Fabián Jaimes

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.

Comparison between logistic regression and neural networks to predict death in patients with suspected sepsis in the emergency room

IntroductionNeural networks are new methodological tools based on nonlinear models. They appear to be better at prediction and classification in biological systems than do traditional strategies such as logistic regression. This paper provides a practical example that contrasts both approaches within the setting of suspected sepsis in the emergency room.MethodsThe study population comprised patients with suspected bacterial infection as their main diagnosis for admission to the emergency room at two University-based hospitals. Mortality within the first 28 days from admission was predicted using logistic regression with the following variables: age, immunosuppressive systemic disease, general systemic disease, Shock Index, temperature, respiratory rate, Glasgow Coma Scale score, leucocyte counts, platelet counts and creatinine. Also, with the same input and output variables, a probabilistic neural network was trained with an adaptive genetic algorithm. The network had three neurone layers: 10 neurones in the input layer, 368 in the hidden layer and two in the output layer. Calibration was measured using the Hosmer-Lemeshow goodness-of-fit test and discrimination was determined using receiver operating characteristic curves.ResultsA total of 533 patients were recruited and overall 28-day mortality was 19%. The factors chosen by logistic regression (with their score in parentheses) were as follows: immunosuppressive systemic disease or general systemic disease (2), respiratory rate 24–33 breaths/min (1), respiratory rate ≥ 34 breaths/min (3), Glasgow Come Scale score ≤12 (3), Shock Index ≥ 1.5 (2) and temperature <38°C (2). The network included all variables and there were no significant differences in predictive ability between the approaches. The areas under the receiver operating characteristic curves were 0.7517 and 0.8782 for the logistic model and the neural network, respectively (P = 0.037).ConclusionA predictive model would be an extremely useful tool in the setting of suspected sepsis in the emergency room. It could serve both as a guideline in medical decision-making and as a simple way to select or stratify patients in clinical research. Our proposed model and the specific development method – either logistic regression or neural networks – must be evaluated and validated in an independent population.

Predicting Bacteremia at the Bedside

Our aim was to develop a clinical prediction rule for detection of bacteremia in a cohort of patients observed prospectively at a reference center in Medellín, Colombia. The significant predictors of bacteremia were an age of >or=30 years (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.19-3.60), a heart rate of >or=90 beats/min (OR, 1.90; 95% CI, 1.13-3.17), a temperature of >or=37.8 degrees C (OR, 2.42; 95% CI, 1.41-4.14), a leukocyte count of >or=12,000 cells/microL (OR, 2.40; 95% CI, 1.41-4.10), use of a central venous catheter (OR, 1.89; 95% CI, 1.02-3.50), and a length of hospitalization of >or=10 days (OR, 2.02; 95% CI, 1.25-3.24). The Hosmer-Lemeshow test revealed a goodness-of-fit of 2.99 (P=.981), and the area under the receiver operating characteristics curve was 0.7186. Simple variables obtained from the clinical history of patients are associated with bloodstream infection in a reproducible fashion and should be instrumental for prioritizing the requests for blood cultures by clinicians.

Lack of microbiological concordance between bone and non-bone specimens in chronic osteomyelitis: an observational study

BackgroundPrognosis of chronic osteomyelitis depends heavily on proper identification and treatment of the bone-infecting organism. Current knowledge on selecting the best specimen for culture is confusing, and many consider that non-bone specimens are suitable to replace bone cultures. This paper compares the microbiology of non-bone specimens with bone cultures, taking the last as the diagnostic gold standard.MethodsRetrospective observational analysis of 50 patients with bacterial chronic osteomyelitis in a 750-bed University-based hospital.ResultsConcordance between both specimens for all etiologic agents was 28%, for Staphylococcus aureus 38%, and for organisms other than S. aureus 19%. The culture of non-bone specimens to identify the causative organisms in chronic osteomyelitis produced 52% false negatives and 36% false positives when compared against bone cultures.ConclusionsDiagnosis and therapy of chronic osteomyelitis cannot be guided by cultures of non-bone specimens because their microbiology is substantially different to the microbiology of the bone.

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.

The systemic inflammatory response syndrome (SIRS) to identify infected patients in the emergency room

ObjectiveEvaluation of the usefulness of criteria for systemic inflammatory response syndrome (SIRS) compared with the final diagnosis of infection in patients admitted to the emergency room of two university-based hospitals.DesignLongitudinal cohort study.SettingHospital Universitario San Vicente de Paul and Hospital General de Medellín, Medellín, Colombia.PatientsSeven hundred thirty-four patients with suspected infection as main diagnosis for admittance into the emergency room.Measurements and resultsSensitivity, specificity, predictive values and likelihood ratios (LR) of SIRS criteria at admission were determined using, as gold standards, the diagnosis at the time of discharge based on clinical history and evolution, and microbiological confirmation of infection. SIRS criteria were met by 503 patients (68.5%); the discharge diagnosis of infection was found in 657 (89.4%) and 276 (37%) had microbiological confirmation. SIRS criteria exhibited a sensitivity of 69%, specificity of 35%, positive predictive value (PPV) of 90%, negative predictive value (NPV) of 12% and positive LR of 1.06. There were no differences between the two gold standards.ConclusionsThe finding of two or more SIRS criteria was of little usefulness for diagnosis of infection. It is necessary to work with new criteria and probably with biological markers, in order to obtain a simple, precise and operative definition of the sepsis phenomenon.

Immunological characterization of compensatory anti-inflammatory response syndrome in patients with severe sepsis: a longitudinal study*.

Objectives:To perform a complete immunological characterization of compensatory anti-inflammatory response syndrome in patients with sepsis and to explore the relationship between these changes and clinical outcomes of 28-day mortality and secondary infections. Design:Prospective single-center study conducted between April 2011 and December 2012. Setting:ICUs from Hospital Universitario San Vicente Fundación at Medellin, Colombia. Patients:One hundred forty-eight patients with severe sepsis. Interventions:None. Measurements and Main Results:At days 0, 1, 3, 5, 10, and 28, we determined the expression of HLA-DR in monocytes and the apoptosis and the proliferation index in T lymphocytes, as well as the levels of tumor necrosis factor-&agr;, interleukin-6, interleukin-1&bgr;, interleukin-10, and transforming growth factor-&bgr; in both plasma and cell culture supernatants of peripheral blood mononuclear cells. The mean percentage of HLA-DR+ was 60.7 at enrollment and increased by 0.9% (95% CI, 0.7–1.2%) per day. The mean percentage of CD4 T cells and CD8 T cells AV+/7-AAD– at enrollment was 37.2% and 20.4%, respectively, but it diminished at a rate of –0.5% (95% CI, –0.7% to –0.3%) and –0.3% (95% CI, –0.4% to –0.2%) per day, respectively. Plasma levels of interleukin-6 and interleukin-10 were 290 and 166 pg/mL and decreased at a rate of –7.8 pg/mL (95% CI, –9.5 to –6.1 pg/mL) and –4 pg/mL (95% CI, –5.1 to –2.8 pg/mL) per day, respectively. After controlling for confounders, only sustained plasma levels of interleukin-6 increase the risk of death (hazard ratio 1.003; 95% CI, 1.001–1.006). Conclusions:We found no evidence to support a two-phase model of sepsis pathophysiology. However, immunological variables did behave in a mixed and time-dependent manner. Further studies should evaluate changes over time of interleukin-6 plasma levels as a prognostic biomarker for critically ill patients.

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.

Usefulness of Severity Scores in Patients with Suspected Infection in the Emergency Department: A Systematic Review

BACKGROUND Score systems for severity of illness and organ dysfunction have been validated and used as tools to predict the risk of death in intensive care unit (ICU) patients, but their usefulness in patients with suspected infection in the emergency department (ED) or hospital ward is unclear. OBJECTIVES The objective of this systematic review was to establish the accuracy of score systems in the prediction of mortality in patients with suspected infection in hospital settings compared to the ICU. METHODS Three researchers independently performed a systematic search and a review of related articles and their references using the PubMed database. The articles were selected by consensus, based on previously defined inclusion and exclusion criteria. RESULTS In total, 21 studies were included, 19 of which were carried out in the ED. The researchers found that the operative characteristics to evaluate the accuracy (calibration and discrimination) of the different scores were insufficiently assessed in most studies. Only two studies evaluated the calibration, using the Hosmer-Lemeshow goodness-of-fit test, and less than half of the studies evaluated the discrimination, using the area under the receiver operator characteristics curve. CONCLUSIONS The reviewed literature did not provide enough information to assess the accuracy of the prognostic models in patients with suspected infection admitted to the ED and hospital ward. Some reports suggest a better accuracy with new scores like the MEDS (Mortality in Emergency Department Sepsis score), but the results are not consistent.

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.