Why Are Crystalloids Used in Sepsis?

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Key Takeaways:

  • Crystalloids are recommended as the first-line fluid for sepsis resuscitation per treatment guidelines.
  • Isotonic crystalloids effectively restore intravascular volume and perfusion in sepsis patients.
  • Crystalloids are safe, inexpensive, and readily available making them well-suited for early sepsis management.
  • Balanced crystalloid solutions may have some advantages over normal saline in sepsis.
  • Albumin is added if crystalloids alone are insufficient to stabilize sepsis patients.

Sepsis is a life-threatening condition triggered by the body’s extreme immune response to an infection. Rapid treatment is critical to halt the progression of sepsis into septic shock and multiple organ failure. One of the first therapies implemented is intravenous (IV) fluid resuscitation to restore adequate circulating volume and tissue perfusion. But why specifically are crystalloid solutions the go-to fluids for early sepsis management?

What Are Crystalloids?

Crystalloids are aqueous solutions of mineral salts or other water-soluble molecules. They contain electrolytes like sodium, chloride, potassium and other small ions. The relatively low molecular weight of these dissolved particles allows crystalloids to distribute rapidly across biological membranes.

Common crystalloid solutions include:

  • Normal saline (0.9% sodium chloride)
  • Lactated Ringer’s solution
  • Plasma-Lyte

These sterile IV fluids are isotonic, meaning their osmolarity (solute concentration) is similar to human plasma. Isotonic crystalloids can effectively increase blood volume without overhydrating or underhydrating cells when the vascular space needs rapid replenishment.

Why Use Crystalloids for Sepsis Resuscitation?

Restoring Intravascular Volume: The top treatment priority in sepsis is to normalize cardiac output and blood pressure to maintain adequate tissue perfusion. Crystalloid solutions are highly effective for expanding the depleted intravascular volume and restoring hemodynamic stability.

Guideline Recommended: Clinical practice guidelines consistently recommend isotonic crystalloids as the first-line resuscitative fluid for sepsis and septic shock.

According to the Surviving Sepsis Campaign’s 2018 guidelines, crystalloids should be administered at a rate of 30 mL/kg within the first hour for hypotensive sepsis patients or those with an elevated lactate level.

Readily Available: Crystalloids are inexpensive to produce, have a long shelf life, and are universally stocked in healthcare settings. Rapid initiation of crystalloid infusions enables fluid resuscitation to begin immediately in sepsis patients before lab results or specialty fluids are available.

Minimal Safety Risks: Crystalloids have relatively few adverse effects compared to other IV fluids. Large volumes can be infused quickly with lower risks of complications like fluid overload. This makes crystalloids well-suited for aggressive early volume expansion in sepsis.

Cost-Effective: Crystalloid solutions are considerably less costly than colloids like albumin. Their low expense facilitates the large volume infusions often required in sepsis without excessive financial burden.

Crystalloid Options for Sepsis

While crystalloids are the consensus first-line fluids for sepsis, there are choices when it comes to which specific solutions to use. Two of the most common options are normal saline and balanced crystalloids.

Normal Saline

Normal saline contains 0.9% sodium chloride in an aqueous solution. It has long been the traditional go-to crystalloid for resuscitation.


  • Isotonic and safe for rapid high-volume infusions
  • Familiar to clinicians and widely available
  • Inexpensive


  • Supraphysiologic chloride content may cause hyperchloremic acidosis
  • Lacks buffering capacity
  • No electrolytes besides sodium and chloride

Balanced Crystalloids

Balanced crystalloids like Lactated Ringer’s or Plasma-Lyte contain electrolytes in concentrations closer to human plasma. In addition to sodium and chloride, they contain physiologic levels of potassium, calcium, magnesium, and buffer agents.


  • Electrolyte composition mimics plasma
  • Buffering capacity helps prevent acid-base disturbances
  • Associated with less kidney injury in some studies


  • Slightly more expensive than normal saline
  • Contains lactate as a buffer which some patients may avoid

There is some evidence that balanced crystalloids like Plasma-Lyte may lead to better outcomes compared to normal saline in sepsis patients. However, more research is still needed.

When to Add Albumin

Although crystalloids are the first-line fluids in sepsis, adjunctive agents like albumin may be added in certain scenarios.

If crystalloids alone are insufficient to stabilize hemodynamics, guidelines recommend considering supplemental albumin. The 2018 Surviving Sepsis Campaign guidelines suggest adding albumin when >30 mL/kg of crystalloids have been administered without hemodynamic improvement.

For profound hypoalbuminemia, albumin may help increase oncotic pressure and fluid retention in the vascular space. Albumin levels <2 g/dL are typically used as a threshold for replacement.

However, several randomized controlled trials have found no mortality benefit from adding albumin to crystalloids for initial sepsis resuscitation. The decision to add albumin should be made individually based on the clinical scenario.

Crystalloids Remain First-Line for Sepsis

In summary, crystalloid solutions remain the consensus first-choice fluid for sepsis and septic shock resuscitation. Clinical practice guidelines universally recommend timely crystalloid administration to rapidly restore intravascular volume and improve tissue perfusion in sepsis. Isotonic crystalloids like normal saline and balanced solutions are safe, effective, inexpensive, and readily available – making them well-suited for early goal-directed therapy. While the optimal crystalloid choice is still debated, balanced fluids may offer some advantages. If crystalloids fail to achieve hemodynamic stability, adding albumin is a guideline-recommended strategy. But crystalloids still form the foundation of initial sepsis fluid resuscitation.

Frequently Asked Questions about Crystalloids in Sepsis

Why use crystalloids rather than colloids for sepsis resuscitation?

Crystalloids are recommended over colloids like starches and gelatins for sepsis fluid resuscitation for several reasons:

  • Crystalloids distribute quickly to expand vascular volume.
  • Are safer with lower risks of adverse effects like kidney injury or coagulopathy.
  • Are considerably less expensive.
  • Do not require blood product compatibility consideration.
  • Are readily available even in low-resource settings.

According to a 2018 Cochrane review, there is no evidence that colloids reduce mortality compared to crystalloids in sepsis. Crystalloids remain first-line.

What are the signs that a sepsis patient needs fluid resuscitation?

The key indications that a sepsis patient requires urgent fluid resuscitation include:

  • Hypotension (systolic BP <90 mmHg)
  • Tachycardia (HR >90)
  • Prolonged capillary refill (>2 sec)
  • Cool, clammy, mottled skin indicating poor perfusion
  • Lactate level >4 mmol/L
  • Oliguria (<0.5 mL/kg/hr urine output)

These signs reflect insufficient circulating volume and tissue hypoperfusion requiring rapid crystalloid infusion to stabilize hemodynamics.

How much crystalloid should be given to a sepsis patient initially?

Guidelines recommend giving 30 mL/kg of crystalloids within the first hour for sepsis patients with hypotension or elevated lactate. This is part of early goal-directed therapy to rapidly restore perfusion.

Ongoing fluid needs are then determined by the patient’s hemodynamic response. Additional boluses of 500-1000 mL crystalloids may be given every 15-30 mins as needed to maintain adequate BP and urine output.

Does sodium bicarbonate have a role in managing sepsis?

Routine use of sodium bicarbonate is not recommended. Studies show it does not improve hemodynamics or mortality in sepsis. However, it may be used as a buffer in life-threatening acidemia (arterial pH <7.1). Bicarbonate therapy requires close monitoring to avoid overshoot alkalosis or sodium overload.

What are signs that a sepsis patient needs a second IV line for fluid administration?

It is appropriate to place a second peripheral IV catheter (or central line) when:

  • Fluid demands exceed capacity of initial IV site.
  • Initial IV site fails or infiltrates.
  • Medications incompatible with currently running fluids need administration.
  • Central access needed for vasopressors or monitoring.

Two large-bore IVs ensure continuous high-volume crystalloid infusion in sepsis.

How do balanced crystalloids compare to albumin for sepsis fluid resuscitation?

Albumin is not superior to crystalloids for initial sepsis resuscitation based on randomized trials. Albumin costs significantly more and carries risks like allergic reactions. However, albumin may be added to crystalloids for refractory shock or profound hypoalbuminemia. In summary:

  • Crystalloids are first-line fluids per guidelines.
  • Albumin is an adjunctive therapy if needed.
  • More research is needed comparing solutions.

What are the signs of fluid overload to monitor for during sepsis resuscitation?

Conservative late fluid management is recommended after the initial resuscitation phase. Signs of fluid overload warrant slowing infusions:

  • Jugular venous distension
  • Crackles on lung exam
  • Peripheral edema
  • Ascites
  • Unexplained weight gain (>10% baseline)
  • Hypoxia or pulmonary congestion on imaging

Fluid balance should be monitored closely to avoid worsening lung function. Diuretics may be used to achieve a net negative fluid balance.

What are relative contraindications to rapid high-volume crystalloid resuscitation?

Crystalloid infusion rates should be reduced with:

  • Severe heart failure at risk of volume overload.
  • End-stage renal disease at risk of hyperkalemia.
  • Severe liver failure at risk of fluid accumulation.

Crystalloids are still used but at lower volumes with more frequent patient reassessment.


In conclusion, crystalloid solutions remain the first-line fluid for sepsis resuscitation per clinical practice guidelines. Isotonic crystalloids effectively expand intravascular volume to rapidly improve tissue perfusion in sepsis patients. They are safe, inexpensive, readily accessible, and easy to administer in high volumes – making them well-suited for early goal-directed therapy. While balanced crystalloids may offer some advantages, normal saline is still commonly used. If crystalloids fail to stabilize hemodynamics, albumin can be added as an adjunct. But crystalloids are still the foundation of initial fluid management in sepsis. Following an evidence-based resuscitation protocol using crystalloids provides the best chance of improving outcomes in this deadly syndrome.

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