Nicardipine or Nitroprusside for Postoperative Blood Pressure Control in Infants After Surgery for Congenital Heart Disease: Single-Center Retrospective Noninferiority and Cost Analysis, 2016-2020.

OBJECTIVES: Postoperative hypertension frequently occurs after surgery for congenital heart disease. Given safety concerns when using calcium channel blockers in infants along with the cost and side-effect profile of nitroprusside, we retrospectively assessed our experience of using nicardipine and nitroprusside for postoperative blood pressure control in infants who underwent surgery for congenital heart disease. We also investigated the cost difference between the medications. DESIGN: This study was a single-center retrospective, pre-post chart review of patients who had surgery for congenital heart disease between 2016 and 2020. The primary aim was a noninferiority comparison of achievement of blood pressure goal at 1-hour post-initiation of an antihypertensive agent. Secondary comparisons included achievement of blood pressure goal at 2 hours after medication initiation, Vasoactive-Inotropic Score (VIS), and blood transfusion, crystalloid volume, and calcium needs. SETTING: Academic quaternary-care center. PATIENTS: Infants under 1 year old who required treatment for hypertension with nitroprusside ( n = 71) or nicardipine ( n = 52) within 24 hours of surgery for congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We failed to identify any difference in proportion of patients that achieved blood pressure control at 1-hour after medication initiation (nitroprusside 52% vs. nicardipine 54%; p = 0.86), with nicardipine noninferior to nitroprusside within a 15% margin. Of patients who did not achieve control at 1-hour post-medication initiation, receiving nicardipine was associated with blood pressure control at 2 hours post-medication initiation (79% vs. 38%; p = 0.003). We also failed to identify an association between antihypertensive types and mean VIS scores, blood transfusion volumes, crystalloid volumes, and quantities of calcium administered. Index cost of using nitroprusside was 16 times higher than using nicardipine, primarily due to difference in wholesale cost. CONCLUSIONS: In our experience of achieving blood pressure control in infants after surgery for congenital heart disease (2016-2020), antihypertensive treatment with nicardipine was noninferior to nitroprusside. Furthermore, nicardipine use was significantly less expensive than nitroprusside. Our contemporary practice is therefore to use nicardipine in preference to nitroprusside.

Early Initiation of Oral Antihypertensives Reduces Intensive Care Unit Stay and Hospital Cost for Patients with Hypertensive Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVE: Intravenous nicardipine infusion is effective for rapid blood pressure control. However, its use requires hemodynamic monitoring in the intensive care unit (ICU) and is associated with high hospital cost. This study aimed to examine the effect of early versus late initiation of oral antihypertensives on ICU length of stay (LOS) and cost of hospitalization in patients with hypertensive intracerebral hemorrhage (ICH). METHODS: This is a single-center retrospective study of patients with hypertensive ICH treated with nicardipine infusion from January 1, 2013, to December 31, 2017. Patients were dichotomized into study and control groups, based on receiving oral antihypertensives within 24 h versus after 24 h of emergency department arrival. Baseline characteristics, duration of nicardipine infusion, LOS in the ICU and hospital, functional outcome at discharge, and hospital cost were compared between the two groups using univariate and multivariate analysis. RESULTS: A total of 90 patients in the study group and 76 in the control group were identified. There was no significant difference in demographics, past medical history, and initial SBP between the two groups. After adjusting for confounding factors with multivariate regression models, early initiation of oral antihypertensives was associated with significant reductions in duration of nicardipine infusion (55.5 ± 60.1 vs 121.6 ± 141.3 h, p <0.005), nicardipine cost ($14,207 vs $29,299, p < 0.01), ICU LOS (2 vs 5 days, p < 0.005), and cost of hospitalization ($24,564 vs $47,366, p < 0.01). There was no significant difference in adversary renal events, favorable outcomes, and mortality between the two groups. CONCLUSIONS: Early initiation of oral antihypertensives is safe and may have a significant financial impact on patients with hypertensive ICH.

Sodium Nitroprusside as a Hyperinflation Drug and Therapeutic Alternatives.

Sodium nitroprusside (SNP) is a generically available and rapid-acting intravenous (IV) vasodilator that has been used clinically for decades. Prior to 2013, the cost of SNP was relatively low, and SNP was an affordable option for the treatment of acute hypertension. However, from 2013 to 2017, average wholesale prices for SNP rose to as high as US$900 per vial, earning the drug its status as a "hyperinflation drug." Hyperinflation drugs pose a significant challenge for pharmacy departments. A multidisciplinary effort involving stakeholders from many backgrounds, including pharmacists, physicians, and nurses, is key to developing an effective cost containment strategy. A therapeutic interchange, wherein a drug with similar efficacy is substituted for another, is often an appropriate strategy to address rising drug costs. Fortunately, alternative drugs with a solid evidence base exist for the management of acute hypertension. The dihydropyridine calcium channel blockers, clevidipine and nicardipine, are IV titratable antihypertensive agents with favorable pharmacokinetic and safety profiles. Various studies indicate that clevidipine and nicardipine are effective alternatives to SNP for indications including hypertensive crisis and postoperative hypertension. Some hospitals have reported significant cost savings without adverse outcomes by substituting clevidipine or nicardipine for SNP. This article is intended to serve as a review of the evidence for clevidipine and nicardipine as potential substitutes for SNP and to provide strategies to successfully implement this therapeutic interchange.

Reducing Cost and Intravenous Duration of Nicardipine in Intracerebral Hemorrhage Patients via an Interdisciplinary Approach.

BACKGROUND: The mainstay of acute management of intracerebral hemorrhage (ICH) is blood pressure reduction. Intravenous (IV) nicardipine is an effective but costly intervention for blood pressure reduction in the intensive care unit (ICU). Earlier transition to oral (PO) antihypertensive agents may reduce ICU length of stay (LOS) and associated costs. We sought to study the effectiveness of an interdisciplinary intervention to start earlier transition to PO antihypertensives. METHODS: From July 2011 to July 2012, patients with ICH who received IV nicardipine were reviewed and screened for eligibility by an interdisciplinary team including physicians and pharmacists. These patients were compared to a control group 1 year prior to this intervention. The duration of nicardipine treatment (median hours), estimated costs, and ICU LOS were measured. RESULTS: A total of 35 patients and 44 controls were studied. The median hours of IV nicardipine use were significantly decreased from a baseline mean of 118 to 30 hours (P < .001); total cost savings per year was $433,566 ($18,475 per patient). The average LOS remained similar (8.4 versus 8.9 days, P < .990). In a follow-up study 1 year later, after the intervention was no longer used, a sample of 21 consecutive patients was reviewed and the duration of IV nicardipine treatment had increased to a mean of 96 hours. CONCLUSION: A physician and pharmacist-led project to initiate oral antihyperintensive medications earlier was successful in reducing the duration of IV nicardipine treatment in patients with ICH while leading to substantial cost savings.

A cost analysis of the impact of a new intravenous antihypertensive in managing perioperative blood pressure during cardiac surgery.

OBJECTIVE: To examine the impact of intravenous antihypertensive selection on hospital health resource utilization using data from the Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events (ECLIPSE) trials. METHODS: Analysis of ECLIPSE trial data comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine and unit costs based on the Premier Hospital database to assess surgery duration, time to extubation, and length of stay (LOS) with the associated cost. RESULTS: A total of 1414 patients from the ECLIPSE trials and the Premier hospital database were included for analysis. The duration of surgery and postoperative LOS were similar across groups. The time from chest closure to extubation was shorter in patients receiving clevidipine group compared with the pooled comparator group (median 7.0 vs 7.6 hours, P = 0.04). There was shorter intensive care unit (ICU) LOS in the clevidipine group versus the nitroglycerin group (median 27.2 vs 33.0 hours, P = 0.03). A trend toward reduced ICU LOS was also seen in the clevidipine compared with the pooled comparator group (median 32.3 vs 43.5 hours, P = 0.06). The costs for ICU LOS and time to extubation were lower with clevidipine than with the comparators, with median cost savings of $887 and $34, respectively, compared with the pooled comparator group, for a median cost savings of $921 per patient. CONCLUSIONS: Health resource utilization across therapeutic alternatives can be derived from an analysis of standard costs from hospital financial data to matched utilization metrics as part of a randomized controlled trial. In cardiac surgical patients, intravenous antihypertensive selection was associated with a shorter time to extubation in the ICU and a shorter ICU stay compared with pooled comparators, which in turn may decrease total costs.

A multicenter comparison of outcomes associated with intravenous nitroprusside and nicardipine treatment among patients with intracerebral hemorrhage.

INTRODUCTION: No clinical data exist to compare outcomes between patients with intracerebral hemorrhage (ICH) treated with different intravenous antihypertensive agents. This study was performed to compare outcomes among patients with ICH who were treated with intravenous infusion of different antihypertensive medications during the first 24 hours after admission. METHODS: We analyzed one-year data (2005-2006) from the Premier database which is a nationally representative hospital discharge database containing data pertaining to admissions in the United States. We compared discharge outcomes, length of stay, and cost of hospitalization between groups of patients who were treated using either intravenous nicardipine or nitroprusside infusion. Chi-square and ANOVA were used for univariate analysis. Logistic and linear regression analyses were performed to adjust for baseline risk of mortality between the two groups. RESULTS: A total of 12,767 admissions with primary diagnosis of ICH were identified. Nicardipine was administered in 926 patients (7.3%) and nitroprusside was administered in 530 (4.3%) patients. There was no difference in baseline disease severity or risk of mortality among patients who were administered nicardipine or nitroprusside. After adjustment for baseline risk of mortality, the risk of in-hospital mortality (odds ratio [OR] 1.7, 95% confidence interval [95% CI] 1.3-2.2) was higher among patients treated with nitroprusside compared with nicardipine. The risk of in-hospital mortality was also higher after adjustment for baseline risk of mortality and hospital characteristics in patients treated with nitroprusside (OR 1.6, 95% CI 1.2-2.1). After exclusion of patients who died during hospitalization, there was no difference in length of stay and total hospital cost in the multivariate analysis. CONCLUSION: Use of nicardipine compared with nitroprusside infusion during the first 24 h after ICH may be associated with reduced risk of in-hospital mortality without any increase in the hospitalization cost or length of stay.

"Pharmacologic" distal protection using prophylactic, intragraft nicardipine to prevent no-reflow and non-Q-wave myocardial infarction during elective saphenous vein graft intervention.

BACKGROUND: Coronary saphenous vein bypass graft (SVG) stenting has been associated with up to a 30% rate of no-reflow or myocardial infarction (MI) when performed without distal protection. METHODS: We evaluated the technique using prophylactic pharmacologic arteriolar vasodilatation with intracoronary nicardipine followed by immediate direct stenting for the treatment of degenerated coronary SVGs without mechanical distal protection. Data were collected from 83 consecutive elective SVG interventions in 68 patients. Quantitative coronary angiographic measurements were performed by the Borgess angiographic core lab. Electrocardiograms (ECGs), CPKs, and CPK-MBs were obtained preprocedure and at 12 to 18 hours after the intervention. Follow-up data at 30 days were obtained in 67/68 (98%) patients. RESULTS: The average graft age was 11.9 +/- 6.6 years with thrombus in 26/83 vessels (31%). The primary adverse endpoint of total CPK >3 times the upper limit of normal (ULN), or CPK-MB >3 times the ULN were seen in 1/68 (1.5%) and 3/68 (4.4%) patients, respectively. No-/slow-reflow was observed transiently in 2/83 SVG interventions (2.4%). Of the patients, 1/68 had persistent, minor ECG changes after stenting (1.4%). No patient had a Q-wave MI. Inhospital major adverse cardiac events (MACE) (death, MI, repeat TLR) were observed in only 3/68 patients (CPK-MB elevation). There were no additional MACE events (0/68) from hospital discharge to 30 days. CONCLUSIONS: (1) Prophylactic vasodilatation with intragraft nicardipine followed by direct stenting appears to be a safe and effective means of performing elective SVG revascularization; (2) this approach may provide a simple and time- and cost-effective alternative or adjunct to mechanical distal protection for elective SVG interventions.