Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial

D. J. Klein, D. Foster, P. M. Walker, S. M. Bagshaw, H. Mekonnen, M. Antonelli

Research output: Contribution to journalArticle

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Abstract

Purpose: The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA ≥ 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6–0.89. Methods: Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA ≥ 0.6–0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline. Results: At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (− 0.5, 19.5) vs. 4 mmHg (− 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P = 0.005]. The median EAA change in the population was − 12.9% (range: increase 49.2%–reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P = 0.08. Conclusions: These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA ≥ 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality. Trial registration: Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

Original languageEnglish
Pages (from-to)2205-2212
Number of pages8
JournalIntensive Care Medicine
Volume44
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Hemoperfusion
Polymyxin B
Endotoxemia
Septic Shock
Mortality
Arterial Pressure
Mechanical Ventilators
Endotoxins
Length of Stay
APACHE
Dialysis
Norepinephrine
Survival
Therapeutics
Growth
Infection
Population

Keywords

  • Endotoxemia
  • Endotoxin
  • Hemoperfusion
  • Polymyxin B
  • Precision medicine
  • Sepsis
  • Septic shock

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia : a post hoc analysis of the EUPHRATES trial. / Klein, D. J.; Foster, D.; Walker, P. M.; Bagshaw, S. M.; Mekonnen, H.; Antonelli, M.

In: Intensive Care Medicine, Vol. 44, No. 12, 01.12.2018, p. 2205-2212.

Research output: Contribution to journalArticle

Klein, D. J. ; Foster, D. ; Walker, P. M. ; Bagshaw, S. M. ; Mekonnen, H. ; Antonelli, M. / Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia : a post hoc analysis of the EUPHRATES trial. In: Intensive Care Medicine. 2018 ; Vol. 44, No. 12. pp. 2205-2212.
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abstract = "Purpose: The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA ≥ 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6–0.89. Methods: Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA ≥ 0.6–0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline. Results: At 28 days, 23 patients of 88 (26.1{\%}) in the PMX group died versus 39 of 106 (36.8{\%}) in the sham group [risk difference 10.7{\%}, OR 0.52, 95{\%} CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95{\%} CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (− 0.5, 19.5) vs. 4 mmHg (− 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20{\%}) vs. sham, 13/31 (41.9{\%}), P = 0.005]. The median EAA change in the population was − 12.9{\%} (range: increase 49.2{\%}–reduction 86.3{\%}). The mortality in the above median EAA change group was PMX: 6/38 (15.7{\%}) vs. sham 15/49 (30.6{\%}), P = 0.08. Conclusions: These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA ≥ 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality. Trial registration: Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.",
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TY - JOUR

T1 - Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia

T2 - a post hoc analysis of the EUPHRATES trial

AU - Klein, D. J.

AU - Foster, D.

AU - Walker, P. M.

AU - Bagshaw, S. M.

AU - Mekonnen, H.

AU - Antonelli, M.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Purpose: The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA ≥ 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6–0.89. Methods: Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA ≥ 0.6–0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline. Results: At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (− 0.5, 19.5) vs. 4 mmHg (− 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P = 0.005]. The median EAA change in the population was − 12.9% (range: increase 49.2%–reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P = 0.08. Conclusions: These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA ≥ 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality. Trial registration: Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

AB - Purpose: The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA ≥ 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6–0.89. Methods: Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA ≥ 0.6–0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline. Results: At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (− 0.5, 19.5) vs. 4 mmHg (− 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P = 0.005]. The median EAA change in the population was − 12.9% (range: increase 49.2%–reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P = 0.08. Conclusions: These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA ≥ 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality. Trial registration: Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

KW - Endotoxemia

KW - Endotoxin

KW - Hemoperfusion

KW - Polymyxin B

KW - Precision medicine

KW - Sepsis

KW - Septic shock

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