Antibiotic Hemoperfusion May Be a Beneficial Adjunct to Sepsis Treatment

Combination therapy of polymyxin B hemoperfusion and conventional therapy significantly improved hemodynamics and organ dysfunction, and reduced 28-day mortality in patients with severe sepsis and/or septic shock from intra-abdominal gram-negative infections, researchers reported in the June 17 JAMA.

“Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis,” explained Dinna N. Cruz, MD, MPH, of St. Bortolo Hospital International Renal Research Institute Vicenza, Italy, and colleagues. In the device, polymycin B—an antibiotic with high affinity for endotoxin—has been immobilized to polystyrene filters.

“High levels of endotoxin activity are associated with worse clinical outcomes,” the authors explained, citing previous research. “However, effectiveness of endotoxin-targeted therapy is still controversial.”

The Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis (EUPHAS) trial—a prospective, multicenter trial conducted between 2004 and 2007—comprised 10 tertiary care ICU units. Dr. Cruz and colleagues randomized patients to receive conventional therapy alone (n = 30; mean age, 67), or conventional therapy with two sessions of polymyxin B hemoperfusion (n = 34; mean age, 61). Severe sepsis and septic shock were defined in accordance with the American College of Chest Physicians and the Society of Critical Care Medicine Consensus Conference, the researchers noted.

Patients were excluded from the analysis if they met any of several criteria, including age younger than 18, pregnancy, inclusion in other ICU studies within the last month, or organ transplantation in the last year.

At 72 hours, mean arterial pressure increased from 76 to 84 mm Hg and vasopressor requirement decreased (inotropic score, from 29.9 to 6.8) in patients in the treatment group, compared with patients in the control group (mean arterial pressure, 74 to 77 mm Hg; inotropic score, 28.6 to 22.4).

In addition, Dr. Cruz and colleagues observed a slight increase in Pao2/Fio2 in patients taking polymyxin B (235 to 264), compared with patients undergoing conventional therapy (217 to 228). Sequential Organ Failure Assessment scores improved with combination therapy, compared with conventional therapy alone (change in score, -3.4 vs -0.1, respectively). Furthermore, the 28-day mortality rate was 32% among patients in the treatment group, compared with 53% among patients in the control group (adjusted odds ratio, 0.36).

Adverse events were reported only in patients in the polymyxin group. In particular, there were four cases of cartridge clotting (6.0%), which were attributed to the low dose of heparin used in the study, one case of hypotension (1.5%) and two cases of tachycardia (3.0%), the investigators noted. There were no adverse events associated with bleeding or events indicative of neurotoxicity or nephrotoxity associated with polymyxin therapy.

“The effects of polymyxin B hemoperfusion on clinical endpoints in patients with sepsis has been debated in recent years, in part due to the paucity of high-quality data in this arena,” the study authors stated. “The results in this study shed light on this controversial matter.

“Larger multicenter studies are indicated to confirm these encouraging findings in other patient populations,” they added. “Furthermore, we advocate further studies to explore the use of newer assays for endotoxin activity both for patient selection, as well as guiding the number of hemoperfusion sessions.”

In an accompanying editorial, John A. Kellum, MD, of the University of Pittsburg, and Shigehiko Uchino, MD, of the Jikei University School of Medicine in Tokyo, suggested that while hemoperfusion therapy is commonly used in Japan, it is not so in the US.

“This kind of cross-community validation is refreshing and necessary but unfortunately only too rare,” they stated. “The results, although preliminary, suggest a number of interesting hypotheses and should provoke further study.”

—Frederique H. Theuvenin

Suggested Reading
Cruz DN, Antonelli M, Fumagalli R, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009;301(23):2445-2452.
Kellum JA, Uchino S. International differences in the treatment of sepsis: are they justified? JAMA. 2009;301(23):2496-2497

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