Perioperative diltiazem or nitroglycerin in on-pump coronary artery bypass: A systematic review and network meta-analysis

Abstract

BackgroundArterial graft spasm is a severe complication after coronary artery bypass graft (CABG). Among numerous potential antispasmodic agents, systemic application of diltiazem and nitroglycerin had been investigated most frequently over the past three decades. However, it remains inconclusive if either or both agents could improve patient outcomes by preventing graft spasm when applied perioperatively, and, if so, which one would be a better choice. The current systematic review and network meta-analysis aims to summarize the data from all available randomized clinical trials of perioperative continuous intravenous infusion of diltiazem and/or nitroglycerin in patients undergoing on-pump CABG in order to define and compare their roles in graft spasm prevention and their impacts on perioperative outcomes.MethodsWe searched Ovid Medline, PubMed, CINAHL, Google Scholar and Cochrane Center for randomized controlled trials that reported outcome effects of perioperative continuous intravenous infusion of diltiazem and/or nitroglycerin in patients undergoing elective on-pump CABG. Conventional meta-analyses were conducted to evaluate the pairwise comparisons (diltiazem vs. placebo; nitroglycerin vs. placebo; diltiazem vs. nitroglycerin) on perioperative outcomes. Network meta-analyses were implemented to compare the three regimens through direct and indirect comparison.ResultsTwenty-seven studies involving 1,660 patients were included. Pairwise and network meta-analyses found no significant difference in mortality among the groups. There are four studies that reported blood flow measurements of internal mammary artery grafts intraoperatively after dissecting or immediately after distal anastomosis while patients were on continuous intravenous infusion of diltiazem and nitroglycerin. Although insufficient for data synthesis, the measured results from all four studies suggest that both diltiazem and nitroglycerin significantly increased blood flow of arterial grafts compared to placebo. For other perioperative outcomes, compared to diltiazem, patients that received nitroglycerin had higher odds of postoperative atrial fibrillation (OR = 2.67, 95% CI: 1.15 to 6.24) and higher peak serum cardiac enzymes. Patients that received placebo had higher odds of atrial fibrillation (OR = 3.00, 95% CI: 1.18 to 7.63) and lower odds of requiring inotrope support (OR = 0.19, 95% CI: 0.04 to 0.73) compared to diltiazem. Data from the network meta-analysis indicated that diltiazem had significantly lower odds of postoperative atrial fibrillation compared to nitroglycerin (OR = 0.39, 95% CI: 0.18 to 0.85). In fact, the rank from highest to lowest rates of postoperative atrial fibrillation was placebo>nitroglycerin>diltiazem. The rank from highest to lowest odds of requiring inotropic support is nitroglycerin> diltiazem>placebo. However, placebo had significantly higher odds of postoperative myocardial infarction than diltiazem (OR = 4.51, 95% CI: 1.34 to 15.25). The rank from highest to lowest odds of postoperative myocardial infarctio...

Perioperative Application of Diltiazem in Patients Undergoing On-Pump Coronary Artery Bypass Grafting

“…However, there has been no de nitive anatomical evidence supporting that perioperative continuous iv application of diltiazem had a direct vasodilatory effect on coronary grafts after the sternum was closed. Diltiazem became the preferred antispasmodic agent because, compared to nitroglycerine, it had more favorable perioperative outcome pro les, including lower incidences of new onset A-b and cardiac ischemia 7,9,21,22 . Noticeably, data from these RCTs also suggest that patients on diltiazem may need prolonged hemodynamic support from inotropic and/or vasoactive support, indicating that the usage of diltiazem may have potential negative perioperative and long-term outcome impacts 22 .…”

Perioperative Cardiac Risk Reduction in Noncardiac Surgery

“…22 A systematic review and meta-analysis from 2018 suggested that calcium channel blockers were highly effective and well tolerated for treating perioperative hypertension, and a 2018 meta-analysis suggested that continuous perioperative intravenous infusion of diltiazem had protective effects against postoperative ischemic cardiac injury and AF. 93,94 However, data from these studies are poor, and larger studies are needed.…”

Behandlungsprinzipien in der herzchirurgischen Intensivmedizin

“…Aufgrund der stetigen Veränderungen der Hämodynamik in der Akutphase der postoperativen Behandlung sollten zunächst vor allem kurzwirksame Substanzen wie Nitroglycerin oder Nitroprussid zum Einsatz kommen [72,73]. Diese medikamentöse Reduktion der linksventrikulären Nachlast nach operativer Korrektur einer vorbestehenden Mitralklappeninsuffizienz ist besonders wichtig, da eine unnötige Nachlaststeigerung den zuvor präoperativ volumenbelasteten linken Ventrikel überfordern und in ein linksventrikuläres Pumpversagen münden kann [74].…”