What is the preferred initial fluid therapy in adult patients with sepsis, considering those with and without significant comorbidities such as severe cardiovascular disease or chronic kidney disease?

Fluid Therapy in Sepsis: Crystalloids First, Balanced Solutions Preferred

Use crystalloids as your initial resuscitation fluid in sepsis, specifically balanced crystalloids (lactated Ringer's or Plasma-Lyte) over normal saline, and administer at least 30 mL/kg within the first 3 hours. 1, 2

Initial Fluid Selection

Crystalloids Are First-Line

• Crystalloids are the fluid of choice for initial resuscitation in severe sepsis and septic shock 3, 1, 2
• This recommendation is based on the absence of clear benefit from colloids compared to crystalloids, combined with the significantly higher cost of colloid solutions 3

Balanced Crystalloids Over Normal Saline

• Balanced crystalloids (lactated Ringer's or Plasma-Lyte) should be preferred over normal saline to reduce the risk of hyperchloremic metabolic acidosis 1, 2
• A large retrospective cohort study of 53,448 septic patients demonstrated that resuscitation with balanced fluids was associated with lower in-hospital mortality (19.6% vs 22.8%; relative risk 0.86) compared to unbalanced fluids 4
• The mortality benefit increased progressively with larger proportions of balanced fluids administered 4
• Normal saline causes hyperchloremic metabolic acidosis and is associated with increased risk of acute kidney injury progression, particularly in patients with pre-existing renal dysfunction 1

Initial Resuscitation Volume

The 30 mL/kg Rule

• Administer at least 30 mL/kg of crystalloid within the first 3 hours of sepsis recognition 3, 1, 2
• More rapid administration and greater amounts may be needed in some patients beyond this initial bolus 3, 2
• A portion of this volume may be albumin equivalent if substantial crystalloids are required 3

Fluid Challenge Technique

Dynamic Assessment Approach

• Continue fluid administration as long as hemodynamic parameters continue to improve 3, 1, 2
• Use dynamic measures (pulse pressure variation, stroke volume variation) preferentially over static variables (arterial pressure, heart rate) when available 3, 2
• Stop fluid administration when no improvement in tissue perfusion occurs, signs of fluid overload develop, or hemodynamic parameters stabilize 1

Fluids to Avoid

Hydroxyethyl Starches Are Contraindicated

• Do NOT use hydroxyethyl starches (HES) for fluid resuscitation in sepsis 3, 1, 2
• The 6S Trial demonstrated increased mortality with 6% HES 130/0.42 compared to Ringer's acetate (51% vs 43%, P=0.03) in septic patients 3
• HES increases the risk of acute kidney injury and mortality, particularly in patients with pre-existing renal dysfunction 1, 2
• A network meta-analysis confirmed higher mortality with starches compared to crystalloids and albumin 5

Role of Albumin

Consider for Large-Volume Resuscitation

• Albumin can be considered when patients require substantial amounts of crystalloids 3
• Network meta-analysis showed lower mortality with albumin compared to crystalloids (moderate confidence) and starches (moderate confidence) 5
• However, albumin remains a second-line option due to cost considerations and lack of consistent superiority over crystalloids in most clinical scenarios 3, 6

Special Populations

Patients with Cardiac Comorbidities

• In patients with severe cardiovascular disease or heart failure, fluid resuscitation must be more cautious to prevent pulmonary edema 7
• Use dynamic measures of fluid responsiveness more aggressively in this population to avoid fluid overload 2
• Consider earlier vasopressor initiation if hypotension persists with modest fluid volumes 1, 2

Patients with Chronic Kidney Disease

• Balanced crystalloids are particularly important in patients with pre-existing chronic kidney disease to avoid worsening acidosis and acute kidney injury 1
• Monitor closely for hypervolemia and consider earlier renal replacement therapy consultation if oliguria persists despite adequate resuscitation 7

Vasopressor Initiation

When Fluids Alone Are Insufficient

• If hypotension persists despite adequate fluid resuscitation, initiate norepinephrine as the first-choice vasopressor, targeting mean arterial pressure ≥65 mmHg 3, 1, 2
• Do not delay vasopressor initiation in patients who remain hypotensive after initial fluid bolus, as prolonged hypotension increases mortality 1

Critical Pitfalls to Avoid

• Do not delay resuscitation due to concerns about fluid overload—delayed resuscitation increases mortality 1
• Do not rely solely on central venous pressure to guide fluid therapy, as it has poor predictive ability for fluid responsiveness 1, 2
• Do not use low-dose dopamine for renal protection—it is ineffective 3, 1
• Avoid normal saline as the sole resuscitation fluid when balanced crystalloids are available 1, 4