Association of dead space fraction to mortality in patients with COVID-19-related ARDS: A historical cohort observational study.

OBJECTIVE: To assess the correlation of dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV) and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation. DESIGN: Observational study of a historical cohort. SETTING: University hospital in Medellin, Colombia. PARTICIPANTS: Patients aged 15 and above with a confirmed COVID-19 diagnosis admitted to the ICU and requiring mechanical ventilation. INTERVENTIONS: Measurement of VD/VT, CMV, and VR in COVID-19 patients. MAIN VARIABLES OF INTEREST: VD/VT, CMV, VR, demographic data, oxygenation indices and ventilatory parameters. RESULTS: During the study period, 1047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. The multivariate analysis revealed independent associations to in-hospital mortality, higher VD/VT (HR 1.24; 95%CI 1.003-1.525; p = 0.046), age (HR 1.024; 95%CI 1.014-1.034; p < 0.001), and SOFA score at onset (HR: 1.036; 95%CI: 1.001-1.07; p = 0.017). CONCLUSIONS: VD/VT demonstrated an association with mortality in COVID-19 patients with ARDS on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease.

A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

BACKGROUND: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals.

BACKGROUND: Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. METHODS: This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. RESULTS: In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. CONCLUSIONS: Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality.

A latent class approach for sepsis diagnosis supports use of procalcitonin in the emergency room for diagnosis of severe sepsis.

BACKGROUND: Given the acknowledged problems in sepsis diagnosis, we use a novel way with the application of the latent class analysis (LCA) to determine the operative characteristics of C-reactive protein (CRP), D-dimer (DD) and Procalcitonin (PCT) as diagnostic tests for sepsis in patients admitted to hospital care with a presumptive infection. METHODS: Cross-sectional study to determine the diagnostic accuracy of three biological markers against the gold standard of clinical definition of sepsis provided by an expert committee, and also against the likelihood of sepsis according to LCA. Patients were recruited in the emergency room within 24 hours of hospitalization and were follow-up daily until discharge. RESULTS: Among 765 patients, the expert committee classified 505 patients (66%) with sepsis, 112 (15%) with infection but without sepsis and 148 (19%) without infection. The best cut-offs points for CRP, DD, and PCT were 7.8 mg/dl, 1616 ng/ml and 0.3 ng/ml, respectively; but, neither sensitivity nor specificity reach 70% for any biomarker. The LCA analysis with the same three tests identified a "cluster" of 187 patients with several characteristics suggesting a more severe condition as well as better microbiological confirmation. Assuming this subset of patients as the new prevalence of sepsis, the ROC curve analysis identified new cut-off points for the tests and suggesting a better discriminatory ability for PCT with a value of 2 ng/ml. CONCLUSIONS: Under a "classical" definition of sepsis three typical biomarkers (CRP, PCT and DD) are not capable enough to differentiate septic from non-septic patients in the ER. However, a higher level of PCT discriminates a selected group of patients with severe sepsis.

Decrease in the intensive care unit-acquired weakness with a multicomponent protocol implementation: A quasi-experimental clinical trial / Disminución de la debilidad muscular adquirida en una unidad de cuidados intensivos con la implementación de un protocolo multicomponente: ensayo clínico cuasiexperimental

Introduction: Intensive care unit-acquired weakness is a frequent complication that affects the prognosis of critical illness during hospital stay and after hospital discharge. Objectives: To determine if a multicomponent protocol of early active mobility involving adequate pain control, non-sedation, non-pharmacologic delirium prevention, cognitive stimulation, and family support, reduces intensive care unit-acquired weakness at the moment of discharge. Materials and methods: We carried out a non-randomized clinical trial in two mixed intensive care units in a high-complexity hospital, including patients over 14 years old with invasive mechanical ventilation for more than 48 hours. We compared the intervention ­the multicomponent protocol­ during intensive care hospitalization versus the standard care. Results: We analyzed 82 patients in the intervention group and 106 in the control group. Muscle weakness acquired in the intensive care unit at the moment of discharge was less frequent in the intervention group (41.3% versus 78.9%, p<0.00001). The mobility score at intensive unit care discharge was better in the intervention group (median = 3.5 versus 2, p < 0.0138). There were no statistically significant differences in the invasive mechanical ventilation-free days at day 28 (18 versus 15 days, p<0.49), and neither in the mortality (18.2 versus 27.3%, p<0.167). Conclusion: A multi-component protocol of early active mobility significantly reduces intensive care unit-acquired muscle weakness at the moment of discharge.

Introducción: La debilidad adquirida en las unidades de cuidados intensivos es una complicación frecuente de los pacientes con enfermedades críticas, que puede tener un impacto negativo en su pronóstico a corto y a largo plazo. OBJETIVOS: Evaluar si la utilización de un protocolo multicomponente, que incluye movilidad activa temprana, manejo efectivo del dolor, reducción de la sedación, medidas no farmacológicas para prevenir el delirium, estimulación cognitiva y apoyo familiar, puede disminuir la incidencia de debilidad adquirida en las unidades de cuidados intensivos al momento del egreso del paciente. Materiales y métodos: Se trata de un ensayo clínico, no aleatorizado, en dos unidades de cuidados intensivos mixtas de un hospital de tercer nivel. Los participantes fueron pacientes mayores de 14 años con ventilación mecánica invasiva por más de 48 horas. Se aplicó como intervención un protocolo multicomponente y como control se utilizó el cuidado usual o estándar. RESULTADOS: Ingresaron 188 pacientes al estudio, 82 al grupo de intervención y 106 al grupo control. La tasa de debilidad adquirida en las unidades de cuidados intensivos al egreso de la unidad fue significativamente menor en el grupo de intervención (41,3 % versus 78,9 %, p<0,00001). La mediana del puntaje de movilidad al momento del alta de la unidad de cuidados intensivos fue mayor en el grupo de intervención (3,5 versus 2, p<0,0138). No se encontraron diferencias estadísticamente significativas en las medianas de días libres de respiración mecánica asistida, ni de unidad de cuidados intensivos al día 28, tampoco en la tasa de mortalidad general al egreso del hospital (18 versus 15 días, p<0,49; 18,2 % versus 27,3 %, p<0,167). CONCLUSIONES: Un protocolo multicomponente que incluía movilidad activa temprana tuvo un impacto significativo en la reducción de la debilidad adquirida en las unidades de cuidados intensivos al egreso en comparación con el cuidado estándar.

D-dimer is a significant prognostic factor in patients with suspected infection and sepsis.

PURPOSE: The aim of the study was to determine whether C-reactive protein (CRP), procalcitonin (PCT), and d-dimer (DD) are markers of mortality in patients admitted to the emergency department (ED) with suspected infection and sepsis. BASIC PROCEDURES: We conducted a prospective cohort in a university hospital in Medellín, Colombia. Patients were admitted between August 1, 2007, and January 30, 2009. Clinical and demographic data and Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores as well as blood samples for CRP, PCT, and DD were collected within the first 24 hours of admission. Survival was determined on day 28 to establish its association with the proposed biomarkers using logistic regression and receiver operating characteristic curves. MAIN FINDINGS: We analyzed 684 patients. The median Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores were 10 (interquartile range [IQR], 6-15) and 2 (IQR, 1-4), respectively. The median CRP was 9.6 mg/dL (IQR, 3.5-20.4 mg/dL); PCT, 0.36 ng/mL (IQR, 0.1-3.7 ng/mL); and DD, 1612 ng/mL (IQR, 986-2801 ng/mL). The median DD in survivors was 1475 ng/mL (IQR, 955-2627 ng/mL) vs 2489 ng/mL (IQR, 1698-4573 ng/mL) in nonsurvivors (P=.0001). The discriminatory ability showed area under the curve-receiver operating characteristic for DD, 0.68; CRP, 0.55; and PCT, 0.59. After multivariate analysis, the only biomarker with a linear relation with mortality was DD, with an odds ratio of 2.07 (95% confidence interval, 0.93-4.62) for values more than 1180 and less than 2409 ng/mL and an odds ratio of 3.03 (95% confidence interval, 1.38-6.62) for values more than 2409 ng/mL. PRINCIPAL CONCLUSIONS: Our results suggest that high levels of DD are associated with 28-day mortality in patients with infection or sepsis identified in the emergency department.

The epidemiology of sepsis in Colombia: a prospective multicenter cohort study in ten university hospitals.

OBJECTIVE: Our aim was to determine the frequency and the clinical and epidemiologic characteristics of sepsis in a hospital-based population in Colombia. DESIGN: Prospective cohort. SETTING: Ten general hospitals in the four main cities of Colombia. PATIENTS: Consecutive patients admitted in emergency rooms, intensive care units, and general wards from September 1, 2007, to February 29, 2008, with confirmation of infection according to the Centers for Disease Control and Prevention definitions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The following information was recorded: demographic, clinical, and microbiologic characteristics; Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores; requirement for intensive care unit; length of stay; and 28-day all-cause mortality. During a period of 6 months, 2,681 patients were recruited: 69% and 31% with community-acquired and hospital-acquired infections, respectively. The mean age was 55 yrs (SD = 21), 51% were female, and the median length of stay was 10 days (interquartile range, 5-19). The mean Acute Physiology and Chronic Health Evaluation score was 11.5 (SD = 7) and the mean Sequential Organ Failure Assessment score was 3.8 (SD = 3). A total of 422 patients with community-acquired infections (16%) were admitted to the intensive care unit as a consequence of their infection and the median length of stay was 4.5 days in the intensive care unit. At admission, 2516 patients (94%) met at least one sepsis criterion and 1,658 (62%) met at least one criterion for severe sepsis. Overall, the 28-day mortality rates of patients with infection without sepsis, sepsis without organ dysfunction, severe sepsis without shock, and septic shock were 3%, 7.3%, 21.9%, and 45.6%, respectively. In community-acquired infections, the most frequent diagnosis was urinary tract infection in 28.6% followed by pneumonia in 22.8% and soft tissue infections in 21.8%. Within hospital-acquired infections, pneumonia was the most frequent diagnosis in 26.6% followed by urinary tract infection in 20.4% and soft tissue infections in 17.4%. CONCLUSIONS: In a general inpatient population of Colombia, the rates of severe sepsis and septic shock are higher than those reported in the literature. The observed mortality is higher than the predicted by the Acute Physiology and Chronic Health Evaluation II score.

Unfractioned heparin for treatment of sepsis: A randomized clinical trial (The HETRASE Study).

OBJECTIVE: The primary aims of this study were to determine the effects of heparin on length of stay and change from baseline multiple organ dysfunction (MOD) score. Secondary objectives were to estimate the effects of heparin on 28-day all-cause mortality, and to determine the possible effect modification on 28-day all-cause mortality, in subgroups defined by site of infection and baseline values of Acute Physiology and Chronic Health Evaluation II score, MOD score, and d-dimer. DESIGN: Randomized, double-masked, placebo-controlled, single-center clinical trial, testing low dose continuous infusion of unfractioned heparin (UFH) as complementary treatment for sepsis. SETTING: Five hundred fifty bed University Hospital and referral center in Medellín, Columbia. PATIENTS: Three hundred nineteen patients admitted at the emergency room with signs indicative of sepsis. INTERVENTIONS: Patients were randomly assigned to receive placebo or UFH (500 units/hour for 7 days). MEASUREMENTS AND MAIN RESULTS: The median length of stay in patients discharged alive in the placebo group was 12.5 days (interquartile range = 8-20), and 12 days (interquartile range = 8-19.5) in the heparin group (p = 0.976). The MOD score improved equally in the two treatments arms with an average decline of 0.13 and 0.11 per day for the placebo and heparin groups (p = 0.240), respectively. The overall 28-day mortality was 16% in the placebo group and 14% in the heparin group (p = 0.652). Subgroup analyses did not show any statistically significant reduction in 28-day mortality with UFH. There was only one serious adverse event on a patient who received heparin but it was fully resolved without complications. CONCLUSIONS: Our findings suggested that UFH may be a feasible and safe intervention in sepsis. However, this study was not able to demonstrate a beneficial effect on the chosen primary outcomes or in the 28-day mortality rate.

Toward an operative diagnosis in sepsis: a latent class approach.

BACKGROUND: Recent data have suggested that 18 million of new sepsis cases occur each year worldwide, with a mortality rate of almost 30%. There is not consensus on the clinical definition of sepsis and, because of lack of training or simply unawareness, clinicians often miss or delay this diagnosis. This is especially worrying; since there is strong evidence supporting that early treatment is associated with greater clinical success. There are some difficulties for sepsis diagnosis such as the lack of an appropriate gold standard to identify this clinical condition. This situation has hampered the assessment of the accuracy of clinical signs and biomarkers to diagnose sepsis. METHODS/DESIGN: Cross-sectional study to determine the operative characteristics of three biological markers of inflammation and coagulation (D-dimer, C-reactive protein and Procalcitonin) as diagnostic tests for sepsis, in patients admitted to hospital care with a presumptive infection as main diagnosis. DISCUSSION: There are alternative techniques that have been used to assess the accuracy of tests without gold standards, and they have been widely used in clinical disciplines such as psychiatry, even though they have not been tested in sepsis diagnosis. Considering the main importance of diagnosis as early as possible, we propose a latent class analysis to evaluate the accuracy of three biomarkers to diagnose sepsis.

Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial.

INTRODUCTION: Critically ill patients can develop hyperglycaemia even if they do not have diabetes. Intensive insulin therapy decreases morbidity and mortality rates in patients in a surgical intensive care unit (ICU) and decreases morbidity in patients in a medical ICU. The effect of this therapy on patients in a mixed medical/surgical ICU is unknown. Our goal was to assess whether the effect of intensive insulin therapy, compared with standard therapy, decreases morbidity and mortality in patients hospitalised in a mixed ICU. METHODS: This is a prospective, randomised, non-blinded, single-centre clinical trial in a medical/surgical ICU. Patients were randomly assigned to receive either intensive insulin therapy to maintain glucose levels between 80 and 110 mg/dl (4.4 to 6.1 mmol/l) or standard insulin therapy to maintain glucose levels between 180 and 200 mg/dl (10 and 11.1 mmol/l). The primary end point was mortality at 28 days. RESULTS: Over a period of 30 months, 504 patients were enrolled. The 28-day mortality rate was 32.4% (81 of 250) in the standard insulin therapy group and 36.6% (93 of 254) in the intensive insulin therapy group (Relative Risk [RR]: 1.1; 95% confidence interval [CI]: 0.85 to 1.42). The ICU mortality in the standard insulin therapy group was 31.2% (78 of 250) and 33.1% (84 of 254) in the intensive insulin therapy group (RR: 1.06; 95%CI: 0.82 to 1.36). There was no statistically significant reduction in the rate of ICU-acquired infections: 33.2% in the standard insulin therapy group compared with 27.17% in the intensive insulin therapy group (RR: 0.82; 95%CI: 0.63 to 1.07). The rate of hypoglycaemia (< or = 40 mg/dl) was 1.7% in the standard insulin therapy group and 8.5% in the intensive insulin therapy group (RR: 5.04; 95% CI: 1.20 to 21.12). CONCLUSIONS: IIT used to maintain glucose levels within normal limits did not reduce morbidity or mortality of patients admitted to a mixed medical/surgical ICU. Furthermore, this therapy increased the risk of hypoglycaemia. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: 4374-04-13031; 094-2 in 000966421.

Disminución de la debilidad muscular adquirida en una unidad de cuidados intensivos con la implementación de un protocolo multicomponente: ensayo clínico cuasiexperimental

Introducción. La debilidad adquirida en las unidades de cuidados intensivos es una complicación frecuente de los pacientes con enfermedades críticas, que puede tener un impacto negativo en su pronóstico a corto y a largo plazo. Objetivos. Evaluar si la utilización de un protocolo multicomponente, que incluye movilidad activa temprana, manejo efectivo del dolor, reducción de la sedación, medidas no farmacológicas para prevenir el delirium, estimulación cognitiva y apoyo familiar, puede disminuir la incidencia de debilidad adquirida en las unidades de cuidados intensivos al momento del egreso del paciente. Materiales y métodos. Se trata de un ensayo clínico, no aleatorizado, en dos unidades de cuidados intensivos mixtas de un hospital de tercer nivel. Los participantes fueron pacientes mayores de 14 años con ventilación mecánica invasiva por más de 48 horas. Se aplicó como intervención un protocolo multicomponente y como control se utilizó el cuidado usual o estándar. Resultados. Ingresaron 188 pacientes al estudio, 82 al grupo de intervención y 106 al grupo control. La tasa de debilidad adquirida en las unidades de cuidados intensivos al egreso de la unidad fue significativamente menor en el grupo de intervención (41,3 % versus 78,9 %, p<0,00001). La mediana del puntaje de movilidad al momento del alta de la unidad de cuidados intensivos fue mayor en el grupo de intervención (3,5 versus 2, p<0,0138). No se encontraron diferencias estadísticamente significativas en las medianas de días libres de respiración mecánica asistida, ni de unidad de cuidados intensivos al día 28, tampoco en la tasa de mortalidad general al egreso del hospital (18 versus 15 días, p<0,49; 18,2 % versus 27,3 %, p<0,167). Conclusiones. Un protocolo multicomponente que incluía movilidad activa temprana tuvo un impacto significativo en la reducción de la debilidad adquirida en las unidades de cuidados intensivos al egreso en comparación con el cuidado estándar.

Introduction. Intensive care unit-acquired weakness is a frequent complication that affects the prognosis of critical illness during hospital stay and after hospital discharge. Objectives. To determine if a multicomponent protocol of early active mobility involving adequate pain control, non-sedation, non-pharmacologic delirium prevention, cognitive stimulation, and family support, reduces intensive care unit-acquired weakness at the moment of discharge. Materials and methods. We carried out a non-randomized clinical trial in two mixed intensive care units in a high-complexity hospital, including patients over 14 years old with invasive mechanical ventilation for more than 48 hours. We compared the intervention -the multicomponent protocol- during intensive care hospitalization versus the standard care. Results. We analyzed 82 patients in the intervention group and 106 in the control group. Muscle weakness acquired in the intensive care unit at the moment of discharge was less frequent in the intervention group (41.3% versus 78.9%, p<0.00001). The mobility score at intensive unit care discharge was better in the intervention group (median = 3.5 versus 2, p < 0.0138). There were no statistically significant differences in the invasive mechanical ventilation-free days at day 28 (18 versus 15 days, p<0.49), and neither in the mortality (18.2 versus 27.3%, p<0.167). Conclusion. A multi-component protocol of early active mobility significantly reduces intensive care unit-acquired muscle weakness at the moment of discharge.

Incidence and risk factors for ventilator-associated pneumonia in a developing country: where is the difference?

BACKGROUND: Latin America exhibits a wide range of differences, compared to developed nations, in genetic background, health services, and clinical research development. It is valid to hypothesize that the incidence and risk factors for ventilator-associated pneumonia (VAP) in our setting may be substantially different of those reported elsewhere. We conducted a study to determine the incidence and risk factors for VAP in a University Hospital from Medellin, Colombia. METHODS: Prospective cohort study in three intensive care units (ICU) (surgical/trauma, medical, cardiovascular) in a 550-bed University Hospital. Critically ill patients (n=270) who required at least 48 h of mechanical ventilation (MV) between June 2002 and October 2003 were followed until ICU discharge, VAP diagnosis or death. RESULTS: Sixty patients (22.2%) developed VAP 5.9+/-3.6 days after admission. The overall incidence of VAP was 29 cases per 1000 ventilator-days. The daily hazard for developing VAP increased until day 8, and then decreased over the duration of stay in the ICU. The only statistically significant factor after multivariable analysis was gender, with being female reducing 57% the risk of pneumonia (hazard ratios (HR): 0.43; 95% confidence intervals (CI): 0.19-0.96). CONCLUSIONS: The epidemiologic profile of VAP in terms of incidence, length of stay and clinical course resembles the general pattern described everywhere. Surprisingly, we could not identify any potentially modifiable risk factor for VAP. A comprehensive multicenter study is warranted. It should provide deep insight about the specific microbiological, genetic and clinic features of VAP in our setting.

[Anticoagulation and sepsis: the opportunity for a new use of heparin?]. / Anticoagulación y sepsis, la oportunidad para un nuevo uso de la heparina?

Sepsis is a leading cause of morbidity and mortality worldwide, and the magnitude of the problem seems higher in developing countries. In the last two decades the accepted standard treatment has resulted in only a slight decrease in mortality, and that decrease has been overshadowed by an almost 300% increase in incidence. Recently has been documented the close relationship between infection, inflammation and coagulation in sepsis has been documented; and although clinically overt disseminated intravascular coagulation may occur in only 30% to 50% of septic patients, the activation of the coagulation cascade is an early and common response to the infectious challenge. Moreover most of the molecules involved in the pro-coagulant state that characterizes sepsis are also powerful generators or amplifiers of the inflammatory response. These findings have fostered a comprehensive body of research regarding biological products with anticoagulant activity, as additional therapies for patients with the most severe states of the sepsis syndrome. This review explains the biological and molecular aspects that support the potential use of anticoagulant treatments in sepsis. Furthermore, we analyze the evidence provided by experimental and pre-clinical studies, which suggest the usefulness of heparin as an effective complementary treatment throughout the clinical stages of the disease.

[Epidemiology and prognosis of patients with bloodstream infection in 10 hospitals in Colombia]. / Epidemiología y pronóstico de pacientes con infección del torrente sanguíneo en 10 hospitales de Colombia.

BACKGROUND: Knowing the local epidemiology and etiology of bloodstream infections allows tailoring the empirical initial antimicrobial therapy to obtain a better outcome for these episodes. AIM: To describe the epidemiological and microbiological aspects as well as the factors associated with mortality in patients with bloodstream infection in Colombian hospitals. METHODS: Sub-analysis of a prospective cohort study of 375 consecutive patients with bloodstream infection in 10 hospitals in Colombia, admitted between September first 2007 and Febrnary 29, 2008. RESULTS: The most frequently isolated bacteria were Gram-negative bacilli in 54% of patients, followed by Gram-positive cocci in 38.4%. The source of infection was known in 67%, unknown in 24% and associated with intravascular catheter in 9%. The most frequently isolated bacteria were Escherichia coli (46%), coagulase-negative Staphylococci (16%), Klebsiella pneumoniae (8.9%) and Staphylococcus aureus (7.8%). Staphylococcus aureus was methicillin sensitive in 82% of patients (46/56). Overall 28-day mortality was 25% and their independent associated factors were age, SOFA score and APACHE II score. CONCLUSIONS: In our study the most frequently isolated bacteria in bloodstream infections were Gram-negative bacilli, contrasting those reported in developed countries. The overall mortality rate was high and the factors associated with mortality were age and severity scores.

Epidemiology of sepsis in Colombian intensive care units.

INTRODUCTION: Currently, there is not enough data available concerning sepsis in developing countries, especially in Latin America. OBJECTIVE: We developed a study aimed at determining the frequency, clinical and epidemiological characteristics, and the consequences of sepsis in patients requiring admission to intensive care units in Colombia. MATERIALS AND METHODS: This was a secondary analysis of a prospective cohort study carried out over a six-month period, from September 1, 2007, to February 28, 2008, in ten medical/surgical intensive care units in four Colombian cities. Patients were considered eligible if they had a probable or confirmed diagnosis of infection according to medical records. We recorded demographic characteristics, first admission diagnosis and co-morbidities, clinical status, and sepsis, severe sepsis or septic shock. RESULTS: During the study period, 826 patients were admitted to the intensive care units. From these patients, 421 (51%) developed sepsis in the community, 361 (44%) in the ICU, and 44 (5%) during hospitalization in the general ward. Two hundred and fifty three patients (30.6%) had involvement of one organ system: 20% had respiratory involvement, followed by kidney and central nervous system involvement with 3.4% and 2.7%, respectively. CONCLUSIONS: In our cohort of septic patients, the prevalence of sepsis treated in ICU is similar to that reported in other studies, as well as the overall mortality.

The potential impact of admission insulin levels on patient outcome in the intensive care unit.

BACKGROUND: Blood levels of insulin in patients with critical illness at admission to the intensive care unit (ICU) and its association with in-hospital mortality are not fully defined. Our objective was to determine this association in a cohort of patients with critical illness who attended in a mixed ICU. METHODS: Prospective cohort was nested in a randomized clinical trial conducted in a 12-bed mixed ICU in a tertiary hospital in Medellin (Colombia). One hundred sixty consecutively admitted patients, 15 years or older, were analyzed. Blood insulin and blood glucose levels were measured at admission to the ICU, as well as Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. A logistic regression model was created with in-hospital mortality as the outcome. RESULTS: In-hospital mortality was 57 (35.6%) of 160. Survivors had lower Acute Physiology and Chronic Health Evaluation II (median, 13 vs. 17) and lower insulin levels (median, 6.5 vs. 9 µU/mL) than did nonsurvivors. More women than men died (27 [48.2%] of 56 vs. 30 [28.8%] of 104), and 39% of the deaths (n = 22) occurred in patients with sepsis. Patients with insulin levels greater than 15 µU/mL had a higher mortality rate compared with patients with values of 5 µU/mL to 15 µU/mL (odds ratio, 3.57; 95% confidence interval, 1.18-10.8). CONCLUSION: At admission to the ICU, patients with critical illness showed hyperglycemia and relatively decreased insulin levels. High levels of insulin were independently associated with in-hospital mortality in this study population. LEVEL OF EVIDENCE: Prognostic study, level II.

[Serum lactate in the emergency department as a prognostic factor in patients with sepsis without hypotension]. / Lactato sérico en urgencias como factor pronóstico en pacientes con sepsis sin hipotensión.

BACKGROUND AND OBJECTIVE: The relationship between lactate and mortality in patients without hypotension has not been appropriately explored. Our aim was to determine the usefulness of serum lactate as a prognostic factor of 28-day mortality in patients admitted to the Emergency Department with clinical diagnosis of sepsis without septic shock. PATIENTS AND METHODS: We performed a secondary analysis of the study The epidemiology of sepsis in Colombia, a prospective cohort of patients from 10 general hospitals in 4 Colombian cities. We analyzed patients without hypotension with serum lactate available and admitted with community-acquired infections, which were confirmed according to the Centers for Disease Control and Prevention CDC criteria. A logistical regression was performed adjusting for age, sex, comorbidities and severity scores. RESULTS: We included 961 patients aged 57.2 ± 21.0 years, 54.2% were females, mean SOFA score was 3.0 ± 2.3 and APACHE score was 11.1±6.4. We observed a linear relationship between serum lactate and the odds of death, and after adjustment there was a significant and independent association between lactate and mortality (odds ratio 1,16, 95% confidence interval 1.02-1.33). CONCLUSION: Serum lactate is independently and significantly associated with 28-day mortality among patients with infection who present to the Emergency Department without hypotension. Besides, mortality increases in a linear way with serum lactate from any detectable value.

Characterization of nCD64 expression in neutrophils and levels of s-TREM-1 and HMGB-1 in patients with suspected infection admitted in an emergency department.

INTRODUCTION: The nCD64 receptor, the soluble triggering receptor expressed in myeloid cells (s-TREM-1), and the high mobility group-box 1 protein (HMGB-1) have been proposed as significant mediators in sepsis. OBJECTIVE: To evaluate the prognostic value of these markers in patients with suspected infection recently admitted in an emergency department (ED). MATERIALS AND METHODS: All patients who presented to the ED with suspected infection were eligible for enrollment in this study. Baseline clinical data, Sequential Organ Failure Assessment score (SOFA) score, APACHE II score, HMGB-1 levels, s-TREM-1 levels, and nCD64 levels were analyzed. The HMGB-1 and sTREM-1 serum concentrations were determined using commercially available ELISA kits, and CD64 on the surface of neutrophils was measured by flow cytometry. RESULTS: . A total of 579 patients with suspected infection as their admission diagnosis were enrolled in this study. The median patient age was 50 years (IQR = 35-68). Morbidity during the 28-day followup period was 11.1% (n=64). The most frequent diagnosis at the time of admission was communityacquired pneumonia (CAP) in 23% (n=133) patients, followed by soft tissue infection in 16.6% (n=96), and urinary tract infection in 15% (n=87). After multivariable analysis, no significant association was identified between any biomarker and 28-day mortality. CONCLUSION: In the context of a tertiary care hospital emergency department in a Latin-American city, the nCD64 receptor, s-TREM-1, and HMGB-1 biomarkers do not demonstrate prognostic utility in the management of patients with infection. The search continues for more reliable prognostic markers in the early stages of infection.

Epidemiología y pronóstico de pacientes con infección del torrente sanguíneo en 10 hospitales de Colombia / Epidemiology and prognosis of patients with bloodstream infection in 10 hospitals in Colombia

Background: Knowing the local epidemiology and etiology of bloodstream infections allows tailoring the empirical initial antimicrobial therapy to obtain a better outcome for these episodes. Aim: To describe the epidemiological and microbiological aspects as well as the factors associated with mortality in patients with bloodstream infection in Colombian hospitals. Methods: Sub-analysis of a prospective cohort study of 375 consecutive patients with bloodstream infection in 10 hospitals in Colombia, admitted between September first 2007 and Febrnary 29, 2008. Results: The most frequently isolated bacteria were Gram-negative bacilli in 54% of patients, followed by Gram-positive cocci in 38.4%. The source of infection was known in 67%, unknown in 24% and associated with intravascular catheter in 9%. The most frequently isolated bacteria were Escherichia coli (46%), coagulase-negative Staphylococci (16%), Klebsiella pneumoniae (8.9%) and Staphylococcus aureus (7.8%). Staphylococcus aureus was methicillin sensitive in 82% of patients (46/56). Overall 28-day mortality was 25% and their independent associated factors were age, SOFA score and APACHE II score. Conclusions: In our study the most frequently isolated bacteria in bloodstream infections were Gram-negative bacilli, contrasting those reported in developed countries. The overall mortality rate was high and the factors associated with mortality were age and severity scores.

Introducción: Conocer la epidemiología y etiología regional de las infecciones del torrente sanguíneo permite orientar una terapia antimicrobiana inicial empírica mejorando el resultado final del episodio. Objetivo: Describir los aspectos epidemiológicos, microbiológicos y factores asociados a la mortalidad de pacientes con infección del torrente sanguíneo en hospitales colombianos. Métodos: Sub-análisis de cohorte prospectivo de 375 pacientes consecutivos en 10 hospitales de Colombia con diagnóstico de infección del torrente sanguíneo, hospitalizados entre 1 de septiembre de 2007 y 29 de febrero de 2008. Resultados: Los microorganismos más frecuentemente aislados fueron los bacilos gramnegativos en 54% de los pacientes; seguidos por las cocáceas grampositivas en 38,4%. La fuente de infección fue secundaria a un foco conocido en 67%, desconocido en 24% y asociada a catéter intravascular en 9%. Los microorganismos más frecuentemente aislados fueron: Escherichia coli 46%, Staphylococcus coagulasa negativa 16%, Klebsiella pneumoniae 8,9% y Staphylococcus aureus 7,8%. Staphylococcus aureus fue sensible a meticilina en 82% de los pacientes (46/56). La mortalidad global fue de 25%. Los factores asociados con mayor mortalidad fueron: edad, puntaje SOFA y puntaje APACHE II. Conclusiones: En nuestro estudio, los microorganismos más frecuentemente aislados en pacientes que cursaron con bacteriemia fueron los bacilos gramnegativos, a diferencia de lo reportado en países desarrollados. La mortalidad general es alta y los factores asociados con riesgo de muerte fueron: la edad y los mayores puntajes de gravedad.

Diagnostic accuracy of HMGB-1, sTREM-1, and CD64 as markers of sepsis in patients recently admitted to the emergency department.

OBJECTIVES: The objectives were to evaluate the diagnostic accuracy for sepsis in an emergency department (ED) population of the cluster of differentiation-64 (CD64) glycoprotein expression on the surface of neutrophils (nCD64), serum levels of soluble triggering receptor expressed on myeloid cells-1 (s-TREM-1), and high-mobility group box-1 protein (HMGB-1). METHODS: Patients with any of the following as admission diagnosis were enrolled: 1) suspected infection, 2) fever, 3) delirium, or 4) acute hypotension of unexplained origin within 24 hours of ED presentation. Levels of nCD64, HMGB-1, and s-TREM-1 were measured within the first 24 hours of the first ED evaluation. Baseline clinical data, Sepsis-related Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE II) score, daily clinical and microbiologic information, and 28-day mortality rate were collected. Because there is not a definitive criterion standard for sepsis, the authors used expert consensus based on clinical, microbiologic, laboratory, and radiologic data collected for each patient during the first 7 days of hospitalization. This expert consensus defined the primary outcome of sepsis, and the primary data analysis was based in the comparison of sepsis versus nonsepsis patients. The cut points to define sensitivity and specificity values, as well as positive and negative likelihood ratios (LRs) for the markers related to sepsis diagnosis, were determined using receiver operative characteristics (ROC) curves. The patients in this study were a prespecified nested subsample population of a larger study. RESULTS: Of 631 patients included in the study, 66% (95% confidence interval [CI] = 62% to 67%, n = 416) had sepsis according with the expert consensus diagnosis. Among these sepsis patients, SOFA score defined 67% (95% CI = 62% to 71%, n = 277) in severe sepsis and 1% (95% CI = 0.3% to 3%, n = 6) in septic shock. The sensitivities for sepsis diagnosis were CD64, 65.8% (95% CI = 61.1% to 70.3%); HMGB-1, 57.5% (95% CI = 52.7% to 62.3%); and s-TREM-1, 60% (95% CI = 55.2% to 64.7%). The specificities were CD64, 64.6% (95% CI = 57.8% to 70.8%), HMGB-1, 57.8% (95% CI = 51.1% to 64.3%), and s-TREM-1, 59.2% (95% CI = 52.5% to 65.6%). The positive LR (LR+) for CD64 was 1.85 (95% CI = 1.52 to 2.26) and the negative LR (LR-) was 0.52 (95% CI = 0.44 to 0.62]; for HMGB-1 the LR+ was 1.36 (95% CI = 1.14 to 1.63) and LR- was 0.73 (95% CI = 0.62 to 0.86); and for s-TREM-1 the LR+ was 1.47 (95% CI = 1.22 to 1.76) and the LR- was 0.67 (95% CI = 0.57 to 0.79). CONCLUSIONS: In this cohort of patients suspected of having any infection in the ED, the accuracy of nCD64, s-TREM-1, and HMGB-1 was not significantly sensitive or specific for diagnosis of sepsis.