Obstructive Urosepsis: Is It Possible to Personalize the Ureteral Endoscopic Treatment?

INTRODUCTION: Urinary tract infection involves mortality rate when combined with ureteral obstruction. Lithotripsy has been contraindicated; however, it has been shown to be safe in selected situations. No specific criteria have been widely accepted to indicate which patients are suitable for definitive treatment. The objective of this study was to identify prognostic factors associated with poor outcome but also those patients whose definitive treatment can be performed. METHODS: Observational cohort study from a prospectively maintained database of septic patients defined by the Sequential Organ Failure Assessment (SOFA). Univariate analysis was used to compare prognostic factors with Δ-SOFA score <2 (group 1) and those with a Δ-SOFA ≥2 (group 2) obtained on day 3 and on admission. Different combinations of neutrophils, lymphocytes and platelets were tested as prognostic factors. Time to decompression calculated from the CT scan report to the end of surgery. RESULTS: A total of 229 patients were enrolled during 11 years. Two patients died. Time from CT scan to urinary tract decompression was higher in the Δ-SOFA≥2 (p = 0.04). Thrombocytopenia and the platelet-to-lymphocyte ratio were associated with Δ-SOFA≥2. Stones were disintegrated in 33.48% in group 1 and 48.84% in group 2. Platelet count and time to decompression were associated with a worse prognosis (p = 0.0008 and 0.0017). On receiver operator curve analysis, platelets count <105,056 and time to decompression >4.72 hours were linked to poorer outcomes. CONCLUSIONS: Personalized treatment, based on accessible biomarkers, can be achieved in most patients. Early surgical decompression was associated with better prognosis and definitive treatment can be performed in selected patients.

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.

A simple bedside approach to therapeutic goals achievement during the management of deceased organ donors--An adapted version of the "VIP" approach.

The disproportion between the supply and demand of transplant organs could be alleviated by improving the quality of clinical management of deceased potential donors. As a large number of donor losses by cardiac arrest occur due to hemodynamic instability, without instituting all essential maintenance measures, it is likely that the application of simplified potential donor maintenance protocols will help to decrease potential donor losses and increase the supply of organs for transplantation. The Ventilation, Infusion and Pumping (VIP) strategy is a mnemonic method that brings together key aspects of the restoration of oxygen delivery to tissues during hemodynamic instability: adequate mechanical Ventilation, volume Infusion and evaluation of heart Pump effectiveness. The inclusion of the additional initials, "P" and "S," refers to Pharmacological treatment and Specificities involved in the etiology of shock. The use of simplified care standards can assist in adhering to essential potential donor management measures. Therefore, using a simplified method as the adapted VIP approach can contribute to improving management standards of potential organ donors and increasing the supply of organs for transplantation.

The effect of brain death protocol duration on potential donor losses due to cardiac arrest.

BACKGROUND: The severe inflammatory reaction that occurs after brain death (BD) tends to amplify over time, contributing to cardiovascular deterioration and occurrence of cardiac arrest (CA). Our purpose is to evaluate the effect of BD protocol duration (BDPD) on potential donor losses due to CA. METHODS: This retrospective analysis included potential donors reported during the period from May 2012 to April 2014. The risk of losses due to CA was analyzed to identify the chronological threshold at which the probability of loss due to CA increases. RESULTS: Three hundred and eighty-four potential donors were analyzed. There was a greater chance of CA after a 30-hour threshold (OR 1.67, 95% CI: 1.38-1.83), and the lowest risk of was identified for the range from 12 to 30 hours (OR 0.32, 95% CI: 0.19-0.52). Multivariate analysis identified the following variables as being associated with lower occurrence of CA: BDPD between 12 and 30 hours, management of a potential donor inside the intensive care unit, and the adherence to a goal-directed protocol. CONCLUSION: A long duration between the first clinical test for BD diagnosis and the procurement of organs may be an important risk factor for the occurrence of cardiac arrest in deceased potential donors.

Effect of Reintubation Within 48 Hours on Mortality in Critically Ill Patients After Planned Extubation.

BACKGROUND: Re-intubation is necessary in 2% to 30% of cases of patients receiving a planned extubation. This procedure is associated with prolonged mechanical ventilation, a greater need for tracheostomy, a higher incidence of ventilator-associated pneumonia, and higher mortality. The aim of this study was to evaluate the effect of re-intubation within 48 h on mortality after planned extubation by using a randomized controlled trial database. METHODS: Secondary analysis of a multi-center randomized trial, which evaluated the effect of reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial, followed by extubation. The study included adult subjects who received invasive mechanical ventilation for > 12 h. The subjects were divided into an extubation failure group and an extubation success group. The outcome was in-hospital mortality. Two multivariate logistic regression models were constructed to identify independent factors associated with mortality. RESULTS: Among the 336 subjects studied, extubation failed in 52 (15.4%) and they were re-intubated within 48 h. Most re-intubations occurred between 12 and 24 h after planned extubation (median [interquartile range] 16 [6-36] h). Mortality of the extubation failure group was higher both in the ICU (32.6% vs 6.6%; odds ratio [OR] 6.77, 95% CI 3.22-14.24; P < .001) and in-hospital (42.3% vs 14.0%; OR 4.47, 95% CI 2.34-8.51; P < .001) versus the extubation success group. Multivariate logistic regression analyses showed that re-intubation within 48 h was independently associated with both ICU mortality (OR 6.10, 95% CI 2.84-13.07; P < .001) and in-hospital mortality (OR 3.36, 95% CI 1.67-6.73; P = .001). In-hospital mortality was also associated with rescue noninvasive ventilation after extubation (OR 2.44, 95% CI 1.25-4.75; P = .009). CONCLUSIONS: Re-intubation within 48 h after planned extubation was associated with mortality in subjects who were critically ill.

Identification of distinct phenotypes and improving prognosis using metabolic biomarkers in COVID-19 patients.

OBJECTIVE: To investigate the relationship between the levels of adipokines and other endocrine biomarkers and patient outcomes in hospitalized patients with COVID-19. METHODS: In a prospective study that included 213 subjects with COVID-19 admitted to the intensive care unit, we measured the levels of cortisol, C-peptide, glucagon-like peptide-1, insulin, peptide YY, ghrelin, leptin, and resistin.; their contributions to patient clustering, disease severity, and predicting in-hospital mortality were analyzed. RESULTS: Cortisol, resistin, leptin, insulin, and ghrelin levels significantly differed between severity groups, as defined by the World Health Organization severity scale. Additionally, lower ghrelin and higher cortisol levels were associated with mortality. Adding biomarkers to the clinical predictors of mortality significantly improved accuracy in determining prognosis. Phenotyping of subjects based on plasma biomarker levels yielded two different phenotypes that were associated with disease severity, but not mortality. CONCLUSION: As a single biomarker, only cortisol was independently associated with mortality; however, metabolic biomarkers could improve mortality prediction when added to clinical parameters. Metabolic biomarker phenotypes were differentially distributed according to COVID-19 severity but were not associated with mortality.

The respiratory oxygenation index for identifying the risk of orotracheal intubation in COVID-19 patients receiving high-flow nasal cannula oxygen.

OBJECTIVE: To assess whether the respiratory oxygenation index (ROX index) measured after the start of high-flow nasal cannula oxygen therapy can help identify the need for intubation in patients with acute respiratory failure due to coronavirus disease 2019. METHODS: This retrospective, observational, multicenter study was conducted at the intensive care units of six Brazilian hospitals from March to December 2020. The primary outcome was the need for intubation up to 7 days after starting the high-flow nasal cannula. RESULTS: A total of 444 patients were included in the study, and 261 (58.7%) were subjected to intubation. An analysis of the area under the receiver operating characteristic curve (AUROC) showed that the ability to discriminate between successful and failed high-flow nasal cannula oxygen therapy within 7 days was greater for the ROX index measured at 24 hours (AUROC 0.80; 95%CI 0.76 - 0.84). The median interval between high-flow nasal cannula initiation and intubation was 24 hours (24 - 72), and the most accurate predictor of intubation obtained before 24 hours was the ROX index measured at 12 hours (AUROC 0.75; 95%CI 0.70 - 0.79). Kaplan-Meier curves revealed a greater probability of intubation within 7 days in patients with a ROX index ≤ 5.54 at 12 hours (hazard ratio 3.07; 95%CI 2.24 - 4.20) and ≤ 5.96 at 24 hours (hazard ratio 5.15; 95%CI 3.65 - 7.27). CONCLUSION: The ROX index can aid in the early identification of patients with acute respiratory failure due to COVID-19 who will progress to the failure of high-flow nasal cannula supportive therapy and the need for intubation.

Antisense therapy to block the Kallikrein-kinin pathway in COVID-19: The ASKCOV randomized controlled trial.

PURPOSE: To assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients. MATERIAL AND METHODS: Randomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use. Patients were randomized to either one subcutaneous dose of ISIS721744, an antisense that blocks prekallikrein, or placebo. The primary outcome was the number of days alive and free of oxygen support up to 15 days (DAFOR15). Secondary endpoints included organ failure score, need and duration of mechanical ventilation up to 15 days, and all-cause mortality at 30 days. Exploratory endpoints included physiological parameters, biomarkers, and quality of life. RESULTS: From October 10, 2020, to December 09, 2020, 111 patients were randomized at thirteen sites in Brazil (56 to treatment and 55 to control group). Average age was 57.5 years, and most patients were male (68.5%). There were no significant differences in DAFOR15 between groups (5.9 ± 5.2 days for the intervention arm and 7.7 ± 5.1 for the control group; mean difference - 0.65, 95% confidence intervals from -2.95 to 1.36, p = 0.520). CONCLUSION: Antisense therapy designed to block the kallikrein-kinin pathway did not demonstrate clinical benefits in increasing days-alive without respiratory support at 15 days in patients with COVID-19 during the first wave in 2020. GOV IDENTIFIER: NCT04549922.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan.

BACKGROUND: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. OBJECTIVE: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. METHODS: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. OUTCOMES: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. CONCLUSION: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

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.

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.

Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial.

INTRODUCTION: Patients undergoing mechanical ventilation (MV) are frequently administered prolonged and/or high doses of opioids which when removed can cause a withdrawal syndrome and difficulty in weaning from MV. We tested the hypothesis that the introduction of enteral methadone during weaning from sedation and analgesia in critically ill adult patients on MV would decrease the weaning time from MV. METHODS: A double-blind randomized controlled trial was conducted in the adult intensive care units (ICUs) of four general hospitals in Brazil. The 75 patients, who met the criteria for weaning from MV and had been using fentanyl for more than five consecutive days, were randomized to the methadone (MG) or control group (CG). Within the first 24 hours after study enrollment, both groups received 80% of the original dose of fentanyl, the MG received enteral methadone and the CG received an enteral placebo. After the first 24 hours, the MG received an intravenous (IV) saline solution (placebo), while the CG received IV fentanyl. For both groups, the IV solution was reduced by 20% every 24 hours. The groups were compared by evaluating the MV weaning time and the duration of MV, as well as the ICU stay and the hospital stay. RESULTS: Of the 75 patients randomized, seven were excluded and 68 were analyzed: 37 from the MG and 31 from the CG. There was a higher probability of early extubation in the MG, but the difference was not significant (hazard ratio: 1.52 (95% confidence interval (CI) 0.87 to 2.64; P = 0.11). The probability of successful weaning by the fifth day was significantly higher in the MG (hazard ratio: 2.64 (95% CI: 1.22 to 5.69; P < 0.02). Among the 54 patients who were successfully weaned (29 from the MG and 25 from the CG), the MV weaning time was significantly lower in the MG (hazard ratio: 2.06; 95% CI 1.17 to 3.63; P < 0.004). CONCLUSIONS: The introduction of enteral methadone during weaning from sedation and analgesia in mechanically ventilated patients resulted in a decrease in the weaning time from MV.

[Analysis of quality of life following hospital discharge among survivors of severe sepsis and septic shock]. / Análise da qualidade de vida após a alta hospitalar em sobreviventes de sepse grave e choque séptico.

OBJECTIVE: Describe the impact of severe sepsis and septic shock on patients' quality of life following hospital discharge. METHODS: A controlled study conducted in two general hospitals of Joinville, Santa Catarina, Brazil, of in-patients with severe sepsis or septic shock during the period of August 2005 through November 2007. The patients were contacted by telephone between June and November 2009. The study group responded to Short Form-36, a questionnaire on the quality of life, two years after being discharged from hospital. The questionnaire was also answered by a control group composed of people who lived at the same residence as the study subjects, had no recent hospitalization, and were close in age. RESULTS: Of 217 patients with severe sepsis or septic shock, 112 (51.6%) survived hospitalization. The survival rate after hospital discharge was 41.02% at 180 days, 37.4% at one year, 34.3% at 18 months, and 32.3% in two years. Thirty-six survivors responded to Short Form-36. There were declines in the quality of life for survivors (No. = 36) in comparison to the control group (No. = 36) in the following areas: physical functioning (59 ± 32 versus 91 ± 18; P < 0.001), vitality (48 ± 13 versus 59 ± 14; P < 0.008), mental health (48 ± 13 versus 59 ± 14; P < 0.03), bodily pain (50 ± 26 versus 76 ± 16; P < 0.001), general health perceptions (53 ± 18 versus 67 ± 13; P < 0.004), physical role functioning (67 ± 45 versus 85 ± 34; P < 0.05), and social role functioning (70 ± 28 versus 90. ± 16; P < 0.05). CONCLUSIONS: Severe sepsis or septic shock can result in significant negative effects on the quality of life, in addition to reducing long-term survival probability.

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.

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.

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.

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.

Use of CPAP as an alternative to the apnea test during the determination of brain death in hypoxemic patients. Report of two cases. / Uso da CPAP como alternativa para realização do teste de apneia durante determinação da morte encefálica em pacientes hipoxêmicos. Relato de dois casos.

The apnea test, which involves disconnection from the mechanical ventilator, presents risks during the determination of brain death, especially in hypoxemic patients. We describe the performance of the apnea test without disconnection from the mechanical ventilator in two patients. The first case involved an 8-year-old boy admitted with severe hypoxemia due to pneumonia. He presented with cardiorespiratory arrest, followed by unresponsive coma due to hypoxic-ischemic encephalopathy. Two clinical exams revealed the absence of brainstem reflexes, and transcranial Doppler ultrasound revealed brain circulatory arrest. Three attempts were made to perform the apnea test, which were interrupted by hypoxemia; therefore, the apnea test was performed without disconnection from the mechanical ventilator, adjusting the continuous airway pressure to 10cmH2O and the inspired fraction of oxygen to 100%. The oxygen saturation was maintained at 100% for 10 minutes. Posttest blood gas analysis results were as follows: pH, 6.90; partial pressure of oxygen, 284.0mmHg; partial pressure of carbon dioxide, 94.0mmHg; and oxygen saturation, 100%. The second case involved a 43-year-old woman admitted with subarachnoid hemorrhage (Hunt-Hess V and Fisher IV). Two clinical exams revealed unresponsive coma and absence of all brainstem reflexes. Brain scintigraphy showed no radioisotope uptake into the brain parenchyma. The first attempt at the apnea test was stopped after 5 minutes due to hypothermia (34.9°C). After rewarming, the apnea test was repeated without disconnection from the mechanical ventilator, showing maintenance of the functional residual volume with electrical bioimpedance. Posttest blood gas analysis results were as follows: pH, 7.01; partial pressure of oxygen, 232.0mmHg; partial pressure of carbon dioxide, 66.9mmHg; and oxygen saturation, 99.0%. The apnea test without disconnection from the mechanical ventilator allowed the preservation of oxygenation in both cases. The use of continuous airway pressure during the apnea test seems to be a safe alternative in order to maintain alveolar recruitment and oxygenation during brain death determination.

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.