endocrine causes

  • Mineralocorticoid excess
  • Hyperthyroidism
  • Hyperparathyroidism
  • Phaechromocytoma
  • Neuroblastoma
  • Hypercalcaemia
  • Congenital adrenal hyperplasia

Neurological causes

  • Raised intracranial pressure
  • Tumours

Drug-related causes including immunosuppressants, NSAID’s, sympathomimetics and antidepressants

 

Investigation of hypertension

The extent to which hypertension is investigated depends on its severity and the information obtained from a careful history and examination. A family history of hypertension, renal disease or endocrine causes may help guide you in a particular direction. Clinical features of any of the aforementioned causes may be detected on examination thus helping focus your investigations. 

Initial investigations to consider:

  • Urinalysis and urine culture
  • U&E’s, Bone profile, LFT’s, CRP and FBC
  • Glucose
  • Lipid profile
  • Thyroid function tests
  • Chest X-ray
  • ECG and echocardiogram
  • Renal USS (± Doppler)
  • Peripheral plasma renin and aldosterone (following 30 minutes of recumbancy and preferably off treatment; ideally taken first thing in the morning after waking)
  • Urine catecholamines
  • 24 hour ambulatory blood pressure monitoring

Secondary investigations 

Secondary investigations are guided by the findings from the above preliminary investigations along with the clinical findings and include: 

  • Renal aetiology suspected
    • DMSA scan to look for renal scarring or loss of cortical function
    • Direct or indirect cystogram e.g. MCUG to look for vesico-ureteric reflux
    • MR Urogram
    • Renal angiography to look for renal artery stenosis
    • Renal biopsy 
  • Catecholamine excess suspected
    • I123 MIBG scan to look for phaeochromocytoma  
    • CT/MRI
    • Abdominal angiography with selective venous sampling
  • Corticosteroid excess suspected
    • Urinary steroid profile
    • Steroid suppression tests  
    • Adrenal CT/MRI 
    • Selective adrenal venous steroid sampling
Management of hypertension

N.B. Investigations should be undertaken prior to the commencement of treatment unless severity dictates immediate management.

From the 2016 European Society for Hypertension guidelines for the management of high blood pressure in children and adolescents2.

Therapeutic lifestyle changes

Most patients will benefit from lifestyle changes irrespective of the aetiology of their hypertension. These include exercise, weight loss, low-salt or no-added-salt diets, and increased intake of fruit, vegetables, fibre and low-fat dairy products.

Short-term treatment of acute hypertension

The most common indication in this category would be the treatment of hypertension secondary to acute nephritis leading to salt and water retention causing volume overload. A well-tolerated combination would be a loop diuretic (e.g. furosemide) plus a vasodilating Ca2+ channel blocker (e.g. nifedipine).

Long-term treatment of chronic hypertension

Pharmacological therapy is considered in patients who do not respond to lifestyle modifications or who have secondary hypertension, symptomatic hypertension or established target-organ damage. The aim is to use a single agent if possible and to select a long-acting once-daily agent to aid compliance. The choice of antihypertensive is dependent on the underlying aetiology. See Appendix III for a detailed list of potential pharmacological agents, including dosing regimens. 

  • Angiotensin-converting enzyme (ACE) inhibitors (e.g. enalapril, lisinopril) or angiotensin-receptor blockers (e.g. irbesartan, losartan). Relatively contraindicated in confirmed or suspected renal artery stenosis and to be used with caution in renal disease. Electrolyte monitoring is required whilst on treatment due to the risk of hyperkalaemia and azotemia. ACE inhibitors have a beneficial anti-proteinuric effect and are therefore useful in nephrotic syndrome. Complications include ascending cholangitis. ACE inhibitors and ARB’s are contraindicated in pregnancy, and females of childbearing age should use reliable contraception.
  • β-blockers (e.g. propranolol, atenolol). Asthma and overt heart failure are contraindications. β-blockers should not be used in insulin-dependent diabetics.
  • Ca2+ channel blockers (e.g. amlodipine, nifedipine)
  • Diuretics (e.g. furosemide) are useful in volume-dependent hypertension (as above). All patients treated with diuretics should have electrolytes monitored shortly after initiating therapy and periodically thereafter. Potassium-sparing diuretics (e.g. spironolactone, amiloride) may cause severe hyperkalaemia especially if given with an ACE inhibitor or ARB. 

European guideline targets for treatment2:

Hypertension without comorbidities

BP goal < 16 years: < 95th percentile
BP goal ≥ 16 years: < 140/90

HTN + diabetes mellitus type 1 or 2

BP goal < 16 years: < 90th percentile
BP goal ≥ 16 years: < 130/80

HTN + CKD

-Without proteinuria 
BP goal < 16 years: < 75th percentile
BP goal ≥ 16 years: < 130/80 

-With proteinuria 
BP goal < 16 years: < 50th percentile
BP goal ≥ 16 years: < 125/75

Treatment of severe, symptomatic hypertension

Symptomatic hypertensive emergencies should be treated without delay to avoid further damage to vital organs. The aim is to lower blood pressure promptly but in a controlled manner. A sudden drop in blood pressure is associated with an increased risk of intracranial bleeding. Short-acting antihypertensives such as nifedipine should be avoided for this reason. The initial aim of therapy is to reduce the mean arterial pressure by approximately 25% over the first 24 hours. This is best done with intravenous antihypertensives. If blood pressure drops more rapidly on initiation of treatment then volume expansion with isotonic 0.9% sodium chloride must be considered. Any serious complications must be managed before, or as, hypertension is being treated (e.g. anticonvulsants should be administered to a seizing patient along with antihypertensive medications). 

Drugs used in hypertensive emergencies include:

  • Sodium nitroprusside
    • Dose: 0.5 micrograms/kg/minute, by intravenous infusion
    • Onset: instantaneous
    • Duration of action: only during infusion
    • Side-effects: headache, chest and abdominal pain
    • Disadvantages: patients require close observation; potential exists for cyanide accumulation
  • Hydralazine
    • Dose: 12.5–50 micrograms/kg/hour (maximum 3 mg/kg in 24 hours for children >1 month), by intravenous infusion
    • Side-effects: tachycardia, headache, flushing, vomiting
    • Disadvantage: may require the introduction of a β-blocker
  • Labetalol
    • Dose: 0.5-1 mg/kg/hour adjusted every 15 minutes according to response to max. 3 mg/kg/hour
    • Side-effects: gastrointestinal upset, scalp tingling, headache, sedation
    • Disadvantage: may precipitate bronchospasm in children with a history of asthma
Appendix I: blood pressure reference ranges for males aged 1-17 by height percentile [1]

Appendix II: blood pressure reference ranges for females aged 1-17 by height percentile [1]

Appendix III: drugs for outpatient management of hypertension in children 1-17 years [1]

Class

Drug

Dose

Dosing Interval

Comments

Angiotensin
Converting
Enzyme
Inhibitor (ACEi)

Captopril

 

Child 1-11 years
Test dose 100 micrograms/kg (max. per dose 6.25 mg), monitor blood pressure carefully for 1–2 hours; usual dose 100–300 micrograms/kg 2–3 times a day, then increased if necessary up to 6 mg/kg daily in divided doses, ongoing doses should only be given if test dose tolerated.

Child 12-17 years
Test dose 100 micrograms/kg, alternatively test dose 6.25 mg, monitor blood pressure carefully for 1–2 hours; usual dose 12.5–25 mg 2–3 times a day, then increased if necessary up to 150 mg daily in divided doses, ongoing doses should only be given if test dose tolerated.

three times daily

  1. All ACEi are contraindicated in pregnancy; females of childbearing age should use reliable contraception.
  2. Check serum potassium and creatinine periodically to monitor for hyperkalaemia and uraemia.
  3. Cough and angioedema are reportedly less common with newer members of this class than with Captopril.

 

 

Enalapril  

Child 1-11 years
Initially 100 micrograms/kg once daily, monitor blood pressure carefully for 1–2 hours, then increased if necessary up to 1 mg/kg daily in 1–2 divided doses.

Child 12-17 years (50kg)
Initially 2.5 mg once daily, monitor blood pressure carefully for 1–2 hours, maintenance 10–20 mg daily in 1–2 divided doses.

Child 12-17 years (> 50kg)
Initially 2.5 mg once daily, monitor blood pressure carefully for 1–2 hours, maintenance 10–20 mg daily in 1–2 divided doses; maximum 40 mg per day.

once -twice daily 

 

Lisinopril  

Child 6-11 years
Initially 70 micrograms/kg once daily (max. per dose 5 mg), increased to up to 600 micrograms/kg once daily, alternatively increased to up to 40 mg once daily, dose to be increased in intervals of 1–2 weeks.

Child 12-17 years
Initially 5 mg once daily; usual maintenance 10–20 mg once daily; maximum 80 mg per day

 once daily

 

Class

Drug

Dose

Dosing Interval

Comments

Angiotensinreceptor blocker (ARB)

Losartan  

Child 6-17 years (20-49kg)
Initially 700 micrograms/kg once daily (max. per dose 25 mg), adjusted according to response to 50 mg daily, lower initial dose may be used in intravascular volume depletion; maximum 50 mg per day.

Child 6-17 years (>50kg)
Initially 50 mg once daily, adjusted according to response to 1.4 mg/kg once daily; maximum 100 mg per day.

once daily

  1. All ARBs are contraindicated in pregnancy; females of childbearing age should use reliable contraception.
  2. Check serum potassium, creatinine periodically to monitor for hyperkalaemia and uraemia.

 

 

Alpha and Beta Blocker

Labetalol  

Child 1-11 years
1–2 mg/kg 3-4 times daily

Child 12-17 years
Initially 50–100 mg twice daily, dose to be increased if required at intervals of 3–14 days; usual dose 200–400 mg twice daily, higher doses to be given in 3–4 divided doses; maximum 2.4 g per day.

three to four times a day 

Twice daily but can be given up to 3-4 times daily

  1. Asthma and overt heart failure are contraindications.
  2. Heart rate is dose-limiting.
  3. May impair athletic performance

 

Beta-Blocker

Atenolol  

Child 1-11 years
0.5–2 mg/kg once daily, dose may be given in 2 divided doses, doses higher than 50 mg daily are rarely necessary

Child 12-17 years 
25–50 mg once daily, dose may be given in 2 divided doses, higher doses are rarely necessary.

once daily-twice daily

  1. Non-cardioselective agents (Propranolol) are contraindicated in asthma and heart failure.
    Heart rate is dose-limiting.
    May impair athletic performance
  2. Should not be used in insulin dependent diabetics.
  3. A sustained-release formulation of Propranolol is available that is dosed once-daily.

 

Metoprolol  

Child 1-11 years

Initially 1 mg/kg twice daily, increased if necessary up to 8 mg/kg daily in 2–4 divided doses (max. per dose 400 mg).

 

Child 12-17 years

 Initially 50–100 mg daily, increased if necessary to 200 mg daily in 1–2 divided doses, high doses are rarely necessary; maximum 400 mg per day.

twice daily

 

Propranolol  

Child 1-11 years
Initially 0.25–1 mg/kg 3 times a day, then increased to 5 mg/kg daily in divided doses, dose should be increased at weekly intervals.

Child 12-17 years
Initially 80 mg twice daily, then increased if necessary up to 160–320 mg daily, dose should be increased at weekly intervals

 

twice daily-three times daily

 

 

Calcium channel blocker

Amlodipine  

Child 1-11 years
Initially 100–200 micrograms/kg once daily; increased if necessary up to 400 micrograms/kg once daily, adjusted at intervals of 1–2 weeks; maximum 10 mg per day.

Child 12-17 years
Initially 5 mg once daily, then increased if necessary up to 10 mg once daily, adjusted at intervals of 1–2 weeks.

once daily

 

 

 

 

 

  1. Extended-release Nifedipine tablets must be swallowed whole.
  2. May cause tachycardia.

 

Nifedipine Modified-
Release
(MR) 

*Child 1-17 years
0.5mg/kg twice daily Maximum: 3mg/kg/day up to 120mg/day

once -twice daily

 

Central αagonist

Clonidine  

Child 2-17 years
Initially 0.5–1 microgram/kg 3 times a day, then increased if necessary up to 25 micrograms/kg daily in divided doses, increase dose gradually; maximum 1.2 mg per day.

three times daily

  1. May cause dry mouth and/or sedation.
  2. Transdermal preparation also available.
  3. Sudden cessation of therapy can lead to severe rebound hypertension.

 

Diuretic

Furosemide  

Child 1-11 years
0.5–2 mg/kg  maximum 80 mg per day; maximum 12 mg/kg per day.

Child 12-17 years
20–40 mg daily; increased to 80–120 mg daily

2–3 times a day

  1. All patients treated with diuretics should have electrolytes monitored shortly after initiating therapy and periodically thereafter.
  2. Useful as add-on therapy in patients being treated with drugs from other drug classes.
  3. Potassium-sparing diuretics (Spironolactone, Amiloride) may cause severe hyperkalaemia, especially if given with ACEi or ARB.
  4. Furosemide is labelled only for treatment of oedema but may be useful as add-on therapy in children with resistant hypertension, particularly in children with renal disease.

 

Spironolactone  

Child 1-11 years
Initially 1–3 mg/kg daily in 1–2 divided doses; increased if necessary up to 9 mg/kg daily,

Child 12-17 years
Initially 50–100 mg daily in 1–2 divided doses; increased if necessary up to 9 mg/kg daily, in maximum 400 mg per day.

once daily-twice daily

 

Amiloride  

Child 1-11 years
100–200 micrograms/kg twice daily; maximum 20 mg per day. 

Child 12-17 years
5–10 mg twice daily.

twice daily

 

 Peripheral αantagonist

 Doxazosin  

*Child 1-5 years
20-100 micrograms/kg once daily

Child 6-11 years
Initially 500 micrograms once daily, then increased to 2–4 mg once daily, dose should be increased at intervals of 1 week.

Child 12-17 years
Initially 1 mg once daily for 1–2 weeks, then increased to 2 mg once daily, then increased if necessary to 4 mg once daily, rarely doses of up to 16 mg daily may be required.

 

 once daily

May cause hypotension and syncope, especially after first dose.

 

 

Prazosin  

Child 1-11 years
Initially 10–15 micrograms/kg 2–4 times a day, initial dose to be taken at bedtime, then increased to 500 micrograms/kg daily in divided doses, dose to be increased gradually; maximum 20 mg per day.

Child 12-17 years
Initially 500 micrograms 2–3 times a day for 3-7 days, initial dose to be taken at bedtime, then increased to 1 mg 2–3 times a day for a further 3–7 days, then increased if necessary up to 20 mg daily in divided doses, dose should be increased gradually.

two to four times daily

 

Vasodilator

Hydralazine  

Child 1-11 years
250–500 micrograms/kg every 8–12 hours, increased if necessary to 7.5 mg/kg daily; maximum 200 mg per day.

Child 12-17 years
25 mg twice daily, increased to 50–100 mg twice daily.

four times daily

  1. Tachycardia and fluid retention are common side effects.
  2. Hydralazine can cause a lupus-like syndrome in slow acetylators.
  3. Prolonged use of Minoxidil can cause hypertrichosis.
  4. Minoxidil is usually reserved for patients with hypertension resistant to multiple drugs.
  5. A beta blocker & diuretic are prescribed with Minoxidil
 

Minoxidil  

Child 1-11 years
Initially 200 micrograms/kg daily in 1–2 divided doses, then increased in steps of 100–200 micrograms/kg, increased at intervals of at least 3 days; maximum 1 mg/kg per day.

Child 12-17 years
Initially 5 mg daily in 1–2 divided doses, then increased in steps of 5–10 mg daily, increased at intervals of at least 3 days, seldom necessary to exceed 50 mg daily; maximum 100 mg per day.

once -twice daily

 

All doses correct at time of completion of the Guideline from online August 2019 BNFc except Doxazosin (1-5years) & Nifedipine MR

* Frank Shann Drug Doses 2017

Appendix IV: Antihypertensive Drugs for Outpatient management of Hypertension available for adults. Use in children only with specialist discussion

Class

Drug

Dosing Interval

 ACE inhibitor (ACEi)

 

Fosinopril

once daily

Quinapril

once daily

 

Angiotensin-receptor blocker (ARB)

Irbesartan

once daily

 

 Calcium channel blocker

 

Felodipine

once daily

Isradipine

three -four times daily

 

Diuretic

 

 

Hydro-chlorothiazide

once daily

Chlorthalidone

once daily

Triamterene

twice daily

 

 Peripheral α-antagonist

Terazosin

once daily

References
  1. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. 2004 Aug;114(2 Suppl 4th Report):555-76.
  2. 2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents. Lurbe et al. J Hypertens 34:1887–1920.
  3. Fifteen-minute consultation: the child with systemic arterial hypertension. Singh C, Jones H, Copeman H, et al. Arch Dis Child Educ Pract Ed. 2017;102:2–7.
Editorial Information

Last reviewed: 31 July 2019

Next review: 30 September 2021

Author(s): Dr Douglas Stewart, Paediatric Senior Trainee; Revised by Dr David Hughes, Consultant Paediatric Nephrologist, RHC

Version: 2

Co-Author(s): Other professionals consulted: Dr Ian Ramage – Consultant Paediatric Nephrologist, RHC

Approved By: Paediatric & Neonatal Clinical Risk & Effectiveness Committee