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The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia.

ABSTRACT: BACKGROUND:Hemoperfusion through a column containing polymyxin B-immobilized fiber (PMX-HP) is beneficial in abdominal sepsis. We assessed the effects of PMX-HP in a model of severe Pseudomonas aeruginosa pneumonia. METHODS:Eighteen pigs with severe P. aeruginosa pneumonia were mechanically ventilated for 76 h. Pigs were randomized to receive standard treatment with fluids and vasoactive drugs, or standard treatment with two 3-h PMX-HP sessions. Antibiotics against P. aeruginosa were never administered. We assessed endotoxemia through the endotoxin activity assay (EA). We measured the static lung elastance, ratio of arterial partial pressure per inspiratory fraction of oxygen (PaO2/FIO2), mean arterial pressure, cardiac output, systemic vascular resistance and inotropic score. Finally, every 24 h, we assessed complete blood count. RESULTS:In comparison with the control group, PMX-HP decreased percentage of circulating neutrophils from 47.4 ± 13.8 to 40.8 ± 11.5 % (p = 0.009). In a subgroup of animals with the worst hemodynamic impairment, EA in the control and PMX-HP groups was 0.50 ± 0.29 and 0.29 ± 0.14, respectively (p = 0.018). Additionally, in the control and PMX-HP groups, static lung elastance was 26.9 ± 8.7 and 25.3 ± 7.5 cm H2O/L (p = 0.558), PaO2/FIO2 was 347.3 ± 61.9 and 356.4 ± 84.0 mmHg (p = 0.118), mean arterial pressure was 81.2 ± 10.3 and 81.6 ± 13.1 mmHg (p = 0.960), cardiac output was 3.30 ± 1.11 and 3.28 ± 1.19 L/min (p = 0.535), systemic vascular resistance was 1982.6 ± 608.4 and 2011.8 ± 750.0 dyne/s/cm(-5) (p = 0.939), and inotropic score was 0.25 ± 0.10 and 0.26 ± 0.18 (p = 0.864). CONCLUSIONS:In mechanically ventilated pigs with severe P. aeruginosa pneumonia, PMX-HP does not have any valuable clinical benefit, and studies are warranted to fully evaluate a potential role of PMX-HP in septic shock associated with severe pulmonary infections.

SUBMITTER: Li Bassi G

PROVIDER: S-EPMC4932027 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia.

Li Bassi Gianluigi G Marti Joan Daniel JD Xiol Eli Aguilera EA Comaru Talitha T De Rosa Francesca F Rigol Montserrat M Terraneo Silvia S Rinaudo Mariano M Fernandez Laia L Ferrer Miguel M Torres Antoni A

Annals of intensive care 20160705 1

<h4>Background</h4>Hemoperfusion through a column containing polymyxin B-immobilized fiber (PMX-HP) is beneficial in abdominal sepsis. We assessed the effects of PMX-HP in a model of severe Pseudomonas aeruginosa pneumonia.<h4>Methods</h4>Eighteen pigs with severe P. aeruginosa pneumonia were mechanically ventilated for 76 h. Pigs were randomized to receive standard treatment with fluids and vasoactive drugs, or standard treatment with two 3-h PMX-HP sessions. Antibiotics against P. aeruginosa w ...[more]

PMID: 27378201

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Project description:ObjectivesRapidly progressive interstitial pneumonia is a fatal disease with no established therapeutic options. The aim of this systematic review is to clarify the efficacy of interstitial pneumonia treatment utilizing direct hemoperfusion with a polymyxin B-immobilized fibre column.MethodsAll patients with adult-onset rapidly progressive interstitial pneumonia including acute exacerbation of underlying chronic interstitial pneumonia were eligible. Primary studies of any design, which compared outcomes of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment such as oxygenation and all-cause mortality with those of conventional therapy, were included. Electronic databases such as Medline and EMBASE were searched through October 7, 2018, and ICHUSHI, the largest database for medical articles in Japan, was also searched. Two reviewers independently extracted the relevant data and assessed the risk of bias in individual studies. The results were reported qualitatively due to substantial heterogeneity between studies.ResultsOut of 775 records retrieved, 10 reports were eligible and 8 of them were included for further analysis. They were all retrospective studies including a total of 327 patients and contained some risk of bias. There was variation in the administration method of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment such as the timing, frequency, duration and interval. Multivariate analyses of only two studies with historical controls demonstrated beneficial effects of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment over conventional therapy with all-cause mortality hazard ratios of 0.345 (95% confidence interval: 0.127-0.936) and 0.505 (95% confidence interval: 0.270-0.904), respectively. A significant difference of an improvement in the ratio of partial arterial oxygen pressure to the fraction of inspired oxygen in-between two treatment groups was also reported in two studies utilizing historical controls with mean differences of 56.8 and 57.5 mmHg, respectively.ConclusionsThere is currently insufficient data to support the use of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment for rapidly progressive interstitial pneumonia. It should be instituted for research purposes only until new evidence is available.

Project description:BackgroundPolymyxin B-immobilized fiber column hemoperfusion (PMX) has been reported to be effective for patients with septic shock. It remains unclear, however, how the efficacy of PMX varies according to the characteristics and underlying conditions of the patients treated. The objective of the present study was to clarify the factors that result in clinical efficacy of PMX treatment.MethodsWe retrospectively investigated 78 consecutive patients with severe sepsis or septic shock who underwent PMX treatment. We reviewed the demographic data, routine biochemistry, microbiological data, infection focus, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, change in mean arterial pressure (MAP), inotropic score, vasopressor dependency index, plasma levels of endotoxin and lactate, PaO2/FIO2 ratio, and survival time. We also divided the patients into two groups for comparison, namely, those whose inotropic scores improved after PMX treatment (improvement group) and those whose inotropic scores did not improve (non-improvement group).ResultsThe inotropic score and the vasopressor dependency index significantly decreased from 18.1 to 9.9 (p < 0.05) and from 0.27 to 0.14 (p < 0.05), respectively, after PMX treatment in the overall study population, while no significant change in the PaO2/FIO2 ratio was observed (p = 0.96). The inotropic score at pre-PMX treatment was significantly higher in the improvement group than in the non-improvement group (p < 0.01). The improvement of the PaO2/FIO2 ratio after PMX treatment was significant in the improvement group (p < 0.05).ConclusionsThe improvement group's inotropic score was higher, because of peripheral blood vessels dilatation and requirement for more catecholamines. Therefore, our study suggests that PMX treatment is particularly useful for improving hemodynamics in septic shock patients with excessively dilated peripheral blood vessels.

Project description:Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB.Trial registrationUniversity Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).

Project description:BACKGROUND:Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells. METHODS:We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level???0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28. RESULTS:Fifty-nine patients were randomized to PMX-HP (n?=?29) and non-PMX-HP (n?=?30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P?=?0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P?=?0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups. CONCLUSION:PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.

Dataset Information

The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia.

Publications

The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia.

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