International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Echocardiography Does not Reduce Mortality in Sepsis: A Re-Evaluation Using the Medical Information Mart for Intensive Care IV Dataset.

OBJECTIVES: Echocardiography is commonly used for hemodynamic assessment in sepsis, but data regarding its association with outcome are conflicting. The aim of this study was to evaluate the association between echocardiography and outcomes in patients with septic shock using the Medical Information Mart for Intensive Care IV database. DESIGN: Retrospective cohort study comparing patients who did or did not undergo transthoracic echocardiography within the first 5 days of admission for the primary outcome of 28-day mortality. SETTING: Admissions to the Beth Israel Deaconess Medical Center intensive care from 2008 to 2019. PATIENTS: Adults 16 years old or older with septic shock requiring vasopressor support within 48 hours of admission. Readmissions and patients admitted to the coronary care unit or cardiovascular intensive care were excluded, as well as patients with ST-elevation myocardial infarction or cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Echocardiography was performed in 1,515 (27%) of 5,697 eligible admissions. The primary outcome was analyzed using a marginal structural model and rolling entry matching to adjust for baseline and time-varying confounders. Patients who underwent echocardiography showed no significant difference in 28-day mortality (adjusted hazard ratio 1.09; 95% CI, 0.95-1.25; p = 0.24). This was consistent across multiple sensitivity analyses. Secondary outcomes were changes in management instituted within 4 hours of imaging. Treatment changes occurred in 493 patients (33%) compared with 431 matched controls (29%), with the most common intervention being the administration of a fluid bolus. CONCLUSIONS: Echocardiography in sepsis was not associated with a reduction in 28-day mortality based on observational data. These findings do not negate the utility of echo in cases of diagnostic uncertainty or inadequate response to initial treatment.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Parthanatos type programmed cell death and septic patient mortality / Muerte celular programada tipo Parthanatos y mortalidad de los pacientes sépticos

Objective: Parthanatos is a form of programmed cell death mediated by apoptosis-inducing factor (AIF). However, there are not data on parthanatos in septic patients. The objective of the current study was to explore whether parthanatos is associated with mortality of septic patients. Design: Observational and prospective study. Setting: Three Spanish Intensive Care Units during 2017. Patients: Patients with sepsis according to Sepsis-3 Consensus criteria. Interventions: Serum AIF concentrations were determined at moment of sepsis diagnosis. Main variable of interest: Mortality at 30 days. Results: There were included 195 septic patients, and non-surviving (n=72) had serum AIF levels (p<0.001), lactic acid (p<0.001) and APACHE-II (p<0.001) that surviving (n=123). Multiple logistic regression analysis showed that patients with serum AIF levels>55.6ng/mL had higher mortality risk (OR=3.290; 95% CI=1.551−6.979; p=0.002) controlling for age, SOFA and lactic acid. Conclusions: Parthanatos is associated with mortality of septic patients. (AU)

Objetivo: Parthanatos es un tipo de muerte celular programada mediada por el factor inductor de apoptosis (AIF). Sin embargo, no hay datos sobre Parthanatos en pacientes sépticos. Por ello, el objetivo de este estudio fue explorar si Parthanatos está asociado con la morlaidad de los pacientes sépticos. Diseño: Estudio observacional y prospective. Ámbito: Tres Unidades de Cuidados Intensivos españolas durante 2017. Pacientes: Pacientes con sepsis en base a los criterios del Consenso Sepsis-3. Intervenciones: Se determinaron las concentraciones séricas de AIF en el momento del diagnóstico de la sepsis. Variable de interés principal: Mortalidad a los 30 días. Resultados: Se incluyeron 195 pacientes sépticos, y los que fallecieron (n=72) presentaron mayores concentraciones séricas de AIF (p<0.001) y de ácido láctico (p<0.001), y mayor puntuación APACHE-II (p<0.001) que los pacientes supervivientes (n=123). El análisis de regresión logística múltiple mostró que los pacientes con concentraciones séricas de AIF>55.6ng/mL tuvieron mayor riesgo de fallecer (OR=3.290; 95% CI=1.551−6.979; p=0.002) controlando por edad, SOFA y ácido láctico. Conclusiones: Parthanatos está asociado con la mortalidad de pacientes sépticos. (AU)

Clinical evaluation of peripheral tissue perfusion as a predictor of mortality in sepsis and septic shock in the intensive care unit: Systematic review and meta-analysis / Evaluación clínica de la perfusión tisular periférica como predictor de mortalidad en sepsis y choque séptico en la unidad de terapia intensiva: Revisión sistemática y metaanálisis

Objective: To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality. Design: Systematic review and meta-analysis. Setting: Intensive care unit. Patients and participants: Patients with sepsis and septic shock. Intervention: Studies of patients with sepsis and/or septic shock that associated clinical monitoring of tissue perfusion with mortality were included. A systematic review was performed by searching the PubMed/MEDLINE, Cochrane Library, SCOPUS, and OVID databases. Main variables of interest: The risk of bias was assessed with the QUADAS-2 tool. Sensitivity and specificity were calculated to evaluate the predictive accuracy for mortality. Review Manager software version 5.4 was used to draw the forest plot graphs, and Stata version 15.1 was used to build the hierarchical summary receiver operating characteristic model. Results: Thirteen studies were included, with a total of 1667 patients and 17 analyses. Two articles evaluated the temperature gradient, four evaluated the capillary refill time, and seven evaluated the mottling in the skin. In most studies, the outcome was mortality at 14 or 28 days. The pooled sensitivity of the included studies was 70%, specificity 75.9% (95% CI, 61.6%–86.2%), diagnostic odds ratio 7.41 (95% CI, 3.91–14.04), and positive and negative likelihood ratios 2.91 (95% CI, 1.80–4.72) and 0.39 (95% CI, 0.30–0.51), respectively. Conclusions: Clinical evaluation of tissue perfusion at the bedside is a useful tool, with moderate sensitivity and specificity, to identify patients with a higher risk of death among those with sepsis and septic shock. (AU)

Objetivo: Determinar el rendimiento diagnóstico de la evaluación clínica de la perfusión tisular periférica en la predicción de mortalidad. Diseño: Revisión sistemática y metaanálisis. Ámbito: Unidad de cuidados intensivos. Pacientes y participantes: Pacientes con sepsis y shock séptico. Intervenciones: Se incluyeron estudios de pacientes con sepsis y/o shock séptico que asociaron la monitorización clínica de la perfusión tisular con la mortalidad. Se realizó una revisión sistemática buscando en las bases de datos PubMed/MEDLINE, Cochrane Library, SCOPUS y OVID. Variables de interés principales: El riesgo de sesgo se evaluó con la herramienta QUADAS-2. Se calcularon la sensibilidad y la especificidad para evaluar la precisión predictiva de la mortalidad. Resultados: Se incluyeron trece estudios, con un total de 1667 pacientes y 17 análisis. Dos artículos evaluaron gradiente de temperatura, cuatro evaluaron tiempo de llenado capilar y siete evaluaron moteado en la piel. La mayoría de los estudios midieron mortalidad a 14 o 28 días. La sensibilidad agrupada de los estudios incluidos fue 70% y especificidad 75,9% (IC del 95%, 61,6%–86,2%), la razón de probabilidad diagnóstica 7,41 (IC del 95%, 3,91–14,04) y la razón de probabilidad positiva y negativa 2,91 (IC del 95%, IC, 1,80–4,72) y 0,39 (IC 95%, 0,30–0,51), respectivamente. Conclusiones: La evaluación clínica de la perfusión tisular es una herramienta útil, con sensibilidad y especificidad moderadas, para identificar pacientes con sepsis y shock séptico con mayor riesgo de muerte. (AU)

Índice leucocitos/eosinófilos como marcador pronóstico del choque séptico / Leukocyte/eosinophil Ratio as a Prognostic Marker of Septic Choque

Introducción: Se ha reconocido mundialmente el choque séptico como causa de una alta incidencia en la mortalidad. La incorporación de nuevos biomarcadores posibilita la obtención de un diagnóstico rápido y preciso. Objetivo: Evaluar la utilidad del índice leucocitos/eosinófilos como marcador pronóstico del choque séptico. Métodos: Se realizó una investigación en dos etapas: la primera descriptiva en la cual se detallaron las características clínicas, epidemiológicas y las variaciones de los estudios de laboratorio y la segunda explicativa de cohorte para estimar el valor predictivo del biomarcador leucocitos/eosinopenia en el choque séptico. Se realizó el recuento de eosinófilos y se obtuvo la media aritmética. Se consideró eosinopenia relativa con valores por debajo de la media de eosinófilos. Resultados: En el estudio se demostró que la leucocitosis fue de (27,4 células*mm3), la disminución del hematocrito (32,2 por ciento) y el descenso del número plaquetario (125,6 célula*mm3) prevalecen en el choque séptico. Además se refleja el descenso de los eosinófilos (18,5 células/mcl), aumento del índice leucocitos/eosinófilos (148,1) y empeoramiento del SOFA (2,8). El aumento del índice leucocitos/eosinófilos se correlaciona con el aumento de la proteína C reactiva y la procalcitonina. Conclusiones: La correlación de la leucocitosis y la eosinopenia mostró la utilidad del índice leucocitos/eosinopenia como factor de predicción del choque séptico(AU)

Introduction: Septic shock has been recognized worldwide as a cause of high incidence of mortality. The incorporation of new biomarkers makes it possible to obtain a rapid and accurate diagnosis. Objective: To evaluate the usefulness of the leukocyte/eosinophil ratio as a prognostic marker of septic shock. Methods: An investigation was carried out in two stages: in the first (the descriptive phase) the clinical and epidemiological characteristics and variations of the laboratory studies were detailed and in the second (the explanatory cohort phase), the predictive value of the leukocytes/eosinopenia biomarker in septic shock was estimated. The eosinophil count was performed and the arithmetic mean was obtained. Relative eosinopenia was considered with eosinophil values below the average. Results: The study showed that leukocytosis was 27.4 cells*mm3, hematocrit decreased in 32.2percent and decreased platelet number (125.6 cells*mm3) prevail in septic shock. In addition, a decrease in eosinophils (18.5 cells/mcl), an increase in the leukocyte/eosinophil ratio (148.1) and worsening of SOFA (2.8) are reflected. The increase in the leukocyte/eosinophil ratio is correlated with the increase in C-reactive protein and procalcitonin. Conclusions: The correlation of leukocytosis and eosinopenia showed the usefulness of the leukocyte/eosinopenia index as a predictor of septic shock(AU)

Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.

Importance: Patients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. ß-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality. Objectives: To assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support. Design, Setting, and Participants: An open-label, multicenter, randomized trial involving 126 adults (≥18 years) with tachycardia (heart rate ≥95/min) and established septic shock treated for at least 24 hours with continuous norepinephrine (≥0.1 µg/kg/min) in 40 UK National Health Service intensive care units. The trial ran from April 2018 to December 2021, with early termination in December 2021 due to a signal of possible harm. Intervention: Sixty-three patients were randomized to receive standard care and 63 to receive landiolol infusion. Main Outcomes and Measures: The primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score from randomization through 14 days. Secondary outcomes included mortality at days 28 and 90 and the number of adverse events in each group. Results: The trial was stopped prematurely on the advice of the independent data monitoring committee because it was unlikely to demonstrate benefit and because of possible harm. Of a planned 340 participants, 126 (37%) were enrolled (mean age, 55.6 years [95% CI, 52.7 to 58.5 years]; 58.7% male). The mean (SD) SOFA score in the landiolol group was 8.8 (3.9) compared with 8.1 (3.2) in the standard care group (mean difference [MD], 0.75 [95% CI, -0.49 to 2.0]; P = .24). Mortality at day 28 after randomization in the landiolol group was 37.1% (23 of 62) and 25.4% (16 of 63) in the standard care group (absolute difference, 11.7% [95% CI, -4.4% to 27.8%]; P = .16). Mortality at day 90 after randomization was 43.5% (27 of 62) in the landiolol group and 28.6% (18 of 63) in the standard care group (absolute difference, 15% [95% CI, -1.7% to 31.6%]; P = .08). There were no differences in the number of patients having at least one adverse event. Conclusion and Relevance: Among patients with septic shock with tachycardia and treated with norepinephrine for more than 24 hours, an infusion of landiolol did not reduce organ failure measured by the SOFA score over 14 days from randomization. These results do not support the use of landiolol for managing tachycardia among patients treated with norepinephrine for established septic shock. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14; isrctn.org Identifier: ISRCTN12600919.

Association between diastolic blood pressure during the first 24 h and 28-day mortality in patients with septic shock: a retrospective observational study.

BACKGROUND: Although the mean arterial pressure (MAP) target of 65 mmHg was achieved, diastolic blood pressure (DBP) was still low in some septic shock patients. The effects of DBP on the prognosis and optimal target for patients with septic shock are unclear. We sought to investigate the relationship between DBP and 28-day mortality in septic shock patients. METHODS: In this retrospective observational study, we obtained data from the Chinese Database in Intensive Care (CDIC). We included patients with an admission diagnosis of septic shock and shock was controlled. DBP was measured every 1 h, and the mean DBP during the first 24 h (mDBP24h) was recorded. The primary outcome was 28-day mortality. Multivariable logistic regression determined the relationship between mDBP24h and 28-day mortality. RESULTS: In total, 1251 patients were finally included. The 28-day mortality of included septic shock patients was 28.3%. The mDBP24h, not mSBP24h, was higher among 28-day survivors compared with non-survivors. 28-day mortality was inversely associated with mDBP24h (unadjusted OR 0.814 per 10 mmHg higher mDBP24h, P = 0.003), with a stepwise increase in 28-day mortality at lower mDBP24h. The 28-day mortality of patients with mDBP24h < 59 mmHg had an absolute risk reduction of 9.4% (P = 0.001). And mDBP24h < 59 mmHg was the remaining high risk factor inversely associated with 28-day mortality after multivariable adjustment (adjusted OR 1.915, 95% CI 1.037-3.536, P = 0.038), while mMAP24h and mSBP24h were not. CONCLUSION: In patients with septic shock after initial resuscitation, we observed an inverse association between mDBP24h and 28-day mortality. The poor outcomes in patients with mDBP24h < 59 mmHg provide indirect evidence supporting a further DBP goal of 59 mmHg for patients with septic shock after MAP of 65 mmHg was achieved.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Papel del Delta de PCO2 en la evaluación pronóstica de morbimortalidad en una cohorte de pacientes de un hospital latinoamericano / Role of PCO2 Delta in the Prognostic Evaluation of Morbidity and Mortality in a Cohort of Patients from a Latin American Hospital

Introducción. El shock séptico es la manifestación más grave de sepsis con tasas de letalidad que pueden llegar hasta el 80%. En los últimos años, ha cobrado relevancia la diferencia arteriovenosa de dióxido de carbono, por su implicación teórica en el metabolismo anaerobio y su significado respecto del normal funcionamiento celular. Por lo antes mencionado, creemos necesario realizar un estudio que nos permita establecer la utilidad de la diferencia arteriovenosa de dióxido de carbono en el paciente con shock séptico de la unidad de cuidados intensivos, como medida indirecta de la perfusión tisular y de la utilización de oxígeno por los tejidos, que nos permita establecer un diagnóstico precoz y el pronóstico de los pacientes críticamente enfermos. Métodos. Estudio observacional, descriptivo y transversal. Muestra de veintiocho pacientes adultos. Resultados. Como se ha registrado en otras series, la mayor parte de los pacientes afectados por shock séptico, en nuestro estudio, fueron hombres mayores de 65 años, con al menos una comorbilidad, siendo el principal sitio de infección el respiratorio (67,9%), asociado a una alta tasa de mortalidad (67%). Conclusiones. Los pacientes con diferencia arteriovenosa de PCO2 mayor a 6 mmHg tienen un riesgo aumentado de muerte de 3,2 veces. (AU)

Introduction. Septic shock is the most serious manifestation of sepsis with mortality rates that can reach up to 80%. In recent years, the arteriovenous carbon dioxide difference has gained relevance, due to its theoretical implication in anaerobic metabolism and its significance with respect to normal cell function. Due to the aforementioned, we believe it is necessary to carry out a study that allows us to establish the usefulness of the arteriovenous carbon dioxide difference in the patient with septic shock in the intensive care unit as an indirect measure of tissue perfusion and utilization. of oxygen through the tissues, which allows us to establish an early diagnosis and prognosis of critically ill patients. Methods. Observational, descriptive and cross-sectional study. Sample of 28 adult patients. Results. As has been reported in other series, most of the patients affected by septic shock in our study were men over 65 years of age, with at least one comorbidity, the main site of infection being respiratory (67.9%), associated with a high mortality rate (67%) Conclusions. Patients with an arteriovenous PCO2 difference greater than 6 mmHg have a 3.2-fold increased risk of death. (AU)

Relationship among Low T3 Levels, Type 3 Deiodinase, Oxidative Stress, and Mortality in Sepsis and Septic Shock: Defining Patient Outcomes.

Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (DIO3) is present in immune cells, but there is no description of its presence in patients with sepsis. Here, we aimed to determine the prognostic impact of thyroid hormones levels (TH), measured on ICU admission, on mortality and evolution to chronic critical illness (CCI) and the presence of DIO3 in white cells. We used a prospective cohort study with a follow-up for 28 days or deceased. Low T3 levels at admission were present in 86.5% of the patients. DIO3 was induced by 55% of blood immune cells. The cutoff value of 60 pg/mL for T3 displayed a sensitivity of 81% and specificity of 64% for predicting death, with an odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 for mortality and 0.75 for evolution to CCI, thus displaying better performance than commonly used prognostic scores. The high expression of DIO3 in white cells provides a novel mechanism to explain the reduction in T3 levels in sepsis patients. Further, low T3 levels independently predict progression to CCI and mortality within 28 days for sepsis and septic shock patients.

Vitamin D deficiency on admission to the emergency department is a mortality predictor for patients with septic shock treated with early protocol-driven resuscitation bundle therapy.

BACKGROUND: Vitamin D is an important immune modulator and is associated with susceptibility to infection. However, past studies have reported inconsistent results regarding the association between vitamin D deficiency and mortality in patients with sepsis, and early-stage data regarding septic shock are limited. This study aimed to determine the relationship between vitamin D deficiency on admission to the emergency department (ED) and mortality in patients with septic shock. METHODS: We analyzed prospectively collected data on adult patients with septic shock who were treated with protocol-driven resuscitation bundle therapy in the ED between September 2019 and February 2021. Septic shock was defined by the sepsis-3 definition and vitamin D deficiency was defined as a 25-hydroxyvitamin D <20 ng/ml. The primary outcome was 30-day mortality. RESULTS: A total of 302 patients were included, 236 (78.1%) patients had vitamin D deficiency; it was significantly higher in non-survivors than in survivors (89.3% vs. 73.9%, P = 0.004). Mortality was higher in vitamin D deficient patients than in non-deficient patients (31.8% vs. 13.6%, P = 0.004). In multivariate analysis, vitamin D deficiency (odds ratio [OR], 2.43; 95 % confidence interval [CI], 1.03-5.74), hyperlactatemia (OR, 3.65; 95 % CI, 1.95-6.83), Sequential Organ Failure Assessment scores (OR, 1.22; 95% CI, 1.09-1.36), and albumin levels (OR, 0.39; 95% CI, 0.21-0.73) were significantly associated with 30-day mortality. CONCLUSIONS: Vitamin D deficiency was prevalent in patients with septic shock visiting the ED and was associated with mortality.

Perfil de pacientes com sepse e choque séptico em um hospital de trauma: estudo transversal / Profile of patients with sepsis and septic shock in a trauma hospital: cross-sectional study / Perfil de pacientes con sepsis y shock séptico en un hospital de trauma: estudio transversal

Objetivo: Avaliar o perfil e o desfecho clínico de pacientes com sepse e choque séptico em um hospital de trauma de Belo Horizonte. Métodos: Trata-se de estudo transversal, retrospectivo e descritivo dos casos de sepse e choque séptico. Resultados: Constatou-se que 97 (73%) pacientes eram do sexo masculino, com idade entre 19 e 59 anos, 87 (65%) previamente hígidos. Principal motivo de internação foi queda da própria altura com 23 (17%) casos e 37 (28%) diagnósticos de trauma crânio encefálico. Oitenta e seis (65%) pacientes tiveram diagnóstico de sepse e 47 (35%) choque séptico, o principal foco de infecção foi pulmonar 83 (62%). Obtivemos 88 (66%) resultados de hemoculturas negativas e 45 (34%) positivas, 64 (48%) pacientes receberam antibiótico em até 60 minutos após o diagnóstico e o tempo de internação mais prevalente após o evento séptico foi de 7 dias, representado por 31 (46%) pacientes que já estavam internados em uma Unidade de Terapia Intensiva (UTI). Mortalidade de 37 (28%) e 96 (72%) sobreviventes da população estudada. Conclusão: O evento séptico é um problema de saúde pública e tem alta letalidade em pacientes traumatizados. (AU)

Objective: To evaluate the profile and clinical outcome of patients with sepsis and septic shock in a trauma hospital in Belo Horizonte. Methods: This is a cross-sectional, retrospective and descriptive study of cases of sepsis and septic shock. Results: It was found that 97 (73%) patients were male, aged 19 to 59 years, 87 (65%) were previously healthy. Main reason for hospitalization was a fall from one's own height with 23 (17%) cases and 37 (28%) diagnosis of traumatic brain injury. Eighty-six (65%) patients were diagnosed with sepsis and 47 (35%) septic shock, the main focus of infection was pulmonary 83 (62%). We got 88 (66%) negative blood culture results and 45 (34%) positive, 64 (48%) patients received antibiotics within 60 minutes after diagnosis and the most prevalent hospital stay after septic event was 7 days, represented by 31 (46%) patients who were already hospitalized in an Intensive Care Unit (ICU). Mortality of 37 (28%) and 96 (72%) survivors of the population studied. Conclusion: Septic event is a public health problem and has high lethality in traumatized patients. (AU)

Objetivo: Evaluar el perfil y el resultado clínico de los pacientes con sepsis y shock séptico en un hospital de trauma en Belo Horizonte. Métodos: Este es un estudio transversal, retrospectivo y descriptivo de casos de sepsis y shock séptico. Resultados: Se encontró que 97 (73%) pacientes eran hombres, de 19 a 59 años, 87 (65%) antes estaban sanos. La razón principal de la hospitalización fue una caída desde la propia altura con 23 (17%) casos y 37 (28%) diagnóstico de lesión cerebral traumática. Ochenta y seis (65%) pacientes fueron diagnosticados con sepsis y 47 (35%) shock séptico, el foco principal de infección fue pulmonar 83 (62%). Tenemos 88 (66%) resultados negativos del cultivo sanguíneo y 45 (34%) positivo, 64 (48%) los pacientes recibieron antibióticos dentro de los 60 minutos posteriores al diagnóstico y la estancia hospitalaria más frecuente después del evento séptico fue de 7 días, representados por 31 (46%) pacientes que ya estaban hospitalizados en una Unidad de Cuidados Intensivos (UCI). Mortalidad de 37 (28%) y 96 (72%) sobrevivientes de la población estudiada. Conclusión: El evento séptico es un problema de salud pública y tiene alta letalidad en pacientes traumatizados. (AU)

Asociación del antígeno carbohidrato 125 con la mortalidad por sepsis en pacientes críticos / Association of carbohydrate 125 antigen with sepsis mortality in critical patients

IntroductionThe increased synthesis of CA125 in mesothelial cells is connected with pathophysiological processes, also present in sepsis, that link inflammation with systemic congestion. We propose to evaluate serum levels of this biomarker in patients with sepsis and to study its association with the severity and evolution of the disease.MethodsLongitudinal retrospective observational study, which included 126 patients admitted to an Intensive Care Unit with sepsis criteria. The main variables analyzed were: CA125 values for 7 days, the variation of its levels according to the source of infection (abdominal, pulmonary, nephrourinary and others), sepsis, septic shock, APACHE-II score and mortality.ResultsCA125 levels remained elevated throughout the study period. The abdominal focus presented higher mean levels of CA125 (62±55.5U/mL; P=.001) and were higher in non-survivors (77.2U/mL; interquartile range 35.9-118.5; P=.0273). CA125 levels>35U/mL throughout the weal had an independently effect on the evolution (relative risk [RR] 3.1; 95% confidence interval [CI] 1.6-6.2; P=.001) and the elevated mean value of CA125 was also associated with mortality (RR 1.004; 95% CI 1.001-1.005; P=.0001).ConclusionsSeptic patients presented high levels of CA125 on the study days, being higher in abdominal infections. In our study, serial determination of CA125 is a prognostic marker of mortality independent of age, origin of infection or severity. (AU)

IntroducciónLa síntesis aumentada de CA125 en las células mesoteliales se asocia a procesos fisiopatológicos presentes en la sepsis, que relacionan la inflamación con la congestión sistémica. Proponemos evaluar los niveles séricos de este biomarcador en la sepsis y estudiar su asociación con la gravedad y evolución de la enfermedad.MétodosEstudio observacional prospectivo longitudinal que incluyó a 126 pacientes que ingresaron en una unidad de cuidados intensivos con criterios de sepsis. Las variables principales analizadas fueron: valores de CA125 durante 7 días, foco causante de la infección (abdominal, pulmonar, nefrourinario y otros), sepsis, shock séptico, escala APACHE-II y mortalidad.ResultadosLos niveles de CA125 se mantuvieron elevados en el período de estudio. El foco abdominal presentó niveles medios de CA125 más elevados (62±55,5U/ml; p=0,001) y fueron superiores en los pacientes que fallecieron (77,2U/ml; rango intercuartil 35,9-118,5; p=0,0273). Los niveles de CA125>35U/ml durante toda la semana tuvieron un efecto sobre la evolución de forma independiente (riesgo relativo [RR] 3,1; intervalo de confianza [IC] 95% 1,6 a 6,2; p=0,001) y el valor medio elevado de CA125 también se asoció a la mortalidad (RR 1,004; IC 95% 1,001-1,005; p=0,0001).ConclusionesLos pacientes sépticos presentaron unos niveles elevados de CA125 en los días de estudio, siendo superiores en infecciones de foco abdominal. En nuestro estudio, la determinación seriada de CA125 es un marcador pronóstico de mortalidad independiente de la edad, el origen de la infección o la gravedad. (AU)

Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

BACKGROUND: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODS: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTS: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONS: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.).

High mortality rate of septic patients with high blood granzyme B concentrations.

Granzyme B could be released from cytotoxic T lymphocytes producing apoptosis activation. The objective of our study was to determine whether an association between septic patient mortality and blood granzyme B concentrations exist. We recruited septic patients admitted in 3 Intensive Care Units. We recorded mortality at 30 days and we determined serum granzyme B concentrations at moment of sepsis diagnosis. We found higher rate of history of diabetes mellitus (P = 0.02), serum granzyme B concentrations (P < 0.001), age (P = 0.001), serum lactic acid levels (P = 0.001) and sepsis-related organ failure assessment (P < 0.001) exhibited non-surviving patients (n = 67) than surviving ones (n = 110). We found in multiple logistic regression analysis an association of serum granzyme B concentrations with mortality (odds ratio = 1.223; 95% confidence interval = 1.104-1.355; P < 0.001) controlling for diabetes mellitus, sepsis-related organ failure assessment, lactic acid and age. That we know, our study is the first reporting the existence of an association of high serum granzyme B concentrations with high septic patients mortality.

Caracterización de los pacientes con enfermedades vasculares periféricas fallecidos en un período de cuatro años / Characterization of patients with peripheral vascular diseases who died in a period of four years

Introducción: Las enfermedades vasculares periféricas constituyen un problema de salud en el ámbito mundial por resultar causa importante de discapacidad y de invalidez. Objetivo: Caracterizar a los pacientes con enfermedades vasculares periféricas fallecidos en un período de cuatro años. Método: Se realizó un estudio descriptivo y analítico en los pacientes fallecidos entre enero de 2015 y diciembre de 2018. Se estudiaron variables sociodemográficas y clínicas. Se estimaron las frecuencias absolutas y relativas, así como la tasa de mortalidad. Se identificó la asociación entre las variables con la causa directa de muerte. Resultados: El 42,7 por ciento de los diabéticos fallecieron; de estos, el 57,5 por ciento estaban descompensados. La hipertensión arterial, el tabaquismo y la diabetes mellitus fueron los factores de riesgo más frecuentes. La tasa de mortalidad total resultó 0,171/1000 ingresos. Como enfermedades arteriales más frecuente aparecieron los AAA (28,1 por ciento ) y la angiopatía diabética (25 por ciento ); y, como parte de esta última, el pie (25,7 por ciento ). La aneurismectomía con injerto por sustitución representó la cirugía revascularizadora más realizada (58,8 por ciento ). El shock hipovolémico y el tromboembolismo pulmonar predominaron como complicaciones posquirúrgicas (15,7 por ciento ). El shock séptico (31,6 por ciento ) y la bronconeumonía bacteriana (25,7 por ciento) fueron las causas directas de muerte. Conclusiones: Se logró caracterizar a los pacientes con enfermedades vasculares periféricas fallecidos en los últimos cuatro años, por lo que estimaron la tasa de prevalencia y la tendencia anual de la mortalidad en el Instituto Nacional de Angiología y Cirugía Vascular en ese período; asimismo, las variables asociadas a las causas directas de muerte(AU)

Introduction: Peripheral vascular diseases are a global health problem because they are a major cause of disability. Objective: Characterize patients with peripheral vascular diseases who died over a period of four years. Method: A descriptive and analytical study was conducted in patients who died between January 2015 and December 2018. Socio-demographic and clinical variables were studied. Absolute and relative frequencies were estimated, as well as the mortality rate. The association between the variables with the direct cause of death was identified. Results: 42.7 percent of diabetic patients died; of these, 57.5 percent were decompensated. High blood pressure, smoking and diabetes mellitus were the most frequent risk factors. The total mortality rate was 0.171/1000 admissions. The most frequent arterial diseases were AAA (28.1 percent) and diabetic angiopathy (25 percent); and, as part of the latter, foot angiopathy (25.7 percent). Aneurysmectomy with graft substitution represented the most performed revascularizing surgery (58.8 percent). Hypovolemic shock and pulmonary thromboembolism predominated as post-surgical complications (15.7 percent). Septic shock (31.6 percent) and bacterial bronchopneumonia (25.7 percent) were the direct causes of death. Conclusions: It was possible to characterize patients with peripheral vascular diseases who died in the last four years, so they estimated the prevalence rate and the annual trend of mortality at the National Institute of Angiology and Vascular Surgery in that period; also, the variables associated with direct causes of death(AU)

Folic acid and vitamin B12 as biomarkers of morbidity and mortality in patients with septic shock / El ácido fólico y la vitamina B12 como biomarcadores de morbilidad y mortalidad en pacientes con shock séptico

Introduction and objective: a study was made of the folic acid (Fol) and vitamin B12 (B12) serum concentrations in critical patients with septic shock upon admission and after three days of stay in the Intensive Care Unit (ICU), with an analysis of their association to inflammatory parameters and patient morbidity-mortality. Methods: a prospective analytical study was made of 30 critically ill patients with septic shock. Demographic data, comorbidities, clinical information and severity scores were recorded. Data collected included serum Fol and B12 levels using the DxI® Autoanalyzer (Beckman Coulter) based on a competitive electrochemoluminescence immunoassay. Results: mean serum Fol was within the reference range stipulated by the laboratory on the first day. Nevertheless, a total of 21.4 % of the patients had high Fol levels, with 14.2 % being Fol deficient. An association was observed between Fol (p < 0.012) status and 28-day mortality, and the number of days of mechanical ventilation, fraction of inspired oxygen (FiO2) and fibrinogen increased in patients with higher Fol levels (p < 0.05). In addition, 85.7 % of cases had B12 levels above the reference values, with a correlation being observed between B12 and Fol. Conclusions: this study proposes Fol as a novel morbidity-mortality biomarker in critical septic patients, and reinforces the usefulness of B12 as a morbidity biomarker. It is thus suggested that the measurement of Fol upon admission and over the first 72 hours of hospital stay could provide prognostic information about the clinical course and outcome of septic shock patients (AU)

Introducción y objetivo: se realizó un estudio de las concentraciones séricas de ácido fólico (Fol) y vitamina B12 (B12) en pacientes críticos con shock séptico al ingreso y después de tres días de estancia en la Unidad de Cuidados Intensivos (UCI), con un análisis de su asociación con los parámetros inflamatorios y la morbimortalidad de los pacientes. Método: se realizó un estudio analítico prospectivo de 30 pacientes críticos con shock séptico. Se registraron datos demográficos, comorbilidades, información clínica y puntuaciones de gravedad. Los datos recopilados incluyeron los niveles séricos de Fol y B12 utilizando el autoanalizador DxI® (Beckman Coulter) basado en un inmunoensayo de electroquimioluminiscencia competitivo. Resultados: la media de Fol sérico estuvo dentro del rango de referencia estipulado por el laboratorio el primer día. Sin embargo, el 21,4 % de los pacientes presentaban niveles altos de Fol y el 14,2 % presentaban deficiencia de Fol. Se observó una asociación entre el estado de Fol (p < 0,012) con la mortalidad a los 28 días, con el número de días de ventilación mecánica, con la fracción de oxígeno inspirado (FiO2) y con el fibrinógeno, que aumentaron en los pacientes con niveles de Fol más altos (p < 0,05). Además, el 85,7 % de los casos tenían niveles de B12 por encima de los valores de referencia, observándose una correlación entre B12 y Fol. Conclusiones: este estudio propone al Fol como nuevo biomarcador de morbimortalidad en los pacientes críticos con sepsis y refuerza la utilidad de la B12 como biomarcador de morbilidad. Por tanto, se sugiere que la medición de Fol al ingreso y durante las primeras 72 horas de estancia hospitalaria podría proporcionar información pronóstica sobre el curso clínico y el resultado de los pacientes con shock séptico (AU)