early administration of norepinephrine in sepsis

Conditions: Sepsis, Severe

Summary: the management of septic states includes, in addition to the specific treatment (antimicrobials and eradication of the source), a restoration of the hemodynamic disorders and assistance of the failing organs. in general, the restoration of hemodynamic disorders begins first with volume expansion, followed by the use of noepinephrine (ne) when the target mean arterial pressure (map) is not reached after optimizing the intravascular volume. recently, several studies have supported the interest of early ne on map, cardiac output and mortality. it is therefore tempting to restrict fluid administration even in the initial phase of hemodynamic management of severe sepsis by starting ne earlier.

sepsis is characterized by systemic inflammation induced by a severe infection resulting in an inappropriate host response against that infection. on the microcirculatory scale, vasoplegia with capillary leakage is distinguished. management of sepsis includes, in addition to specific treatment which includes antimicrobials and eradication of the source, restoration of hemodynamic disorders and assistance to failing organs. in general, the restoration of hemodynamic disorders begins first with volume expansion, followed by the use of vasopressors (mainly norepinephrine: ne as first-line therapy) when the mean arterial pressure target (map: reflecting the perfusion pressure organs) is not reached after optimizing the intravascular volume. recently, several studies have supported the benefit of administering ne at the start of resuscitation of sepsis. indeed, its administration at an earlier phase than usually recommended improved map and cardiac output with a favorable effect on mortality. at a median interval of 1.3 hours from icu admission and exclusive administration of ne, map was adequately restored within a relatively short time (30 min) and was associated with a better survival rate than that predicted by the severity scores of similar patients from other series reported in the literature. in the recent thai "censer" trial, shock was controlled in 76% of patients in the early ne group versus 48% (p\<0.001). on the other hand, the administration of a large quantity of fluids inevitably increases the risk of fluid overload, which is a frequent complication in septic patients. in front of all these arguments, it is therefore tempting to restrict fluid administration even to the initial phase of the hemodynamic management of sepsis by starting ne earlier.

Eligibility criteria:
inclusion criteria: * age 18 or older. * the patient or his/her legal representative has given informed consent in writing. * diagnosis of sepsis according to the definitions updated by the consensus of sepsis 3. * mean arterial pressure \< 65 mmhg exclusion criteria: * diagnosis of septic shock prior to randomization (where na requirements exceed those of the trial protocol) * pregnancy, * need for immediate surgery, * neoplasia at an advanced stage * circumstances where water restriction is the rule: * acute pulmonary edema * acute coronary syndrome,

Keywords: sepsis septic shock norepinephrine volume expansion mortality