Acute Kidney Injury, Septic Shock
Conditions
Brief summary
Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock.
Interventions
DRUGAngiotensin II
Angiotensin II infusion
DRUGVasopressin
Vasopressin infusion
DRUGNorepinephrine
Standard care vasopressor therapy, norepinephrine infusion
Sponsors
European Society of Intensive Care Medicine
Royal Centre for Defence Medicine
King's College Hospital NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Within 48 hours of intensive care admission * Evidence of suspected or confirmed infection * Sequential Organ Failure (SOFA) score increase of 2 or more (assuming a baseline of 0 if no previous measures) * Requirement for norepinephrine infusion as the sole vasopressor agent in a dose of \>0.1mcg/kg/min * Lactate \>2mmol/L at any stage prior to randomisation
Exclusion criteria
* Known intolerance to Sonovue™ contrast medium, vasopressin or angiotensin II * Patients receiving other vasoactive drugs in addition to norepinephrine * Patients with known chronic kidney disease (CKD) stage 4 or 5 (baseline glomerular filtration rate (GFR) \<30mls/min) * Patients receiving extra corporal membrane oxygenation (ECMO) * Patients with acute occlusive coronary syndromes requiring intervention * Patients with mesenteric ischaemia * Patients with a history or presence of aortic dissection or abdominal aortic aneurysm * Patients with Raynaud's syndrome or acute vaso-occlusive conditions * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cortical mean transit time (mTT) measured in seconds | Measured at +24 hours following study vasopressor infusion starting | Contrast enhanced ultrasound measure of renal cortical tissue blood flow |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cortical perfusion index (PI) measured in arbitrary units | Measured at +1 hour and +24 hours following study vasopressor infusion starting | Contrast enhanced ultrasound measures of renal cortical tissue blood flow |
| Cortical wash in rate (WiR) measured in arbitrary units | Measured at +1 hour and +24 hours following study vasopressor infusion starting | Contrast enhanced ultrasound measures of renal cortical tissue blood flow |
| Urinary oxygen tension (pO2) across 24 hours study period measured in millimetres of mercury (mmHg) | Across 24 hours study period | Mean urinary pO2 |
| Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7). Both measured in nanograms per millilitre (ng/ml) | Measured at baseline and +24 hours following study vasopressor infusion starting | Biomarker analysis - regulatory proteins involved in initiating cell cycle arrest and associated with AKI |
| Cortical mean transit time (mTT) measured in seconds | Measured at +1 hour and +24 hours following study vasopressor infusion starting | Contrast enhanced ultrasound measures of renal cortical tissue blood flow |
Other
| Measure | Time frame | Description |
|---|---|---|
| Syndecan 1, angiopoietin 1 & 2, Interleukin 6 & 8 (IL-6, IL-8) and tissue necrosis factor (TNF). All measured in nanograms per millilitre (ng/ml) | Measured at baseline and +24 hours following study vasopressor infusion starting | Biomarker analysis - markers of inflammation and endothelial activation/function |
| Microvascular flow index (MFI) (unitless score from 0 to 3 where 3 is the value see in health). | Measured at +1 hour and +24 hours following study vasopressor infusion starting | Incident dark field video microscopy measures of the systemic microcirculation |
| Perfused vessel density (PVD) measured in millimetres per square millimetre | Measured at +1 hour and +24 hours following study vasopressor infusion starting | Incident dark field video microscopy measures of the systemic microcirculation |
Countries
United Kingdom
Contacts
Primary ContactSam Hutchings
Outcome results
None listed