Intraoperative milrinone versus dobutamine in cardiac surgery patients: a retrospective cohort study on mortality

Abstract

BackgroundSeveral choices of inotropic therapy are available and used in relation to cardiac surgery. Comparisons are necessary to select optimal therapy. In Denmark, dobutamine and milrinone are the two inotropic agents most commonly used to treat post-bypass low cardiac output syndrome. This study compares all-cause mortality with these drugs.MethodsIn a retrospective observational study we investigated 10,700 consecutive patients undergoing cardiac surgery from 1 April 2006 to 31 December 2013 at Aarhus and Aalborg University Hospitals in the Central and Northern Denmark Region. Prospectively entered data in the Western Danish Heart Registry on intraoperative use of inotropes were used to identify 952 patients treated with milrinone, 418 patients treated with dobutamine, and 82 patients receiving a combination of the two inotropes. All-cause mortality among patients receiving dobutamine was compared to all-cause mortality among milrinone receivers.Multiple logistic regression analyses including preoperative and intraoperative variables along with g-formula analyses were used to model 30-day and 1-year mortality risks. Reported were standardized mortality risk differences between the treatment groups.ResultsAmong patients receiving intraoperative dobutamine, 18 (4.3%) died within 30 days and 49 (11.7%) within 1 year. Corresponding 30-day and 1-year mortality for milrinone receivers were 81 (8.5%) and 170 (17.9%). Risk of death within 30 days and 1 year was increased for intraoperative milrinone compared to dobutamine with a standardized risk difference of 4.06% (confidence interval (CI) 1.23; 6.89, p = 0.005) and 4.77% (CI 0.39; 9.15, p = 0.033), respectively. Sensitivity analyses including adjustment for milrinone preference, hemodynamic instability prior to cardiopulmonary bypass, and separate analyses on hospital level all confirmed a sign toward increased mortality among milrinone receivers.ConclusionsIntraoperative use of milrinone in cardiac surgery may be associated with an increase in all-cause mortality compared to use of dobutamine.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-1969-1) contains supplementary material, which is available to authorized users.

Milrinone in Adult Cardiac Surgery: More Evidence Is Needed to Support Routine Inhalation Administration

“…milrinone (IvMil) and inhaled milrinone (iMil) have been trialed in cardiac surgery, but the best route of administration remains debatable. [14][15][16][17][18][19][20][21][22] As a phosphodiesterase-3 inhibitor, milrinone prevents the degradation of cyclic adenosine monophosphate in vascular smooth muscles and cardiac myocytes. [14][15][16][17][18][19][20] The increased concentration of cyclic adenosine monophosphate results in further phosphorylation of protein kinase A, activating calcium channels and thereby increasing intracellular concentration of calcium in cardiac myocytes and augmenting myocardial systolic performance.…”

“…In addition, milrinone provides systemic and pulmonary vasodilation, thereby reducing biventricular filling pressures and afterload. [8][9][13][14][15][16][17][18][19][20] Theoretically, milrinone's proposed mechanisms of action would translate well toward the management of patients with LV dysfunction, LCOS, PH, and RVD after CPB. However, to date, there is conflicting evidence regarding milrinone's benefits.…”

“…However, to date, there is conflicting evidence regarding milrinone's benefits. [14][15][16][17][18][19][20][21][22] Most notably, the Prospective Randomized Milrinone Survival Evaluation (PROMISE) study by Packer et al reported a 28% and 34% increase in overall and cardiovascular mortality, respectively, with the use of oral milrinone in the management of patients with congestive heart failure. 15 Another recent study, by Nielsen et al, also showed increased all-cause mortality with milrinone compared with dobutamine in cardiac surgery patients.…”

“…15 Another recent study, by Nielsen et al, also showed increased all-cause mortality with milrinone compared with dobutamine in cardiac surgery patients. 16 The overriding concern regarding the safety of milrinone is its propensity to cause systemic hypotension and end-organ hypoperfusion when administered intravenously. This prompted the development of iMil.…”

“…18,23 Whereas IvMil has been widely adopted during cardiac surgery, data regarding cardiovascular safety and efficacy of iMil continue to be inconclusive. [14][15][16][17][18][19][20][21][22] In this issue of the Journal of Cardiothoracic and Vascular Anesthesia, Rong et al 17 add to the body of knowledge regarding the usefulness of iMil and IvMil in adult cardiac surgery. The authors present a meta-analysis assessing the hemodynamic, echocardiographic, and clinical effects of iMil and IvMil in patients undergoing cardiac surgery.…”