Gisela De La Rosa

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

IntroductionCritically 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.MethodsThis 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.ResultsOver 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 (≤ 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).ConclusionsIIT 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 Registrationclinicaltrials.gov Identifiers: 4374-04-13031; 094-2 in 000966421

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.

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.

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.

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.

Toward an operative diagnosis in sepsis: a latent class approach

BackgroundRecent 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/designCross-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.DiscussionThere 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.

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

BackgroundSepsis 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.MethodsThis 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.ResultsIn 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.ConclusionsIntraabdominal 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 randomized clinical trial of unfractioned heparin for treatment of sepsis (the HETRASE study): design and rationale [NCT00100308].

IntroductionInfection promotes coagulation via a large number of molecular and cellular mechanisms, and this procoagulant activity has boosted basic and clinical research using anticoagulant molecules as therapeutic tools in sepsis. Heparin, which is a naturally occurring proteoglycan that acts by reducing thrombin generation and fibrin formation, has not been rigorously tested in a randomized clinical trial.MethodsRandomized, double-masked, placebo-controlled, single-center clinical trial. Patients are recruited through the emergency room at Hospital Universitario San Vicente de Paul. This is a 650-bed University Hospital in Medellín, Colombia and is a referral center for a region with approximately 3 million habitants. The recruitment process started on July 2005 and will finish on June 2007. Patients aged 18 years or older, males or females, hospitalized with clinically or microbiological confirmed sepsis, have been included. The interventions are unfractioned heparin in low dose continuous infusion (500 units per hour for 7 days) or placebo, additionally to the standard of care for sepsis patients in Colombia.ResultsOur primary aims are to estimate the effects of heparin on hospital length of stay and change from baseline Multiple Organ Dysfunction (MOD) score. Secondary objectives are to estimate the effects of heparin on 28-day all-cause mortality, and to estimate the possible effect modification on 28-day all-cause mortality, in subgroups defined by source and site of infection, and baseline values of APACHE II score, MOD score and D-dimer.ConclusionThe available literature in animal and human research, and the understanding of the molecular biology regarding inflammation and coagulation, supports a randomized clinical trial for the use of heparin in sepsis. Our study will provide appropriate power to detect differences in valid surrogate outcomes, and it will explore important preliminary data for efficacy regarding the clinical end-point of mortality.

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.