CENSER
Trial question
What is the role of early use of norepinephrine in patients with septic shock?
Study design
Single center
Double blinded
RCT
Population
Characteristics of study participants
52.0% female
48.0% male
N = 310
310 patients (162 female, 148 male).
Inclusion criteria: adult patients diagnosed with sepsis with hypotension.
Key exclusion criteria: septic shock diagnostic criteria for > 1 hour before randomization, acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, active gastrointestinal hemorrhage.
Interventions
N=155 early norepinephrine (infusion of a dose of 0.05 mcg/kg/min of body weight plus fluid resuscitation).
N=155 placebo (5% dextrose in water plus standard treatment).
Primary outcome
Shock control rate by 6 hours after initiation of resuscitation
76.1%
48.4%
76.1 %
57.1 %
38.0 %
19.0 %
0.0 %
Early
norepinephrine
Placebo
Significant
increase ▲
NNT = 3
Significant increase in shock control rate by 6 hours after initiation of resuscitation (76.1% vs. 48.4%; OR 3.4, 95% CI 2.09 to 5.53).
Secondary outcomes
No significant difference in the rate of death by day 28 (15.5% vs. 21.9%; RR 0.79, 95% CI 0.53 to 1.11).
No significant difference in hospital death (22.6% vs. 24.5%; RR 0.95, 95% CI 0.72 to 1.24).
Significant increase in achievement of target mean arterial BP by 6 hours (86.5% vs. 67.1%; RR 3.13, 95% CI 1.77 to 5.53).
Safety outcomes
No significant differences in limb ischemia, intestinal ischemia, ARDS, hospital-acquired infection, upper gastrointestinal hemorrhage, skin necrosis.
Significant differences in cardiogenic pulmonary edema (14.4% vs. 27.7%), new-onset arrhythmia (11% vs. 20%).
Conclusion
In adult patients diagnosed with sepsis with hypotension, early norepinephrine was superior to placebo with respect to shock control rate by 6 hours after initiation of resuscitation.
Reference
Chairat Permpikul, Surat Tongyoo, Tanuwong Viarasilpa et al. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1097-1105.
Open reference URL