What is the preferred fluid for resuscitation in sepsis, Ringer lactate or Normal saline?

Ringer Lactate vs Normal Saline in Sepsis

Lactated Ringer's solution should be used preferentially over normal saline for fluid resuscitation in sepsis, as it reduces mortality, shortens hospital length of stay, and avoids the hyperchloremic metabolic acidosis associated with normal saline. 1, 2

Guideline Recommendations

The American College of Critical Care Medicine and Surviving Sepsis Campaign guidelines recommend balanced crystalloids (lactated Ringer's or Plasma-Lyte) over normal saline when available for initial resuscitation 1. While the 2016 Surviving Sepsis Campaign guidelines recommend crystalloids as the fluid of choice, they do not explicitly distinguish between balanced and unbalanced solutions in their primary recommendations 3. However, the most recent guideline synthesis strongly recommends balanced crystalloids specifically to reduce the risk of hyperchloremic metabolic acidosis 1, 4.

Mortality and Clinical Outcomes

The highest quality and most recent evidence demonstrates a significant mortality benefit with lactated Ringer's solution. A 2025 secondary analysis of the CLOVERS trial (1,563 patients with sepsis-induced hypotension) showed that lactated Ringer's reduced mortality compared to normal saline (12.2% vs 15.9%; adjusted HR 0.71,95% CI 0.51-0.99, p=0.043) 2. This represents a 29% relative risk reduction in death before discharge by day 90.

Additional benefits of lactated Ringer's include:

• More hospital-free days at 28 days (16.6 vs 15.4 days; adjusted mean difference 1.6 days, p=0.009) 2
• Shorter hospital length of stay (subdistribution HR 1.39,95% CI 1.15-1.67) 5
• Lower blood transfusion requirements on the first day (606 ml vs 782 ml, p=0.046) 6
• Reduced total fluid volume requirements over the first three days (5,092 ml vs 5,470 ml, p=0.009) 6

Metabolic Complications

Normal saline causes significant metabolic derangements that lactated Ringer's avoids:

• Hyperchloremia occurs in 25% of patients receiving normal saline vs 13.2% with lactated Ringer's (OR 2.179, p=0.036) 6
• Hyperlactacidemia is more common with normal saline (86.0% vs 71.4%, OR 2.457, p=0.012) 6
• Decreased serum bicarbonate levels occur with normal saline compared to lactated Ringer's 2
• Hyperchloremic metabolic acidosis is a well-documented complication of normal saline that balanced crystalloids prevent 1, 4

Special Populations and Caveats

Chronic Pulmonary Disease

Lactated Ringer's provides greater mortality benefit in patients with chronic pulmonary disease compared to those without this comorbidity 5. The protective effect is most pronounced in this subgroup.

Chronic Kidney Disease and Liver Disease

The mortality benefit of lactated Ringer's is smaller and non-significant in patients with chronic kidney disease or moderate to severe liver disease 5. However, this does not mean normal saline is superior—rather, the advantage is less pronounced. Balanced crystalloids remain preferred to avoid worsening metabolic acidosis in these vulnerable populations 1, 7.

Serum Lactate Monitoring

Serum lactate levels rise slightly higher with lactated Ringer's (0.12 mg/dL/h higher, 95% CI 0.03-0.21), particularly in patients with chronic liver disease 5. This is due to the lactate content of the solution itself, not worsening tissue hypoperfusion. Clinicians should not misinterpret this as treatment failure—the resuscitation efficacy is equivalent between fluid types 5.

Traumatic Brain Injury

Do not use lactated Ringer's in patients with traumatic brain injury, as it increases mortality more than saline in this specific population 5. This is the only clinical scenario where normal saline is preferred.

Implementation Strategy

Administer at least 30 mL/kg of lactated Ringer's within the first 3 hours of sepsis recognition 3, 1, 4. Continue fluid administration using a fluid challenge technique as long as hemodynamic parameters improve 3, 4. Monitor for:

• Blood pressure, heart rate, and mean arterial pressure (target MAP ≥65 mmHg) 3
• Urine output, mental status, and peripheral perfusion 4
• Dynamic measures of fluid responsiveness (pulse pressure variation, stroke volume variation) rather than static measures like CVP 1, 4

If hypotension persists despite adequate fluid resuscitation, initiate norepinephrine as the first-choice vasopressor 3, 4.

Common Pitfalls

• Do not delay resuscitation due to concerns about fluid overload—delayed resuscitation increases mortality 1
• Do not rely on CVP alone to guide fluid therapy, as it has poor predictive ability for fluid responsiveness 1, 7
• Do not misinterpret rising lactate levels with lactated Ringer's as treatment failure—this reflects the lactate content of the solution, not worsening sepsis 5
• Do not use hydroxyethyl starches under any circumstances, as they increase mortality and acute kidney injury 3, 1, 4, 7