Ventilando a los pacientes con SDRA: cuando menos es mejor

En el año 2000 se publicó un artículo del ARDS Network que cambió la forma de ventilar a los pacientes con SDRA. De forma tradicional, los pacientes con SDRA eran ventilados con volúmenes cercanos a los 10-15 ml/kg para poder mantener la PaCO2 dentro de los límites normales. Sin embargo, la utilización de volúmenes corrientes más pequeños demostró mejorar la supervivencia de los pacientes con SDRA, y en el momento actual los valores estándares de ventilación para los pacientes con lesión pulmonar aguda y SDRA son un volumen corriente ≤ 6 ml/kg del peso ideal y una presión meseta en la vía aérea ≤ 30 cmH2O. No obstante, incluso utilizando valores como éstos de volumen corriente y de presión en la vía aérea, la ventilación mecánica puede a su vez dañar el pulmón ya lesionado. Esto es debido a la heterogeneidad anatómica de las lesiones que subyacen en el pulmón con SDRA, lo cual genera una respuesta inflamatoria difusa. De hecho, cualquier volumen corriente, por muy pequeño que sea, puede dañar el pulmón con SDRA debido a una sobredistensión de los alvéolos no lesionados y al colapso cíclico de la vía aérea más distal llena de líquido. Uno de los problemas que limita la utilización de un volumen corriente pequeño en el paciente con SDRA es el aumento en la PaCO2 y la aparición de una acidosis respiratoria progresiva, mayor cuanto mayor es la disminución en el volumen corriente. Terragni et al evalúan en este artículo que se comenta, el impacto de ventilar con un volumen corriente de 4 ml/kg a un grupo de pacientes con SDRA que presentan una presión meseta de 28-30 cm H2O al ser ventilados con un volumen corriente de 6 ml/kg; el exceso de CO2 y la acidosis respiratoria fue controlado mediante la utilización de un circuito extracorpóreo modificado a partir de un circuito de hemofiltración veno-venosa continuo (en el artículo hay un dibujo que ilustra el dispositivo utilizado)

Comparación de la dexmedetomidina con el midazolam en la sedación del paciente crítico: Riker RR, Shehabi Y, Bokesch PM, Cersao D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG, for the SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients. A randomized trial. JAMA 2009; 301: 489-99.

Los fármacos que en la actualidad utilizamos en las unidades de cuidados críticos para sedar a los pacientes, estén o no en ventilación mecánica, son los agonistas del receptor ácido γ-aminobutírico (GABA), como el propofol y las benzodiacepinas (dentro de éstas el más utilizado es el midazolam). Se han realizado estudios comparando resultados entre ambos tipo de sedantes, pero son escasos los estudios comparando los efectos sedantes con otras familias de fármacos. mecanismo-de-accion-dexmedetomidina La dexmedetomidina es un agonista de los receptores α2-adrenérgicos, proporcionando sedación y ansiolisis por medio de los receptores situados en el locus cerúleo, analgesia vía los receptores situados en la médula espinal y atenuación de la respuesta al estrés sin depresión respiratoria significativa. Este ensayo multicéntrico realizado en cinco países compara los efectos de la dexmedetomidina con midazolam en pacientes sometidos a ventilación mecánica

El tratamiento antibiótico óptimo para la neumonía por SARM: buscando "el Dorado": Jung YJ, Koh Y, Hong S-B, Chung JW, Choi SH, Kim NJ, Kim MN, Choi IS, Han AY, Kim WD, Yun S-C, Lim C-M. Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia. Crit Care Med 2010; 38:175-180

La neumonía por Staphylococcus aureus resistente a la meticilina (SARM) es una de las infecciones nosocomiales más comunes y está asociada con una elevada mortalidad y coste sanitario. De hecho, la tasa de mortalidad hospitalaria asociada con infecciones por SARM es superior al 20% en la mayoría de las series y es más alta en pacientes con bacteremia y neumonía. Aunque la vancomicina sigue siendo la primera opción de tratamiento para la neumonía por SARM en muchos centros, varios estudios han sugerido que podría no ser el antibiótico óptimo para tratar este tipo de infección (3). La vancomicina, una molécula hidrofílica (PM=1449 Daltons), penetra muy pobremente dentro del parénquima pulmonar. Como consecuencia, el nivel de vancomicina en el epitelio pulmonar es sólo una sexta parte del nivel en la sangre, y es esta concentración tisular tan baja de antibiótico uno de los responsables en el fallo del tratamiento con vancomicina de la neumonía por SARM. Recientemente se ha también se ha objetivado que una concentración mínima inhibitoria de vancomicina frente a SARM superior a 1,5 se asocia a un mayor fallo terapéutico e incluso una mayor mortalidad. La rifampicina (RFP), un antibiótico que se ha usado principalmente para el tratamiento de la tuberculosis, y es conocida por ejercer efectos bactericidas contra muchos microorganismos grampositivos, incluyendo SARM. La RFP difunde bien en todo el cuerpo y alcanza una concentración efectiva en diferentes órganos, como puede notarse por la decoloración en varios fluidos corporales. La RFP se ha utilizado con éxito como tratamiento coadyuvante a la vancomicina en endocarditis estafilocócica, infecciones de derivaciones ventrículo-peritoneales, y bacteriemia. Considerando la mortalidad tan elevada de la neumonía nosocomial por SARM con la utilización de vancomicina, los autores de este estudio se propusieron investigar si añadir RFP a la vancomicina podría ofrecer mejores resultados

Critically ill patients with community-onset intraabdominal infections: influence of healthcare exposure on resistance rates and mortality

Intraabdominal infections; Healthcare exposure; Intensive care unitsInfeccions intraabdominals; Exposició per tractaments de salut; Unitats de cures intensivesInfecciones intraabdominales; Exposición por tratamientos de salud; Unidades de cuidados intensivosThe concept of healthcare-associated infections (as opposed to hospital-acquired infections) in intraabdominal infections (IAIs) is scarcely supported by data in the literature. The aim of the present study was to analyse community-onset IAIs (non-postoperative/non-nosocomial) in patients admitted to intensive care units (ICUs), to investigate differences in resistance patterns linked to healthcare exposure and mortality-associated factors. A one-year prospective observational study (17 Spanish ICUs) was performed distributing cases as healthcare-associated infections (HCAI), community-acquired infections (CAI) and immunocompromised patients (ICP). Bacteria producing extended-spectrum β-lactamases (ESBL) and/or carbapenemase (CPE), high-level aminoglycoside- and/or methicillin- and/or vancomycin- resistance were considered antimicrobial resistant (AMR). Mortality-associated factors were identified by regression multivariate analysis. Of 345 patients included (18.8% HCAI, 6.1% ICP, 75.1% CAI), 51.6% presented generalized peritonitis; 32.5% were >75 years (55.4% among HCAI). Overall, 11.0% cases presented AMR (7.0% ESBL- and/or CPE), being significantly higher in HCAI (35.4%) vs. CAI (5.8%) (p75 years (OR = 6.67, 95%CI = 2.56–17.36,p75 years, severity and Candida isolation but not with AMR.This multicentre study was possible due to the generous implication of the personnel in the 17 participating ICUs. The study did not receive external funding. One of the authors [MJG] is employee of a commercial company (PRISM-AG) which was not funder of the present study. This company only provided support in the form of the salary for this author [MJG], but did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section

Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain

Carbapenemasa; Infeccions gramnegatives; Infeccions associades a l'assistència sanitàriaCarbapenemasa; Infecciones gramnegativas; Infecciones asociadas a la asistencia sanitariaCarbapenemase; Gram-negative infections; Healthcare-associated infectionsIntroduction. Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals. Methods. The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) attributable to CRGN pathogens. Results. In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. Conclusion. Our results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain

Introduction. Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals. Methods. The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/ VABP) attributable to CRGN pathogens. Results. In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbap enems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. Conclusion. Our results reflect the high burden and un met needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.Funding: Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy

Pseudomonas aeruginosa is characterized by a notable intrinsic resistance to antibiotics, mainly mediated by the expression of inducible chromosomic β-lactamases and the production of constitutive or inducible efflux pumps. Apart from this intrinsic resistance, P. aeruginosa possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. The progressive increase in resistance rates in P. aeruginosa has led to the emergence of strains which, based on their degree of resistance to common antibiotics, have been defined as multidrug resistant, extended-resistant and panresistant strains. These strains are increasingly disseminated worldwide, progressively complicating the treatment of P. aeruginosa infections. In this scenario, the objective of the present guidelines was to review and update published evidence for the treatment of patients with acute, invasive and severe infections caused by P. aeruginosa. To this end, mechanisms of intrinsic resistance, factors favoring development of resistance during antibiotic exposure, prevalence of resistance in Spain, classical and recently appeared new antibiotics active against P. aeruginosa, pharmacodynamic principles predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment were reviewed to elaborate recommendations by the panel of experts for empirical and directed treatment of P. aeruginosa invasive infections

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project.

PURPOSE: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). METHODS: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. RESULTS: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. CONCLUSION: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study

Background: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. Methods: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero (2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. Findings: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16-0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26-0·57; p<0·0001, compared with the VIR-N1-Storm group). Interpretation: The presence of a so-called viral storm is associated with increased all-cause death in patients admitted to the intensive care unit with severe COVID-19. Preventing this viral storm could help to reduce poor outcomes. Viral storm could be an enrichment marker for treatment with antivirals or purification devices to remove viral components from the blood.This work was supported by grants from the Instituto de Salud Carlos III (FONDO-COVID19, COV20/00110, CIBERES, 06/06/0028; AT), Proyectos de Investigación en Salud (PI19/00590; JFB-M), Miguel Servet (CP20/00041; DdG-C), Sara Borrell (CD018/0123; APT), and Predoctorales de Formación en Investigación en Salud (FI20/00278; AdF). We also received funds from Programa de Donaciones Estar Preparados, UNESPA (Madrid, Spain), and from the Canadian Institutes of Health Research (CIHR OV2–170357; DJK and JFB-M), Research Nova Scotia, Li-Ka Shing Foundation (DJK), and finally by a Research Grant 2020 from ESCMID (APT). COV20/00110, PI19/00590, CP20/00041, CD018/0123, FI20/00278 were co-funded by European Regional Development Fund and European Social Fund (A way to make Europe, and Investing in your future). We thank the IRB-Lleida Biobank 119 (B.0000682) and Plataforma Biobancos PT17/0015/0027 in Lleida, the Hospital Clinic Barcelona (HCB)-IDIBAPS biobank in Barcelona, and the National DNA Bank and the Hospital Universitario de Salamanca biobank (both in Salamanca) for their logistical support with sample processing and storage. We are indebted to the Fundació Glòria Soler for its contribution and support to the COVIDBANK of HCBIDIBAPS Biobank. This work was not supported by any pharmaceutical company or other agency.S