Upregulation of Alpha-1 Receptors Upon Septic Shock?

Study Overview
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Brief Summary
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The hallmarks of septic shock are hypovolemia and reduced pressor response to endogenous noradrenaline. The working hypothesis is that the higher the plasma concentration of endogenous noradrenaline will be, the lower the pressor response to exogenous noradrenaline will be. This will be tested in patients presenting with septic shock, following state of the art management (including repeated assessment of vena cava diameter and compliance, and response to dynamic indices of loading) following placebo vs clonidine administration (1 mcg.kg-1.h-1 over 24 h without bolus) and administration of increasing doses of noradrenaline (1 mcg, 2 mcg, etc. up to a delta systolic blood pressure circa 25-30 mm Hg).

Official Title
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Up Regulation of Alpha-1 Receptors Upon Septic Shock ?

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Clonidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients presenting to the CCU with septic shock : SBP<90 mm Hg refractory to volume load (>30 ml.kg-1 within 6 h before inclusion) thus in need administration of noradrenaline for >1 h (0.1 mcg.kg-1.h-1 i.e. >0.5 mg.h-1/70 kg) to maintain mean BP>65 mm Hg. criteria for sepsis :temperature>38.5 or <36°C ; WBC>12 000 or <4000/ml ; tachypnea (>20 cycles par min) or mechanical ventilation ; tachycardia : >90 bpmin written informed consent by the patient or next of kin or signature by the investigators of the form emergency inclusion Exclusion Criteria: age<18 ans pregnancy mental illness making informed consent impossible Absence of consent as signed by the patient or next of kin or signature of emergency inclusion form individual without social security coverage or participating in another biomedical research Contre-indications to clonidine (uncorrected hypovolemia, sick sinus syndrom, III grade AV block) HR<70 bp/min pre-exitus

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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>saline administration over 24 h following full optimization of patient according to current guidelines | Drug: Placebo<br> <br> |
| Active Comparator: clonidine<br>clonidine 1 mcg.kg-1.h-1 over 24 h following full optimization of the patient according to current guidelines | Drug: Clonidine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in pressor response to exogenous noradrenaline | bolus of exogenous noradrenaline (1 mcg and up) are administered to the patient to evoke an increase in delta systolic blood pressure by 25-30 mm Hg. Administration of increasing dose of noradrenaline is stopped as soon as delta systolic blood pressure has reached 25-30 mm Hg. | 0 and 24 h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in heart rate response to increasing doses of dobutamine (100 mcg and up) to evoke an increase in heart rate up to 20 beats per min. |  | 0 and 24 h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pressor response, chronotropic response