The intervention arm consists of an exchange of one volume of plasma equivalent to the patient's total calculated blood volume (1.0 plasma volume plasma exchange) performed daily until discontinuation of vasopressors, death or up to a maximum of 5 days. Frozen plasma (FP) will be used as the replacement fluid. The control group will receive standard of care for the treatment of septic shock in accordance with local practice and informed by national and international guidelines.~The management of septic shock, including but not limited to, antibiotic therapy, infection source control, fluid therapy, mechanical ventilation, and nutrition, will be at the discretion of the treating PLEXSIS medical team, and will be recorded and reported.~The investigators will monitor for development of coagulopathy by measure the INR and fibrinogen levels daily. These are expected to normalize with the use of plasma as replacement fluid. The investigators will monitor for adverse reactions related to central venous access devices (insertion related complications, infection, thrombosis), TPE (including reaction to plasma, allergic reactions and hypotension). Venous access devices will be inserted by trained, experienced personnel using real-time ultrasound guidance.~To further our understanding of the biologic impact of TPE in sepsis, the investigators will collect plasma and whole blood samples at randomization (day 1), post TPE on day 1, prior to TPE treatment on day 3, and 48 hours after completion of TPE to evaluate markers of coagulation (D-dimer, thrombin-antithrombin (TAT) complexes, protein C levels, plasminogen-activator inhibitor 1) and ADAMTS13.
At the Health Sciences Centre and St. Boniface Hospital in Winnipeg, Manitoba, the investigators propose to conduct a two-center randomized trial comparing therapeutic plasma exchange to standard of care in patients diagnosed with septic shock.