In an otherwise stable adult patient, is a 24‑hour interval after a 1‑liter bolus of 0.9% normal saline concerning?

Is an Anion Gap of 24 After a 1-Liter Bolus of 0.9% Normal Saline Concerning?

Yes, an anion gap of 24 after a 1-liter bolus of 0.9% normal saline is concerning and warrants immediate investigation for the underlying cause of metabolic acidosis, as the saline itself should not produce an elevated anion gap acidosis.

Understanding the Clinical Picture

The key issue here is distinguishing between what the normal saline caused versus what it revealed or failed to correct:

What Normal Saline Does NOT Cause

• 0.9% saline causes hyperchloremic NON-anion gap metabolic acidosis, not an elevated anion gap acidosis 1, 2, 3
• When saline causes acid-base disturbances, you see elevated chloride with a normal anion gap (typically 8-12 mEq/L) 1
• The acidosis from saline is due to dilutional effects on bicarbonate and direct chloride load 4

What an Anion Gap of 24 Means

An anion gap of 24 indicates high anion gap metabolic acidosis (normal is typically 8-12 mEq/L), suggesting accumulation of unmeasured anions such as:

• Lactate (shock, tissue hypoperfusion, sepsis)
• Ketones (diabetic ketoacidosis, starvation, alcohol)
• Uremic acids (acute or chronic kidney injury)
• Toxic ingestions (methanol, ethylene glycol, salicylates)

Immediate Assessment Algorithm

Step 1: Check vital signs and perfusion status

• Blood pressure, heart rate, respiratory rate, mental status
• Capillary refill, skin temperature, urine output
• Look for signs of shock or inadequate tissue perfusion 5

Step 2: Obtain critical laboratory values

• Lactate level (most common cause in acute settings)
• Glucose and ketones (rule out DKA)
• Creatinine and BUN (assess renal function)
• Complete metabolic panel to calculate anion gap accurately

Step 3: Determine the primary pathology

• If lactate >4 mmol/L: Suspect septic shock, hemorrhagic shock, or tissue hypoperfusion requiring aggressive resuscitation 5
• If glucose >250 mg/dL with ketones: Diabetic ketoacidosis
• If creatinine significantly elevated: Acute kidney injury with uremic acidosis

Clinical Pitfalls to Avoid

Common Mistake: Attributing the Anion Gap to Saline

The 1-liter saline bolus is not the cause of the elevated anion gap. While research shows that saline can cause hyperchloremic acidosis, increase lactate slightly in healthy volunteers 6, and worsen renal function 1, 2, it does not directly cause high anion gap acidosis. The anion gap of 24 indicates a separate, serious underlying metabolic derangement that either:

• Pre-existed before the saline administration
• Developed due to inadequate resuscitation (the 1 liter was insufficient)
• Represents ongoing tissue hypoperfusion despite the fluid bolus

The Saline May Have Made Things Worse

Evidence suggests that 0.9% saline has several harmful effects that could compound the underlying problem:

• Causes renal vasoconstriction and decreased kidney perfusion 1, 2
• Increases risk of acute kidney injury compared to balanced crystalloids 1, 2, 3
• Can worsen tissue edema and impair oxygen delivery 6
• In healthy volunteers, a 2-liter saline bolus caused sustained hyperchloremia for >6 hours and slower sodium/water excretion compared to balanced solutions 4

What Should Have Been Done Differently

Balanced crystalloids (Lactated Ringer's or Plasmalyte) should be used instead of 0.9% saline for resuscitation 1, 2, 3. The evidence is clear:

• The SMART trial (15,802 ICU patients) showed balanced crystalloids reduced major adverse kidney events compared to saline 1, 2
• The SALT trial (974 critically ill patients) demonstrated lower mortality and less renal dysfunction with balanced crystalloids 1
• Multiple guidelines now recommend balanced crystalloids over saline, especially when significant volumes are needed 1, 2, 3

Immediate Management

For the patient with anion gap 24 after 1L saline:

1. Switch to balanced crystalloid immediately (Lactated Ringer's or Plasmalyte) 1, 2, 3

2. If hypotensive or showing signs of shock:

   • Administer additional fluid boluses (500-1000 mL) of balanced crystalloid over 15-30 minutes 5
   • Reassess after each bolus for response (improved blood pressure, decreased heart rate, improved perfusion) 5
   • Consider vasopressors (norepinephrine first-line) if MAP <65 mmHg despite adequate fluid resuscitation 5

3. Monitor for fluid overload: Watch for jugular venous distension, pulmonary crackles, peripheral edema 5

4. Target the underlying cause:

   • If septic shock: Antibiotics within 1 hour, source control
   • If DKA: Insulin infusion, potassium repletion
   • If AKI: Nephrology consultation, consider dialysis if severe

Bottom Line

The anion gap of 24 is NOT from the saline—it signals serious underlying pathology requiring urgent investigation and treatment. The saline may have worsened renal function and delayed appropriate resuscitation. Switch to balanced crystalloids immediately and aggressively pursue the cause of the high anion gap acidosis while providing adequate resuscitation guided by clinical response and hemodynamic parameters.