Automatic Tube Compensation During Spontaneous Breathing Trials.

BACKGROUND: Automatic tube compensation (ATC) is an option available in any ICU ventilator that compensates for the resistive pressure drop due to the endotracheal tube. The goal of the present study was to compare ATC to other patient triggered modes of support in terms of spontaneous breathing trial (SBT) and extubation success. METHODS: Two authors (JB and PCF), independently and blinded to each other, searched through PubMed, Web of Science, and Cochrane from inception-May 26, 2021, with the following search terms entered as MeSH terms in all fields: "Automatic Tube Compensation." INCLUSION CRITERIA: randomized studies that included subjects > 16 y old undergoing an SBT. EXCLUSION CRITERIA: crossover studies, pediatric studies, animal studies, or experimental studies on test lungs or on computer simulation; other languages than French, Spanish, or English; studies not published in a full-text format (eg, abstract or letter); and reviews. A frequentist network meta-analysis was conducted with the aim to investigate the effectiveness of ATC on SBT and extubation outcomes. SBT was defined as successful if patients could tolerate the SBT based on predetermined criteria, whether it was followed by extubation. Successful extubation was defined as the absence of re-intubation, noninvasive ventilation, or signs of respiratory distress within the 48 h after extubation. The pooled analyses used random-effect models, and the effect size was expressed as relative risk or mean difference for categorical and continuous variables, respectively. P-scores were used to rank all treatments and to identify the intervention with the highest probability of being the best. RESULTS: Of the 234 retrieved papers, 7 met the inclusion criteria. In terms of SBT success, ATC100+PEEP < 7.5 and PS10+PEEP < 7.5 were superior to T-piece. Likewise, PS10+PEEP < 7.5 was the intervention with the highest probability of being the best (P-score: 0.90). In terms of extubation success, ATC100+PEEP < 7.5 cm H2O was significantly better than PEEP < 7.5 and T-piece. Likewise, it had the highest probability of being the best (P-score= 0.90). CONCLUSIONS: ATC is the modality with the highest probability of extubation success but not in terms of SBT success.

Safety and Efficacy of Devices Delivering Inhaled Antibiotics among Adults with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and a Network Meta-Analysis.

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) and via nebulizers (SVN) among adult patients with NCFB. Inclusion criteria were randomized-controlled trials, adults (≥18 years) with NCFB, and inhaled antibiotics administered via DPI as intervention. Search strategy was performed in PubMed, Web of Science, and Cochrane Library from 2000 to 2019. Sixteen trials (2870 patients) were included. Three trials (all ciprofloxacin) used DPIs and thirteen used SVN (three ciprofloxacin). Both DPI and SVN devices achieved similar safety outcomes (adverse events, antibiotic discontinuation, severe adverse events, and bronchospasm). Administration of ciprofloxacin via DPI significantly improved time to first exacerbation (87 days, 95% CI 34.3-139.7) and quality of life (MD -7.52; 95% CI -13.06 to -1.98) when compared with via SVN. No other significant differences were documented in clinical efficacy (at least one exacerbation, FEV1% predicted) and microbiologic response (bacterial eradication, emergence of new potential pathogens, and emergence of antimicrobial resistance) when comparing devices. Our NMA documented that time to first exacerbation and quality of life, were more favorable for DPIs. Decisions on the choice of devices should incorporate these findings plus other criteria, such as simplicity, costs or maintenance requirements.

Right-side colectomy with complete mesocolic excision vs conventional right-side colectomy in the treatment of colon cancer: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aims to investigate the role of complete mesocolic excision (CME) in the treatment of right-side colon cancer when compared with standard right-side hemicolectomy, focusing on oncological outcomes, mortality and morbidity rates. MATERIALS AND METHODS: A systematic literature search was performed on MEDLINE and EMBASE archives, including studies on CME in right-side colon cancer. Primary outcomes were five-year disease-free survival and five-year overall survival. Secondary outcomes investigated were mortality and morbidity rates, intraoperative blood loss, anastomotic leakage, postoperative ileus, day of postoperative flatus, pulmonary infection, duration of hospital stay and number of lymph nodes harvested. RESULTS: Seventeen studies have been included in this meta-analysis for a total of 3918 patients. The five-year disease-free survival (DFS) and overall survival (OS) results improved in the CME group with respect to conventional right-side colectomy with an OR 1.88 (95% CI 1.02-3.45) and OR 2.77 (95% CI 1.33-5.74), respectively. The incidence of mortality and morbidity was comparable between the two groups. Moreover, conventional surgery time was faster than CME (MD 33.69 min, 95% CI 12.79-54.59), while no significant differences were reported in mean blood loss and hospital stay. Furthermore, the CME group showed a higher mean number of harvested lymph nodes (MD 7.08 lymph nodes 95% CI 4.90-9.27). CONCLUSION: Complete mesocolic excision of the right-side colectomy improves oncological outcomes without increasing mortality and morbidity rates compared to standard right-side hemicolectomy. CME should therefore be routinely performed in the treatment of right-side colon cancer.

Empiric antibiotics for community-acquired pneumonia in adult patients: a systematic review and a network meta-analysis.

OBJECTIVE: The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) . METHOD: Inclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish. EXCLUSION CRITERIA: (1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format. DATA SOURCES: Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane's tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation. STATISTICAL ANALYSES: frequentist method performed with the 'netmeta' library, R package. RESULTS: 27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. For cure, two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). For mortality, three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate. CONCLUSION: For cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692).

Estudio comparativo entre la gastrectomía total y subtotal en el cáncer distal de estómago: metaanálisis de estudios prospectivos y retrospectivos / Comparative study between total and subtotal gastrectomy for distal gastric cancer: Meta-analysis of prospective and retrospective studies

El tipo de gastrectomía, total (GT) o distal (GD), en el cáncer gástrico medio o distal no está claramente consensuada, sobre todo cuando es indiferenciado o difuso de Lauren. Pretendemos en este metaanálisis definir en términos de supervivencia y morbimortalidad cuál de las 2 técnicas debiera ser recomendada. Se han incluido trabajos prospectivos y retrospectivos que comparen ambas técnicas hasta un total de 6.303 pacientes (3.641 GD y 2.662 GT). La GD se asoció de forma significativa con menos complicaciones, menos fístulas anastomóticas y menos mortalidad peroperatoria. El número de ganglios en la GD fue significativamente menor, pero siempre por encima de 15. Por último, la supervivencia a 5 años de la GD fue también superior. Por tanto, la GD, siempre que se obtenga un margen de seguridad e independientemente del tipo histológico, debe efectuarse en la cirugía de cáncer distal de estómago

There is no clear agreement on the type of gastrectomy to be used (either total [TG] or distal [DG]) in middle or distal gastric cancer, especially when it is undifferentiated or Lauren diffuse type. In this meta-analysis, we intend to define which of the 2 techniques should be recommended, based on survival, morbidity and mortality rates. Prospective and retrospective studies comparing both techniques have been included for a total of 6303 patients (3,641 DG and 2,662 TG). DG was significantly associated with fewer complications, fewer anastomotic fistulae, and less perioperative mortality. The number of lymph nodes in DG was significantly lower, but always above 15. Finally, even the 5-year survival of DG was also higher. Therefore, DG, as long as a safety margin is obtained and regardless of the histological type, should be performed in surgery for distal stomach cancer

Desarrollo de un modelo predictivo para mortalidad y otro para reingreso hospitalario en una cohorte de paciente con infección que requieren hospitalización / Development of a predictive model for hospital mortality and re-admission in a cohort of infected patients that require hospitalization

INTRODUCCIÓN: Los objetivos del estudio fueron: identificar variables asociadas a mortalidad intrahospitalaria y reingreso hospitalario a 3 meses; identificar el impacto de la demora en el inicio de la antibioticoterapia en la mortalidad y reportar la tasa de antibioticoterapia inapropiada. MATERIAL Y MÉTODOS: Estudio observacional de cohortes retrospectivo realizado en el Hospital Universitario HM Sanchinarro en Madrid. Los criterios de inclusión fueron: edad>18 años de edad, hospitalización desde urgencias durante el periodo 1 de septiembre 2012 al 31 de marzo del 2013 con diagnóstico de infección bacteriana. Los criterios de exclusión fueron: sospecha de infección viral y cultivos bacteriológicos negativos, expectativa de vida inferior a 6 meses, falta de información clínica, asistencia exclusivamente por el servicio de urgencias traumatológicas. Se realizaron dos modelos logísticos (mortalidad y reingreso hospitalarios). RESULTADOS: Se incluyeron 517 pacientes. Variables asociadas a mortalidad (30 fallecidos): frecuencia respiratoria (OR 1,12; IC95% 1,02; 1,22), saturación de oxígeno (OR 0,92; IC95% 0,87; 0,98), creatinina (OR 2,33; IC95% 1,62; 3,36), EPOC (OR 3,02; IC95% 1,06; 8,21), cáncer OR 3,34; IC95% 1,07; 9,98) y quimioterapia en los últimos 3 meses (OR 4,83; IC95% 1,54; 16,41). Variables asociadas a reingreso hospitalario (28 fallecidos): hepatopatía, GPT, antecedente de ictus e hipertensión arterial. Ambos modelos se destacan por su elevada especificidad y capacidad discriminativa pero baja sensibilidad. La demora en el inicio de la antibioticoterapia no influyo en la mortalidad ni reingreso. En 56 pacientes se identificó el microorganismo causal y el tratamiento antibiótico fue inapropiado en 11. CONCLUSIONES: Se registro un 5,8% de mortalidad hospitalaria y un 5,7% de reingresos. Las variables asociadas a la mortalidad intrahospitalaria difieren de las asociadas al reingreso. La demora en el inicio de la antibioticoterapia no se asoció a un efecto deletéreo. La antibioticoterapia inadecuada fue de casi el 20%

INTRODUCTION: The aims of the study were: to develop a predictive model for hospital mortality and another for hospital re-admission, to identify the impact of antibiotic delay in the mortality rate and, to report the rate of inappropriate antibiotic therapy. MATERIAL AND METHODS: A cohort and retrospective study was conducted at the HM Sanchinarro University Hospital during the period September 1st, 2012 to March 31th, 2013. The inclusion criteria were: age> 18 years, hospital admission from the ED with a diagnosis of bacterial infection. The exclusion criteria were: suspected viral infection, negative bacteriological cultures, life expectancy less than 6 months, lack of clinical information, assistance exclusively by the trauma emergency department. Two logistic models were made (hospital mortality and hospital re-admission). RESULTS: A total of 517 patients were included. The final mortality model (30 deaths) include the following variables: respiratory rate (OR 1.12; IC95% 1.02; 1.22), oxygen saturation (OR 0.92; IC95% 0.87; 0.98), creatinine (OR 2.33; IC95% 1.62; 3.36), COPD (OR 3.02; IC95% 1.06; 8.21), cancer (OR 3.34; IC95% 1.07; 9.98) and chemotherapy in the last 3 months (OR 4.83; IC95% 1.54; 16.41). The final model for hospital re-admission (28 re-admissions) include the following variables: hepatopathy (OR 5.51; IC95% 1.57; 16.88), GPT (OR 1.005; IC95% 1.003; 1.008), history of stroke (OR 5.06; IC95% 1.04; 18.80) and arterial hypertension (OR 3.15; IC95% 1.38; 7.56). The antibiotic therapy delays not influenced the mortality or re-admission rate. In 24.3% the causative microorganism was identified and antibiotic treatment was inappropriate 19.6%. CONCLUSION: Hospital mortality rate was 5.8% and readmission rate was 5.7%. Variables associated with mortality differ from those associated with re-admission. The delay in the antibiotic initiation was not associated with a deleterious effect. Antibiotic therapy was inadequate in almost 20% of patients

Comparative study between total and subtotal gastrectomy for distal gastric cancer: Meta-analysis of prospective and retrospective studies. / Estudio comparativo entre la gastrectomía total y subtotal en el cáncer distal de estómago: metaanálisis de estudios prospectivos y retrospectivos.

There is no clear agreement on the type of gastrectomy to be used (either total [TG] or distal [DG]) in middle or distal gastric cancer, especially when it is undifferentiated or Lauren diffuse type. In this meta-analysis, we intend to define which of the 2techniques should be recommended, based on survival, morbidity and mortality rates. Prospective and retrospective studies comparing both techniques have been included for a total of 6303 patients (3,641 DG and 2,662 TG). DG was significantly associated with fewer complications, fewer anastomotic fistulae, and less perioperative mortality. The number of lymph nodes in DG was significantly lower, but always above 15. Finally, even the 5-year survival of DG was also higher. Therefore, DG, as long as a safety margin is obtained and regardless of the histological type, should be performed in surgery for distal stomach cancer.

Pretreatment with adalimumab reduces ventilator-induced lung injury in an experimental model. / Tratamento prévio com adalimumabe reduz lesão pulmonar induzida por ventilação mecânica em um modelo experimental.

OBJECTIVE: To determine whether adalimumab administration before mechanical ventilation reduces ventilator-induced lung injury (VILI). METHODS: Eighteen rats randomized into 3 groups underwent mechanical ventilation for 3 hours with a fraction of inspired oxygen = 0.40% including a low tidal volume group (n = 6), where tidal volume = 8mL/kg and positive end-expiratory pressure = 5cmH2O; a high tidal volume group (n = 6), where tidal volume = 35mL/kg and positive end-expiratory pressure = 0; and a pretreated + high tidal volume group (n = 6) where adalimumab (100ug/kg) was administered intraperitoneally 24 hours before mechanical ventilation + tidal volume = 35mL/kg and positive end-expiratory pressure = 0. ANOVA was used to compare histological damage (ATS 2010 Lung Injury Scoring System), pulmonary edema, lung compliance, arterial partial pressure of oxygen, and mean arterial pressure among the groups. RESULTS: After 3 hours of ventilation, the mean histological lung injury score was higher in the high tidal volume group than in the low tidal volume group (0.030 versus 0.0051, respectively, p = 0.003). The high tidal volume group showed diminished lung compliance at 3 hours (p = 0.04) and hypoxemia (p = 0,018 versus control). Pretreated HVt group had an improved histological score, mainly due to a significant reduction in leukocyte infiltration (p = 0.003). CONCLUSION: Histological examination after 3 hours of injurious ventilation revealed ventilator-induced lung injury in the absence of measurable changes in lung mechanics or oxygenation; administering adalimumab before mechanical ventilation reduced lung edema and histological damage.

Hospital Mortality and Effect of Adjusting PaO2/FiO2 According to Altitude Above the Sea Level in Acclimatized Patients Undergoing Invasive Mechanical Ventilation. A Multicenter Study / Mortalidad hospitalaria y efecto de ajustar el cociente PaO2/FiO2 de acuerdo con la altitud por encima del nivel del mar en pacientes aclimatados que se someten a ventilación mecánica invasiva. Un estudio multicéntrico

OBJECTIVE: (I) Analyze the effect of altitude above the sea level on the mortality rate in patients undergoing invasive mechanical ventilation. (II) Validate the traditional equation for adjusting PaO2/FiO2 according to the altitude. DESIGN: A prospective, observational, multicenter and international study conducted during August 2016. PATIENTS: Inclusion criteria: (I) age between 18 and 90 years old, (II) admitted to intensive care unit (ICU) situated at the same altitude above the sea level (AASL) in which the patients has stayed, at least, during the previous 40 days and (III) received invasive MV for at least 12 h. MATERIAL AND METHODS: All variables were registered the day of intubation (day 0). Patients were followed until death, ICU discharge or day 28. PaO2/FiO2 ratio was adjusted by the AASL according to: PaO2/FiO2 * (barometric pressure/760). Categorical variables were compared with χ2 and Cochran-Mantel-Haenszel test. Continuous variables with Mann-Whitney. Correlation between continuous variables was analyzed graphically and analytically. Logistic regression model was constructed to identify factors associated to mortality. Kapplan-Meier method was used to estimate the probability of survival according to the altitude. A 2-side p value < 0.05 was consider significant. RESULTS: 249 patients (< 1500 m n = 55; 1500 to < 2500 m n = 20; 2500 to < 3500 m n=155 and ≥ 3500 m n=19) were included. Adjusted and non-adjusted PaO2/FiO2 were correlated with several respiratory and non respiratory variables. None discordances between non adjusted and adjusted PaO2/FiO2 were identified. However, several correlations were appreciated only in patients situated < 1500 m or in > 1500 m. Seventy-nine patients died during the ICU stayed (32%). The mortality curve was not affected by the altitude above the sea level. Variables independently associated to mortality are: PEEP, age, systolic arterial blood pressure, and platelet count. AUROC: 0.72. CONCLUSION: In acclimatized patients undergoing invasive mechanical ventilation, the traditional equation for adjusting PaO2/FiO2 according the elevation above the sea level seems to be inaccurate and the altitude above the sea level does not affect the mortality risk

OBJETIVO: 1) Analizar el efecto de la altitud por encima del nivel del mar en la tasa de mortalidad de pacientes sometidos a ventilación mecánica invasiva, y 2) Validar la ecuación tradicional de ajuste de PaO2/FiO2, de acuerdo con la altitud. DISEÑO: Estudio internacional prospectivo, observacional y multicéntrico realizado durante agosto de 2016. PACIENTES: Criterios de inclusión: 1 Edad comprendida entre 18 y 90 años, 2 Haber sido ingresado en una unidad de cuidados intensivos (UCI) situada a la misma altitud por encima del nivel del mar (AASL) en la cual el paciente haya estado durante al menos los 40 días previos al estudio, y 3) Haber recibido ventilación mecánica (VM) durante al menos 12 h. MATERIALES Y MÉTODOS: Todas las variables se registraron el día de la intubación (día 0). El seguimiento se realizó hasta la muerte del paciente, el alta de la UCI o el día 28. El cociente PaO2/FiO2 se ajustó según los criterios de la AASL de acuerdo con: PaO2/FiO2 * (presión barométrica/760). Las variables categóricas se compararon mediante la prueba de χ2 y el test Cochran-Mantel-Haenszel, y las variables continuas con el test de Mann-Whitney. La correlación entre las variables continuas se analizó de forma gráfica y analítica. Para identificar los factores asociados a la mortalidad se elaboró un modelo de regresión logística. Se utilizó el método de Kaplan-Meier para estimar la probabilidad de supervivencia de acuerdo con la altitud. Un valor de p < 0,05 en la prueba bilateral se consideró como significativo. RESULTADOS: Se incluyeron 249 pacientes (< 1.500 m, n = 55; 1.500 a < 2.500 m, n = 20; 2.500 a < 3.500 m, n = 155 y ≥ 3.500 m, n = 19). El cociente PaO2/FiO2 mostró correlación con las variables graves tanto respiratorias como no respiratorias. No se registraron discordancias entre el cociente PaO2/FiO2 ajustado y sin ajustar. Únicamente se observaron diversas correlaciones entre los pacientes situados a < 1.500 m o a > 1.500 m. Setenta y nueve pacientes (32%) murieron durante la estancia en la UCI. La altitud sobre el nivel del mar no afectó a la curva de mortalidad. Las variables asociadas de forma independiente con la mortalidad fueron la presión positiva al final de la espiración (PEEP), la edad, la presión arterial sistólica y el recuento de plaquetas. El área bajo la curva ROC (AUROC) fue de 0,72. CONCLUSIÓN: En pacientes aclimatados sometidos a ventilación mecánica invasiva la ecuación tradicional para ajustar el cociente PaO2/FiO2, de acuerdo con la elevación sobre el nivel del mar parece inexacta. Por otro lado, la altitud por encima del nivel del mar no afecta al riego de mortalidad

Tratamento prévio com adalimumabe reduz lesão pulmonar induzida por ventilação mecânica em um modelo experimental / Pretreatment with adalimumab reduces ventilator-induced lung injury in an experimental model

RESUMO Objetivo: Determinar se a administração de adalimumabe previamente à ventilação mecânica reduz a lesão pulmonar induzida por ventilação mecânica. Métodos: Randomizaram-se 18 ratos em três grupos submetidos à ventilação mecânica por 3 horas com uma fração inspirada de oxigênio de 0,40%. Os três grupos foram assim caracterizados: um grupo com baixo volume corrente (n = 6), no qual se utilizaram volume corrente de 8mL/kg e pressão expiratória final positiva de 5cmH2O; um grupo com alto volume corrente (n = 6), no qual se utilizaram volume corrente de 35mL/kg e pressão expiratória final positiva de zero; e um grupo pré-tratado com alto volume corrente (n = 6), no qual se administraram adalimumabe (100µg/kg) por via intraperitoneal 24 horas antes do início da ventilação mecânica, volume corrente de 35mL/kg e pressão expiratória final positiva de zero. Realizou-se ANOVA para comparação de dano histológico (com utilização de escores segundo o ATS 2010 Lung Injury Scoring System), edema pulmonar, complacência pulmonar, pressão parcial de oxigênio arterial e pressão arterial média entre os grupos. Resultados: Após 3 horas de ventilação, o escore médio de lesão histológica pulmonar foi mais elevado no grupo com alto volume corrente do que no grupo com baixo volume corrente (0,030 versus 0,0051; p = 0,003). O grupo com alto volume corrente demonstrou complacência pulmonar diminuída após 3 horas (p = 0,04) e hipoxemia (p = 0,018 versus controle). O grupo alto volume corrente tratado previamente teve melhora do escore histológico, principalmente devido à redução significante da infiltração leucocitária (p = 0,003). Conclusão: O exame histológico após 3 horas de ventilação lesiva revelou lesão pulmonar induzida por ventilação mecânica na ausência de modificações mensuráveis na mecânica pulmonar e na oxigenação; a administração de adalimumabe antes da ventilação mecânica diminuiu o edema pulmonar e o dano histológico.

ABSTRACT Objective: To determine whether adalimumab administration before mechanical ventilation reduces ventilator-induced lung injury (VILI). Methods: Eighteen rats randomized into 3 groups underwent mechanical ventilation for 3 hours with a fraction of inspired oxygen = 0.40% including a low tidal volume group (n = 6), where tidal volume = 8mL/kg and positive end-expiratory pressure = 5cmH2O; a high tidal volume group (n = 6), where tidal volume = 35mL/kg and positive end-expiratory pressure = 0; and a pretreated + high tidal volume group (n = 6) where adalimumab (100ug/kg) was administered intraperitoneally 24 hours before mechanical ventilation + tidal volume = 35mL/kg and positive end-expiratory pressure = 0. ANOVA was used to compare histological damage (ATS 2010 Lung Injury Scoring System), pulmonary edema, lung compliance, arterial partial pressure of oxygen, and mean arterial pressure among the groups. Results: After 3 hours of ventilation, the mean histological lung injury score was higher in the high tidal volume group than in the low tidal volume group (0.030 versus 0.0051, respectively, p = 0.003). The high tidal volume group showed diminished lung compliance at 3 hours (p = 0.04) and hypoxemia (p = 0,018 versus control). Pretreated HVt group had an improved histological score, mainly due to a significant reduction in leukocyte infiltration (p = 0.003). Conclusion: Histological examination after 3 hours of injurious ventilation revealed ventilator-induced lung injury in the absence of measurable changes in lung mechanics or oxygenation; administering adalimumab before mechanical ventilation reduced lung edema and histological damage.

Hospital Mortality and Effect of Adjusting PaO2/FiO2 According to Altitude Above the Sea Level in Acclimatized Patients Undergoing Invasive Mechanical Ventilation. A Multicenter Study.

OBJECTIVE: (i) Analyze the effect of altitude above the sea level on the mortality rate in patients undergoing invasive mechanical ventilation. (ii) Validate the traditional equation for adjusting PaO2/FiO2 according to the altitude. DESIGN: A prospective, observational, multicenter and international study conducted during August 2016. PATIENTS: Inclusion criteria: (i) age between 18 and 90 years old, (ii) admitted to intensive care unit (ICU) situated at the same altitude above the sea level (AASL) in which the patients has stayed, at least, during the previous 40 days and (iii) received invasive MV for at least 12h. MATERIAL AND METHODS: All variables were registered the day of intubation (day 0). Patients were followed until death, ICU discharge or day 28. PaO2/FiO2 ratio was adjusted by the AASL according to: PaO2/FiO2*(barometric pressure/760). Categorical variables were compared with χ2 and Cochran-Mantel-Haenszel test. Continuous variables with Mann-Whitney. Correlation between continuous variables was analyzed graphically and analytically. Logistic regression model was constructed to identify factors associated to mortality. Kapplan-Meier method was used to estimate the probability of survival according to the altitude. A 2-side p value <0.05 was consider significant. RESULTS: 249 patients (<1500m n=55; 1500 to <2500m n=20; 2500 to <3500m n=155 and ≥3500m n=19) were included. Adjusted and non-adjusted PaO2/FiO2 were correlated with several respiratory and non respiratory variables. None discordances between non adjusted and adjusted PaO2/FiO2 were identified. However, several correlations were appreciated only in patients situated <1500m or in >1500m. Seventy-nine patients died during the ICU stayed (32%). The mortality curve was not affected by the altitude above the sea level. Variables independently associated to mortality are: PEEP, age, systolic arterial blood pressure, and platelet count. AUROC: 0.72. CONCLUSION: In acclimatized patients undergoing invasive mechanical ventilation, the traditional equation for adjusting PaO2/FiO2 according the elevation above the sea level seems to be inaccurate and the altitude above the sea level does not affect the mortality risk.

Predicting the Impact of Diffuse Alveolar Damage through Open Lung Biopsy in Acute Respiratory Distress Syndrome-The PREDATOR Study.

The aim of this retrospective and international study is to identify those clinical variables associated with diffuse alveolar damage (DAD), and to explore the impact of DAD on hospital mortality risk. Inclusion criteria were: adult patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy (OLB) during their intensive care unit (ICU) management. The main end-points were: DAD and hospital mortality. In the training (n = 193) and validation cohorts (n = 65), the respiratory rate (odd ratio (OR) 0.956; confidence interval (CI) 95% 0.918; 0.995) and coronary ischemia (OR 5.974; CI95% 1.668; 21.399) on the day of ARDS had an average area under the receiver operating characteristic curve (AUROC) of 0.660 (CI95% 0.585; 0.736) and 0.562 (0.417; 0.706), respectively. PEEP (OR 1.131; CI95% 1.051; 1.218) and coronary ischemia (OR 6.820; CI95% 1.856; 25.061) on the day of OLB had an average AUROC of 0.696 (CI95% 0.621; 0.769) and 0.534 (CI95% 0.391; 0.678), respectively, to predict DAD. DAD (OR 2.296; CI95% 1.228; 4.294), diabetes mellitus requiring insulin (OR 0.081; CI95% 0.009; 0.710) and the respiratory rate (OR 1.045; CI95% 1.001; 1.091) on the day of ARDS had an average AUROC of 0.659 (CI95% 0.583; 0.737) and 0.513 (CI95% 0.361; 0.664) to predict hospital mortality and DAD (OR 2.081; CI95% 1.053; 4.114), diabetes mellitus requiring insulin (OR 0.093; CI95% 0.009; 0.956), PaCO2 (OR 1.051; CI95% 1.019; 1.084), and platelets count (OR 0.999; CI95% 0.999; 0.999) the day of OLB had an average AUROC of 0.778 (CI95% 0.710; 0.843) and 0.634 (CI95%0.481; 0.787) to predict hospital mortalty in the training and validation cohorts, respectively. In conclusion, DAD could not to be predicted clinically and was significantly associated with hospital mortality.

What have we learned from network meta-analyses applied to critical care?

It is widely accepted in modern medicine that medical decisions must be supported by scientific evidence. Identifying the best intervention when several options are available constitute a great challenge for every clinician. Traditional meta-analysis (TMA) allows summarizing evidence from studies that compare the same two interventions for one event (head to head studies or direct comparisons). Network meta-analysis (NMA) is a relatively new procedure that allows to compare multiple interventions for one event, even when non-head to head studies have been conducted (indirect evidence). Other advantages of NMA include increasing the accuracy of the results and ranking all the interventions according to their effectiveness. These features are of paramount importance as: 1) they summarize information from events (e.g. diseases or outcomes) that has more than two possible interventions (e.g. treatments or procedures); 2) they strengthen the level of guideline recommendations; and 3) they identify new hypotheses based on indirect comparison. As this is a narrative review, all manuscripts have been selected from PubMed according to our best knowledge with the aim to illustrate different features, options or applications of NMA in critical care. First, we provide a description of the usefulness, interpretation, assumptions and main plots related to NMAs. Second, we analyzed some examples of NMAs related to critical care medicine. Third, we include a pragmatic approach about how results from NMAs can improve the clinical practice as well an R script with a database to conduct an NMAs and reproduce figures and tables that have been shown here. As a conclusion, NMA is an established, robust, objective and reproducible statistic technique that has been applied to several critical care areas. Clinical practice guidelines have started to include NMA evidence to support their recommendations. In future years, it seems highly probable that this technique will increase it applicability in almost all areas of critical care medicine.

Airway Pathological Alterations Selectively Associated With Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage - Narrative Review / Alteraciones patológicas de las vías respiratorias relacionadas con el síndrome de distrés respiratorio agudo y el daño alveolar difuso. Revisión narrativa

Acute respiratory distress syndrome (ARDS) is a frequent and life-threatening entity. Recently, it has been demonstrated that diffuse alveolar damage (DAD), which is considered the histological hallmark in spite of presenting itself in only half of living patients with ARDS, exerts a relevant effect in the ARDS outcome. Despite the fact that the bronchial tree constitutes approximately 1% of the lung volume, discovering a relation between DAD and bronchial tree findings could be of paramount importance for a few reasons; (a) it could improve the description of ARDS with DAD as a clinical-pathological entity, (b) it could subrogate DAD findings with the advantage of their more accessible and safer analysis and (c) it could allow the discovery of new therapeutic targets. This narrative review is focused on pathological airway changes associated to Diffuse Alveolar Damage in the context of Acute Respiratory Distress Syndrome. It is organized into five sections: main anatomical and functional features of the human airway, why it is necessary to study airway features associated to DAD in patients with ARDS, pathological airway changes associated with DAD in animal models of ARDS, pathological airway changes associated with DAD in patients with ARDS, and the newest techniques for studying the histology of the bronchial tree and lung parenchyma

El síndrome de distrés respiratorio agudo (SDRA) es una patología frecuente con riesgo asociado para la vida de los pacientes. Recientemente, se ha demostrado que el daño alveolar difuso (DAD), considerado como la manifestación histológica característica del síndrome, además de presentarse en la mitad de los pacientes que padecen SDRA, posee un papel relevante en la evolución de este. A pesar del hecho de que el árbol bronquial constituye aproximadamente un 1% del volumen pulmonar, el descubrimiento de una asociación entre el DAD y hallazgos en el árbol bronquial podría ser muy importante por algunas razones: (a) podría mejorar el diagnóstico del SDRA con DAD como entidad clínico-patológica, (b) podría subrogar marcadores de DAD, cuyo análisis sea más seguro y accesible, (c) podría favorecer el descubrimiento de nuevas dianas terapéuticas. Esta revisión narrativa se centra en las alteraciones patológicas de las vías respiratorias asociadas al daño alveolar difuso en el contexto del síndrome de distrés respiratorio agudo. El texto se compone de cinco secciones: principales características anatómicas y funcionales de las vías respiratorias en humanos, por qué es necesario estudiar las características de las vías respiratorias asociadas al daño alveolar difuso en los pacientes con síndrome de distrés respiratorio agudo, alteraciones patológicas de las vías respiratorias asociadas con DAD en modelos animales de SDRA, alteraciones patológicas de las vías respiratorias asociadas con DAD en pacientes con SDRA y nuevas técnicas para el estudio histológico del árbol bronquial y el parénquima pulmonar

Identification of novel metabolomic biomarkers in an experimental model of septic acute kidney injury.

The aim of this study is the identification of metabolomic biomarkers of sepsis and sepsis-induced acute kidney injury (AKI) in an experimental model. Pigs were anesthetized and monitored to measure mean arterial pressure (MAP), systemic blood flow (QT), mean pulmonary arterial pressure, renal artery blood flow (QRA), renal cortical blood flow (QRC), and urine output (UO). Sepsis was induced at t = 0 min by the administration of live Escherichia coli ( n = 6) or saline ( n = 8). At t = 300 min, animals were killed. Renal tissue, urine, and serum samples were analyzed by nuclear magnetic resonance (NMR) spectroscopy. Principal component analyses were performed on the processed NMR spectra to highlight kidney injury biomarkers. Sepsis was associated with decreased QT and MAP and decreased QRA, QRC, and UO. Creatinine serum concentration and neutrophil gelatinase-associated lipocalin (NGAL) serum and urine concentrations increased. NMR-based metabolomics analysis found metabolic differences between control and septic animals: 1) in kidney tissue, increased lactate and nicotinuric acid and decreased valine, aspartate, glucose, and threonine; 2) in urine, increased isovaleroglycine, aminoadipic acid, N-acetylglutamine, N-acetylaspartate, and ascorbic acid and decreased myoinositol and phenylacetylglycine; and 3) in serum, increased lactate, alanine, pyruvate, and glutamine and decreased valine, glucose, and betaine concentrations. The concentration of several metabolites altered in renal tissue and urine samples from septic animals showed a significant correlation with markers of AKI (i.e., creatinine and NGAL serum concentrations). NMR-based metabolomics is a potentially useful tool for biomarker identification of sepsis-induced AKI.

Airway Pathological Alterations Selectively Associated With Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage - Narrative Review.

Acute respiratory distress syndrome (ARDS) is a frequent and life-threatening entity. Recently, it has been demonstrated that diffuse alveolar damage (DAD), which is considered the histological hallmark in spite of presenting itself in only half of living patients with ARDS, exerts a relevant effect in the ARDS outcome. Despite the fact that the bronchial tree constitutes approximately 1% of the lung volume, discovering a relation between DAD and bronchial tree findings could be of paramount importance for a few reasons; (a) it could improve the description of ARDS with DAD as a clinical-pathological entity, (b) it could subrogate DAD findings with the advantage of their more accessible and safer analysis and (c) it could allow the discovery of new therapeutic targets. This narrative review is focused on pathological airway changes associated to Diffuse Alveolar Damage in the context of Acute Respiratory Distress Syndrome. It is organized into five sections: main anatomical and functional features of the human airway, why it is necessary to study airway features associated to DAD in patients with ARDS, pathological airway changes associated with DAD in animal models of ARDS, pathological airway changes associated with DAD in patients with ARDS, and the newest techniques for studying the histology of the bronchial tree and lung parenchyma.