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

BACKGROUND: Several 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. METHODS: In 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. RESULTS: Among 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. CONCLUSIONS: Intraoperative use of milrinone in cardiac surgery may be associated with an increase in all-cause mortality compared to use of dobutamine.

A sensitive and specific high performance liquid chromatographic assay for milrinone in rat and human plasma using a commercially available internal standard and low sample volume.

PURPOSE: To develop an alternate high performance liquid chromatographic method (HPLC) for the analysis of the positive inotropic agent, milrinone, in rat and human plasma. METHODS: To plasma samples (0.1 mL), containing milrinone and the commercially available internal standard, amrinone, were added 0.15 mL of water and 0.35 mL of acetonitrile. Tubes were briefly vortex-mixed and centrifuged. The supernatant was transferred to clean tubes and 3 mL of methanol: diethyl ether (5:95) was added. The tubes were vortex mixed, centrifuged, and reconstituted with the mobile phase and injected into the HPLC. Separation was accomplished using a reverse phase chromatography using C18 analytical column, and detection was afforded by monitoring the eluent at an ultraviolet wavelength of 326 nm. RESULTS: Standard curves were highly linear over the range 10 to 10000 ng/mL (r2 >0.99). Recovery ranged from 52-69% over a 40-fold range of plasma concentrations from 50 to 2000 ng/mL. Intra- and inter-day coefficient of variation and mean error in were less than 20% at plasma concentrations ranging from 10 to 1000 ng/mL. The utility of the assay was demonstrated in a pharmacokinetic evaluation of milrinone in two rats given intravenous bolus doses. CONCLUSION: The developed assay was sensitive, specific and appropriate for monitoring milrinone in rat or human plasma samples.