Lets talk about fluid resuscitation and what is the best type of fluid to resuscitate with: LR vs NS vs Plasma-Lyte A. To understand the questions it is helpful to know that LR and Plasma-Lyte and Normisol are all called balanced fluids.  This is going to get deep, so hold on.

This is actually a big question and has been looked at with a number of large studies and in a number of settings. Some studies look at ER patients going home, others at admitted regular old floor patients and other studies at patients in the medical ICU and they found . . .  (feel free to skip to the end if your not feeling especially geeky today)

First lets talk about why this makes med geeks and nephrologist excited.  The normal electrolytes values for the major components of blood are around the following:

Sodium 140 mEq/L
Chloride 100 mEq/L
potassium 4 mEq/L
Ca 10 mEq/L
pH of about 7.40
Serum Osmolality 295

And when we give Normal Saline we give the following:

Na 154 mEq/L
Cl 154 mEq/L
Ca 0 mEq/L
K 0 mEq/L
pH 5.5
Osmolality 308


Everyone loves Lactated Ringers and it is composed of the following:

Na 130 mEq/L
Cl 109 mEq/L
K 4 mEq/L
Ca 3 mEq/L
pH 6.5
Osmolality 272
Bicarb 28 meq/L
And some lactate is thrown in too.

Let’s look at some of the components of LR and see if they make sense.

What about that potassium? I have definitely thought twice about giving LR to a patient with an elevated K, because it contains potassium. That is probably the wrong way to look at it.  First, 4 meq/L is less concentrated than the 6 meq/L a patient I was worried about hyper-K in would have, so LR should dilute the K not raise it.

Second, and more important, is that most of the potassium in the body is intracellular, and the quickest way to raise the serum potassium is to induce acidosis. Think of potassium and hydrogen ions (particles of acid) as exchangeable currency, like putting a dollar into the change machine at the arcade and getting back quarters. If you have a lot of hydrogen ions in fluid (like NS), the cells are going to take those H+ into the cell and spit potassium out of the cell. This raises the extracellular potassium; that is the key process we should consider when we think about fluids. Normal saline is waaaay more acidic than LR. Studies have shown that NS generally raises the serum potassium in sick patients and LR does not.

Lactate: Don’t we measure lactate to see how sick a sepsis patient is? Why would we give more of that? It turns out that lactate isn’t bad stuff.  In-fact lactate is a potent energy source for the heart and the brain; when the body is under stress lactate acts as a special fuel. Giving more of that fuel (lactate) should not be a problem and it has not been the in studies that looked at giving LR to sepsis patients.

Cost: They are close to equivalent, probably <1$ more per per liter of LR.

Does any of this matter? It depends on how sick the patient is.

ICU Patients:

There was a recent trial called the SMART trail (I’ll spare you the full study name), where they took around 16K patients—all comers to the Vanderbuildt ICUs (medical/trauma/neurologic/cardiovascular/surgical)—and found an insignificant mortality benefit and significantly less renal complications in patients who received balanced fluids for their resuscitation.  RIght off the bat, this was not that informative.

It took a subgroup analysis of the SMART Trial to see that SEPTIC patients benefited more than other patients from balanced fluids. The subgroup of septic patients included 1,641 people and the in-hospital mortality rate was 26.3% in the balanced crystalloids group and  31.2% in the normal saline group. That was a significant decrease.

Two other recent studies supported the use of balanced solutions in resuscitation of the sickest of patients. A 2015 study from the anesthesia literature demonstrated a reduced risk of mortality when balanced solutions were used for sepsis resuscitation in ICU patients. (They also interesting found that mortality went up when colloids (albumin) was used as part of a resuscitation.) Another small ER based study also found a mortality benefit when balanced solutions resuscitated septic patients.

This is all in contrast to the most recent Cochran review on the same subject for critically ill patients. That review found STRONG evidence of no mortality benefit from a balanced fluid resuscitation. With that said, the math pointed toward a possible mortality benefit, where balanced solutions could “reduce mortality by 21 per 1000 or could increase mortality by 1 per 1000.” To me that appears to be very close to significant, and I think this will probably be flipped by these recent studies.

$$$: for the CRITICALLY ILL patient it appears that there may be a mortality benefit to using balanced solutions for resuscitation.

General Hospitalized Patients: SMART, SALT, SPLIT trials—>these guys come up with cool names for their studies

Another 2019 study looked at Normisol (a different balanced solution) vs NS in resuscitation for all-comers with sepsis being admitted the the hospital (floor and ICU). This study found no difference in any major outcomes—mortality, renal injury, ICU days. This was similar to the SPLIT and SALT trials which explored the same questions. In these studies renal injury had different definitions, but when they looked at a 200% increase in creatinine, the balanced solutions had some protective effect, but there was no change in the number of people needing renal replacement therapy (RRT/dialysis).

Finally, the SMART trial had an arm for non-critically ill-patients. They did this lame combination of factors and reported that balanced solutions “did result in a lower incidence of the composite of death, new renal-replacement therapy, and persistent renal dysfunction.” In reality mortality was about the same, and RRT was higher but they didn’t report confidence intervals to show if that was significant (even in the appendix), so the sentence should have been, “there was less of a bump in creatinine in the patients who received balanced solutions, and we will make the information about the meaningful endpoints supper-fuzzy so the data looks good.”


Walking Well:
This leaves the cohort of patient who will likely go home. Studies on these patients have shown that no matter which solution you pick patients report similar improvement, have similar rates of bounce back and pick up their other prescriptions at similar rates.


. . . TAKE HOME POINT: If the patient has significant acidosis, hyperkalemia or is critically ill, resuscitating them with a balanced solution (LR, Normisol, Plasma-Lyte A) probably has a mortality benefit.  USE BALANCED SOLUTIONS FOR YOUR SICK-SICK PATIENTS.

For all other patients there is no evidence that the choice of IVF makes a real difference. There is a lot of data on this, so it likely really doesn’t matter what you choose.

I general resus with LR if your patient is sick-sick and NS if they are going home. If they are coming into the floor—>dealers choice.



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