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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., SCOPUS: ar.j, info:eu-repo/semantics/published

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.

Background We aimed to analyze compliance with 2010 European guidelines' quality criteria for external chest compressions (ECC) during 2 minutes of uninterrupted cardiopulmonary resuscitation. Methods Seventy-two healthy nurses and physicians trained in advanced cardiopulmonary resuscitation performed 2 uninterrupted minutes of ECC on a training manikin (Resusci Anne Advanced SkillTrainer; Laerdal Medical AS, Stavanger, Norway) that enabled us to measure the depth and rate of ECC. When professionals agreed to participate in the study, we recorded their age, body mass index (BMI), smoking habit, and their own subjective estimation of their physical fitness. To measure fatigue, we analyzed participants' heart rates, percentage of maximum tolerated heart rate (MHR), and subjective perception of their fatigue on a visual analog scale. Results Nearly half (48.6%) the rescuers failed to achieve a minimum average ECC depth of 50 mm. Only 48.1% of ECCs fulfilled the 2010 guidelines' quality criteria; quality deteriorated mainly after the first minute. Poor ECC quality and deteriorating quality after the first minute were associated with BMI 2 . Rescuers with BMI ≥ 23 kg/m 2 fulfilled the quality criteria throughout the 2 minutes, whereas those with BMI 2 fulfilled them for 80% of ECCs during the first minute, but for only 30% at the end of the 2 minutes. Conclusions Compliance with the 2010 guidelines' quality criteria is often poor, mainly due to lack of proper depth. The greater depth recommended in the 2010 guidelines with respect to previous guidelines requires greater force, so BMI 2 could hinder compliance. Limiting each rescuer's uninterrupted time doing ECC to 1 minute could help ensure compliance.