Septic shock: early norepinephrine improves shock control in prospective CENSER

  • Permpikul C & al.
  • Am J Respir Crit Care Med
  • 1 Feb 2019

  • curated by Jenny Blair, MD
  • Clinical Essentials
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Takeaway

  • For patients with septic shock, early norepinephrine during resuscitation resulted in better short-term shock control but no improvement in mortality as a secondary outcome.
  • Larger trials are needed.

Why this matters

  • Despite promising retrospective studies, few prospective data were previously available to support this intervention. 
  • Patients randomly assigned earlier than in 3 previous studies of early goal-directed therapy (ProCESS, ARISE, and ProMISe), according to authors.

Key results

  • Median time from emergency department arrival to norepinephrine: 93 minutes.
  • Norepinephrine vs standard treatment (95% CIs):
    • Shock control: 76.1% vs 48.4%; OR, 3.4 (2.09-5.53); P<.001.>
    • 28-day mortality: 15.5% vs 21.9%; relative risk, 0.79 (0.53-1.11); P=.15.
    • No differences in respiratory failure requiring ventilator support, renal failure requiring renal replacement therapy, organ support-free days, or limb or intestinal ischemia.
  • With norepinephrine, less cardiogenic pulmonary edema, new-onset arrhythmia.

Study design

  • Single-center randomized controlled double-masked CENSER trial (n=310). 
  • Adults with sepsis and hypotension randomly assigned to early norepinephrine vs standard treatment (2012 Surviving Sepsis guidelines). 
  • Outcome: shock control at 6 hours.
  • Funding: Siriraj Critical Care Research Funding (Bangkok, Thailand).

Limitations

  • Single-center trial.
  • Fluid rates were not controlled.
  • Primary outcome was not patient-centered.
  • Many patients had to be managed on the ward, not the ICU.

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