The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock
- Conditions
- Septic ShockAcute Kidney Injury
- Interventions
- Registration Number
- NCT06234592
- Lead Sponsor
- King's College Hospital NHS Trust
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 45
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vasopressin Infusion Vasopressin Vasopressin infusion commenced alongside standard care vasopressor therapy (norepinephrine). Vasopressin up titrated in a protocolised manner to a target/maximum dose of 0.04 IU/min whilst noradrenaline down titrated in order to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician. Vasopressin Infusion Norepinephrine Vasopressin infusion commenced alongside standard care vasopressor therapy (norepinephrine). Vasopressin up titrated in a protocolised manner to a target/maximum dose of 0.04 IU/min whilst noradrenaline down titrated in order to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician. Norepinephrine Infusion Norepinephrine Standard care vasopressor therapy which recruited participants already receiving, titrated to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician. Angiotensin II Infusion Angiotensin II Angiotensin II infusion commenced alongside standard care vasopressor therapy (norepinephrine). Angiotensin II up titrated in a protocolised manner to a target/maximum dose of 40 ng/kg/min whilst noradrenaline down titrated in order to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician. Angiotensin II Infusion Norepinephrine Angiotensin II infusion commenced alongside standard care vasopressor therapy (norepinephrine). Angiotensin II up titrated in a protocolised manner to a target/maximum dose of 40 ng/kg/min whilst noradrenaline down titrated in order to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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
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
Trial Locations
- Locations (1)
King's College Hospital
🇬🇧London, United Kingdom