Crystalloids therapy

Crystalloids used in hospital commonly are

  1. Normal saline
  2. Lactated Ringer or Hartmann’s solution which is very similar (though not identical)

Contents of different fluids:

1L of Hartmann’s solution contains:

  • 131 mEq of sodium ion = 131 mmol/L.
  • 111 mEq of chloride ion = 111 mmol/L.
  • 29 mEq of lactate = 29 mmol/L.
  • 5 mEq of potassium ion = 5 mmol/L.
  • 4 mEq of calcium ion = 2 mmol/L.
  • 0 mEq of magnesium ion = 0 mmol/L

What’s the osmolality of each crystalloid?

  • NS = 154 + 154 = 308 mOsm/L
  • LR = 130 + 109 + 28 + 4 + 1.5 (3 mEq/L of calcium = 1.5 mmol/L of calcium) = 272.5 mOsm/L
  • HS = 131 + 111 + 29 + 5 + 2 = 278 mOsm/L

The normal osmolality of our body is about 285-295 mOsm/L, so three of those crystalloids can be considered isotonic solutions. Among three of these, NS is most commonly used in ED, while LR/HS is usually reserved in surgical patients.

Ok, so all those crystalloids are the same? Not so….

Before starting the whole discussion, we need to consider Stewart’s approach to acid base:

  • To simplify it, Stewart proposed that H+ and HCO3- concentrations are affected by concentrations of the other ions in solution.
  • H+ and HCO3- are only dependant variables. They are dependant on many independant variables, namely SID, Atot and PCO2.
  • Body has to stay neutral in its charges. So an increase in anions eg CL- will result in an increase of cations eg H+ to make the body stay neutral. Therefore, there is acidosis.

To talk about the difference between crystalloids, we need to talk about SID and weak acids:
SID (Strong Ion Difference)

  • [SID] = [Na+] + [K+] + [Ca2+] + [MG2+] – [CL-] – [Other Strong Anions].
  • Normal SID that we have to consider = Na+ – CL- = 140 – 102 = 38 mEq/L
  • SID of NS = 154 – 154 = 0
  • SID of HS = 131 – 111 = 20
  • SID of LR = 130 – 109 = 21

Weak acids (A-)

  • Atot = [phosphate] + [protein] + [albumin]

Remember that our body is neutral to slightly alkalotic (normal pH of body = 7.4) with a high SID of 38.

  • Infusion of NS will reduce the SID (by increasing CL- which leads to more H+), which easily overwhelms the concurrent alkalosis induced by a reduction in Atot due to dilution.**
    – Not only NS, but using dextrose solution or only pure water with 0 SID would decrease the pH and leads to dilutional acidosis.
  • We need around 24-28 extra anions to account for the weak acids present (“balanced fluid”)
    – RL and LR have SID of around 20, so they can be considered to be balanced fluids.

** You may ask, doesn’t the SID stay the same because you are increasing BOTH Na+ and CL- simultaneously?

  • When you give NaCl to a patient, NaCl + H2O -> NaOH + HCl
  • Normally, these both will cancel out each other.
  • However, because the normal level of Na and CL in body is 140 and 102 respectively,  infusion of NS will increase Cl a lot more than Na.

So we can see that NS is NOT a neutral solution, it is an isotonic and acidic crystalloid. Infusion of NS can often lead to NAGMA (non-anion gap metabolic acidosis)

Is NAGMA clinically significant?

  • Pathophysiologically, increased Cl load will activate macula densa and causes vasoconstriction in afferent arterioles. This causes a reduced renal blood flow and possibly will lead to AKI.
  • However, infusion of small amount of NS (1-2L) seems to be okay according to SPLIT trial. However, SPLIT trial studied patients with low risk of AKI so it remains to be seen whether patients with high risk (eg sepsis and DKA) which often need a large volume of NS will have worse clinical outcome due to NAGMA.
  • Yunos 2012 performed an open-label prospective study evaluating the effect of a restricting the use of chloride-rich fluids among critically ill patients. Implementation of a chloride-restrictive strategy reduced the incidence of renal failure and the need for dialysis.

Treatment of NS induced NAGMA

  • Animal studies show that total bicarbonate level is actually increases during rapid volume expansion and that a decrease in lab value is due to a decrease in concentration (= not true deficit).
  • pH will normalize if infusion is stopped and body is able to get rid of that extra water and restores the normal extracellular concentration of bicarbonate.
  • In the presence of sepsis and DKA, lactate (sepsis) and ketoacids (DKA) will be metabolized in liver to generate bicarbonate. During the recovery period, there will be a loss of lactate and ketoacids via kidney, and there will be a deficiency of HCO3 precursor. And now, there is an excess of chloride to bicarbonate therefore contributing to NAGMA.
  • So is there a role of bicarbonate? I think yes but need to remember that bicarbonate is NOT deficient, it maybe increased even but it’s just that chloride increase is more than bicarbonate increase.

To understand acid base, I refer you to this excellent lecture on EMcrit


  2. Donald D. Mathes, MD; Robert C. Morell, MD; Michael S. Rohr, MD, PhD. Dilutional Acidosis: Is It a Real Clinical Entity? Anesthesiology 2. 1997; Vol.86: 501-503
  3. Rinaldo Bellomo. Bench-to-bedside review: Lactate and the kidney. Crit Care. 2002; 6(4): 322–326

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