The Effects of Blood Pressure on Renal Function and Oxygenation in Septic Shock

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate renal effects of 3 different levels of mean arterial pressure in early case of septic shock. In 8 patients diagnosed with early septic shock, we will adjust mean arterial pressure (MAP) to three different levels, using norepinephrine. At each level of MAP, central and renal hemodynamics and oxygenation states will be measured. Analysis will be made to describe the pathophysiology at MAP 75 mmHg, and then to evaluate at which MAP renal function and oxygenation is least affected negatively.

Detailed Description
-----------------
It is under debate what level of mean arterial pressure is the most appropriate for organ perfusion in septic shock. The kidneys are usually used for end-organ evaluation of appropriate perfusion and appropriate blood pressure level. What adequate blood pressure means is today unclear. The purpose of this study is to chart the renal perfusion, oxygenation and function, and moreover to evaluate renal effects of 3 different levels of mean arterial pressure, in early phase of septic shock. Patients will be included within the first 24 hrs after admission to the ICU diagnosed with septic shock. The patients will be sedated, mechanically ventilated and in need for norepinephrine for adequate blood pressure levels. After 60 mins of steady state at MAP 75 mmHg, norepinephrine will be adjusted achieve MAP of 60 and 90 mmHg respectively, MAP being held at each level for 30 mins. At the end of each 30 mins period, central and renal hemodynamics will be measured, blood and urine samples will be collected. Central hemodynamics will be measured by, and blood samples collected via a pulmonary catheter and an arterial line. Renal hemodynamics will be measured using a renal vein catheter for retrograde thermodilution giving at hand renal blood flow (RBF), renal vein blood samples and urine collection provides extraction of Cr-EDTA for filtration fraction (FF) and glomerular filtration rate (GFR), renal oxygen consumption, and renal oxygen extraction as a measure of balance between renal oxygen delivery and consumption. Via renal vein catheterisation and retrograde thermodilution, the study group have the unique possibility to actually evaluate renal blood flow, renal oxygenation and renal function in humans in vivo. After finishing the data collection, analysis will be made to answer the question: which MAP is the most optimal concerning RBF, GFR and renal oxygenation in patients with septic shock?

Official Title
-----------------
Goal Directed Therapy in Septic Shock - the Effects of Mean Arterial Pressure Levels, Adjusted With Norepinephrine, on Renal Perfusion, Function and Oxygenation.

Conditions
-----------------
Septic Shock, Acute Kidney Injury

Intervention / Treatment
-----------------
* Other: MAP 60 mmHg
* Other: MAP 75 mmHg
* Other: MAP 90 mmHg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: stable septic shock normovolemic norepinephrine intubated/ventilated normal s-creatinine according to local laboratory regards.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 60 mmHg<br>Norepinephrine adjusted to reach MAP 60 mmHg | Other: MAP 60 mmHg<br>* Norepinephrine adjusted to reach MAP 60 mmHg<br>* Other names: Norepinephrine;|
| Active Comparator: 75 mmHg<br>Norepinephrine adjusted to reach MAP 75 mmHg | Other: MAP 75 mmHg<br>* Norepinephrine adjusted to reach MAP 75 mmHg<br>* Other names: Norepinephrine;|
| Active Comparator: 90 mmHg<br>Norepinephrine adjusted to reach MAP 90 mmHg | Other: MAP 90 mmHg<br>* Norepinephrine adjusted to reach MAP 90 mmHg<br>* Other names: Norepinephrine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular filtration rate (GFR) | Renal function, ml/min | 195 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Blood Flow (RBF) | ml/min | 195 mins | 
| Renal Oxygen consumption | ml/min | 195 mins | 
| Filtration fraction | glomerular filtration rate (GFR) to the renal plasma flow (RPF). Filtration Fraction, Ratio of GFR to renal plasma flow, % | 195 mins | 
| Renal oxygen supply/demand relationship | Renal oxygen consumption compared to renal oxygen delivery (CaO2-CrvO2/CaO2). | 195 min | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
renal blood flow, renal oxygenation, glomerular filtration rate, filtration fraction, blood pressure