Upregulation of Alpha-1 Receptors Upon Septic Shock?

Phase 3TerminatedNCT01856517

Direction Centrale du Service de Santé des Armées40 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

TRIPLE

Enrollment

Conditions

Septic Shock

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 0 and 24 h

Secondary Outcomes

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.