Thread by @WellingtonICU

This week's Tweetorial is by @doctorsinfuga & is on the #CENSER study published by @ATSBlueEditor last week showing early noradrenaline is associated with increased shock control by 6 hours:
atsjournals.org/doi/pdf/10.116…
#atsjournals #sepsis #vasopressors

CENSER was a phase II, randomized, double-blind, placebo-controlled clinical single center trial conducted in Bangkok during the October 2013 to March 2017

Adults aged ≥18 years who presented to the emergency room with MAP<65mmHg and suspected infection were eligible for inclusion

Exclusion criteria included shock diagnostic criteria for more than 1 hour before randomisation, acute cerebral vascular event, acute coronary syndrome, acute pulmonary oedema, status asthmaticus, active cardiac arrhythmias, & active gastrointestinal hemorrhage.

Patients were randomly assigned in a 1:1 ratio to either early noradrenaline or or placebo.

Patients who required endotracheal intubation/mechanical ventilation, renal replacement therapy and or invasive hemodynamic monitoring were transferred to ICU; other patients were admitted to the general medical ward.

The primary outcome of this study was shock control rate by 6 hours after diagnosis of sepsis with hypotension. The secondary outcomes were 28-day mortality and hospital mortality.

310 patients completed the study, 155 to each of the two groups. Median APACHE-II score: 20, MAP 56 mmHg and serum lactate level: 2.8 mmol/L. No patients in either group required mechanical ventilator or renal replacement therapy before randomisation

Median time from door-to-noradrenaline was significantly shorter in the early noradrenaline group than in the standard treatment group (93 min [IQR:72-114] vs 192 min [IQR:150-298]; P<0.001). No difference in proportion of ICU admissions.

The shock control rate by 6 hours after the initiation of resuscitation was higher in the early noradrenaline group than in the standard treatment group (76.1% vs. 48.4%; odds ratio [OR]: 3.4; 95% confidence interval [CI]: .09–5.53; P<0.001)

Individual endpoints by 6 hours: the achievement of target MAP>65 mmHg, urine output (>0.5 mL/kg) and lactate clearance (>10%) were all significantly higher in the early noradrenaline group (all P<0.05).

More patients in the early noradrenaline group who achieved all targets by 6 hours (31.0% vs. 17.4%; P=0.005) and also who achieved both target MAP and target urine output (35.5% vs. 24.5%; P=0.04).

No significant difference between groups for the total volume of intravenous fluid administered although no details were given for the type of fluids used

Mortality at 28 days was 15.5% in the early noradrenaline group and 21.9%
in the standard treatment group (relative risk [RR]: 0.79, 95%CI: 0.53-1.11; P=0.15).

Patients in the early noradrenaline group had a lower rate of cardiogenic pulmonary oedema (14.4% vs. 27.7%; P=0.004) and new-onset arrhythmia (11% vs. 20%; P=0.03).

This is a promising result, and more and larger studies are needed to confirm the findings.

Side note from @dogICUma
this is an interesting single centre study but external validity is potentially a problem here. It's also worth having a look at the recently published @REFRESH_trial pilot
link.springer.com/article/10.100…

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