Personalized Mean Arterial Pressure Management on Renal Function During Septic Shock

Study Overview
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Brief Summary
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Sepsis is the most severe complication of infections. Sepsis-associated Acute kidney injury (AKI) is commonly encountered in critically ill patients and independently predicts poor outcome. Unfortunately, no drug or management strategy was able to reduce incidence of AKI. To adapt the level of mean arterial pressure according to local renal hemodynamic evaluated by renal Doppler could lead to a better renal perfusion, and then less AKI.

Detailed Description
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Acute Kidney Injury (AKI) is a frequent and serious complication of sepsis. Renal ischemia plays a major role in the pathophysiology of sepsis-associated AKI. There is currently no treatment to prevent or to treat AKI. It has been shown that a resistivity index (RI) greater than 0.74 of patients with septic shock could predict the occurrence of renal failure, and that increase mean arterial pressure (MAP) with norepinephrine could decrease RI. Hence, we propose to compare the frequency and the severity of the sepsis-associated AKI according to the early hemodynamic management of septic shock. Patients will be randomized in a classic group (MAP 65 mmHg) and an interventional group (MAP 85 mmHg). We can thus determine whether the level of MAP influences renal function, and whether this influence of MAP is dependent of renal perfusion assessed by renal Doppler. Participants will be followed for the duration of hospital stay, an expected average of 4 weeks. Primary endpoint: -Presence and severity of sepsis-associated AKI at day 7. Secondary endpoints: Acute renal failure measured by Classification AKI at day 28. Acute renal failure as measured by the RIFLE classification in the fourth to seventh day and 28th day. Use of renal replacement therapy during hospitalization in intensive care unit Mortality at day 28 Duration of study: Recruitment: 10 months, the patient monitoring: 28 days ± 3 days, total test duration: 11 months

Official Title
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Personalized Haemodynamic Management of Septic Shock: Influence of Mean Arterial Pressure Level on Renal Function: Randomized Controlled Trial

Conditions
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Septic Shock, Acute Kidney Injury

Intervention / Treatment
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* Other: Haemodynamic management
* Other: Haemodynamic management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient with septic shock may be included in the next 6 to 16h Age > 18 years old and <= 80 years Exclusion Criteria: Chronic renal failure (Baseline serum creatinine > 120 mmol/L) Chronic cardiac failure (Left ventricle ejection fraction < 40%) Pregnancy Urinary Tract Infection Patients with a left ventricular dysfunction ( ventricular ejection fraction <40%)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group<br>Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In the first group (study group, n=30), mean arterial pressure will be increased to 85 mm Hg for 72 hours by increasing the dose of norepinephrine in patients (A maximum dose of 1.2 mcg / kg / min is not exceeded). Key details, e.g., for drugs include dosage form, dosage, frequency and duration. | Other: Haemodynamic management<br>* Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In this group (control group, n=30), mean arterial pressure will be maintained at 65 mm Hg.<br>|
| Active Comparator: Control group<br>Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In this group (control group, n=30), mean arterial pressure will be maintained at 65 mm Hg. | Other: Haemodynamic management<br>* Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In the first group (study group, n=30), mean arterial pressure will be increased to 85 mm Hg for 72 hours by increasing the dose of norepinephrine in patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute kidney injury according to RIFLE score |  | at 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for renal replacement therapy | including metabolic indications (Azotemia Serum urea ≥ 36mmol/L (100 mg/dL) ; Uremic complications : encephalopathy, pericarditis, bleeding ; Hyperkalemia K+ ≥ 6 mmol/L and/or electrocardiogram abnormalities ; Hypermagnesemia ≥4 mmol/L and/or anuria/absent deep tendon reflexes ; Acidosis Serum pH ≤ 7.15), Oligo-anuria Urine output <200mL/12 h or anuria, Fluid overload like Diuretic-resistant organ edema in the presence of acute kidney injury. | during hospitalization | 
| All cause mortality | All Cause mortality at 28 days, including refractory shock, refractory hypoxia, multiple organ failure, decisions to forgo life-sustaining therapies (DFLSTs) | at 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Acute kidney injury, Mean arterial pressure, Catecholamines, Renal doppler