Hypertension in paediatrics, Renal Unit RHC

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 (5^th 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. 

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

• 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

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. 

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

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