Milrinone Versus Dobutamine in Critically Ill Patients
Mots clés
Abstrait
La 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.
Rendez-vous
| Dernière vérification: | 05/31/2020 |
| Première soumission: | 06/26/2017 |
| Inscription estimée soumise: | 06/29/2017 |
| Première publication: | 07/01/2017 |
| Dernière mise à jour soumise: | 06/28/2020 |
| Dernière mise à jour publiée: | 06/29/2020 |
| Date de début réelle de l'étude: | 08/29/2017 |
| Date d'achèvement primaire estimée: | 06/11/2020 |
| Date estimée d'achèvement de l'étude: | 06/11/2020 |
Condition ou maladie
Intervention / traitement
Drug: Milrinone
Drug: Dobutamine
Phase
Groupes d'armes
| Bras | Intervention / traitement |
|---|---|
| Active Comparator: Left ventricular [LV] +/- Biventricular dysfunction Assessment of left ventricular [LV] or biventricular dysfunction will be based on clinical assessment, available imaging (echocardiogram, left ventriculogram, MUGA/RNA scan, cardiac MRI, etc.) and known past medical history (if available and contributory). Patients identified as having biventricular dysfunction will be randomized within the LV dysfunction arm of the trial. Patients in this arm will be randomized in a 1:1 fashion to Milrinone or Dobutamine. | |
| Active Comparator: Right ventricular [RV] dysfunction Assessment of right ventricular [RV] dysfunction will be based on clinical assessment, available imaging (echocardiogram, left ventriculogram, MUGA/RNA scan, cardiac MRI, etc.) and known past medical history (if available and contributory). Patients in this arm will be randomized in a 1:1 fashion to Milrinone or Dobutamine. |
Critère d'éligibilité
| Âges éligibles aux études | 18 Years À 18 Years |
| Sexes éligibles à l'étude | All |
| Accepte les bénévoles en santé | Oui |
| Critères | 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) |
Résultat
Mesures des résultats primaires
1. Composite Primary End Point [Through duration of hospitalization, up to 12 weeks following admission]
2. All-cause in-hospital death [Through duration of hospitalization, up to 12 weeks following admission]
3. Non-fatal myocardial infarction [MI] [Through duration of hospitalization, up to 12 weeks following admission]
4. Transient ischemic attack [TIA] or cerebrovascular accident [CVA] [Through duration of hospitalization, up to 12 weeks following admission]
5. Stay in CCU greater than or equal to 7 days [Through duration of hospitalization, up to 12 weeks following admission]
6. Acute kidney injury requiring renal replacement therapy [Through duration of hospitalization, up to 12 weeks following admission]
7. 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]
Mesures des résultats secondaires
1. Time on inotropes [Through duration of hospitalization, up to 12 weeks following admission]
2. Non-invasive or invasive mechanical ventilation [Through duration of hospitalization, up to 12 weeks following admission]
3. Change in cardiac index ([CI] [Through duration of hospitalization, up to 12 weeks following admission]
4. Change in pulmonary capillary wedge pressure [PCWP] [Through duration of hospitalization, up to 12 weeks following admission]
5. Change in pulmonary vascular resistance [PVR] [Through duration of hospitalization, up to 12 weeks following admission]
6. Change in systemic vascular resistance [SVR] [Through duration of hospitalization, up to 12 weeks following admission]
7. Presence of acute kidney injury [Through duration of hospitalization, up to 12 weeks following admission]
8. Serum lactate [Through duration of hospitalization, up to 12 weeks following admission]
9. Arrhythmia requiring medical team intervention [Through duration of hospitalization, up to 12 weeks following admission]
Autres mesures des résultats
1. Sustained hypotension of systolic BP [Through duration of hospitalization in CCU, up to 12 weeks following admission]
2. Atrial arrhythmias requiring medical intervention [Through duration of hospitalization in CCU, up to 12 weeks following admission]
3. Need for intravenous or oral anti-arrhythmic therapy [Through duration of hospitalization in CCU, up to 12 weeks following admission]
4. Ventricular arrhythmias [Through duration of hospitalization in CCU, up to 12 weeks following admission]
5. Need for up-titration or addition of new vasopressor therapy [Through duration of hospitalization in CCU, up to 12 weeks following admission]
