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Cleveland Clinic Journal of Medicine (CCJM)Do Patients with Sepsis Benefit from Intravenous Albumin?

Albumin vs. Crystalloids in Sepsis: Fluid Resuscitation Strategies and Their Impact on Patient Outcomes

Intravenous (IV) fluid resuscitation is a critical component in managing sepsis, but the choice between albumin and crystalloid solutions remains a subject of debate. Recent studies and meta-analyses have shed light on the efficacy and cost-effectiveness of these interventions, providing clinicians with evidence-based guidance for fluid management in septic patients.

Key Points:

  • Sepsis is defined as the presence of 2 or more systemic inflammatory response syndrome criteria plus a suspected or confirmed infectious source.
  • Severe sepsis involves end-organ dysfunction, hypotension, or hypoperfusion; septic shock requires vasopressors despite adequate fluid resuscitation.
  • IV fluids are categorized as crystalloid solutions (electrolytes and glucose in water) and colloid solutions (proteins in water).
  • Human serum albumin is a purified blood product available in 5% and 25% formulations.
  • Albumin theoretically increases intravascular colloid osmotic pressure, but physiologic studies show inconsistent clinical effects.
  • Albumin carries risks such as transfusion-related acute lung injury and potential disease transmission.
  • One albumin bolus can cost up to 60 times more than an equivalent crystalloid bolus.
  • The SAFE study (2004) found no overall benefit of albumin over saline in ICU patients, including those with sepsis.
  • The ALBIOS trial (2014) showed no significant difference in outcomes between albumin and crystalloid in severe sepsis patients.
  • A post hoc analysis of ALBIOS suggested a potential mortality benefit in septic shock patients, but further confirmation is needed.
  • Recent meta-analyses indicate improved hemodynamics with colloids but no consistent mortality benefit in sepsis patients without shock.
  • The Surviving Sepsis Campaign guidelines recommend balanced crystalloid solutions (e.g., lactated Ringer’s or Plasma-Lyte A) for initial resuscitation.
  • The SMART trial demonstrated a mortality benefit for balanced crystalloids over normal saline in a subset of sepsis patients.
  • Albumin has proven benefits in specific conditions such as large-volume paracentesis, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis patients.
  • For most hospitalized sepsis patients, crystalloid fluids are recommended over albumin due to lower risks and costs without proven mortality benefit.
  • Hypotensive sepsis patients should receive crystalloid resuscitation first, followed by vasopressors if needed.

In a meta-analysis of 15 studies that included 20,329 adults with sepsis, balanced crystalloids (BC) was associated with lower overall mortality, 28/30-day mortality, and acute kidney injury (AKI) than normal saline (NS), with similar 90-day mortality, need for renal replacement therapy (RRT), and ICU length-of-stay (LOS) between BC and NS.


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