Risk Factors For Severe Sepsis Research Articles

Clinical value of TAT, PIC and t-PAIC as predictive markers for severe sepsis in pediatric patients.

Sepsis in pediatric patients can progress to severe sepsis, and identifying biomarkers of this progression may permit timely intervention to prevent it. This study aimed to investigate the ability of thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC) and tissue-type plasminogen activator-inhibitor complex (t-PAIC) to predict severe sepsis in pediatrics early. 148 eligible pediatric sepsis patients were enrolled in this study, and were then divided into those who progressed to severe sepsis (n = 50) or not (n = 98). Serum levels of TAT, PIC, and t-PAIC were analysed, and simplified pediatric critical illness score (PCIS) and DIC score were calculated on the day of pediatric sepsis diagnosis. Compared with sepsis patients, severe sepsis patients had higher levels of TAT, PIC and t-PAIC. Correlation analysis revealed that TAT, PIC and t-PAIC were significantly correlated with simplified PCIS and DIC score. ROC curve analysis suggested that TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis with the AUC up to 0.862, 0.759 and 0.851, respectively. Stratified analysis demonstrated that the patients with increased levels of TAT, PIC and t-PAIC had worse illness severity and clinical outcome. Univariate logistic regression analysis revealed that TAT, PIC and t-PAIC were all risk factors for severe sepsis, yet only TAT and t-PAIC were independent risk factors in multivariate model. TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis, and correlated with illness severity in pediatrics, what's more, serum levels of TAT and t-PAIC may be independent risk factors for pediatric severe sepsis.

Abstract 17153: Mitochondrial Cx43 and Gja1-20k Contribute to Sex-Specific Differences of Mitochondrial Response in Septic Cardiomyopathy

Introduction: Cardiac dysfunction contributes to morbidity and mortality of severe sepsis. Preserving mitochondrial (mito) activity is key to maintaining cardiac function. While epidemiological studies consistently report that male sex is an important risk factor for severe sepsis, it is unknown if male heart mito are susceptible to septic injury. We have shown that male cardiomyocyte mito were more vulnerable to TNFα- or H 2 O 2 -induced stress than females. We have also demonstrated that mito connexin 43 (Cx43 or Gja1) and its smaller isoform - Gja1-20k are implicated in sex-related heart response following myocardial ischemia. Hypothesis : In this study, we hypothesize that during sepsis, female (F) hearts exhibit preserved mito Cx43 and Gja1-20k to confer mitochondrial protection, thus improving cardiac function compared to male (M) myocardium. Methods: Age-matched adult M & F C57BL/6 mice received LPS (7.5 mg/kg BW, i.p.) or PBS (n > 6 mice/group). Cardiac function was detected 20h post LPS by 2D echocardiography. Cx43, Gja1-20k, OXPHOS, & PGC-1 were evaluated in M & F mouse heart mito 24h after LPS by Western Blot (n>3 hearts/group). Mito Cx43 was also detected by Immuno-electron microscopy (EM). Mito membrane potential (ΔΨm) was analyzed in cardiomyocytes (from adult M & F mice, n>3 hearts/group) +/- 1h LPS (1 μg/ml) using JC1 fluorescent probe. Mito respiration capacity was further assessed in H9c2 cells transfected with Gja1 siRNA upon LPS exposure by Seahorse XF Mito Stress test. Results: Decreased cardiac function was observed in M mice after LPS injection, but not in F. Higher mito levels of Cx43, Gja1-20k, OXPHOS, & PGC1 were noticed in F mouse hearts compared to M after LPS. Despite no difference in total Cx43 particles between M & F hearts by EM, more gold Cx43 particles were observed in F heart mito compared to M mito following LPS. LPS reduced ΔΨm in M cardiomyocytes, but not in F. Cx43 knockdown decreased mito maximal respiration capacity & ATP production in H9c2 cells with LPS stress. Conclusions: The mitochondria-derived protective mechanism is preserved in F mice, leading to better cardiac function than M mice following LPS-induced sepsis. F cardiac mito are more resistant to LPS challenge than M mito, partially due to preserved mito Cx43 and/or Gja1-20k.

Severe Sepsis After Living Donor Liver Transplantation: Risk Factors and Outcomes.

The post-operative mortality and morbidity rates associated with living-donor liver transplantation (LDLT) are still relatively high. Several papers have reported the risk factors associated with post-operative infectious complications, but few have analyzed the risk factors with respect to the severity of sepsis. The aim of this study was to clarify the risk factors that affect severe sepsis after LDLT. For 63 LDLT patients at our institute, we compared peri-operative characteristics in 29 patients who developed sepsis after surgery and 34 patients who didnot. The sepsis group was further divided into severe sepsis (n= 16) and sepsis (n= 13) subgroups to identify significant peri-operative risk factors. Multivariate analysis identified 3 significant risk factors for post-operative sepsis after LDLT: ABO incompatibility (P= .015), low estimated glomerular filtration rates (<90mL/min/1.73 m(2); P= .074), and low peripheral lymphocyte counts (<850/μL; P=.008). Multivariate analysis showed that the only significant risk factor for severe sepsis was a low pre-operative lymphocyte count (<850/μL; P= .01). In the 2 sepsis subgroups, the 5- and 10-year survival rates for the severe sepsis subgroup (37.5% and37.5%) were significantly lower than for the sepsis subgroup (83.3% and 62.5%; P= .05). The lung was the most common site of severe sepsis (n= 8; 50.0%). Patients who developed severe sepsis after LDLT had poor long-term survival, with pre-operative lymphocyte counts<850/μL being the significant risk factor. Pre-operative nutritional intervention and rehabilitation should be considered to improve LDLT outcomes.

Risk factors for severe sepsis in community-onset bacteraemic urinary tract infection: Impact of antimicrobial resistance in a large hospitalised cohort

To determine risks factors associated with severe sepsis or septic shock (SS) at admission in patients with community-onset bacteraemic urinary tract infection (CO-BUTI) including the impact of multidrug-resistant (MDR) bacteria. We analysed a prospective cohort of all consecutive episodes of CO-BUTI requiring hospitalisation in 8 tertiary hospitals of Spain between October 2010 and June 2011. Of an overall of 525 CO-BUTI episodes, 175 (33%) presented with SS at admission. MDR bacteria were isolated in 29% (51/175) of episodes with SS and in 33% (117/350) of those without SS (p = 0.32). The main MDR microorganism was Escherichia coli in both groups (25% and 28% respectively). Independent risk factors associated with SS at admission were: having fatal underlying conditions, McCabe score II/III (OR 1.90; 95%CI 1.23-2.92; p = 0.004), presence of an indwelling urethral catheter (OR 3.01; 95%CI 1.50-6.03; p = 0.002) and a history of urinary tract obstruction (OR 1.56; 95%CI 1.03-2.34; p = 0.03). After considering interactions, indwelling urethral catheters were a risk factor only for patients without fatal underlying conditions. SS at hospital admission occurred in a third of CO-BUTI. Mainly host factors, and not the causative microorganisms or antimicrobial resistance patterns had an impact on the presence of SS.

Risk of developing severe sepsis after acute kidney injury: a population-based cohort study

IntroductionSepsis has been a factor of acute kidney injury (AKI); however, little is known about dialysis-requiring AKI and the risk of severe sepsis after survival to discharge.MethodsWe conducted a population-based cohort study based on the Taiwan National Health Insurance Research Database from 1999 to 2009. We identified patients with AKI requiring dialysis during hospitalization and survived for at least 90 days after discharge, and matched them with those without AKI according to age, sex, and concurrent diabetes. The primary outcome was severe sepsis, defined as sepsis with a diagnosis of acute organ dysfunction. Individuals who recovered enough to survive without acute dialysis were further analyzed.ResultsWe identified 2983 individuals (mean age, 62 years; median follow-up, 3.96 years) with dialysis-requiring AKI and 11,932 matched controls. The incidence rate of severe sepsis was 6.84 and 2.32 per 100 person-years among individuals with dialysis-requiring AKI and without AKI in the index hospitalization, respectively. Dialysis-requiring AKI patients had a higher risk of developing de novo severe sepsis than the non-AKI group. In subgroup analysis, even individuals with recovery from dialysis-requiring AKI were at high risk of developing severe sepsis.ConclusionsAKI is an independent risk factor for severe sepsis. Even patients who recovered from AKI had a high risk of long-term severe sepsis.

UP-01.123 Risk Factor for Severe Infection in Patients With Urosepsis

The underlying UTI is almost exclusively a complicated one with involvement of urogenital organs. In urosepsis, the severity of sepsis depends mostly upon the host response. We, therefore, examined the incidence rate, microbiology, outcome, and antimicrobial resistance in patients with urosepsis, to identify risk factors for severe sepsis.

Genomic polymorphisms within alpha 7 nicotinic acetylcholine receptor and severe sepsis in Chinese Han population

Alpha 7 nicotinic acetylcholine receptor, a kind of ligand-gated ion channel mainly expressed in macrophages, plays a crucial role in improving survival in sepsis via suppressing proinflammatory cytokines. The predisposition of genomic polymorphisms within alpha 7 nicotinic acetylcholine receptor gene (CHRNA7) to sepsis has not been investigated. The current association study was performed to analyse six common genetic variations within 5'-upstream region of CHRNA7 gene in 229 patients with severe sepsis and 267 controls. Neither allelic frequencies nor genotype distributions were significantly different between patients and controls, as well as between surviving and nonsurviving patients. The frequencies of estimated haplotypes were also comparable between above defined groups. The present study suggests that genomic polymorphisms in the 5'-upstream region of CHRNA7 gene may not be a major risk factor for severe sepsis in Chinese Han population.

Lipoproteins and CETP levels as risk factors for severe sepsis in hospitalized patients

The magnitude of lipoprotein level reduction during the acute-phase response may be associated with the severity and mortality of sepsis. However, it remains to be determined whether low lipoprotein levels can be considered a risk factor for developing sepsis. We aimed to investigate lipoprotein levels as risk factors for sepsis in hospitalized patients, and also describe sequential changes in lipoprotein and cholesterol ester transfer protein (CETP) levels during sepsis. This is a prospective cohort study and case-control analysis from selected hospitalized patients. Blood samples were collected at admission, and participants were monitored for severe sepsis. Total cholesterol, high density lipoprotein (HDL), low density lipoprotein, and triglyceride levels were compared between sepsis cases and controls. Cholesterol, apolipoprotein, phospholipid and CETP concentrations were monitored in the case group. Of 1719 enrolled patients, 51 developed severe sepsis and were paired with 71 controls by age, gender, presence of infection at admission and chronic disease. HDL cholesterol level at admission was a risk factor for severe sepsis (OR = 0.969; 95% CI: 0.944-0.995). Mean CETP levels diminished between hospital admission and day 3 of sepsis. The magnitude of this variation (Delta CETP) was more pronounced in non-survivors (0.78 +/- 1.08 microg mL(-1)) than that in survivors (0.02 +/- 0.58 microg mL(-1), P = 0.01). HDL cholesterol may have a protective effect against sepsis. Each 1 mg dL(-1) increase in HDL decreased the odds of severe sepsis by 3% during hospitalization. The reduction of plasma CETP was associated with mortality.

Predictive Factors of Severe Sepsis and Septic Shock in Patients with Hematological Malignancies and Pseudomonas Infections.

Abstract 4552 BackgroundPseudomonas aeruginosa is a leading cause of nosocomial infections usually associated with high mortality. The aim of this study was to determine the predictive factors of severe sepsis or septic shock in patients with hematological malignancies and pseudomonas infections. MethodsThis study was conducted in a teaching hospital (Aziza Othmana University Hospital, Tunis, Tunisia) to evaluate the clinical profile of infections due to Pseudomonas species and to determine risk factors for severe sepsis or septic shock defined according to the criteria of the ACCP/SCCM. Pearson test was used for univariate analysis, and logistic regression for multivariate analysis. ResultsBetween 2004 and 2009,a total of 73 pseudomonas isolates (70 P, aeruginosa) was collected in 60 patients : 47 with acute leukemia (78%), 7 with lymphoma (12%), and 6 with others hematological disorders (10%).The median age was 29 yrs (range, 2-64). Most common sites of the isolates were from bloodstream (45%), and skin lesions (31.5%). At least 11 patients (18%) had 2 or more infections due to Pseudomonas. The most common clinical signs observed were isolated fever (18%), respiratory symptoms (15%), diarrhea (21%), and skin lesions (29%).Susceptibility to major anti-pseudomonas antibiotics revealed that isolates tested were resistant to:piperacillin/tazobactam (40%), cefatazidim (28%), ciprofloxacin (20.5%), imipenem (22%), and amikacin (22%).Severe sepsis or septic shock occurred in 49% of episodes. Crude mortality was (18%, 11 of the 60 patients) all caused by septic shock. In univariate analysis factors associated with severe sepsis or septic shock were: Isolates from more than one site (p=0.04), Absolute neutrophil count < 0.1 × 109/l (p=0.003), concomitant infection with other microorganism (p=0.019), fever lasting for more than 3 days in patients with antibiotherapy (p=0.003), C-reactive protein > 100 mg/l (p <0.0001), serum lactate >2.2 mmol/l (p< 0.0001), serum bicarbonate < 19 mmol/l (p=0.002), hemoglobin level < 70g/l (p<0.0001), renal failure (p=0.006), hypophosphatemia <0.8mmol/l (p=0.003), total bilirubin > 50 μmol/l (p=0.03), and hypoproteinemia <64g/l (p<0.0001). By multivariate analysis, antibiotherapy for more than 3 days (p=0.025,OR=0.217, 95%CI:0.05-0.82), absolute neutrophil count <0.1× 109/l (p=0.046,OR=170;95% CI:1-267), C-reactive protein >100 (p=0.04,OR=15,95%CI: 1,1-219,8), hemoglobin level <70g/l (p=0.037,OR=17,95%CI: 1,1- 243), and hypophosphatemia (p=0.02,OR=148,95%CI:2.2-942) remained as independent predictors of severe sepsis or septic shock. ConclusionsThis study revealed that several factors such as level of neutrophil count, C-reactive protein, hemoglobin level, severe hypophosphatemia, and antibiotherapy > 72 h before microbiological documentation may play a significant and independent role for the development of severe sepsis/septic shock and increase mortality of Pseudomonas infections in patients with hematological malignancies. Disclosures:No relevant conflicts of interest to declare.

Protein Z G79A Polymorphism in Patients With Severe Sepsis

The aim of the study is to investigate whether the presence of a protein Z polymorphism is a risk factor for the development and outcome of sepsis. Sepsis is a clinical syndrome characterized by the presence of systemic signs and symptoms of inflammation. When sepsis leads to organ failure, the term severe sepsis and septic shock is used. The genetic causes of severe sepsis are not fully explained. Protein Z is a vitamin K- dependent glycoprotein and a member of the coagulation cascade. The study included 53 patients with severe sepsis and 70 control healthy volunteers without a familial history of thrombosis. The G79A polymorphism of intron F of the protein Z gene was analyzed by the method of polymerase chain reaction-based DNA analysis. The protein Z intron F G79A polymorphism frequencies of the patients and controls were 43.4% and 40%, respectively. Carrying 79 AA genotype could be a risk factor for severe sepsis and septic shock (OR = 4.5, 95% CI: 0.45-46.1), but it could not find any difference between survivor and nonsurvivor groups. They concluded that the frequency of intron F G79A polymorphism of protein Z gene was higher in patients than controls, and carrying 79 AA genotype could be a risk factor for severe sepsis and septic shock.

Severe sepsis in autologous stem cell transplant recipients: Microbiological aetiology, risk factors and outcome

Infectious complications are the main reason for early treatment-related mortality after autologous stem cell transplantation (ASCT). We evaluated retrospectively microbiological aetiology, risk factors and clinical consequences of severe sepsis in this patient cohort. From 1996 to 2006 a total of 319 patients underwent ASCT at our institution. Antibacterial prophylaxis was not used. Neutropenic fever occurred in 83% (n=265) and was complicated by severe sepsis in 5% (n=17) of patients. Severe sepsis tended to be more common in patients with non-Hodgkin's lymphoma (NHL) than in other patients (9% vs 3%, p=0.009). Bacteraemia was observed more commonly in patients with severe sepsis (76% vs 22%, p<0.001); Pseudomonas sp. was found in 30% (n=5) of these patients. Kinetics of C-reactive protein (CRP) more commonly coincided with, rather than predicted, the development of severe sepsis. All other observed risk factors for severe sepsis (length of neutropenia, fever and blood culture findings) were late indicators. Severe sepsis was fatal in 9 patients (53%), and all had NHL (p=0.003 compared to other patients). Severe sepsis is an important cause of early mortality after ASCT, especially in NHL patients. Ways to prevent development of severe sepsis or predict its development might reduce early mortality among ASCT recipients.

A multicentre case-control study of nonsteroidal anti-inflammatory drugs as a risk factor for severe sepsis and septic shock.

IntroductionWe aimed to establish whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during evolving bacterial community-acquired infection in adults is associated with severe sepsis or septic shock.MethodsWe conducted a multicentre case-control study in eight intensive care units. Cases were all adult patients admitted for severe sepsis or septic shock due to a bacterial community-acquired infection. Control individuals were patients hospitalized with a mild community-acquired infection. Each case was matched to one control for age, presence of diabetes and site of infection.ResultsThe main outcome measures were the proportions of cases and controls exposed to NSAIDs or aspirin during the period of observation. In all, 152 matched pairs were analyzed. The use of NSAIDs or aspirin during the observation period did not differ between cases and controls (27% versus 28; odds ratio = 0.93, 95% confidence interval [CI] = 0.52 to 1.64). If aspirin was not considered or if a distinction was made between acute and chronic drug treatment, there remained no difference between groups. However, the median time to prescription of effective antibiotic therapy was longer for NSAID users (6 days, 95% CI = 3 to 7 days) than for nonusers (3 days, 95% CI = 2 to 3 days; P = 0.02).ConclusionsIn this study, the use of NSAIDs or aspirin during evolving bacterial infection was frequent and occurred in one-quarter of the patients with such infection. Although the use of NSAIDs by patients with severe sepsis or septic shock did not differ from their use by those with mild infection at the same infected site, we observed a longer median time to prescription of effective antibiotic therapy in NSAID users.

Predictors of Severe Sepsis Not Clinically Apparent During the First Twenty-Four Hours of Hospitalization in Children With Cancer, Neutropenia, and Fever

Severe sepsis is not clinically apparent during the first 24 hours of hospitalization in most children with cancer and febrile neutropenia (FN), delaying targeted interventions that could impact mortality. The aim of this study was to prospectively evaluate biomarkers obtained within 24 hours of hospitalization as predictors of severe sepsis before it becomes clinically evident. Children with cancer, admitted with FN at high risk for an invasive bacterial infection in 6 public hospitals in Santiago, Chile, were monitored throughout their clinical course for occurrence of severe sepsis. Clinical, demographic and 6 biomarkers [eg, blood urea nitrogen, serum glucose, lactic dehydrogenase, serum C-reactive protein (CRP), interleukin (IL)-8, and procalcitonin] were obtained at the time of admission and after 24 hours. Biomarkers independently associated with severe sepsis diagnosed after the first 24 hours of hospitalization were identified by logistic regression analysis. A total of 601 high risk FN episodes were enrolled between June 2004 and October 2006; 151 (25%) developed severe sepsis of which 116 (77%) were not clinically apparent during the first 24 hours of hospitalization. Risk factors for severe sepsis were age > or =12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41-6.15], admission CRP > or =90 mg/L (OR: 2.03; 95% CI: 1.32-3.14), admission IL-8 > or =200 pg/mL (OR: 2.39; 95% CI: 1.51-3.78), 24-hour CRP > or =100 mg/L (OR: 3.06; 95% CI: 1.94-4.85), and 24-hour IL-8 > or =300 pg/mL (OR: 3.13; 95% CI 1.92-5.08). Age > or =12 years and admission or 24-hour values of CRP > or =90/100 mg/L and IL-8 > or =200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.

Searching for Alleles Associated With Complicated Outcomes After Burn Injury

Sepsis is a serious and growing health problem among patients admitted to intensive care units. When accompanied by organ failure, sepsis carries a 30-50% case-fatality rate. Although our understanding of burn pathophysiology has grown in recent years, we are still unable to identify accurately patients who are at increased risk for infectious complications and death. Genetic predisposition is likely to explain a portion of this variation. Understanding which genes and allelic variants contribute to disease risk would increase our ability to predict who is at increased risk and intervene accordingly, as well as identify molecular targets for novel and individualized therapies. Several obstacles exist to identification of which specific alleles and loci contribute to patient risk, including achievement of sufficient statistical power, population admixture and epistatic interaction among multiple genes and environmental factors. Although increasing sample size will resolve most, if not all, of these issues, slow patient accrual often makes this solution impractical for a single institution within a reasonable timeframe. This situation is complicated by the fact that traditional analysis methods perform poorly in the face of data sparseness. Identification of risk factors for severe sepsis and death after burn injury will likely require collaborative patient enrollment as well as development of advanced analytical methodologies. While overcoming these obstacles may prove difficult, the effort is warranted, as the ultimate benefit to patients is considerable.

Risk factors for severe sepsis in secondary peritonitis.

The incidence and risk factors for severe sepsis (SS, organ failure associated with infection) in the context of peritonitis are not well established; thus, it is not clear which patients require more aggressive operative or pharmacologic intervention. We set out to determine risk factors for severe sepsis in a large cohort of patients with intra-abdominal infection. Patients admitted for peritonitis over a four-year interval were identified using a Washington State administrative hospital discharge database. This cohort was identified by ICD-9 CM diagnoses and diagnosis-related group (DRG) assignment. Patients with organ failure were identified by ICD-9 CM diagnoses codes using a previously validated classification scheme. Independent risk factors for SS were identified using stepwise Poisson regression. A total of 11,202 patients with peritonitis were identified, 11% of whom developed SS. The crude relative risk of death in patients with SS was 13 (95% CI, 11.1-15.2) times greater than those without. Severe sepsis was present in 424 (62%) of the 686 decedents. Multivariate analysis showed that source of infection, extent of peritonitis, increasing age, and pre-existing organ dysfunction were independently associated with SS. Severe sepsis complicates the course of 11% of all patients with peritonitis. Risk factor analysis identifies a subset of patients at greatest risk for severe sepsis. These are the patients who should be targeted for evaluation of novel pharmacologic interventions or more aggressive surgical intervention.