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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. .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketone ester followed by placebo | Experimental |
| |
| Placebo followed by ketone ester | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketone ester | Dietary Supplement | Ketone ester: 3-hydroxybutyrate as enteral bolus (500 mg/kg) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Global longitudinal strain | Echocardiographic measure obtained from transthoracic echocardiography | From intervention to 3 hours after intervention (this is assessed for both treatment arms) |
| Measure | Description | Time Frame |
|---|---|---|
| Left ventricular ejection fraction | Echocardiographic measure obtained from transthoracic echocardiography | From intervention to 3 hours after intervention (this is assessed for both treatment arms) |
| Mean arterial pressure |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Katrine F Bernholm, MD | Contact | 0045 24909488 | katrine.feldballe.bernholm@regionh.dk |
| Name | Affiliation | Role |
|---|---|---|
| Tor Biering-Sørensen, MD, MPH, MSc, PhD | Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte | Principal Investigator |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007662 | Ketosis |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| C524675 | formic acid 4-(3-oxobutyl)phenyl ester |
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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.
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| Placebo | Dietary Supplement | Maltodextrin (isovolumic and isocaloric placebo) as enteral bolus |
|
Obtained from invasive blood pressure measurement (arterial line)
| From intervention to 3 hours after intervention (this is assessed for both treatment arms) |
| Cardiac output | Obtained from transthoracic echocardiography | From intervention to 3 hours after intervention (this is assessed for both treatment arms) |
| 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) |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |