CMS recently produced a new sepsis measure/bundle that has many EM and critical care docs up in arms.  I’m not going to focus on their definition of sepsis (save your rage for later), but instead on the fact that their definition of resuscitative crystalloid specifies ONLY LR or NS.  So to be truly within guidelines, isolyte/plasmalyte is not allowed.  Does this matter?

First, a break-down of the composition of these resuscitative fluids:Fluids

  • Although NS is the most common crystalloid used in EDs for small volume resuscitations, there have been many studies which have supported the use of balanced salt solutions like plasmalyte and LR over NS in large volume resuscitations.  The reasons for this include:
    • Avoidance of hyperchloremic metabolic acidosis (high chloride concentrations in NS induce worsening acidosis in these hypoperfused patients)
    • Multiple cohort studies have shown hyperchloremia in these patients to be an independent predictor of death
    • Increased chloride load has been shown to increase risk for renal failure (2/2 reduced renal perfusion from afferent arterial constriction)
    • Studies in surgical patients showed greater risk for coagulopathy in NS as compared with LR (unclear pathogenesis)
  • As for isolyte/plasmalyte versus LR:
    • One prospective RCT comparing HS (similar to LR) to plasmalyte in patients undergoing liver resection showed more frequent complications in the HS group; however, this is the only study showing a difference and septic patients were not included
    • Although isolyte/plasmalyte is thought to be more alkalinizing than LR, this has been shown not to be clinically true
      • The reason behind this is that while plasmalyte’s organic anions sodium acetate and sodium gluconate metabolize to bicarbonate (for theoretically greater alkalinization), clinically, most of the sodium gluconate is excreted unchanged in the kidneys (leading to a modest osmotic diuretic effect that could potentially confuse UO as a marker of sepsis progression)
    • LR is sometimes avoided due to concerns regarding lactic acidosis; however, unless the patient has significant liver failure, accumulation of lactate is minimal and possibly beneficial as the heart and brain use lactate as fuel in ischemic conditions

So where do we stand?  The most recent RCT, SPLIT, showed no difference between plasmalyte and NS in the outcomes of AKI and in-hospital mortality; however, most patients were elective post-op, only 4% were septic, and patients received a median of 2L IVF. All in all, not sufficient to debunk all of the above support that balanced fluids (LR/plasmalyte) are superior to NS in large volume resuscitations.  As for LR v plasmalyte, further studies are needed, but it seems that LR should be sufficient (though not necessarily superior).  So, the exclusion of plasmalyte from sepsis bundles isn’t warranted, but also shouldn’t be harmful (assuming you have access to LR).


  • Marik, PE. Iatrogenic salt water drowning and the hazards of a high central venous pressure. Annals of Intensive Care 2014, 4:21.
  • Weinberg, L et al. The effects of plasmalyte-148 versus hartmann’s solution during major liver resection: a multicentre, double-blind, randomized controlled trial. Minerva Anestesiol 2014, Nov 19.
  • Young, P et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Units: The SPLIT Randomized Clinical Trial. JAMA 2015;314(16):1701-1710.