Question 15

College Answer

As with any drug/fluid there are problems associated with the use of normal saline as the sole fluid to  resuscitate the extracellular  fluid  deficit  of  DKA. Diabetic  ketoacidosis  is associated  with  a number of metabolic  disturbances, but most of the acute clinical  problems  are due to a lack of insulin (hyperglycaemia,  ketone  body  formation)  and  resultant  osmotic  diuresis  (severe  volume depletion [loss  of  water  and  sodium],  total  body electrolyte  depletion  [eg. K, Mg, PO.],  lactic acidosis. renal  insufficiency).  The  major  contributors  to  the  initial  metabolic  acidosis  are  the presence of ketone  bodies (increased anion gap), lactic acidosis (increased  anion gap), and hyperchloraemia  (normal   anion  gap).  The  first  two  of  these  will  be adequately   treated  by intravascular volume expansion and administration of exogenous insulin. Administration of isotonic saline (0.9% sodium  chloride)  may result in delayed correction of bicarbonate (ie. persistence of metabolic acidosis), now due predominantly to hyperchloraemia (normal anion gap).

Delayed correction of bicarbonate:
•   may  increase  the  time  that  the  patient  will  need  to  be  monitored  closely  (potentially confusing assessment patient response to treatment)
•  increases  the minute ventilation  (and work of breathing)  required to maintain steady state
(lower col for a given pH)
•  increases  the  temptation  to  administer  exogenous  bicarbonate  (with  associated  risks of hypokalaemia, hypophosphataemia, hypematraemia etc.)

Alternative crystalloid  solutions  are available  (eg. hartrnannslringers  lactate/plasmalyte/hypotonic saline) and should be considered  early  in the fluid resuscitation  of these patients. Choice of fluid should be based on the response of the patient to therapy (ie. ongoing, repeated assessment of Na [corrected for glucose], K, HC03 and Chloride).

Discussion

One cannot simply "comment briefly" on such a statement as this.

One must critically evaluate it.

Rationale for discussion

• DKA patients have a significant fluid deficit due to glucose and ketone diuresis
• Rehydration is a major part of therapy for DKA
• Isotonic saline is a standard rehydration fluid
• However, the large volumes which will be required may have undesirable consequences

Physiological basis for the statement

• Isotonic saline contains 150mmol/L of chloride
• The excess of chloride may contribute to the metabolic acidosis
• This contribution may delay recovery from ketoacidosis

Advantages

• Isotonic saline is a cheap widely available fluid
• Its high sodium content can promote the retention of fluid in the intravascular space
• It is safe to use in most settings
• Volume replacement will result in a more rapid resolution of ketoacidosis and lactic acidosis in DKA
• Normal anion gap acidosis due to the extra chloride may be mild and transient

Disadvantages

• Normal anion gap metabolic acidosis may develop
• Work of breathing may increase due to acidosis
• Existing (already near-depleted) buffer systems may be further depleted by this NAGMA.

Evidence and opinion in the literature

• Most guidelines for DKA resuscitation were written by endocrinologists rather than critical care specialists.
• Most of these guidelines still promote the use of normal saline, even though the acidosis-promoting effects of saline are well recognised.
• Normal saline has been treated as the default fluid of choice because the evidence for other fluids had been lacking.
• Most recent evidence comparing a "balanced" resuscitation crystalloid solution (Plasmalyte 148) with saline has suggested that though the metabolic acidosis resolves faster with Plasmalyte, the duration of ICU stay is not affected.
• Furthermore, there is some evidence that lactate-containing solutions (eg. Harmanns) may delay the resolution of ketoacidosis and achievement of normoglycaemia by contributing substrate (lactate) for hepatic gluconeogenesis, and thus by contributing additional glucose to the already hyperglycaemic patient.

In summary:

• This matter is far from settled. The choice of resuscitation fluid in DKA must rely on careful electrolyte and acid-base monitoring, and may need to be tailored to individual scenarios.
• Balanced fluid solutions may be beneficial in critically acidotic patients whose buffer systems are all but exhausted.
• Normal saline is likely a safe and inexpensive alternative in patients with mild DKA.

Dhatariya, Ketan K. "Diabetic ketoacidosis." BMJ: British Medical Journal334.7607 (2007): 1284.

 

LeRoith D, Taylor SI, Olefsky JM. Diabetes mellitus. A fundamental and clinical text. Philadelphia: Lippincott Williams and Wilkins, 2000

 

Skellett, S., et al. "Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation." Archives of disease in childhood 83.6 (2000): 514-516.

 

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

 

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.

 

Van Zyl, Danie G., Paul Rheeder, and E. Delport. "Fluid management in diabetic-acidosis—Ringer's lactate versus normal saline: a randomized controlled trial." Qjm 105.4 (2012): 337-343.