Author: Dr. Collin Wulff, DO

Study Question: Does early low-dose norepinephrine improve shock control in those with sepsis with hypotension?


Mostly good buzzwords here; single center, randomized, double-blind, placebo controlled clinical trial, smallish study (310 total). The study group received a fairly low dose of norepi infusion (0.05 mcg/kg/min). The primary outcome was not great, but was as follows: shock control rate – MAP>65 plus either urine flow>0.5 ml/kg/hr x2 hours or 10% lactate clearance in 6 hours. Secondary outcomes were more patient oriented (mortality, organ failure, etc). 


 Early Standard care 
Sample size 155 155 
Time to NE admin (min) 93 192 
Shock control rate 76.1% 48.4% 
Time to shock control (hr) 4:45 6:02 
Pulmonary edema 14.4% 27.7% 
New arrhythmia  11.0% 20.0% 


This was a fairly well done study, albeit one that came from a single center outside of the US, so the external validity may be brought into attention. Otherwise groups were well matched. I found the low, nonadjustable rate of pressor to be a bit strange and not consistent with how we would typically run things. That said, a significance was found, in favor of early NE use in regards to the primary outcome. Secondary outcomes, aka the ones we care about, showed a trend towards improvement in early NE use, but this was not statistically significant. Other limitations include likelihood of unblinding, their powering study for a monitor oriented outcome, and external validity. Does their sepsis protocol differ from many places in the west? Their primary outcome was also quite weird, a lactate clearance of 10% in 6 hours is pretty minimal, and honestly feels like a change of 10% could fall within lab error for some POC machines. Nonetheless, there was a trend towards improvement in the outcomes we care about, but we have to take that with a grain of salt given the lack of significance. Is this practice changing? I might give it a try and throw on a little low dose norepinephrine if the patient looks pretty bad or has signs of end organ failure that I think is related to sepsis. I would just be careful to ensure that if this is going through a peripheral line, that the nurse was very confident in the quality of the line. It can always be stopped, and maybe it’ll expedite their recovery.  

Take away:​

This is a small study that wasn’t powered to show a significant difference in a patient oriented outcome with early use of norepinephrine, but did show a trend in that direction, and may suggest that early use of norepinephrine in sepsis with hypotension is a handy trick to keep in the back pocket.  


  • Permpikul, C. Tongyoo, S. Viarasilpa, T. Trainarongsakul, T. Chakorn, T. Udompanturak, S. 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

Leave a Reply