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Author(s): Giacomo Grasselli [sup.1] [sup.2], Carolyn S. Calfee [sup.3], Luigi Camporota [sup.4] [sup.5], Daniele Poole [sup.6], Marcelo B. P. Amato [sup.7], Massimo Antonelli [sup.8] [sup.9], Yaseen M. Arabi [sup.10] [sup.11] [...], The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

Author(s): Tracey H. Fan [sup.1], Merry Huang [sup.2], Aron Gedansky [sup.2], Carrie Price [sup.3], Chiara Robba [sup.4], Adrian V. Hernandez [sup.5] [sup.6], Sung-Min Cho [sup.7] Author Affiliations: (1) grid.32224.35, 0000 [...], Objectives Acute respiratory distress syndrome (ARDS) in patients with traumatic brain injury (TBI) is associated with increased mortality. Information on the prevalence of ARDS and its neurological outcome after TBI is sparse. We aimed to systematically review the prevalence, risk factors, and outcome of ARDS in TBI population. Data Sources PubMed and four other databases (Embase, Cochrane Library, Web of Science Core Collection, and Scopus) from inception to July 6, 2020. Study Selection Randomized controlled trials (RCTs) and observational studies in patients older than 18 years old. Data Extraction Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for RCTs, the Newcastle-Ottawa Scale for cohort and case-control studies. Good neurological outcome was defined as Glasgow Outcome Scale [greater than or equal to] 4. Random-effects meta-analyses were conducted to estimate pooled outcome prevalence and their 95% confidence intervals (CI). Data Synthesis We included 20 studies (n = 2830) with median age of 44 years (interquartile range [IQR] = 35-47, 64% male) and 79% (n = 2237) suffered severe TBI. In meta-analysis, 19% patients (95% CI = 0.13-0.27, I.sup.2 = 93%) had ARDS after TBI. The median time from TBI to ARDS was 3 days (IQR = 2-5). Overall survival at discharge for the TBI cohort was 70% (95% CI = 0.64-0.75; I.sup.2 = 85%) and good neurological outcome at any time was achieved in 31% of TBI patients (95% CI = 0.23-0.40; I.sup.2 = 88%). TBI cohort without ARDS had higher survival (67% vs. 57%, p = 0.01) and good neurological outcomes (34% vs. 23%, p = 0.02) compared to those with ARDS. We did not find any specific risk factors for developing ARDS. Conclusion In this meta-analysis, approximately one in five patients had ARDS shortly after TBI with the median time of 3 days. The presence of ARDS was associated with worse neurological outcome and mortality in TBI. Further research on prevention and intervention strategy of TBI-associated ARDS is warranted.

Author(s): Mélanie Fromentin [sup.1] [sup.3], Jean-Damien Ricard [sup.2] [sup.3], Damien Roux [sup.2] [sup.3] Author Affiliations: (1) grid.411784.f, 0000 0001 0274 3893, Anesthesiology and Intensive Care Department, AP-HP, Hôpital Cochin, , [...], The respiratory microbiome has been less explored than the gut microbiome. Despite the speculated importance of dysbiosis of the microbiome in ventilator-associated pneumonia (VAP) and acute respiratory distress syndrome (ARDS), only few studies have been performed in invasively ventilated ICU patients. And only the results of small cohorts have been published. An overlap exists between bacterial populations observed in the lower respiratory tract and the oropharyngeal tract. The bacterial microbiota is characterized by relatively abundant bacteria difficult to cultivate by standard methods. Under mechanical ventilation, a dysbiosis occurs with a drop overtime in diversity. During VAP development, lung dysbiosis is characterized by a shift towards a dominant bacterial pathogen (mostly Proteobacteria) whereas enrichment of gut-associated bacteria mainly Enterobacteriaceae is the specific feature discriminating ARDS patients. However, the role of this dysbiosis in VAP and ARDS pathogenesis is not yet fully understood. A more in-depth analysis of the interplay between bacteria, virus and fungi and a better understanding of the host-microbiome interaction could provide a more comprehensive view of the role of the microbiome in VAP and ARDS pathogenesis. Priority should be given to validate a consensual and robust methodology for respiratory microbiome research and to conduct longitudinal studies. A deeper understanding of microbial interplay should be a valuable guide for care of ARDS and VAP preventive/therapeutic strategies. We present a review on the current knowledge and expose perspectives and potential clinical applications of respiratory microbiome research in mechanically ventilated patients.

Author(s): Ahmed Hasanin [sup.1] , Maha Mostafa [sup.1 ] Author Affiliations: (1) grid.7776.1, 0000 0004 0639 9286, Department of Anesthesia and Critical Care Medicine, Faculty of Medicine, Cairo University, , [...]

Author(s): Gang Li [sup.1], Liangtian Zhang [sup.2], Nannan Han [sup.1], Ke Zhang [sup.1], Hengjie Li [sup.1] Author Affiliations: (1) grid.417401.7, 0000 0004 1798 6507, Department of Emergency Medicine, Zhejiang Provincial [...], Purpose This study was conducted to investigate the percentages of Th22 and Th17 cells in the peripheral blood of septic patients with and without acute lung injury (ALI) and their clinical significance. Methods A total of 479 patients were divided into non-ALI and ALI groups. The percentages of Th22 and Th17 cells and the levels of interleukin 22 (IL-22), 6 (IL-6), and 17 (IL-17) were determined. Receiver operating characteristic curve analysis was performed to assess the diagnostic value of Th22 and Th17 cells to predict sepsis-induced ALI. Results The lung injury prediction score (LIPS), IL-6, IL-17, and IL-22 levels and the percentages of Th17 and Th22 cells were significantly higher in the ALI group (P < 0.05). They were significant factors affecting sepsis-induced ALI (P < 0.05). Multivariate logistic regression analysis showed that the LIPS (OR = 1.130), IL-17 (OR = 1.982), IL-22 (OR = 2.612) and the percentages of Th17 (OR = 2.211) and Th22 (OR = 3.230) cells were independent risk factors for ALI. The area under the curve of Th22 cells was 0.844 to predict ALI with a cutoff value of 6.81%. The sensitivity and specificity for early diagnosis of sepsis-induced ALI by the Th22 cell percentage were 78.72% and 89.13%, respectively. Conclusions Th22 and Th17 cells in peripheral blood are significantly increased in septic patients with ALI and they may be used as biomarkers for early diagnosis of sepsis-induced ALI.

Author(s): Deasy Natalia Adriana[sup.1], Titong Sugihartono[sup.2], Iswan Abbas Nusi[sup.2], Poernomo Boedi Setiawan[sup.2], Herry Purbayu[sup.2], Ummi Maimunah[sup.2], Ulfa Kholili[sup.2], Budi Widodo[sup.2], Husin Thamrin[sup.2], Amie Vidyani[sup.2], Hasan Maulahela[sup.3], Yoshio Yamaoka[sup.2,4,5,6] and Muhammad [...], Background Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) appear to be substantial. Fecal calprotectin is a promising biomarker in COVID-19 associated gastrointestinal inflammation; however, its role in the severity of COVID-19 remains limited. We conducted a study to analyze the relationship between the severity of COVID-19 and hypoxic intestinal damage. Methods We assessed the severity of 44 hospitalized COVID-19 pneumonia patients based on the PaO2/FiO2 (P/F) ratio. Inflammatory markers were measured from blood samples, and fecal calprotectin was obtained from stool samples. Results Median levels of fecal calprotectin in COVID-19 patients involved in this study (n = 44) were found to be markedly elevated along with the severity of hypoxemia, as seen in the non-acute respiratory distress syndrome (ARDS) group 21.4 [micro]g/g (5.2-120.9), mild ARDS 54.30 [micro]g/g (5.2-1393.7), moderate ARDS 169.6 [micro]g/g (43.4-640.5), and severe ARDS 451.6 [micro]g/g (364.5-538.6). We also found significant differences in fecal calprotectin levels based on the severity of ARDS (P < 0.001), and although the patients were divided into ARDS and non-ARDS groups (P < 0.001). Furthermore, we found a strong negative correlation between the P/F ratio and fecal calprotectin levels (r = - 0.697, P < 0.001). Conclusion Our findings support the potential role of fecal calprotectin as a biomarker of intestinal inflammation in COVID-19 as a consequence of hypoxic intestinal damage and as suggested by the reduced P/F ratio. Keywords: Fecal calprotectin, P/F ratio, COVID-19, Infectious disease

Author(s): Ewan C. Goligher [sup.1] [sup.2] [sup.3], Alain Combes [sup.4], Daniel Brodie [sup.5] [sup.6], Niall D. Ferguson [sup.1] [sup.2] [sup.3] [sup.7] [sup.8], Antonio M. Pesenti [sup.9] [sup.10], V. Marco Ranieri [...], Purpose To describe the variability and determinants of the effect of extracorporeal CO.sub.2 removal (ECCO.sub.2R) on tidal volume (V.sub.t), driving pressure ([DELTA]P), and mechanical power (Power.sub.RS) and to determine whether highly responsive patients can be identified for the purpose of predictive enrichment in ECCO.sub.2R trial design. Methods Using data from the SUPERNOVA trial (95 patients with early moderate acute respiratory distress syndrome), the independent effects of alveolar dead space fraction (ADF), respiratory system compliance (Crs), hypoxemia (PaO.sub.2/FiO.sub.2), and device performance (higher vs lower CO.sub.2 extraction) on the magnitude of reduction in V.sub.t, [DELTA]P, and Power.sub.RS permitted by ECCO.sub.2R were assessed by linear regression. Predicted and observed changes in [DELTA]P were compared by Bland-Altman analysis. Hypothetical trials of ECCO.sub.2R, incorporating predictive enrichment and different target CO.sub.2 removal rates, were simulated in the SUPERNOVA study population. Results Changes in V.sub.t permitted by ECCO.sub.2R were independently associated with ADF and device performance but not PaO.sub.2/FiO.sub.2. Changes in [DELTA]P and Power.sub.RS were independently associated with ADF, Crs, and device performance but not PaO.sub.2/FiO.sub.2. The change in [DELTA]P predicted from ADF and Crs was moderately correlated with observed change in [DELTA]P (R.sup.2 0.32, p < 0.001); limits of agreement between observed and predicted changes in [DELTA]P were ± 3.9 cmH.sub.2O. In simulated trials, restricting enrollment to patients with a larger predicted decrease in [DELTA]P enhanced the average reduction in [DELTA]P, increased predicted mortality benefit, and reduced sample size and screening size requirements. The increase in statistical power obtained by restricting enrollment based on predicted [DELTA]P response varied according to device performance as specified by the target CO.sub.2 removal rate. Conclusions The lung-protective benefits of ECCO.sub.2R increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance. ADF and Crs, rather than severity of hypoxemia, should be the primary factors determining whether to enroll patients in clinical trials of ECCO.sub.2R.

Author(s): Christophe Guervilly [sup.1], Magali Bisbal [sup.2] [sup.3], Jean Marie Forel [sup.1], Malika Mechati [sup.3], Samuel Lehingue [sup.1], Jeremy Bourenne [sup.3], Gilles Perrin [sup.3], Romain Rambaud [sup.1], Melanie Adda [sup.1], [...], Purpose To investigate whether neuromuscular blocking agents (NMBA) exert beneficial effects in acute respiratory distress syndrome (ARDS) by reason of their action on respiratory mechanics, particularly transpulmonary pressures (P.sub.L). Methods A prospective randomised controlled study in patients with moderate to severe ARDS within 48 h of the onset of ARDS. All patients were monitored by means of an oesophageal catheter and followed up for 48 h. Moderate ARDS patients were randomised into two groups according to whether they were given a 48-h continuous infusion of cisatracurium besylate or not (control group). Severe ARDS patients did not undergo randomisation and all received cisatracurium besylate per protocol. The changes during the 48-h study period in oxygenation and in respiratory mechanics, including inspiratory and expiratory P.sub.L and driving pressure, were assessed and compared. Delta P.sub.L (âP.sub.L) was defined as inspiratory P.sub.L minus expiratory P.sub.L. Results Thirty patients were included, 24 with moderate ARDS and 6 with severe ARDS. NMBA infusion was associated with an improvement in oxygenation in both moderate and severe ARDS, accompanied by a decrease in both plateau pressure and total positive end-expiratory pressure. The mean inspiratory and expiratory P.sub.L were higher in the moderate ARDS group receiving NMBA than in the control group. In contrast, there was no change in either driving pressure or âP.sub.L related to NMBA administration. Conclusions NMBA could exert beneficial effects in patients with moderate ARDS, at least in part, by limiting expiratory efforts.

Author(s): Ann C. Long [sup.1], Erin K. Kross [sup.1], Ruth A. Engelberg [sup.1], Lois Downey [sup.1], Elizabeth L. Nielsen [sup.1], Anthony L. Back [sup.2], J. Randall Curtis [sup.1] Author Affiliations: [...], Objective Although most intensive care unit (ICU) admissions originate in the emergency department (ED), a substantial number of admissions arrive from hospital wards. Patients transferred from the hospital ward often share clinical characteristics with those admitted from the ED, but family expectations may differ. An understanding of the impact of ICU admission source on family perceptions of end-of-life care may help improve patient and family outcomes by identifying those at risk for poor outcomes. Design and setting This was a cohort study of patients with chronic illness and acute respiratory failure requiring mechanical ventilation who died after admission to an ICU in any of the 14 participating hospitals in the Seattle-Tacoma area between 2003 and 2008 (n = 1,500). Measurements Using regression models adjusted for hospital site and patient-, nurse- and family-level characteristics, we examined associations between ICU admission source (hospital ward vs. ED) and (1) family ratings of satisfaction with ICU care; (2) family and nurse ratings of quality of dying; (3) chart-based indicators of palliative care. Main results Admission from the hospital ward was associated with lower family ratings of quality of dying [[beta] -0.90, 95 % confidence interval (CI) -1.54, -0.26, p = 0.006] and satisfaction (total score [beta] -3.97, 95 % CI -7.89, -0.05, p = 0.047; satisfaction with care domain score [beta] -5.40, 95 % CI -9.44, -1.36, p = 0.009). Nurses did not report differences in quality of dying. Patients from hospital wards were less likely to have family conferences [odds ratio (OR) 0.68, 95 % CI 0.52, 0.88, p = 0.004] or discussion of prognosis in the first 72 h after ICU admission (OR 0.72, 95 % CI 0.56, 0.91, p = 0.007) but were more likely to receive spiritual care (OR 1.48, 95 % CI 1.14, 1.93, p = 0.003) or have life support withdrawn (OR 1.38, 95 % CI 1.04, 1.82, p = 0.025). Conclusion Admission from the hospital ward is associated with family perceptions of a lower quality of dying and less satisfaction with ICU care. Differences in receipt of palliative care suggest that family of patients from the hospital ward receive less communication. Nurse ratings of quality of dying did not significantly differ by ICU admission source, suggesting dissimilarities between family and nurse perspectives. This study identifies a patient population at risk for poor quality palliative and end-of-life care. Future studies are needed to identify interventions to improve care for patients who deteriorate on the wards following hospital admission.

Author(s): Takeshi Umegaki [sup.1], Sachiyo Sakamoto [sup.1], Kenichiro Nishi [sup.1], Akihisa Okamoto [sup.1], Aki Onose [sup.2], Nobuyuki Hamano [sup.1], Etsuko Yamazaki [sup.3], Koh Shingu [sup.1] Author Affiliations: (1) grid.410783.9, Department [...], Purpose To investigate the association between steroid medication before hospital admission and barotrauma in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). Methods An observational single-center retrospective study was conducted using patients admitted to the general intensive care unit (ICU) of a university hospital in Japan. We analyzed 149 mechanically ventilated patients with ARDS hospitalized between March 2008 and March 2011. ARDS was identified according to criteria from the Berlin Definition. Barotrauma was defined as pneumothorax, subcutaneous emphysema, or mediastinal emphysema occurring during mechanical ventilation in the ICU. The influence of steroid medication before hospital admission on barotrauma was studied using multiple logistic regression analysis. Results There were no differences in baseline patient characteristics except for congestive heart failure, peak pressure during mechanical ventilation, and steroid pulse therapy between the barotrauma and non-barotrauma groups. Logistic regression analysis showed that peak pressure [greater than or equal to]35 cmH.sub.2O was associated with barotrauma in patients with ARDS [odds ratio (OR), 17.34; P < 0.01], whereas steroid medication before hospital admission was not a significant factor for barotrauma (OR, 1.63; P = 0.51). Conclusions Barotrauma in ARDS patients was associated with higher pressure during mechanical ventilation but not with steroid medication before hospital admission.

Author(s): Anna Maria Brambilla [sup.1], Stefano Aliberti [sup.2], Elena Prina [sup.1], Francesco Nicoli [sup.1], Manuela Del Forno [sup.3], Stefano Nava [sup.3], Giovanni Ferrari [sup.4], Francesco Corradi [sup.5], Paolo Pelosi [sup.5], [...], Purpose The efficacy of noninvasive continuous positive airway pressure (CPAP) to improve outcomes in severe hypoxemic acute respiratory failure (hARF) due to pneumonia has not been clearly established. The aim of this study was to compare CPAP vs. oxygen therapy to reduce the risk of meeting criteria for endotracheal intubation (ETI). Methods In a multicenter randomized controlled trial conducted in four Italian centers patients with severe hARF due to pneumonia were randomized to receive helmet CPAP (CPAP group) or oxygen delivered with a Venturi mask (control group). The primary endpoint was the percentage of patients meeting criteria for ETI, including either one or more major criteria (respiratory arrest, respiratory pauses with unconsciousness, severe hemodynamic instability, intolerance) or at least two minor criteria (reduction of at least 30 % of basal PaO.sub.2/FiO.sub.2 ratio, increase of 20 % of PaCO.sub.2, worsening of alertness, respiratory distress, SpO.sub.2 less than 90 %, exhaustion). Results Between February 2010 and 2013, 40 patients were randomized to CPAP and 41 to Venturi mask. The proportion of patients meeting ETI criteria in the CPAP group was significantly lower compared to those in the control group (6/40 = 15 % vs. 26/41 = 63 %, respectively, p < 0.001; relative risk 0.24, 95 % CI 0.11-0.51; number needed to treat, 2) two patients were intubated in the CPAP group and one in the control group. The CPAP group showed a faster and greater improvement in oxygenation in comparison to controls (p < 0.001). In either study group, no relevant adverse events were detected. Conclusions Helmet CPAP reduces the risk of meeting ETI criteria compared to oxygen therapy in patients with severe hARF due to pneumonia.

Author(s): Elmi Messaï [sup.1], Abdesselam Bouguerra [sup.2], Guy Harmelin [sup.3], Gabriella Di Lascio [sup.3], Giovanni Cianchi [sup.4], Massimo Bonacchi [sup.3] Author Affiliations: (1) Service de réanimation, Centre hospitalier de Cholet, [...], Purpose Venovenous extracorporeal membrane oxygenation (VV-ECMO) is used to treat severe forms of acute respiratory distress syndrome (ARDS). VV-ECMO management may be confusing due to the lack of information about the interplay between the determinant parameters and their impact on oxygenation. We found a relationship between arterial oxygen saturation (SaO.sub.2) and its relevant parameters. The aim of this study was to assess the validity of this model. Methods We report our experience in 17 patients under VV-ECMO for severe ARDS. We compared, at two different levels of pump flow, SaO.sub.2 and the oxygen saturation measured in the pulmonary artery (SpaO.sub.2) with the predicted saturation using the formula: SpaO.sub.2 = (EF/CO)SmO.sub.2 + (1 - EF/CO)SvO.sub.2 + 10.sup.-2PmO.sub.2, where PF is pump flow, R is recirculation, EF is effective flow [= (1 - R)PF], SmO.sub.2 is saturation of the oxygenator outgoing blood, CO is cardiac output, SvO.sub.2 is saturation of mixed venous blood, and PmO.sub.2 is oxygen partial pressure of the oxygenator outgoing blood. Results There was no significant difference between predicted and measured SpaO.sub.2: the mean predicted and measured SpaO.sub.2 values were 90.7 ± 2.8 % and 90.4 ± 2.7 %, respectively (p = 0.696, r = 0.966). Bland-Altman analysis showed good agreement between predicted and measured SpaO.sub.2. Predicted SpaO.sub.2 and SaO.sub.2 was well correlated (r = 0.80). Conclusions We have presented an explicit relationship between SaO.sub.2 and its direct determinants during VV-ECMO. Good agreement was found with the measured values of SaO.sub.2, but the model remains to be fully validated before its use in clinical practice.

Author(s): Tommaso Mauri [sup.1] [sup.2], Giacomo Bellani [sup.1] [sup.2], Giacomo Grasselli [sup.2], Andrea Confalonieri [sup.2], Roberto Rona [sup.2], Nicolo' Patroniti [sup.1] [sup.2], Antonio Pesenti [sup.1] [sup.2] Author Affiliations: (1) grid.415025.7, [...], Purpose Patients with acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO) usually present very low respiratory system compliance (Cst.sub.rs) values (i.e., severe restrictive respiratory syndrome patients). As a consequence, they are at high risk of experiencing poor patient-ventilator interaction during assisted breathing. We hypothesized that monitoring of diaphragm electrical activity (EAdi) may enhance asynchrony assessment and that neurally adjusted ventilatory assist (NAVA) may reduce asynchrony, especially in more severely restricted patients. Methods We enrolled ten consecutive ARDS patients with very low Cst.sub.rs values undergoing ECMO after switching from controlled to pressure support ventilation (PSV). We randomly tested (30 min) while recording EAdi: (1) PSV30 (PSV with an expiratory trigger at 30 % of flow peak value); (2) PSV1 (PSV with expiratory trigger at 1 %); (3) NAVA. During each step, we measured the EAdi-based asynchrony index (AI.sub.EAdi) = flow-, pressure- and EAdi-based asynchrony events/EAdi-based respiratory rate x 100. Results AI.sub.EAdi was high during all ventilation modes, and the most represented asynchrony pattern was specific for this population (i.e., premature cycling). NAVA was associated with significantly decreased, although suboptimal, AI.sub.EAdi values in comparison to PSV30 and PSV1 (p < 0.01 for both). The PSV30-NAVA and PSV1-NAVA differences in AI.sub.EAdi values were inversely correlated with patients' Cst.sub.rs (R.sup.2 = 0.545, p = 0.01 and R.sup.2 = 0.425, p < 0.05; respectively). Conclusions EAdi allows accurate analysis of asynchrony patterns and magnitude in ARDS patients with very low Cst.sub.rs undergoing ECMO. In these patients, NAVA is associated with reduced asynchrony.

Author(s): Damon P. Eisen [sup.1] Author Affiliations: (1) grid.416153.4, 0000000406241200, Victorian Infectious Diseases Service, Royal Melbourne Hospital, , Grattan St, 3050, Parkville, VIC, Australia Introduction Acetyl salicylic acid (ASA) or [...], Introduction Acetyl salicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) may have potential as adjunctive agents for sepsis. Materials This review considers the large body of literature that indicates a basis for sepsis therapy with ASA and suggests an agenda for future intervention studies in sepsis prevention and treatment. ASA and NSAIDs have beneficial effects in numerous experimental models of sepsis. Low doses of ASA of 100 mg/day or less trigger synthesis of lipoxins that are anti-inflammatory and aid in resolution of inflammation. Higher doses of ASA and NSAIDs act to reduce NF-[kappa]B stimulation and inhibit numerous septic pathways. While a previous randomised controlled trial of ibuprofen failed to show a reduction in mortality in sepsis, it did reduce clinical manifestations of sepsis. More recent observational studies have shown reduction in sepsis or acute lung injury leading to lower mortality in ICU patients treated with ASA. Conclusions Low-dose ASA appears to be beneficial in the prevention and treatment of sepsis and SIRS. If proven, this intervention would have a major, cost-effective impact on sepsis care.

Author(s): Christopher E. Cox [sup.1], Laura S. Porter [sup.2], Catherine L. Hough [sup.3], Douglas B. White [sup.4] [sup.5], Jeremy M. Kahn [sup.4] [sup.5], Shannon S. Carson [sup.6], James A. Tulsky [...], Purpose Survivors of acute lung injury (ALI) and their informal caregivers have difficulty coping with the physical and emotional challenges of recovery from critical illness. We aimed to develop and pilot test a telephone-based coping skills training intervention for this population. Methods Fifty-eight participants were enrolled overall. A total of 21 patients and 23 caregivers participated in a cross-sectional study to assess coping and its association with psychological distress. This also informed the development of an ALI coping skills training intervention in an iterative process involving content and methodological experts. The intervention was then evaluated in seven patients and seven caregivers in an uncontrolled, prospective, pre-post study. Outcomes included acceptability, feasibility, and symptoms of psychological distress measured with the Hospital Anxiety and Depression Scale (HADS) and Post-Traumatic Symptom Scale (PTSS). Results Survivors and their caregivers used adaptive coping infrequently, a pattern that was strongly associated with psychological distress. These findings informed the development of a 12-session intervention for acquiring, applying, and maintaining coping skills. In the evaluation phase, participants completed 77 (92 %) of a possible 84 telephone sessions and all (100 %) reported the intervention's usefulness in their daily routine. Mean change scores reflecting improvements in the HADS (7.8 U) and PTSS (10.3 U) were associated with adaptive coping (r = 0.50-0.70) and high self-efficacy (r = 0.67-0.79). Conclusions A novel telephone-based coping skills training intervention was acceptable, feasible, and may have been associated with a reduction in psychological distress among survivors of ALI and their informal caregivers. A randomized trial is needed to evaluate the intervention.

Author(s): Giacomo Grasselli [sup.1], Jennifer Beck [sup.2] [sup.3], Lucia Mirabella [sup.4], Antonio Pesenti [sup.1], Arthur S. Slutsky [sup.2] [sup.5], Christer Sinderby [sup.2] [sup.5] Author Affiliations: (1) grid.7563.7, 0000000121741754, Department of [...], Purpose During neurally adjusted ventilatory assist (NAVA), it is difficult to quantify the relative contribution of the patient versus the ventilator to the inspiratory tidal volume (Vt.sub.insp). To solve this problem, we developed an index, the 'patient-ventilator breath contribution' (PVBC), using the inspiratory deflection of the diaphragmatic electrical activity (âEAdi) and Vt.sub.insp during assisted and non-assisted breaths. This study evaluated the PVBC index in an experimental setup. Method Nine intubated and sedated rabbits were studied during repeated ramp increases of the NAVA level. One breath was non-assisted at each NAVA level. The PVBC index was evaluated during resistive loading and after acute lung injury. PVBC was calculated by relating Vt.sub.insp/âEAdi of a non-assisted breath to that of the preceding assisted breath. The PVBC was compared to the relative contribution of esophageal pressure (âPes) to transpulmonary pressure deflections (âP.sub.L,dyn). Results The relationship between PVBC and âPes/âP.sub.L,dyn was slightly curvilinear with an intercept different from zero (y = -1x.sup.2 + 1.64x + 0.21) and a determination coefficient (R.sup.2) of 0.95. Squaring the PVBC values resulted in a near perfect linear relationship (y = 1.02x + 0.05) between PVBC.sup.2 and âPes/âP.sub.L,dyn with an R.sup.2 of 0.97. Conclusion This study shows that Vt.sub.insp and EAdi can be used to predict the contribution of the inspiratory muscles versus that of the ventilator during NAVA. If clinically applicable, this could serve to quantify and standardize the adjustment of the level of assist, and hence reduce the risks of excessive ventilatory assist. Further studies are required to evaluate if this method is clinically applicable.

Author(s): Cíntia L. Santos [sup.1] [sup.2], Lillian Moraes [sup.1], Raquel S. Santos [sup.1], Mariana G. Oliveira [sup.1], Johnatas D. Silva [sup.1], Tatiana Maron-Gutierrez [sup.1] [sup.3], Débora S. Ornellas [sup.1] [sup.3], [...], Purpose We hypothesized that: (1) intraabdominal hypertension increases pulmonary inflammatory and fibrogenic responses in acute lung injury (ALI); (2) in the presence of intraabdominal hypertension, higher tidal volume reduces lung damage in extrapulmonary ALI, but not in pulmonary ALI. Methods Wistar rats were randomly allocated to receive Escherichia coli lipopolysaccharide intratracheally (pulmonary ALI) or intraperitoneally (extrapulmonary ALI). After 24 h, animals were randomized into subgroups without or with intraabdominal hypertension (15 mmHg) and ventilated with positive end expiratory pressure = 5 cmH.sub.2O and tidal volume of 6 or 10 ml/kg during 1 h. Lung and chest wall mechanics, arterial blood gases, lung and distal organ histology, and interleukin (IL)-1[beta], IL-6, caspase-3 and type III procollagen (PCIII) mRNA expressions in lung tissue were analyzed. Results With intraabdominal hypertension, (1) chest-wall static elastance increased, and PCIII, IL-1[beta], IL-6, and caspase-3 expressions were more pronounced than in animals with normal intraabdominal pressure in both ALI groups; (2) in extrapulmonary ALI, higher tidal volume was associated with decreased atelectasis, and lower IL-6 and caspase-3 expressions; (3) in pulmonary ALI, higher tidal volume led to higher IL-6 expression; and (4) in pulmonary ALI, liver, kidney, and villi cell apoptosis was increased, but not affected by tidal volume. Conclusions Intraabdominal hypertension increased inflammation and fibrogenesis in the lung independent of ALI etiology. In extrapulmonary ALI associated with intraabdominal hypertension, higher tidal volume improved lung morphometry with lower inflammation in lung tissue. Conversely, in pulmonary ALI associated with intraabdominal hypertension, higher tidal volume increased IL-6 expression.