It's a typical day in the ED.  You are asked to see your next patient who is a 60 year old male, recently discharged from the hospital after being treated for cellulitis presenting with abdominal pain and diarrhea.  He’s tachycardic and hypotensive to 75/40.  The patient is mentating well.  After taking a more thorough history your differential diagnosis narrows in on intra-abdominal sepsis associated with significant volume losses.  The lactate returns at 6.  On volume assessment by physical exam and POCUS, the patient is significantly volume down.  You know that getting the antibiotics and fluids on board is the cornerstone of treatment, but they will take some time to be given.  You wonder if you should temporize your resuscitation with pressors during the time it takes for the fluids and antibiotics to be administered.

When to give fluids and when to give pressors has been an age old debate.  It used to be thought that all doses of pressors required a central line. So, in addition to considering appropriate physiologic management, the physician was also confronted with the logistical issue of placing the line.  Recent research has demonstrated that low to moderate dose pressors can be safely administered via peripheral IVs when placed with the intention of minimizing the extravasation risk.  Using peripheral vasopressors is best done in the setting of an institutional protocol to ensure patient safety and clinician comfort across disciplines.  

In parallel to the research examining peripherally administered vasopressors, a series of studies emerged showing that earlier administration of vasopressors (typically norepinephrine) is associated with improvements in mortality and, secondarily, reduced time to achieve mean arterial pressure targets as well as reduced total volume of fluids given.  This includes a single center randomized controlled trial that evaluated norepinephrine given at the same time as crystalloids versus norepinephrine given only after the patient has completed an initial fluid bolus and failed to achieve goals1.

A recent meta-analysis of RCTs of early versus late pressors has been published and affirmed the individual study findings of improved mortality when pressors are given earlier in conjunction with fluids rather than later after failure of fluids or due to persistent hypotension2.  Each individual study included was limited by their single center nature as well as being unblinded to the treating team.  That being said, the overarching signal is that mitigating hypotension with the early use of pressors, even in the setting of hypovolemia, can result in improved outcomes.

References:

1. Elbouhy MA, Soliman M, Gaber A, Taema KM, Abdel-Aziz A. Early Use of Norepinephrine Improves Survival in Septic Shock: Earlier than Early. Arch Med Res. 2019;50(6):325-332. doi:10.1016/j.arcmed.2019.10.003

2. Li Y, Li H, Zhang D. Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis. Critical Care. 2020;24(1). doi:10.1186/s13054-020-03204-x