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Updating the Update: The Final Word on Milrinone and Mortality After Cardiac Surgery?
Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
Contents lists available at ScienceDirect
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Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
Letter to the Editor Updating the Update: The Final Word on Milrinone and Mortality After Cardiac Surgery?
To the Editor: The recently updated meta-analysis by Ushio et al1 addressing the impact of milrinone on patients undergoing cardiac surgery followed 2 previous meta-analyses also published in the Journal of Cardiothoracic and Vascular Anesthesia.2,3 Many of the trials included in this update were relatively small (n ¼ 22 to n ¼ 80) and cumulatively analyzed a total of 537 patients from 12 randomized controlled trials. It was unfortunate that the inclusion search dates ended on July 3, 2016, as on July 28, 2016, the single largest (n ¼ 124) trial of milrinone subsequently was published by Denault et al.4 To obviate the need for any further “updates to the update,” the results of this multicenter study were entirely consistent with those shown by Ushio et al; that is, no effect of milrinone on arrhythmias or on 1-year mortality. Importantly, the Denault et al study addressed the potential mechanisms of why milrinone might conceivably have an impact on mortality or ventricular arrhythmias; that is, through a reduction in pulmonary artery pressure and an increase in cardiac output. Despite these beneficial hemodynamic effects, their study did not have an effect of increasing the successful weaning of patients from cardiopulmonary bypass, essentially demonstrating that milrinone could have a potent physiologic effect on the pulmonary vasculature, but this was not reflected in the overall ability of the heart to perform better in this setting. One could extrapolate that if the milrinone did not have a sustained and significant enough
http://dx.doi.org/10.1053/j.jvca.2017.02.031 1053-0770/& 2017 Elsevier Inc. All rights reserved.
impact on cardiovascular function in the post-bypass period, then it would be unexpected to have any long-term effect on either arrhythmia potential or mortality. Thus, the metaanalysis from Ushio et al, even if arguably incomplete (due to the limitations imposed by calendar inclusion), is important because it reinforced the emerging negative studies that continue to appear in the literature with respect to milrinone. Furthermore, the similarity of results of Ushio et al1 and Denault et al4 makes the need for any further updated metaanalysis likely unnecessary unless further (even larger) trials also are published. References 1 Ushio M, Egi M, Wakabayashi J, et al. Impact of milrinone administration in adult cardiac surgery patients: Updated meta-analysis. J Cardiothorac Vasc Anesth 2016;30:1454–60. 2 Zangrillo A, Biondi-Zoccai G, Ponschab M, et al. Milrinone and mortality in adult cardiac surgery: A meta-analysis. J Cardiothorac Vasc Anesth 2012;26:70–7. 3 Majure DT, Greco T, Greco M, et al. Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: An update. J Cardiothorac Vasc Anesth 2013;27:220–9. 4 Denault AY, Bussières JS, Arellano R, et al. A multicentre randomizedcontrolled trial of inhaled milrinone in high-risk cardiac surgical patients. Can J Anesth 2016;63:1140–53.
Hilary P. Grocott, MD, FRCPC Departments of Anesthesia & Perioperative Medicine and Surgery University of Manitoba Winnipeg, Canada E-mail address: [email protected]
Contents lists available at ScienceDirect
HOSTED BY
Journal of Cardiothoracic and Vascular Anesthesia ] (]]]]) ]]]–]]]
Letter to the Editor Updating the Update: The Final Word on Milrinone and Mortality After Cardiac Surgery?
To the Editor: The recently updated meta-analysis by Ushio et al1 addressing the impact of milrinone on patients undergoing cardiac surgery followed 2 previous meta-analyses also published in the Journal of Cardiothoracic and Vascular Anesthesia.2,3 Many of the trials included in this update were relatively small (n ¼ 22 to n ¼ 80) and cumulatively analyzed a total of 537 patients from 12 randomized controlled trials. It was unfortunate that the inclusion search dates ended on July 3, 2016, as on July 28, 2016, the single largest (n ¼ 124) trial of milrinone subsequently was published by Denault et al.4 To obviate the need for any further “updates to the update,” the results of this multicenter study were entirely consistent with those shown by Ushio et al; that is, no effect of milrinone on arrhythmias or on 1-year mortality. Importantly, the Denault et al study addressed the potential mechanisms of why milrinone might conceivably have an impact on mortality or ventricular arrhythmias; that is, through a reduction in pulmonary artery pressure and an increase in cardiac output. Despite these beneficial hemodynamic effects, their study did not have an effect of increasing the successful weaning of patients from cardiopulmonary bypass, essentially demonstrating that milrinone could have a potent physiologic effect on the pulmonary vasculature, but this was not reflected in the overall ability of the heart to perform better in this setting. One could extrapolate that if the milrinone did not have a sustained and significant enough
http://dx.doi.org/10.1053/j.jvca.2017.02.031 1053-0770/& 2017 Elsevier Inc. All rights reserved.
impact on cardiovascular function in the post-bypass period, then it would be unexpected to have any long-term effect on either arrhythmia potential or mortality. Thus, the metaanalysis from Ushio et al, even if arguably incomplete (due to the limitations imposed by calendar inclusion), is important because it reinforced the emerging negative studies that continue to appear in the literature with respect to milrinone. Furthermore, the similarity of results of Ushio et al1 and Denault et al4 makes the need for any further updated metaanalysis likely unnecessary unless further (even larger) trials also are published. References 1 Ushio M, Egi M, Wakabayashi J, et al. Impact of milrinone administration in adult cardiac surgery patients: Updated meta-analysis. J Cardiothorac Vasc Anesth 2016;30:1454–60. 2 Zangrillo A, Biondi-Zoccai G, Ponschab M, et al. Milrinone and mortality in adult cardiac surgery: A meta-analysis. J Cardiothorac Vasc Anesth 2012;26:70–7. 3 Majure DT, Greco T, Greco M, et al. Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: An update. J Cardiothorac Vasc Anesth 2013;27:220–9. 4 Denault AY, Bussières JS, Arellano R, et al. A multicentre randomizedcontrolled trial of inhaled milrinone in high-risk cardiac surgical patients. Can J Anesth 2016;63:1140–53.
Hilary P. Grocott, MD, FRCPC Departments of Anesthesia & Perioperative Medicine and Surgery University of Manitoba Winnipeg, Canada E-mail address: [email protected]