The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock

King's College Hospital NHS Trust45 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Enrollment

Conditions

Septic Shock Acute Kidney Injury

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Cortical mean transit time (mTT) measured in seconds

Contrast enhanced ultrasound measure of renal cortical tissue blood flow

Time frame: Measured at +24 hours following study vasopressor infusion starting

Secondary Outcomes

Cortical mean transit time (mTT) measured in seconds

Contrast enhanced ultrasound measures of renal cortical tissue blood flow

Time frame: Measured at +1 hour and +24 hours following study vasopressor infusion starting

Cortical perfusion index (PI) measured in arbitrary units

Contrast enhanced ultrasound measures of renal cortical tissue blood flow

Time frame: Measured at +1 hour and +24 hours following study vasopressor infusion starting

Cortical wash in rate (WiR) measured in arbitrary units

Contrast enhanced ultrasound measures of renal cortical tissue blood flow

Time frame: Measured at +1 hour and +24 hours following study vasopressor infusion starting

Urinary oxygen tension (pO2) across 24 hours study period measured in millimetres of mercury (mmHg)

Mean urinary pO2

Time frame: Across 24 hours study period

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)

Biomarker analysis - regulatory proteins involved in initiating cell cycle arrest and associated with AKI

Time frame: Measured at baseline and +24 hours following study vasopressor infusion starting

The Effect of Vasopressor Therapy on Renal Perfusion in Septic Shock

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts