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Medication

Medication Summary

Most medications discussed in this article have not been specifically studied in newborns^{[16, 27]}; however, through the empiric use of these medications, reasonable clinical experience has been accumulated.

As previously stated, assess the clinical status of the infant and correct any easily correctable iatrogenic causes of hypertension (eg, infusions of inotropic agents, volume overload, pain) prior to instituting drug therapy. Next, choose an antihypertensive agent that is most appropriate for the specific clinical situation.^[26]

A study by Blowey et al assessing pharmacologic treatment in neonates with hypertension (excluding patients with congenial cardiac disorders) demonstrated that multiple drugs are commonly prescribed for hypertensive neonates; the distribution of medication classes used was as follows^[3]:

Vasodilators - 64.2% of patients
Angiotensin-converting enzyme (ACE) inhibitors - 50.8% of patients
Calcium channel blockers - 24% of patients
Alpha and beta blockers - 18.4% of patients

The authors also determined that more than one antihypertensive agent was used in 45% of the neonates with hypertension.

Class Summary

These agents relax blood vessels, thereby decreasing peripheral vascular resistance.

Hydralazine

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Hydralazine decreases systemic resistance through direct vasodilation of arterioles.

Sodium nitroprusside (Nitropress)

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Sodium nitroprusside produces vasodilation and increases inotropic activity of the heart.

Class Summary

These agents block calcium channels in vascular smooth muscle, which leads to vasodilatation.

Amlodipine (Norvasc)

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Amlodipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. This agent is a good choice for long-term outpatient treatment. It may be compounded into a stable suspension (1mg/mL).

Isradipine (DynaCirc CR)

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Isradipine is a dihydropyridine calcium channel blocker. It binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and smooth muscle. The resultant effect is arteriole dilation, which reduces systemic resistance and blood pressure, with a small increase in resting heart rate. Isradipine has a rapid onset of action. It may be compounded into a stable suspension.

Nicardipine (Cardene)

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Nicardipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery and reduces myocardial oxygen consumption. Intravenous nicardipine is the drug of choice for initial management of severe neonatal hypertension.

Class Summary

These agents decrease heart rate and cardiac output.

Labetalol (Normodyne, Trandate)

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Labetalol blocks beta1-adrenergic, alpha-adrenergic, and beta2-adrenergic receptor sites, decreasing blood pressure.

Propranolol (Inderal, InnoPran XL)

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Propranolol has membrane-stabilizing activity and decreases the automaticity of contractions.

It is not suitable for the emergency treatment of hypertension. Do not administer propranolol intravenously in hypertensive emergencies.

Esmolol (Brevibloc)

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Esmolol is an excellent drug for use in patients at risk for experiencing complications from beta blockade, particularly individuals with reactive airway disease, mild to moderate left ventricular dysfunction, and/or peripheral vascular disease. Its short half-life of 8 minutes allows for titration to the desired effect and quick discontinuation if needed.

Class Summary

These agents inhibit the conversion of angiotensin I to angiotensin II.

Captopril

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Captopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and reduces aldosterone secretion.

Enalapril (Vasotec)

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Enalapril is a competitive inhibitor of ACE. It reduces angiotensin II levels, decreasing aldosterone secretion.

Class Summary

These agents decrease plasma volume and promote excretion of water and electrolytes by the kidneys. They may be used as monotherapy or combination therapy to treat hypertension.

Chlorothiazide (Diuril)

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Chlorothiazide inhibits the reabsorption of sodium in the distal tubules, causing increased excretion of sodium and water as well as of potassium and hydrogen ions.

Hydrochlorothiazide (Microzide)

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Hydrochlorothiazide inhibits the reabsorption of sodium in the distal tubules, causing increased excretion of sodium and water as well as potassium and hydrogen ions. It is a good second agent to add to angiotensin-converting enzyme (ACE) ̶ inhibitor or vasodilator therapy.

Spironolactone (Aldactone)

Spironolactone is a potassium-sparing diuretic that is used for the management of hypertension. It may block the effects of aldosterone on arteriolar smooth muscles.

Class Summary

These agents decrease central adrenergic output.

Clonidine (Catapres)

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Clonidine stimulates alpha2-adrenoreceptors in the brain stem, activating an inhibitory neuron, which, in turn, results in reduced sympathetic outflow. These effects produce a decrease in vasomotor tone and heart rate.

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Media Gallery

Neonatal Hypertension. Normal blood pressure percentile curves for older infants. From the Second (1987) Task Force on Blood Pressure Control in Childhood; National Heart, Lung, and Blood Institute.

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Table 1. Neonatal Blood Pressures and Potential Treatment Parameters. Adapted from Dionne et al.*

Postconceptual Age	50th Percentile	95th Percentile	99th Percentile
44 weeks
SBP	88	105	110
DBP	50	68	73
MAP	63	80	85
42 weeks
SBP	85	98	102
DBP	50	65	70
MAP	62	76	81
40 weeks
SBP	80	95	100
DBP	50	65	70
MAP	60	75	80
38 weeks
SBP	77	92	97
DBP	50	65	70
MAP	59	74	79
36 weeks
SBP	72	87	92
DBP	50	65	70
MAP	57	72	77
34 weeks
SBP	70	85	90
DBP	40	55	60
MAP	50	65	70
32 weeks
SBP	68	83	88
DBP	40	55	60
MAP	49	64	69
30 weeks
SBP	65	80	85
DBP	40	55	60
MAP	48	63	68
28 weeks
SBP	60	75	80
DBP	38	50	54
MAP	45	58	63
26 weeks
SBP	55	72	77
DBP	30	50	56
MAP	38	57	63

Table 2. Intravenous Drugs for Severe Hypertension in Neonates ^[21]

Drug	Class	Intravenous (IV) Dosage	Comments
Esmolol	Beta blocker	100-300 mcg/kg/min IV infusion	Very short acting; constant IV infusion necessary
Hydralazine	Vasodilator (arteriolar)	0.15-0.6 mg/kg/dose IV bolus or 0.75-5mcg/kg/min IV constant infusion	Tachycardia is frequent adverse effect; must administer every 4 hours when administered as IV bolus
Labetalol	Alpha blocker and beta blocker	0.2-1 mg/kg/dose IV bolus or 0.25-3 mg/kg/h IV constant infusion	Heart failure, bronchopulmonary dysplasia (BPD), relative contraindications
Nicardipine	Calcium channel blocker	1-5 mcg/kg/min IV constant infusion	May cause reflex tachycardia
Sodium nitroprusside	Vasodilator (arteriolar and venous)	0.5-10 mcg/kg/min IV constant infusion	Thiocyanate toxicity can occur with prolonged use (>72 h) or in renal failure; usual maintenance dose is below 2 mcg/kg/min; may use 10 mcg/kg/min for short duration (ie, < 10-15 min)

Table 3. Oral Antihypertensive Agents Useful for Treatment of Neonatal Hypertension ^[21]

Drug	Class	Oral Dosage	Comments
Captopril	Angiotensin-converting enzyme (ACE) inhibitor	Under age 3 months: 0.01-0.5 mg/kg/dose 3 times daily; not to exceed 2 mg/kg/day At or above age 3 months: 0.15-0.3 mg/kg/dose 3 times daily; not to exceed 6 mg/kg/day	Monitor serum creatinine and potassium levels
Clonidine	Central agonist	0.05-0.1 mg/dose 2-3 times daily	Adverse effects include dry mouth and sedation; rebound hypertension with abrupt discontinuation
Enalapril	ACE inhibitor	0.08-0.6 mg/kg/day, given once or twice daily	Monitor serum creatinine and potassium levels
Hydralazine	Vasodilator (arteriolar)	0.25-1 mg/kg/dose 3-4 times daily; not to exceed 7.5 mg/kg/day	Suspension stable up to 1 wk; tachycardia and fluid retention are common adverse effects; lupuslike syndrome may develop in slow acetylators
Isradipine	Calcium channel blocker	0.05-0.15 mg/kg/dose 4 times daily; not to exceed 0.8 mg/kg/d or 20 mg/day	Suspension may be compounded; useful for both acute and chronic hypertension
Amlodipine	Calcium channel blocker	0.1-0.3 mg/kg/dose twice daily; not to exceed 0.6 mg/kg/d or 20 mg/d	Less likely to cause sudden hypotension than isradipine
Minoxidil	Vasodilator (arteriolar)	0.1-0.2 mg/kg/dose 2-3 times daily	Most potent oral vasodilator; excellent for refractory hypertension
Propranolol	Beta-blocker	0.5-1 mg/kg/dose 3 times daily	Maximal dose depends on heart rate; may administer as much as 8-10 mg/kg/d if no bradycardia; avoid in infants with BPD
Labetalol	Alpha and beta blocker	1 mg/kg/dose 2-3 times daily, up to 12 mg/kg/d	Monitor heart rate; avoid in infants with BPD
Spironolactone	Aldosterone antagonist	0.5-1.5 mg/kg/dose twice daily	Potassium-sparing diuretic; monitor electrolytes; several days necessary to observe maximum effectiveness
Hydrochlorothiazide	Thiazide diuretic	2-3 mg/kg/d orally every day or divided twice daily	Monitor electrolytes
Chlorothiazide	Thiazide diuretic	5-15 mg/kg/dose twice daily	Monitor electrolytes