What is the role of hydralazine in treating hypertension in pediatric patients?

Hydralazine in Pediatric Hypertension Management

Hydralazine is indicated for pediatric hypertension as a vasodilator agent, typically reserved for resistant hypertension or acute hypertensive episodes, with a recommended oral dosage of 0.75 mg/kg/day initially (up to 7.5 mg/kg/day or 200 mg daily maximum) divided into four daily doses. 1, 2

Indications and Role in Treatment Algorithm

• Hydralazine is not considered a first-line agent for pediatric hypertension management but serves as an adjunctive therapy when first-line medications are insufficient 1
• It is primarily used in the following scenarios:
  • As part of multi-drug therapy for resistant hypertension 1
  • For acute management of severe hypertension requiring rapid blood pressure reduction 1
  • In specific clinical situations such as pulmonary hypertension associated with chronic lung disease 1

Dosing Guidelines

Oral Administration

• Starting dose: 0.75 mg/kg/day divided into four doses (QID) 1, 2
• Maximum dose: 7.5 mg/kg/day up to 200 mg daily 2
• Gradual dose escalation over 3-4 weeks is recommended to reach effective dosing 2

Intravenous Administration

• For acute hypertensive episodes: 0.1-0.2 mg/kg/dose 3, 4
• IV administration should be carefully monitored due to variable response and risk of excessive blood pressure reduction 4
• Studies show that approximately 31% of children may experience excessive blood pressure reduction (>25% decrease in mean arterial pressure) with IV hydralazine 4

Efficacy and Clinical Considerations

• Hydralazine acts as a direct peripheral arterial vasodilator, reducing blood pressure by decreasing systemic vascular resistance 5
• Clinical response is variable - studies show that IV hydralazine produces a median reduction of 8.5% in systolic BP and 11.5% in diastolic BP in hospitalized children 3
• Only about 10% of children achieve blood pressure below the 95th percentile after a single IV dose 3
• The 2017 AAP Clinical Practice Guidelines recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, long-acting calcium channel blockers, or thiazide diuretics as first-line agents for pediatric primary hypertension 1

Adverse Effects and Monitoring

• Common adverse effects include:
  • Tachycardia and fluid retention due to reflex sympathetic activation 1
  • Risk of lupus-like syndrome in slow acetylators with prolonged use 1
• Safety monitoring should include:
  • Regular blood pressure and heart rate measurements 3, 4
  • Monitoring for symptoms of hypotension, particularly with IV administration 4
  • Awareness that the blood pressure response can be unpredictable, with some patients experiencing increased rather than decreased blood pressure 3

Special Considerations

• Hydralazine is FDA-approved for pediatric use, though clinical trials establishing efficacy and safety are limited 2
• It is often used in combination with beta-blockers to counteract the reflex tachycardia 1
• For resistant hypertension in children, the 2017 ESC guidelines suggest considering spironolactone before hydralazine in the treatment algorithm 1
• In neonates and infants with pulmonary hypertension, hydralazine has been used but with limited evidence of efficacy 1

Clinical Pearls

• Hydralazine is typically administered four times daily (QID), which may affect medication adherence 1
• The response to hydralazine is influenced by acetylator status, with slow acetylators experiencing more pronounced and prolonged effects 6
• Continuous infusion of hydralazine has been described in limited case reports for specific situations like afterload reduction in cardiac patients, but this approach is not standard practice 5
• Inappropriate use of IV hydralazine for non-urgent hypertension should be avoided due to unpredictable responses and risk of hypotension 7