Myth: Normal Saline Is the IV Fluid of Choice

Which fluid is superior, normal (0.9%) saline or balanced crystalloids (ie, lactated Ringer’s)? Balanced fluids, in theory, are defined as fluids that are more physiologic in several parameters when compared to normal saline (NS).

It appears we have a critical mass of sufficient evidence suggesting NS needs to take a back seat to lactated Ringer’s (LR).

LR has been criticized for being physiologically hypotonic, (reduced “actual osmolality” or tonicity) and thus may diffuse to extravascular spaces too quickly, limiting their effectiveness for volume expansion. Such diffusion results from osmotic pressure (ie, solutes and their associated osmotic coefficients).¹ As an example, sodium and chloride only partially dissociate when dissolved and thus the solutes are only partially osmotically active (osmotic coefficient 0.926). The osmolarity of NaCl 0.9% is 308 mOsmol/L, but its actual osmolality is 286 mOsmol/kg H2O. The osmolarity of LR is 273 mOsm/L, but its osmolality is 254 mOsm/kg.¹ This difference in tonicity may result in a shorter half-life for LR.

Hahn et al reported, “The T1/2 for crystalloids is usually 20 to 40 min in conscious humans but might extend to 80  min or longer in the presence of preoperative stress, dehydration, blood loss of <1 l or pregnancy.”² Drobin and Hahn published data from 10 healthy male subjects, noting the half-life for NS and LR was 110 min and 50 min, respectively.³ The data is not without significant limitations. However, it does imply a longer half-life for NS, which is theorized to be, in part, from the renal vasoconstriction from the high chloride content or NS.^1,2

If you are buying that half-life, as a function of tonicity, predicts outcomes, I’d be cautious. Although the individual properties of the fluids (ie, tonicity) cannot be isolated, outcomes appear to be better with balanced fluids. For instance, a meta-analysis of 14 randomized controlled trials including 18,916 patients treated for sepsis noted a mortality benefit from LR compared to NS (odds ratio 0.78).⁴

Some critics of LR have proposed that the infusion of lactate may worsen metabolic acidosis. However, much like the concern over lower tonicity, this concern is also a physiologic argument as opposed to evidence-based. Sodium lactate, the additive in LR, is hepatically metabolized to bicarbonate and is not an acid.

So, what happens when lactate is infused? Despite the limitations of the study, Ross et al found no such effect in 157 blood donors (500 ml) with an estimated less than 15 percent blood loss. Post-donation, all groups had lactate levels between 1.05 and 1.10. However, post infusion, the picture changed. After 2 L of intravenous fluid, the lactate was higher in the LR group (1.46), compared to both the NS and no infusion groups, which were 1.0 and 1.36, respectively. The base deficit for NS was 10 times that of LR, and the pH was the lowest for NS (7.32 for NS, 7.34 for LR, 7.36 for the controls).⁵ While not definitive, the study suggests buffers in fluids may positively impact acid–base status.

Quite the contrary, it is NS that has been proved to promote metabolic acidosis. Although theories vary, the dilutional effect on bicarbonate concentrations and an increase in unpaired anions (Cl-) resulting in a non-gap acidosis are two common explanations.¹

On March 1, 2018, Self et al published two studies from Vanderbilt on this topic, one focusing on the critically ill and the second on those not critically ill but admitted from the emergency department. Although un-blinded, the studies provide valuable insights. The first found that, “Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline.”⁶ Although there was no difference in the hospital-free days in the non-critically ill study, the authors found that, “balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7 percent vs. 5.6 percent; adjusted odds ratio, 0.82; 95 percent CI, 0.70 to 0.95; P=0.01).”⁷

In most cases, it may be time to check your saline at the door in favor of LR.

References

1. Severs D, Hoorn EJ, Rookmaaker MB. A critical appraisal of intravenous fluids: from the physiological basis to clinical evidence. Nephrol Dial Transplant. 2015;30(2):178-187.
2. Hahn RG, Lyons G. The half-life of infusion fluids: an educational review. Eur J Anaesthesiol. 2016;33(7):475-482.
3. Drobin D, Hahn RG. Kinetics of isotonic and hypertonic plasma volume expanders. Anesthesiology. 2002;96:1371-1380.
4. Rochwerg B, Alhazzani W, Sindi A, et al. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014;161:347-355.
5. Ross SW, Christmas AB, Fischer PE, et al. Impact of common crystalloid solutions on resuscitation markers following Class I hemorrhage: a randomized control trial. J Trauma Acute Care Surg. 2015;79(5):732-740.
6. Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:829-839.
7. Self WH, Semler MW, Wanderer JP, et al. Balanced crystalloids versus saline in noncritically ill adults. N Engl J Med. 2018;378:819-828.