Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial.
BACKGROUND
Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative-induced abdominal sepsis is likely associated with high circulating endotoxin. Reducing circulating endotoxin levels with polymyxin B hemoperfusion could potentially improve patient clinical outcomes.


OBJECTIVE
To determine whether polymyxin B hemoperfusion added to conventional medical therapy improves clinical outcomes (mean arterial pressure [MAP], vasopressor requirement, oxygenation, organ dysfunction) and mortality compared with conventional therapy alone.


METHODS
A prospective, multicenter, randomized controlled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]) conducted at 10 Italian tertiary care intensive care units between December 2004 and December 2007. Sixty-four patients were enrolled with severe sepsis or septic shock who underwent emergency surgery for intra-abdominal infection.


METHODS
Patients were randomized to either conventional therapy (n=30) or conventional therapy plus 2 sessions of polymyxin B hemoperfusion (n=34).


METHODS
Primary outcome was change in MAP and vasopressor requirement, and secondary outcomes were PaO(2)/FIO(2) (fraction of inspired oxygen) ratio, change in organ dysfunction measured using Sequential Organ Failure Assessment (SOFA) scores, and 28-day mortality.


RESULTS
MAP increased (76 to 84 mm Hg; P = .001) and vasopressor requirement decreased (inotropic score, 29.9 to 6.8; P < .001) at 72 hours in the polymyxin B group but not in the conventional therapy group (MAP, 74 to 77 mm Hg; P = .37; inotropic score, 28.6 to 22.4; P = .14). The PaO(2)/FIO(2) ratio increased slightly (235 to 264; P = .049) in the polymyxin B group but not in the conventional therapy group (217 to 228; P = .79). SOFA scores improved in the polymyxin B group but not in the conventional therapy group (change in SOFA, -3.4 vs -0.1; P < .001), and 28-day mortality was 32% (11/34 patients) in the polymyxin B group and 53% (16/30 patients) in the conventional therapy group (unadjusted hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20-0.94; adjusted HR, 0.36; 95% CI, 0.16-0.80).


CONCLUSIONS
In this preliminary study, polymyxin B hemoperfusion added to conventional therapy significantly improved hemodynamics and organ dysfunction and reduced 28-day mortality in a targeted population with severe sepsis and/or septic shock from intra-abdominal gram-negative infections.


BACKGROUND
clinicaltrials.gov Identifier: NCT00629382.
Cruz
Dinna N
DN
Department of Nephrology, Dialysis, and Transplantation, St Bortolo Hospital and International Renal Research Institute Vicenza, 36100 Vicenza, Italy.
Antonelli
Massimo
M
Fumagalli
Roberto
R
Foltran
Francesca
F
Brienza
Nicola
N
Donati
Abele
A
Malcangi
Vincenzo
V
Petrini
Flavia
F
Volta
Giada
G
Bobbio Pallavicini
Franco M
FM
Rottoli
Federica
F
Giunta
Francesco
F
Ronco
Claudio
C
D000005:Abdomen; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D004066:Digestive System Diseases / Q000401:mortality / Q000628:therapy*; D016905:Gram-Negative Bacterial Infections / Q000401:mortality / Q000628:therapy*; D006439:Hemodynamics; D006464:Hemoperfusion / Q000295:instrumentation*; D006801:Humans; D011112:Polymyxin B / Q000627:therapeutic use; D011446:Prospective Studies; D015657:Respiratory Transport; D012772:Shock, Septic / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*
D000900:Anti-Bacterial Agents; D011112:Polymyxin B