Intravenous nicardipine for the treatment of severe hypertension.

PURPOSE: Severe hypertension responds to treatment with nifedipine given orally or sublingually. Nicardipine hydrochloride, a water soluble dihydropyridine analogue similar to nifedipine, has less of a negative ionotropic effect and produces less reflex tachycardia than nifedipine. Our purpose was to assess the antihypertensive efficacy and safety of intravenous nicardipine in a group of patients with severe hypertension (defined as a supine diastolic blood pressure of more than 120 mm Hg). PATIENTS AND METHODS: Eighteen patients with severe hypertension received treatment with intravenous nicardipine. Nicardipine titration was performed using doses of 4 to 15 mg/hour to achieve therapeutic goal (diastolic blood pressure 95 mm Hg or less or decrease in diastolic blood pressure of more than 25 mm Hg). After this therapeutic end-point was reached, patients received maintainance therapy with nicardipine for varying lengths of time: one hour (Group I), six hours (Group II), or 24 hours. When blood pressure control was lost, patients in Groups I and II entered a second maintenance period lasting a maximum of 24 hours. Onset and offset of action of nicardipine at various infusion rates and times of infusion were measured. RESULTS: Onset time to achieve therapeutic response was rapid at 15 mg/hour (0.31 +/- 0.13 hours) when compared with lower doses (1.11 +/- 0.36 hours at 4 mg/hour; 0.54 +/- 0.09 hours at 5 mg/hour; 0.52 +/- 0.09 hours at 7 to 7.5 mg/hour). Those who showed a therapeutic response received maintenance infusions with nicardipine for one (n = 7), six (n = 6), or 24 (n = 5) hours. Sustained blood pressure control at a constant rate of nicardipine infusion was seen in all patients during the maintenance period. After discontinuation of nicardipine, the time for offset of action (increase in diastolic blood pressure of 10 mm Hg or more) was independent of duration of infusion. Decreases in both systolic and diastolic pressures correlated well with plasma nicardipine levels. Heart rate increased by about 10 beats/minute, but this increase did not correlate with plasma nicardipine levels. Side effects were minimal, consisting of headache and flushing. In seven patients, local phlebitis developed at the site of infusion. This occurred after at least 14 hours of infusion at a single site, and the incidence can probably be reduced by shortening the infusion time at a single site. CONCLUSION: Nicardipine appears to be a safe and effective drug for intravenous use in the treatment of severe hypertension.

Esmolol, the first ultra-short-acting intravenous beta blocker for use in critically ill patients.

Esmolol is the first intravenous, short-acting, titratable beta-blocker available for use in critical care and surgical settings. The predominant pharmacodynamic actions of the drug include a reduction in HR, BP, rate-pressure product, LVEF, and cardiac index. A desirable pharmacokinetic feature of esmolol is its esterase-induced rapid metabolic inactivation, which results in a return of all hemodynamic parameters to pretreatment levels within 30 minutes after discontinuation of the infusion. Control over the magnitude and duration of beta-blockade and the relative cardioselectivity of esmolol make it an ideal agent for use in critically ill patients, including those who, because of other conditions, are at risk if treated with beta-blockers. The clinical indications for esmolol therapy include SVT and perioperative tachycardia and hypertension. In patients with myocardial ischemic conditions (acute myocardial infarction and unstable angina), esmolol was safe and produced clinically significant reductions in HR and rate-pressure product. In general, untoward reactions to esmolol have been minimal, mild, and transient. Although attention must be given to the possibility of systolic hypotension during esmolol administration, this complication often occurs at doses beyond those which provide optimal therapeutic response and may be avoided by titrating to the minimal effective dose. If systolic hypotension occurs, it is reversible by either reducing the dose or discontinuing the esmolol infusion. A nursing plan of care should be developed for patients receiving esmolol therapy. Dosage and administration must be individualized. Careful titration of the esmolol infusion and monitoring of therapeutic and safety parameters by nursing professionals will promote the achievement of maximum beta-blocker effect while avoiding persistent and unnecessary adverse reactions.

Clinical experience with esmolol, a short-acting beta-adrenergic blocker in cardiac arrhythmias and myocardial ischemia.

The efficacy and safety of esmolol, an ultra-short-acting beta-adrenergic blocking agent (elimination half-life, 9 min), was investigated in 358 patients with supraventricular tachyarrhythmias (SVTs) in three multicenter studies (placebo-controlled, propranolol-controlled, and open-label baseline-controlled) and in 19 patients with myocardial ischemia (acute myocardial infarction or unstable angina) in a single-center, open-label study. Esmolol was infused intravenously in doses ranging from 25 micrograms/kg/min to 300 micrograms/kg/min. In SVT studies, efficacy was judged by one or more of the following: a reduction of at least 15% to 20% from the average baseline heart rate, heart rate less than 100 beats/min, or conversion to normal sinus rhythm (NSR). Results revealed that esmolol was superior to placebo and equal to propranolol in controlling heart rate in SVT patients. Conversion to NSR was comparable in patients treated with esmolol (14%) and in those treated with propranolol (16%). The majority of patients achieved therapeutic response at esmolol doses of 200 micrograms/kg/min or less. Among esmolol-treated patients, recovery from beta blockade (i.e., heart rate approaching baseline levels) was achieved within ten minutes after discontinuation of infusion, indicating a brief duration of action of esmolol. In contrast, beta blockade persisted 4.5 hours after discontinuation of propranolol. In patients with myocardial ischemia, esmolol effectively reduced heart rate and blood pressure, thereby decreasing rate-pressure product. The most frequent adverse effect in patients treated with esmolol was hypotension. No clinically significant laboratory abnormalities were reported in esmolol-treated patients. Esmolol was well tolerated in patients infused for durations of up to 24 hours and in patients with conditions for which treatment with beta blockers is inappropriate. These results suggest that esmolol effectively and rapidly controls the heart rate in patients with SVT and in patients with acute myocardial ischemia. Furthermore, because of its short half-life, esmolol offers excellent benefits as compared with the currently available beta-adrenergic blockers in the treatment of critically ill patients. Esmolol was well tolerated by patients for whom beta blockers in general would be unsuitable.

Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. The Esmolol vs Placebo Multicenter Study Group.

The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).

Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachyarrhythmias: a multicenter double-blind clinical trial.

The efficacy and safety of intravenous esmolol infusion was compared to that of intravenous propranolol injection in patients with supraventricular tachyarrhythmias (SVT) in a multicenter double-blind parallel study. A total of 127 patients were randomized to either the esmolol (n = 64) or propranolol (n = 63) group. Therapeutic response was achieved in 72% of esmolol and 69% of propranolol patients (p = NS). The average dose of esmolol in responders was 115 +/- 11 micrograms/kg/min. Therapeutic response was sustained in the 4-hour maintenance period in 67% of esmolol and 58% of propranolol patients (p = NS). Rate of conversion to normal sinus rhythm was similar in the two treatment groups. After discontinuation, rapid recovery from beta blockade (decrease in heart rate reduction) was observed in esmolol patients (within 10 minutes) compared to propranolol patients (no change in heart rate up to 4.3 hours). The principal adverse effect was hypotension, reported in 23 esmolol (asymptomatic in 19) and four propranolol (asymptomatic in three) patients. In the majority of esmolol patients, hypotension resolved quickly (within 30 minutes) after esmolol was discontinued. It was concluded that esmolol was comparable in efficacy and safety to propranolol in the treatment of patients with SVT. Unlike propranolol, because of the short half-life of esmolol, rapid control of beta blockade is possible with esmolol in clinical conditions when required.