Hospital Pharmacy - July/August 2017 - 503
503
Gibson et al.
Materials and Methods
A literature search using the MEDLINE database was undertaken to identify published studies reporting on the use of
sodium nitroprusside in the CABG setting. Keywords entered
in the search were "sodium nitroprusside" or "nitroprusside"
and "CABG" or "coronary artery bypass grafting." Articles
were limited to in vitro studies or studies of adult patients
which were published in English. Manual review of the reference lists of the retrieved articles was performed to identify
additional relevant studies. Studies were reviewed to determine the impact of vasodilator selection on CABG outcomes
and complications.
Results
Several studies discussing the impact of sodium nitroprusside on postoperative hypertension, postoperative atrial
fibrillation (AF), AKI, conduit vasospasm, and inflammation
were identified.
Postoperative Hypertension
Postoperative hypertension during cardiac surgery affects
22% to 54% of patients.5 BP excursions in the perioperative
period increase the risk of bleeding, myocardial ischemia
and infarction, cardiac arrhythmia, heart failure, and stroke.6
Acute hypertension has also been reported to worsen reperfusion injury and the inflammatory response, indicating that
adverse events resulting from postoperative hypertension are
due to multiple mechanisms.7
In a prospective randomized trial, sodium nitroprusside
0.5 µg/kg/min titrated to response was compared with nicardipine 10 mg/h titrated to response after surgery. Nicardipine
is a dihydropyridine calcium channel blocker commonly
used for the treatment of hypertensive urgency and emergency that selectively dilates arteries with no effect on veins.
Of the 139 patients enrolled in the trial, 43 underwent cardiac
surgery. Both agents were equally effective at reducing BP in
the postoperative cardiac patients (defined as >15% reduction from the pretreatment BP). However, nicardipine controlled BP more rapidly than sodium nitroprusside (14.0 ± 1
minutes vs 30.4 ± 3.5 minutes, respectively; P = .0029).
Increased heart rate among cardiac surgery patients treated
with sodium nitroprusside was observed from baseline to the
end of titration (84 ± 3 to 95 ± 4 beats/min, P < .05); however, both arms had an increase in heart rate from baseline by
the end of maintenance therapy. Similar rates of adverse
effects were observed in both arms.8
One arm of the open-label ECLIPSE trials randomly
assigned patients undergoing cardiac surgery (CABG alone
in 70.6% or CABG plus valve surgery in 10.7%) in a 1:1
fashion to receive sodium nitroprusside or clevidipine.
Clevidipine is a rapid-acting dihydropyridine calcium channel blocker which, like nicardipine, selectively vasodilates
arteries without impacting venous circulation. The majority
of CABG procedures in the study were performed with cardiopulmonary bypass (CPB). Clevidipine was initiated at 0.4
µg/kg/min and titrated per algorithm to response. There was
no protocol dictating dosing of sodium nitroprusside, and
investigators were encouraged to administer the agent in
accordance with their usual practice. The primary outcome,
safety as assessed by the incidence of myocardial infarction,
stroke, renal dysfunction, and all-cause mortality at 30 days,
was similar between arms for all endpoints, except for an
increased risk of mortality in the sodium nitroprusside arm
(4.7% vs 1.7%, P = .0445). After multiple logistic regression
adjusting for other risk factors, mortality was similar between
arms. However, clevidipine was significantly more effective
than sodium nitroprusside at keeping BP within prespecified
target range, as measured by the median area under the curve
analysis of BP excursions beyond predetermined limits. In
addition, sodium nitroprusside patients had more systolic
blood pressure (SBP)-time excursions both above and below
the target BP range than clevidipine patients. The authors
stipulate that difficulty maintaining goal BPs may be due to
difficulty titrating the medication without "overshooting"
and causing hypotension as well as unpredictable swings in
BP that may occur in sodium nitroprusside-treated patients
with diastolic dysfunction or hypovolemia due to the venodilatory effects of sodium nitroprusside.9
Atrial Fibrillation
Postoperative AF is another potential consequence of CABG
surgery impacting about one-third of patients, and is associated with substantial morbidity and mortality.10 To determine
whether sodium nitroprusside prevents postoperative AF, a
blinded pilot study enrolled 100 patients undergoing elective
on-pump CABG. Fifty patients received a 60-minute infusion of sodium nitroprusside 0.5 to 1 µg/kg/min titrated to
maintain a mean arterial pressure (MAP) near 65 mmHg, and
50 patients received a placebo infusion with the same MAP
goal. All patients received left internal mammary artery
grafts. After discontinuation of the aortic cross-clamp, 9
patients in the sodium nitroprusside and 24 patients in the
placebo group required cardiac defibrillation (P = .001).
Postoperative AF developed in 12% of sodium nitroprusside
patients versus 36% of control patients (P = .005), and the
duration of AF was shorter in the sodium nitroprusside group
(5.33 ± 1.86 vs 7.55 ± 1.94 hours, P = .023). The length of
intensive care unit (ICU) stay was similar between groups,
but the total duration of hospitalization was shorter in the
sodium nitroprusside group (7.34 ± 0.72 vs 9.10 ± 1.22
days). After multivariate analysis, sodium nitroprusside use
was found to be an independent protective factor against
development of postoperative AF (odds ratio: 4.282, 95%
confidence interval [CI]: 1.495-12.267).11
The causes of postoperative AF are multifactorial, and
include alterations in electrical conduction, operative trauma,
Table of Contents for the Digital Edition of Hospital Pharmacy - July/August 2017
The Evolution of Drug Information Centers and Specialists
Letter: Sodium Phosphates Injection—Osmolarity Labeling Correction
ISMP Adverse Drug Reactions
Drug Monographs: Avelumab and Ribociclib
Formulary Drug Review: Naldemedine
Chimeric Antigen Receptor T-Cell Therapy for Lymphomas: A Review of a Drug Class or Therapeutic Class in a Late Stage of Clinical Development
International Mentoring Programs: Leadership Opportunities to Enhance Worldwide Pharmacy Practice
Compounded Apixaban Suspensions for Enteral Feeding Tubes
Impact of Developing Adult Ketamine Order Panels for the Emergency Department
Critical Appraisal of Biomedical Literature With a Succinct Journal Club Template: The ROOTs Format
Effect of a Rivaroxaban Patient Assistance Kit (R-PAK) for Patients Discharged With Rivaroxaban: A Randomized Controlled Trial
Examining the Use of Sodium Nitroprusside in Coronary Artery Bypass Grafting: Is the Benefit Worth the Cost?
Successful Implementation of an Antimicrobial Stewardship Program at an Academic Medical Center
Hospital Pharmacy - July/August 2017 - 445
Hospital Pharmacy - July/August 2017 - 446
Hospital Pharmacy - July/August 2017 - 447
Hospital Pharmacy - July/August 2017 - 448
Hospital Pharmacy - July/August 2017 - 449
Hospital Pharmacy - July/August 2017 - 450
Hospital Pharmacy - July/August 2017 - 451
Hospital Pharmacy - July/August 2017 - The Evolution of Drug Information Centers and Specialists
Hospital Pharmacy - July/August 2017 - 453
Hospital Pharmacy - July/August 2017 - Letter: Sodium Phosphates Injection—Osmolarity Labeling Correction
Hospital Pharmacy - July/August 2017 - ISMP Adverse Drug Reactions
Hospital Pharmacy - July/August 2017 - 456
Hospital Pharmacy - July/August 2017 - 457
Hospital Pharmacy - July/August 2017 - 458
Hospital Pharmacy - July/August 2017 - Drug Monographs: Avelumab and Ribociclib
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Hospital Pharmacy - July/August 2017 - 470
Hospital Pharmacy - July/August 2017 - International Mentoring Programs: Leadership Opportunities to Enhance Worldwide Pharmacy Practice
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Hospital Pharmacy - July/August 2017 - Examining the Use of Sodium Nitroprusside in Coronary Artery Bypass Grafting: Is the Benefit Worth the Cost?
Hospital Pharmacy - July/August 2017 - 503
Hospital Pharmacy - July/August 2017 - 504
Hospital Pharmacy - July/August 2017 - 505
Hospital Pharmacy - July/August 2017 - 506
Hospital Pharmacy - July/August 2017 - 507
Hospital Pharmacy - July/August 2017 - Successful Implementation of an Antimicrobial Stewardship Program at an Academic Medical Center
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