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.

High-value care for critically ill oncohematological patients: what do we know thus far?

The number of patients with cancer requiring intensive care unit admission is increasing around the world. The improvement in the pathophysiological understanding of this group of patients, as well as the increasingly better and more targeted treatment options for their underlying disease, has led to a significant increase in their survival over the past three decades. Within the organizational concepts, it is necessary to know what adds value in the care of critical oncohematological patients. Practices in medicine that do not benefit patients and possibly cause harm are called low-value practices, while high-value practices are defined as high-quality care at relatively low cost. In this article, we discuss ten domains with high-value evidence in the care of cancer patients: (1) intensive care unit admission policies; (2) intensive care unit organization; (3) etiological investigation of hypoxemia; (4) management of acute respiratory failure; (5) management of febrile neutropenia; (6) urgent chemotherapy treatment in critically ill patients; (7) patient and family experience; (8) palliative care; (9) care of intensive care unit staff; and (10) long-term impact of critical disease on the cancer population. The disclosure of such policies is expected to have the potential to change health care standards. We understand that it is a lengthy process, and initiatives such as this paper are one of the first steps in raising awareness and beginning a discussion about high-value care in various health scenarios.

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

High-value care for critically ill oncohematological patients: what do we know thus far? / Cuidados de alto valor para pacientes oncohematológicos graves: o que sabemos até agora?

ABSTRACT The number of patients with cancer requiring intensive care unit admission is increasing around the world. The improvement in the pathophysiological understanding of this group of patients, as well as the increasingly better and more targeted treatment options for their underlying disease, has led to a significant increase in their survival over the past three decades. Within the organizational concepts, it is necessary to know what adds value in the care of critical oncohematological patients. Practices in medicine that do not benefit patients and possibly cause harm are called low-value practices, while high-value practices are defined as high-quality care at relatively low cost. In this article, we discuss ten domains with high-value evidence in the care of cancer patients: (1) intensive care unit admission policies; (2) intensive care unit organization; (3) etiological investigation of hypoxemia; (4) management of acute respiratory failure; (5) management of febrile neutropenia; (6) urgent chemotherapy treatment in critically ill patients; (7) patient and family experience; (8) palliative care; (9) care of intensive care unit staff; and (10) long-term impact of critical disease on the cancer population. The disclosure of such policies is expected to have the potential to change health care standards. We understand that it is a lengthy process, and initiatives such as this paper are one of the first steps in raising awareness and beginning a discussion about high-value care in various health scenarios.

RESUMO O número de pacientes oncológicos com necessidade de internação em unidades de terapia intensiva está aumentando em todo o mundo. A maior compreensão fisiopatológica desse grupo de pacientes, bem como opções de tratamento cada vez melhores e mais direcionadas à doença subjacente, tem levado a um aumento significativo da sobrevida nas últimas três décadas. Dentro dos conceitos organizacionais é necessário saber o que agrega valor ao cuidado de pacientes onco-hematológicos graves. As práticas terapêuticas não benéficas aos pacientes e possivelmente causadoras de danos são chamadas práticas de baixo valor, enquanto as práticas de alto valor são definidas como cuidados de alta qualidade a um custo relativamente baixo. Neste artigo discutimos dez domínios com evidências de alto valor no cuidado de pacientes com câncer: (1) políticas de internação na unidade de terapia intensiva; (2) organização da unidade de terapia intensiva; (3) investigação etiológica da hipoxemia; (4) manejo da insuficiência respiratória aguda; (5) manejo da neutropenia febril; (6) tratamento quimioterápico de urgência em pacientes graves; (7) experiência do paciente e da família; (8) cuidados paliativos; (9) cuidados com a equipe da unidade de terapia intensiva; e (10) impacto a longo prazo da doença grave na população oncológica. Esperase que a divulgação dessas políticas traga mudanças aos padrões atuais do cuidado em saúde. Entendemos que é um processo longo, e iniciativas como o presente artigo são um dos primeiros passos para aumentar a conscientização e possibilitar discussão sobre cuidados de alto valor em vários cenários de saúde.

Postoperative hypothermia following non-cardiac high-risk surgery: A prospective study of temporal patterns and risk factors.

BACKGROUND AND OBJECTIVES: Hypothermia occurs commonly during surgery and can cause postoperative complications. We aimed to describe the characteristics and outcomes of hypothermia in patients undergoing major surgeries. METHODS: This prospective, observational, multicenter study of a nationally representative sample included all patients over 18 years of age admitted to an intensive care unit (ICU). Thirty ICUs were selected randomly at national level. The main outcome measure was the proportion of patients who developed postoperative hypothermia in the first 24 hours of ICU admission. Patients were divided into three groups based on temperature: <35°C, <36°C, and ≥36°C (no hypothermia). Patients' characteristics, postoperative complications, and risk factors were evaluated in all groups. To verify whether hypothermia was a strong risk factor for postoperative complications, a Kaplan-Meier curve was generated and adjusted using a Cox regression model. RESULTS: In total, 738 patients had their temperatures measured. The percentage of patients with temperature <35°C (median [Q1-Q3], 34.7°C [34.3-34.9°C]) was 19.1% (95% confidence interval [CI] = 16.1-22.5) and that of patients with temperature <36°C (median [Q1-Q3], 35.4°C [35.0-35.8°C]) was 64% (95% CI = 58.3-70.0). The percentage of surgical complications was 38.9%. Patients with hypothermia were older, had undergone abdominal surgeries, had undergone procedures of longer duration, and had more comorbidities. A postoperative temperature ≤35°C was an independent risk for composite postoperative complications (hazard ratio = 1.523, 95% CI = 1.15-2.0), especially coagulation and infection. CONCLUSIONS: Inadvertent hypothermia was frequent among patients admitted to the ICU and occurred more likely after abdominal surgery, after a long procedure, in elderly patients, and in patients with a higher number of comorbidities. Low postoperative temperature was associated with postoperative complications.

Referral to immediate postoperative care in an intensive care unit from the perspective of anesthesiologists, surgeons, and intensive care physicians: a cross-sectional questionnaire.

INTRODUCTION AND OBJECTIVE: Due to the high cost and insufficient offer, the request for Intensive Care (ICU) beds for postoperative recovery needs adequate criteria. Therefore, we studied the characteristics of patients referred to postoperative care at an ICU from the perspective of anesthesiologists, surgeons, and intensive care physicians. METHODS: A questionnaire on referrals to postoperative intensive care was applied to physicians at congresses in Brazil. Anesthesiologists, surgeons, and intensive care physicians who agreed to fill out the questionnaire were included. The questionnaire consisted of hypothetical clinical scenarios and cases for participants to choose which would be the priority for referral to the ICU. RESULTS: 360 physicians participated in the study, with median time of 10 (5-18) years after graduation. Of the interviewees, 36.4% were anesthesiologists, 30.0% surgeons, and 33.6% intensive care physicians. We found that anesthesiologists were more conservative, and surgeons less conservative in ICU referrals. As to patients with risk of bleeding, 75.0% of the surgeons would refer them to the ICU, in contrast with 52.1% of the intensive care physicians, and 43.5% of the anesthesiologists (p < 0.001). As to elderly persons with limited reserve, 62.0% of the surgeons would refer them to the ICU, in contrast with 47.1% of the intensive care physicians, and 22.1% of the anesthesiologists (p < 0.001). As to patients with risk of respiratory complications, 64.5% of the surgeons would recommend the ICU, versus 43.0% of the intensive care physicians, and 32.1% of the anesthesiologists (p < 0.001). Intensive care physicians classified priorities better in indicating ICU, and the main risk indicator was the ASA physical status in all specialties (p < 0.001). There was no agreement among the specialties and surgeries on prioritizing post-operative intensive care. CONCLUSION: Anesthesiologists, surgeons, and intensive care physicians presented different perspectives on postoperative referral to the ICU.

Statistical analysis plan for the Balanced Solution versus Saline in Intensive Care Study (BaSICS). / Plano de análise estatística para o estudo Balanced Solution versus Saline in Intensive Care Study (BaSICS).

OBJECTIVE: To report the statistical analysis plan (first version) for the Balanced Solutions versus Saline in Intensive Care Study (BaSICS). METHODS: BaSICS is a multicenter factorial randomized controlled trial that will assess the effects of Plasma-Lyte 148 versus 0.9% saline as the fluid of choice in critically ill patients, as well as the effects of a slow (333mL/h) versus rapid (999mL/h) infusion speed during fluid challenges, on important patient outcomes. The fluid type will be blinded for investigators, patients and the analyses. No blinding will be possible for the infusion speed for the investigators, but all analyses will be kept blinded during the analysis procedure. RESULTS: BaSICS will have 90-day mortality as its primary endpoint, which will be tested using mixed-effects Cox proportional hazard models, considering sites as a random variable (frailty models) adjusted for age, organ dysfunction and admission type. Important secondary endpoints include renal replacement therapy up to 90 days, acute renal failure, organ dysfunction at days 3 and 7, and mechanical ventilation-free days within 28 days. CONCLUSION: This manuscript provides details on the first version of the statistical analysis plan for the BaSICS trial and will guide the study's analysis when follow-up is finished.

OBJETIVO: Relatar o plano de análise estatística (primeira versão) para o estudo Balanced Solutions versus Saline in Intensive Care Study (BaSICS). MÉTODOS: O estudo BaSICS é um ensaio multicêntrico fatorial e randomizado que avaliará os efeitos da administração dos fluidos Plasma-Lyte 148 em comparação com solução salina 0,9% como fluido de escolha em pacientes críticos, assim como os efeitos de uma velocidade de infusão lenta (333mL/hora) em comparação com uma velocidade de infusão rápida (999mL/hora) durante desafios com volume, em importantes desfechos do paciente. O tipo de fluido será mantido cego para os investigadores, pacientes e nas análises. Não será possível, entretanto, ocultar dos investigadores a velocidade de infusão, mas os procedimentos de análise serão mantidos cegos quanto a esse aspecto. RESULTADOS: O estudo BaSICS terá como parâmetro primário a mortalidade em 90 dias, que será testada com utilização de modelos de risco proporcional de Cox de efeitos mistos, considerando os centros de estudo como variável randômica (modelos de fragilidade) ajustada por idade, disfunção de órgãos e tipo de admissão. Os parâmetros secundários importantes incluem terapia de substituição renal até 90 dias, insuficiência renal aguda, disfunção de órgãos nos dias 3 e 7 e dias sem ventilação mecânica em 28 dias. CONCLUSÃO: Este artigo fornece detalhes referentes à primeira versão do plano de análise estatística para o estudo BaSICS e orientará a análise do estudo após a conclusão do seguimento.

Plano de análise estatística para o estudo Balanced Solution versus Saline in Intensive Care Study (BaSICS) / Statistical analysis plan for the Balanced Solution versus Saline in Intensive Care Study (BaSICS)

RESUMO Objetivo: Relatar o plano de análise estatística (primeira versão) para o estudo Balanced Solutions versus Saline in Intensive Care Study (BaSICS). Métodos: O estudo BaSICS é um ensaio multicêntrico fatorial e randomizado que avaliará os efeitos da administração dos fluidos Plasma-Lyte 148 em comparação com solução salina 0,9% como fluido de escolha em pacientes críticos, assim como os efeitos de uma velocidade de infusão lenta (333mL/hora) em comparação com uma velocidade de infusão rápida (999mL/hora) durante desafios com volume, em importantes desfechos do paciente. O tipo de fluido será mantido cego para os investigadores, pacientes e nas análises. Não será possível, entretanto, ocultar dos investigadores a velocidade de infusão, mas os procedimentos de análise serão mantidos cegos quanto a esse aspecto. Resultados: O estudo BaSICS terá como parâmetro primário a mortalidade em 90 dias, que será testada com utilização de modelos de risco proporcional de Cox de efeitos mistos, considerando os centros de estudo como variável randômica (modelos de fragilidade) ajustada por idade, disfunção de órgãos e tipo de admissão. Os parâmetros secundários importantes incluem terapia de substituição renal até 90 dias, insuficiência renal aguda, disfunção de órgãos nos dias 3 e 7 e dias sem ventilação mecânica em 28 dias. Conclusão: Este artigo fornece detalhes referentes à primeira versão do plano de análise estatística para o estudo BaSICS e orientará a análise do estudo após a conclusão do seguimento.

Abstract Objective: To report the statistical analysis plan (first version) for the Balanced Solutions versus Saline in Intensive Care Study (BaSICS). Methods: BaSICS is a multicenter factorial randomized controlled trial that will assess the effects of Plasma-Lyte 148 versus 0.9% saline as the fluid of choice in critically ill patients, as well as the effects of a slow (333mL/h) versus rapid (999mL/h) infusion speed during fluid challenges, on important patient outcomes. The fluid type will be blinded for investigators, patients and the analyses. No blinding will be possible for the infusion speed for the investigators, but all analyses will be kept blinded during the analysis procedure. Results: BaSICS will have 90-day mortality as its primary endpoint, which will be tested using mixed-effects Cox proportional hazard models, considering sites as a random variable (frailty models) adjusted for age, organ dysfunction and admission type. Important secondary endpoints include renal replacement therapy up to 90 days, acute renal failure, organ dysfunction at days 3 and 7, and mechanical ventilation-free days within 28 days. Conclusion: This manuscript provides details on the first version of the statistical analysis plan for the BaSICS trial and will guide the study's analysis when follow-up is finished.

The Effects of Melatonin Supplementation on Sleep Quality and Assessment of the Serum Melatonin in ICU Patients: A Randomized Controlled Trial.

OBJECTIVES: To evaluate whether the use of exogenous melatonin affects sleep, reduces the prevalence of delirium, and decreases the need for analgosedation and to assess whether serum melatonin indices correlate with exogenous administration in critically ill patients. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: Multicenter ICUs of two tertiary hospitals. PATIENTS: A total of 203 adult patients who were admitted to the ICU and administered with analgesics and/or sedatives. INTERVENTIONS: Oral melatonin (10 mg) or placebo for up to seven consecutive nights. MEASUREMENTS AND MAIN RESULTS: The number of observed sleeping hours at night was assessed by the bedside nurse. Sleep quality was evaluated using the Richards Campbell Questionnaire Sleep (RCSQ). The prevalence of delirium, pain, anxiety, adverse reactions, duration of mechanical ventilation, length of ICU and hospital stays, and doses of sedative and analgesic drugs administered were recorded. The use of analgesics and sedatives was assessed daily. Melatonin levels were determined by enzyme-linked immunosorbent assay. Based on the RCSQ results, sleep quality was assessed to be better in the melatonin group than that in the placebo group with a mean (SD) of 69.7 (21.2) and 60.7 (26.3), respectively (p = 0.029). About 45.8% and 34.4% of participants in the melatonin and placebo groups had very good sleep (risk ratio, 1.33; 95% CI, 0.94-1.89), whereas 3.1% and 14.6% had very poor sleep (risk ratio, 0.21; 95% CI, 0.06-0.71), respectively. No significant difference was observed regarding the days free of analgesics or sedatives, the duration of night sleep, and the occurrence of delirium, pain, and anxiety. Melatonin serum peak levels at 2 AM were 150 pg/mL (range, 125-2,125 pg/mL) in the melatonin group and 32.5 pg/mL (range, 18.5-35 pg/mL) in the placebo group (p < 0.001). CONCLUSIONS: Melatonin was associated with better sleep quality, which suggests its possible role in the routine care of critically ill patients in the future.

Characteristics and short-term outcomes of patients with esophageal cancer with unplanned intensive care unit admissions: a retrospective cohort study. / Características e desfechos em curto prazo de pacientes com câncer esofágico em admissões não planejadas a unidades de terapia intensiva: um estudo de coorte retrospectiva.

OBJECTIVE: To depict the clinical presentation and outcomes of a cohort of critically ill patients with esophageal cancer. METHODS: We carried out a multicenter retrospective study that included patients with esophageal cancer admitted to intensive care units with acute illness between September 2009 and December 2017. We collected the demographic and clinical characteristics of all included patients, as well as organ-support measures and hospital outcomes. We performed logistic regression analysis to identify independent factors associated with in-hospital mortality. RESULTS: Of 226 patients included in the study, 131 (58.0%) patients died before hospital discharge. Squamous cell carcinoma was more frequent than adenocarcinoma, and 124 (54.9%) patients had metastatic cancer. The main reasons for admission were sepsis/septic shock and acute respiratory failure. Mechanical ventilation (OR = 6.18; 95%CI 2.86 - 13.35) and metastatic disease (OR = 7.10; 95%CI 3.35 - 15.05) were independently associated with in-hospital mortality. CONCLUSION: In this cohort of patients with esophageal cancer admitted to intensive care units with acute illness, the in-hospital mortality rate was very high. The requirement for invasive mechanical ventilation and metastatic disease were independent prognostic factors and should be considered in discussions about the short-term outcomes of these patients.

Características e desfechos em curto prazo de pacientes com câncer esofágico em admissões não planejadas a unidades de terapia intensiva: um estudo de coorte retrospectiva / Characteristics and short-term outcomes of patients with esophageal cancer with unplanned intensive care unit admissions: a retrospective cohort study

RESUMO Objetivo: Mostrar o quadro clínico e os desfechos de uma coorte de pacientes críticos com câncer esofágico. Métodos: Conduzimos um estudo multicêntrico retrospectivo que incluiu pacientes com câncer esofágico admitidos a unidades de terapia intensiva em razão de doença aguda entre setembro de 2009 e dezembro de 2017. Colhemos os dados demográficos e as características clínicas de todos os pacientes incluídos, assim como as medidas de suporte a órgãos e os desfechos no hospital. Realizamos uma análise de regressão logística para identificar os fatores associados de forma independente com mortalidade hospitalar. Resultados: Dentre os 226 pacientes incluídos no estudo, 131 (58,0%) faleceram antes de receber alta hospitalar. O carcinoma espinocelular foi mais frequente do que o adenocarcinoma, e 124 (54,9%) pacientes tinham câncer metastático. As principais razões para admissão foram sepse/choque séptico e insuficiência respiratória aguda. Uso de ventilação mecânica (RC = 6,18; IC95% 2,86 - 13,35) e doença metastática (RC = 7,10; IC95% 3,35 - 15,05) tiveram associação independente com mortalidade hospitalar. Conclusão: Nesta coorte de pacientes com câncer esofágico admitidos à unidades de terapia intensiva em razão de doença aguda, a taxa de mortalidade hospitalar foi muito elevada. A necessidade de utilizar ventilação mecânica invasiva e a presença de doença metastática foram fatores independentes de prognóstico e devem ser levados em conta nas discussões a respeito dos desfechos destes pacientes em curto prazo.

ABSTRACT Objective: To depict the clinical presentation and outcomes of a cohort of critically ill patients with esophageal cancer. Methods: We carried out a multicenter retrospective study that included patients with esophageal cancer admitted to intensive care units with acute illness between September 2009 and December 2017. We collected the demographic and clinical characteristics of all included patients, as well as organ-support measures and hospital outcomes. We performed logistic regression analysis to identify independent factors associated with in-hospital mortality. Results: Of 226 patients included in the study, 131 (58.0%) patients died before hospital discharge. Squamous cell carcinoma was more frequent than adenocarcinoma, and 124 (54.9%) patients had metastatic cancer. The main reasons for admission were sepsis/septic shock and acute respiratory failure. Mechanical ventilation (OR = 6.18; 95%CI 2.86 - 13.35) and metastatic disease (OR = 7.10; 95%CI 3.35 - 15.05) were independently associated with in-hospital mortality. Conclusion: In this cohort of patients with esophageal cancer admitted to intensive care units with acute illness, the in-hospital mortality rate was very high. The requirement for invasive mechanical ventilation and metastatic disease were independent prognostic factors and should be considered in discussions about the short-term outcomes of these patients.

Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil. / Epidemiologia e desfecho dos pacientes de alto risco cirúrgico admitidos em unidades de terapia intensiva no Brasil.

OBJECTIVE: To define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil. METHODS: This was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated. RESULTS: Twenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051). CONCLUSION: Higher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.

Epidemiologia e desfecho dos pacientes de alto risco cirúrgico admitidos em unidades de terapia intensiva no Brasil / Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil

RESUMO Objetivo: Definir o perfil epidemiológico e os principais determinantes de morbimortalidade dos pacientes cirúrgicos não cardíacos de alto risco no Brasil. Métodos: Estudo prospectivo, observacional e multicêntrico. Todos os pacientes cirúrgicos não cardíacos admitidos nas unidades de terapia intensiva, ou seja, considerados de alto risco, no período de 1 mês, foram avaliados e acompanhados diariamente por, no máximo, 7 dias na unidade de terapia intensiva, para determinação de complicações. As taxas de mortalidade em 28 dias de pós-operatório, na unidade de terapia intensiva e hospitalar foram avaliadas. Resultados: Participaram 29 unidades de terapia intensiva onde foram realizadas cirurgias em 25.500 pacientes, dos quais 904 (3,5%) de alto risco (intervalo de confiança de 95% - IC95% 3,3% - 3,8%), tendo sido incluídos no estudo. Dos pacientes envolvidos, 48,3% eram de unidades de terapia intensiva privadas e 51,7% de públicas. O tempo de internação na unidade de terapia intensiva foi de 2,0 (1,0 - 4,0) dias e hospitalar de 9,5 (5,4 - 18,6) dias. As taxas de complicações foram 29,9% (IC95% 26,4 - 33,7) e mortalidade em 28 dias pós-cirurgia 9,6% (IC95% 7,4 - 12,1). Os fatores independentes de risco para complicações foram Simplified Acute Physiology Score 3 (SAPS 3; razão de chance − RC = 1,02; IC95% 1,01 - 1,03) e Sequential Organ Failure Assessment Score (SOFA) da admissão na unidade de terapia intensiva (RC =1,17; IC95% 1,09 - 1,25), tempo de cirurgia (RC = 1,001; IC95% 1,000 - 1,002) e cirurgias de emergências (RC = 1,93; IC95% 1,10 - 3,38). Em adição, foram associados com mortalidade em 28 dias idade (RC = 1,032; IC95% 1,011 - 1,052) SAPS 3 (RC = 1,041; IC95% 1,107 - 1,279), SOFA (RC = 1,175; IC95% 1,069 - 1,292) e cirurgias emergenciais (RC = 2,509; IC95% 1,040 - 6,051). Conclusão: Pacientes com escores prognósticos mais elevados, idosos, tempo cirúrgico e cirurgias emergenciais estiveram fortemente associados a maior mortalidade em 28 dias e mais complicações durante permanência em unidade de terapia intensiva.

ABSTRACT Objective: To define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil. Methods: This was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated. Results: Twenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051). Conclusion: Higher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.

Oncologists' and Intensivists' Attitudes Toward the Care of Critically Ill Patients with Cancer.

BACKGROUND: Patients with cancer represent an important proportion of intensive care unit (ICU) admissions. Oncologists and intensivists have distinct knowledge backgrounds, and conflicts about the appropriate management of these patients may emerge. METHODS: We surveyed oncologists and intensivists at 2 academic cancer centers regarding their management of 2 hypothetical patients with different cancer types (metastatic pancreatic cancer and metastatic breast cancer with positive receptors for estrogen, progesterone, and HER-2) who develop septic shock and multiple organ failure. RESULTS: Sixty intensivists and 46 oncologists responded to the survey. Oncologists and intensivists similarly favored withdrawal of life support measures for the patient with pancreatic cancer (33/46 [72%] vs 48/60 [80%], P = .45). On the other hand, intensivists favored more withdrawal of life support measures for the patient with breast cancer compared to oncologists (32/59 [54%] vs 9/44 [21%], P < .001). In the multinomial logistic regression, the oncology specialists were more likely to advocate for a full-code status for the patient with breast cancer (OR = 5.931; CI 95%, 1.762-19.956; P = .004). CONCLUSIONS: Oncologists and intensivists share different views regarding life support measures in critically ill patients with cancer. Oncologists tend to focus on the cancer characteristics, whereas intensivists focus on multiple organ failure when weighing in on the same decisions. Regular meetings between oncologists and intensivists may reduce possible conflicts regarding the critical care of patients with cancer.

Goal-directed therapy in patients with early acute kidney injury: a multicenter randomized controlled trial.

OBJECTIVES: Acute kidney injury is associated with many conditions, and no interventions to improve the outcomes of established acute kidney injury have been developed. We performed this study to determine whether goal-directed therapy conducted during the early stages of acute kidney injury could change the course of the disease. METHODS: This was a multicenter prospective randomized controlled study. Patients with early acute kidney injury in the critical care unit were randomly allocated to a standard care (control) group or a goal-directed therapy group with 8h of intensive treatment to maximize oxygen delivery, and all patients were evaluated during a period of 72h. ClinicalTrials.gov: NCT02414906. RESULTS: A total of 143 patients were eligible for the study, and 99 patients were randomized. Central venous oxygen saturation was significantly increased and the serum lactate level significantly was decreased from baseline levels in the goal-directed therapy group (p=0.001) compared to the control group (p=0.572). No significant differences in the change in serum creatinine level (p=0.96), persistence of acute kidney injury beyond 72h (p=0.064) or the need for renal replacement therapy (p=0.82) were observed between the two groups. In-hospital mortality was significantly lower in the goal-directed therapy group than in the control group (33% vs. 51%; RR: 0.61, 95% CI: 0.37-1.00, p=0.048, number needed to treat=5). CONCLUSIONS: Goal-directed therapy for patients in the early stages of acute kidney injury did not change the disease course.

Goal-directed therapy in patients with early acute kidney injury: a multicenter randomized controlled trial

OBJECTIVES: Acute kidney injury is associated with many conditions, and no interventions to improve the outcomes of established acute kidney injury have been developed. We performed this study to determine whether goal-directed therapy conducted during the early stages of acute kidney injury could change the course of the disease. METHODS: This was a multicenter prospective randomized controlled study. Patients with early acute kidney injury in the critical care unit were randomly allocated to a standard care (control) group or a goal-directed therapy group with 8h of intensive treatment to maximize oxygen delivery, and all patients were evaluated during a period of 72h. ClinicalTrials.gov: NCT02414906. RESULTS: A total of 143 patients were eligible for the study, and 99 patients were randomized. Central venous oxygen saturation was significantly increased and the serum lactate level significantly was decreased from baseline levels in the goal-directed therapy group (p=0.001) compared to the control group (p=0.572). No significant differences in the change in serum creatinine level (p=0.96), persistence of acute kidney injury beyond 72h (p=0.064) or the need for renal replacement therapy (p=0.82) were observed between the two groups. In-hospital mortality was significantly lower in the goal-directed therapy group than in the control group (33% vs. 51%; RR: 0.61, 95% CI: 0.37-1.00, p=0.048, number needed to treat=5). CONCLUSIONS: Goal-directed therapy for patients in the early stages of acute kidney injury did not change the disease course.

Metabolic Acidosis Assessment in High-Risk Surgeries: Prognostic Importance.

BACKGROUND: Metabolic acidosis frequently is present in surgical patients; however, different types of metabolic acidosis (hyperlactatemia, hyperchloremia, and others) may have different relationships to perioperative outcomes. We hypothesized that in postoperative surgical patients, distinctive types of metabolic acidosis would correlate differently with the outcomes of high-risk surgeries. METHODS: A prospective, multicenter observational study was performed in 3 different tertiary care hospitals. Patients who required postoperative admission to the intensive care unit (ICU) were included in this study. Patients with a short life expectancy (those with untreated cancer and limited treatment), hepatic failure, renal failure, or a diagnosis of diabetes were excluded. Patients were classified at ICU admission according to the presence and type of metabolic acidosis into 4 groups: those without acidosis, those with a base excess <-4 mmol/L and albumin-corrected anion gap ≤12 mmol/L (hyperchloremic), those with a base excess <-4 mmol/L and increased albumin-corrected anion gap >12 mmol/L, and those with a base excess <-4 mmol/L and hyperlactatemia >2 mmol/L. Furthermore, patients were reclassified 12 hours after admission to the ICU to verify the metabolic acidosis behavior and outcome differences among the groups. RESULTS: The study included 618 patients. The incidence of acidosis at ICU admission was 59.1%; 23.9% presented with hyperchloremia, 21.3% with hyperlactatemia, 13.9% with increased anion gap, and 40.9% of the patients presented without metabolic acidosis. Patients whose metabolic acidosis persisted for 12 hours had an incidence of ICU complications rates in hyperlactatemia group of 68.8%, increased anion gap of 68.6%, hyperchloremic of 65.8%, and those without acidosis over 12 hours of 59.3%. A Cox regression model for postoperative 30-day mortality showed: in hyperlactatemic acidosis, hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.02-2.96; increased anion gap acidosis, HR = 1.68, 95% CI = 0.85-3.81; hyperchloremic acidosis, HR = 1.47, 95% CI = 0.75-2.89, and 10.3% of 30-day mortality rate in patients without acidosis. An adjusted survival curve by Cox regression found a worse 30-day survival in the hyperlactatemic group compared with the other groups (P = .03). Furthermore, in multiple comparisons among groups, patients with hyperlactatemic acidosis were more likely to develop renal dysfunction (P < .001) up to the seventh day postoperatively. CONCLUSIONS: We found that among patients with different types of acidosis, patients who developed hyperlactatemic metabolic acidosis postoperatively showed greater rates of renal dysfunction within 7 days and hyperlactatemic acidosis represented an independent factor on 30-day mortality in high-risk surgical patients.

Nurses' knowledge to identify early acute kidney injury.

OBJECTIVE: To evaluate the knowledgeof nurses on early identification of acute kidney injury (AKI) in intensive care, emergency and hospitalization units. METHOD: A prospective multi-center study was conducted with 216 nurses, using a questionnaire with 10 questions related to AKI prevention, diagnosis, and treatment. RESULTS: 57.2% of nurses were unable to identify AKI clinical manifestations, 54.6% did not have knowledge of AKI incidence in patients admitted to the ICU, 87.0% of the nurses did not know how to answer as regards the AKI mortality rate in patients admitted to the ICU, 67.1% answered incorrectly that slight increases in serum creatinine do not have an impact on mortality, 66.8% answered incorrectly to the question on AKI prevention measures, 60.4% answered correctly that loop diuretics for preventing AKI is not recommended, 77.6% answered correctly that AKI does not characterize the need for hemodialysis, and 92.5% said they had no knowledge of the Acute Kidney Injury Networkclassification. CONCLUSION: Nurses do not have enough knowledge to identify early AKI, demonstrating the importance of qualification programs in this field of knowledge. OBJETIVO: Avaliar o conhecimento do enfermeiro na identificação precoce da Injúria Renal Aguda (IRA) em Unidade de Terapia Intensiva, Unidade de Internação e Emergência. MÉTODO: Estudo multicêntrico, prospectivo.Participaram do estudo 216 enfermeiros,por meio de questionário com 10 questões relacionadas à prevenção, ao diagnóstico e ao tratamento da IRA. RESULTADOS: 57,2% não souberam identificar as manifestações clínicas da IRA, 54,6% não têm conhecimento da incidência de IRA em pacientes internados na UTI, 87,0% dos enfermeiros não souberam responder ao índice de mortalidade de IRA em pacientes internados na UTI, 67,1% responderam incorretamente que aumentos discretos da creatinina sérica não têm impacto na mortalidade, 66,8% responderam incorretamente à questão sobre as medidas de prevenção da IRA, 60,4% acertaram quando responderam que não é recomendada a utilização de diuréticos de alça na prevenção da IRA, 77,6% acertaram ao responder que IRA não caracteriza necessidade de hemodiálise e 92,5% disseram não conhecer a classificação AKIN. CONCLUSÃO: Enfermeiros não têm conhecimento suficiente para a identificação precoce da IRA, mostrando a importância de programas de capacitação nesta área do conhecimento.

Nurses' knowledge to identify early acute kidney injury / Conocimiento del enfermero para la identificación precoz de la insuficiencia renal aguda / Conhecimento do enfermeiro para identificação precoce da Injúria Renal Aguda

Abstract OBJECTIVE To evaluate the knowledgeof nurses on early identification of acute kidney injury (AKI) in intensive care, emergency and hospitalization units. METHOD A prospective multi-center study was conducted with 216 nurses, using a questionnaire with 10 questions related to AKI prevention, diagnosis, and treatment. RESULTS 57.2% of nurses were unable to identify AKI clinical manifestations, 54.6% did not have knowledge of AKI incidence in patients admitted to the ICU, 87.0% of the nurses did not know how to answer as regards the AKI mortality rate in patients admitted to the ICU, 67.1% answered incorrectly that slight increases in serum creatinine do not have an impact on mortality, 66.8% answered incorrectly to the question on AKI prevention measures, 60.4% answered correctly that loop diuretics for preventing AKI is not recommended, 77.6% answered correctly that AKI does not characterize the need for hemodialysis, and 92.5% said they had no knowledge of the Acute Kidney Injury Networkclassification. CONCLUSION Nurses do not have enough knowledge to identify early AKI, demonstrating the importance of qualification programs in this field of knowledge.

Resumen OBJETIVO Evaluar el conocimiento del enfermero en la identificación precoz de la Insuficiencia Renal Aguda (IRA) en Unidad de Cuidados Intensivos, Unidad de Estancia Hospitalaria y Urgencias. MÉTODO Estudio multicéntrico, prospectivo.Participaron en el estudio 216 enfermeros, mediante cuestionario con 10 preguntas relacionadas con la prevención, el diagnóstico y el tratamiento de la IRA. RESULTADOS el 57,2% no supieron identificar las manifestaciones clínicas de la IRA, el 54,6% no tienen conocimiento de la incidencia de IRA en pacientes ingresados en la UCI, el 87,0% de los enfermeros no supieron responder al índice de mortalidad de IRA en pacientes ingresados en la UCI, el 67,1% respondieron incorrectamente que aumentos discretos de la creatinina sérica no tienen impacto en la mortalidad, el 66,8% respondieron incorrectamente a la pregunta acerca de las medidas de prevención a la IRA, el 60,4% acertaron cuando respondieron que no se recomienda la utilización de diuréticos de asa en la prevención de la IRA, el 77,6% acertaron al responder que la IRA no caracteriza necesidad de hemodiálisis y el 92,5% dijeron no conocer la clasificación AKIN. CONCLUSIÓN Enfermeros no tienen conocimiento suficiente para la identificación precoz de la IRA, mostrando la importancia de programas de capacitación en esa área del conocimiento.

Resumo OBJETIVO Avaliar o conhecimento do enfermeiro na identificação precoce da Injúria Renal Aguda (IRA) em Unidade de Terapia Intensiva, Unidade de Internação e Emergência. MÉTODO Estudo multicêntrico, prospectivo.Participaram do estudo 216 enfermeiros,por meio de questionário com 10 questões relacionadas à prevenção, ao diagnóstico e ao tratamento da IRA. RESULTADOS 57,2% não souberam identificar as manifestações clínicas da IRA, 54,6% não têm conhecimento da incidência de IRA em pacientes internados na UTI, 87,0% dos enfermeiros não souberam responder ao índice de mortalidade de IRA em pacientes internados na UTI, 67,1% responderam incorretamente que aumentos discretos da creatinina sérica não têm impacto na mortalidade, 66,8% responderam incorretamente à questão sobre as medidas de prevenção da IRA, 60,4% acertaram quando responderam que não é recomendada a utilização de diuréticos de alça na prevenção da IRA, 77,6% acertaram ao responder que IRA não caracteriza necessidade de hemodiálise e 92,5% disseram não conhecer a classificação AKIN. CONCLUSÃO Enfermeiros não têm conhecimento suficiente para a identificação precoce da IRA, mostrando a importância de programas de capacitação nesta área do conhecimento.

The effect of excess fluid balance on the mortality rate of surgical patients: a multicenter prospective study.

INTRODUCTION: In some studies including small populations of patients undergoing specific surgery, an intraoperative liberal infusion of fluids was associated with increasing morbidity when compared to restrictive strategies. Therefore, to evaluate the role of excessive fluid infusion in a general population with high-risk surgery is very important. The aim of this study was to evaluate the impact of intraoperative fluid balance on the postoperative organ dysfunction, infection and mortality rate. METHODS: We conducted a prospective cohort study during one year in four ICUs from three tertiary hospitals, which included patients aged 18 years or more who required postoperative ICU after undergoing major surgery. Patients who underwent palliative surgery and whose fluid balance could change in outcome were excluded. The calculation of fluid balance was based on preoperative fasting, insensible losses from surgeries and urine output minus fluid replacement intraoperatively. RESULTS: The study included 479 patients. Mean age was 61.2 ± 17.0 years and 8.8% of patients died at the hospital during the study. The median duration of surgery was 4.0 (3.2 to 5.5) h and the value of the Simplified Acute Physiology Score (SAPS) 3 score was 41.8 ± 14.5. Comparing survivors and non-survivors, the intraoperative fluid balance from non-survivors was higher (1,950 (1,400 to 3,400) mL vs. 1,400 (1,000 to 1,600) mL, P <0.001). Patients with fluid balance above 2,000 mL intraoperatively had a longer ICU stay (4.0 (3.0 to 8.0) vs. 3.0 (2.0 to 6.0), P <0.001) and higher incidence of infectious (41.9% vs. 25.9%, P = 0.001), neurological (46.2% vs. 13.2%, P <0.001), cardiovascular (63.2% vs. 39.6%, P <0.001) and respiratory complications (34.3% vs. 11.6%, P <0.001). In multivariate analysis, the fluid balance was an independent factor for death (OR per 100 mL = 1.024; P = 0.006; 95% CI 1.007 to 1.041). CONCLUSIONS: Patients with excessive intraoperative fluid balance have more ICU complications and higher hospital mortality.