Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality.

BACKGROUND: Uncontrolled proteolysis contributes to cell injury and organ dysfunction in animal models of circulatory shock. We investigated in humans the relationship between septic shock, proteolysis, and outcome. METHODS: Intensive care patients with septic shock (n=29) or sepsis (n=6) and non-hospitalised subjects (n=9) were recruited as part of the prospective observational trial 'ShockOmics' (ClinicalTrials.gov Identifier NCT02141607). A mass spectrometry-based approach was used to analyse the plasma peptidomes and the origin of circulating peptides from proteolysis in the enrolled subjects. RESULTS: Evidence of systemic proteolysis was indicated by a larger number of circulating peptides in septic shock patients, compared with septic patients and non-hospitalised healthy subjects. The peptide count and abundance in the septic shock patients were greater in patients who died (n=6) than in survivors (n=23), suggesting an association between magnitude of proteolysis and outcome. In silico analysis of the peptide sequences and of the sites of cleavage on the proteins of origin indicated a predominant role for serine proteases, such as chymotrypsin, and matrix metalloproteases in causing the observed proteolytic degradation. CONCLUSIONS: Systemic proteolysis is a novel fundamental pathological mechanism in septic shock. Plasma peptidomics is proposed as a new tool to monitor clinical trajectory in septic shock patients. CLINICAL TRIAL REGISTRATION: NCT02141607.

Declining mortality due to severe sepsis and septic shock in Spanish intensive care units: A two-cohort study in 2005 and 2011.

OBJECTIVE: To analyze the evolution of sepsis-related mortality in Spanish Intensive Care Units (ICUs) following introduction of the Surviving Sepsis Campaign (SSC) guidelines and the relationship with sepsis process-of-care. DESIGN: A prospective cohort study was carried out, with the inclusion of all consecutive patients presenting severe sepsis or septic shock admitted to 41 Spanish ICUs during two time periods: 2005 (Edusepsis study pre-intervention group) and 2011 (ABISS-Edusepsis study pre-intervention group). SCOPE: Patients with severe sepsis or septic shock admitted to Spanish ICUs. PATIENTS: All ICU admissions from the emergency department or wards and all ICU patients with a diagnosis of severe sepsis or septic shock. A total of 1348 patients were included: 630 in the 2005 group and 718 in the 2011 group. INTERVENTION: None. PRIMARY ENDPOINTS: ICU mortality, 28-day mortality and Hospital mortality, hospital length of stay, ICU length of stay and compliance with the resuscitation bundle. RESULTS: Compliance with the resuscitation bundle was significantly greater in the 2011 group (5.7% vs. 9.9%; p=0.005), and was associated to lower mortality (OR 0.602 [0.365-0.994]; p=0.048). The 2011 group had lower absolute in-hospital mortality (44.0% vs. 32.6%; p=0.01), 28-day mortality (36.5% vs. 23.0%; p=0.01), and adjusted mortality (OR 0.64 [0.49-0.83], p=0.001). CONCLUSIONS: Mortality related to severe sepsis or septic shock in Spain decreased between two patient cohorts in 2005 and 2011, and was attributable to earliness and improvement in sepsis care.

Extracorporeal CO2 removal: Technical and physiological fundaments and principal indications.

In recent years, technological improvements have reduced the complexity of extracorporeal membrane oxygenation devices. This have enabled the development of specific devices for the extracorporeal removal of CO2. These devices have a simpler configuration than extracorporeal membrane oxygenation devices and uses lower blood flows which could reduce the potential complications. Experimental studies have demonstrated the feasibility, efficacy and safety of extracorporeal removal of CO2 and some of its effects in humans. This technique was initially conceived as an adjunct therapy in patients with severe acute respiratory distress syndrome, as a tool to optimize protective ventilation. More recently, the use of this technique has allowed the emergence of a relatively new concept called "tra-protective ventilation"whose effects are still to be determined. In addition, the extracorporeal removal of CO2 has been used in patients with exacerbated hypercapnic respiratory failure with promising results. In this review we will describe the physiological and technical fundamentals of this therapy and its variants as well as an overview of the available clinical evidence, focused on its current potential.