Does LR Worsen HyperK? Not if you’re SMART about it!

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It makes sense that if you have a sick patient with hyperkalemia, you might not want to…you know..give more potassium. However, just because that “makes sense” doesn’t mean it’s right. This is the crux of the reviewed secondary analysis of the SMART trial by the crew at Vanderbilt. The SMART trial was a landmark paper that came out largely in favor of critically ill patients receiving balanced crystalloids vs. normal saline. This time around, those same investigators wanted to see if LR or Plasma-lyte worsened hyperkalemia, acute kidney injury (AKI), need for renal replacement therapy (RRT), or death (i.e. MAKE30). 

Study Design:

This retrospective secondary analysis of the SMART data-set analyzed a select subgroup of the 15,802 ICU patients from the original study. To make it into this analysis, the patients had to have hyperkalemia prior to enrollment (K >6.5mmol/L) or new/ worsening AKI from baseline. Because analysis in this way cancels out the benefit of randomization present in the original SMART study, a fair amount of sensitivity analysis was performed to correct for this. 


The number of patients fitting their definitions was pretty small (187 patients with hyperkalemia and 1,324 patients with AKI). That having been said, they had some cool findings that largely favors balanced crystalloids in these subgroups:

  • Worsening hyperkalemia: No difference between groups
  • Worsening AKI: Patients in the balanced crystalloid group had significantly less AKI than those in the normal saline group (aOR = 0.47)
  • Need for new RRT: patients in the balanced crystalloid group needed new RRT much less frequently (aOR 0.4)
  • If someone had acute-on-chronic kidney injury, their need for RRT was similarly reduced if they received balanced crystalloid rather than normal saline (aOR 0.69)


As with any posthoc analysis of a patient data set, we can’t draw conclusions about causal natures of intervention, only associations. Since the original SMART trial was not powered for this analysis nor the subgroups prespecified, it’s hard to argue this is definitive. Moreover, the initial benefit of the SMART trial was randomization in block fashion of patients getting balanced crystalloids or NS. This analysis essentially cherry-picks patients such that we lose the benefit of randomization.


Despite the limitations associated with a secondary analysis  the authors produced a pretty compelling piece of literature. The conclusions fall nicely in line with expected signal strength and reproducibility of other studies including  SMART and SALT-ED. It’s hard to imagine these data are not based in reality simply because it’s not an RCT. 

Going back to the original “conventional wisdom” of not giving hyperkalemia patients more potassium. On the surface, that makes sense, but it falls apart with some critical thinking. If you are making soup and you add  one too many bouillon cubes, the stock will be pretty salty. If you make an additional cup of stock with the right amount of bullion and add it to your soup, you won’t get a saltier taste; the soup’s overall concentration will go down. When compared to NS, , LR and Plasmalyte have none of the baggage of the damaging effects of hyperchloremia. Additionally, balanced crystalloids  also include pH buffers which mitigates acidosis and potassium shifting. 

While I would not advocate for changing practice based on this level of evidence alone, this piece certainly places another proverbial  “nail in the coffin” when it comes to normal saline. LR and/or Plasmalyte should be the fluid of choice when it comes to crystalloid resuscitation for most patients. This seems to be especially true for patients with hyperkaleima and acute kidney injury.

Reviewed Article:

Toporek AH, Semler MW, Self WH, Bernard GR, Wang L, Siew ED, Stollings JL, Wanderer JP, Rice TW, Casey JD; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults with Hyperkalemia or Acute Kidney Injury: Secondary Analysis of a Clinical Trial. Am J Respir Crit Care Med. 2021 Jan 27. doi: 10.1164/rccm.202011-4122LE. Epub ahead of print. PMID: 33503391.


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