Septic Shock
Conditions
Keywords
pressor response, chronotropic response
Brief summary
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).
Interventions
DRUGClonidine
DRUGPlacebo
Sponsors
Direction Centrale du Service de Santé des Armées
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in pressor response to exogenous noradrenaline | 0 and 24 h | 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. |
Secondary
| Measure | 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 |
Countries
France
Outcome results
None listed