Question 2

a)    What do you understand by the term ‘balanced crystalloid solution’?    (10% marks)

b)    Compare and contrast the constituents of normal saline and any one balanced crystalloid solution. (20% marks)

c)    Discuss the advantages and disadvantages of balanced crystalloid solutions and normal saline in the fluid management of diabetic ketoacidosis.    (70% marks)

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College answer

Not available.


a) "Balanced crystalloids have a sodium, potassium, and chloride content closer to that of extracellular fluid and, when given intravenously, have fewer adverse effects on acid–base balance." Semler & Kellum, 2019


Any from the broad range of available balanced crystalloids should have been appropriate here, and the real trick would have been to remember the exact goddamn numbers for the chloride and sodium concentrations. The table presented here (cut-and-pasted from Semler & Kellum) is available for reference.

Fluid Sodium Potassium Calcium Magnesium Chloride Acetate Gluconate Malate Lactate Osmolarity
Plasma 135–145 4.5–5.0 2.2–2.6 0.8–1.0 94–111 0.02–0.2     1–2 275–295
Plasma-Lyte A 140 5.0   3.0 98 27 23     294
Normosol-R 140 5.0   3.0 98 27 23     295
Isolyte S 141 5.0   3.0 98 27 23     295
Ringer’s acetate 145 4.0 2.5 1.0 127 24   5   309
Lactated Ringer’s 130 4.0 2.7   109       28 273
Hartmann’s solution 131 5.4 1.8   112       28 280
0.9% sodium chloride 154       154         308

c) Advantages and disadvantages of normal saline and balanced crystalloid in the management of DKA:

You could have answered this as a table, or as a set of pointform notes. Observe:

  Normal saline Balanced crystalloid
  • Cheaper
  • Widely available
  • Extensive experience with its use
  • Supported by DKA guidelines 
  • Well tolerated by the (healthy, young) DKA population
  • Evidence demonstrates a more rapid resolution of acidosis
  • Theroretically may decrease the risk of AKI
  • May be cost saving if it decreases the length of ICU/hospital stay
  • The large volume required in DKA means a large chloride load
  • Increases chloride load, which:
    • Predisposes to AKI
    • Delays recovery from acidosis
  • More expensive, per litre
  • May slow the rate of ketone renal clearance and metabolism
  • Evidence does not show any benefit in paediatric DKA
  • Broadly, balanced crystalloids do not seem to affect patient-centred outcomes in large trials involving all patients (not just DKA)

Or, in point form:

  • Arguments for the use of balanced crystalloid in DKA
    • DKA often presents with life-threatening acidaemia, which should improve with the use of balanced crystalloid, and which could deteriorate with the use of saline.
    • The volume of resuscitation fluid which is expected for severe DKA is substantial (could be up to ~10-15% of the patients body weight in fluid), which means the dose of chloride would be very great (eg. 10L crystalloid = 1540 mmol of chloride).
    • The cost of balanced electrolyte solutions is relatively low and may represent a cost saving if they result in a shorter duration of ICU or hospital stay by increasing the speed of recovery from acidosis.
    • Hyperchloraemia often develops in the recovery phase of DKA because of the loss of ketones in the urine, which represents the loss of potential bicarbonate precursors (Lopes et al, 2011). It therefore makes sense to replace bicarbonate precursors, and limit the chloride intake.
    • Excess load of chloride is thought to have deleterious effects on renal function through renal microvascular vasoconstriction (Wilcox, 1983), and patients with DKA often already have a degree of kidney injury as the result of dehydration
  • Arguments against the use of balanced crystalloid in DKA
    • Acidaemia in DKA is due to ketosis rather than a normal anion gap metabolic acidosis. The consumption of ketones is therefore the goal of therapy, i.e. the use of balanced crystalloid is quite peripheral to the specific management of this condition (as it is the insulin that does all the heavy lifting)
    • Balanced crystalloids are viewed as alkalinising bicarbonate precursors, but the use of sodium bicarbonate is known to be counterproductive in DKA (Okuda et al, 1996), as the metabolism and elimination of ketones are more efficient in the presence of metabolic acidosis
    • Patients with DKA are often young and otherwise fit, which makes them better capable of tolerating the cardiovascular and respiratory consequences of metabolic acidosis, making acid-base rebalancing less of a priority for them.
    • These young DKA patients also usually have functionally normal kidneys, and their "kidney injury" is usually pre-renal, which means they are rapidly able to renormalise their creatinine and excrete the extra chloride.
  • Evidence regarding balanced crystalloid in DKA
    • Small observational studies have demonstrated a faster rate of metabolic acidosis resolution (Chua et al, 2012)
    • Subgroup analysis of large trials (SALT-ED and SMART, by Hobensack et al, 2020, and Self et al, 2020) also demonstrated a faster rate of recovery from DKA and a more rapid restoration of normal acid-base balance. However, the trials themselves did not demonstrate any difference in patient-centered outcomes with the use of balanced crystalloid.
    • In children with DKA, the SPinK trial (Williams et al, 2021) found absolutely no difference between NS and Plasma-Lyte, in terms of any variables (including resolution of AKI, acidosis, ICU stay, etc).


Semler, Matthew W., and John A. Kellum. "Balanced crystalloid solutions." American journal of respiratory and critical care medicine 199.8 (2019): 952-960.

Curran, Jeffrey D., et al. "Comparison of Balanced Crystalloid Solutions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Critical care explorations 3.5 (2021).

WIGGINS, WALTER S., et al. "The effect of salt loading and salt depletion on renal function and electrolyte excretion in man." Circulation 3.2 (1951): 275-281.

Hobensack, Michael. "Clinical Effects of Balanced Crystalloids vs Saline in Adults with Diabetic Ketoacidosis: Self WH, Evans CS, Jenkins CA, et al. JAMA Network Open. 2020; 3 (11): e2024596." Journal of Emergency Medicine 60.4 (2021): 578-579.

Lopes, Anselmo Dantas, Alexandre Toledo Maciel, and Marcelo Park. "Evolutive physicochemical characterization of diabetic ketoacidosis in adult patients admitted to the intensive care unit." Journal of critical care 26.3 (2011): 303-310.

Okuda, Y. U. K. I. C. H. I., et al. "Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis." The Journal of Clinical Endocrinology & Metabolism 81.1 (1996): 314-320.

Wilcox, Christopher S. "Regulation of renal blood flow by plasma chloride." The Journal of clinical investigation 71.3 (1983): 726-735.

Chua, Horng-Ruey, et al. "Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis." Journal of critical care 27.2 (2012): 138-145.

Self, Wesley H., et al. "Clinical effects of balanced crystalloids vs saline in adults with diabetic ketoacidosis: a subgroup analysis of cluster randomized clinical trials." JAMA network open 3.11 (2020): e2024596-e2024596.

Williams, Vijai, et al. "0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial." Critical Care 24.1 (2020): 1-10.