Newsdesk
International Sepsis Forum 2014 The 2014 International Sepsis Forum was held in Paris (Dec 2–5). The conference covered topics from the basic molecular biology of sepsis to clinical trials. Raffaella Bosurgi reports. Fluid resuscitation in sepsis: crystalloids or colloids? Simon Finfer (George Institute for Global Health, Sydney, NSW, Australia) gave a presentation on whether crystalloids or colloids are the best fluid resuscitation to be used for septic shock. Results of a crosssectional study of 391 intensive care units in 25 countries showed that colloids were given to more patients than were crystalloids (1234 [23·4%] vs 782 [14·8%]) over 24 h. The latest Cochrane meta-analysis from 2013 showed that there is no evidence from clinical trials that resuscitation with colloids reduces risk of death more effectively than resuscitation with crystalloids in patients with trauma or burns, or after surgery. Present guidelines suggest using crystalloids and favour albumin in patients who do not stabilise.
ProCESS trial Derek Angus (University of Pittsburgh, USA) presented the latest findings from the ProCESS trial of early septic shock in 31 US emergency departments. 1341 patients received 6 h of resuscitation in one of three randomly assigned groups: protocol-based early goal-directed therapy (EGDT), protocolbased treatment, or usual care. There were two sequential hypotheses: is protocol-based resuscitation superior to usual care? And is EGDT superior to protocol-based resuscitation? For patients with early septic shock who were promptly recognised and given intravenous bolus for hypotension and intravenous antibiotics, there was no apparent benefit of protocol-based resuscitation.
ARISE trial Anthony Delaney (University of Sidney, Australia) gave a presentation www.thelancet.com/infection Vol 15 February 2015
on the international, multicentre ARISE trial—the largest trial of EGDT for patients with early septic shock. The trial tested the hypothesis that, compared with usual care, EGDT would decrease 90-day all-cause mortality in adults presenting to the emergency department with early septic shock. EGDT use was associated with increased use of intravenous fluids and vasopressors, but not with decreased mortality. These findings, together with those from the PROCESS trial, show that implementation of EGDT for all patients with severe sepsis and septic shock is not justified at present.
Sirtuins as a new target for sepsis Steven Opal (Brown University, Providence, RI, USA) discussed sirtuins as possible new targets for treatment of severe sepsis. Sirtuin-1 represses transcriptional activity of NF-κB by de-acetylation of the p65 subunit of Nf-κB. It also activates the transcriptional co-repressor TLE-1. Other sirtuin-1 targets in sepsis include activation of PGC-1α, which supports mitochondrial function and biogenesis and inhibits p53 and other apoptotic factors. Sirtuins can then alter several signalling pathways that are engaged during sepsis.
GM-CSM trials Petra Reinke (Charité, Universitätsmedizin Berlin, Germany) gave a presentation on granulocyte-macrophage colony-stimulating factor (GM-CSF), a monomeric glycoprotein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells, and fibroblasts that functions as a cytokine. A meta-analysis published in 2011 identified 12 randomised controlled trials with a total of 2380 patients. However, these studies did not stratify
patients and no standardised tests were used. She presented data from a more recent trial showing that GM-CSM is safe, can reconstitute monocyte function in patients with sepsis, and can shorten the need for ventilation.
Stem cells for sepsis Pierre Francois Laterre (Saint-Luc UCL, Brussels, Belgium) gave a presentation on stem cells in sepsis. After damage, injury, or sepsis, stem cells seem to augment the immune response, improving bacterial clearance, delaying bacterial growth, and reducing the release of cytokines. They enhance integrity of vascular barriers, have an anti-apoptotic effect, and improve survival. In animal models, expanded stem cells extracted from adipose tissue (eASCs) can decrease proinflammatory mediators and increase anti-inflammatory mediators, and have antimicrobial effects. Cx611 (an allogenic product for eASCS in the treatment of sepsis) significantly reduced mortality in two animal models of sepsis. Investigators are planning clinical studies to test the laboratory findings.
EUPHRATES trial Phillip Dellinger (Cooper University Health Care, USA) gave a presentation on the EUPHRATES study, an ongoing randomised controlled trial assessing polymyxin B haemoperfusion for adults treated for endotoxaemia and septic shock. 360 patients with Gram-negative or Gram-positive bacterial infection were included from 50 intensive care units in the USA and Canada. The study, which is assessing 28-day mortality, is scheduled to finish in 2016.
Raffaella Bosurgi 155
International Sepsis Forum 2014 The 2014 International Sepsis Forum was held in Paris (Dec 2–5). The conference covered topics from the basic molecular biology of sepsis to clinical trials. Raffaella Bosurgi reports. Fluid resuscitation in sepsis: crystalloids or colloids? Simon Finfer (George Institute for Global Health, Sydney, NSW, Australia) gave a presentation on whether crystalloids or colloids are the best fluid resuscitation to be used for septic shock. Results of a crosssectional study of 391 intensive care units in 25 countries showed that colloids were given to more patients than were crystalloids (1234 [23·4%] vs 782 [14·8%]) over 24 h. The latest Cochrane meta-analysis from 2013 showed that there is no evidence from clinical trials that resuscitation with colloids reduces risk of death more effectively than resuscitation with crystalloids in patients with trauma or burns, or after surgery. Present guidelines suggest using crystalloids and favour albumin in patients who do not stabilise.
ProCESS trial Derek Angus (University of Pittsburgh, USA) presented the latest findings from the ProCESS trial of early septic shock in 31 US emergency departments. 1341 patients received 6 h of resuscitation in one of three randomly assigned groups: protocol-based early goal-directed therapy (EGDT), protocolbased treatment, or usual care. There were two sequential hypotheses: is protocol-based resuscitation superior to usual care? And is EGDT superior to protocol-based resuscitation? For patients with early septic shock who were promptly recognised and given intravenous bolus for hypotension and intravenous antibiotics, there was no apparent benefit of protocol-based resuscitation.
ARISE trial Anthony Delaney (University of Sidney, Australia) gave a presentation www.thelancet.com/infection Vol 15 February 2015
on the international, multicentre ARISE trial—the largest trial of EGDT for patients with early septic shock. The trial tested the hypothesis that, compared with usual care, EGDT would decrease 90-day all-cause mortality in adults presenting to the emergency department with early septic shock. EGDT use was associated with increased use of intravenous fluids and vasopressors, but not with decreased mortality. These findings, together with those from the PROCESS trial, show that implementation of EGDT for all patients with severe sepsis and septic shock is not justified at present.
Sirtuins as a new target for sepsis Steven Opal (Brown University, Providence, RI, USA) discussed sirtuins as possible new targets for treatment of severe sepsis. Sirtuin-1 represses transcriptional activity of NF-κB by de-acetylation of the p65 subunit of Nf-κB. It also activates the transcriptional co-repressor TLE-1. Other sirtuin-1 targets in sepsis include activation of PGC-1α, which supports mitochondrial function and biogenesis and inhibits p53 and other apoptotic factors. Sirtuins can then alter several signalling pathways that are engaged during sepsis.
GM-CSM trials Petra Reinke (Charité, Universitätsmedizin Berlin, Germany) gave a presentation on granulocyte-macrophage colony-stimulating factor (GM-CSF), a monomeric glycoprotein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells, and fibroblasts that functions as a cytokine. A meta-analysis published in 2011 identified 12 randomised controlled trials with a total of 2380 patients. However, these studies did not stratify
patients and no standardised tests were used. She presented data from a more recent trial showing that GM-CSM is safe, can reconstitute monocyte function in patients with sepsis, and can shorten the need for ventilation.
Stem cells for sepsis Pierre Francois Laterre (Saint-Luc UCL, Brussels, Belgium) gave a presentation on stem cells in sepsis. After damage, injury, or sepsis, stem cells seem to augment the immune response, improving bacterial clearance, delaying bacterial growth, and reducing the release of cytokines. They enhance integrity of vascular barriers, have an anti-apoptotic effect, and improve survival. In animal models, expanded stem cells extracted from adipose tissue (eASCs) can decrease proinflammatory mediators and increase anti-inflammatory mediators, and have antimicrobial effects. Cx611 (an allogenic product for eASCS in the treatment of sepsis) significantly reduced mortality in two animal models of sepsis. Investigators are planning clinical studies to test the laboratory findings.
EUPHRATES trial Phillip Dellinger (Cooper University Health Care, USA) gave a presentation on the EUPHRATES study, an ongoing randomised controlled trial assessing polymyxin B haemoperfusion for adults treated for endotoxaemia and septic shock. 360 patients with Gram-negative or Gram-positive bacterial infection were included from 50 intensive care units in the USA and Canada. The study, which is assessing 28-day mortality, is scheduled to finish in 2016.
Raffaella Bosurgi 155
