Normal Saline or Balanced Crystalloids? An Update

Healthful Vitality | 04/16/2019 | By Dr Anand Lakhkar, MD, PhD | Normal Saline or Balanced Crystalloids? An Update

Crystalloid solutions are widely used for fluid therapy for correcting fluid and electrolyte balance. A 70kg adult has approximately 40 L of fluid. In this 40L, 25L is intra-cellular while 15 L is extra-cellular. In this 15 L, 12 L is interstitial (between the cells) while 3L is intra-vascular (fluid present in the blood vessel). With crystalloid therapy, we are mainly targeting the fluid losses which take place in the interstitial compartment

Normal Saline is not Normal

Normal saline is one of the most widely used crystalloid for maintaining fluid and electrolyte balance.  However normal saline is not really normal. It has higher levels of chloride and sodium and can lead to a condition known as hyperchloremic metabolic acidosis. These excess levels of chloride present in normal saline can be detrimental for the kidney since it can lead to a decrease in Glomerular Filtration Rate, kidney function and urine output by activating the tubule-glomerular feedback.

Tubulo-Glomerular Feedback

The kidneys regulate the glomerular filtration rate and urine formation by a mechanism known as tubulo-glomerular feedback. The main cells responsible for this mechanism are a group of special cells called as macula densa cells. These cells use the salt content of the fluid flowing through the kidney tubules as a signal to regulate. When the salt content of the fluid is high, they cause a decrease in renal blood flow, glomerular filtration and urine production. On the other when the salt content of the fluid is low, the macula densa cells cause an increase in renal blood flow, GFR and urine output.

Saline and the Kidney

When we give a large infusion of saline, the macula densa cells sense increased levels of sodium and chloride since the sodium and chloride levels present in normal saline are higher than normal. As a result, there is decrease in renal blood flow, GFR and urine output which can be detrimental for the kidney.  The same is depicted in figure 1. When we give balanced crystalloids, activation of tubule glomerular feedback will not take place since the sodium and chloride levels of balanced crystalloids are similar to plasma.

What are Balanced Crystalloids?

Balanced crystalloids are solutions which are more balanced with respect to plasma. They contain physiological levels of sodium and chloride; they contain buffering agents and are more isotonic with respect to plasma.

Balanced Crystalloids can be classified as:

1. Old balanced crystalloids – Ringer Lactate, Ringer Acetate
2. New balanced Crystalloids –Plasmalyte, Sterofundin

Balanced crystalloids and Kidney Transplantation

One of the reasons why nephrologists prefer saline to balanced crystalloids during renal transplantation is because saline does not contain potassium. They feel that solutions without potassium are safer in patients undergoing renal transplantation. Recent literature has demonstrated that this is not necessarily true.

Firstly, the belief that solutions containing potassium cause hyperkalemia is not true. Balanced cystalloids like contains a potassium of 5 Mmol/l while the normal plasma potassium is around 4.5-5.5 Mmol/l ⁽²⁾. Potassium has a volume of distribution which is greater than the extracellular fluid. There will be no effect on the serum potassium level with an infusion of a balanced salt solution like plasmalyte which has a near normal potassium level. Most of the potassium content in the body (98%) is intracellular (inside the cells). Large infusion of saline will result in hyperchloremic metabolic acidosis which will trigger a transcellular movement of potassium from inside of the cell to the outside which will result in the development of hyperkalemia. Acetate buffered balanced crystalloids like plasmalyte will not cause this shift since they do not cause hyperchloremic metabolic acidosis

Hyperkalemia studies

In a study by Potura et al, 150 patients were randomized to receive either saline or an acetate buffered balanced crystalloid. The main objective of the study was to check for the incidence of hyperkalemia. This study concluded that the incidence of hyperkalemia was similar between patients who received saline and those who received acetate buffered balanced crystalloids ⁽³⁾.

A double-blind study randomized was carried out in 90 patients who were undergoing a renal transplant. The study included 90 patients who were divided into 3 groups with each group having 30 patients. One group received 0.9% saline, another group received Ringer Lactate and a third group received an acetate buffered balanced crystalloid. Patients who received saline developed hyperchloremic metabolic acidosis while patients who received Ringer Lactate had increased lactate levels. The best metabolic profile was maintained by patients who received acetate buffered balanced crystalloids ⁽⁴⁾.  Another study demonstrated that patients undergoing a deceased renal transplantation who received saline had a higher incidence of hyperkalemia, hyperchloremia and were more academic compared to patients who received acetate buffered balanced crystalloids ⁽⁵⁾.

Balanced Crystalloids in Sepsis

SMART Study ⁽⁶⁾

One of the main clinical trials which was published last year in the New England Journal of Medicine was the SMART study conducted in critically ill ICU patients. This study compared saline (7860 patients) with balanced crystalloids (7940 patients. In Balanced group, 44% of the fluid used was lactate buffered while 56% was acetate buffered. The primary outcome was – Major Adverse Kidney Events within 30 days (MAKE30). MAKE30 has good clinical validity and is recommended as a patient-centred outcome for phase clinical trials ⁽⁶⁾.

Results of SMART Study

• Patients using balanced crystalloids had a 1.1% absolute significant decrease in MAKE 30
• Replacing saline with balanced crystalloids might stop 1 patient amid every 94 patients admitted to an intensive care unit from the need for new renal-replacement therapy or from having a persistent dysfunction of the kidney or from death.

Conclusion of SMART study

Use of balanced crystalloids in place of saline for intravenous fluid adminstration in critically ill adults can reduces the incidence of death and also protects the patients from developing persistent renal dysfunction and the requirement of new renal replacement therapy.

Summary

1. Large infusion of saline causes hyperchloremic metabolic acidosis which can result in the development of hyperkalemia.
2. Unlike saline, large volumes of acetate buffered balanced crystalloids don’t activate tubuloglomerular feedback and do not cause a decreased in GFR, renal blood flow and urine output.
3. Crystalloid therapy is the mainstay for fluid management in sepsis patients.
4. The SMART study is the largest prospective clinical study conducted till date comparing saline and balanced fluids in critically ill patients.
5. This study has clearly demonstrated that 0.9% saline can lead to more major adverse kidney events in critically ill patients when they are given saline instead of balanced crystalloids.

Also Read: Knowing Stress Sore Throat Symptoms and Treatments

References:

1. Li H, et al: 0.9% saline is neither normal nor physiological. J Zhejiang Univ Sci B 2016;17:181-187
2. Corrêa TD, Cavalcanti AB, de Assunção MSC. Balanced crystalloids for septic shock resuscitation. Revista Brasileira de Terapia Intensiva. 2016;28 (4):463-471.
3. Potura E, Lindner G, Biesenbach P, et al. An acetate-buffered balanced crystalloid versus 0.9 % saline in patients with end-stage renal disease undergoing cadaveric renal transplantation: a prospective randomized controlled trial. Anesth Analg. 2015;120:123–9.
4. Hadimioglu N, Saadawy I, Saglam T, Ertug Z, Dinckan A. The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation. Anesth Analg 2008;107:264-269
5. Weinberg, L., Harris, L., Bellomo, R. et al, Effects of intraoperative and early postoperative normal saline or Plasma-Lyte 148^® on hyperkalaemia in deceased donor renal transplantation: a double-blind randomized trial. Br J Anaesth. 2017;119:606–615
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.