Milrinone Versus Dobutamine in Critically Ill Patients

Phase 4CompletedNCT03207165

Ottawa Heart Institute Research Corporation192 enrolled

Overview

The investigators are interested in determining if there is a meaningful difference between two of the most commonly used medications used to improve the pumping function of the heart among critically ill patients admitted to the Coronary Care Unit (CCU) at the University of Ottawa Heart Institute (UOHI). To do this, the investigators will randomly assign patients who are felt to require use of these medications by their treating physicians to one of the two most commonly used agents in Canada: Milrinone or Dobutamine. Each patient will be closely monitored by their healthcare team, and their medication will be adjusted based on each patient's clinical status. Information from blood work (e.g. kidney and liver function, complete blood counts, and other markers of how effectively blood is circulating in the body), assessment of end-organ function (e.g. urine output, mentation), abnormal heart rhythms noted on monitoring and results of imaging studies (e.g. angiogram, echocardiograms.) will be collected for analysis. All patients will be followed for the duration of their hospital stay at UOHI.

The use of various inotropes in the care of critically ill cardiac patients has become increasingly widespread: while predominantly used in decompensated heart failure, they have also been used in cardiogenic shock complicating acute coronary syndrome (ACS) and septic shock. Purported mechanisms of efficacy include improved cardiac output, improved end-organ perfusion, and vasodilation of both pulmonary and systemic circulations. Two of the most commonly used agents are Milrinone, a phosphodiesterase 3 inhibitor, and Dobutamine, a synthetic catecholamine with affinity for both beta-1 and 2 receptors. Both the American College of Cardiology (ACC) and the European Society of Cardiology (ESC) support inotropes for acute and chronic heart failure management with low cardiac output states. Furthermore, the ACC recommends consideration of inotropic therapy within the STEMI guidelines when ACS is complicated by cardiogenic shock, heart failure or for hemodynamic support in isolated right ventricle infarctions. Beyond primarily cardiac etiologies, inotropes have been identified as first-line additive therapy for cardiac augmentation to Norepinephrine in patients with septic shock complicated by myocardial dysfunction. Despite the lack of convincing data supporting a morbidity or mortality benefit with the use of inotropes in severe, decompensated heart failure, cardiogenic or septic shock, or in ACS, inotropic therapy is still widely used across various critical care settings. Furthermore, to date, there has been no head to head comparison of the two more commonly used positive inotropes: Dobutamine and Milrinone. Selection of one inotrope over another is often guided by physician and center preference, and consideration of and purported avoidance of possible adverse effects. In this pilot study, the investigators aim to describe that characteristics of patients receiving inotropic support in the CCU setting and identify possible differences in morbidity and mortality between Dobutamine and Milrinone among a heterogeneous population of patients admitted to the CCU at UOHI, which may help to inform a larger clinical trial in the future. The purpose of this pilot study is to: (a) describe the characteristics of patients receiving inotropic support in the coronary care unit (CCU) setting (hemodynamics prior to inotrope initiation, etiology of cardiogenic shock state, use of PA catheter and values if deemed necessary by medical team) and (b) identify possible differences in morbidity \[atrial and ventricular arrhythmias, hepatic and renal function, markers of end-organ perfusion (lactate, urine output, mentation status), use of vasopressors, sustained hypotension of systolic blood pressure less than or equal to 90 mmHg for greater than 30 minutes, need for mechanical support, cardiac transplant, total length of CCU stay, length of CCU stay greater than 14 days\] and mortality between patients in cardiogenic shock treated with Dobutamine versus Milrinone.

Interventions

MilrinoneDRUG

Patients will be initiated on Milrinone at 0.125 mcg/kg/min \[stage 1\] and will be titrated according to a blinded protocol from stages 2 to 5 \[0.250, 0.375, 0.5 and \>0.5 ug/kg/min\]. All orders to initiate and titrate the dose of the allocated inotrope will be written in the chart as follows: 'Study inotrope dose to be \[increased/decreased/maintained\] at stage \[1-5\]' so as to ensure that treating physicians remain blinded to the allocated drug.

DobutamineDRUG

Patients will be initiated on Dobutamine at 2.5 mcg/kg/min \[stage 1\] and will be titrated according to a blinded protocol from stages 2 to 5 \[5.0, 7.5, 10 and \>10 ug/kg/min\]. All orders to initiate and titrate the dose of the allocated inotrope will be written in the chart as follows: 'Study inotrope dose to be \[increased/decreased/maintained\] at stage \[1-5\]' so as to ensure that treating physicians remain blinded to the allocated drug.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have one or more of the following: * Low cardiac output state, evidenced by sustained hypotension (systolic blood pressure \<90 mmHg) and end organ dysfunction (altered level of consciousness, elevated lactate, renal or hepatic dysfunction) * Clinical evidence of systemic and/or pulmonary congestion despite use of vasodilators and/or diuretics * ACS complicated by cardiogenic shock (defined as persistent hypotension with systolic blood pressure \<90 mmHg with severe reduction in cardiac index \[\<1.8 L/min/m2 without support or \<2.2 L/min/m2 with support\], left ventricular end-diastolic pressure \>18 mmHg) * Augmentation of cardiac output when patient already on maximal vasopressor therapy * Or medical team's decision that patient needs inotropic therapy Exclusion Criteria: * Unwillingness or inability to provide informed consent by the patient or substitute decision maker for healthcare decisions * Female participants who are currently pregnant * Patients presenting with an out-of-hospital cardiac arrest (OOHCA) * Healthcare team preference for use of specific inotrope (Milrinone or Dobutamine)

Outcomes

Primary Outcomes

Composite Primary End Point

Composite of all-cause in-hospital death, non-fatal MI, TIA or CVA diagnosed by a Neurologist, renal failure requiring renal replacement therapy, need for cardiac transplant or new mechanical support, any atrial or ventricular arrhythmia leading to cardiac arrest and resuscitation.