Traditional parenteral antihypertensive treatment

Profile of an ideal parenteral antihypertensive Treatment choice should be based on each patient’s presentation and specific to underlying conditions and the organ at risk. Ideally, the antihypertensive should have: A rapid onset High vascular selectivity Rapid reversibility Minimal safety risk of excessive BP lowering (ie, overshooting target BP zone) Too great a reduction may lead to hypoperfusion, resulting in ischemia and infarction.

JNC 7: Parenteral antihypertensive treatment A number of parenteral antihypertensive options are available, offering a range of onset and duration of action.

Sodium nitroprusside: Profile Sodium nitroprusside is a nonselective vasodilator and is the most rapid acting of available parenteral BP-lowering treatments. However, it is associated with a number of adverse effects and may compromise venous return and reduce cardiac output, which in turn may impair organ perfusion. It is also light sensitive and, therefore, requires a special delivery system.

Esmolol: Profile Esmolol is a relatively cardioselective beta-blocker, with a rapid onset and an intermediate duration of action. It is a suitable agent for situations in which cardiac output and heart rate are increased.

Fenoldopam: Profile Fenoldopam was the last antihypertensive to be approved for parenteral use in this country. Fenoldopam mediates peripheral vasodilation by acting on peripheral dopamine-1 receptors. It improves renal blood flow, urine flow rates, and sodium clearance.

Labetolol: Profile Labetalol is a combined alpha-1-adrenergic and beta-1-adrenergic blocker. It is associated with decreased peripheral vascular resistance (via alpha blockade) and has minimal or no effect on heart rate (via beta blockade). It has an intermediate onset but a relatively long duration of action.

Nicardipine: Profile Intravenous dihydropyridine calcium channel blockers are attractive options for use in acute hypertension, since they produce arterial vasodilation without negative inotropic (contraction) or dromotropic (conduction) effects. Like labetalol, nicardipine has an intermediate onset.

BP reduction with IV nicardipine The response to IV nicardipine in a female patient is shown. Nicardipine was maintained at 15 mg/h until 6:00 AM when BP was 157/65 (MAP=92), at which time the dose was decreased to 10 mg/h. At 9:00 AM, her BP was 158/73 mm Hg (MAP=102 mm Hg), and the dose was again lowered to 8 mg/h. MAPs remained between 100 mm Hg and 110 mm Hg on that dose through the rest of the day. An oral -blocker was started.

Nicardipine vs SNP for perioperative hypertension The results of this study demonstrated that intravenous nicardipine was as effective as SNP in reducing BP in both noncardiac and cardiac surgery patients. However, the time to target BP was significantly faster with nicardipine compared to nitroprusside. Fewer dose changes were required with nicardipine to reach target BP. Additionally, significantly fewer adverse events were seen in the nicardipine-treated patients. Twelve nitroprusside-treated patients and five nicardipine-treated patients experienced adverse effects due to their medication. Six patients treated with nitroprusside had to discontinue the study due to tachycardia (n = 4) and hypotension (n = 2). Most notably, none of the patients who received nicardipine were discontinued (P < 0.05).

Fenoldopam vs SNP in acute hypertension: Similar hemodynamic effects Study subjects (N = 183, n = 153 with evaluable data) were randomized to sodium nitroprusside (SNP) or fenoldopam. Diastolic blood pressure (DBP) was titrated to 95 mm Hg to 110 mm Hg, with a maximum reduction of 40 mm Hg. The two drugs were equivalent in controlling and maintaining DBP, with similar adverse effect profiles. This study enrolled patients with DBP of 120 mm Hg or greater. The primary efficacy parameter was DBP. However, SBP is emerging as a more important clinical target. In addition, organ system damage was not a study requirement, implying that some patients may have had hypertensive urgencies rather than emergencies.

Fenoldopam vs dopamine: Similar effects on perioperative renal function Fenoldopam increases renal blood flow. Some data suggest that this drug may protect against postoperative renal dysfunction. Accordingly, fenoldopam was compared with standard of care (dopamine). To more fully define the effects of fenoldopam on postoperative renal function, Bove et al randomized 80 patients undergoing cardiac surgery with cardiopulmonary bypass to either fenoldopam or dopamine (standard treatment). Study subjects were at high risk of postoperative renal dysfunction, as assessed by a Continuous Improvement in Cardiac Surgery Score of greater than 10. The incidence of acute renal failure was not statistically different between the two groups regardless of the definition used.

Currently available parenteral antihypertensive treatment: Summary