Sodium nitroprusside lowers blood pressure by dilating both the arterial and venous side of the circulation, dramatically increasing the size of the capillary beds and decreasing systemic vascular resistance. Its quick onset of action makes it a very useful drug for hypertensive emergencies. The short half-life of the drug allows for easy titration and in fact, blood pressures will return to baseline within minutes of turning off a sodium nitroprusside drip. In addition, as it does not act as a negative inotrope, it is an ideal candidate for patients with congenital heart malformations.7 The starting dose of nitroprusside is 0.3 to 0.5 μg/kg/min with a maximum of 10 μg/kg/min.8
Side effects for nitroprusside include an increase in intracranial pressure, so it should be used with caution in the setting of head injury or hypertensive encephalopathy. Also, nitroprusside is metabolized into cyanide by the red blood cells, which is then metabolized into thiocyanate by the liver and then excreted by the kidneys. Prolonged use and/or higher doses in small children can lead to cyanide poisoning. Thiocyanate levels need to be followed in prolonged administration and the drug should be discontinued after approximately 48 hours. Because of its metabolic pathway, it should be used with caution in children with renal insufficiency or liver impairment.9
Labetolol has been used for many years in both adult and pediatric hypertensive crises. It acts as both an α- and a β-blocker; smooth muscle relaxation peripherally allows a decrease in blood pressure with little reflex tachycardia or reduction in peripheral perfusion. Despite its efficacy, there are a few drawbacks to this drug. Its half-life is quite a bit longer than that of nitroprusside, approximately 3 to 5 hours. Thus, overshooting the desired blood pressure decrease cannot be easily reversed. It may precipitate hyperkalemia or hypoglycemia, and because of its β-blockade, it is contraindicated in children who suffer from asthma or chronic lung disease.7 It also is a negative inotrope and should probably not be used with children with congenital heart disease.8
Esmolol is a selective β-blocker that appears to be more cardioselective, and some people recommend its use in children with hypertensive crisis in the setting of congenital heart disease, especially coarctation of the aorta.7
There are drugs such as prazosin and clonidine that are selective α-inhibitors that have the benefit of not worsening bronchospasm. The main drawback with clonidine is its oral administration and a severe rebound hypertension once the drug is withdrawn.
There are two drugs in the calcium-channel blocker class that can be used to treat hypertension in children: nicardipine and nifedipine. Nicardipine is administered intravenously and can be titrated carefully with its rapid onset of action and short half-life. Also, because it has some cardiac activity, it can decrease the systemic vascular resistance (SVR) without causing an increase in heart rate.7 There is little published data on the use of this drug in children but case reports have been published especially for those in whom other agents are contraindicated. Nifedipine is an oral agent available in liquid-filled capsules and is not used often in acute settings. The capsule can be opened and administered sublingually as a last resort for children with hypertensive emergency, when IV access is an issue. This agent should be used with great caution as it can be difficult to dose and can cause excessive drop in blood pressure.10 Also, it has a short half-life with potential for rebound hypertension.8 Its use is better restricted to long-term management of hypertension in its extended release form.
This class of drugs inhibits ACE that converts renin to angiotensin. Angiotensin is a potent vasoconstrictor, so the result of inhibiting ACE is vascular relaxation and decrease in blood pressure. There are many oral forms that have been studied and are both efficacious and safe in pediatric populations. There is also an intravenous version of enalopril (enaloprilat) that can theoretically be used for pediatric hypertensive emergency, although it is found to be most effective with children who have high renin states.9
Hydralazine is a drug that has, in the past, been given for rapid lowering of blood pressure; this is accomplished by pure arteriolar dilatation. It appears to be no more effective than sodium nitroprusside, can have a less predictable effect on blood pressure, and can also cause significant tachycardia.9 At this time, there are numerous superior choices to hydralazine for blood pressure lowering, however it may be useful as an oral agent while IV agents are being prepared.7
Diuretics work by decreasing intra- and extravascular volumes. Unfortunately, the body becomes accustomed to this effect, leading to medication resistance. The most commonly used agents are loop diuretics, thiazides, and potassium-sparing diuretics, and all are safe to use initially. Side effects of these medications are mainly electrolyte imbalances that should be evaluated in patients who take them for prolonged periods of time. Both loop diuretics and thiazides can cause hypokalemia and hyperlipidemia; loop diuretics also cause hypercalcemia and thiazides can cause calciuria.9