PMID- 17068736
OWN - NLM
STAT- MEDLINE
DCOM- 20070702
LR  - 20181201
IS  - 0393-5590 (Print)
IS  - 0393-5590 (Linking)
VI  - 23 Suppl 36
DP  - 2006 May-Jun
TI  - [Polymyxin-B direct hemoperfusion (PMX-DHP) in gram negative sepsis].
PG  - S94-102
AB  - Severe sepsis and septic shock have a mortality rate that may range between 28 
      and 50%. It is estimated that approximately 200,000 patients die per annum in the 
      USA as a consequence of sepsis. The reduction of plasma endotoxin levels to 
      achieve a favourable outcome for septic patients has been previously demonstrated 
      but the effectiveness of treatments targeting single inflammatory mediators 
      during established sepsis has been disappointing. Furthermore,some clinical study 
      clinically showed valuable reduction in cytokine levels by hemofiltration alone. 
      The prompt removal of endotoxins could be an effective way to reduce the 
      immunological activation and the amount of NO produced by endotoxin-activated 
      inducible NO-synthase in many tissues and cells. The polymyxin B cartridge is an 
      extracorporeal hemoperfusion device (PMX-DHP) known to remove circulating 
      endotoxins. Open-label clinical trials testing PMX-DHP have demonstrated its 
      safety in the septic shock treatment while the overall survival rate 
      significantly improved in comparison with the control groups. The purpose of this 
      study was to investigate the effects of PMX-DHP on redox status, inflammatory 
      cytokine profile, monocytes and PMN leukocyte activation in Gram-negative sepsis. 
      Prospective study: six patients, 2 males and 4 females 60.5+/-24.5 years old, in 
      ICU for severe Gram-negative sepsis (emergency surgery for intra abdominal 
      infection). Two PMX-DHP runs, at T0 and T1; 2 hours each; the first within 24 
      hours from sepsis diagnosis or 12 hours after emergency surgery, the first 
      PMX-DHP at T0, the second after 24 hours.; APACHE II score at T0: 20.1+/-3.7; 
      SOFA score 14.2+/-2.5; organ failure: 3+/-1.5; norepinephrine(Ne) in 1 patient; 
      Ne + dopamine (DA) in 4 patients; DA in 1 patient only. Mean dosage: Ne 0.24 
      mcg/kg/min; DA 8.9 mcg/kg/min. Four patients in CRRT (continuous veno-venous 
      hemofiltration, AN69 hemofilter) for the entire length of the study. QB 100+/-10 
      ml/min. Pre and post PMX-DHP, plasma endotoxins as well as anti-IL 1-beta, IL2, 
      IL4, IL5, IL6, IL8, IL10, TNF-alpha, GM-CSF, IFN-gamma levels were measured. 
      Expression of CD64 on monocytes and PMN leukocytes and I -2r CD25 on CD4+ T cells 
      by flow cytometry. Total and reduced plasma cysteine, homocysteine, glutathione 
      (GSH); plasma glutathione peroxidase (GSH-Px) and reductase (GSH-Rx); erythrocyte 
      GSH (eGSH), eGSH-Px and eGSH-Rx; NADP and NADPH and their ratio assessed pre and 
      post PMX-DHP, all compared with 15 age and gender-matched healthy subjects for 
      complete REDOX characterization. RESULTS: We observed a significant reduction of 
      endotoxin levels post PMX-DHP; CD64 monocytes and PMN leukocytes overexpression 
      returned to normal; pro-inflammatory cytokines Il6, Il 10 and TNF-alpha were 
      significantly reduced. We detected no differences in plasma levels of anti-IL 
      1-beta, IL2, IL4, IL5, IL8, GM-CSF, IFN-gamma pre versus post PMX-DHP. SOFA score 
      from 14.2+/-2.5 to 8.9+/-2.1 post PMX-DHP runs. Four out of six patients survived 
      and were discharged; mortality was 33% versus the anticipated 51%. CONCLUSION: 
      PMX-DHP reduces circulating endotoxins, down-activates monocytes and PMN 
      leukocytes, reduces pro-Inflammatory cytokines and corrects the redox environment 
      imbalance preventing oxidative damage to endothelial cells and the metabolic and 
      functional microvascular derangements that usually lead to multi-organ failure 
      and septic shock.
FAU - Perego, A F
AU  - Perego AF
AD  - A.O. Ospedale Niguarda Ca', Granda, Milano. angeloperego@hotmail.com
FAU - Morabito, S
AU  - Morabito S
FAU - Graziani, G
AU  - Graziani G
FAU - Casella, G P
AU  - Casella GP
FAU - Parodi, O
AU  - Parodi O
LA  - ita
PT  - Clinical Trial
PT  - Journal Article
TT  - L'moperfusione diretta con Polimixina-B (PMX-DHP) nel trattamento della sepsi da 
      gram negativi.
PL  - Italy
TA  - G Ital Nefrol
JT  - Giornale italiano di nefrologia : organo ufficiale della Societa italiana di 
      nefrologia
JID - 9426434
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cytokines)
RN  - 0 (Endotoxins)
RN  - J2VZ07J96K (Polymyxin B)
SB  - IM
EIN - G Ital Nefrol. 2007 Nov-Dec;24(6):628-9
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-Bacterial Agents
MH  - Cytokines/analysis
MH  - Endotoxins
MH  - Female
MH  - Gram-Negative Bacterial Infections/*complications
MH  - *Hemoperfusion
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Oxidation-Reduction
MH  - Polymyxin B
MH  - Prospective Studies
MH  - Sepsis/*immunology/microbiology/physiopathology/*therapy
EDAT- 2006/10/28 09:00
MHDA- 2008/03/14 09:00
CRDT- 2006/10/28 09:00
PHST- 2006/10/28 09:00 [pubmed]
PHST- 2008/03/14 09:00 [medline]
PHST- 2006/10/28 09:00 [entrez]
PST - ppublish
SO  - G Ital Nefrol. 2006 May-Jun;23 Suppl 36:S94-102.