Evaluation of the Mortality in Emergency Department Sepsis score combined with procalcitonin in septic patients

Objective

To determine an effective method for predicting severity of sepsis and 28-day mortality of emergency department (ED) patients, we compared the Mortality in Emergency Department Sepsis (MEDS) score with procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) and evaluated the MEDS score combined with relevant biomarkers.

Methods

A total of 501 adult ED patients with sepsis were selected for this prospective clinical study. The optimal combination was assessed by logistic regression. All cases were divided into the sepsis group (319 cases) and the severe sepsis and septic shock group (182 cases) according to the severity of sepsis, as well as the survivor group (367 cases) and nonsurvivor group (134 cases) according to the 28-day outcomes.

Results

The area under the curve of the MEDS score, PCT, IL-6, and CRP was 0.793, 0.712, 0.695, and 0.681 for severity of sepsis and 0.776, 0.681, 0.692, and 0.661 for 28-day mortality, respectively. Only PCT was an independent predictor when combined with the MEDS score. The new combination of the MEDS score with PCT improved the area under the curve for severity (0.852) and mortality (0.813). This new combination for evaluation of severity had better sensitivity (63.2%), specificity (92.2%), and positive predictive (82.1%) and negative predictive (81.4%) values.

Conclusions

The predictive ability of the MEDS score for severity and 28-day mortality of septic ED patients is better than PCT, IL-6, and CRP levels. The MEDS score combined with PCT enhances the ability of risk stratification and prognostic evaluation.     

Diagnostic and prognostic value of neutrophil gelatinase-associated lipocalin,matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinases-1 for sepsis in the Emergency Department: an observational study

Introduction

The aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED).

Methods

In total, 480 consecutive adult patients were enrolled in this study. They fulfilled the systemic inflammatory response syndrome (SIRS) criteria and were admitted to the ED of Beijing Chaoyang Hospital from February 2013 to August 2013. A total of 40 healthy controls comprised the control group. The patients were classified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Serum NGAL, MMP-9, TIMP-1 and PCT were measured, and MEDS score was calculated at enrollment. The prognostic values of NGAL, MMP-9 and TIMP-1 were compared with PCT and MEDS score. A 28-day follow-up was performed for all patients.

Results

The median levels of serum NGAL and TIMP-1 increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of NGAL or TIMP-1 were greater than those of PCT and MEDS score in diagnosing and predicting 28-day mortality, and the AUC of a combination of NGAL and MEDS score or TIMP-1 and MEDS score was more significant. Serum NGAL, MMP-9 and TIMP-1 levels were significantly higher in non-survivors than survivors at 28 days’ follow-up. In addition, the level of NGAL was much higher in septic patients with acute kidney injury (AKI) than those without AKI. NGAL, TIMP-1, MMP-9 and MEDS score were found to be independent predictors of 28-day mortality in septic patients. The levels of serum NGAL and TIMP-1 were positively correlated with PCT and MEDS score in every septic group.

Conclusions

NGAL and TIMP-1 are valuable for the risk stratification, early diagnosis and prognostication of sepsis in the ED. NGAL is also a valuable biomarker for prognosis of septic patients with AKI in the ED.     

Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department

Introduction

Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis.

Methods

This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann–Whitney U tests.

Results

On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days’ follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group.

Conclusion

Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED.     

Diagnostic role of soluble triggering receptor expressed on myeloid cell-1 in patients with sepsis

BACKGROUND:

Biomarkers may be helpful in risk stratification and prediction of mortality in septic patients. This study aimed to investigate the diagnostic role of soluble triggering receptor expressed on myeloid cell-1(sTREM-1), procalcitonin (PCT), C-reactive protein (CRP) and other inflammatory markers in patients with sepsis.

METHODS:

A total of 56 patients with systemic inflammation response syndrome (SIRS) who had been admitted to the ICU department of the Second Hospital of Tianjin Medical University between May 2009 and July 2010 were enrolled. They were divided into a sepsis group (n=32) and a SIRS group (n=24). Twenty-five non-SIRS patients served as controls. The sepsis group was sub-divided into a survival group and a death group according to 28-day prognosis. The values of sTREM-1, PCT, CRP, white blood cell (WBC), and neutrophil count percentage (N) were measured. Acute physiology and chronic health evaluation II (APACHE II) score were determined within 24 hours. The correlation between sTREM-1 and APACHE II score was analyzed. Quantitative data were analyzed by the F test or the Kruskal-Wallis test.

RESULTS:

The plasma level of sTREM-1 in the sepsis group was significantly higher than that in the SIRS group and control group. The plasma level of sTREM-1 in the non-survival group was significantly higher than that in the survival group. In the sepsis group, the plasma sTREM-1 level was positively correlated with APACHE II score (r=0.426, P= 0.032). The area under the ROC curve of sTREM-1 was 0.935, larger than that of PCT and CRP.

CONCLUSION:

Plasma sTREM-1 is useful in the diagnosis of sepsis at early stage. The increased level of sTREM-1 during the first 24 hours may be correlated with poor outcome of patients with sepsis.KEY WORDS: Sepsis, sTREM-1, Acute physiology and chronic health evaluation II score, Enzyme-linked immunosorbent assay, Procalcitonin, C-reactive protein     

Prognostic value of adrenomedullin in septic patients in the ED

Objective

The aims of the present study were to evaluate the prognostic value of adrenomedullin (AM) in septic patients in the emergency department (ED) and to compare it with procalcitonin (PCT) and Mortality in Emergency Department Sepsis (MEDS) score.

Methods

We enrolled 837 consecutive patients who fulfilled the systemic inflammatory response syndrome criteria and were admitted to the ED of Beijing Chaoyang Hospital and 100 age-matched healthy controls. Serum AM and PCT were determined, and MEDS score was calculated at enrollment. The prognostic value of AM was compared with PCT and MEDS score. Primary outcome was in-hospital mortality.

Results

On admission, mean levels of AM were 28.66 ± 6.05 ng/L in 100 healthy controls, 31.65 ± 6.47 ng/L in 153 systemic inflammatory response syndrome patients, 33.24 ± 8.59 ng/L in 376 sepsis patients, 34.81 ± 8.33 ng/L in 210 severe sepsis patients, and 45.15 ± 9.87 ng/L in 98 septic shock patients. The differences between the 2 groups were significant. Adrenomedullin level was higher in nonsurvivors than in survivors in every group. The area under receiver operating characteristic curve of AM for predicting in-hospital mortality in septic patients was 0.773, which was better than PCT (0.701) and MEDS score (0.721). Combination of AM and MEDS score improved the accuracy of AM and MEDS score in predicting the risk of in-hospital mortality (area under receiver operating characteristic curve, 0.817). In logistic regression analysis, AM and MEDS score were independent predictors of in-hospital mortality.

Conclusions

Adrenomedullin is valuable for prognosis in septic patients in the ED.     

The prognostic and risk-stratified value of heart-type fatty acid–binding protein in septic patients in the emergency department

Purpose

To evaluate the prognostic and risk-stratified ability of heart-type fatty acid–binding protein (H-FABP) in septic patients in the emergency department (ED).

Materials and Methods

From August to November 2012, 295 consecutive septic patients were enrolled. Circulating H-FABP was measured. The predictive value of H-FABP for 28-day mortality, organ dysfunction on ED arrival, and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was assessed by the receiver operating characteristic curve and logistic regression and was compared with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Mortality in Emergency Department Sepsis (MEDS) score, and Sequential Organ Failure Assessment score.

Results

The 28-day mortality, APACHE II, MEDS, and Sequential Organ Failure Assessment scores were much higher in H-FABP–positive patients. The incidence of organ dysfunction at ED arrival and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was higher in H-FABP–positive patients. Heart-type fatty acid–binding protein was an independent predictor of 28-day mortality and organ dysfunction. The area under the receiver operating characteristic curve for H-FABP predicting 28-day mortality and organ dysfunction was 0.784 and 0.755, respectively. Combination of H-FABP and MEDS improved the performance of MEDS in predicting organ dysfunction, and the difference of AUC was statistically significant (P < .05). The combinations of H-FABP and MEDS or H-FABP and APACHE II also improved the prognostic value of MEDS and APACHE II, but the areas under the curve were not statistically different.

Conclusions

Heart-type fatty acid–binding protein was helpful for prognosis and risk stratification of septic patients in the ED.     

The utility of presepsin in diagnosis and risk stratification for the emergency patients with sepsis

Objectives

To evaluate the value of presepsin in diagnosis and risk stratification of septic patients in emergency department, and investigate the utility in differentiation of gram-positive and gram-negative bacterial infection.

Risk stratification of severe sepsis patients in the emergency department

Objective

To determine the efficacy of the Mortality in Emergency Department Sepsis (MEDS) score in the stratification of patients who presented to the emergency department (ED) with severe sepsis.

Methods

Adults who presented to the ED with severe sepsis were retrospectively recruited and divided into group A (MEDS score <12) and group B (MEDS score ⩾12). Their outcomes were evaluated with 28 day hospital mortality rate, length of hospital stay, Kaplan‐Meier survival analysis, and receiver operating characteristic (ROC) analysis. Discriminatory power of the MEDS score in mortality prediction was further compared with the Acute Physiology and Chronic Health Evaluation (APACHE) II model.

Results

In total, 276 patients (44.6% men and 55.4% women) were analysed, with 143 patients placed in group A and 133 patients in group B. Patients with MEDS score ⩾12 had a significantly higher mortality rate (48.9% v 17.5%, p<0.01) and higher median APACHE II score (25 v 20 points, p<0.01). Significant difference in mortality risk was also demonstrated with Kaplan‐Meier survival analysis (log rank test, p<0.01). No difference in the length of hospital stay was found between the groups. ROC analysis indicated a better performance in mortality prediction by the MEDS score compared with the APACHE II score (ROC 0.75 v 0.62, p<0.01).

Conclusion

Our results showed that mortality risk stratification of severe sepsis patients in the ED with MEDS score is effective. The MEDS score also discriminated better than the APACHE II model in mortality prediction.     

Risk stratification and prediction value of procalcitonin and clinical severity scores for community-acquired pneumonia in ED

Objective

Community-acquired pneumonia (CAP) is a common presentation to the emergency department (ED) and has high mortality rates. The aim of our study is to investigate the risk stratification and prognostic prediction value of precalcitonin (PCT) and clinical severity scores on patients with CAP in ED.

Neutrophil-to-lymphocyte ratio as a prognostic marker in critically-ill septic patients

Background

We evaluated the associations between the neutrophil-to-lymphocyte ratio (NLR) or changes in NLR and outcomes in septic patients.

Procalcitonin-guided antibiotics in severe sepsis

Citation

Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J: Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008, 177: 498–505 [1].

Background

The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. Procalcitonin (PCT)-guided antibiotic use reduces antibiotic exposure in community-acquired pneumonia. Whether it might also reduce antibiotic exposure in severe sepsis is unknown.

Methods

Objective

To test the hypothesis that an algorithm based on serial measurements of PCT allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.

Design

Single-center, non-blinded randomized controlled trial.

Setting

Mixed medical and surgical ICU at a university teaching hospital.

Subjects

79 adult patients with suspected severe sepsis or septic shock.

Intervention

All patients had circulating PCT levels drawn daily. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 mg/L) or Day 5 (if baseline PCT levels were >1 mg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.

Outcome

Systemic antibiotic exposure, measured using three variables: 1) duration of antibiotic treatment, 2) antibiotic exposure days per 1000 inpatient days, and 3) days alive without antibiotics within the 28-day follow-up period.

Results

Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).

Conclusion

Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.     

Arterial lactate improves the prognostic performance of severity score systems in septic patients in the ED

Objective

To evaluate the prognostic performance of lactate in septic patients in the emergency department (ED) and investigate how to add lactate to the traditional score systems.

Methods

This was a single-centered, prospective, observational cohort study conducted in ED of Beijing Chao-Yang Hospital. The study enrolled adult septic patients admitted to the ED. Arterial lactate was measured in every patient. Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), and Mortality in Emergency Department Sepsis (MEDS) scores were calculated on ED arrival. The primary outcome was 28-day mortality.

Results

The average levels of lactate, MEDS, APACHE II, and SOFA were much higher in nonsurvivors than in survivors (P < .001), and they were the independent predictors of 28-day mortality. Area under receiver operating characteristic (AUC) curves of MEDS, APACHE II, SOFA, and lactate were 0.74, 0.74, 0.75, and 0.79, respectively. The AUCs of combination lactate and MEDS, APACHE II, and SOFA were 0.81, 0.81, and 0.82, respectively and were much higher than that of score systems alone (P < .05). The AUCs of modified MEDS, APACHE II, and SOFA were 0.80, 0.80, and 0.81, respectively. The prognostic value of the modified score systems was superior to the original score systems and similar to the combination of the lactate and original score systems.

Conclusions

Lactate is a prognostic predictor in septic patients in the ED, and it may improve the performance of APACHE II, SOFA, and MEDS scores in predicting mortality.     

Initial fractal exponent of heart rate variability is associated with success of early resuscitation in patients with severe sepsis or septic shock: a prospective cohort study

Introduction

Heart rate variability (HRV) reflects autonomic nervous system tone as well as the overall health of the baroreflex system. We hypothesized that loss of complexity in HRV upon intensive care unit (ICU) admission would be associated with unsuccessful early resuscitation of sepsis.

Methods

We prospectively enrolled patients admitted to ICUs with severe sepsis or septic shock from 2009 to 2011. We studied 30 minutes of electrocardiogram, sampled at 500 Hz, at ICU admission and calculated heart rate complexity via detrended fluctuation analysis. Primary outcome was vasopressor independence at 24 hours after ICU admission. Secondary outcome was 28-day mortality.

Results

We studied 48 patients, of whom 60% were vasopressor independent at 24 hours. Five (10%) died within 28 days. The ratio of fractal alpha parameters was associated with both vasopressor independence and 28-day mortality (P = .04) after controlling for mean heart rate. In the optimal model, Sequential Organ Failure Assessment score and the long-term fractal α parameter were associated with vasopressor independence.

Conclusions

Loss of complexity in HRV is associated with worse outcome early in severe sepsis and septic shock. Further work should evaluate whether complexity of HRV could guide treatment in sepsis.     

Procalcitonin as a diagnostic marker for sepsis/septic shock in the emergency department; a study based on Sepsis-3 definition

Introduction

The recent definition of sepsis was modified based on a scoring system focused on organ failure (Sepsis-3). It would be a time-consuming process to detect the sepsis patient using Sepsis-3. Procalcitonin (PCT) is a well-known biomarker for diagnosing sepsis/septic shock and monitoring the efficacy of treatment. We conducted a study to verify the predictability of PCT for diagnosing sepsis based on Sepsis-3 definition.

The quick sequential organ failure assessment (qSOFA) identifies septic patients in the out-of-hospital setting

Background

Recently a multispecialty, multinational task force convened to redefine the criteria for organ dysfunction, sepsis, severe sepsis, and septic shock. The study recommended the quick sequential organ failure assessment (qSOFA) score to identify sepsis patients. The qSOFA is felt to be the initial screen to prompt a more in-depth sepsis workup. This may be particularly true in resource-limited environments such as the prehospital arena.

Development and validation of a parsimonious and pragmatic CHARM score to predict mortality in patients with suspected sepsis

Background

We aimed to derive and validate a parsimonious and pragmatic clinical prediction rule using the concepts of Predisposition, Infection, Response, and Organ Dysfunction to predict in-hospital mortality; and to compare it with other prediction rules, as well as with conventional biomarkers for evaluating the mortality risk of patients with suspected sepsis in the emergency department (ED).

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis

Purpose

The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis.

Methods

A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%.

Results

Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003).

Conclusions

Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.     

Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis

Objectives

The Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score has been shown to accurately predict mortality in septic patients and is part of recently proposed diagnostic criteria for sepsis. We sought to ascertain the sensitive of the score in diagnosing sepsis, as well as the diagnostic timeliness of the score when compared to traditional systemic inflammatory response syndrome (SIRS) criteria in a population of emergency department (ED) patients treated in the ED, admitted, and subsequently discharged with a diagnosis of sepsis.

Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection

Background

Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection.

Impact of serial measurements of lysophosphatidylcholine on 28-day mortality prediction in patients admitted to the intensive care unit with severe sepsis or septic shock

Purpose

The purpose of this study is to investigate the effect of serial lysophosphatidylcholine (LPC) measurement on 28-day mortality prediction in patients with severe sepsis or septic shock admitted to the medical intensive care unit (ICU).

Methods

This is a prospective observational study of 74 ICU patients in a tertiary hospital. Serum LPC, white blood cell, C-reactive protein, and procalcitonin (PCT) levels were measured at baseline (day 1 of enrollment) and day 7. The LPC concentrations were compared with inflammatory markers using their absolute levels and relative changes.

Results

The LPC concentration on day 7 was significantly lower in nonsurvivors than in survivors (68.45 ± 42.36 μmol/L and 99.76 ± 73.65 μmol/L; P = .04). A decreased LPC concentration on day 7 to its baseline as well as a sustained high concentration of PCT on day 7 at more than 50% of its baseline value was useful for predicting the 28-day mortality. Prognostic utility was substantially improved when combined LPC and PCT criteria were applied to 28-day mortality outcome predictions. Furthermore, LPC concentrations increased over time in patients with appropriate antibiotics but not in those with inappropriate antibiotics.

Conclusions

Serial measurements of LPC help in the prediction of 28-day mortality in ICU patients with severe sepsis or septic shock.