Utilidad de la proteína C reactiva sérica en el diagnóstico y tratamiento del adulto inmunocompetente hospitalizado por neumonía adquirida en la comunidad / Immunocompetent adults hospitalized for a community-acquired pneumonia: Serum C-reactive protein as a prognostic marker

Background: C-reactive protein (CRP) is used to monitor patients' response during treatment of infectious diseases. Morbidity and mortality associated with community-acquired pneumonia (CAP) is high, particularly in hospitalized patients. Better risk prediction during hospitalization could improve management and ultimately reduce mortality rates. Aim: To evaluate CRP measured at admission and the third day of hospitalization as a predictor for adverse events in CAP. Material and Methods: A prospective cohort study of adult patients hospitalized with CAP at an academic hospital. Major adverse outcomes were admission to ICU, mechanical ventilation, prolonged hospital length of stay, hospital complications and 30-day mortality. Predictive associations between CRP (as absolute levels and relative decline at third day) and adverse events were analyzed. Results: Eight hundred and twenty-three patients were assessed, 19% were admitted to ICU and 10.6% required mechanical ventilation. The average hospital stay was 8.8 ± 8.2 days, 42% had nosocomial complications and 8.1% died within 30 days. Ninety eight percent of patients had elevated serum CRP on admission to the hospital (18.1 ± 14.1 mg/dL). C-reactive protein measured at admission was associated with the risk of bacterial pneumonia, bacteremic pneumonia, septic shock and use of mechanical ventilation. Lack of CRP decline within three days of hospitalization was associated with high risk of complications, septic shock, mechanical ventilation and prolonged hospital stay. Conclusions: CRP responses at third day of hospital admission was a valuable predictor of adverse events in hospitalized CAP adult patients.

Avaliação da interleucina 3 como marcador prognóstico na sepse / Role of interleukin-3 as a prognostic marker in septic patients

RESUMO Objetivo: Avaliar a acurácia dos níveis de interleucina 3 para predizer prognóstico em pacientes sépticos. Métodos: Conduzimos uma coorte prospectiva que incluiu pacientes adultos internados em unidade de terapia intensiva, que apresentassem sepse ou choque séptico iniciados há até 48 horas. Mediram-se os níveis séricos de interleucina 3 quando da inclusão (dia 1) e nos dias 3 e 7. O desfecho primário analisado foi a mortalidade hospitalar por qualquer causa. Resultados: Foram incluídos 120 pacientes. Os níveis séricos de interleucina 3 dosados à inclusão foram significativamente mais elevados em pacientes que faleceram em comparação aos que sobreviveram à internação hospitalar (91,2pg/mL versus 36pg/mL; p = 0,024). Em modelo de sobrevivência de Cox com inclusão de idade e valores sequenciais de SOFA, os níveis de interleucina 3 mensurados na inclusão mantiveram-se independentemente associados à mortalidade hospitalar (HR 1,032; IC95% 1,010 - 1,055; p = 0,005). Em curva Característica de Operação do Receptor construída para investigação adicional da acurácia da interleucina 3 na predição do prognóstico, encontrou-se área sob a curva de 0,62 (IC95% 0,51 - 0,73; p = 0,024) para mortalidade hospitalar. Valores iniciais de interleucina 3 acima de 127,5pg/mL mostraram-se significativamente associados à mortalidade hospitalar (p = 0,019; OR = 2,97; IC95% 1,27 - 6,97; p = 0,019), entretanto com baixo desempenho (especificidade de 82%, sensibilidade de 39%, valor preditivo positivo de 53%, valor preditivo negativo de 72%, razão de verossimilhança negativa de 0,73 e razão de verossimilhança positiva de 2,16). Conclusão: Níveis elevados de interleucina 3 mostraram-se independentemente associados à mortalidade hospitalar em pacientes sépticos, entretanto com baixo desempenho clínico.

ABSTRACT Objective: To evaluate the accuracy of IL-3 to predict the outcome of septic patients. Methods: Prospective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality. Results: One hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio). Conclusion: Higher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

Influence of perfusion status on central and mixed venous oxygen saturation in septic patients / Influência do status perfusional nas saturações venosas de oxigênio central e mista em pacientes sépticos

Abstract Background and objectives Although there is controversy regarding the role of venous oxygen saturation in the initial resuscitation of septic patients with hypoperfusion these markers are still widely used. This study aimed to evaluate the correlation and concordance between central (SvcO2) and mixed (SvO2) oxygen saturation in septic shock patients with or without hypoperfusion in addition to the impact of these differences in patient conduction. Methods Patients with septic shock were monitored with pulmonary artery catheter and the following subgroups of hypoperfusion were analyzed: 1) lactate > 28 mg.dL-1; 2) base excess ≤ -5 mmol.L-1; 3) venoarterial CO2 gradient > 6 mmHg; 4) SvO2 < 65%; 5) SvcO2 < 70%; 6) lactate > 28 mg.dL-1 and SvO2 < 70%; 7) lactate > 28 mg.dL-1 and SvcO2 < 75%. Results Seventy-seven samples from 24 patients were included. There was only a moderate correlation between SvO2 and SvcO2 (r = 0.72, p = 0.0001) and there was no good concordance between these variables (7.35% bias and 95% concordance limits of -3.0% to 17.7%). Subgroup analysis according to the presence of hypoperfusion showed no differences in concordance between variables. There was discordance regarding clinical management in 13.8% (n = 9) of the cases. Conclusions There is a moderate correlation between SvO2 and SvcO2; however, the concordance between them is inadequate. It was not possible to demonstrate that the presence of hypoperfusion alters the concordance between SvO2 and SvcO2. The use of SvO2 instead of SvcO2 may lead to changes in clinical management in a small but clinically relevant portion of patients.

Resumo Justificativa e objetivos Embora haja controvérsias sobre o papel das saturações venosas de oxigênio na ressuscitação inicial do paciente séptico com hipoperfusão, esses marcadores são ainda bastante usados. Este estudo procurou avaliar a correlação e a concordância entre as saturações venosas central (SvcO2) e mista (SvO2) de oxigênio em pacientes com choque séptico, na presença ou não de hipoperfusão, além do impacto dessas diferenças na condução clínica do paciente. Métodos Foram incluídos pacientes com choque séptico monitorados com cateter de artéria pulmonar e analisados os seguintes subgrupos de hipoperfusão: 1) Lactato > 28 mg.dL-1; 2) Excesso de bases ≤ -5 mmoL.L-1; 3) Gradiente venoarterial de CO2 > 6 mmHg; 4) SvO2 < 65%; 5) SvcO2 < 70%; 6) Lactato > 28 mg.dL-1 e SvO2 < 70%; 7) Lactato > 28 mg.dL-1 e SvcO2 < 75%. Resultados Foram incluídas 70 amostras de 24 pacientes. Houve apenas correlação moderada entre SvO2 e SvcO2 (r = 0,72; p = 0,0001) e não houve boa concordância entre essas variáveis (viés de 7,35% e limites de concordância de 95% de -3,0%-17,7%). A análise dos subgrupos de acordo com a presença de hipoperfusão não mostrou diferenças na concordância entre as variáveis. Houve discordância na conduta clínica em 13,8% dos casos (n = 9). Conclusões Existe correlação moderada entre SvO2 e SvcO2, entretanto a concordância entre elas é inadequada. Não foi possível demonstrar que a presença de hipoperfusão altera a concordância entre a entre SvO2 e SvcO2. O uso da SvO2 em vez da SvcO2 pode levar a alterações na conduta clínica numa parcela pequena, porém clinicamente relevante, dos pacientes.

Procalcitonin determined at emergency department as an early indicator of progression to septic shock in patient with sepsis associated with ureteral calculi

ABSTRACT Introduction: To investigate the role of initial procalcitonin (PCT) level as an early predictor of septic shock for the patient with sepsis induced by acute pyelonephritis (APN) secondary to ureteral calculi. Materials and Methods: The data from 49 consecutive patients who met criteria of sepsis due to APN following ureteral stone were collected and divided into two groups: with (n=15) or without (n=34) septic shock. The clinical variables including PCT level for this outcome were retrospectively compared by univariate analysis, followed by multivariable logistic regression model. Results: All subjects had hydronephrosis, and were hospitalized with the mean of 11.8 days (3–42 days). The mean size of the ureteral stones was 7.5mm (3–30mm), and 57% were located in upper ureter. At univariate analysis, patients with septic shock were significantly older, a higher proportion had hypertension, lower platelet count and serum albumin level, higher CRP and PCT level, and higher positive blood culture rate. Multivariate models indicated that lower platelet count and higher PCT level are independent risk factors (p=0.043 and 0.046, respectively). In ROC curve, the AUC was significantly wider in PCT (0.929), compared with the platelet count (0.822, p=0.004). At the cut-off of 0.52ng/mL, the sensitivity and specificity were 86.7% and 85.3%. Conclusion: Our study demonstrated elevated initial PCT levels as an early independent predictor to progress into septic shock in patients with sepsis associated with ureteral calculi.

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.

Nonthyroidal illnesses syndrome in full-term newborns with sepsis

ABSTRACT Objective To assess hormonal changes in nonthyroidal illness syndrome (NTIS) in full-term newborns (NT) with sepsis. Materials and methods We included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A(A), 16 NT with improvement in up to 8 days; and group B(B), 12 NT improvement after 8 days. Among the 28 NT, 15 NT progressed to septic shock, with 5 NT group A and 10 NT in group B. NT were excluded when they showed severe sepsis and asphyxia, and congenital malformations, as well as those whose mothers had thyroid disease and IUGR. Results 17 NT (60.7%) presented NTIS. Low T3 was observed in NTIS in 10 NT (58.8%), and low T4 and T3 in 5 NT (29.5%), all of them with septic shock. Two NT showed mixed changes (11.7%). After sepsis was cured, there was no hormonal change, except in 3 NT. Administration of dopamine, furosemide, and corticosteroids did not affect the results. Conclusions This study indicates that nonthyroidal illness syndrome may be transiently present during sepsis in full-term newborns, especially in cases of prolonged sepsis. Low T3 can occur without changes in reverse T3 (different from adults), and low T4 and T3 occur mainly in patients with septic shock. Arch Endocrinol Metab. 2015;59(6):528-34.

Valor predictivo de la procalcitonina en niños con sospecha de sepsis / Predictive value of procalcitonin in children with suspected sepsis Abstract

Introducción: El uso de biomarcadores podría constituir una herramienta en el diagnóstico, pronóstico y estratificación en la sepsis. El objetivo fue analizar el valor de la procalcitonina (PCT), proteína C reactiva (PCR) y lactato en la predicción de shock séptico, mortalidad y en la estratificación en niños con sospecha de sepsis. Pacientes y método: Estudio prospectivo en 81 pacientes en los cuales se midió niveles plasmáticos de PCT, PCR y lactato al ingreso en la unidad de cuidados intensivos. Los pacientes se categorizaron en síndrome de respuesta inflamatoria sistémica, sepsis, sepsis grave y shock séptico. Resultados: Las concentraciones de la PCT (ng/mL) aumentaron significativamente de acuerdo a la gravedad de la sepsis: 0,36 (0-1,2) para síndrome de respuesta inflamatoria sistémica; 1,96 (0,4-3,5) para sepsis; 7,5 (3,9-11,1) en sepsis grave; y 58,9 (35,1-82,7) para shock séptico (p < 0,001). Comparada con la PCR y el lactato, el área bajo la curva ROC reveló un poder discriminativo favorable de la PCT para predecir shock séptico y mortalidad: 0,91 (IC95%: 0,83-0,97) y 0,80 (IC95%: 0,69-0,88), respectivamente. Conclusiones: A diferencia de la PCR y el lactato, la determinación de la PCT al ingreso en la unidad de cuidados intensivos es un buen predictor de shock séptico y mortalidad, y permite estratificar a los pacientes de acuerdo a la gravedad de la sepsis.

Introduction: The use of biomarkers could be a tool for diagnosis, prognosis and stratifying children with sepsis. Our main goal was to analyze the value of procalcitonin (PCT), C reactive protein (CRP) and lactate in predicting mortality, septic shock and the stratification in children with suspected sepsis Patients and method: Prospective study in 81 patients. Plasma levels of PCT, CRP and lactate were measured at admission in the pediatric intensive care unit. Patients were categorized into systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock. Results: Concentrations of PCT (ng/mL) increased significantly according to the severity of sepsis: 0.36 (0-1.2) for systemic inflammatory response syndrome; 1.96 (0.4-3.5) for sepsis; 7.5 (3.9-11.1) for severe sepsis; and 58.9 (35.1-82.7) for septic shock (P <.001). Compared to CRP and lactate, the area under the ROC curve revealed a good discriminative power of PCT to predict septic shock and mortality, 0.91 (95% CI: 0.83-0.97) and 0.80 (95% CI: 0.69-0.88), respectively. Conclusions: In contrast to CRP and lactate, the determination of PCT in pediatric intensive care unit admission is a good predictor of mortality and septic shock and can stratify patients according to severity of sepsis.

Transfusões de sangue no choque séptico: 7, 0g/dL é mesmo o limite adequado? / Blood transfusions in septic shock: is 7. 0g/dL really the appropriate threshold?

Objetivo: Avaliar os efeitos imediatos da transfusão de hemácias nos níveis de saturação venosa central de oxigênio e de lactato em pacientes com choque séptico usando diferentes níveis gatilho de hemoglobina para indicar transfusão. Métodos: Incluímos pacientes com diagnóstico de choque séptico nas últimas 48 horas e níveis de hemoglobina abaixo de 9,0g/dL. Os pacientes foram randomizados para receber imediatamente transfusão se as concentrações se mantivessem acima de 9,0g/dL (Grupo Hb9) ou adiar a transfusão até que a hemoglobina caísse abaixo de 7,0g/dL (Grupo Hb7). Os níveis de hemoglobina, lactato e saturação venosa central de oxigênio foram determinados antes e 1 hora após cada transfusão. Resultados: Incluímos 46 pacientes, totalizando 74 transfusões. Os pacientes do Grupo Hb7 tiveram uma redução significante nos níveis medianos de lactato de 2,44 (2,00 - 3,22) mMol/L para 2,21 (1,80 - 2,79) mMol/L; p = 0,005. Isto não foi observado no Grupo Hb9 [1,90 (1,80 - 2,65) mMol/L para 2,00 (1,70 - 2,41) mMol/L; p = 0,23]. A saturação venosa central de oxigênio aumentou no Grupo Hb7 [68,0 (64,0 - 72,0)% para 72,0 (69,0 - 75,0)%; p < 0,0001], mas não no Grupo Hb9 [72,0 (69,0 - 74,0)% para 72,0 (71,0 - 73,0)%; p = 0,98]. Pacientes com elevados níveis de lactato ou saturação venosa central de oxigênio menor que 70% na avaliação basal tiveram um aumento significante nessas variáveis, independentemente dos níveis basais de hemoglobina. Pacientes com valores normais não demonstraram diminuição em quaisquer dos grupos. Conclusão: A transfusão de hemácias aumentou a saturação venosa central de oxigênio e diminuiu os níveis de lactato em pacientes com hipoperfusão, independentemente de seus níveis basais de hemoglobina. A transfusão não pareceu influenciar essas variáveis em pacientes sem hipoperfusão. ClinicalTrials.gov NCT01611753 .

Objective: To evaluate the immediate effects of red blood cell transfusion on central venous oxygen saturation and lactate levels in septic shock patients with different transfusion triggers. Methods: We included patients with a diagnosis of septic shock within the last 48 hours and hemoglobin levels below 9.0g/dL Patients were randomized for immediate transfusion with hemoglobin concentrations maintained above 9.0g/dL (Group Hb9) or to withhold transfusion unless hemoglobin felt bellow 7.0g/dL (Group Hb7). Hemoglobin, lactate, central venous oxygen saturation levels were determined before and one hour after each transfusion. Results: We included 46 patients and 74 transfusions. Patients in Group Hb7 had a significant reduction in median lactate from 2.44 (2.00 - 3.22) mMol/L to 2.21 (1.80 - 2.79) mMol/L, p = 0.005, which was not observed in Group Hb9 [1.90 (1.80 - 2.65) mMol/L to 2.00 (1.70 - 2.41) mMol/L, p = 0.23]. Central venous oxygen saturation levels increased in Group Hb7 [68.0 (64.0 - 72.0)% to 72.0 (69.0 - 75.0)%, p < 0.0001] but not in Group Hb9 [72.0 (69.0 - 74.0)% to 72.0 (71.0 - 73.0)%, p = 0.98]. Patients with elevated lactate or central venous oxygen saturation < 70% at baseline had a significant increase in these variables, regardless of baseline hemoglobin levels. Patients with normal values did not show a decrease in either group. Conclusion: Red blood cell transfusion increased central venous oxygen saturation and decreased lactate levels in patients with hypoperfusion regardless of their baseline hemoglobin levels. Transfusion did not appear to impair these variables in patients without hypoperfusion. ClinicalTrials.gov NCT01611753 .

A combination of early warning score and lactate to predict intensive care unit transfer of inpatients with severe sepsis/septic shock

BACKGROUND/AIMS: The modified early warning score (MEWS) is used to predict patient intensive care unit (ICU) admission and mortality. Lactate (LA) in the blood lactate (BLA) is measured to evaluate disease severity and treatment efficacy in patients with severe sepsis/septic shock. The usefulness of a combination of MEWS and BLA to predict ICU transfer in severe sepsis/septic shock patients is unclear. We evaluated whether use of a combination of MEWS and BLA enhances prediction of ICU transfer and mortality in hospitalized patients with severe sepsis/septic shock. METHODS: Patients with severe sepsis/septic shock who were screened or contacted by a medical emergency team between January 2012 and August 2012 were enrolled at a university-affiliated hospital with ~2,700 beds, including 28 medical ICU beds. RESULTS: One hundred patients were enrolled and the rate of ICU admittance was 38%. MEWS (7.37 vs. 4.85) and BLA concentration (5 mmol/L vs. 2.19 mmol/L) were significantly higher in patients transferred to ICU than those in patients treated in general wards. The combination of MEWS and BLA was more accurate than MEWS alone in terms of ICU transfer (C-statistics: 0.898 vs. 0.816, p = 0.019). The 28-day mortality rate was 19%. MEWS was the only factor significantly associated with 28-day mortality rate (odds ratio, 1.462; 95% confidence interval, 1.122 to 1.905; p = 0.005). CONCLUSIONS: The combination of MEWS and BLA may enhance prediction of ICU transfer in patients with severe sepsis/septic shock.

sRAGE no choque séptico: um potencial biomarcador de mortalidade / sRAGE in septic shock: a potential biomarker of mortality

Objetivo: Avaliar e compreender as implicações clínicas dos níveis plasmáticos de uma isoforma solúvel de um receptor de produtos finais de glicação avançada (do inglês receptor for advanced glycation end products - sRAGE) em diferentes fases da sepse. Métodos: Os valores do sRAGE sérico em pacientes divididos nos grupos controle na unidade de terapia intensiva, sepse grave, choque séptico e recuperação de choque séptico foram analisados do ponto de vista estatístico para avaliar a quantidade (Kruskal-Wallis), variabilidade (teste de Levine) e correlação (teste Spearman rank) em relação a certos mediadores inflamatórios (IL-1 α, IL-6, IL-8, IL-10, IP-10, G-CSF, MCP-1, IFN-γ e TNF-α). Resultados: Não se observaram modificações nos níveis de sRAGE entre os grupos; contudo o grupo com choque séptico demonstrou diferenças na variabilidade do sRAGE em comparação aos demais grupos. Foi relatada, no grupo com choque séptico, uma correlação positiva com todos os mediadores inflamatórios. Conclusão: Os níveis de sRAGE se associaram com desfechos piores nos pacientes com choque séptico. Entretanto, uma análise de correlação estatística com outras citocinas pró-inflamatórias indicou que as vias que levam a esses desfechos são diferentes, dependendo dos níveis de sRAGE. ...

Objective: To evaluate and understand the clinical implications of the plasma levels of a soluble isoform of a receptor for advanced glycation end products (sRAGE) in different stages of sepsis. Methods: Serum sRAGE values in patients who were divided into intensive care unit control, severe sepsis, septic shock and recovery from septic shock groups were statistically analyzed to assess quantity (Kruskal-Wallis), variability (Levine test) and correlation (Spearman rank test) with certain inflammatory mediators (IL-1 α, IL-6, IL-8, IL-10, IP-10, G-CSF, MCP-1, IFN-γ and TNF-α). Results: No changes in sRAGE levels were observed among the groups; however, the septic shock group showed differences in the variability of sRAGE compared to the other groups. A positive correlation with all the inflammatory mediators was reported in the septic shock group. Conclusion: sRAGE levels are associated with worse outcomes in patients with septic shock. However, a statistical correlation analysis with other proinflammatory cytokines indicated that the pathways leading to those outcomes are different depending on the sRAGE levels. Future studies to elucidate the pathophysiological mechanisms involving sRAGE in models of sepsis are of great clinical importance for the safe handling of this biomarker. .

El tiempo de llene capilar prolongado es predictor de una saturación venosa central de oxígeno disminuida / A prolonged capillary refill is predictor of low central venous oxygen saturation

Introduction: Educational programs in pediatric life support endorse a capillary refill time > 2 s as an indicator of shock. In the emergency room, a barrier to the implementation of an early goal directed therapy, aiming at central venous oxygen saturation (ScvO2) ≥ 70% is the insertion of central venous catheter (CVC). Objective: To establish the predictive value of capillary refill time > 2 s to detect ScvO2 < 70% in children admitted to Intensive Care Units. Patients and Method: Prospective study. We included 48 children admitted in the first 24 hours in ICU with superior vena cava CVC. Simultaneously, we measured ScvO2 and capillary refill time in the heel of upper extremity or toe. Results: There were 75 paired measurements ScvO2 (75,9 ± 8,4%) and capillary refill capillary (1,9 ± 1,0 s). We found an inverse correlation between capillary refill time and ScvO2 (r - 0,58 ). The ROC curve analysis revealed an excellent ability for the capillary fill time > 2 s to predict ScvO2 < 70% (AUC 0,94) (95% CI 0,87-0,98). Conclusions: A prolonged capillary refill time > 2 s, is a predictor of ScvO2 < 70% in children admitted to ICU, which supports the current recommendations. This finding may be relevant in emergency units where the use of CVC is limited and ScvO2 is not available.

Introducción: Programas educativos de reanimación pediátrica establecen que un tiempo de llene capilar > 2 s es un indicador de shock. En unidades de emergencia, una barrera para la implementación de una reanimación precoz guiada por metas, teniendo como objetivo una saturación venosa central de oxígeno (ScvO2) ≥ 70%, es la inserción de un catéter venoso central (CVC). Objetivo: Determinar el valor predictivo de un tiempo de llene capilar > 2 s en la detección de ScvO2 < 70% en niños ingresados a la Unidad de Cuidados Intensivos. Pacientes y Método: Estudio prospectivo. Se incluyeron 48 niños ingresados en las primeras 24 h en UCI con CVC en la vena cava superior. De manera simultánea se determinaron ScvO2 y tiempo de llene capilar en talón o dedo de extremidad superior. Resultados: Se obtuvieron 75 mediciones pareadas de ScvO2 (75,9 ± 8,4%) y llene capilar (1,9 ± 1,0 s), observándose una correlación inversa entre llene capilar y ScvO2 (r = -0,58). El análisis de la curva ROC reveló una excelente capacidad del tiempo de llene capilar > 2 s para predecir una ScvO2 < 70% (AUC = 0,94, IC 95% = 0,87-0,98). Conclusiones: La prolongación del tiempo de llene capilar > 2 s es predictor de ScvO2 < 70% en niños críticamente enfermos. Este hallazgo apoya las recomendaciones actuales y podría ser relevante en unidades de emergencia donde el uso de CVC es limitado y la ScvO2 no está disponible.

Dosagens séricas de proteína C-reativa na fase inicial da sepse abdominal e pulmonar / Serum C-reactive protein concentrations in early abdominal and pulmonary sepsis

OBJETIVO: Avaliar os níveis séricos de proteína C-reativa em pacientes com sepse pulmonar e abdominal nos primeiros 5 dias de progressão da sepse. MÉTODOS: Estudo de coorte retrospectivo em hospital universitário. Foram selecionados 345 pacientes admitidos em unidade de terapia intensiva e diagnosticados com sepse de origem pulmonar ou abdominal. A dosagem sérica de proteína C-reativa foi realizada por imunoensaio turbidimétrico. Para análises da proteína C-reativa, o dia 1 foi definido como o do diagnóstico clínico da sepse. RESULTADOS: Foram avaliados 34 pacientes com sepse (9,8%), 114 com sepse grave (33,0%) e 197 com choque séptico (57,2%). A idade dos pacientes foram 56,4±19,8 anos. Concentrações séricas de proteína C-reativa foram mais elevadas no dia do diagnóstico de sepse no grupo com infecção de origem abdominal em comparação ao grupo com sepse pulmonar (17,8±10,1 mg/dL versus 14,9±11,1 mg/dL; p=0,025) e mantiveram-se significativamente mais elevadas nos primeiros 5 dias de evolução da sepse. CONCLUSÃO: As concentrações séricas de proteína C-reativa foram significativamente mais elevadas nos pacientes com sepse de origem abdominal do que em pacientes com sepse de origem pulmonar nos 5 primeiros dias de evolução da sepse.

OBJECTIVES: To evaluate the C-reactive protein serum levels in patients with pulmonary and abdominal sepsis during the first five days of sepsis progression. METHODS: The present investigation was a retrospective cohort study conducted at the university hospital with 345 patients who were admitted to the intensive care unit and diagnosed with sepsis of pulmonary or abdominal origin. Serum C-reactive protein concentrations were measured by the turbidimetric immunoassay. For analysis of C-reactive protein, day 1 was defined as the day on which the patient was clinically diagnosed with sepsis. RESULTS: Thirty-four patients with sepsis (9.8%), 114 patients with severe sepsis (33.0%), and 197 patients with septic shock (57.2%) were evaluated. The age of the patients was 56.4±19.8 years. The serum C-reactive protein concentrations were higher on the day of sepsis diagnosis in the group with abdominal infection compared with the group with pulmonary sepsis (17.8±10.1 mg/dL versus 14.9±11.1 mg/dL, p=0.025) and remained significantly higher during the first five days of sepsis progression. CONCLUSION: The serum C-reactive protein concentrations were significantly higher in the patients with abdominal sepsis compared with the patients with pulmonary sepsis during the first five days of sepsis progression.

Dynamics of brain natriuretic peptide in critically ill patients with severe sepsis and septic shock

Changes of B-type natriuretic peptide [BNP] in sepsis and its utility in predicting intensive care unit outcomes remains a conflicting issue. To investigate the changes in plasma levels of BNP in patients with severe sepsis/septic shock and to study the association of BNP levels with the severity of the disease and prognosis of those patients. Thirty patients with severe sepsis or septic shock were enrolled in our study. BNP measurements and echocardiography were carried out on admission and on 4[th] and 7[th] days. Blood concentrations of BNP were measured by commercially available assays [Abbott methods]. In-hospital mortality and length of stay were recorded multivariate analyses adjusted for acute physiology and chronic health evaluation score II [APACHE II score] was used for mortality prediction. Twenty patients admitted with the diagnosis of severe sepsis and 10 patients with septic shock. The in-hospital mortality was 23.3% [7 patients]. Admission BNP was significantly higher in the non-survivors 1123 +/- 236.08 versus 592.7 +/- 347.1 [P<0.001]. By doing multivariate logestic regression, the predicatable variables for mortality was APACHE II score, BNP, and then EF. BNP concentrations were increased in patients with severe sepsis or septic shock and poor outcome was associated with high BNP levels; thus, it may serve as a useful laboratory marker to predict survival in these patients

Procalcitonina como biomarcador de prognóstico da sepse grave e choque séptico / Procalcitonin as a prognostic biomarker of severe sepsis and septic shock

OBJETIVO: Avaliar a tendência da concentração plasmática e do clearance de procalcitonina (PCT-c) como biomarcadores de prognóstico de pacientes com sepse grave e choque séptico, comparado a um outro marcador precoce de prognóstico representado pelo número de critérios de SIRS no momento do diagnóstico da sepse. MÉTODOS: Estudo de coorte prospectivo observacional onde foram incluídos pacientes com sepse grave e choque séptico. A concentração sérica de procalcitonina foi determinada no momento do diagnóstico da sepse e após 24 e 48 horas. Foram coletados dados demográficos, escore APACHE IV, escore SOFA na chegada, número de critérios de SIRS no momento do diagnóstico, sitio da infecção e resultados microbiológicos. RESULTADOS: Vinte e oito pacientes foram incluídos, 19 clínicos e nove cirúrgicos. Em 13 (46,4%) a fonte da sepse foi pulmonar, em sete abdominal (25,0%), em cinco urinária (17,9%) e de partes moles em três casos (10,7%). Quinze pacientes tinham sepse grave e 13 choque séptico. A mortalidade global foi cinco pacientes (17,9%), três deles com choque séptico. Vinte e oito determinações de PCT foram realizadas no momento do diagnóstico da sepse, 27 após 24 horas e 26 após 48 horas. A concentração inicial não se mostrou expressivamente diferente entre os grupos sobreviventes e não sobreviventes, mas as diferenças entre os dois grupos após 24 e 48 horas alcançaram significância estatística expressiva. Não se observou diferença em relação ao número de critérios de SIRS. O clearance de procalcitonina de 24 horas mostrou-se expressivamente mais elevado no grupo de sobreviventes (-3,0 versus -300,0, p=0,028). Embora o clearance de procalcitonina de 48 horas tenha mostrado resultado mais elevado no grupo de sobreviventes comparado aos não sobreviventes, a diferença não alcançou significância estatística. CONCLUSÃO: Concentrações persistentemente elevadas de procalcitonina no plasma, assim como, redução do PCT-c 24 horas, associaram-se à elevação expressiva da mortalidade de pacientes com sepse grave e choque séptico.

OBJECTIVE: To evaluate the tendency of the plasma concentration and clearance of procalcitonin (PCT-c) as biomarkers of prognosis of patients with severe sepsis and septic shock, compared to another early prognosis marker, the number of SIRS criteria at sepsis diagnosis. METHODS: We conducted a prospective, observational, cohort study, with patients with severe sepsis and septic shock. The serum procalcitonin was determined at diagnosis of sepsis and after 24 and 48 hours. Demographic data, APACHE IV, SOFA score on arrival, number of SIRS criteria at diagnosis, site of infection and microbiological results were recorded. RESULTS: Twenty-eight patients were included, 19 clinical and nine surgical. In 13 (46.4%) the source of sepsis was pulmonary, abdominal in seven (25.0%), urinary in five (17.9%) and soft tissue in three cases (10.7%). Fifteen patients had severe sepsis and 13 septic shock. Overall mortality was 17.9% (five patients), three with septic shock. Twenty-eight PCT determinations were performed at sepsis diagnosis, 27 after 24 hours and 26 after 48 hours. The initial concentration was not significantly different between survivors and non-survivors groups, but the differences between the two groups after 24 and 48 hours were statistically significant. There was no difference in the number of SIRS criteria. The 24-hour procalcitonin clearance proved to be significantly higher in the group of survivors (-3.0 versus -300.0, p = 0.028). Although the 48-hour procalcitonin clearance has shown to be higher in the group of survivors when compared to non-survivors, the difference did not reach statistical significance. CONCLUSION: Persistently high procalcitonin concentrations in plasma, as well as reduced 24-hours PCT clearence, were associated with a significant increase in mortality in patients with severe sepsis and septic shock.

Observancia de las guías internacionales de manejo temprano en sepsis grave y choque séptico / Adherence to international guidelines on early management in severe sepsis and septic shock

Introducción. La observancia completa del tratamiento temprano dirigido por objetivos, disminuye significativamente la mortalidad a 28 días, mientras que la observancia parcial no tiene ningún beneficio. Objetivos. Determinar la observancia de las guías internacionales en sepsis grave y choque séptico, mediante el conjunto de medidas (bundle) de reanimación de las primeras seis horas en pacientes mayores de 16 años de edad, en un centro de referencia de alta complejidad. Materiales y métodos. Se presenta un estudio de cohorte, prospectivo y descriptivo, llevado a cabo durante un período de seis meses, en pacientes con sepsis grave o choque séptico admitidos a los servicios de urgencias, unidades de cuidados intensivos y cuidados especiales. Se midió la observancia del conjunto de medidas mediante ocho intervenciones: 1) medición del lactato sérico, 2) inicio temprano de antibióticos, 3) toma de hemocultivos, 4) infusión de líquidos intravenosos, 5) uso de medicamentos vasopresores, 6) inserción de catéter venoso central, 7) presión venosa central mayor de 8 mm Hg, y 8) saturación venosa central de oxígeno mayor de 70 %. Resultados. Se tamizaron 723 pacientes; 16 % (n=116) cumplieron los criterios de inclusión, 92,2 % (n=107) cumplieron los criterios para sepsis grave y 37,9 % (n=44) para choque séptico. El 62,9 % (n=73) fue subdiagnosticado. La observancia completa de las 8 intervenciones del conjunto de medidas fue de 0 %; de 6 a 7, 19 % (n=22); de 3 a 5, 67,2 % (n=78), y de 0 a 2, 98,3 % (n=114). Conclusión. La completa observancia de las guías internacionales de manejo en sepsis grave y choque séptico en las primeras seis horas es nula y solo se cumple de manera parcial.

Introduction. Complete adherence to early goal-directed therapy has shown a significant reduction in 28-day mortality rate, whereas partial adherence has not shown beneficial effect. Objectives. The effect of adherence to 6 hour sepsis bundle treatment was evaluated on patients with severe sepsis and septic shock. Materials and methods. A prospective cohort study was conducted during a six-month period. The patients were limited to those 16 years or older and included admissions to intensive care units, special care units or emergency departments with severe sepsis or septic shock. The adherence to the 6-hour sepsis bundle was evaluated through 8 interventions as follows: (1) serum lactate measure,( 2) early antibiotic administration, (3) blood culture samples, (4) infusion of intravenous fluids, (5) vasopressor use, (6) central venous catheter, (7) central venous pressure >8 mm Hg, and (8) central venous oxygen saturation >70%. Results. Seven hundred and twenty three patients were screened; 16% (n=116) met the inclusion criteria; 92.2% (n=107) met the criteria for severe sepsis and 37.9% (44) for septic shock; 62.9% (n=73) were subdiagnosed. Complete adherence to the 8 interventions of 6-hour sepsis bundle was 0%; 6 to 7 (19%, n=22), 3 to 5 (67.2%, n=78), and 0 to 2 (98.3%, n=114). Conclusion. Adherence to 6-hour sepsis bundle treatment for severe sepsis and septic shock was not done for the full 8 interventions and only partial accomplishment of the first 4 interventions.

Globulinas totales y recuento linfocitario como marcadores de mortalidad en sepsis y shock séptico / Total globulins and lymphocyte count as markers of mortality in sepsis and septic shock

Background: There are no studies probing if patients in sepsis or septic shock with lower levels of total plas-matic globulins and/or lymphocyte count have higher mortality. Patients and Method: Prospective cohort study of 103 patients admitted in Intensive Care Unit followed daily at the Dr. Gustavo Fricke Hospital between June and November of 2009, with sepsis or septic shock criteria. Results: There was association between mortality and lymphocytic count measured from the third day of their hospitalization (P < 0.05), but not when compared with the plasmatic globulin measurements (P > 0.05). The area under ROC curve for the mean lymphocyte count at the third day was 0.68 (95% CI 0.53-0.82), with a sensitivity of 75%, specificity of 52%, LR(+) 1.57 and LR(-) 0.48 for a cut-off at 510 lymphocytes/mm³, behaving also as an independent risk factor of mortality (OR 3.67, 95% CI 1.03-13.1). Discussion: Lymphocyte count is early and independently associated with increased mortality in patients with sepsis or septic shock.

Introducción: No existen estudios que demuestren si pacientes en sepsis o shock séptico que presentan globulinas plasmáticas totales y/o recuento linfocitario plasmático disminuidos, tendrían mayor mortalidad. Pacientes y Método: Estudio de cohorte prospectivo de 103 pacientes ingresados a la Unidad de Cuidados Intensivos, que cumplían criterios de sepsis o shock séptico, seguidos diariamente en el Hospital Dr. Gustavo Fricke entre junio y noviembre de 2009. Resultados: Hubo asociación entre mortalidad y recuento linfocitario medido a partir del tercer día (valor p < 0,05), pero no al comparar mortalidad con mediciones de globulinas plasmáticas (valor p > 0,05). El área bajo la curva ROC del recuento linfocitario medido al tercer día fue 0,68 (IC 95% 0,530,82), con una sensibilidad de 75%, especificidad 52%, LR(+) 1,57 y LR(-) 0,48 para un punto de corte de 510 linfocitos/mm³, comportándose además como factor de riesgo independiente de mortalidad (OR 3,67, IC 95% 1,03-13,1). Discusión: El recuento linfocitario se asocia precozmente y en forma independiente al pronóstico de mayor mortalidad en estos pacientes.

Propolis derivatives inhibit the systemic inflammatory response and protect hepatic and neuronal cells in acute septic shock

BACKGROUND: Severe pathogenic infection triggers excessive release of cytokines as part of the massive inflammatory response associated with septic shock. OBJECTIVES: To investigate the protective effect of caffeic acid phenethye ester (CAPE) against lipopolysaccharide (LPS) induced endotoxemia, hepatic and neuronal damage and the associated systemic inflammatory response (SIR). METHODS: Fifty male Wister rats were divided into: control, LPS, and CAPE+LPS groups. Plasma concentrations of various cytokines, including TNF-α, IL-1α, IL-1β, IL-6, IL-4, IL-10, and sICAM-1 were evaluated. In addition, the histopathological changes in the hepatic and neural cells were assessed. RESULTS: The LPS group showed high inflammatory cytokines and sICAM-1 levels reflecting the presence of SIR. Hepatocyte necrosis, apoptosis, extensive hemorrhage and inflammatory cellular infiltration together with brain astrocytes swelling, early neuron injury and presence of inflammatory foci confirmed the toxic tissue damage. Use of CAPE decreased the inflammatory cytokines and increased the anti-inflammatory cytokines levels. This biochemical evidence of decreased SIR was confirmed histologically by decreased cellular infiltration in the liver and brain tissue which coincides with preserved structure and protection of the liver and brain cells from the toxic effects of LPS. CONCLUSION: The ability of CAPE to alleviate the SIR, hepatic and neuronal cell damage induced by LPS and galactosamine could be attributed to its ability to reverse the imbalance of the pro- and anti-inflammatory cytokines which may lead to the inhibition of adhesion molecules' expression. CAPE is a promising agent that could help in the prophylaxis and treatment of septic shock.

Niveles bajos de procalcitonina ¿descartan bacteriemia en shock séptico adquirido en la unidad de cuidados intensivos? aprendizaje desde una serie de casos / Low levels of procalcitonin in the diagnosis of bacteremia in septic shock acquired in the intensive care unit

La procalcitonina representa un sustancial avance en el diagnóstico de infección bacteriana. Sin embargo, debe correlacionarse con el cuadro clínico y los otros marcadores de laboratorio ya que la sensibilidad reportada en bacteriemia es menor a 90 por ciento. Presentamos 6 pacientes críticos en shock séptico durante su estadía en la unidad de cuidados intensivos (UCI). Como parte de su estudio y porque en su mayoría se trataba de pacientes con causas de respuesta inflamatoria sistémica no infecciosas como cuadro de base, se solicitó la procalcitonina con la idea de discriminar. Estos pacientes habían sido tratados (o estaban en tratamiento) por alguna infección previa. Posteriormente, se demostró que 5 de los 6 pacientes tenían ambos hemocultivos positivos de los 2 tomados dentro del mismo día de la toma de procalcitonina con los valores promedio y desviación estándar: 0,66 +/- 0,44 ng/ml y un retraso de toma respecto al hemocultivo de 11,5 +/- 4,9 horas(siempre posterior a este último).Discusión: Se destaca que en esta serie de pacientes críticos en shock séptico y bacteriémicos, donde por nivel de gravedad gravedad y tiempo de toma de la procalcitonina sería esperable encontrar valores mayores a 2 ng/ml (asociado con sepsis para la mayoría de los laboratorios), situación claramente diferente. Dado lo complejo de los pacientes críticos y la cinética de la procalcitonina, su valor puntual aún bajo, no reemplaza al juicio clínico, que en estos casos fue correcto habiéndose iniciado tratamiento empírico y no suspendido sólo por un valor aislado.

Procalcitonin represents a substantial advance in the diagnosis of bacterial infection. However, it should correlate with the clinical and other laboratory markers, because the sensitivity reported in bacteraemia is less than 90 percent. We present six critical patients in septic shock during their stay in the intensive care unit (ICU). Because most of these were patients with noninfectious systemic inflammatory response, procalcitonin was requested with the idea of discriminating as part of the study. These patients had been treated (or were in treatment) for some previous infection. Subsequently, it was demonstrated that 5 of the 6 patients had positive blood cultures 2 of 2 the same day of collection of procalcitonin, with average values and standard deviation: 0.66 +/- 0.44 ng /ml. The sampling delay in respect of the blood culture was 11.5 +/- 4.9 hours (always after the latter). Discussion: It should be noted that these ICU patients in septic shock and bacteraemia, where by levels of severity and time of making the procalcitonin, it would be expected to find values greater than 2 ng / ml (associated with sepsis for most laboratories), a situation clearly different. Given the complexity of critically ill patients and the kinetics of procalcitonin, its precise value (still low), does not replace clinical assessment. In these cases the clinic was correct, beginning empirical treatment and not suspended it only by an isolated value.

C-reactive protein is not a useful indicator for infection in surgical intensive care units / Proteína C-reativa não é um marcador útil de infecção em unidade de terapia intensiva cirúrgica

CONTEXT AND OBJECTIVE: C-reactive protein (CRP) is commonly used as a marker for inflammatory states and for early identification of infection. This study aimed to investigate CRP as a marker for infection in patients with postoperative septic shock. DESIGN AND SETTING: Prospective, single-center study, developed in a surgical intensive care unit at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: This study evaluated 54 patients in the postoperative period, of whom 29 had septic shock (SS group) and 25 had systemic inflammatory response syndrome (SIRS group). All of the patients were monitored over a seven-day period using the Sequential Organ Failure Assessment (SOFA) score and daily CRP and lactate measurements. RESULTS: The daily CRP measurements did not differ between the groups. There was no correlation between CRP and lactate levels and the SOFA score in the groups. We observed that the plasma CRP concentrations were high in almost all of the patients. The patients presented an inflammatory state postoperatively in response to surgical aggression. This could explain the elevated CRP measurements, regardless of whether the patient was infected or not. CONCLUSIONS: This study did not show any correlation between CRP and infection among patients with SIRS and septic shock during the early postoperative period.

CONTEXTO E OBJETIVO: A proteína C reativa (PCR) é muito usada como marcador de estados inflamatórios e na identificação precoce de infecção. Este estudo teve como proposta investigar a PCR como marcadora de infecção em pacientes em choque séptico no período pós-operatório. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, monocêntrico, desenvolvido numa unidade de terapia intensiva pós-operatória do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foram avaliados 54 pacientes no pós-operatório, sendo 29 deles com choque séptico (grupo SS) e 25 com síndrome da resposta inflamatória sistêmica (grupo SI). Todos os pacientes foram acompanhados durante sete dias pelo escore SOFA (Sequential Organ Failure Assessment) e com dosagens diárias de PCR e lactato. RESULTADOS: As dosagens de PCR não diferiram entre os grupos. Não foi observada correlação entre dosagem de PCR e lactato ou escore SOFA nos grupos estudados. Observamos que as concentrações plasmáticas de PCR estavam elevadas em quase todos os pacientes avaliados. Os pacientes no pós-operatório apresentam estado inflamatório em resposta à agressão cirúrgica, sendo este fato capaz de explicar as dosagens de PCR elevadas, independentemente de o paciente estar ou não infectado. CONCLUSÕES: Este estudo não evidenciou correlação entre PCR e infecção nos pacientes com síndrome da resposta inflamatória sistêmica e choque séptico no período pós-operatório precoce.