BP Control in Cardiac Surgery: Nitroprusside Alternatives

June 13, 2017

Pharmacists must find good alternative therapeutic substitutions for sodium nitroprusside in the face of price gouging and drug shortages.

Price gouging and shortages of generic and critical drugs have become hot-topic issues.1,2 In the hospital setting, massive price increases to widely-used generic injectable drugs, such as sodium nitroprusside (SNP), have left many institutions scrambling for evidence-based alternatives that make less of an impact on drug budgets. Some alternatives that have been identified as replacements for SNP to manage perioperative hypertension are the calcium channel blockers clevidipine and nicardipine.3

The Evaluation of Clevidipine in the Perioperative Treatment of Hypertension Assessing Safety Events (ECLIPSE) trial compared the safety (primary endpoint) and efficacy (secondary endpoint) of clevidipine head-to-head with SNP, nitroglycerin, and nicardipine in the cardiac surgery setting.4

Clevidipine had similar safety and efficacy profiles as SNP, with a possible advantage in maintaining a specified target blood pressure range. The primary safety outcomes assessed included death, MI, stroke, and renal dysfunction. A statistically significant difference in mortality was identified between clevidipine and SNP (clevidipine 1.7% vs. SNP 4.7%; p = 0.04). Researchers noted that methodological concerns limit the applicability of this result.4

Safety profiles were similar for nicardipine and clevidipine; however, this comparison was limited to the postoperative period. Some pharmacokinetic differences between clevidipine and nicardipine were cited as the driver of this difference.4 Yet, it is not possible to draw direct conclusons about their relative risk/benefit profile in the pre- or intraoperative timeframe based on this study alone. There are few data evaluating nicardipine as an intraoperative antihypertensive agent,3 but the drug is still used by some institutions because of practitioner familiarity and cost concerns.

Because of its short half-life, fast onset of action, and ease of titration, SNP had been the standard of care for hypertension associated with cardiac surgery for decades. SNP was relatively inexpensive, but due to a series of sales and acquisitions, its cost ballooned by nearly 1900%. Other drugs with similar effects and/or pharmacokinetics were thus proposed as alternatives to rein-in exploding costs without adversely affecting patient care.3

Pharmacists around the country must remain vigilant in coming up with creative, operationally feasible therapeutic substitutions, in the face of price gouging and drug shortages. The choice to interchange one drug product for another should be directed by a rational and evidence-based approach and guided by the policy statements from major professional pharmacy organizations such as the American Society for Health-System Pharmacists and the American College of Clinical Pharmacy.5,6   


1. Rockoff JD, Silberman E. Pharmaceutical companies buy rivals’ drugs, then jack up the prices. The Wall Street Journal. https://www.wsj.com/articles/pharmaceutical-companies-buy-rivals-drugs-then-jack-up-the-prices-1430096431.
2. Fink S. The New York Times. Drug shortages forcing hard decisions on rationing treatments. The New York Times. https://www.nytimes.com/2016/01/29/us/drug-shortages-forcing-hard-decisions-on-rationing-treatments.html
3. Cruz JE, Thomas Z, Lee D, et al. Therapeutic interchange of clevidipine for sodium nitroprusside in cardiac surgery. PT. 2016;41(10):635–639.
4. Aronson S, Dyke CM, Stierer KA, et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg. 2008;107:1110-1121.
5. American Society of Health-System Pharmacists. ASHP guidelines on the pharmacy and therapeutics committee and the formulary system. Am J Health-Syst Pharm. 2008; 65:1272–1283.
6. Gray T, Bertch K, Galt K, et al. Guidelines for therapeutic interchange-2004. Pharmacotherapy. 2005;25:1666-1680.