UMEÅ, SWEDEN—In severe sepsis, the risk of death increases with the presence of renal failure; when sepsis results in shock or multiple organ dysfunction syndrome (MODS), the risk of death can exceed 80%. A recent retrospective study found that in 76 patients with MODS and acute renal failure, plasma exchange added to usual ICU care significantly increased survival.[1]

18-YEAR RETROSPECTIVE STUDY

Swedish researchers reviewed data for patients who underwent plasma exchange at one of two study hospitals in the past 18 years. All patients had progressive sepsis with disseminated intravascular coagulation (DIC) and MODS unresponsive to conventional therapy. In addition, they had acute renal failure and progressive respiratory failure necessitating supplemental oxygen. Seventy-two percent of patients required mechanical ventilation.

Plasma exchange was initiated as rescue therapy in the ICU. Plasma corresponding to about 30 to 35 mL/kg of body weight was removed and replaced with stored plasma or fresh-frozen plasma. The process was repeated until the patient’s condition was stabilized. Up to six times per week, patients underwent hemodialysis for three to four hours. In addition, all patients received fluids and antibiotics, and three quarters were given either heparin or low-molecular-weight heparin.

The majority of patients received intravenous hydrocortisone at an initial dosage of 100 to 400 mg/d, with the dose tapering over the next two to five days. Fifty-seven percent of the patients were receiving more than one vasoactive drug.

HIGH SURVIVAL RATE SEEN

Sixty-two patients survived; this 82% survival rate is substantially higher than the average survival reported in the literature. There were no severe or life-threatening adverse events during any of the 221 plasma exchange sessions.

The survival rate of 82% was also markedly higher than that reported in other studies. Bernd G. Stegmayr, MD, PhD, Professor of Medicine (Nephrology) at University Hospital in Umeå, Sweden, noted that although the use of other drugs with plasma exchange could have affected survival, “[we] tried most drugs before deciding to use plasma exchange as rescue therapy.”

A NEED FOR MORE STUDIES

In an editorial,[2] Bulent Cuhaci, MD, noted that plasma exchange has been used since the 1970s, with the greatest success rate in patients with thrombotic thrombocytopenic purpura. In those patients, plasma exchange increased the survival rate to 90%. Dr. Cuhaci added that it is unknown whether this improvement was due to the removal of harmful plasma or its replacement with healthy plasma.

“I think plasma exchange should be added if conventional therapy alone is not sufficient, and when septic shock progresses despite the use of vasoactive drugs,” said Dr. Stegmayr. “If my patients with septic shock have received optimal conventional ICU care, I consider plasma exchange. I believe that it is necessary to add plasma from healthy donors to compensate for the loss of vital plasma products,” he noted.

While observing that plasma exchange with concomitant use of anticoagulants and corticosteroids is not part of standard sepsis care in the United States, Dr. Cuhaci wrote, “[W]e cannot ignore [the] 82% survival rate in this group with severe sepsis and multiple organ failure including acute renal failure.”

According to Dr. Stegmayr, “Once DIC or MODS has developed, other organ systems will often be affected. Thus, it seems plausible to consider plasma exchange in patients with acute respiratory distress syndrome or milder acute renal failure, to halt the progress of MODS. This has to be proven by further studies.”

Dr. Cuhaci also recommended prospective, randomized, controlled trials to better define the potential role of plasma exchange in sepsis and multiple organ failure.

An Open Invitation to Participate in an Upcoming Multicenter Trial

A large multicenter study is being planned to assess the efficacy of plasma exchange in addition to conventional ICU care in patients with septic shock. To be eligible, patients must have septic shock that has progressed to a stage necessitating vasoactive drugs; disseminated intravascular coagulopathy; and failure of at least two organs, including acute renal failure. Each center may apply to join the study through its local ethics committee. Centers must have at least three patients with the above criteria each year. The study is run through an Internet site for which an access code can be requested. After directing your browser to www.iml.umu.se/medicin, go to the Intensive Care heading and from there go to Plasma Exchange Sepsis Trial. To test the system, log on using the testing code AL61TMS. After logging on, you can download a PDF version of the study protocol. Principal investigator Dr. Bernd Stegmayr can be contacted by e-mail for more information (e-mail: bernd.stegmayr@medicin.umu.se).

—Gale Jurasek

References
1. Stegmayr BG, Banga R, Berggren L, et al. Plasma exchange as rescue therapy in multiple organ failure including acute renal failure. Crit Care Med. 2003;31:1730-1736.
2. Cuhaci B. Plasma exchange in multiple organ failure: changing gears in sepsis and organ failure. Crit Care Med. 2003;31:1875-1877.

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