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.

Customization and external validation of the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU) in Brazilian critically ill patients.

PURPOSE: To customize and externally validate the recently proposed Simplified Mortality Score for the ICU (SMS-ICU, a simple score for 90-day mortality that has no need for ancillary testing results) for in-hospital mortality and to compare its performance to SAPS 3. MATERIAL AND METHODS: We used data from two distinct large cohorts of adult Brazilian patients with unplanned ICU admissions to perform a first-level customization (43,017 patients admitted to 78 ICUs) of the original SMS-ICU score for in-hospital mortality and, sequentially, externally validate it (313,365 patients admitted to 99 ICUs). Performance of SMS-ICU was assessed through measurements of discrimination and calibration and compared with SAPS 3. RESULTS: In the validation cohort, median SMS-ICU was 13 (IQR 8-16) points and median SAPS 3 was 44 (IQR 36-51). Discrimination of SMS-ICU was good (AUC 0.817; 95% CI 0.814-0.819) but slightly lower than of SAPS 3 (AUC 0.845; 95% CI 0.843-0.848;). The customized SMS-ICU predictions were comparable to SAPS 3 in terms of calibration. CONCLUSION: In this external validation of the SMS-ICU in a large Brazilian cohort, we observed good discrimination of SMS-ICU and acceptable calibration after first-level customization. SMS-ICU can be used as a measure of illness severity for acutely admitted ICU patients in clinical studies.

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.

Effect of Increasing Blood Pressure With Noradrenaline on the Microcirculation of Patients With Septic Shock and Previous Arterial Hypertension.

OBJECTIVES: To assess whether an increase in mean arterial pressure in patients with septic shock and previous systemic arterial hypertension changes microcirculatory and systemic hemodynamic variables compared with patients without arterial hypertension (control). DESIGN: Prospective, nonblinded, interventional study. SETTING: Three ICUs in two teaching hospitals. PATIENTS: After informed consent, we included patients older than 18 years with septic shock for at least 6 hours, sedated, and under mechanical ventilation. We paired patients with and without arterial hypertension by age. INTERVENTIONS: After obtaining systemic and microcirculation baseline hemodynamic variables (time 0), we increased noradrenaline dose to elevate mean arterial pressure up to 85-90 mm Hg before collecting a new set of measurements (time 1). MEASUREMENTS AND MAIN RESULTS: We included 40 patients (20 in each group). There was no significant difference in age between the groups. After the rise in mean arterial pressure, there was a significant increase in cardiac index and a slight but significant reduction in lactate in both groups. We observed a significant improvement in the proportion of perfused vessels (control: 57.2 ± 14% to 66 ± 14.8%; arterial hypertension: 61.4 ± 12.3% to 70.8 ± 7.1%; groups: p = 0.29; T0 and T1: p < 0.001; group and time interaction: p = 0.85); perfused vessels density (control: 15.6 ± 4 mm/mm to 18.6 ± 4.5 mm/mm; arterial hypertension: 16.4 ± 3.5 mm/mm to 19.1 ± 3 mm/mm; groups: p = 0.51; T0 and T1: p < 0.001; group and time interaction: p = 0.70), and microcirculatory flow index (control: 2.1 ± 0.6 to 2.4 ± 0.6; arterial hypertension: 2.1 ± 0.5 to 2.6 ± 0.2; groups: p = 0.71; T0 and T1: p = 0.002; group and time interaction: p = 0.45) in both groups. CONCLUSIONS: Increasing mean arterial pressure with noradrenaline in septic shock patients improves density and flow in small vessels of sublingual microcirculation. However, this improvement occurs both in patients with previous arterial hypertension and in those without arterial hypertension.

Clinical Features of Kidney Transplant Recipients Admitted to the Intensive Care Unit.

INTRODUCTION: There is a paucity of data regarding the complications in kidney transplant patients who may require intensive care unit (ICU) management, despite being the most common solid organ transplant worldwide. OBJECTIVE: To identify the main reasons for ICU admission and to determine the factors associated with hospital mortality in kidney transplant recipients. DESIGN: This single-center retrospective cohort study was conducted between September 2013 and June 2014, including all consecutive kidney transplant patients requiring ICU admission. We collected data on patient demographics, transplant characteristics, clinical data, and prognostic scores. The independent determinants of hospital mortality were identified by multiple logistic regression analysis. We also assessed the performance of Simplified Acute Physiology Score 3 (SAPS 3) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. RESULTS: We analyzed data from 413 patients, the majority of whom were admitted late after renal transplantation (1169 days; 63-3003 days). The main reason for admission was sepsis (33.2%), followed by cardiovascular disease (16%). Age (odds ratio [OR] 1.05, confidence interval [CI], 1.01-1.09), SAPS 3 score (OR 1.04, CI, 1.01-1.08), the need for mechanical ventilation (OR 26.47, CI, 10.30-68.08), and vasopressor use (OR 3.34, CI, 1.37-8.13) were independently associated with hospital mortality. The performance of SAPS 3 and APACHE II scores was poor in this population and overestimated the mortality rates. CONCLUSION: Sepsis was the main reason for ICU admission in kidney transplant recipients, followed by cardiovascular disease. Age and disease severity were associated with hospital mortality.

Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline

OBJECTIVES: To assess the impact of vasopressin on the microcirculation and to develop a predictive model to estimate the probability of microcirculatory recruitment in patients with septic shock. METHODS: This prospective interventional study included patients with septic shock receiving noradrenaline for less than 48 hours. We infused vasopressin at 0.04 U/min for one hour. Hemodynamic measurements, including sidestream dark-field imaging, were obtained immediately before vasopressin infusion, 1 hour after vasopressin infusion and 1 hour after vasopressin withdrawal. We defined patients with more than a 10% increase in total vascular density and perfused vascular density as responders. ClinicalTrials.gov: NCT02053675. RESULTS: Eighteen patients were included, and nine (50%) showed improved microcirculation after infusion of vasopressin. The noradrenaline dose was significantly reduced after vasopressin (p=0.001) and was higher both at baseline and during vasopressin infusion in the responders than in the non-responders. The strongest predictor for a favorable microcirculatory response was the dose of noradrenaline at baseline (OR=4.5; 95% CI: 1.2-17.0; p=0.027). For patients using a noradrenaline dose higher than 0.38 mcg/kg/min, the probability that microcirculatory perfusion would be improved with vasopressin was 53% (sensitivity 78%, specificity 77%). CONCLUSIONS: In patients with septic shock for no longer than 48 h, administration of vasopressin is likely to result in an improvement in microcirculation when the baseline noradrenaline dose is higher than 0.38 mcg/kg/min.

Prevalência de doença por citomegalovírus em transplantados renais em unidade de terapia intensiva / Prevalence of cytomegalovirus disease in kidney transplant patients in an intensive care unit

RESUMO Objetivos: Definir frequência de doença por citomegalovírus dentre pacientes transplantados renais na unidade de terapia intensiva nos quais houve a suspeita desta complicação; identificar fatores predisponentes e possível impacto na evolução clínica. Métodos: Estudo retrospectivo observacional, no qual foram incluídos pacientes transplantados renais acima de 18 anos, internados por quaisquer motivos em uma unidade de terapia intensiva, com pelo menos uma coleta de antigenemia ou reação em cadeia da polimerase para citomegalovírus durante internação. Doença por citomegalovírus foi definida por antigenemia positiva ou reação em cadeia da polimerase acima de 500 cópias/mL, na presença de sintomas, no contexto clínico apropriado, conforme julgamento do médico assistente. Resultados: Foram incluídos 99 pacientes (idade: 53,4 ± 12,8 anos, 71,6% homens). A doença por citomegalovírus foi diagnosticada em 39 pacientes (39,4%). Sintomas respiratórios (51%), piora clínica inespecífica (20%) ou sintomas gastrintestinais (14%) foram os principais motivos para coleta de exames. O tempo de transplante foi menor naqueles com doença por citomegalovírus em relação àqueles sem este diagnóstico (6,5 meses e 31,2 meses; p = 0,001), bem como uso de pulsoterapia nos últimos 6 meses (41% e 16,9%; p = 0,008) e uso prévio de timoglobulina no último ano (35,9% e 6,8%; p < 0,001). No modelo de regressão logística, somente o tempo de transplante e o uso de timoglobulina associaram-se à maior frequência de citomegalovírus. Não houve diferença na evolução clínica entre pacientes com ou sem doença por citomegalovírus. Conclusão: Em pacientes transplantados renais com suspeita de doença por citomegalovírus, a prevalência foi alta. O tempo de transplante menor que 6 meses e o uso de timoglobulina no último ano devem aumentar a suspeita do intensivista para esta complicação.

ABSTRACT Objectives: To define the frequency of cytomegalovirus disease among kidney transplant patients in an intensive care unit in which this complication was suspected and to identify predisposing factors and their possible impact on clinical outcome. Methods: Retrospective observational study in which kidney transplant patients over the age of 18 years were hospitalized for any reason in an intensive care unit with at least one collection of samples to test for the presence of antigenemia or cytomegalovirus via polymerase chain reaction during hospitalization. Cytomegalovirus disease was defined as positive antigenemia or polymerase chain reaction above 500 copies/mL in the presence of symptoms and in the appropriate clinical setting, as judged by the attending physician. Results: A total of 99 patients were included (age: 53.4 ± 12.8 years, 71.6% male). Cytomegalovirus disease was diagnosed in 39 patients (39.4%). Respiratory symptoms (51%), non-specific clinical worsening (20%) or gastrointestinal symptoms (14%) were the main reasons for exam collection. Transplant time was lower in those with cytomegalovirus disease than in those without this diagnosis (6.5 months and 31.2 months, p = 0.001), along with pulse therapy in the last 6 months (41% and 16.9%, p = 0.008) and previous use of thymoglobulin in the last year (35.9% and 6.8%, p < 0.001). In the logistic regression model, only the transplant time and the use of thymoglobulin were associated with a higher frequency of cytomegalovirus. There was no difference in clinical evolution between patients with and without cytomegalovirus disease. Conclusion: In kidney transplant patients suspected of cytomegalovirus disease, the prevalence was high. Transplant time less than 6 months, and the use of thymoglobulin in the last year should increase the intensivist's suspicion for this complication.

Factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit with acute respiratory failure / Fatores associados à mortalidade hospitalar em pacientes com transplante renal admitidos na unidade de terapia intensiva com insuficiência respiratória aguda

Abstract Introduction: The lungs are often involved in a variety of complications after kidney transplantation. Acute respiratory failure (ARF) is one of the most serious manifestations of pulmonary involvement. Objective: To describe the main causes of ARF in kidney transplant patients who require intensive care and identify the factors associated with mortality. Methods: This retrospective study evaluated adult patients with ARF admitted to the intensive care unit of a center with high volume of transplants from August 2013 to August 2015. Demographic, clinical, and transplant characteristics were analyzed. Multivariate logistic regression analysis was performed to identify factors associated with hospital mortality. Results: 183 patients were included with age of 55.32 ± 13.56 years. 126 (68.8%) were deceased-donor transplant, and 37 (20.2%) patients had previous history of rejection. The ICU admission SAPS3 and SOFA score were 54.39 ± 10.32 and 4.81 ± 2.32, respectively. The main cause of hospitalization was community-acquired pneumonia (18.6%), followed by acute pulmonary edema (15.3%). Opportunistic infections were common: PCP (9.3%), tuberculosis (2.7%), and cytomegalovirus (2.2%). Factors associated with mortality were requirement for vasopressor (OD 8.13, CI 2.83 to 23.35, p < 0.001), invasive mechanical ventilation (OD 3.87, CI: 1.29 to 11.66, p = 0.016), and SAPS3 (OD 1.04, CI 1.0 to 1.08, p = 0.045). Conclusion: Bacterial pneumonia is the leading cause of ARF requiring intensive care, followed by acute pulmonary edema. Requirement for vasopressor, invasive mechanical ventilation and SAP3 were associated with hospital mortality.

Resumo Introdução: Os pulmões são frequentemente envolvidos em uma variedade de complicações após o transplante renal. A insuficiência respiratória aguda (IRA) é uma das manifestações mais graves do envolvimento pulmonar. Objetivo: Descrever as principais causas de IRA em pacientes transplantados de rim que necessitaram de cuidados intensivos e identificar os fatores associados à mortalidade. Métodos: Estudo retrospectivo que avaliou pacientes adultos com diagnóstico de insuficiência respiratória aguda internados na unidade de terapia intensiva (UTI) de um centro com alto volume de transplantes, no período de agosto de 2013 a agosto de 2015. Dados demográficos, clínicos e características do transplante foram analisados. Análise de regressão logística multivariada foi realizada para identificar os fatores associados a mortalidade hospitalar. Resultados: Foram incluídos 183 pacientes com idade de 55,32 ± 13,56 anos. 126 (68,8%) receberam rim de doador falecido e 37 (20,2%) tiveram histórico prévio de rejeição. O SAPS3 de admissão na UTI foi de 54,39 ± 10,32 e o SOFA de 4,81 ± 2,32. A principal causa de internação foi pneumonia comunitária (18,6%), seguida de edema agudo de pulmão (15,3%). Infecções oportunistas foram comuns, como pneumocistose (9,3%), tuberculose (2,7%) e citomegalovírus (2,2%). Os fatores associados a mortalidade foram necessidade de vasopressor (OD 8,13, IC 2,83-23,35, p < 0,001), ventilação mecânica invasiva (OD 3,87, IC: 1,29-11,66, p = 0,016) e SAPS3 (OD 1,04, IC 1,0-1,08, p = 0,045). Conclusão: Pneumonia bacteriana foi a principal causa de insuficiência respiratória aguda com necessidade de cuidados intensivos, seguida por edema agudo de pulmão. Necessidade de vasopressor, ventilação mecânica invasiva e SAP3 foram associados a mortalidade.

Short-term effects of passive mobilization on the sublingual microcirculation and on the systemic circulation in patients with septic shock.

BACKGROUND: Active mobilization is not possible in patients under deep sedation and unable to follow commands. In this scenario, passive therapy is an interesting alternative. However, in patients with septic shock, passive mobilization may have risks related to increased oxygen consumption. Our objective was to evaluate the impact of passive mobilization on sublingual microcirculation and systemic hemodynamics in patients with septic shock. METHODS: We included patients who were older than 18 years, who presented with septic shock, and who were under sedation and mechanical ventilation. Passive exercise was applied for 20 min with 30 repetitions per minute. Systemic hemodynamic and microcirculatory variables were compared before (T0) and up to 10 min after (T1) passive exercise. p values <0.05 were considered significant. RESULTS: We included 35 patients (median age [IQR 25-75%]: 68 [49.0-78.0] years; mean (±SD) Simplified Acute Physiologic Score (SAPS) 3 score: 66.7 ± 12.1; median [IQR 25-75%] Sequential Organ Failure Assessment (SOFA) score: 9 [7.0-12.0]). After passive mobilization, there was a slight but significant increase in proportion of perfused vessels (PPV) (T0 [IQR 25-75%]: 78.2 [70.9-81.9%]; T1 [IQR 25-75%]: 80.0 [75.2-85.1] %; p = 0.029), without any change in other microcirculatory variables. There was a reduction in heart rate (HR) (T0 (mean ± SD): 95.6 ± 22.0 bpm; T1 (mean ± SD): 93.8 ± 22.0 bpm; p < 0.040) and body temperature (T0 (mean ± SD): 36.9 ± 1.1 °C; T1 (mean ± SD): 36.7 ± 1.2 °C; p < 0.002) with no change in other systemic hemodynamic variables. There was no significant correlation between PPV variation and HR (r = -0.010, p = 0.955), cardiac index (r = 0.218, p = 0.215) or mean arterial pressure (r = 0.276, p = 0.109) variation. CONCLUSIONS: In patients with septic shock after the initial phase of hemodynamic resuscitation, passive exercise is not associated with relevant changes in sublingual microcirculation or systemic hemodynamics.

Effects of the positive end-expiratory pressure increase on sublingual microcirculation in patients with acute respiratory distress syndrome / Efeitos do aumento de pressão positiva ao final da expiração sobre a microcirculação sublingual em pacientes com síndrome do desconforto respiratório agudo

Abstract Objective: The aim of this study was to evaluate the impact of increased positive end-expiratory pressure on the sublingual microcirculation. Methods: Adult patients who were sedated, under mechanical ventilation, and had a diagnosis of circulatory shock and acute respiratory distress syndrome were included. The positive end-expiratory pressure level was settled to obtain a plateau pressure of 30 cm H2O and then maintained at this level for 20 minutes. Microcirculatory (obtained by videomicroscopy) and hemodynamic variables were collected at baseline and compared with those at the end of 20 min. Results: Twelve patients were enrolled. Overall, the microcirculation parameters did not significantly change after increasing the positive end-expiratory pressure. However, there was considerable interindividual variability. There was a negative, moderate correlation between the changes in the De Backer score (r = -0.58, p = 0.048), total vessel density (r = -0.60, p = 0.039) and baseline values. The changes in total vessel density (r = 0.54, p = 0.07) and perfused vessel density (r = 0.52, p = 0.08) trended toward correlating with the changes in the mean arterial pressure. Conclusion: Overall, the microcirculation parameters did not significantly change after increasing the positive end-expiratory pressure. However, at individual level, such response was heterogeneous. The changes in the microcirculation parameters could be correlated with the baseline values and changes in the mean arterial pressure.

Resumo Objetivo: O objetivo deste estudo foi avaliar o impacto do aumento de pressão positiva no fim da expiração (PEEP) sobre a microcirculação sublingual. Métodos: Os pacientes adultos que foram sedados, sob ventilação mecânica, com diagnóstico de choque circulatório e síndrome do desconforto respiratório agudo foram incluídos. O nível da PEEP foi estabelecido para obter uma pressão de platô de 30 cmH2O e depois mantido nesse nível por 20 minutos. As variáveis de microcirculação (obtida por microscopia de vídeo) e hemodinâmica foram registradas na fase basal e comparadas com aquelas no fim de 20 min. Resultados: Doze pacientes foram incluídos. Em geral, os parâmetros da microcirculação não apresentaram alterações significativas após o aumento da PEEP. Porém, houve considerável variabilidade interindividual. Houve uma correlação negativa, moderada, entre as alterações no escore de De Backer (r = -0,58, p = 0,048), na densidade total do vaso (r = -0,60, p = 0,039) e nos valores basais. As alterações na densidade total do vaso (r = 0,54, p = 0,07) e na densidade do vaso perfundido (r = 0,52, p = 0,08) apresentaram tendência de correlação com as alterações na pressão arterial média. Conclusão: Em geral, os parâmetros da microcirculação não apresentaram alterações significativas após o aumento da PEEP. No entanto, individualmente, essa resposta foi heterogênea. As alterações nos parâmetros da microcirculação puderam ser correlacionadas com os valores basais e alterações na pressão arterial média.

[Effects of the positive end-expiratory pressure increase on sublingual microcirculation in patients with acute respiratory distress syndrome]. / Efeitos do aumento de pressão positiva ao final da expiração sobre a microcirculação sublingual em pacientes com síndrome do desconforto respiratório agudo.

OBJECTIVE: The aim of this study was to evaluate the impact of increased positive end-expiratory pressure on the sublingual microcirculation. METHODS: Adult patients who were sedated, under mechanical ventilation, and had a diagnosis of circulatory shock and acute respiratory distress syndrome were included. The positive end-expiratory pressure level was settled to obtain a plateau pressure of 30cmH2O and then maintained at this level for 20minutes. Microcirculatory (obtained by videomicroscopy) and hemodynamic variables were collected at baseline and compared with those at the end of 20min. RESULTS: Twelve patients were enrolled. Overall, the microcirculation parameters did not significantly change after increasing the positive end-expiratory pressure. However, there was considerable interindividual variability. There was a negative, moderate correlation between the changes in the De Backer score (r=-0.58, p=0.048), total vessel density (r=-0.60, p=0.039) and baseline values. The changes in total vessel density (r=0.54, p=0.07) and perfused vessel density (r=0.52, p=0.08) trended toward correlating with the changes in the mean arterial pressure. CONCLUSION: Overall, the microcirculation parameters did not significantly change after increasing the positive end-expiratory pressure. However, at individual level, such response was heterogeneous. The changes in the microcirculation parameters could be correlated with the baseline values and changes in the mean arterial pressure.

The diagnostic yield and complications of open lung biopsies in kidney transplant patients with pulmonary disease.

BACKGROUND: The purpose of this study was to assess the efficacy of open lung biopsy (OLB) in determining the specific diagnosis and the related complications in patients with undiagnosed diffuse pulmonary infiltrates. METHODS: This single center, retrospective study included adult kidney transplant patients who underwent OLB. The patients had diffuse pulmonary infiltrates without definitive diagnoses and failed to respond to empiric antibiotic treatment. We analyzed the number of specific diagnoses, changes in treatment and the occurrence of complications in these patients. A logistic regression was used to determine which variables were predictors of hospital mortality. RESULTS: From April 2010 to April 2014, 87 patients consecutively underwent OLB. A specific diagnosis was reached in 74 (85.1%) patients. In 46 patients (53%), their therapeutic management was changed after the OLB results. Twenty-five (28.7%) patients had complications related to the OLB. The hospital mortality rate was 25.2%. Age, SAPS3 score and complications related to the procedure were independent predictors of all-cause mortality. CONCLUSIONS: OLB is a high-risk procedure with a high diagnostic yield in kidney transplant patients with diffuse pulmonary infiltrates who did not have a definitive diagnosis and who failed to respond to empiric antibiotic treatment. Complications related to OLB were common and were independently associated with intra-hospital mortality.

Sepsis in Solid-Organ Transplant Patients.

The growing population of solid organ transplant (SOT) recipients is at a significantly increased risk for developing infections. In some patients, the infection can lead to a dysregulated systemic inflammatory response with acute organ dysfunction. SOT recipients with sepsis tend to have less fever and leukocytosis instances. Moreover, they have diminished symptoms and attenuated clinical and radiologic findings. The current management of sepsis is similar to general patients. It relies mainly on early recognition and treatment, including appropriate administration of antibiotics and resuscitation with intravenous fluids and vasoactive drugs when needed. The infusion of fluids should be closely monitored because elevated central venous pressure levels and fluid overload can be particularly harmful. There is no consensus on how to manage immunosuppressive therapies during sepsis, although dose reduction or withdrawal is suggested to improve the host immunological response. There is compelling evidence suggesting that infections are associated with reduced allograft and patient survival. However, the traditional belief that SOT patients who develop sepsis have worse outcomes than non-transplanted patients has been challenged.

Prevalence of cytomegalovirus disease in kidney transplant patients in an intensive care unit. / Prevalência de doença por citomegalovírus em transplantados renais em unidade de terapia intensiva.

OBJECTIVES: To define the frequency of cytomegalovirus disease among kidney transplant patients in an intensive care unit in which this complication was suspected and to identify predisposing factors and their possible impact on clinical outcome. METHODS: Retrospective observational study in which kidney transplant patients over the age of 18 years were hospitalized for any reason in an intensive care unit with at least one collection of samples to test for the presence of antigenemia or cytomegalovirus via polymerase chain reaction during hospitalization. Cytomegalovirus disease was defined as positive antigenemia or polymerase chain reaction above 500 copies/mL in the presence of symptoms and in the appropriate clinical setting, as judged by the attending physician. RESULTS: A total of 99 patients were included (age: 53.4 ± 12.8 years, 71.6% male). Cytomegalovirus disease was diagnosed in 39 patients (39.4%). Respiratory symptoms (51%), non-specific clinical worsening (20%) or gastrointestinal symptoms (14%) were the main reasons for exam collection. Transplant time was lower in those with cytomegalovirus disease than in those without this diagnosis (6.5 months and 31.2 months, p = 0.001), along with pulse therapy in the last 6 months (41% and 16.9%, p = 0.008) and previous use of thymoglobulin in the last year (35.9% and 6.8%, p < 0.001). In the logistic regression model, only the transplant time and the use of thymoglobulin were associated with a higher frequency of cytomegalovirus. There was no difference in clinical evolution between patients with and without cytomegalovirus disease. CONCLUSION: In kidney transplant patients suspected of cytomegalovirus disease, the prevalence was high. Transplant time less than 6 months, and the use of thymoglobulin in the last year should increase the intensivist's suspicion for this complication.

OBJETIVOS: Definir frequência de doença por citomegalovírus dentre pacientes transplantados renais na unidade de terapia intensiva nos quais houve a suspeita desta complicação; identificar fatores predisponentes e possível impacto na evolução clínica. MÉTODOS: Estudo retrospectivo observacional, no qual foram incluídos pacientes transplantados renais acima de 18 anos, internados por quaisquer motivos em uma unidade de terapia intensiva, com pelo menos uma coleta de antigenemia ou reação em cadeia da polimerase para citomegalovírus durante internação. Doença por citomegalovírus foi definida por antigenemia positiva ou reação em cadeia da polimerase acima de 500 cópias/mL, na presença de sintomas, no contexto clínico apropriado, conforme julgamento do médico assistente. RESULTADOS: Foram incluídos 99 pacientes (idade: 53,4 ± 12,8 anos, 71,6% homens). A doença por citomegalovírus foi diagnosticada em 39 pacientes (39,4%). Sintomas respiratórios (51%), piora clínica inespecífica (20%) ou sintomas gastrintestinais (14%) foram os principais motivos para coleta de exames. O tempo de transplante foi menor naqueles com doença por citomegalovírus em relação àqueles sem este diagnóstico (6,5 meses e 31,2 meses; p = 0,001), bem como uso de pulsoterapia nos últimos 6 meses (41% e 16,9%; p = 0,008) e uso prévio de timoglobulina no último ano (35,9% e 6,8%; p < 0,001). No modelo de regressão logística, somente o tempo de transplante e o uso de timoglobulina associaram-se à maior frequência de citomegalovírus. Não houve diferença na evolução clínica entre pacientes com ou sem doença por citomegalovírus. CONCLUSÃO: Em pacientes transplantados renais com suspeita de doença por citomegalovírus, a prevalência foi alta. O tempo de transplante menor que 6 meses e o uso de timoglobulina no último ano devem aumentar a suspeita do intensivista para esta complicação.

Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline.

OBJECTIVES: To assess the impact of vasopressin on the microcirculation and to develop a predictive model to estimate the probability of microcirculatory recruitment in patients with septic shock. METHODS: This prospective interventional study included patients with septic shock receiving noradrenaline for less than 48 hours. We infused vasopressin at 0.04 U/min for one hour. Hemodynamic measurements, including sidestream dark-field imaging, were obtained immediately before vasopressin infusion, 1 hour after vasopressin infusion and 1 hour after vasopressin withdrawal. We defined patients with more than a 10% increase in total vascular density and perfused vascular density as responders. ClinicalTrials.gov: NCT02053675. RESULTS: Eighteen patients were included, and nine (50%) showed improved microcirculation after infusion of vasopressin. The noradrenaline dose was significantly reduced after vasopressin (p=0.001) and was higher both at baseline and during vasopressin infusion in the responders than in the non-responders. The strongest predictor for a favorable microcirculatory response was the dose of noradrenaline at baseline (OR=4.5; 95% CI: 1.2-17.0; p=0.027). For patients using a noradrenaline dose higher than 0.38 mcg/kg/min, the probability that microcirculatory perfusion would be improved with vasopressin was 53% (sensitivity 78%, specificity 77%). CONCLUSIONS: In patients with septic shock for no longer than 48 h, administration of vasopressin is likely to result in an improvement in microcirculation when the baseline noradrenaline dose is higher than 0.38 mcg/kg/min.

Factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit with acute respiratory failure.

INTRODUCTION: The lungs are often involved in a variety of complications after kidney transplantation. Acute respiratory failure (ARF) is one of the most serious manifestations of pulmonary involvement. OBJECTIVE: To describe the main causes of ARF in kidney transplant patients who require intensive care and identify the factors associated with mortality. METHODS: This retrospective study evaluated adult patients with ARF admitted to the intensive care unit of a center with high volume of transplants from August 2013 to August 2015. Demographic, clinical, and transplant characteristics were analyzed. Multivariate logistic regression analysis was performed to identify factors associated with hospital mortality. RESULTS: 183 patients were included with age of 55.32 ± 13.56 years. 126 (68.8%) were deceased-donor transplant, and 37 (20.2%) patients had previous history of rejection. The ICU admission SAPS3 and SOFA score were 54.39 ± 10.32 and 4.81 ± 2.32, respectively. The main cause of hospitalization was community-acquired pneumonia (18.6%), followed by acute pulmonary edema (15.3%). Opportunistic infections were common: PCP (9.3%), tuberculosis (2.7%), and cytomegalovirus (2.2%). Factors associated with mortality were requirement for vasopressor (OD 8.13, CI 2.83 to 23.35, p < 0.001), invasive mechanical ventilation (OD 3.87, CI: 1.29 to 11.66, p = 0.016), and SAPS3 (OD 1.04, CI 1.0 to 1.08, p = 0.045). CONCLUSION: Bacterial pneumonia is the leading cause of ARF requiring intensive care, followed by acute pulmonary edema. Requirement for vasopressor, invasive mechanical ventilation and SAP3 were associated with hospital mortality.

Comparison between respiratory changes in the inferior vena cava diameter and pulse pressure variation to predict fluid responsiveness in postoperative patients.

PURPOSE: The objective of our study was to assess the reliability of the distensibility index of the inferior vena cava (dIVC) as a predictor of fluid responsiveness in postoperative, mechanically ventilated patients and compare its accuracy with that of the pulse pressure variation (PPV) measurement. MATERIALS AND METHODS: We included postoperative mechanically ventilated and sedated patients who underwent volume expansion with 500mL of crystalloids over 15minutes. A response to fluid infusion was defined as a 15% increase in the left ventricular outflow tract velocity time integral according to transthoracic echocardiography. The inferior vena cava diameters were recorded by a subcostal view using the M-mode and the PPV by automatic calculation. The receiver operating characteristic (ROC) curves were generated for the baseline dIVC and PPV. RESULTS: Twenty patients were included. The area under the ROC curve for dIVC was 0.84 (95% confidence interval, 0.63-1.0), and the best cutoff value was 16% (sensitivity, 67%; specificity, 100%). The area under the ROC curve for PPV was 0.92 (95% confidence interval, 0.76-1.0), and the best cutoff was 12.4% (sensitivity, 89%; specificity, 100%). A noninferiority test showed that dIVC cannot replace PPV to predict fluid responsiveness (P=.28). CONCLUSION: The individual PPV discriminative properties for predicting fluid responsiveness in postoperative patients seemed superior to those of dIVC.

Concentrações séricas de vitamina D e disfunção orgânica em pacientes com sepse grave e choque séptico / Serum concentrations of vitamin D and organ dysfunction in patients with severe sepsis and septic shock

RESUMO Objetivo: Avaliar as concentrações séricas e a variação de vitamina D em pacientes com sepse grave ou choque séptico e indivíduos controles na admissão e após 7 dias de internação na unidade de terapia intensiva, correlacionando-os com a gravidade da disfunção orgânica. Métodos: Estudo caso-controle, prospectivo e observacional em pacientes com mais de 18 anos com sepse grave ou choque séptico pareados com grupo controle. Foi realizada dosagem sérica de vitamina D na inclusão (D0) e no sétimo dia (D7). Definiu-se deficiência grave se vitamina D < 10ng/mL, deficiência se entre 10 e 20ng/mL, insuficiência se entre 20 e 30ng/mL e suficiência se ≥ 30ng/mL. Consideramos melhora a modificação para qualquer classificação mais elevada, associada ao incremento de 50% dos valores absolutos. Resultados: Incluímos 51 pacientes (26 sépticos e 25 controles). A prevalência de concentrações de vitamina D ≤ 30ng/mL foi de 98%. Não houve correlação entre a concentração sérica de vitamina D no D0 e o escore SOFA no D0 ou com sua variação após 7 dias, tanto na população geral quanto nos sépticos. Pacientes com melhora da deficiência tiveram melhora no escore SOFA no D7 (p = 0,013). Conclusão: Na população estudada, os pacientes sépticos apresentaram melhora das concentrações séricas de vitamina D no sétimo dia em comparação com controles. Encontramos associação entre a melhora das concentrações de vitamina D e a maior redução da intensidade de disfunção orgânica.

ABSTRACT Objectives: To evaluate the serum concentrations of vitamin D and their variations in patients with severe sepsis or septic shock and in control subjects upon admission and after 7 days of hospitalization in the intensive care unit and to correlate these concentrations with the severity of organ dysfunction. Methods: This case-control, prospective, observational study involved patients aged > 18 years with severe sepsis or septic shock paired with a control group. Serum vitamin D concentrations were measured at inclusion (D0) and on the seventh day after inclusion (D7). Severe deficiency was defined as vitamin D levels < 10ng/ml, deficiency as levels between 10 and 20ng/ml, insufficiency as levels between 20 and 30ng/ml, and sufficiency as levels ≥ 30ng/mL. We considered a change to a higher ranking, together with a 50% increase in the absolute concentration, to represent an improvement. Results: We included 51 patients (26 with septic shock and 25 controls). The prevalence of vitamin D concentration ≤ 30ng/ml was 98%. There was no correlation between the serum concentration of vitamin D at D0 and the SOFA score at D0 or D7 either in the general population or in the group with septic shock. Patients with improvement in vitamin D deficiency had an improved SOFA score at D7 (p = 0.013). Conclusion: In the population studied, patients with septic shock showed improvement in the serum concentrations of vitamin D on the seventh day compared with the controls. We also found a correlation between higher vitamin D concentrations and a greater decrease in the severity of organ dysfunction.

O sangue venoso coletado do acesso femoral é adequado para estimar a saturação venosa central de oxigênio e os níveis de lactato arterial em pacientes graves? / Is venous blood drawn from femoral access adequate to estimate the central venous oxygen saturation and arterial lactate levels in critically ill patients?

RESUMO Objetivos: Testar se amostras de sangue venoso coletadas do acesso femoral podem ser utilizadas para estimar a saturação venosa central de oxigênio e os níveis de lactato arterial em pacientes graves. Métodos: Foram utilizadas a análise de Bland-Altman e correlações de Spearman para comparar a saturação venosa femoral de oxigênio e a saturação venosa central de oxigênio, assim como os níveis de lactato arterial e femoral. Foi conduzida uma análise predeterminada de subgrupos nos pacientes com sinais de hipoperfusão. Além disso, foi também investigada a concordância clínica. Resultados: Foram obtidas amostras sanguíneas de 26 pacientes. Em 107 amostras pareadas, observou-se correlação moderada (r = 0,686; p < 0,0001) entre a saturação venosa central de oxigênio e a saturação venosa femoral de oxigênio, com um viés de 8,24 ± 10,44 (limites de concordância de 95%: -12,23 a 28,70). Em 102 amostras pareadas, houve forte correlação entre os níveis arteriais de lactato e os níveis de lactato femoral (r = 0,72, p < 0,001) com um viés de -2,71 ± 9,86 (limites de concordância de 95%: -22,3 a 16,61). A presença de hipoperfusão não modificou de forma significante os resultados. A concordância clínica para saturação venosa foi inadequada, com diferentes decisões terapêuticas em 22,4% das situações; para o lactato, isto ocorreu em apenas 5,2% das situações. Conclusão: A saturação venosa de oxigênio femoral não deve ser utilizada em substituição da saturação venosa central de oxigênio. No entanto, os níveis femorais de lactato podem ser utilizados na prática clínica, mas com cautela.

ABSTRACT Objectives: The purpose of this study was to test if venous blood drawn from femoral access can be used to estimate the central venous oxygen saturation and arterial lactate levels in critically ill patients. Methods: Bland-Altman analysis and Spearman correlations were used to compare the femoral venous oxygen saturation and central venous oxygen saturation as well as arterial lactate levels and femoral lactate. A pre-specified subgroup analysis was conducted in patients with signs of hypoperfusion. In addition, the clinical agreement was also investigated. Results: Blood samples were obtained in 26 patients. In 107 paired samples, there was a moderate correlation (r = 0.686, p < 0.0001) between the central venous oxygen saturation and femoral venous oxygen saturation with a bias of 8.24 ± 10.44 (95% limits of agreement: -12.23 to 28.70). In 102 paired samples, there was a strong correlation between the arterial lactate levels and femoral lactate levels (r = 0.972, p < 0.001) with a bias of -2.71 ± 9.86 (95% limits of agreement: -22.03 to 16.61). The presence of hypoperfusion did not significantly change these results. The clinical agreement for venous saturation was inadequate, with different therapeutic decisions in 22.4% of the situation; for lactate, this was the case only in 5.2% of the situations. Conclusion: Femoral venous oxygen saturation should not be used as a surrogate of central venous oxygen saturation. However, femoral lactate levels can be used in clinical practice, albeit with caution.

Is venous blood drawn from femoral access adequate to estimate the central venous oxygen saturation and arterial lactate levels in critically ill patients?

OBJECTIVES: The purpose of this study was to test if venous blood drawn from femoral access can be used to estimate the central venous oxygen saturation and arterial lactate levels in critically ill patients. METHODS: Bland-Altman analysis and Spearman correlations were used to compare the femoral venous oxygen saturation and central venous oxygen saturation as well as arterial lactate levels and femoral lactate. A pre-specified subgroup analysis was conducted in patients with signs of hypoperfusion. In addition, the clinical agreement was also investigated. RESULTS: Blood samples were obtained in 26 patients. In 107 paired samples, there was a moderate correlation (r = 0.686, p < 0.0001) between the central venous oxygen saturation and femoral venous oxygen saturation with a bias of 8.24 ± 10.44 (95% limits of agreement: -12.23 to 28.70). In 102 paired samples, there was a strong correlation between the arterial lactate levels and femoral lactate levels (r = 0.972, p < 0.001) with a bias of -2.71 ± 9.86 (95% limits of agreement: -22.03 to 16.61). The presence of hypoperfusion did not significantly change these results. The clinical agreement for venous saturation was inadequate, with different therapeutic decisions in 22.4% of the situation; for lactate, this was the case only in 5.2% of the situations. CONCLUSION: Femoral venous oxygen saturation should not be used as a surrogate of central venous oxygen saturation. However, femoral lactate levels can be used in clinical practice, albeit with caution.