What is the preferred choice between balanced crystalloids (e.g. lactated Ringer's solution, Plasma-Lyte) and normal saline for fluid resuscitation in adult patients with and without underlying conditions such as impaired renal (kidney) function or heart failure?

Balanced Crystalloids vs Normal Saline for Fluid Resuscitation

Balanced crystalloids (lactated Ringer's or Plasma-Lyte) should be used as the default first-line fluid for resuscitation in most adult patients, as they reduce mortality and major adverse kidney events compared to normal saline. 1, 2

Primary Evidence Supporting Balanced Crystalloids

The most compelling evidence comes from large randomized trials demonstrating superior outcomes with balanced crystalloids:

• The SMART trial (15,802 ICU patients) showed balanced crystalloids reduced 30-day mortality (OR 0.84,95% CI 0.74-0.95) and decreased major adverse kidney events by 1.1% absolute risk reduction compared to normal saline 1
• The SALT trial demonstrated lower 30-day in-hospital mortality and reduced need for renal replacement therapy with balanced crystalloids versus 0.9% saline 1
• Meta-analyses including 35,884 critically ill patients concluded that balanced crystalloids are associated with reduced mortality in the general ICU population 3

Clinical Decision Algorithm

Use Balanced Crystalloids (Lactated Ringer's or Plasma-Lyte) for:

• Sepsis and septic shock - strongly recommended as first-line therapy, with benefits most pronounced when initiated in the emergency department 1, 4
• General trauma resuscitation (without severe traumatic brain injury) - reduces mortality and adverse renal events 1, 5
• Emergency laparotomy and surgical patients - recommended for resuscitation and intravascular volume maintenance 1
• Hemorrhagic shock - favored as initial crystalloid solution over colloids 1
• Acute kidney injury - reduces risk of further kidney injury and major adverse kidney events 1, 6
• Diabetic ketoacidosis - results in faster DKA resolution (median 13.0 vs 16.9 hours) and shorter insulin infusion duration 7
• Burns resuscitation - recommended as first-line balanced fluid due to electrolyte composition close to plasma 5
• Kidney transplant recipients - strongly recommended to reduce delayed graft function 1, 5

Use Normal Saline (0.9% NaCl) ONLY for:

• Severe traumatic brain injury or increased intracranial pressure - lactated Ringer's is hypotonic (273-277 mOsm/L vs plasma 275-295 mOsm/L) and can worsen cerebral edema 1, 5
• Rhabdomyolysis or crush syndrome - avoid potassium-containing balanced solutions due to risk of hyperkalemia with reperfusion 5

If normal saline must be used in other scenarios, limit to maximum 1-1.5 L to minimize hyperchloremic effects 1, 6

Why Balanced Crystalloids Are Superior

Metabolic Advantages

• Normal saline contains supraphysiologic chloride (154 mmol/L) in a non-physiological 1:1 ratio with sodium, causing hyperchloremic metabolic acidosis 1, 2
• Balanced crystalloids have near-physiological chloride concentrations (108-109 mmol/L), preventing acidosis 1, 2
• The lactate in lactated Ringer's metabolizes to bicarbonate, helping correct acidosis 6

Renal Protection

• Large volumes of normal saline cause renal vasoconstriction, decreased urine output, and increased risk of acute kidney injury 1, 6
• Hyperchloremia from normal saline is associated with increased 30-day mortality in a propensity-matched study of 22,851 surgical patients 1, 6
• Balanced crystalloids maintain renal perfusion and reduce major adverse kidney events 1

Mortality Benefit

• Among critically ill adults with sepsis, balanced fluid resuscitation was associated with lower in-hospital mortality (19.6% vs 22.8%; RR 0.86,95% CI 0.78-0.94) 4
• Mortality was progressively lower among patients receiving larger proportions of balanced fluids 4

Special Populations

Patients with Impaired Renal Function

Balanced crystalloids remain preferred even with renal impairment, as they reduce risk of further kidney injury 5, 6

• The potassium content in balanced solutions (4-5 mmol/L) should not be considered a contraindication unless severe hyperkalemia (>6.5 mmol/L) exists 5
• In renal transplant recipients, patients receiving normal saline actually developed higher potassium levels than those receiving lactated Ringer's 5
• From a physiological standpoint, it is not possible to create potassium excess using a fluid with potassium concentration equal to or lower than plasma concentration 5

Patients with Heart Failure

Balanced crystalloids should be used with careful volume monitoring to avoid overload 3

• Point-of-care ultrasonography (TTE) provides assessment of cardiac function, inferior vena cava preload, and helps guide resuscitation 3
• Monitor dynamic changes in stroke volume, stroke volume variation, or pulse pressure variation with fluid boluses 3
• Ongoing accurate hemodynamic monitoring is essential during fluid resuscitation to avoid overresuscitation 3

Patients with Cirrhosis and ACLF

Albumin may be preferred over crystalloids in specific cirrhosis scenarios, but when crystalloids are used, balanced solutions are superior to normal saline 3

• In cirrhotic patients with sepsis-induced hypotension, albumin showed higher rates of shock reversal and higher 1-week survival (43.5% vs 38.3%, p=0.03) compared to normal saline 3
• A meta-analysis in sepsis patients reported that balanced crystalloids and albumin decreased mortality more than normal saline 3
• The PLUS study (largest RCT to date) found no difference in mortality or AKI between Plasma-Lyte 148 and saline in critically ill adults, though an updated meta-analysis concluded balanced crystalloids reduce mortality 3

Critical Pitfalls to Avoid

Common Errors

• Using normal saline based on outdated protocols from before 2018 - modern evidence strongly favors balanced crystalloids 1
• Assuming potassium addition makes normal saline safer for large volume use - this does not address the fundamental chloride toxicity 1
• Using lactated Ringer's in severe traumatic brain injury - its hypotonic nature can worsen cerebral edema and increase intracranial pressure 1, 5
• Avoiding balanced crystalloids due to mild hyperkalemia or renal dysfunction - this is not a contraindication except in rhabdomyolysis/crush syndrome 5

Monitoring Requirements

When using any crystalloid for resuscitation:

• Monitor chloride and acid-base status with large volume resuscitation 5
• Assess serum electrolytes, particularly chloride levels 6
• Monitor renal function and urine output 6
• Track fluid balance to avoid volume overload 6
• In patients with hyponatremia, ensure osmolality change does not exceed 3 mOsm/kg/h 6

Colloids Are Not Recommended

Isotonic crystalloids (balanced preferred) are recommended over colloids for initial resuscitation 3, 8

• Moderate-certainty evidence shows little or no difference in mortality between colloids (starches, dextrans, gelatins, albumin/FFP) and crystalloids 8
• Starches probably slightly increase the need for blood transfusion (RR 1.19) and renal replacement therapy (RR 1.30) 8
• Synthetic colloids (hydroxyethyl starch, gelatin) should be avoided due to renal failure risk and lack of mortality benefit 1