Milrinone Vs Dobutamine for the Management of Cardiogenic Shock: Implications of Renal Function and Injury

Overview

Journal JACC Adv

Specialty Cardiology & Vascular Diseases

Date 2024 Jun 28

PMID 38938997

Authors

Pietro Di Santo

Kooroush Dehghan

Brennan Mao

Richard G Jung

Daniel Fadare

John Paydar

Simon Parlow

Pouya Motazedian

Graeme Prosperi-Porta

Omar Abdel-Razek

Joanne Joseph

Cheng Yee Goh

Kevin Chung

Andrew Mulloy

F Daniel Ramirez

Trevor Simard

Benjamin Hibbert

Rebecca Mathew

Juan J Russo

Affiliations

Soon will be listed here.

Abstract

Background: Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction.

Objectives: This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function.

Methods: In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy.

Results: Baseline eGFR <60 ml/min/1.73 m and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome ( interaction = 0.02) and death ( interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI.

Conclusions: In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

Citing Articles

Managing Arrhythmias in Cardiogenic Shock: Insights Into Milrinone and Dobutamine Therapy.

Fletcher J, Poornima Halaharvi S, Manuvel C, Brooks A, Wannakuwatte R, Lucano Gomez E Cureus. 2025; 16(12):e76089.

PMID: 39835019 PMC: 11743927. DOI: 10.7759/cureus.76089.

References

Hasei M, Uchiyama A, Nishimura M, Mashimo T, Fujino Y . Correlation between plasma milrinone concentration and renal function in patients with cardiac disease. Acta Anaesthesiol Scand. 2008; 52(7):991-6. DOI: 10.1111/j.1399-6576.2008.01671.x. View

Ronco C, Haapio M, House A, Anavekar N, Bellomo R . Cardiorenal syndrome. J Am Coll Cardiol. 2008; 52(19):1527-39. DOI: 10.1016/j.jacc.2008.07.051. View

Harjola V, Lassus J, Sionis A, Kober L, Tarvasmaki T, Spinar J . Clinical picture and risk prediction of short-term mortality in cardiogenic shock. Eur J Heart Fail. 2015; 17(5):501-9. DOI: 10.1002/ejhf.260. View

Lauridsen M, Gammelager H, Schmidt M, Rasmussen T, Shaw R, Botker H . Acute kidney injury treated with renal replacement therapy and 5-year mortality after myocardial infarction-related cardiogenic shock: a nationwide population-based cohort study. Crit Care. 2015; 19:452. PMC: 4699352. DOI: 10.1186/s13054-015-1170-8. View

Ballo P, Chechi T, Spaziani G, Fibbi V, Conti D, Ferro G . Prognostic comparison between creatinine-based glomerular filtration rate formulas for the prediction of 10-year outcome in patients with non-ST elevation acute coronary syndrome treated by percutaneous coronary intervention. Eur Heart J Acute Cardiovasc Care. 2017; 7(8):689-702. DOI: 10.1177/2048872617697452. View

Klein L, Massie B, Leimberger J, OConnor C, Pina I, Adams Jr K . Admission or changes in renal function during hospitalization for worsening heart failure predict postdischarge survival: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure.... Circ Heart Fail. 2009; 1(1):25-33. DOI: 10.1161/CIRCHEARTFAILURE.107.746933. View

Khwaja A . KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012; 120(4):c179-84. DOI: 10.1159/000339789. View

Koreny M, Delle Karth G, Geppert A, Neunteufl T, Priglinger U, Heinz G . Prognosis of patients who develop acute renal failure during the first 24 hours of cardiogenic shock after myocardial infarction. Am J Med. 2002; 112(2):115-9. DOI: 10.1016/s0002-9343(01)01070-1. View

Rangaswami J, Bhalla V, Blair J, Chang T, Costa S, Lentine K . Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association. Circulation. 2019; 139(16):e840-e878. DOI: 10.1161/CIR.0000000000000664. View

10.

Stroshane R, KOSS R, Biddlecome C, Luczkowec C, Edelson J . Oral and intravenous pharmacokinetics of milrinone in human volunteers. J Pharm Sci. 1984; 73(10):1438-41. DOI: 10.1002/jps.2600731029. View

11.

Tarvasmaki T, Haapio M, Mebazaa A, Sionis A, Silva-Cardoso J, Tolppanen H . Acute kidney injury in cardiogenic shock: definitions, incidence, haemodynamic alterations, and mortality. Eur J Heart Fail. 2017; 20(3):572-581. DOI: 10.1002/ejhf.958. View

12.

Marenzi G, Assanelli E, Campodonico J, De Metrio M, Lauri G, Marana I . Acute kidney injury in ST-segment elevation acute myocardial infarction complicated by cardiogenic shock at admission. Crit Care Med. 2009; 38(2):438-44. DOI: 10.1097/CCM.0b013e3181b9eb3b. View

13.

Fliser D, Laville M, Covic A, Fouque D, Vanholder R, Juillard L . A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines on acute kidney injury: part 1: definitions, conservative management and contrast-induced nephropathy. Nephrol Dial Transplant. 2012; 27(12):4263-72. PMC: 3520085. DOI: 10.1093/ndt/gfs375. View

14.

Saltzman H, Sharma K, Mather P, Rubin S, Adams S, Whellan D . Renal dysfunction in heart failure patients: what is the evidence?. Heart Fail Rev. 2007; 12(1):37-47. DOI: 10.1007/s10741-007-9006-5. View

15.

Mathew R, Di Santo P, Jung R, Marbach J, Hutson J, Simard T . Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N Engl J Med. 2021; 385(6):516-525. DOI: 10.1056/NEJMoa2026845. View

16.

Fuernau G, Poenisch C, Eitel I, Denks D, de Waha S, Poss J . Prognostic impact of established and novel renal function biomarkers in myocardial infarction with cardiogenic shock: A biomarker substudy of the IABP-SHOCK II-trial. Int J Cardiol. 2015; 191:159-66. DOI: 10.1016/j.ijcard.2015.04.242. View

17.

Levey A, Stevens L, Schmid C, Zhang Y, Castro 3rd A, Feldman H . A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150(9):604-12. PMC: 2763564. DOI: 10.7326/0003-4819-150-9-200905050-00006. View

18.

Larsson R, Liedholm H, Andersson K, Keane M, Henry G . Pharmacokinetics and effects on blood pressure of a single oral dose of milrinone in healthy subjects and in patients with renal impairment. Eur J Clin Pharmacol. 1986; 29(5):549-53. DOI: 10.1007/BF00635891. View

19.

van Diepen S, Katz J, Albert N, Henry T, Jacobs A, Kapur N . Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017; 136(16):e232-e268. DOI: 10.1161/CIR.0000000000000525. View