TABLE 37.5 MOST COMMONLY USED ANTIHYPERTENSIVE AGENTS FOR THE TREATMENT OF HYPERTENSIVE URGENCIES AND EMERGENCIES IN CHILDREN a , b Sodium Nitroprusside Nitroprusside is a powerful vasodilator, affecting both arteriolar and venous smooth muscle Its onset is almost immediate, and its duration of action is extremely short, allowing for easy titration of the drug to the desired blood pressure Because of its venous dilatory effects, nitroprusside reduces preload and often improves cardiac output in CHF It may increase intracerebral blood flow, though this may be offset by a concomitant drop in systemic pressure Because nitroprusside is metabolized to thiocyanate and cyanide, cyanide toxicity is a risk of its use, particularly for infusions lasting more than 24 to 48 hours or in those with liver or renal impairment In such cases, thiocyanate levels should be monitored daily Because of this known risk of toxicity, the FDA has added a black box warning to the labeling of the drug Nitroprusside is given as an intravenous infusion, starting at a dosage of 0.3 to 0.5 μg/kg/min and titrating upward as needed to μg/kg/min The average dosage required for the control of hypertension is approximately μg/kg/min Because nitroprusside has an extremely short half-life, blood pressure returns to pretreatment levels within to 10 minutes of the cessation of the infusion Esmolol Esmolol is an ultra–short-acting cardioselective β1 -blocker originally used in the treatment of postoperative hypertension following repair of congenital heart disease It has an onset of action of approximately 60 seconds and a duration of action of 10 to 20 minutes It is usually administered by continuous infusion after an initial bolus dose It is given as an initial bolus of 100 to 500 μg/kg followed by an infusion of 100 μg/kg/min, titrating to effect Metabolism is independent of both hepatic and renal processes, making a good choice for use in patients with multiorgan failure Although reported use in hypertensive children outside of the postoperative setting is limited, the drug certainly has potential for use in the ED setting Because of its β- blocking effects, contraindications are similar to those of labetalol, and include second- and third-degree heart block, bradycardia, cardiac failure, and cardiogenic shock Hydralazine Hydralazine is an arteriolar vasodilator that can be given intravenously, intramuscularly, and orally Onset of action is in the order of 10 to 30 minutes when administered intravenously, with a duration ranging from to 12 hours Once the most commonly used agent for hypertension associated with pregnancy, it has largely been replaced by labetalol and nicardipine Side effects include reflex tachycardia, fluid retention, facial flushing, and increased intracranial pressure Hydralazine is given at a dose of 0.2 to 0.6 mg/kg intravenously or intramuscularly, or at a dose of 0.25 mg/kg orally to a maximum of 25 mg Phentolamine Phentolamine is an α-adrenergic receptor antagonist whose use should be limited to treatment of hypertension associated with catecholamine-induced hypertensive crises, as seen with pheochromocytoma or sympathomimetic toxicity Dosing recommendations vary widely Some recommend 0.05 to 0.1 mg/kg/dose intravenously to a maximum of mg, and others recommend a pediatric dose of mg administered intravenously or intramuscularly, repeated as needed to achieve appropriate blood pressure control Enalaprilat Enalaprilat is an angiotensin-converting enzyme inhibitor that can be useful in high renin states It is contraindicated for use in patients with bilateral renal artery stenosis Because of the high incidence of renovascular disease in the pediatric population, and limited pediatric experience with its use, caution must be exercised before using this agent for the treatment of severe hypertension in the ED It should be administered at a dose of 0.05 to 0.1 mg/kg intravenously up to a maximum of 1.25 mg Fenoldopam Fenoldopam is a selective dopamine agonist causing vasodilation of the renal, coronary, cerebral, and splanchnic vasculature, resulting in a decrease in mean arterial pressure The use of fenoldopam in pediatric patients has increased in recent years Its use has been reported for controlled perioperative hypotension and in the intensive care setting when conventional therapy has failed Recent reports in children showed that although fenoldopam resulted in a decrease in blood pressure levels, this required higher doses than for adults and the decrease was less than that observed in adults Peak effects are observed within 15 minutes, with steady-state serum levels achieved in 30 to 60 minutes Initial infusion rates of 0.2 to 0.8 μg/kg/min are recommended Side effects include reflex tachycardia, increased intracranial pressure, and increased intraocular pressure Although pediatric experience with fenoldopam is limited, it appears to be a reasonable alternative when more conventional therapies fail Clevidipine Clevidipine is an ultra–short-acting third-generation dihydropyridine calcium channel antagonist It has high specificity for arteriolar smooth muscle, reducing peripheral resistance while increasing stroke volume and cardiac output Its halflife is approximately minute with more rapid onset and offset than even nicardipine, which eases titration, and is metabolized in plasma, independent of the liver or kidney Combined, these characteristics make it a strong contender for the management of severe elevations in blood pressure levels in the ED Clevidipine has not yet been approved for use in pediatric patients Initial dosing recommendations in children suggest a starting dose of 0.5 to μg/kg/min titrating upward Oral Antihypertensive Medications Nifedipine Short-acting nifedipine is a calcium channel blocker that decreases peripheral vascular resistance Its use in children remains controversial, owing to the serious hypotensive side effects of the drug experienced in adults However, similar exaggerated effects have not been clearly demonstrated in children Although previously administered sublingually, absorption is more predictable when the capsule is bitten and swallowed Nifedipine is administered at a dose of 0.25 to 0.5 mg/kg up to a maximum of 10 mg Onset of action is within 20 to 30 minutes; duration of action is approximately hours Precipitous decreases in mean arterial pressure (>25%) have been associated with doses exceeding 0.25 mg/kg Isradipine A second-generation dihydropyridine calcium channel blocker, isradipine is another safe alternative for children with severe hypertension Onset of action is usually 30 minutes to hours, with a half-life of to hours It has selective action on vascular smooth muscle, allowing it to be used in children with compromised myocardial function Dosing ranges from 0.05 to 0.1 mg/kg per dose to a maximum of mg, given two to four times daily Clonidine Clonidine is an α2 -adrenergic agonist that works by reducing cerebral sympathetic output Its onset of action is 15 to 30 minutes following administration It is recommended by some for the management of hypertensive urgencies, although most studies have evaluated its use as a treatment of chronic primary hypertension in children older than 12 years SUMMARY It is not unusual that a child presenting to the ED will have an elevation in blood pressure levels In many cases, the blood pressure level will normalize with rest or acclimation to the environment Occasionally, however, the elevation in blood ... renal artery stenosis Because of the high incidence of renovascular disease in the pediatric population, and limited pediatric experience with its use, caution must be exercised before using this... Some recommend 0.05 to 0.1 mg/kg/dose intravenously to a maximum of mg, and others recommend a pediatric dose of mg administered intravenously or intramuscularly, repeated as needed to achieve... splanchnic vasculature, resulting in a decrease in mean arterial pressure The use of fenoldopam in pediatric patients has increased in recent years Its use has been reported for controlled perioperative