What is the initial management of sepsis, including fluid resuscitation and pressor use, in the inpatient setting?

Sepsis and Fluid Resuscitation Management in the Inpatient Setting

Immediate Recognition and Initial Actions

Sepsis and septic shock are medical emergencies requiring immediate treatment and resuscitation. 1

• Recognize sepsis through clinical examination evaluating heart rate, blood pressure, oxygen saturation, respiratory rate, temperature, and urine output 2
• Obtain blood cultures (at least two sets, aerobic and anaerobic) before antibiotics if this causes no significant delay (>45 minutes) 1, 2
• Administer broad-spectrum IV antibiotics within one hour of recognition, covering all likely pathogens based on clinical syndrome and local epidemiology 3, 2

Fluid Resuscitation Protocol

Initial Bolus (First 3 Hours)

Administer at least 30 mL/kg of IV crystalloid fluid within the first 3 hours for patients with sepsis-induced hypoperfusion (hypotension or lactate ≥4 mmol/L). 1, 4, 3, 2

Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) as first-line fluid choice over normal saline. 4

• Balanced crystalloids reduce risk of hyperchloremic metabolic acidosis and acute kidney injury compared to normal saline 4
• Crystalloids are strongly recommended over hydroxyethyl starches, which increase mortality and worsen acute kidney injury 1, 3
• Consider adding albumin when patients require substantial amounts of crystalloids (weak recommendation) 1

Ongoing Fluid Administration

Continue fluid administration using a fluid challenge technique as long as hemodynamic parameters continue to improve. 1

• Use dynamic measures (pulse pressure variation, stroke volume variation) over static measures (CVP) to predict fluid responsiveness 1
• Monitor clinical parameters: blood pressure, heart rate, mental status, urine output, capillary refill, skin mottling, peripheral pulses 1, 2
• Stop fluids when no improvement in tissue perfusion occurs, signs of fluid overload develop, or hemodynamic parameters stabilize 4

Critical Nuance on Fluid Volume

While guidelines recommend 30 mL/kg, emerging evidence suggests this may be excessive in some patients. Recent observational data shows medium-volume resuscitation (20-30 mL/kg) within the first 1-2 hours was associated with lower 28-day mortality (22.8%) compared to high-volume (>30 mL/kg, mortality 48.3%) or low-volume (<20 mL/kg) approaches 5. However, the guideline recommendation of at least 30 mL/kg remains the standard of care 1, with the understanding that "more rapid administration and greater amounts may be needed in some patients" while avoiding fluid overload 1.

Vasopressor Therapy

When to Initiate

Start vasopressors if hypotension persists despite adequate fluid resuscitation, targeting a mean arterial pressure (MAP) of 65 mmHg. 1, 3, 2

Vasopressor Selection Algorithm

First-line: Norepinephrine 1, 3, 2

• Norepinephrine is the first-choice vasopressor (strong recommendation, moderate quality evidence) 1

Second-line additions when MAP target not achieved:

• Add vasopressin 0.03 units/minute to norepinephrine to raise MAP or decrease norepinephrine dosage 1
• Vasopressin dosing per FDA label: start at 0.01 units/minute for septic shock, titrate by 0.005 units/minute every 10-15 minutes (maximum studied dose 0.07 units/minute) 6
• Alternatively, add epinephrine to norepinephrine 1
• Epinephrine dosing per FDA label: 0.05-2 mcg/kg/min, titrated every 10-15 minutes in increments of 0.05-0.2 mcg/kg/min 7

Avoid or use only in specific circumstances:

• Dopamine: only in highly selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia 1
• Phenylephrine: not recommended except when norepinephrine causes serious arrhythmias, cardiac output is known to be high with persistently low blood pressure, or as salvage therapy 1
• Do not use low-dose dopamine for renal protection—it is ineffective 4

Important vasopressin caveat: Low-dose vasopressin should not be used as the single initial vasopressor; doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy 1

Lactate Monitoring

• Measure lactate at diagnosis and guide resuscitation to normalize lactate in patients with elevated levels as a marker of tissue hypoperfusion 1, 3, 2
• Repeat lactate measurement within 6 hours if initially elevated 2

Source Control

Identify or exclude anatomic diagnosis of infection requiring emergent source control as rapidly as possible, and implement intervention as soon as medically and logistically practical. 1, 2

• Remove intravascular access devices that are possible sources of infection after establishing other vascular access 1
• Use the least physiologically invasive intervention (e.g., percutaneous drainage over surgical) 1

Critical Pitfalls to Avoid

Do not delay resuscitation due to concerns about fluid overload—delayed resuscitation increases mortality. 4

Do not rely solely on central venous pressure (CVP) to guide fluid therapy—it has poor predictive ability for fluid responsiveness. 4

Avoid fluid overresuscitation after initial stabilization, which can delay organ recovery, prolong ICU stay, and increase mortality. 3

Do not use hydroxyethyl starches—they increase mortality and acute kidney injury. 1, 3

Avoid normal saline when balanced crystalloids are available—saline causes hyperchloremic acidosis and may worsen kidney injury. 4