The Vitals: IV Fluids – (Ab)Normal Saline

The Pre-brief

Hendersson-Hasselbach, Stewart, Bronsted-Lowry, and many others are common names in the world of acid-base analysis provide unique insights into the mechanisms of the precise acid-base balance maintained by the human body. The Stewart approach has become more prevalent in recent years because of its clinical utility, while the Hendersson-Hasselbach method is the most commonly discussed in medical school. This post is meant to cover none of these approaches in depth, but to present in simpler terms why normal saline, with its abnormal properties is not the best fluid for resuscitation of critically ill and hypovolemic patients.

Some definitions and compositions to keep in mind:

The extracellular fluid, composed primarily of plasma and interstitial fluid, contains high concentrations of sodium, chloride, bicarbonate, and proteins with lower concentrations of potassium, magnesium, and phosphate.

The intracellular fluid, composed primarily of cellular cytoplasm, has high concentrations of potassium, magnesium, phosphate, and proteins with lower concentrations of sodium, chloride, and bicarbonate.

The primary acid-base buffer system in the body is the relationship between H+ and HCO3– and as documented above is also impacted by forces of electroneutrality with the Stewart approach. The infusion of high volumes of sodium chloride in normal saline drives chloride content up, primarily in the extracellular fluid. This causes an inward shift of bicarbonate ions, hindering the body’s ability to manage shock states.

Multiple forces contribute to the effects of pH and acidosis on the body’s ability to respond to shock states and specific mechanisms are still being delineated. However, it has been shown that acidosis leads to a decrease in vascular tone through the ‘acidic-metabolic vasodilation phenomenon’. Further, it has been demonstrated that the perivascular acidosis that accompanies shock states causes resistance to vasoconstrictors and difficulty with maintaining adequate blood pressure. This is due to multiple factors including decreased calcium ion transport into cells, decreased myofilament contraction ability, and modification of cell surface receptors.

A common complication of large volume normal saline infusion is hyperchloremic metabolic acidosis, and coupling this with an already acidotic state like sepsis or diabetic ketoacidosis creates an additional obstacle in the management of critically ill patients. Additionally, as demonstrated in the SALT-ED Trial, normal saline infusion comes with an increase in mortality and acute kidney injury.

The Debrief

• (Ab)normal saline and the excessive chloride content prevent the body’s natural buffer system, H+ and HCO3-, from functioning optimally.
• Excess chloride causes bicarbonate to shift intracellularly to theoretically maintain electroneutrality which ultimately inhibits bicarbonates ability to buffer acidotic states (i.e. sepsis and other shock physiologies).
• Critically ill patients require a fine tuned approach to their resuscitation including consideration of the underlying physiology (such as severe acidosis from sepsis) and the impact of fluid resuscitation (and its relation to the underlying physiology).
• Mounting evidence suggests that (ab)normal saline is not the optimal fluid for resuscitation of our critically ill patients.

References

1. Sharma S, Hashmi MF, Aggarwal S. Hyperchloremic Acidosis. [Updated 2021 Feb 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482340/
2. Brinkman JE, Dorius B, Sharma S. Physiology, Body Fluids. [Updated 2020 May 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482447/
3. Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. The New England Journal of Medicine. 2018; 378(9):829-839. PMID: 29485925. 
4. Lewis SR, Pritchard MW, Evans DJ, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018;8(8):CD000567. Published 2018 Aug 3. doi:10.1002/14651858. PMID: 30073665.
5. Semler MW, Kellum JA. Balanced Crystalloid Solutions Am J Respir Crit Care Med. 2019; 199(8): 952–960. PMID: 30407838.
6. Castera MR, Borhade MB. Fluid Management. [Updated 2020 Apr 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532305/
7. Shrimanker I, Bhattarai S. Electrolytes. [Updated 2020 Sep 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541123/
8. Sterns RH. Strong ions and the analysis of acid-base disturbances (Stewart approach). In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2021.
9. Wallace HA, Regunath H. Fluid Resuscitation. [Updated 2020 Jun 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534791/
10. Waterhouse BR, Farmery AD. The organization and composition of body fluids. Anaesthesia and Intensive Care Medicine. 2012; 13(12): 603-608.
11. Doberer D, Funk GC, Kirchner K, Schneeweiss B. A critique of Stewart’s approach: the chemical mechanism of dilutional acidosis. Intensive Care Med. 2009 Dec;35(12):2173-80. doi: 10.1007/s00134-009-1528-y. PMID: 19533091.