Date: June 2nd, 2020

Reference: Permpikul et al. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER): A Randomized Trial. Respir Crit Care Med 2019.

Guest Skeptic: Dr. Max Hockstein trained as an Emergency Medicine physician at University of Texas Southwestern and is finishing his Intensive Care fellowship at Emory. Max is then going to Georgetown to be an attending in both EM and ICU.

Case: It’s another day in your emergency department (ED).  Six hours into your shift, you finish dispo’ing the “really quick sign-out” from the night before.  The triage nurse places a 61 year-old-man with fever, hypotension, cough into the smallest room in the ED.  You scan through the EMR and see the blood pressure is 60/40.  Being an astute emergency physician, you surmise that this value is one number column short of normal.  It’s uncomfortably low – is it time to start a norepinephrine infusion?

Background: I think we have covered sepsis more often than any other topic on the SGEM. It was the landmark paper published 19 years ago by Dr. Emanuel Rivers on early goal directed therapy in the treatment of severe sepsis and septic shock that sensitized the medical community (Rivers et al NEJM 2001).

* SGEM#44: Pause (Etomidate and Rapid Sequence Intubation in Sepsis)

* SGEM#69: Cry Me A River (Early Goal Directed Therapy) ProCESS Trial

* SGEM#90: Hunting High and Low (Best MAP for Sepsis Patients)

* SGEM#92: ARISE Up, ARISE Up (EGDT vs. Usual Care for Sepsis)

* SGEM#113: EGDT – ProMISe(s) ProMISe(s)

* SGEM#174: Don’t Believe the Hype – Vitamin C Cocktail for Sepsis

* SGEM#207: Ahh (Don’t) Push It – Pre-Hospital IV Antibiotics for Sepsis.

One of the goals of the early treatment of septic shock is to restore end-organ perfusion.  Significant effort has been placed on the administration of IV crystalloids to address concerns for hypovolemia in septic shock.  However, it has become evident that patients are often over-resuscitated with IV fluids which adversely impacts outcome.  As such, the idea of the early norepinephrine administration to restore end-organ perfusion in septic shock has been suggested.

Trials that examine outcomes in shock, historically, have examined two types of outcomes: patient-oriented outcomes (POOs) and monitor-oriented outcomes (MOOs).  POOs focus on occurrences that matter to patients while MOOs do not.  Many trials examining vasoactive infusions use MOOs as an endpoint(s) targeted to the medication’s intended use (i.e. increase in MAP).  Much like titrating a therapy to an outcome, MOOs are frequently easier to monitor (ex: blood pressure, heart rate, mean arterial pressure, oxygen saturation, etc).

An old adage in resuscitating the hypotensive patient “first, fill the tank” has gone largely unchallenged over the past several years.  Oddly enough, however, shortening the duration of shock time-to-shock-resolution hasn’t translated to any measurably better outcomes.

Clinical Question: Does starting norepinephrine earlier in septic shock lead to earlier shock control?

Reference: Permpikul et al.