Acute Coronary Syndrome, Cardiogenic Shock, Low Cardiac Output Syndrome, Pulmonary Edema
Conditions
Keywords
Cardiogenic shock, Inotropes, Low cardiac output syndrome
Brief summary
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.
Detailed description
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
DRUGMilrinone
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.
DRUGDobutamine
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.
Sponsors
Ottawa Heart Institute Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study participants, treating medical team and research team will be blinded to randomization; the pharmacy staff, CCU nurses and allied healthcare team members will not be blinded to the randomization.
Intervention model description
Consecutive patients admitted to the Coronary Care Unit (CCU) at the Ottawa Heart Institute from start of study (tentatively set for August 2017 with anticipated end date of June 2020) and identified by the treating medical team as requiring initiation of inotrope therapy will be screened and randomized based on the healthcare team's clinical assessment of predominantly LV or RV systolic dysfunction (biventricular dysfunction will be assigned to predominantly LV dysfunction). All decisions to initiate inotrope therapy will be made by the primary care team with no involvement from the research team.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Need for advanced mechanical support [specifically, intra-aortic balloon pump, Impella, ventricular assist device or extra-corporeal membrane oxygenation] or cardiac transplant | Through duration of hospitalization, up to 12 weeks following admission | Need for new mechanical support or cardiac transplant |
| Non-fatal myocardial infarction [MI] | Through duration of hospitalization, up to 12 weeks following admission | As defined by Thygesen et al., 2012 (Circulation) |
| Acute kidney injury requiring renal replacement therapy | Through duration of hospitalization, up to 12 weeks following admission | Acute kidney injury requiring renal replacement therapy (intermittent hemodialysis or continuous renal replacement therapy) |
| Stay in CCU greater than or equal to 7 days | Through duration of hospitalization, up to 12 weeks following admission | Stay in CCU greater than or equal to 7 days |
| Transient ischemic attack [TIA] or cerebrovascular accident [CVA] | Through duration of hospitalization, up to 12 weeks following admission | Transient ischemic attack or cerebrovascular accident as diagnosed by a Neurologist either clinically and/or radiographically |
| Composite Primary End Point | Through duration of hospitalization, up to 12 weeks following admission | 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. |
| All-cause in-hospital death | Through duration of hospitalization, up to 12 weeks following admission | All-cause in-hospital death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum lactate | Through duration of hospitalization, up to 12 weeks following admission | Normalization of serum lactate |
| Arrhythmia requiring medical team intervention | Through duration of hospitalization, up to 12 weeks following admission | Arrhythmia requiring medical team intervention, either through electrical or chemical cardioversion or any intravenous anti-arrhythmia medication administration |
| Change in systemic vascular resistance [SVR] | Through duration of hospitalization, up to 12 weeks following admission | Change in systemic vascular resistance measured with PA catheter |
| Time on inotropes | Through duration of hospitalization, up to 12 weeks following admission | Total time on inotropes (in hours) |
| Non-invasive or invasive mechanical ventilation | Through duration of hospitalization, up to 12 weeks following admission | Total number of days requiring non-invasive or invasive mechanical ventilation |
| Change in cardiac index ([CI] | Through duration of hospitalization, up to 12 weeks following admission | Change in cardiac index measured with PA catheter |
| Change in pulmonary capillary wedge pressure [PCWP] | Through duration of hospitalization, up to 12 weeks following admission | Change in pulmonary capillary wedge pressure measured with PA catheter |
| Change in pulmonary vascular resistance [PVR] | Through duration of hospitalization, up to 12 weeks following admission | Change in pulmonary vascular resistance measured with PA catheter |
| Presence of acute kidney injury | Through duration of hospitalization, up to 12 weeks following admission | Presence of acute kidney injury (defined by KDIGO as creatinine increased by 26.5 umol/L, 1.5 times baseline within prior 7 days, or urine volume \<0.5 mL/kg/hour for greater than or equal to 6 hours |
Other
| Measure | Time frame | Description |
|---|---|---|
| Sustained hypotension of systolic BP | Through duration of hospitalization in CCU, up to 12 weeks following admission | Sustained systolic blood pressure hypotension of less than or equal to 90 mmHg for greater than or equal to 30 minutes (or requiring medical intervention) |
| Need for up-titration or addition of new vasopressor therapy | Through duration of hospitalization in CCU, up to 12 weeks following admission | Need for up-titration or addition of new vasopressor therapy |
| Ventricular arrhythmias | Through duration of hospitalization in CCU, up to 12 weeks following admission | Ventricular arrhythmias (monomorphic or polymorphic ventricular tachycardia \[VT\] greater than 30 seconds or hemodynamically unstable ventricular arrhythmia requiring intervention, or VF) |
| Need for intravenous or oral anti-arrhythmic therapy | Through duration of hospitalization in CCU, up to 12 weeks following admission | Initiation of intravenous or oral anti-arrhythmic therapy |
| Atrial arrhythmias requiring medical intervention | Through duration of hospitalization in CCU, up to 12 weeks following admission | Atrial flutter, fibrillation or tachycardia requiring medical intervention |
Countries
Canada
Outcome results
None listed