Personalized Mean Arterial Pressure Management on Renal Function During Septic Shock (DORESEP)

• Need for renal replacement therapy [ Time Frame: during hospitalization ] [ Designated as safety issue: Yes ]
  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.
• All cause mortality [ Time Frame: at 28 days ] [ Designated as safety issue: Yes ]
  All Cause mortality at 28 days, including refractory shock, refractory hypoxia, multiple organ failure, decisions to forgo life-sustaining therapies (DFLSTs)

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.

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 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 decreaseRI. Thus, we propose to include in the early hemodynamic management of septic shock, an adaptation of the level of MAP according to the RI evaluated by renal Doppler and to evaluate whether this strategy will prevent the occurrence of sepsis-associated AKI. After completing the recommended level of MAP, the dose of norepinephrine will be adjusted to obtain an IR ≤ 0.70. Improved renal hemodynamics by increasing mean arterial pressure being guided by the criteria of renal perfusion will prevent the sepsis-associated AKI.

Main objective: to measure the effects of increasing mean arterial pressure according to renl doppler on renal function in septic shockDesign: prospective, randomized, open-label studyPatients: 60 patients with a diagnosis of septic shock Interventions: 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 (control group, n=30), mean arterial pressure will be maintained at 65 mm Hg. In the second group (study group, n=30), the renal resistivity index (RI) will be determined with renal doppler in patients. If RI is greater than 0.70, mean arterial pressure will be increased to 80 mm Hg for 72 hours by increasing the dose of norepinephrine in patients. If RI is less or equal to à.70, then mean arterial pressure will be maintained at 65 mm Hg.

Participants will be followed for the duration of hospital stay, an expected average of 5 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

• Septic Shock
• Acute Kidney Injury

• Other: Haemodynamic management
  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 (control group, n=30), mean arterial pressure will be maintained at 65 mm Hg.
• Other: Haemodynamic management
  In the second group (study group, n=30), the renal resistivity index (RI) will be determined with renal doppler in patients. If RI is greater than 0.70, mean arterial pressure will be increased to 80 mm Hg for 72 hours by increasing the dose of norepinephrine in patients. If RI is less or equal to à.70, then mean arterial pressure will be maintained at 65 mm Hg.

• Experimental: Test group

  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.

  The renal resistivity index (RI) will be determined with renal doppler in patients.

  If RI is greater than 0.70, mean arterial pressure will be increased to 80 mm Hg for 72 hours by increasing the dose of norepinephrine in patients. If RI is less or equal to à.70, then mean arterial pressure will be maintained at 65 mm Hg.Key details, e.g., for drugs include dosage form, dosage, frequency and duration.

  Intervention: Other: Haemodynamic management
• Active Comparator: Control group
  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 (n=30), mean arterial pressure will be maintained at 65 mm Hg.
  Intervention: Other: Haemodynamic management

Inclusion Criteria:

• Any patient with septic shock in intensive care may be included in the next 6 to 16h
• Age > 18 years old

Exclusion Criteria:

• Chronic renal failure (Baseline serum creatinine > 120 mmol/L)
• Chronic cardiac failure (Left ventricle ejection fraction < 40%)
• Pregnancy