Hospital Pharmacy - July/August 2017 - 504

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perioperative medications, rapid rewarming after cardioplegic arrest, and reflex sympathetic tone.5 Nitric oxide (NO)
may be disrupted during reperfusion injury after CABG.
Sodium nitroprusside may be protective against postoperative AF due to replacement of NO. NO-induced reduction of
calcium release in myocytes may protect cardiomyocytes
from AF-induced calcium overload and/or attenuation of the
inflammatory process after surgery.5 The postoperative AF
study previously described also found that C-reactive protein
levels were lower in the sodium nitroprusside group than placebo, supporting the hypothesis that inflammation plays a
role in postoperative complications.11

Acute Kidney Injury
Another potential consequence of CABG surgery is AKI. A
meta-analysis of 33 randomized controlled trials revealed
incidences of AKI after off-pump and on-pump CABG of
19.1% and 22.2%, respectively.12 AKI after cardiac surgery
is caused by decreased renal perfusion, enhanced vasoconstriction due to sympathetic nervous system activation, the
inflammatory response, and reperfusion injury.13 Avoiding
AKI in CABG patients receiving sodium nitroprusside is
crucial, as use of sodium nitroprusside in kidney impairment
may result in accumulation of toxic metabolites. A randomized, blinded study investigated the impact of sodium nitroprusside versus placebo on renal function in 240 elective
on-pump CABG patients with a left ventricular ejection
fraction (LVEF) ≤50% and an estimated glomerular filtration rate (eGFR) >30 mL/min. Sodium nitroprusside was
infused at a starting dose of 0.1 mg/kg/h (equivalent to 1.66
µg/kg/min) at the initiation of the rewarming period and
titrated to maintain a MAP of 50 to 70 mmHg. Placebo
patients received routine medical management to maintain
MAPs at goal. Sodium nitroprusside patients excreted more
urine during the surgery than placebo (P < .05); however,
this effect attenuated during the first 24 hours after surgery.
Postoperative serum creatinine peaks were significantly
higher, and eGFR was significantly lower on postoperative
days 1 to 5 in the placebo group, but the clinical significance of these findings is small, as serum creatinine differences between groups ranged from 0.05 to 0.14 mg/dL and
eGFR differences ranged from 3 to 6 mL/min at each time
point. However, despite similar renal function at baseline,
the percent of patients with a new baseline creatinine clearance <50 mL/min was 14.7% in the sodium nitroprusside
group versus 38.3% in the placebo arm (P < .001). In addition, the percent creatinine increase from baseline was 50%
to 99% in 28.5% of placebo and 12.1% in sodium nitroprusside patients, and >100% in 6.9% of placebo and 1.6% of
sodium nitroprusside patients (P < .001). Overall, the study
suggests that sodium nitroprusside administration during
the rewarming period of on-pump CABG surgery is associated with improved renal function compared with conventional management.14

Hospital Pharmacy 52(7)

Inflammation
CPB is known to trigger an acute inflammatory response as a
result of blood contact with artificial surfaces in the pump,
the use of priming solutions, and reperfusion injury.15
Increases in leukocytes, platelets, C-reactive protein, and
inflammatory mediators including tumor necrosis factor α
(TNF-α), interleukin 6 (IL-6), and IL-8 have been documented after CABG.15,16 Sodium nitroprusside, which functions as an NO donor, has been shown to attenuate the
inflammatory response after surgery.17
Massoudy and colleagues conducted a prospective, randomized trial comparing administration of sodium nitroprusside 0.5 µg/kg/min or placebo for 20 minutes immediately
after release of the aortic cross-clamp during elective CABG
surgery in 22 patients with an LVEF of ≥55%. In patients who
received sodium nitroprusside, circulating IL-6 levels were
reduced within a minute of sodium nitroprusside infusion, and
IL-8 levels were reduced 15 minutes after the cessation of the
sodium nitroprusside infusion. No differences in clinical outcomes such as need for dopamine or duration of ICU stay were
observed.17 Later, Massoudy and colleagues conducted a similar prospective, double-blind study comparing sodium nitroprusside 0.5 µg/kg/min with placebo, this time enrolling 30
elective CABG patients with an LVEF ≤40% and increasing
the duration of infusion to 60 minutes after cross-clamp
removal. In this study, arterial levels of IL-6 and IL-8 were
similar between groups. However, there was a trend toward
lower concentrations of IL-6 and TNF-α in the coronary sinus
in the sodium nitroprusside group, with decreases in the
sodium nitroprusside arm reaching statistical significance for
IL-6 at the 5-minute and for TNF-α at the 75-minute postperfusion time point. The study showed that sodium nitroprusside
reduces the transcardiac release of some inflammatory mediators. Again, no clinical differences were observed between the
groups.18 The sodium nitroprusside-mediated reductions in
IL-6 and IL-8 levels may improve myocardial function.
Because cytokines are known to exert negative inotropic
effects,19 Freyholdt and colleagues later conducted a prospective, double-blind study comparing the impact of sodium
nitroprusside 0.5 µg/kg/min or placebo infused for 60 minutes after aortic cross-clamp removal on myocardial performance in 30 patients with LVEF ≤40% undergoing elective
CABG.20 Cardiac index (CI) was significantly higher in the
sodium nitroprusside group at the 35th minute of reperfusion
(immediately after termination of CPB: 4.4 ± 0.3 L/min/m2
vs 3.7 ± 0.7 L/min/m2, respectively) and the 75th minute of
reperfusion (after operation complete: 3.8 ± 0.3 L/min/m2 vs
3.0 ± 0.2 L/min/m2, respectively). MAP was significantly
lower in the sodium nitroprusside group at the same time
points (67.7 ± 2.6 vs 77.1 ± 3.1 mmHg and 77.9 ± 3.7 vs 75.5
± 3.5 mmHg, respectively), and mean pulmonary capillary
wedge pressure was significantly higher in the sodium nitroprusside group at the same time points (13.9 ± 1.1 vs 11.5 ±
0.7 mmHg and 13.4 ± 0.9 vs 11.1 ± 0.7 mmHg, respectively),



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
Hospital Pharmacy - July/August 2017 - 460
Hospital Pharmacy - July/August 2017 - 461
Hospital Pharmacy - July/August 2017 - 462
Hospital Pharmacy - July/August 2017 - 463
Hospital Pharmacy - July/August 2017 - Formulary Drug Review: Naldemedine
Hospital Pharmacy - July/August 2017 - 465
Hospital Pharmacy - July/August 2017 - 466
Hospital Pharmacy - July/August 2017 - 467
Hospital Pharmacy - July/August 2017 - 468
Hospital Pharmacy - July/August 2017 - Chimeric Antigen Receptor T-Cell Therapy for Lymphomas: A Review of a Drug Class or Therapeutic Class in a Late Stage of Clinical Development
Hospital Pharmacy - July/August 2017 - 470
Hospital Pharmacy - July/August 2017 - International Mentoring Programs: Leadership Opportunities to Enhance Worldwide Pharmacy Practice
Hospital Pharmacy - July/August 2017 - 472
Hospital Pharmacy - July/August 2017 - 473
Hospital Pharmacy - July/August 2017 - 474
Hospital Pharmacy - July/August 2017 - 475
Hospital Pharmacy - July/August 2017 - 476
Hospital Pharmacy - July/August 2017 - 477
Hospital Pharmacy - July/August 2017 - Compounded Apixaban Suspensions for Enteral Feeding Tubes
Hospital Pharmacy - July/August 2017 - 479
Hospital Pharmacy - July/August 2017 - 480
Hospital Pharmacy - July/August 2017 - 481
Hospital Pharmacy - July/August 2017 - 482
Hospital Pharmacy - July/August 2017 - Impact of Developing Adult Ketamine Order Panels for the Emergency Department
Hospital Pharmacy - July/August 2017 - 484
Hospital Pharmacy - July/August 2017 - 485
Hospital Pharmacy - July/August 2017 - 486
Hospital Pharmacy - July/August 2017 - 487
Hospital Pharmacy - July/August 2017 - Critical Appraisal of Biomedical Literature With a Succinct Journal Club Template: The ROOTs Format
Hospital Pharmacy - July/August 2017 - 489
Hospital Pharmacy - July/August 2017 - 490
Hospital Pharmacy - July/August 2017 - 491
Hospital Pharmacy - July/August 2017 - 492
Hospital Pharmacy - July/August 2017 - 493
Hospital Pharmacy - July/August 2017 - 494
Hospital Pharmacy - July/August 2017 - 495
Hospital Pharmacy - July/August 2017 - Effect of a Rivaroxaban Patient Assistance Kit (R-PAK) for Patients Discharged With Rivaroxaban: A Randomized Controlled Trial
Hospital Pharmacy - July/August 2017 - 497
Hospital Pharmacy - July/August 2017 - 498
Hospital Pharmacy - July/August 2017 - 499
Hospital Pharmacy - July/August 2017 - 500
Hospital Pharmacy - July/August 2017 - 501
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
Hospital Pharmacy - July/August 2017 - 509
Hospital Pharmacy - July/August 2017 - 510
Hospital Pharmacy - July/August 2017 - 511
Hospital Pharmacy - July/August 2017 - 512
Hospital Pharmacy - July/August 2017 - 513
Hospital Pharmacy - July/August 2017 - 514
Hospital Pharmacy - July/August 2017 - 515
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