Evidence-Based Checklist to Delay Cardiac Arrest in Brain-Dead Potential Organ Donors: The DONORS Cluster Randomized Clinical Trial.

Importance: The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear. Objective: To evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU). Design, Setting, and Participants: The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020. Interventions: Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care. Main Outcomes and Measures: The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group. Results: Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006). Conclusions and Relevance: This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist. Trial Registration: ClinicalTrials.gov Identifier: NCT03179020.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study.

BACKGROUND: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. METHODS: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. CONCLUSION: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. CLINICALTRIALS.GOV REGISTRY: NCT05558098.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study / Dapagliflozina em pacientes com doença crítica: justificativa e desenho do estudo DEFENDER

ABSTRACT Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry: NCT05558098

RESUMO Antecedentes: A doença crítica é um importante ônus permanente da assistência médica em todo o mundo e está associada a altas taxas de mortalidade. Os inibidores do cotransportador de sódio-glicose do tipo 2 têm demonstrado consistentemente benefícios nos desfechos cardiovasculares e renais. Os efeitos dos inibidores do cotransportador de sódio-glicose do tipo 2 em doenças agudas ainda não foram devidamente investigados. Métodos: O DEFENDER é um estudo de iniciativa do investigador, multicêntrico, randomizado, aberto, desenhado para avaliar a eficácia e a segurança da dapagliflozina em 500 participantes adultos com disfunção orgânica aguda hospitalizados na unidade de terapia intensiva. Os participantes aptos serão randomizados 1:1 para receber 10mg de dapagliflozina e o tratamento padrão por até 14 dias ou apenas o tratamento padrão. O desfecho primário é um composto hierárquico de mortalidade hospitalar, início de terapia renal substitutiva e tempo de internação na unidade de terapia intensiva, até 28 dias. O monitoramento da segurança será rigoroso durante todo o estudo. Conclusão: O DEFENDER é o primeiro estudo desenvolvido para investigar o uso de um inibidor do cotransportador de sódio-glicose do tipo 2 em pacientes de unidade de terapia intensiva geral com disfunção orgânica aguda. O estudo fornecerá informações relevantes sobre o uso de medicamentos dessa classe promissora em pacientes críticos. Registro ClincalTrials.gov: NCT05558098

Histological, Laboratorial, and Clinical Benefits of an Optimized Maintenance Strategy of a Potential Organ Donor-A Rabbit Experimental Model.

INTRODUCTION: Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection. Objectives: The objective of this animal model of brain death (BD) was to evaluate the effect of the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects. Methods: Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist. Results: In Group D, we observed fewer number and lesser volume of infusions (p = 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (p = 0.008). Group D had better glycemic control when compared with group C (p = 0.016). Sodium values were elevated in group B in relation to groups C and D (p = 0.021). In Group D, the organ perfusion was better. Conclusion: The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.

Coagulation biomarkers and coronavirus disease 2019 phenotyping: a prospective cohort study.

BACKGROUND: Because severe acute respiratory syndrome coronarivus 2 (SARS-CoV-2) leads to severe conditions and thrombus formation, evaluation of the coagulation markers is important in determining the prognosis and phenotyping of patients with COVID-19. METHODS: In a prospective study that included 213 COVID-19 patients admitted to the intensive care unit (ICU) the levels of antithrombin, C-reactive protein (CRP); factors XI, XII, XIII; prothrombin and D-dimer were measured. Spearman's correlation coefficient was used to assess the pairwise correlations between the biomarkers. Hierarchical and non-hierarchical cluster analysis was performed using the levels of biomarkers to identify patients´ phenotypes. Multivariate binary regression was used to determine the association of the patient´s outcome with clinical variables and biomarker levels. RESULTS: The levels of factors XI and XIII were significantly higher in patients with less severe COVID-19, while factor XIII and antithrombin levels were significantly associated with mortality. These coagulation biomarkers were associated with the in-hospital survival of COVID-19 patients over and above the core clinical factors on admission. Hierarchical cluster analysis showed a cluster between factor XIII and antithrombin, and this hierarchical cluster was extended to CRP in the next step. Furthermore, a non-hierarchical K-means cluster analysis was performed, and two phenotypes were identified based on the CRP and antithrombin levels independently of clinical variables and were associated with mortality. CONCLUSION: Coagulation biomarkers were associated with in-hospital survival of COVID-19 patients. Lower levels of factors XI, XII and XIII and prothrombin were associated with disease severity, while higher levels of both CRP and antithrombin clustered with worse prognosis. These results suggest the role of coagulation abnormalities in the development of COVID-19 and open the perspective of identifying subgroups of patients who would benefit more from interventions focused on regulating coagulation.

Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

Antivirals for adult patients hospitalised with SARS-CoV-2 infection: a randomised, phase II/III, multicentre, placebo-controlled, adaptive study, with multiple arms and stages. COALITION COVID-19 BRAZIL IX - REVOLUTIOn trial.

Background: Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering SARS-CoV2 viral load of COVID-19 patients. Methods: REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO2 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087. Findings: Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 [95% CI, -0.03 to 0.12], -0.02 [95% CI, -0.09 to 0.06], and -0.03 [95% CI, -0.11 to 0.04] for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups. Interpretation: No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less. Funding: Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13).

Incidence of Delirium in Critically Ill Patients With and Without COVID-19.

BACKGROUND: It is known that patients with COVID-19 are at high risk of developing delirium. The aim of the study was to compare the incidence of delirium between critically ill patients with and without a diagnosis of COVID-19. METHODS: This is a retrospective study conducted in a southern Brazilian hospital from March 2020 to January 2021. Patients were divided into two groups: the COVID-19 group consisted of patients with a diagnosis of COVID-19 confirmed by reverse transcription-polymerase chain reaction (RT-PCR) or serological tests who were admitted to specific ICUs. The non-COVID-19 group consisted of patients with other surgical and medical diagnoses who were admitted to non-COVID ICUs. All patients were evaluated daily using the Intensive Care Delirium Screening Checklist (ICDSC). The two cohorts were compared in terms of the diagnosis of delirium. RESULTS: Of the 649 patients who remained more than 48 h in the ICU, 523 were eligible for the study (COVID-19 group: 292, non-COVID-19 group: 231). There were 119 (22.7%) patients who had at least one episode of delirium, including 96 (32.9%) in the COVID-19 group and 23 (10.0%) in the non-COVID-19 group (odds ratio [OR] 4.42; 95% confidence interval [CI], 2.69 to 7.26; p < 0.001). Among patients mechanically ventilated for two days or more, the incidence of delirium did not differ between groups (COVID-19: 89/211, 42.1% vs non-COVID-19: 19/47, 40.4%; p = 0.82). Logistic regression showed that the duration of mechanical ventilation was the only independent factor associated with delirium (p = 0.001). CONCLUSION: COVID-19 can be associated with a higher incidence of delirium among critically ill patients, but there was no difference in this incidence between groups when mechanical ventilation lasted two days or more.

Antivirals for adult patients hospitalized with SARS-CoV-2 infection: A randomized, Phase II/III, multicenter, placebo-controlled, adaptive study, with multiple arms and stages. COALITION COVID-19 BRAZIL IX - REVOLUTIOn: protocol and statistical analysis plan. / Antivirais para pacientes adultos hospitalizados com infecção por SARS-CoV-2: Um estudo de Fase II/III, randomizado, multicêntrico, controlado por placebo, adaptativo, com múltiplos braços e estágios. COALITION COVID-19 BRAZIL IX - REVOLUTIOn: protocolo e plano de análise estatística.

Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial. ClinicalTrials.gov identifier: NCT04468087.

Os medicamentos reaproveitados são importantes em contextos de recursos limitados porque as intervenções estão mais rapidamente disponíveis, já foram testadas com segurança em outras populações e são, em geral, mais baratas. Os medicamentos reaproveitados são uma solução eficaz, especialmente para doenças emergentes, como a COVID-19. O estudo REVOLUTIOn visa avaliar três medicamentos antivirais reaproveitados: atazanavir, daclatasvir e sofosbuvir, já utilizados em pacientes infectados pelo HIV ou pelo vírus da hepatite C, em um estudo randomizado, controlado por placebo, adaptativo, multibraço e em múltiplos estágios. Os medicamentos serão testados simultaneamente em um ensaio de Fase II para primeiro identificar se algum deles, isoladamente ou em combinação, reduz a carga viral. Se reduzirem, será iniciado um estudo de Fase III para investigar se tais medicamentos são capazes de aumentar o número de dias sem suporte respiratório. Os participantes devem ser adultos hospitalizados com idade ≥ 18 anos com início dos sintomas ≤ 9 dias e saturação de oxigênio ≤ 94% em ar ambiente ou necessidade de oxigênio suplementar para manter saturação de oxigênio > 94%. O tamanho total esperado da amostra varia entre 252 e 1.005 participantes, dependendo do número de estágios que serão concluídos no estudo. Assim, o protocolo é aqui descrito em detalhes, juntamente do plano de análise estatística. Em conclusão, o estudo REVOLUTIOn foi concebido para fornecer evidências se o atazanavir, o daclatasvir ou o sofosbuvir reduzem a carga viral de SARS-CoV-2 em pacientes com COVID-19 e aumentam o número de dias em que os pacientes ficam sem suporte respiratório. Neste artigo de protocolo, descrevem-se a fundamentação, o desenho e a situação do ensaio. Identificador do ClinicalTrials.gov: NCT04468087.

Antivirais para pacientes adultos hospitalizados com infecção por SARS-CoV-2: Um estudo de Fase II/III, randomizado, multicêntrico, controlado por placebo, adaptativo, com múltiplos braços e estágios. COALITION COVID-19 BRAZIL IX - REVOLUTIOn: protocolo e plano de análise estatística / Antivirals for adult patients hospitalized with SARS-CoV-2 infection: A randomized, Phase II/III, multicenter, placebo-controlled, adaptive study, with multiple arms and stages. COALITION COVID-19 BRAZIL IX - REVOLUTIOn: protocol and statistical analysis plan

RESUMO Os medicamentos reaproveitados são importantes em contextos de recursos limitados porque as intervenções estão mais rapidamente disponíveis, já foram testadas com segurança em outras populações e são, em geral, mais baratas. Os medicamentos reaproveitados são uma solução eficaz, especialmente para doenças emergentes, como a COVID-19. O estudo REVOLUTIOn visa avaliar três medicamentos antivirais reaproveitados: atazanavir, daclatasvir e sofosbuvir, já utilizados em pacientes infectados pelo HIV ou pelo vírus da hepatite C, em um estudo randomizado, controlado por placebo, adaptativo, multibraço e em múltiplos estágios. Os medicamentos serão testados simultaneamente em um ensaio de Fase II para primeiro identificar se algum deles, isoladamente ou em combinação, reduz a carga viral. Se reduzirem, será iniciado um estudo de Fase III para investigar se tais medicamentos são capazes de aumentar o número de dias sem suporte respiratório. Os participantes devem ser adultos hospitalizados com idade ≥ 18 anos com início dos sintomas ≤ 9 dias e saturação de oxigênio ≤ 94% em ar ambiente ou necessidade de oxigênio suplementar para manter saturação de oxigênio > 94%. O tamanho total esperado da amostra varia entre 252 e 1.005 participantes, dependendo do número de estágios que serão concluídos no estudo. Assim, o protocolo é aqui descrito em detalhes, juntamente do plano de análise estatística. Em conclusão, o estudo REVOLUTIOn foi concebido para fornecer evidências se o atazanavir, o daclatasvir ou o sofosbuvir reduzem a carga viral de SARS-CoV-2 em pacientes com COVID-19 e aumentam o número de dias em que os pacientes ficam sem suporte respiratório. Neste artigo de protocolo, descrevem-se a fundamentação, o desenho e a situação do ensaio. Identificador do ClinicalTrials.gov:NCT04468087

ABSTRACT Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial. ClinicalTrials.gov identifier:NCT04468087

Resuscitation fluid practices in Brazilian intensive care units: a secondary analysis of Fluid-TRIPS. / Práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras: uma análise secundária do estudo Fluid-TRIPS.

OBJECTIVE: To describe fluid resuscitation practices in Brazilian intensive care units and to compare them with those of other countries participating in the Fluid-TRIPS. METHODS: This was a prospective, international, cross-sectional, observational study in a convenience sample of intensive care units in 27 countries (including Brazil) using the Fluid-TRIPS database compiled in 2014. We described the patterns of fluid resuscitation use in Brazil compared with those in other countries and identified the factors associated with fluid choice. RESULTS: On the study day, 3,214 patients in Brazil and 3,493 patients in other countries were included, of whom 16.1% and 26.8% (p < 0.001) received fluids, respectively. The main indication for fluid resuscitation was impaired perfusion and/or low cardiac output (Brazil: 71.7% versus other countries: 56.4%, p < 0.001). In Brazil, the percentage of patients receiving crystalloid solutions was higher (97.7% versus 76.8%, p < 0.001), and 0.9% sodium chloride was the most commonly used crystalloid (62.5% versus 27.1%, p < 0.001). The multivariable analysis suggested that the albumin levels were associated with the use of both crystalloids and colloids, whereas the type of fluid prescriber was associated with crystalloid use only. CONCLUSION: Our results suggest that crystalloids are more frequently used than colloids for fluid resuscitation in Brazil, and this discrepancy in frequencies is higher than that in other countries. Sodium chloride (0.9%) was the crystalloid most commonly prescribed. Serum albumin levels and the type of fluid prescriber were the factors associated with the choice of crystalloids or colloids for fluid resuscitation.

OBJETIVO: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. MÉTODOS: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. RESULTADOS: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. CONCLUSÃO: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.

Avaliação do impacto do tempo de espera para admissão em Unidade de Terapia Intensiva no desfecho clínico do paciente crítico / Assessment of the impact of waiting time until admission in the Intensive Care Unit on the clinical outcome of critical patients

RESUMO: Este estudo tem por base a premissa de que com um maior número de leitos de Unidade de Terapia Intensiva (UTI) disponíveis o tempo de espera para admissão em UTI é menor, o que resulta no melhor desfecho clínico, justifi-cando, portanto, a importância do presente estudo. Objetivo: Avaliar se o tempo de espera no Departamento de Emergência até a admissão em UTI tem influência no desfecho clínico do paciente crítico. Metodologia: Estudo ob-servacional, retrospectivo, do tipo antes e depois, realizado em um hospital público do município de Joinville/SC no ano de 2019. Foram incluídos os dados referentes aos pacientes adultos admitidos na UTI com até 72 horas de es-pera no Departamento de Emergência desde a chegada ao hospital. Comparou-se o último trimestre de 2017 (fase 1), período durante o qual havia 14 leitos de UTI no hospital, e último trimestre de 2018 (fase 2), período durante o qual havia 30 leitos de UTI. Resultados: Analisaram-se 173 prontuários elegíveis de 2017 e 2018. Houve diferen-ça estatisticamente significativa no tempo decorrido na emergência até a admissão em UTI entre 2017 e 2018 (me-diana de 22 vs. 15; p=0,0002). A diferença estatística também foi relevante para a mortalidade em até 24 horas após a admissão em UTI, comparando-se os dois anos em questão (9,61% vs. 2,47%; p=0,04). Não houve diferen-ça estatística significante na mortalidade hospitalar entre 2017 e 2018 (34,6% vs. 35,5%; p=0,57). Também não houve diferença estatisticamente relevante entre os demais parâmetros analisados. Conclusão: Comparando-se 2017 a 2018, percebeu-se que o tempo de espera pelo leito de UTI diminuiu, bem como a mortalidade em até 24h da admissão intensiva. No entanto, isto não se refletiu na mortalidade hospitalar. (AU)

ABSTRACT: The premise that underpins this study is that the more Intensive Care Unit (ICU) beds available, the shorter the waiting time for ICU admission, resulting in better clinical outcomes, which justifies the relevance of this study. Objective: Assess if the waiting time in the Emergency Room until ICU admission influences on the clinical outcome of critical patients. Methods: An observational longitudinal retrospective study performed in a public hospital in Joinville/SC in 2019. This study analyzed data from patients admitted to the ICU with up to 72h of waiting time in the Emergency Room. It compares Q4'2017 (phase 1), when there were 14 ICU beds in the hospital vs. Q4'2018 (phase 2), when there were 30 ICU beds. Results: 173 medical records were analyzed in 2017-2018. There was a statistically significant difference in the time for ICU admission between 2017 and 2018 (median 22h vs. 15h; p=0.0002). There was also a statistically significant difference for mortality rates up to 24h of admission (9.61% vs. 2.47%; p=0.04). There was no statistically significant difference for hospital mortality rates (34.6% vs. 35.5%; p=0.57). There was also no statistically significant difference between the other parameters analyzed. Conclusion:Comparing 2017 and 2018, waiting time for an ICU bed was shorter in 2018, and the mortality rates up to 24 hours of ICU admission were lower. However, waiting time in the Emergency Room until ICU admission did not show as-sociation with hospital mortality rates. (AU)

Brazilian guidelines for the management of brain-dead potential organ donors. The task force of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network, and the General Coordination of the National Transplant System. / Diretrizes brasileiras para o manejo de potenciais doadores de órgãos em morte encefálica. Uma força-tarefa composta por Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network e Coordenação Geral do Sistema Nacional de Transplantes.

OBJECTIVE: To contribute to updating the recommendations for brain-dead potential organ donor management. METHODS: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, answered questions related to the following topics were divided into mechanical ventilation, hemodynamics, endocrine-metabolic management, infection, body temperature, blood transfusion, and checklists use. The outcomes considered were cardiac arrests, number of organs removed or transplanted as well as function / survival of transplanted organs. The quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system to classify the recommendations. RESULTS: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong, 11 as weak and 1 was considered a good clinical practice. CONCLUSION: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak.

OBJETIVO: Fornecer recomendações para nortear o manejo clínico do potencial doador em morte encefálica. MÉTODOS: O presente documento foi formulado em dois painéis compostos por uma força tarefa integrada por 27 especialistas de diferentes áreas que responderam a questões dirigidas aos seguintes temas: ventilação mecânica, hemodinâmica, suporte endócrino-metabólico, infecção, temperatura corporal, transfusão sanguínea, e uso de checklists. Os desfechos considerados foram: parada cardíaca, número de órgãos retirados ou transplantados e função/sobrevida dos órgãos transplantados. A qualidade das evidências das recomendações foi avaliada pelo sistema Grading of Recommendations Assessment, Development, and Evaluation. RESULTADOS: Foram geradas 19 recomendações a partir do painel de especialistas. Dessas, 7 foram classificadas como fortes, 11 fracas e uma foi considerada boa prática clínica. CONCLUSÃO: Apesar da concordância entre os membros do painel em relação à maior parte das recomendações, o grau de recomendação é fraco em sua maioria.

The Effect of Reconnection to Mechanical Ventilation for 1 Hour After Spontaneous Breathing Trial on Reintubation Among Patients Ventilated for More Than 12 Hours: A Randomized Clinical Trial.

BACKGROUND: The resting of the respiratory musculature after undergoing the spontaneous breathing trial (SBT) to prevent extubation failures in critically ill patients needs to be studied further. RESEARCH QUESTION: Is the reconnection to mechanical ventilation (MV) for 1 h after a successful SBT able to reduce the risk of reintubation? STUDY DESIGN AND METHODS: Randomized clinical trial conducted in four ICUs between August 2018 and July 2019. Candidates for tracheal extubation who met all screening criteria for weaning were included. After achieving success in the SBT using a T-tube, the patients were randomized to the following groups: direct extubation (DE) or extubation after reconnection to MV for 1 h (R1h). The primary outcome was reintubation within 48 h. RESULTS: Among the 336 patients studied (women, 41.1%; median age, 59 years [interquartile range, 45-70 years]), 12.9% (22/171) in the R1h group required reintubation within 48 h vs 18.2% (30/165) in the DE group (risk difference, 5.3 [95% CI, -2.49 to 13.12]; P = .18). No differences were found in mortality, length of ICU or hospital stay, causes of reintubation, or signs of extubation failure. A prespecified exploratory analysis showed that among the 233 patients (69.3%) who were ventilated for more than 72 h, the incidence of reintubation was 12.7% (15/118) in the R1h group compared with 22.6% (26/115) observed in the DE group (P = .04). INTERPRETATION: Reconnection to MV after a successful SBT, compared with DE, did not result in a statistically significant reduction in the risk of reintubation in mechanically ventilated patients. Subgroup exploratory findings suggest that the strategy may benefit patients who were ventilated for more than 72 h, which should be confirmed in further studies. TRIAL REGISTRY: Brazilian Clinical Trials Registry; No.: RBR-3x8nxn; URL: www.ensaiosclinicos.gov.br.

Diretrizes brasileiras para o manejo de potenciais doadores de órgãos em morte encefálica. Uma força-tarefa composta por Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network e Coordenação Geral do Sistema Nacional de Transplantes / Brazilian guidelines for the management of brain-dead potential organ donors. The task force of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network, and the General Coordination of the National Transplant System

RESUMO Objetivo: Fornecer recomendações para nortear o manejo clínico do potencial doador em morte encefálica. Métodos: O presente documento foi formulado em dois painéis compostos por uma força tarefa integrada por 27 especialistas de diferentes áreas que responderam a questões dirigidas aos seguintes temas: ventilação mecânica, hemodinâmica, suporte endócrino-metabólico, infecção, temperatura corporal, transfusão sanguínea, e uso de checklists. Os desfechos considerados foram: parada cardíaca, número de órgãos retirados ou transplantados e função/sobrevida dos órgãos transplantados. A qualidade das evidências das recomendações foi avaliada pelo sistema Grading of Recommendations Assessment, Development, and Evaluation. Resultados: Foram geradas 19 recomendações a partir do painel de especialistas. Dessas, 7 foram classificadas como fortes, 11 fracas e uma foi considerada boa prática clínica. Conclusão: Apesar da concordância entre os membros do painel em relação à maior parte das recomendações, o grau de recomendação é fraco em sua maioria.

Abstract Objective: To contribute to updating the recommendations for brain-dead potential organ donor management. Methods: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, answered questions related to the following topics were divided into mechanical ventilation, hemodynamics, endocrine-metabolic management, infection, body temperature, blood transfusion, and checklists use. The outcomes considered were cardiac arrests, number of organs removed or transplanted as well as function / survival of transplanted organs. The quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system to classify the recommendations. Results: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong, 11 as weak and 1 was considered a good clinical practice. Conclusion: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak.

Brazilian guidelines for the management of brain-dead potential organ donors. The task force of the AMIB, ABTO, BRICNet, and the General Coordination of the National Transplant System.

OBJECTIVE: To contribute to updating the recommendations for brain-dead potential organ donor management. METHOD: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, joined a task force formed by the General Coordination Office of the National Transplant System/Brazilian Ministry of Health (CGSNT-MS), the Brazilian Association of Intensive Care Medicine (AMIB), the Brazilian Association of Organ Transplantation (ABTO), and the Brazilian Research in Intensive Care Network (BRICNet). The questions were developed within the scope of the 2011 Brazilian Guidelines for Management of Adult Potential Multiple-Organ Deceased Donors. The topics were divided into mechanical ventilation, hemodynamic support, endocrine-metabolic management, infection, body temperature, blood transfusion, and use of checklists. The outcomes considered for decision-making were cardiac arrest, number of organs recovered or transplanted per donor, and graft function/survival. Rapid systematic reviews were conducted, and the quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Two expert panels were held in November 2016 and February 2017 to classify the recommendations. A systematic review update was performed in June 2020, and the recommendations were reviewed through a Delphi process with the panelists between June and July 2020. RESULTS: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong (lung-protective ventilation strategy, vasopressors and combining arginine vasopressin to control blood pressure, antidiuretic hormones to control polyuria, serum potassium and magnesium control, and antibiotic use), 11 as weak (alveolar recruitment maneuvers, low-dose dopamine, low-dose corticosteroids, thyroid hormones, glycemic and serum sodium control, nutritional support, body temperature control or hypothermia, red blood cell transfusion, and goal-directed protocols), and 1 was considered a good clinical practice (volemic expansion). CONCLUSION: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak. The observed lack of robust evidence on the topic highlights the importance of the present guideline to improve the management of brain-dead potential organ donors.

Can the behavior of blood pressure after elevation of the positive end-expiratory pressure help to determine the fluid responsiveness status in patients with septic shock? / O comportamento da pressão arterial após elevação da pressão parcial positiva final pode auxiliar na determinação do status de fluido-responsividade em pacientes com choque séptico?

OBJECTIVE: To evaluate whether the decrease in blood pressure caused by the increase in the positive end-expiratory pressure corresponds to the pulse pressure variation as an indicator of fluid responsiveness. METHODS: This exploratory study prospectively included 24 patients with septic shock who were mechanically ventilated and subjected to three stages of elevation of the positive end-expiratory pressure: from 5 to 10cmH2O (positive end-expiratory pressure level 1), from 10 to 15cmH2O (positive end-expiratory pressure level 2), and from 15 to 20cmH2O (positive end-expiratory pressure level 3). Changes in systolic blood pressure, mean arterial pressure, and pulse pressure variation were evaluated during the three maneuvers. The patients were classified as responsive (pulse pressure variation ≥ 12%) or unresponsive to volume replacement (pulse pressure variation < 12%). RESULTS: The best performance at identifying patients with pulse pressure variation ≥ 12% was observed at the positive end-expiratory pressure level 2: -9% systolic blood pressure variation (area under the curve 0.73; 95%CI: 0.49 - 0.79; p = 0.04), with a sensitivity of 63% and specificity of 80%. Concordance was low between the variable with the best performance (variation in systolic blood pressure) and pulse pressure variation ≥ 12% (kappa = 0.42; 95%CI: 0.19 - 0.56). The systolic blood pressure was < 90mmHg at positive end-expiratory pressure level 2 in 29.2% of cases and at positive end-expiratory pressure level 3 in 41.63% of cases. CONCLUSION: Variations in blood pressure in response to the increase in positive end-expiratory pressure do not reliably reflect the behavior of the pulse pressure as a measure to identify the fluid responsiveness status.

OBJETIVO: Avaliar se a diminuição da pressão arterial provocada pela elevação da pressão parcial positiva final corresponde à variação da pressão de pulso como indicador de fluido-responsividade. MÉTODOS: Estudo de caráter exploratório que incluiu prospectivamente 24 pacientes com choque séptico ventilados mecanicamente e submetidos a três etapas de elevação da pressão parcial positiva final: de 5 para 10cmH2O (nível da pressão parcial positiva final 1), de 10 para 15cmH2O (nível da pressão parcial positiva final 2) e de 15 para 20cmH2O (nível da pressão parcial positiva final 3). Alterações da pressão arterial sistólica, da pressão arterial média e da variação da pressão de pulso foram avaliadas durante as três manobras. Os pacientes foram classificados como responsivos (variação da pressão de pulso ≥ 12%) e não responsivos a volume (variação da pressão de pulso < 12%). RESULTADOS: O melhor desempenho para identificar pacientes com variação da pressão de pulso ≥ 12% foi observado no nível da pressão parcial positiva final 2: variação de pressão arterial sistólica de -9% (área sob a curva de 0,73; IC95%: 0,49 - 0,79; p = 0,04), com sensibilidade de 63% e especificidade de 80%. A concordância foi baixa entre a variável de melhor desempenho (variação de pressão arterial sistólica) e a variação da pressão de pulso ≥ 12% (kappa = 0,42; IC95%: 0,19 - 0,56). A pressão arterial sistólica foi < 90mmHg no nível da pressão parcial positiva final 2 em 29,2% dos casos e em 41,6,3% no nível da pressão parcial positiva final 3. CONCLUSÃO: Variações da pressão arterial em resposta à elevação da pressão parcial positiva final não refletem de modo confiável o comportamento da variação da pressão de pulso para identificar o status da fluido-responsividade.