Effect of Hydrocortison on Post-ischemic Flow-mediated Dilation and on Thenar Oxygen Saturation in Human Septic Shock.

Study Overview
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Brief Summary
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The main objectives of the study are 1)to examine the immediate (2 hours) and delayed (8 hours) effects of intravenous hydrocortison on macro and microvascular post-ischemic vasoreactivity, in septic shock adult patients; 2) to examine possible correlations between post-ischemic flow-mediated dilation (FMD) of the brachial artery (assessed by ultrasound imaging) and post-ischemic recovery slope of the thenar oxygen saturation (StO2) (assessed by near-infrared spectroscopy).

Detailed Description
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Two primary end points, considered as reflecting vasoreactivity will be assessed : Flow-mediated dilation (FMD) of the brachial artery, measured by ultrasound imaging, expressed in mm or in percentage, will be calculated from artery diameters measured before and after a vascular occlusion test (cuff around arm or forearm). recovery slope of thenar oxygen saturation (StO2), assessed by near infrared spectroscopy (NIRS), expressed in %/second, will be recorded after the vascular occlusion test. The two primary end points (FMD and recovery slope of StO2)will be assessed at the following timepoints : baseline (before first injection of placebo or hydrocortison) 2 hours after first injection of placebo or hydrocortison 2 hours after second injection of placebo or hydrocortison (i.e. 8 hours after first injection) 4 to 6 hours after third injection 4 to 6 hours after fourth injection (optional)

Official Title
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Effect of Intravenous Hydrocortison on Post-ischemic Brachial Artery Dilation and on Thenar Oxygen Saturation in Adult Septic Shock. A Human Placebo-controlled Randomized Study.

Conditions
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Septic Shock, Adult

Intervention / Treatment
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* Drug: hydrocortison hemisuccinate
* Drug: placebo followed by hydrocortisone hemisuccinate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age over 18 yrs consent obtained septic shock (according to international definition) patient sedated and submitted to invasive mechanical ventilation no need for surgery expected within 24 hours after enrollment patient has received at least one dose of large spectrum antibiotics superior vena cava catheter in place patient carrying a thermodilution device for cardiac output measurement stable mean arterial pressure within 65-5 mmHg limits for at least 2 hours; Exclusion Criteria: pregnancy age below 18 years patient treated with iv continuous epinephrine chronic occlusive arteriopathy of the upper limbs regular or recent treatment with glibenclamide or glipizide regular or recent treatment with steroids known surrenal insufficiency

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>10 mL normal saline iv at H0 and H6 (2 first injections blinded), followed by hydrocortison (open label) 50 mg iv at H8, H14 and H20 | Drug: placebo followed by hydrocortisone hemisuccinate<br> <br> |
| Active Comparator: hydrocortison<br>50 mg hydrocortison iv at H0 and H6 (2 first injections blinded), followed by hydrocortison (open label) 50 mg iv at H12, H18 and H24 | Drug: hydrocortison hemisuccinate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasoreactivity |  | every 6 hours over the first 24 hours of intervention |