Effects of intravenous fenoldopam (SK&F 82526-J) on blood pressure in severe hypertension

Dear Sir, Fenoldopam (SK&F 82526-J) is a selective postsynaptic dopaminergic receptor (DA 1) agonist under clinical investigation for intravenous use, with potent vasodilating and natriuretic properties [1-3]. When administered intravenously, it promptly reduces blood pressure with a rapid onset and a short duration of action; it is well tolerated, thus appearing to be a useful agent for immediate t reatment of severe hypertension [4-10]. We carried out two consecutive studies in two groups of patients: an open uncontrolled trial of intravenous fenoldopam in 22 patients with severe hypertension to assess its efficacy and time course of action, and an open controlled randomized parallel trial of intravenous fenoldopam vs. sodium nitroprusside on 17 patients (nine allocated to t rea tment with fenoldopam and eight to t rea tment with sodium nitroprusside). Inclusion criteria were diastolic blood pressure ->120 mmHg and -< 150 m m H g in patients aged 20-80 years. The patients had not received any antihypertensive agent in the 12 hours preceding drug infusion. Thirty-one patients (22 in the uncontrolled study and nine in the comparative study) were treated with fenoldopam. The initial infusion rate was 0.1 p~g/kg/ min; each dose increment was 0.1 ~g/kg/min, up to a maximum infusion rate of 1.6 }xg/kg/min. The minimum interval between dose adjustments was 30 minutes in the open uncontrolled study and 10 minutes in the comparative one. Eight patients were allocated to t rea tment with sodium nitroprusside at an ifiitial rate of infusion of 0.5 ~g/kg/min. The maximum dose increment allowed was 1 txg/kg/min, and the maximum reached infusion rate was 8 }xg/kg/min, with a minimum interval between dose adjustments of 10 minutes. Infusions of fenoldopam and sodium nitroprusside were t i trated upward to reduce diastolic blood pressure to <110 mmHg, unless the clinical status of the patient suggested cessation of titration at a higher blood pressure level. When the target diastolic blood pressure reduction was achieved, the infusion rate reached during the upward titration phase was maintained for at least 6 hours and for no longer than 18 hours. Twenty-one out of the 22 patients of the uncontrolled study reached the target BP reduction, with a mean maintenance infusion rate of fenoldopam of 0.4 -+ 0.2 ~g/kg/ min, within a mean period of 148 -+ 53 minutes (mean -+ SD). Heart rate was not significantly altered by the administration of fenoldopam; in only one case was the infusion discontinued early in the upward titration phase because of the occurrence of a clinically significant sinus tachycardia (150 beats/min) with no apparent effect on blood pressure. All nine patients treated with fenoldopam in the comparative study reached the target BP reduction with a mean maintenance infusion rate of fenoldopam of 0.37 -+ 0.I ~g/kg/min in 43.3 -+ 17.5 minutes, the corresponding figures for sodium nitroprusside being 1.37 -+ 0.4 ~g/kg/min and 29.3 _+ 17.2 minutes. One patient did not complete sodium nitroprusside treatment because of severe hypotension. Both treatments were effective in reducing systolic and diastolic blood pressure as requested by the protocol. During the maintenance phase BP was stable and no rebound effects were observed in either group on cessation of the infusions. Overall fenoldopam caused only mild side effects, possibly due to the vasodilating activity of the drug (headache or flushing) in about 25% of the patients (8/ 31); they did not require any dose adjustments. Sodium nitroprusside infusion was associated with side effects in the majority of the patients (7/8): nausea, vomiting, flushing, and headache. Overall, no labora-