Renal safety of liposomal amphotericin B in critically ill mechanically ventilated patients with SARS-CoV-2 pneumonia

Introduction: Liposomal amphotericin B (L-AmB) represent a good treatment strategy for critically ill patients according to its unique pharmacological characteristics and a relatively broad spectrum of action. The aim of the present study is to asses the impact on renal function of L-AmB during the first days of ICU admission in critically ill patients. Method(s): Retrospective, single-center case series of patients with SARS-CoV-2 pneumonia admitted in ICU. Setting(s): 19-bed medical-surgical ICU of a community hospital. Time of study: 2 years. Study variables: APACHE II and SOFA at admission, clinical characteristics, oliguria and creatinine level at admission and 72 h after L-AmB treatment were recorded. Oliguria was defined as urinary output less than 400 ml per day or less than 20 ml per hour. Two groups of patients were selected according to whether or not they received anticipated antifungal treatment pending microbiologic confirmation or discarding of aspergillosis;dosage of L-AmB was 3 mg/kg/d. Statistical analysis: Data were analyzed by SPSS 18 and quantitative variables were expressed as a mean +/- standard deviation. Result(s): 160 patients were included, 102 who received 3 days of anticipated treatment with L-AmB at ICU admission or at the beginning of mechanical ventilation were compared with patients without this treatment. There were not differences in age, median 65 [57-71] years, gender with 28% female and BMI (kg/m2), 30,4 [26,6-33,2]. APACHE II at admission was higher in the treated group of patients 17 [12-23] vs 12 [9-14]. SOFA was 7 [4-8] in the treated group of patients vs 6 [3-8]. There were not differences in urinary output between groups during the three first days of ICU stay. Table 1 shows creatinine levels. Conclusion(s): According to our retrospective analysis, L-AmB is safe in the first days of treatment in critically ill patients admitted in ICU requiring mechanical ventilation.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients Una consideración terapéutica diferencial para el uso de corticoesteroides en COVID-19 según los diferentes fenotipos clínicos establecidos en pacientes críticos

Objective To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design A secondary analysis derived from multicenter, observational study. Setting Critical Care Units. Patients Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions Corticosteroids vs. no corticosteroids. Main variables of interest Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0;95% CI: 0.98–1.15). Corticosteroids were administered in 298/537 (55.5%) patients of “A” phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55–1.33]). A total of 338/623 (54.2%) patients in “B” phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49–1.05]). Finally, 535/857 (62.4%) patients in “C” phenotype received corticosteroids. In this phenotype HR (0.75 [0.58–0.98]) and sHR (0.79 [0.63–0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study Factores predictivos de la mortalidad a las seis semanas en pacientes críticos con SARS-CoV-2: estudio multicéntrico prospectivo

Objective The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. Design Prospective descriptive multicenter cohort study. Setting 26 Intensive care units (ICU) from Andalusian region in Spain. Patients or participants Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. Interventions None. Variables Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. Results 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%;14 days mortality: 81/422 (19.2%);28 days mortality: 121/422 (28.7%);6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470 U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72 h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. Conclusion Age, APACHE II, SOFA > value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units☆ Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

[Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU]. / Manejo de las complicaciones infecciosas asociadas con la infección por coronavirus en pacientes graves ingresados en UCI.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

[Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients in the coronavirus disease (COVID-19)]. / Recomendaciones de «hacer¼ y «no hacer¼ en el tratamiento de los pacientes críticos ante la pandemia por coronavirus causante de COVID-19 de los Grupos de Trabajo de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC).

On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.

[Ethical recommendations for a difficult decision-making in intensive care units due to the exceptional situation of crisis by the COVID-19 pandemia: A rapid review & consensus of experts]. / Recomendaciones éticas para la toma de decisiones difíciles en las unidades de cuidados intensivos ante la situación excepcional de crisis por la pandemia por COVID-19: revisión rápida y consenso de expertos.

In view of the exceptional public health situation caused by the COVID-19 pandemic, a consensus work has been promoted from the ethics group of the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC), with the objective of finding some answers from ethics to the crossroads between the increase of people with intensive care needs and the effective availability of means.In a very short period, the medical practice framework has been changed to a 'catastrophe medicine' scenario, with the consequent change in the decision-making parameters. In this context, the allocation of resources or the prioritization of treatment become crucial elements, and it is important to have an ethical reference framework to be able to make the necessary clinical decisions. For this, a process of narrative review of the evidence has been carried out, followed by a unsystematic consensus of experts, which has resulted in both the publication of a position paper and recommendations from SEMICYUC itself, and the consensus between 18 scientific societies and 5 institutes/chairs of bioethics and palliative care of a framework document of reference for general ethical recommendations in this context of crisis.

Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients in the coronavirus disease (COVID-19)

On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic. Resumen El 11 de marzo de 2020 el director general de la Organización Mundial de la Salud (OMS) declaró la enfermedad causada por el SARS-CoV-2 (COVID-19) como una pandemia. La propagación y evolución de la pandemia está poniendo a prueba los sistemas sanitarios de decenas de países y ha dado lugar a una miríada de artículos de opinión, planes de contingencia, series de casos e incipientes ensayos. Abarcar toda esta literatura es complejo. De forma breve y sintética, en la línea de las anteriores recomendaciones de los Grupos de Trabajo, la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) ha elaborado esta serie de recomendaciones básicas para la asistencia a pacientes en el contexto de la pandemia.