The investigators prospective, randomized adult clinical trial investigates the therapeutic efficacy of early therapeutic plasma exchange as adjunct treatment to standard therapy in patients with refractory septic shock and multiple organ failure.

Inclusion Criteria:

• Adult patients are eligible for inclusion if they have sepsis with refractory shock and evidence of organ failure.

Exclusion Criteria:

• Persons who are pregnant

• Persons who are incarcerated

• Acute surgical catastrophe without potential for intervention or source control

• Cardiac arrest with unknown neurologic status, including patients being treated with therapeutic hypothermia

• Presence of severe acute brain injury or severe dementia

• Cardiogenic, neurogenic, obstructive, or post-cardiotomy shock

• Acute pancreatitis with no established source of infection

• Diabetic ketoacidosis as primary pathology

  • Note: Septic patients who develop DKA are eligible for inclusion. However, patients in whom organ dysfunction and hemodynamic instability are due primarily to volume depletion and acidosis from DKA should not be included.

• Need for mechanical circulatory support

• Prolonged acute illness with > 24 hours of pressor needs at enrollment and/or end organ damage with further care deemed to be "futile."

  • NOTE: The time resets if a new inciting event leads to SAMOF.
  • For example, if a patient has sepsis stabilized but requires operative intervention for source control within the initial 24 hours of admission and returns to the ICU with SAMOF, the patient is again eligible for randomization for the next 24 hours.

• Bedbound state or poor baseline functional status with ECOG performance status score ≥ 3

• Underlying terminal illness/malignancy with < 6 months life expectancy

• Advanced chronic liver disease/cirrhosis with evidence of portal hypertension

• Asplenia

• HIV with HARRT non-compliance