Sepsis Induced Cardiomyopathy
Conditions
Keywords
Sepsis induced cardiomyopathy, Sepsis, Hemodynamics, Ketone ester, Ketones, Echocardiography, Randomized controlled trial, Cross-over trial, Cardiovascular
Brief summary
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with a high mortality rate in the ICU. Sepsis induced cardiomyopathy (SICM) is a multi-factorial process that appears in approximately 50% of patients with sepsis/septic shock and is associated with increased mortality. It is suggested that ketone bodies are more efficient substrates of energy metabolism than glucose, with a lower oxygen consumption per ATP-molecule produced and that the failing human heart increases the capacity to metabolize ketones. Previous studies have found acute beneficial hemodynamic effects of ketone esters in patients with chronic heart failure and cardiogenic shock, respectively. Improved hemodynamics and reduced systemic oxygen consumption as an effect of ketone esters might be of great benefit in patients admitted to the ICU. Thus, the investigators aim to investigate the hemodynamic effects of ketone esters in patients with sepsis induced cardiomyopathy in this randomized, placebo-controlled, double-blinded, cross-over, acute intervention study. .
Interventions
DIETARY_SUPPLEMENTKetone ester
Ketone ester: 3-hydroxybutyrate as enteral bolus (500 mg/kg)
DIETARY_SUPPLEMENTPlacebo
Maltodextrin (isovolumic and isocaloric placebo) as enteral bolus
Sponsors
Tor Biering-Sørensen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
As this is a cross-over trial participants will receive both active treatment and placebo. Participants will be randomized 1:1 to receive A) active treatment followed by placebo or B) placebo followed by active treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years of age admitted to the the intensive care unit (ICU) * LVEF \< 50% determined by a screening echocardiography and analysed according to the Simpson biplane method * Ability for study personnel to perform transthoracic echocardiography * Suspected or documented infection (suspected infection is defined as ongoing antibiotic treatment and/or body fluid culture sampling performed within 72 hours before screening)
Exclusion criteria
* Diagnosis of heart failure with reduced ejection fraction prior to ICU admission according to health records * Surgical cause of ICU admission * For patients in shock: Other primary causes of shock than sepsis (i.e. hypovolemia, haemorrhage, cardiogenic etiology, pulmonary embolism, anaphylaxis) * Blood pH \< 7.20 * Severe gastroparesis * Inability to position a nasogastric tube
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global longitudinal strain | From intervention to 3 hours after intervention (this is assessed for both treatment arms) | Echocardiographic measure obtained from transthoracic echocardiography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular ejection fraction | From intervention to 3 hours after intervention (this is assessed for both treatment arms) | Echocardiographic measure obtained from transthoracic echocardiography |
| Mean arterial pressure | From intervention to 3 hours after intervention (this is assessed for both treatment arms) | Obtained from invasive blood pressure measurement (arterial line) |
| Cardiac output | From intervention to 3 hours after intervention (this is assessed for both treatment arms) | Obtained from transthoracic echocardiography |
| Peripheral blood oxygen saturation | From intervention to 3 hours after intervention (this is assessed for both treatment arms) | — |
| Arterial blood pH | From intervention to 3 hours after intervention (this is assessed for both treatment arms) | — |
| Arterial blood lactate | From intervention to 3 hours after intervention (this is assessed for both treatment arms) | — |
| Accumulated norepinephrine | From intervention to 3 hours after intervention (this is assessed for both treatment arms) | — |
Contacts
CONTACTKatrine F Bernholm, MD
PRINCIPAL_INVESTIGATORTor Biering-Sørensen, MD, MPH, MSc, PhD
Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
Outcome results
None listed