Use of bedside echocardiography in the care of critically ill patients - a joint consensus document of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Medicina de Emergência, and Sociedade Brasileira de Medicina Hospitalar. Part 1 - Competence in bedside echocardiography.

The use of echocardiography by physicians who are not echocardiographers has become common throughout the world across highly diverse settings where the care of acutely ill patients is provided. Echocardiographic evaluation performed in a point-of-care manner can provide relevant information regarding the mechanism of causes of shock, for example, increasing the rates of correct diagnosis and allowing for faster informed decision-making than through evaluation methods. Considering that the accurate diagnosis of life-threatening situations is essential for professionals working with acutely ill patients, several international associations recommend that physicians responsible for critically ill patients acquire and develop the ability to perform bedside ultrasound examinations, including echocardiographic examinations. However, there is no consensus in the literature regarding which specific applications should be included in the list of skills for nonechocardiographer physicians. Taking into account the multiplicity of applications of echocardiography in different scenarios related to acutely ill patients; the differences in the published protocols, with regard to both the teaching methodology and competence verification; and the heterogeneity of training among highly diverse specialties responsible for their care at different levels, this consensus document aimed to reflect the position of representatives of related Brazilian medical societies on the subject and may thus serve as a starting point both for standardization among different specialties and for the transmission of knowledge and verification of the corresponding competencies.

The use of bedside echocardiography in the care of critically ill patients - a joint consensus document of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Medicina de Emergência and Sociedade Brasileira de Medicina Hospitalar. Part 2 - Technical aspects.

Echocardiography in critically ill patients has become essential in the evaluation of patients in different settings, such as the hospital. However, unlike for other matters related to the care of these patients, there are still no recommendations from national medical societies on the subject. The objective of this document was to organize and make available expert consensus opinions that may help to better incorporate echocardiography in the evaluation of critically ill patients. Thus, the Associação de Medicina Intensiva Brasileira, the Associação Brasileira de Medicina de Emergência, and the Sociedade Brasileira de Medicina Hospitalar formed a group of 17 physicians to formulate questions relevant to the topic and discuss the possibility of consensus for each of them. All questions were prepared using a five-point Likert scale. Consensus was defined a priori as at least 80% of the responses between one and two or between four and five. The consideration of the issues involved two rounds of voting and debate among all participants. The 27 questions prepared make up the present document and are divided into 4 major assessment areas: left ventricular function, right ventricular function, diagnosis of shock, and hemodynamics. At the end of the process, there were 17 positive (agreement) and 3 negative (disagreement) consensuses; another 7 questions remained without consensus. Although areas of uncertainty persist, this document brings together consensus opinions on several issues related to echocardiography in critically ill patients and may enhance its development in the national scenario.

Prognostic value of Doppler waveform analysis of common femoral vein in septic patients: a prospective cohort study.

OBJECTIVES: To assess whether there is an association between abnormal common femoral vein (CFV) Doppler waveform and intensive care unit (ICU) mortality in patients with sepsis. METHODS: Patients admitted to the ICU with sepsis were included. Pulsed-wave Doppler was performed by examining the CFV in the short axis without angle correction and in the long axis with angle correction. An abnormal CFV Doppler waveform was determined by a retrograde velocity peak (RVP) > 10 cm/s in the long axis or RVP > 50% of the antegrade velocity peak in the short axis. TAPSE < 17 mm was defined as right ventricular (RV) dysfunction. The primary outcome was ICU mortality. RESULTS: One hundred and ten patients were included. There was no association between abnormal CFV Doppler waveforms in the long (p = 0.709) and short axes (p = 0.171) and ICU mortality. TAPSE measurements were performed in 16 patients. RV dysfunction was identified in 8 (50.0%) patients. There was no association between the diagnosis of RV dysfunction based on TAPSE measurement and the identification of abnormal CFV Doppler waveforms in the long axis (p = 1.000) and in the short axis (p = 1.000). CONCLUSION: Abnormal CFV Doppler waveforms were not associated with ICU mortality in patients with sepsis. Furthermore, in the exploratory analysis, these alterations were not useful in identifying RV dysfunction in these patients.

VExUS Score in the Management of Patients With Acute Kidney Injury in the Intensive Care Unit: AKIVEX Study.

OBJECTIVES: Venous congestion is a potential cause of acute kidney injury (AKI) and venous excess ultrasound (VExUS) score is a potentially useful tool in this scenario. The aim of this study is to verify whether the VExUS score can serve as a guide to decongestion in patients with severe AKI and whether the modification of the score can be associated with an increase in the number of renal replacement therapy (RRT)-free days in 28 days. METHODS: This quasi-experimental study was conducted in patients admitted to the intensive care unit who developed severe AKI. The intervention was to suggest to the attending physician the use of diuretic in patients with VExUS >1. After 48 hours, a new VExUS assessment was performed. Primary outcome was RRT-free days at Day 28. RESULTS: Ninety patients were included. Patients with a VExUS score >1 (n = 36) at enrollment had a greater use of diuretics in the following 48 hours (75.0%, n = 27) than patients with a VExUS ≤1 (n = 54) at enrollment (38.9%, n = 21), P = .001. Patients who reduced the VExUS score had a significantly greater number of RRT-free days at Day 28 (28.0; 8.0-28.0) when compared with those who did not reduce (15.0; 3.0-27.5), P = .012. CONCLUSIONS: We found a higher diuretic use in patients with a higher VExUS score, and patients who reduced the VExUS in 48 hours had significantly more RRT-free days in 28 days.

Association between prolonged corticosteroids use in COVID-19 and increased mortality in hospitalized patients: a retrospective study with inverse probability of treatment weighting analysis.

BACKGROUND: Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality. METHODS: This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use. RESULTS: We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24-1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21-1.78). CONCLUSIONS: Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality.

Use of bedside echocardiography in the care of critically ill patients - a joint consensus document of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Medicina de Emergência, and Sociedade Brasileira de Medicina Hospitalar. Part 1 - Competence in bedside echocardiography / Uso da ecocardiografia à beira do leito no cuidado do paciente grave - um documento conjunto de consenso da Associação de Medicina Intensiva Brasileira, Associação Brasileira de Medicina de Emergência e Sociedade Brasileira de Medicina Hospitalar. Parte 1 - Competência em ecocardiografia à beira do leito

ABSTRACT The use of echocardiography by physicians who are not echocardiographers has become common throughout the world across highly diverse settings where the care of acutely ill patients is provided. Echocardiographic evaluation performed in a point-of-care manner can provide relevant information regarding the mechanism of causes of shock, for example, increasing the rates of correct diagnosis and allowing for faster informed decision-making than through evaluation methods. Considering that the accurate diagnosis of life-threatening situations is essential for professionals working with acutely ill patients, several international associations recommend that physicians responsible for critically ill patients acquire and develop the ability to perform bedside ultrasound examinations, including echocardiographic examinations. However, there is no consensus in the literature regarding which specific applications should be included in the list of skills for nonechocardiographer physicians. Taking into account the multiplicity of applications of echocardiography in different scenarios related to acutely ill patients; the differences in the published protocols, with regard to both the teaching methodology and competence verification; and the heterogeneity of training among highly diverse specialties responsible for their care at different levels, this consensus document aimed to reflect the position of representatives of related Brazilian medical societies on the subject and may thus serve as a starting point both for standardization among different specialties and for the transmission of knowledge and verification of the corresponding competencies.

RESUMO O emprego da ecocardiografia por médicos não ecocardiografistas tem se tornado comum em todo o mundo nos mais diversos ambientes em que se dá o cuidado do paciente agudamente doente. A avaliação ecocardiográfica realizada de forma point-of-care pode fornecer informações pertinentes em relação ao mecanismo das causas de choque, por exemplo, incrementando as taxas de diagnóstico correto e possibilitando a tomada de decisão fundamentada de forma mais rápida do que por meio dos métodos tradicionais de avaliação. Considerando que o diagnóstico preciso de situações ameaçadoras à vida é indispensável a profissionais atuando junto a pacientes agudamente enfermos, diversas entidades associativas internacionais recomendam que médicos responsáveis por pacientes gravemente doentes devam adquirir e desenvolver a habilidade para realizar exames ultrassonográficos à beira do leito, inclusive ecocardiográficos. Entretanto, não há consenso na literatura acerca de quais aplicações específicas devam compor o rol de habilidades do médico não ecocardiografista. Levando-se em consideração a multiplicidade de aplicações da ecocardiografia em diversos cenários relativos ao paciente agudamente enfermo; as diferenças nos protocolos publicados, tanto no que diz respeito à metodologia de ensino como de verificação de competências, bem como a heterogeneidade da formação entre as mais diversas especialidades responsáveis pelo seu cuidado em diferentes níveis, este documento de consenso teve o objetivo de refletir o posicionamento de representantes de sociedades médicas brasileiras afins acerca do tema, podendo, assim, servir de ponto de partida para a uniformização entre diferentes especialidades, bem como para a transmissão de conhecimento e a verificação das competências correspondentes.

The use of bedside echocardiography in the care of critically ill patients - a joint consensus document of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Medicina de Emergência and Sociedade Brasileira de Medicina Hospitalar. Part 2 - Technical aspects / O uso da ecocardiografia à beira do leito no cuidado do paciente grave - um documento conjunto de consenso da Associação de Medicina Intensiva Brasileira, Associação Brasileira de Medicina de Emergência e Sociedade Brasileira de Medicina Hospitalar. Parte 2 - Aspectos técnicos

ABSTRACT Echocardiography in critically ill patients has become essential in the evaluation of patients in different settings, such as the hospital. However, unlike for other matters related to the care of these patients, there are still no recommendations from national medical societies on the subject. The objective of this document was to organize and make available expert consensus opinions that may help to better incorporate echocardiography in the evaluation of critically ill patients. Thus, the Associação de Medicina Intensiva Brasileira, the Associação Brasileira de Medicina de Emergência, and the Sociedade Brasileira de Medicina Hospitalar formed a group of 17 physicians to formulate questions relevant to the topic and discuss the possibility of consensus for each of them. All questions were prepared using a five-point Likert scale. Consensus was defined a priori as at least 80% of the responses between one and two or between four and five. The consideration of the issues involved two rounds of voting and debate among all participants. The 27 questions prepared make up the present document and are divided into 4 major assessment areas: left ventricular function, right ventricular function, diagnosis of shock, and hemodynamics. At the end of the process, there were 17 positive (agreement) and 3 negative (disagreement) consensuses; another 7 questions remained without consensus. Although areas of uncertainty persist, this document brings together consensus opinions on several issues related to echocardiography in critically ill patients and may enhance its development in the national scenario.

RESUMO A ecocardiografia do paciente grave tem se tornado fundamental na avaliação de pacientes em diferentes cenários e ambientes hospitalares. Entretanto, ao contrário de outras áreas relativas ao cuidado com esses pacientes, ainda não existem recomendações de sociedades médicas nacionais acerca do assunto. O objetivo deste documento foi organizar e disponibilizar opiniões de consenso de especialistas que possam auxiliar a melhor incorporação dessa técnica na avaliação de pacientes graves. Dessa forma, a Associação de Medicina Intensiva Brasileira, a Associação Brasileira de Medicina de Emergência e a Sociedade Brasileira de Medicina Hospitalar compuseram um grupo de 17 médicos para formular questões pertinentes ao tópico e debater a possibilidade de consenso de especialistas para cada uma delas. Todas as questões foram elaboradas no formato de escala Likert de cinco pontos. Consenso foi definido, a priori, como um somatório de, ao menos, 80% das respostas entre um e dois ou entre quatro e cinco. A apreciação das questões envolveu dois ciclos de votação e debate entre todos os participantes. As 27 questões elaboradas compõem o presente documento e estão divididas em 4 grandes áreas de avaliação: da função ventricular esquerda; da função ventricular direita; diagnóstica dos choques e hemodinâmica. Ao fim do processo, houve 17 consensos positivos (concordância) e 3 negativos (discordância); outras 7 questões persistiram sem consenso. Embora persistam áreas de incerteza, este documento reúne opiniões de consenso para diversas questões relativas à ecocardiografia do paciente grave e pode potencializar seu desenvolvimento no cenário nacional.

Rapid prognostic stratification using Point of Care ultrasound in critically ill COVID patients: The role of epicardial fat thickness, myocardial injury and age.

PURPOSE: The burden of critical COVID-19 patients in intensive care units (ICU) demands new tools to stratify patient risk. We aimed to investigate the role of cardiac and lung ultrasound, together with clinical variables, to propose a simple score to help predict short-term mortality in these patients. MATERIAL AND METHODS: We collected clinical and laboratorial data, and a point-of-care cardiac and lung ultrasound was performed in the first 36 h of admission in the ICU. RESULTS: Out of 78 patients (61 ± 12y-o, 55% male), 33 (42%) died during the hospitalization. Deceased patients were generally older, had worse values for SOFA score, baseline troponin levels, left ventricular ejection fraction (LVEF), LV diastolic function, and increased epicardial fat thickness (EFT), despite a similar prevalence of severe lung ultrasound scores. Based on the multivariable model, we created the POCOVID score, including age (>60 years), myocardial injury (LVEF<50% and/or usTnI>99til), and increased EFT (>0.8 cm). The presence of two out of these three criteria identified patients with almost twice the risk of death. CONCLUSIONS: A higher POCOVID score at ICU admission can be helpful to stratify critical COVID-19 patients with increased in-hospital mortality and to optimize medical resources allocation in more strict-resource settings.

Convalescent plasma for COVID-19 in hospitalised patients: an open-label, randomised clinical trial.

BACKGROUND: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients. METHODS: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment. RESULTS: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48-68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8-12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference -3.7%, 95% CI -18.8-11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups. CONCLUSIONS: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone.

Mechanism of a Flexible ICU Visiting Policy for Anxiety Symptoms Among Family Members in Brazil: A Path Mediation Analysis in a Cluster-Randomized Clinical Trial.

OBJECTIVES: To investigate whether the effect of a flexible ICU visiting policy that includes flexible visitation plus visitor education on anxiety symptoms of family members is mediated by satisfaction and involvement in patient care. DESIGN: We embedded a multivariable path mediation analysis within a cluster-randomized crossover trial as a secondary analysis of The ICU Visits Study (ClinicalTrials.gov number: NCT02932358). SETTING: Thirty-six medical-surgical ICUs in Brazil. PATIENTS: Closest relatives of adult ICU patients. INTERVENTIONS: Flexible visitation (12 hr/d) supported by family education or usual restricted visitation (median, 1.5 hr/d). MEASUREMENTS AND MAIN RESULTS: Overall, 863 family members were assessed (mean age, 44.7 yr; women, 70.1%). Compared with the restricted visitation (n = 436), flexible visitation (n = 427) resulted in better mean anxiety scores (6.1 vs 7.8; mean difference, -1.78 [95% CI, -2.31 to -1.22]), as well as higher standardized scores of satisfaction (67% [95% CI, 55-79]) and involvement in patient care (77% [95% CI, 64-89]). The mediated effect of flexible visitation on mean anxiety scores through each incremental sd of satisfaction and involvement in patient care were -0.47 (95% CI, -0.68 to -0.24) and 0.29 (95% CI, 0.04-0.54), respectively. Upon exploratory analyses, emotional support, helping the ICU staff to understand patient needs, helping the patient to interpret ICU staff instructions, and patient reorientation were the domains of involvement in patient care associated with increased anxiety. CONCLUSIONS: A flexible ICU visiting policy reduces anxiety symptoms among family members and appears to work by increasing satisfaction. However, increased participation in some activities of patient care as a result of flexible visitation was associated with higher severity of anxiety symptoms.

Incidence of venous thromboembolism among patients with severe COVID-19 requiring mechanical ventilation compared to other causes of respiratory failure: a prospective cohort study.

Previous studies have suggested that COVID-19 pneumonia is associated with an increased risk of venous thromboembolism (VTE). This study aimed to investigate the incidence of VTE among mechanically ventilated adults with COVID-19 pneumonia, compared to patients with respiratory failure related to other causes. Prospective study that enrolled critically ill adults with suspected COVID-19 pneumonia between June 2, 2020 and August 11, 2020. Critically ill adults with suspected COVID-19 pneumonia who required mechanical ventilation within 24 h after hospital admission were followed until death or hospital discharge. Sequential ultrasonography screening of the lower extremities and catheter insertion sites, as well as testing for plasma biochemical markers, were performed at the intensive care unit admission, day 3, day 7, and day 14. The primary outcome was a composite of deep venous thrombosis, pulmonary embolism, and thrombosis at the central catheter insertion sites. We enrolled 70 patients, including 57 patients with COVID-19 and 13 patients without COVID-19, and all patients completed follow-up. The incidence of the primary outcome was higher among patients with COVID-19 than among patients with respiratory failure related to other etiologies (36.8% vs. 0%, p = 0.023). Multivariate regression analysis revealed that VTE was independently associated with a COVID-19 diagnosis (odds ratio: 6.28, 95% confidence interval: 1.19-68.07) and D-dimer concentration (1-ng/mL increase, odds ratio: 1.15, 95% confidence interval: 1.05-1.30). The incidence of VTE was higher among critically ill mechanically ventilated patients, relative to among patients with respiratory failure related to other causes.

Early antiretroviral therapy for HIV-infected patients admitted to an intensive care unit (EARTH-ICU): A randomized clinical trial.

BACKGROUND: Highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality at all stages of infection and reduced transmission of HIV. Currently, the immediate start of HAART is recommended for all HIV patients, regardless of the CD4 count. There are several concerns, however, about starting treatment in critically ill patients. Unpredictable absorption of medication by the gastrointestinal tract, drug toxicity, drug interactions, limited reserve to tolerate the dysfunction of other organs resulting from hypersensitivity to drugs or immune reconstitution syndrome, and the possibility that subtherapeutic levels of drug may lead to viral resistance are the main concerns. The objective of our study was to compare the early onset (up to 5 days) with late onset (after discharge from the ICU) of HAART in HIV-infected patients admitted to the ICU. METHODS: This was a randomized, open-label clinical trial enrolling HIV-infected patients admitted to the ICU of a public hospital in southern Brazil. Patients randomized to the intervention group had to start treatment with HAART within 5 days of ICU admission. For patients in the control group, treatment should begin after discharge from the ICU. The patients were followed up to determine mortality in the ICU, in the hospital and at 6 months. The primary outcome was hospital mortality. The secondary outcome was mortality at 6 months. RESULTS: The calculated sample size was 344 patients. Unfortunately, we decided to discontinue the study due to a progressively slower recruitment rate. A total of 115 patients were randomized. The majority of admissions were for AIDS-defining illnesses and low CD4. The main cause of admission was respiratory failure. Regarding the early and late study groups, there was no difference in hospital (66.7% and 63.8%, p = 0.75) or 6-month (68.4% and 79.2%, p = 0.20) mortality. After multivariate analysis, the only independent predictors of in-hospital mortality were shock and dialysis during the ICU stay. For the mortality outcome at 6 months, the independent variables were shock and dialysis during the ICU stay and tuberculosis at ICU admission. CONCLUSIONS: Although the early termination of the study precludes definitive conclusions being made, early HAART administration for HIV-infected patients admitted to the ICU compared to late administration did not show benefit in hospital mortality or 6-month mortality. ClinicalTrials.gov, NCT01455688. Registered 20 October 2011, https://clinicaltrials.gov/show/NCT01455688.

Infecção por SARS-CoV-2 em paciente com agamaglobulinemia ligada ao X tratado com altas doses de imunoglobulina endovenosa e plasma de convalescente / SARS-CoV-2 infection in a patient with X-linked agammaglobulinemia treated with high doses of intravenous immunoglobulin and convalescent plasma

A pandemia pelo vírus SARS-CoV-2 atingiu adultos, crianças e penalizou indivíduos idosos e com comorbidades como diabetes, doença cardíaca, hipertensão e obesidade. A maioria dos infectados são assintomáticos ou têm sintomas leves, entretanto 15% podem apresentar pneumonia e 5% síndrome respiratória aguda grave. Apresentamos um caso de agamaglobulinemia ligada ao X (XLA) em paciente masculino de 27 anos que se infectou com SARS-CoV-2. Os pacientes com XLA não possuem linfócitos B e não produzem anticorpos devido a uma mutação no gene Bruton tirosino-quinase (BTK), responsável pela maturação dos linfócitos B. Ele infectou-se e foi internado em hospital de Ivoti/RS. A evolução da pneumonia foi rápida, necessitando transferência para o Hospital de Clínicas de Porto Alegre (HCPA) no 10° dia de evolução. Iniciou com infusão de imunoglobulinas, tendo utilizado o total de 400 gramas devido ao intenso catabolismo da IgG, mantendo-se sua concentração entre 700-900 mg/dL. Necessitou de ventilação mecânica, oxigenação por membrana extracorpórea (ECMO) e hemodiálise. Foi administrado plasma de convalescente (PC), 300 mL, por duas vezes, com melhora clínico-radiológica e retirada da ventilação mecânica. Piorou e repetiu outras 4 infusões de PC (total de 1717 mL), negativando o vírus na orofaringe (RT-PCR). Em 3 ocasiões teve sepse, debelada rapidamente. Apresentou anemia, com necessidade de transfusão frequente. Identificou-se linfopenia de CD3, CD4, CD8, NK e ausência de linfócitos B. A linfopenia foi revertida com a recuperação clínica e a alta hospitalar aconteceu no 70° dia de internação.

The SARS-CoV-2 pandemic has affected adults and children and penalized older people and those with comorbidities such as diabetes, heart disease, hypertension and obesity. Most of those infected are asymptomatic or have mild symptoms, but 15% may have pneumonia and 5% acute respiratory distress syndrome. We report a case of X-linked agammaglobulinemia (XLA) in a 27-yearold man who was infected with SARS-CoV-2. XLA patients do not have B lymphocytes and do not produce antibodies because of mutations in the Bruton tyrosine-kinase gene, responsible for the maturation of B cells. This patient was infected and then admitted to a hospital in Ivoti, southern Brazil. Pneumonia progressed rapidly, requiring transfer to the Hospital de Clínicas de Porto Alegre on the 10th day. Intravenous immunoglobulin infusions were initiated, using a total of 400 grams because of an intense catabolism of IgG, and the concentration was kept around 700- 900 mg/dL. Mechanical ventilation, extracorporeal membrane oxygenation and hemodialysis were necessary. Convalescent plasma (CP) was administered (2x300 mL) and then followed by clinical and radiological improvement and interruption of mechanical ventilation. Then he got sicker and had to return to invasive support and received 4 extra CP infusions (total of 1717 mL), until a negative reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 was obtained. On 3 occasions he had sepsis, promptly managed. He had anemia, requiring frequent transfusion, and lymphopenia (CD3, CD4, CD8, NK), with absence of B lymphocytes. Lymphopenia was reverted during recovery, and he was discharged from the hospital on the 70th day.

Effect of Flexible Family Visitation on Delirium Among Patients in the Intensive Care Unit: The ICU Visits Randomized Clinical Trial.

Importance: The effects of intensive care unit (ICU) visiting hours remain uncertain. Objective: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium. Design, Setting and Participants: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018. Interventions: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation. Main Outcomes and Measures: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory). Results: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, -1.7% [95% CI, -6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, -0.8% [95% CI, -2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, -3.8% [95% CI, -4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, -1.6 [95% CI, -2.3 to -0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, -1.2 [95% CI, -2.0 to -0.4]; P = .003) were significantly better with flexible visitation. Conclusions and Relevance: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium. Trial Registration: ClinicalTrials.gov Identifier: NCT02932358.

Renal Outcomes of Vasopressin and Its Analogs in Distributive Shock: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVES: To systematically review the literature and synthesize evidence concerning the effects of vasopressin and its analogs compared with other vasopressors in distributive shock, focusing on renal outcomes. DATA SOURCES: We performed a systematic review in MEDLINE, Embase, Cochrane Central, and Clinicaltrials.gov databases. STUDY SELECTION: Randomized clinical trials that compared vasopressin and its analogs with other vasopressors and reported renal outcomes in adult patients with distributive shock. DATA EXTRACTION: Paired reviewers independently screened citations, conducted data extraction and assessed risk of bias. Three prespecified subgroup analyses were conducted. Three main outcomes related to acute renal failure were analyzed: the need for renal replacement therapy, acute kidney injury incidence, and acute kidney injury-free days. I test was used to evaluate heterogeneity between studies. Substantial heterogeneity was defined as I greater than 50%. A random-effects model with Mantel-Haenszel weighting was used for all analyses. Heterogeneity was explored using subgroup analysis. The quality of evidence for intervention effects was summarized using Grading of Recommendations Assessment, Development, and Evaluation methodology. This study was registered in the PROSPERO database (CRD42017054324). DATA SYNTHESIS: Three-thousand twenty-six potentially relevant studies were identified, and 30 articles were reviewed in full. Seventeen studies met the inclusion criteria, including a total of 2,833 individuals. Of these, 11 studies (2,691 individuals) were suitable for quantitative meta-analysis. Overall, the evidence was of low to moderate quality. Patients who received vasopressin and its analogs had a reduced need for renal replacement therapy (odds ratio, 0.59 [0.37-0.92]; p = 0.02; I = 49%) and a lower acute kidney injury incidence (odds ratio, 0.58 [0.37-0.92]; p = 0.02; I = 63%). These results should be interpreted with caution, due to excessive heterogeneity. Acute kidney injury-free data was not pooled, since the small number of studies and extreme heterogeneity. CONCLUSIONS: In patients with distributive shock, vasopressin and its analogs use is associated with a reduced need for renal replacement therapy and lower acute kidney injury incidence. These results are supported by high risk of bias evidence.

Statistical analysis plan for a cluster-randomized crossover trial comparing the effectiveness and safety of a flexible family visitation model for delirium prevention in adult intensive care units (the ICU Visits Study).

BACKGROUND: Most adult intensive care units (ICUs) worldwide adopt restrictive family visitation models (RFVMs). However, evidence, mostly from non-randomized studies, suggests that flexible adult ICU visiting hours are safe policies that can result in benefits such as prevention of delirium and increase in satisfaction with care. Accordingly, the ICU Visits Study was designed to compare the effectiveness and safety of a flexible family visitation model (FFVM) vs. an RFVM on delirium prevention among ICU patients, and also to analyze its potential effects on family members and ICU professionals. METHODS/DESIGN: The ICU Visits Study is a cluster-randomized crossover trial which compares an FFVM (12 consecutive ICU visiting hours per day) with an RFVM (< 4.5 ICU visiting hours per day) in 40 Brazilian adult ICUs. Participant ICUs are randomly assigned to either an FFVM or RFVM in a 1:1 ratio. After enrollment and follow-up of 25 patients, each ICU is crossed over to the other visitation model, until 25 more patients per site are enrolled and followed. The primary outcome is the cumulative incidence of delirium measured by the Confusion Assessment Method for the ICU. Secondary and tertiary outcomes include relevant measures of effectiveness and safety of ICU visiting policies among patients, family members, and ICU professionals. Herein, we describe all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of this study. This pre-specified statistical analysis plan was written and submitted without knowledge of the study data. DISCUSSION: This a priori statistical analysis plan aims to enhance the transparency of our study, facilitating unbiased analyses of ICU visit study data, and provide guidance for statistical analysis for groups conducting studies in the same field. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02932358 . Registered on 11 October 2016.

Pressure-support ventilation or T-piece spontaneous breathing trials for patients with chronic obstructive pulmonary disease - A randomized controlled trial.

BACKGROUND: Little is known about the best strategy for weaning patients with chronic obstructive pulmonary disease (COPD) from mechanical ventilation. Spontaneous breathing trials (SBT) using a T-piece or pressure-support ventilation (PSV) have a central role in this process. Our aim was to compare T-piece and PSV SBTs according to the duration of mechanical ventilation (MV) in patients with COPD. METHODS: Patients with COPD who had at least 48 hours of invasive MV support were randomized to 30 minutes of T-piece or PSV at 10 cm H2O after being considered able to undergo a SBT. All patients were preemptively connected to non-invasive ventilation after extubation. Tracheostomized patients were excluded. The primary outcome was total invasive MV duration. Time to liberation from MV was assessed as secondary outcome. RESULTS: Between 2012 and 2016, 190 patients were randomized to T-piece (99) or PSV (91) groups. Extubation at first SBT was achieved in 78% of patients. The mean total MV duration was 10.82 ± 9.1 days for the T-piece group and 7.31 ± 4.9 days for the PSV group (p < 0.001); however, the pre-SBT duration also differed (7.35 ± 3.9 and 5.84 ± 3.3, respectively; p = 0.002). The time to liberation was 8.36 ± 11.04 days for the T-piece group and 4.06 ± 4.94 for the PSV group (univariate mean ratio = 2.06 [1.29-3.27], p = 0.003) for the subgroup of patients with difficult or prolonged weaning. The study group was independently associated with the time to liberation in this subgroup. CONCLUSIONS: The SBT technique did not influence MV duration for patients with COPD. For the difficult/prolonged weaning subgroup, the T-piece may be associated with a longer time to liberation, although this should be clarified by further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01464567, at November 3, 2011.