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Clevidipine was also compared with nitroglycerin in the
same study and was found to be more effective at keeping BP
within goal range than nitroglycerin (P = .0006). Adverse
events including postoperative AF were similar between all
treatment arms.13
Based on the ECLIPSE trials, clevidipine and nicardipine
may be preferred over sodium nitroprusside and nitroglycerin
for managing postoperative hypertension. When selecting the
most appropriate agent, clinicians should also consider pharmacokinetic differences between the 2 calcium channel
blockers. Nicardipine plasma concentrations decline triexponentially with alpha, beta, and terminal half-lives of 3 minutes, 45 minutes, and 14 hours, consecutively. In contrast,
clevidipine displays biphasic elimination with an initial halflife of 1 minute (predominant) and a terminal half-life of
about 15 minutes. The longer half-life of nicardipine compared with clevidipine may interfere with rapid titration and
increase the risk of hypotension. The Efficacy Study of
Clevidipine Assessing Its Postoperative Antihypertensive
Effect in Cardiac Surgery 2 (ESCAPE-2) trial provides additional evidence supporting the use of clevidipine in the setting
of cardiac surgery. This placebo controlled, double blind trial
which randomized 110 patients with a post-operative SBP
≥140 mm Hg warranting at least a 15% reduction after cardiac surgery to receive either clevidipine (n = 61) or placebo
(n = 49). The treatment failure rate was lower in the clevidipine group versus placebo (8.2% vs. 79.6% respectively, p <
0.0001). The median time to target SBP with clevidipine was
5.3 minutes. The clevidipine group showed a significantly
greater decrease in MAP than placebo. There were no differences between the clevidipine and placebo groups in rates of
reflex tachycardia or other adverse events.26
Literature supporting the use of sodium nitroprusside in
CABG patients is largely based on placebo-controlled rather
than head-to-head trials. Indeed, both the studies demonstrating a reduction in AKI and post-operative atrial fibrillation with use of sodium nitroprusside utilized a placebo
comparator arm. To our knowledge, there are no head-tohead studies designed to compare rates of postoperative
atrial fibrillation based on vasodilator selection. However in
the ECLIPSE trial, rates of atrial fibrillation were similar
between all treatment arms (clevidipine, nicardipine, nitroglycerin, and sodium nitroprusside).13 In addition, a recent
meta-analysis confirms that there is no difference in rates of
atrial fibrillation between clevidipine and comparator arms
in published studies.27
While sodium nitroprusside improves rates of renal dysfunction after CABG compared to placebo, the rates of renal
dysfunction were also similar between all treatment arms in
the ECLIPSE trial.13 Little data is available about the best
vasodilator for reducing the risk of AKI after CABG. However,
it is known that increased magnitude and/or duration of SBP
excursions outside the target range are independent predictors
of postoperative AKI (OR 1.8, p = 0.0119).28 Since clevidipine
seems to mitigate BP excursions compared to nitroglycerin,

Hospital Pharmacy 52(7)
nicardipine, and sodium nitroprusside, it may be the most
effective agent at reducing rates of postoperative AKI.
Additional purported benefits of sodium nitroprusside
include reductions in inflammation after surgery. While
sodium nitroprusside has been shown to reduce the hospital
length of stay compared to placebo, head to head trials are
needed to determine if this is a vasodilator class effect or a
specific property of the drug. Little is known about other
vasodilators in this setting.

Conclusions
In summary, sodium nitroprusside is an intravenous vasodilator which is frequently utilized in the perioperative CABG
setting. It effectively attenuates the inflammatory response
caused by surgery, reduces the risk of postoperative AF, and
improves kidney function compared with placebo.
However, it performs similarly to nicardipine and is less
effective than clevidipine at maintaining perioperative BP
within target range.
In contrast to the increase in AWP for sodium nitroprusside, a 50-mL vial of clevidipine 25 mg/50 mL was $79.62
at the time of this publication.29 In response to rising drug
costs and an evidence-based class review of vasodilators,
one hospital has described a therapeutic interchange program substituting clevidipine for sodium nitroprusside in
cardiac surgery patients. The program is projected to result
in a net cost avoidance of about $300 000 over 1 year at a
520-bed institution which performs more than 300 cardiac
surgeries annually.30
Clevidipine is generally well-tolerated, quickly titratable,
and has no clinically relevant metabolic drug interactions. It
can be administered through peripheral or central lines.
Clevidipine formulations contain soya bean oil and egg
phospholipids, so use is contraindicated in patients with egg
or soy allergy. Potential adverse events are hypotension and
nausea. Increased serum triglycerides or acute pancreatitis
are possible with prolonged infusions.
For patients undergoing cardiac surgery, clevidipine is
more effective than sodium nitroprusside, nicardipine, and
nitroglycerin at reducing BP excursions, which may also be
protective against AKI. Current data suggest similar rates of
postoperative AF compared with other agents. This evidence
compounded by the high costs of sodium nitroprusside lends
support to utilizing clevidipine as an alternative to sodium
nitroprusside after CABG surgery.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

Table of Contents for the Digital Edition of Hospital Pharmacy - July/August 2017