Utility of nicardipine in the management of hypertensive crises in adults with reduced ejection fractions

Abstract

Background

Nicardipine is commonly used in the management of hypertensive crises, except those involving cardiac contractility defects despite its ability to reduce afterload and pulmonary congestion. Consequently, there is limited literature evaluating nicardipine’s role for this indication. The purpose of this study was to evaluate the efficacy and safety of nicardipine in adults with reduced ejection fractions presenting with acute heart failure with hypertension (AHF-H).

Methods

This was a retrospective study conducted at an academic Level 1 trauma center with an annual Emergency Department (ED) volume surpassing 100,000. The purpose of this study was to determine the efficacy and safety of nicardipine in adults with reduced ejection fractions presenting to the ED with AHF-H. Efficacy was determined by achievement of the physician prescribed blood pressure target range. The primary safety endpoints included the number of individuals who experienced bradycardia (< 60 beats per minute, bpm) or hypotension (systolic blood pressure, SBP, < 90 mmHg) while receiving nicardipine and for up to 15 min after its discontinuation. Patients were included if they were ≥ 18 years of age, received a continuous intravenous nicardipine infusion within six hours of presenting to the ED, and had an ejection fraction ≤ 40% per an echocardiogram obtained within three months of the study visit. Pregnant and incarcerated patients were excluded.

Results

Of the 500 patient charts reviewed, 38 met inclusion criteria. The median (interquartile, IQR) ejection fraction and brain natriuretic peptide (BNP) were 35% (25–40) and 731 pg/nL (418–3277), respectively. The median baseline heart rate and SBP were 90 bpm and 193 mmHg, respectively. The median physician specified SBP goal was 160 mmHg and all patients met this endpoint in a median time of 18 min. One (2.6%) patient in the total population developed both hypotension and bradycardia. This patient had an ejection fraction of 20%, was intubated, and received nicardipine in addition to esmolol for an aortic dissection without experiencing an adverse event until 30 min after dexmedetomidine was initiated.

Conclusion

In this non-interventional study evaluating the use of nicardipine in patients with reduced ejection fractions presenting to the ED with AHF-H, nicardipine was found to be safe and effective. To our knowledge this is the largest study to date evaluating nicardipine in this patient population and positively contributes to the existing literature.

1 Introduction

Hypertensive emergencies are characterized by acute marked elevations in blood pressure associated with end organ damage and require an immediate reduction in blood pressure to prevent further damage [ ]. In comparison, hypertensive urgencies are characterized by acute marked elevations in blood pressure without end organ damage and do not require a prompt decrease in blood pressure. Collectively, hypertensive urgency and emergency episodes are referred to as hypertensive crises. In the management of hypertensive emergencies, the initial blood pressure goal and choice of antihypertensive are determined by the organ affected and patient comorbidities [ ].

Nitroglycerin remains the standard of therapy in the management of acute heart failure with hypertension (AHF-H) despite a lack of data demonstrating improved outcomes in hospitalized patients with its use [ , ]. In the management of AHF-H nitroglycerin may prevent or alleviate pulmonary congestion through reducing preload and afterload at low and high doses, respectively [ ]. However, its effects are not always observed due to the development of tachyphylaxis in patients on chronic nitrate therapy or those receiving prolonged infusion durations [ ].

Nicardipine, a dihydropyridine calcium channel blocker (CCB), is also commonly used in the management of hypertensive crises, except those involving cardiac contractility defects despite its ability to reduce afterload and pulmonary congestion [ , ]. Dihydropyridine CCBs are possibly infrequently used in patients with reduced ejection fractions due to concerns they may reduce contractility and cardiac output. However, in comparison to non-dihydropyridine CCBs (i.e. diltiazem, verapamil), dihydropyridine CCBs display greater selectivity for calcium channels in vascular smooth muscle cells and minimal to no myocardial depressant activity [ , ]. Despite these pharmacological differences, literature to date evaluating the use of nicardipine in this population is limited and it remains unknown if nicardipine can be used for this indication. The purpose of this study was to evaluate the efficacy and safety of nicardipine in adults with reduced ejection fractions presenting with AHF-H.

2 Methods

This retrospective study was conducted at an academic Level 1 trauma center with an annual Emergency Department (ED) volume surpassing 100,000. All study measures and procedures were approved by the local Institutional Review Board and there are no conflicts of interest to report.

The purpose of this study was to determine the efficacy and safety of nicardipine in adults with reduced ejection fractions presenting to the ED with AHF-H. Efficacy was determined by achievement of the physician prescribed blood pressure goal. The upper limit of the goal blood pressure range was documented and the time to achieving this outcome was determined. The primary safety endpoints included the number of individuals who experienced bradycardia (< 60 beats per minute, bpm) or hypotension [systolic blood pressure (SBP) < 90 mmHg] while receiving nicardipine and for up to 15 min after its discontinuation.

Patients were included if they were ≥ 18 years of age, received a continuous intravenous nicardipine infusion within six hours of presenting to the ED, and had an ejection fraction ≤ 40% per an echocardiogram obtained within three months of the study visit. Pregnant and incarcerated patients were excluded. The investigators generated a report that identified all adults who received nicardipine within six hours of presenting to the ED between 2018 and 2022. From this list the investigators reviewed the first 500 patient charts for study inclusion.

Past medical history, baseline laboratory values [serum creatinine, brain natriuretic peptide (BNP), and troponin], vitals, ejection fraction per echocardiogram, chest imaging (x-ray and computed tomography), concomitant medications, and nicardipine administration data were obtained from the electronic medical record. For patients whose ejection fraction was reported as a range, the lowest value of the range was documented. The prescribers’ progress notes were reviewed to identify additional nicardipine indications for use. Descriptive statistics were used to summarize patient demographics and outcomes.

3 Results

Of the 500 patient charts reviewed, 38 met inclusion criteria. The included population’s baseline characteristics are shown in Table 1 . Nearly all patients had a documented past medical history of hypertension and almost half of the population had radiographic findings of edema/congestion. The median (interquartile, IQR) ejection fraction and BNP were 35% (25–40) and 731 pg/nL (418–3277), respectively. The median baseline heart rate and SBP was 90 bpm and 193 mmHg, respectively. Of the 13 patients who received nicardipine while mechanically ventilated, 11 (84.6%) were intubated for airway protection in the setting of a cerebrovascular accident and one for airway protection in the setting of an aortic dissection. One patient was intubated for pulmonary edema and received nicardipine after being intubated. Twenty-six (60.5%) patients concurrently received antihypertensives.

Table 1

Patient characteristics.

N	38
Male, n (%)	28 (73.7)
Age, y	62 (51–75)
Past medical history, n (%)
Hypertension	37 (97.4)
Coronary artery disease	14 (36.8)
Chronic kidney disease	13 (34.2)
Baseline labs and imaging
Ejection fraction, %	35 (25–40)
Brain natriuretic peptide, pg/nL	731 (418–3277)
Serum creatinine, mg/dL	1.2 (0.88–2.2)
Troponin, ng/mL	0.055 (0.049–0.15)
Radiographic findings of edema/congestion, n (%)	16 (42.1)
Baseline vitals
Heart rate, beats per minute	90 (78–99)
Systolic blood pressure, mmHg	193 (162–210)
Ventilation, n (%)	14 (36.8)
Non-invasive ventilation	1 (2.6)
Invasive ventilation	13 (34.2)
Concurrently received antihypertensives, n (%)	26 (60.5)