Sepsis and the Importance of Fluid Resuscitation
Sepsis is a life-threatening condition caused by a dysregulated host response to infection, leading to organ dysfunction. It is a medical emergency requiring rapid intervention to restore tissue perfusion, reverse hypotension, and prevent multi-organ failure. Intravenous fluid resuscitation is a primary intervention for patients with sepsis-induced hypoperfusion or septic shock.
The goal of initial fluid therapy is to rapidly expand intravascular volume to support blood pressure and improve microcirculation. The Surviving Sepsis Campaign (SSC) guidelines recommend administering at least 30 mL/kg of intravenous crystalloid fluid within the first three hours of resuscitation. However, the specific type of fluid—crystalloid versus colloid—and the optimal resuscitation strategy have been subjects of extensive research and debate.
Crystalloids: The First-Line Treatment
Crystalloids are the universally recommended first-line fluid for sepsis resuscitation due to their availability, low cost, and proven effectiveness. There are two main types used in practice: normal saline and balanced crystalloids.
Normal Saline (0.9% Sodium Chloride)
For decades, 0.9% normal saline (NS) was the standard resuscitative fluid in many parts of the world. It is an isotonic solution containing supraphysiologic levels of chloride (154 mEq/L).
Risks Associated with Normal Saline:
- Hyperchloremic metabolic acidosis: Large volumes of NS can cause an increase in serum chloride concentration, leading to a non-anion gap metabolic acidosis.
- Acute Kidney Injury (AKI): The hyperchloremia can cause renal vasoconstriction, potentially increasing the risk of AKI, especially in large-volume resuscitation.
Balanced Crystalloids (e.g., Lactated Ringer's, Plasma-Lyte)
Balanced crystalloids (BCs) have an electrolyte composition that more closely mirrors that of human plasma. Lactated Ringer's (LR) and Plasma-Lyte are two common examples. Recent large, randomized trials and meta-analyses have provided compelling evidence supporting their use over NS.
Key Findings for Balanced Crystalloids:
- SMART Trial: A large trial comparing BCs to saline in critically ill adults found that BCs resulted in a lower rate of major adverse kidney events and, in a subgroup of sepsis patients, a significant reduction in 30-day in-hospital mortality.
- Meta-analyses: Several network meta-analyses, including a recent one from June 2025, indicate that BCs are associated with the lowest all-cause mortality and best overall outcomes compared to other fluid types.
- Mechanism: BCs may reduce the risk of hyperchloremic acidosis and improve kidney function, which is particularly important in sepsis patients with underlying renal dysfunction.
Colloids: A Second-Line or Targeted Therapy
Colloids contain high-molecular-weight substances that, in theory, remain within the intravascular space longer, requiring smaller volumes for resuscitation. However, their use is more controversial.
Types of Colloids and Evidence:
- Albumin: Some studies, such as the ALBIOS trial, have shown that albumin administration, after initial crystalloid resuscitation, can lead to improved hemodynamic parameters and potentially reduced mortality in the septic shock subgroup. However, other large studies and meta-analyses have shown inconsistent or no overall mortality benefit. The SSC 2021 guidelines suggest considering albumin in patients who have received large volumes of crystalloids.
- Synthetic Colloids (e.g., Hydroxyethyl Starch - HES): HES has been robustly studied and is associated with increased incidence of AKI and higher mortality, and should be avoided in sepsis resuscitation.
Comparison of Resuscitation Fluids
| Feature | Normal Saline (0.9%) | Balanced Crystalloids (e.g., LR) | Albumin (Colloid) |
|---|---|---|---|
| Composition | High chloride (154 mEq/L), no buffers | Physiologic electrolyte concentrations, contains buffers (e.g., lactate) | Plasma-derived protein in crystalloid solution |
| Cost | Low | Low | High |
| Availability | Widely available | Widely available | Can be limited |
| Initial Choice | Was standard, now discouraged in large volumes | Preferred first-line fluid | Not first-line |
| Clinical Effect | Risk of hyperchloremic acidosis and AKI with large volumes | Reduced risk of acidosis and potentially lower AKI rates, especially in large-volume resuscitation | Improved hemodynamics; uncertain mortality benefit |
| Risks | Hyperchloremia, acidosis, AKI | Generally low risk; caution with potential electrolyte issues | Variable findings, potentially higher costs, possible adverse events in specific subgroups |
Fluid Management Strategy
Beyond the choice of fluid, the strategy of administration is equally important. The consensus has evolved from simple fluid boluses to a more nuanced, dynamic approach.
- Initial Resuscitation: For patients with sepsis-induced hypotension or elevated lactate, initial resuscitation with 30 mL/kg of crystalloids is recommended within the first few hours. This phase focuses on achieving initial hemodynamic stability.
- Dynamic Reassessment: Following the initial bolus, further fluid administration should be guided by dynamic measures of fluid responsiveness rather than static parameters like central venous pressure (CVP). Dynamic measures include assessing the response to a passive leg raise, stroke volume variation, or pulse pressure variation. This helps avoid unnecessary fluid accumulation.
- Restrictive vs. Liberal Fluid Therapy: The optimal volume of fluid resuscitation has also been debated. The CLOVERS trial compared a restrictive fluid strategy (early vasopressors) with a liberal strategy (delayed vasopressors) and found no significant difference in 90-day mortality. This suggests that overly liberal fluid administration should be avoided and that a more personalized approach is needed to minimize potential harm from fluid overload.
Conclusion
Based on the latest evidence, balanced crystalloids are the fluid of choice for initial fluid resuscitation in sepsis. While normal saline remains a widely available option, the potential risks of hyperchloremic acidosis and kidney injury associated with large-volume administration favor balanced solutions like Lactated Ringer's. Colloids, such as albumin, are not recommended as a first-line option but may be considered for patients who have received large volumes of crystalloids or in specific subgroups like septic shock. Synthetic colloids like HES should be avoided due to safety concerns. A dynamic and individualized approach to fluid management, guided by frequent reassessment of fluid responsiveness, is paramount to ensure adequate tissue perfusion while avoiding the risks of fluid overload.
For more information on the most current sepsis treatment protocols, consult the official Surviving Sepsis Campaign guidelines, which are regularly updated based on new evidence.
Outbound Link: Surviving Sepsis Campaign: International Guidelines
