Simulators and Simulations for Extracorporeal Membrane Oxygenation: An ECMO Scoping Review

Classification; Extracorporeal life support; Simulation trainingClassificació; Suport vital extracorpòri; Formació en simulacióClasificación; Soporte vital extracorpóreo; Formación en simulaciónHigh-volume extracorporeal membrane oxygenation (ECMO) centers generally have better outcomes than (new) low-volume ECMO centers, most likely achieved by a suitable exposure to ECMO cases. To achieve a higher level of training, simulation-based training (SBT) offers an additional option for education and extended clinical skills. SBT could also help to improve the interdisciplinary team interactions. However, the level of ECMO simulators and/or simulations (ECMO sims) techniques may vary in purpose. We present a structured and objective classification of ECMO sims based on the broad experience of users and the developer for the available ECMO sims as low-, mid-, or high-fidelity. This classification is based on overall ECMO sim fidelity, established by taking the median of the definition-based fidelity, component fidelity, and customization fidelity as determined by expert opinion. According to this new classification, only low- and mid-fidelity ECMO sims are currently available. This comparison method may be used in the future for the description of new developments in ECMO sims, making it possible for ECMO sim designers, users, and researchers to compare accordingly, and ultimately improve ECMO patient outcomes.This research was funded by the 2022 “Boost Your Research” Fund in the Priority Program SPP 2014 “Towards an Implantable Lung” by the DFG, the German Research Foundation, grant number 20003297 UKA

Nuevas perspectivas en trasplante de pulmón

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018Dos de las complicaciones que tienen más impacto en la supervivencia tras el trasplante de pulmón (TP) son la disfunción primaria del injerto (DPI) y la infección respiratoria. El presente trabajo de tesis está compuesto por dos investigaciones sobre estas complicaciones. En el primer trabajo se ha estudiado el papel del biomarcador proadrenomedulina en la DPI. El objetivo del trabajo fue investigar la asociación entre sus niveles en plasma (medidos mediante inmunofluorescencia) en los primeros tres días del postoperatorio y la función del injerto [definida mediante el cociente presión arterial de oxígeno/fracción inspiratoria de oxígeno (PaO2/FIO2)], los diferentes grados de DPI y la mortalidad en la unidad de cuidados intensivos (UCI). Para ello, se diseñó un estudio prospectivo que incluyó 100 receptores de TP ingresados en la UCI tras la cirugía. Se confirmó la presencia de asociación entre los valores del biomarcador y el índice PaO2/FIO2 en los primeros tres días. Los niveles de proadrenomedulina medidos a las 24 horas fueron significativamente más elevados en la población de enfermos que a las 72 horas presentaba DPI grado tres, único grado asociado a una mayor mortalidad en la UCI. Los niveles de proadrenomedulina medidos a las 48 y a las 72 horas fueron significativamente más elevados en los pacientes que fallecieron en la UCI. Por último, el área debajo de la curva ROC de la DPI grado tres a las 72 horas para predecir la mortalidad en la UCI fue optimizada añadiendo al modelo la de los niveles de proadrenomedulina medidos a las 72 horas. Tras la investigación se puede concluir que los niveles elevados de proadrenomedulina medidos en el postoperatorio inmediato del TP están significativamente asociados con el grado más grave de DPI y con la mortalidad precoz. Estos hallazgos tienen implicación en el pronóstico de estos pacientes y son relevantes para investigaciones futuras sobre DPI. En el segundo trabajo se ha estudiado la repercusión de la infección respiratoria en el postoperatorio inmediato del TP. El objetivo principal de la investigación fue evaluar el efecto de la neumonía y la traqueobronquitis asociadas a ventilación mecánica (VAP y VAT respectivamente) en el tiempo de estancia en la UCI y en el hospital y con la mortalidad. Como objetivos secundarios, se identificaron los gérmenes causantes de dichas infecciones y los factores de riesgo de aparición de las mismas. Para ello se diseñó un estudio retrospectivo donde se analizaron los datos clínicos de 170 receptores de TP ingresados en la UCI tras la cirugía. Los pacientes que sufrieron infección respiratoria asociada a ventilación mecánica estuvieron más tiempo en UCI y en el hospital. Asimismo, la mortalidad fue más elevada en los pacientes que sufrieron VAP, no así en los pacientes con VAT. Pseudomonas aeruginosa fue el germen que más frecuentemente causó infección asociada a ventilación mecánica. En el caso de la VAP, 8/12 fueron Pseudomonas aeruginosa multirresistente. En el análisis multivariado, se encontró que la paresia gástrica fue un factor de riesgo independiente para el desarrollo de VAP, asociación que se mantuvo al ajustar el análisis por los días de ventilación mecánica. Asimismo, se evidenció que la paresia gástrica y la paresia frénica fueron factores de riesgo para el desarrollo de VAT. Se puede concluir que la prevención de VAP disminuiría la mortalidad precoz en receptores de TP, que el tratamiento empírico de la misma ha de cubrir gérmenes multirresistentes, que la prevención de paresia gástrica disminuiría la incidencia de VAP y que la prevención de paresia frénica disminuiría la incidencia de VAT.Two of the complications that have the greatest impact on survival after lung transplantation (LT) are primary graft dysfunction (PGD) and respiratory infections. This thesis includes two studies on these complications. The first of these studies analyzed the role of the biomarker proadrenomedullin (proADM) in PGD. The objective was to assess the association between proADM plasma levels (measured by immunofluorescence) in the first three days after surgery and graft function [defined by the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FIO2) ratio], the different degrees of PGD and mortality in the intensive care unit (ICU). In this prospective study including 100 LT recipients admitted to the ICU after surgery, a significant association was confirmed between the biomarker levels and the PaO2/FIO2 ratio in the first three days. Proadrenomedullin levels measured at 24 hours were significantly higher in the population of patients who presented grade 3 PGD at 72 hours, the only degree associated with increased ICU mortality. Proadrenomedullin levels measured at 48 and 72 hours were significantly higher in patients who died in the ICU. Finally, adding the individual predictive utility for ICU mortality of grade 3 PGD at 72 hours to that of proADM measured at 72 hours improved the model's predictive value. The conclusion was that higher proADM levels measured following LT are associated with the most severe grade of PGD and with early mortality. These findings may have implications for prognosis in LT recipients and may also be relevant to future research works into PGD. The second study assessed the impact of respiratory infections in the immediate postoperative period after LT. The main objective was to evaluate the effect of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT) on ICU and hospital length of stay and on early mortality. Secondary objectives were to identify their causative organisms and their potential risk factors. A retrospective study was designed in which the clinical data of 170 consecutive LT recipients admitted to the ICU after surgery were analyzed. Suffering ventilator-associated respiratory infection was associated with more days of mechanical ventilation and with longer ICU and hospital stays. Mortality in the ICU was higher in patients who had VAP, but not in patients with VAT. Pseudomonas aeruginosa was the most frequent germ causing ventilator-associated respiratory infection. In the VAP cases, 8/12 were multidrug resistant. The multivariate analysis showed that gastric paresis was an independent risk factor for the development of VAP, an association that remained significant when adjusting for days of mechanical ventilation. Further, both gastric and phrenic paresis were risk factors for the development of VAT. In conclusion, prevention of VAP following LT may reduce early mortality. The empirical treatment of ventilator-associated respiratory infections should cover multidrug resistant pathogens. Finally, prevention of gastroparesis may reduce the incidence of VAP and prevention of phrenic paresis may reduce the incidence of VAT

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

COVID-19; Mechanical ventilation; Ventilatory ratioCOVID-19; Respiració assistida; Relació ventilatòriaCOVID-19; Ventilación mecánica; Relación ventilatoriaBackground Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0–171.2] to 180.0 [135.4–227.9] mmHg and the ventilatory ratio from 1.73 [1.33–2.25] to 1.96 [1.61–2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01–1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01–1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93–1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.Financial support was provided by the Instituto de Salud Carlos III de Madrid (COV20/00110, ISCIII), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa", and by the Centro de Investigación Biomedica En Red – Enfermedades Respiratorias (CIBERES). DdGC has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by European Social Fund (ESF)/”Investing in your future”

Higher frequency of comorbidities in fully vaccinated patients admitted to the ICU due to severe COVID-19: a prospective, multicentre, observational study

Severe COVID-19 disease requiring ICU admission is possible in the fully vaccinated population, especially in those with immunocompromised status and other comorbidities. Interventions to improve vaccine response might be necessary in this population.Peer ReviewedArticle signat per 23 autors/es: Anna Motos, Alexandre López-Gavín, Jordi Riera, Adrián Ceccato, Laia Fernández-Barat, Jesús F. Bermejo-Martin, Ricard Ferrer, David de Gonzalo-Calvo, Rosario Menéndez, Raquel Pérez-Arnal, Dario García-Gasulla, Alejandro Rodriguez, Oscar Peñuelas, José Ángel Lorente, Raquel Almansa, Albert Gabarrus, Judith Marin-Corral, Pilar Ricart, Ferran Roche-Campo, Susana Sancho Chinesta, Lorenzo Socias, Ferran Barbé, Antoni Torres on behalf of the CIBERESUCICOVID Project (COV20/00110, ISCIII).Postprint (published version

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis

Background: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. Methods: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Results: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. Conclusions: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannula.Financial support was provided by the Instituto de Salud Carlos III de Madrid (COV20/00110, ISCIII), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa", and the Centro de Investigación Biomedica En Red – Enfermedades Respiratorias (CIBERES). DdGC has received financial support from the Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by European Social Fund (ESF)/”Investing in your future”.Peer ReviewedArticle signat per 70 autors/es: Jordi Riera*1,2; Enric Barbeta*2,3,4; Adrián Tormos5; Ricard Mellado-Artigas2,3; Adrián Ceccato6; Anna Motos4; Laia Fernández-Barat4; Ricard Ferrer1; Darío García-Gasulla5; Oscar Peñuelas7; José Ángel Lorente7; Rosario Menéndez8; Oriol Roca1,2; Andrea Palomeque4,9; Carlos Ferrando2,3; Jordi SoléViolán10; Mariana Novo11; María Victoria Boado12; Luis Tamayo13; Ángel Estella14, Cristóbal Galban15; Josep Trenado16; Arturo Huerta17; Ana Loza18; Luciano Aguilera19; José Luís García Garmendia20; Carme Barberà21; Víctor Gumucio22; Lorenzo Socias23; Nieves Franco24; Luis Jorge Valdivia25; Pablo Vidal26; Víctor Sagredo27; Ángela Leonor Ruiz-García28; Ignacio Martínez Varela29; Juan López30; Juan Carlos Pozo31; Maite Nieto32; José M Gómez33; Aaron Blandino34; Manuel Valledor35; Elena Bustamante-Munguira36; Ángel Sánchez-Miralles37; Yhivian Peñasco38; José Barberán39; Alejandro Ubeda40; Rosario Amaya-Villar41; María Cruz Martín42; Ruth Jorge43; Jesús Caballero44; Judith Marin45; José Manuel Añón46; Fernando Suárez Sipmann47; Guillermo Muñiz2,48;Álvaro Castellanos-Ortega49; Berta Adell-Serrano50; Mercedes Catalán51; Amalia Martínez de la Gándara52; Pilar Ricart53; Cristina Carbajales54; Alejandro Rodríguez55; Emili Díaz6; Mari C de la Torre56; Elena Gallego57; Luisa Cantón-Bulnes58; Nieves Carbonell59, Jessica González60, David de Gonzalo-Calvo60, Ferran Barbé60 and Antoni Torres2,4,9 on behalf of the CiberesUCICOVID Consortium. // 1. Critical Care Department, Hospital Universitari Vall d’Hebron; SODIR, Vall d’Hebron Institut de Recerca, Barcelona, Spain. 2. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. 3.Surgical Intensive Care Unit, Hospital Clínic de Barcelona, Barcelona, Spain. 4. Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Spain. 5. Barcelona Supercomputing Center (BSC), Barcelona, Spain. 6. Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Sabadell, Spain. Universitat Autonoma de Barcelona (UAB), Spain. 7. Hospital Universitario de Getafe, Universidad Europea, Madrid, Spain. 8. Pneumology Department, Hospital Universitario y Politécnico La Fe/Instituto de Investigación Sanitaria (IIS) La Fe, 46026 Valencia, Spain; Pneumology Department, Hospital Universitario y Politécnico La Fe, Avda, Fernando Abril Martorell 106, 46026 Valencia, Spain. 9.Respiratory Intensive Care Unit, Hospital Clínic de Barcelona, Barcelona, Spain. 10. Critical Care Department, Hospital Dr. Negrín Gran Canaria. Universidad Fernando Pessoa. Las Palmas, Gran Canaria, Spain. 11. Servei de Medicina Intensiva, Hospital Universitari Son Espases, Palma de Mallorca, Illes Balears, Spain. 12. Hospital Universitario de Cruces, Barakaldo, Spain. 13. Critical Care Department, Hospital Universitario Río Hortega de Valladolid, Valladolid, Spain. 14. Departamento Medicina Facultad Medicina Universidad de Cádiz. Hospital Universitario de Jerez, Jerez de la Frontera, Spain. 15. Department of Medicine, CHUS, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. 16. Servicio de Medicina Intensiva, Hospital Universitario Mútua de Terrassa, Terrassa, Barcelona, Spain. 17. Pulmonary and Critical Care Division; Emergency Department, Clínica Sagrada Família, Barcelona, Spain. 18. Hospital Virgen de Valme, Sevilla, Spain. 19. Hospital de Basurto, Bilbao, Spain. 20. Intensive Care Unit, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla, Spain. 21. Hospital Santa Maria; IRBLleida, Lleida, Spain. 22. Department of Intensive Care. Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain. Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. 23. Intensive Care Unit, Hospital Son Llàtzer, Palma de Mallorca, Illes Balears, Spain. 24. Hospital Universitario de Móstoles, Madrid, Spain. 25. Hospital Universitario de León, León, Spain. 26. Complexo Hospitalario Universitario de Ourense, Ourense, Spain. 27. Hospital Universitario de Salamanca, Salamanca, Spain. 28. Servicio de Microbiología Clínica, Hospital Universitario Príncipe de Asturias – Departamento de Biomedicina y Biotecnología, Universidad de Alcalá de Henares, Madrid, Spain. 29. Critical Care Department, Hospital Universitario Lucus Augusti, Lugo, Spain. 30. Complejo Asistencial Universitario de Palencia, Palencia, Spain. 31. UGC-Medicina Intensiva, Hospital Universitario Reina Sofia, Instituto Maimonides IMIBIC, Córdoba, Spain. 32. Hospital Universitario de Segovia, Segovia, Spain. 33. Hospital General Universitario Gregorio Marañón, Madrid, Spain. 34. Servicio de Medicina Intensiva, Hospital Universitario Ramón y Cajal, Madrid, Spain. 35. Hospital Universitario "San Agustín", Avilés, Spain. 36. Department of Intensive Care Medicine, Hospital Clínico Universitario Valladolid, Valladolid, Spain. 37. Servicio de Medicina Intensiva. Hospital Universitario Sant Joan d´Alacant, Alicante, Spain. 38. Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 39. Hospital Universitario HM Montepríncipe, Universidad San Pablo-CEU, Madrid, Spain. 40. Servicio de Medicina Intensiva, Hospital Punta de Europa, Algeciras, Spain. 41. Intensive Care Clinical Unit, Hospital Universitario Virgen de Rocío, Sevilla, Spain. 42. Hospital Universitario Torrejón- Universidad Francisco de Vitoria, Madrid, Spain. 43. Intensive Care Department, Hospital Nuestra Señora de Gracia, Zaragoza, Spain. 44. Critical Care Department, Hospital Universitari Arnau de Vilanova; IRBLleida, Lleida, Spain. 45. Critical Care Department, Hospital del Mar-IMIM, Barcelona, Spain. 46. Hospital Universitario la Paz, Madrid, Spain. 47. Intensive Care Unit, Hospital Universitario La Princesa, Madrid, Spain. 48. Departamento de Biología Funcional. Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo; Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Central de Asturias, Oviedo, Spain. 49. Hospital Universitario y Politécnico la Fe, Valencia, Spain. 50. Hospital de Tortosa Verge de la Cinta, Tortosa, Tarragona, Spain. 51. Department of Intensive Care Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain. 52. Hospital Universitario Infanta Leonor, Madrid, Spain. 53. Servei de Medicina Intensiva, Hospital Universitari Germans Trias, Badalona, Spain. 54. Intensive Care Unit, Hospital Álvaro Cunqueiro, Vigo, Spain. 55. Hospital Universitari Joan XXIII de Tarragona, Tarragona, Spain. 56. Hospital de Mataró de Barcelona, Spain. 57. Unidad de Cuidados Intensivos, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain. 58. Unidad de Cuidados Intensivos, Hospital Virgen Macarena, Sevilla, Spain. 59. Intensive Care Unit, Hospital Clínico y Universitario de Valencia, Valencia, Spain. 60. Translational Research in Respiratory Medicine, Respiratory Department, Hospital Universitari Aranu de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.Postprint (published version

Pulmonary Air Embolism in a Patient with COVID-19 with Extracorporeal Membrane Oxygenation Support

Embòlia aèria pulmonar; COVID-19Embolia aérea pulmonar; COVID-19Pulmonary air embolism; COVID-1

Pulmonary function and radiologic features in survivors of critical COVID-19: a 3-month prospective cohort

© 2021 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/BACKGROUND: More than 20% of hospitalized patients with COVID-19 demonstrate ARDS requiring ICU admission. The long-term respiratory sequelae in such patients remain unclear. RESEARCH QUESTION: What are the major long-term pulmonary sequelae in critical patients who survive COVID-19? STUDY DESIGN AND METHODS: Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-min walking test [6MWT]), and chest CT imaging. RESULTS: One hundred twenty-five patients admitted to the ICU with ARDS secondary to COVID- 19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median distance in the 6MWT was 400 m (interquartile range, 362-440 m). CT scans showed abnormal results in 70.2% of patients, demonstrating reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT scan showed worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT scan were age and length of invasive mechanical ventilation during the ICU stay. INTERPRETATION: Three months after hospital discharge, pulmonary structural abnormalities and functional impairment are highly prevalent in patients with ARDS secondary to COVID- 19 who required an ICU stay. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months after discharge.This study was supported in part by the Instituto de Salud Carlos III [Grant CIBERESUCICOVID, COV20/00110] and was cofunded by European Regional Development Funds, “Una manera de hacer Europa.” D. d. G.-C. has received financial support from the Instituto de Salud Carlos III [Grant Miguel Servet 2020: CP20/00041], co-funded by the European Social Fund “Investing in Your Future.” L. P. acknowledges receiving financial support from the Ministry of Science, Innovation and Universities for the Training of University Lecturers (FPU19 / 03526).Peer ReviewedPostprint (author's final draft

Nuevas perspectivas en trasplante de pulmón

Dos de las complicaciones que tienen más impacto en la supervivencia tras el trasplante de pulmón (TP) son la disfunción primaria del injerto (DPI) y la infección respiratoria. El presente trabajo de tesis está compuesto por dos investigaciones sobre estas complicaciones. En el primer trabajo se ha estudiado el papel del biomarcador proadrenomedulina en la DPI. El objetivo del trabajo fue investigar la asociación entre sus niveles en plasma (medidos mediante inmunofluorescencia) en los primeros tres días del postoperatorio y la función del injerto [definida mediante el cociente presión arterial de oxígeno/fracción inspiratoria de oxígeno (PaO2/FIO2)], los diferentes grados de DPI y la mortalidad en la unidad de cuidados intensivos (UCI). Para ello, se diseñó un estudio prospectivo que incluyó 100 receptores de TP ingresados en la UCI tras la cirugía. Se confirmó la presencia de asociación entre los valores del biomarcador y el índice PaO2/FIO2 en los primeros tres días. Los niveles de proadrenomedulina medidos a las 24 horas fueron significativamente más elevados en la población de enfermos que a las 72 horas presentaba DPI grado tres, único grado asociado a una mayor mortalidad en la UCI. Los niveles de proadrenomedulina medidos a las 48 y a las 72 horas fueron significativamente más elevados en los pacientes que fallecieron en la UCI. Por último, el área debajo de la curva ROC de la DPI grado tres a las 72 horas para predecir la mortalidad en la UCI fue optimizada añadiendo al modelo la de los niveles de proadrenomedulina medidos a las 72 horas. Tras la investigación se puede concluir que los niveles elevados de proadrenomedulina medidos en el postoperatorio inmediato del TP están significativamente asociados con el grado más grave de DPI y con la mortalidad precoz. Estos hallazgos tienen implicación en el pronóstico de estos pacientes y son relevantes para investigaciones futuras sobre DPI. En el segundo trabajo se ha estudiado la repercusión de la infección respiratoria en el postoperatorio inmediato del TP. El objetivo principal de la investigación fue evaluar el efecto de la neumonía y la traqueobronquitis asociadas a ventilación mecánica (VAP y VAT respectivamente) en el tiempo de estancia en la UCI y en el hospital y con la mortalidad. Como objetivos secundarios, se identificaron los gérmenes causantes de dichas infecciones y los factores de riesgo de aparición de las mismas. Para ello se diseñó un estudio retrospectivo donde se analizaron los datos clínicos de 170 receptores de TP ingresados en la UCI tras la cirugía. Los pacientes que sufrieron infección respiratoria asociada a ventilación mecánica estuvieron más tiempo en UCI y en el hospital. Asimismo, la mortalidad fue más elevada en los pacientes que sufrieron VAP, no así en los pacientes con VAT. Pseudomonas aeruginosa fue el germen que más frecuentemente causó infección asociada a ventilación mecánica. En el caso de la VAP, 8/12 fueron Pseudomonas aeruginosa multirresistente. En el análisis multivariado, se encontró que la paresia gástrica fue un factor de riesgo independiente para el desarrollo de VAP, asociación que se mantuvo al ajustar el análisis por los días de ventilación mecánica. Asimismo, se evidenció que la paresia gástrica y la paresia frénica fueron factores de riesgo para el desarrollo de VAT. Se puede concluir que la prevención de VAP disminuiría la mortalidad precoz en receptores de TP, que el tratamiento empírico de la misma ha de cubrir gérmenes multirresistentes, que la prevención de paresia gástrica disminuiría la incidencia de VAP y que la prevención de paresia frénica disminuiría la incidencia de VAT.Two of the complications that have the greatest impact on survival after lung transplantation (LT) are primary graft dysfunction (PGD) and respiratory infections. This thesis includes two studies on these complications. The first of these studies analyzed the role of the biomarker proadrenomedullin (proADM) in PGD. The objective was to assess the association between proADM plasma levels (measured by immunofluorescence) in the first three days after surgery and graft function [defined by the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FIO2) ratio], the different degrees of PGD and mortality in the intensive care unit (ICU). In this prospective study including 100 LT recipients admitted to the ICU after surgery, a significant association was confirmed between the biomarker levels and the PaO2/FIO2 ratio in the first three days. Proadrenomedullin levels measured at 24 hours were significantly higher in the population of patients who presented grade 3 PGD at 72 hours, the only degree associated with increased ICU mortality. Proadrenomedullin levels measured at 48 and 72 hours were significantly higher in patients who died in the ICU. Finally, adding the individual predictive utility for ICU mortality of grade 3 PGD at 72 hours to that of proADM measured at 72 hours improved the model’s predictive value. The conclusion was that higher proADM levels measured following LT are associated with the most severe grade of PGD and with early mortality. These findings may have implications for prognosis in LT recipients and may also be relevant to future research works into PGD. The second study assessed the impact of respiratory infections in the immediate postoperative period after LT. The main objective was to evaluate the effect of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT) on ICU and hospital length of stay and on early mortality. Secondary objectives were to identify their causative organisms and their potential risk factors. A retrospective study was designed in which the clinical data of 170 consecutive LT recipients admitted to the ICU after surgery were analyzed. Suffering ventilator-associated respiratory infection was associated with more days of mechanical ventilation and with longer ICU and hospital stays. Mortality in the ICU was higher in patients who had VAP, but not in patients with VAT. Pseudomonas aeruginosa was the most frequent germ causing ventilator-associated respiratory infection. In the VAP cases, 8/12 were multidrug resistant. The multivariate analysis showed that gastric paresis was an independent risk factor for the development of VAP, an association that remained significant when adjusting for days of mechanical ventilation. Further, both gastric and phrenic paresis were risk factors for the development of VAT. In conclusion, prevention of VAP following LT may reduce early mortality. The empirical treatment of ventilator-associated respiratory infections should cover multidrug resistant pathogens. Finally, prevention of gastroparesis may reduce the incidence of VAP and prevention of phrenic paresis may reduce the incidence of VAT

A statistical study of ship domains

SIGLELD:D50265/84 / BLDSC - British Library Document Supply CentreGBUnited Kingdo