ED identification of patients with severe sepsis/septic shock decreases mortality in a community hospital

Study objectives

Our objective was to quantify the mortality difference between patients with severe sepsis/septic shock (SS/SS) identified in the emergency department (EDI) vs those not identified in the emergency department (NEDI) within our community hospital.

Methods

We conducted a retrospective review of all patients with SS/SS from July 2007 to January 2010 who were admitted to the intensive care unit within our community hospital. Our primary outcome measure was the difference in mortality rates of patients with SS/SS between the EDI and NEDI cohorts. Our secondary outcome measures included the final disposition, the length of stay, and direct cost (DC) for both groups. The data were analyzed using a 2 × 2 contingency table and the Fisher exact test for significance to compare the mortality rates between groups. Lengths of stay and DC between both groups were reported as medians, and significance was calculated using the Mann-Whitney U test.

Results

A total of 267 patients with SS/SS were identified during the 31-month study period. Of these patients, 155 were EDI patients with a mortality rate of 27.7%, and 112 were NEDI patients with a mortality rate of 41.1%. This represents an absolute difference in mortality rates of 13.4% between the 2 groups (P = .0257). The median length of stay between both groups was 7 days for the EDI group and 12.5 days for the NEDI group, translating to median DCs of $9861.01 vs $16 031.07.

Conclusions

Emergency department identification of patients with SS/SS in the community hospital significantly improves mortality.     

De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock

Purposes

We set out to assess the safety and the impact on in-hospital and 90-day mortality of antibiotic de-escalation in patients admitted to the ICU with severe sepsis or septic shock.

Methods

We carried out a prospective observational study enrolling patients admitted to the ICU with severe sepsis or septic shock. De-escalation was defined as discontinuation of an antimicrobial agent or change of antibiotic to one with a narrower spectrum once culture results were available. To control for confounding variables, we performed a conventional regression analysis and a propensity score (PS) adjusted-multivariable analysis.

Results

A total of 712 patients with severe sepsis or septic shock at ICU admission were treated empirically with broad-spectrum antibiotics. Of these, 628 were evaluated (84 died before cultures were available). De-escalation was applied in 219 patients (34.9 %). By multivariate analysis, factors independently associated with in-hospital mortality were septic shock, SOFA score the day of culture results, and inadequate empirical antimicrobial therapy, whereas de-escalation therapy was a protective factor [Odds-Ratio (OR) 0.58; 95 % confidence interval (CI) 0.36–0.93). Analysis of the 403 patients with adequate empirical therapy revealed that the factor associated with mortality was SOFA score on the day of culture results, whereas de-escalation therapy was a protective factor (OR 0.54; 95 % CI 0.33–0.89). The PS-adjusted logistic regression models confirmed that de-escalation therapy was a protective factor in both analyses. De-escalation therapy was also a protective factor for 90-day mortality.

Conclusions

De-escalation therapy for severe sepsis and septic shock is a safe strategy associated with a lower mortality. Efforts to increase the frequency of this strategy are fully justified.     

Prompt antibiotic administration and goal-directed hemodynamic support in patients with severe sepsis and septic shock

PURPOSE OF REVIEW: Treatment protocols targeting the rapid administration of appropriate antibiotics and hemodynamic support are now recognized as a key measure in the initial care of patients presenting with severe sepsis and septic shock. Strong evidence exists showing that time parameters, particularly in the emergency department, are as important as the nature of the treatment administered. The concept of sepsis bundles integrates evidence-based and time-sensitive issues, derived from international sepsis guidelines, to ensure that all eligible patients receive the right treatment as early as possible. RECENT FINDINGS: Several studies have demonstrated that patients resuscitated according to sepsis bundles had a significantly lower mortality. SUMMARY: It seems logical that timely and protocolized treatment for patients presenting with severe sepsis and septic shock will impact on outcome. It remains to be shown, however, whether translating evidence into clinical practice will increase adherence to the bundles and positively impact on survival.     

Endotoxaemia in patients with severe sepsis or septic shock

Objective: To examine the incidence and the bacteriological and clinical significance of endotoxaemia in ICU patients with severe sepsis or septic shock. Design: Prospective review. Setting: A 15-bed general ICU in a university hospital. Patients: One hundred sixteen patients hospitalised in our ICU fulfilling Bone's criteria for severe sepsis or septic shock and with an available early endotoxin assay (chromogenic limulus assay). Interventions: None. Measurements and results: The clinical characteristics of the population were: age 63.6 ± 11.4 years; SAPS II: 45.4 ± 15.6; mechanical ventilation: 72.4 %; septic shock: 51.7 % (n = 60); bacteraemia: 28.4 % (n = 33); gram-negative bacteria (GNB) infection 47.4 % (n = 55); ICU mortality: 39.6 % (n = 46). Detectable endotoxin occurred in 61 patients (51.2 %; mean level: 310 ± 810 pg/ml). There was no relationship between detectable endotoxin and severity of infection at the moment of the assay. Endotoxaemia was associated with a higher incidence of bacteraemia (39.3 % vs 16.3 %; p = 0.01). There was a trend (p = 0.09) towards an association between positive endotoxin and gram-negative bacteraemia or GNB infection but this was non-significant. This relationship became significant only in the case of bacteraemia associated with GNB infection irrespective of the site of infection. Conclusion: Early detection of endotoxaemia appeared to be associated with GNB infection only in cases of bacteraemic GNB infection. Early endotoxaemia correlated neither to occurrence of organ dysfunction nor mortality in patients with severe sepsis or septic shock. This study suggests that the use of endotoxaemia as a diagnostic or a prognostic marker in daily practice remains difficult. Received: 28 September 1999 Final revision received: 31 January 2000 Accepted: 1 February 2000     

Prognostic factors of mortality in patients with community-acquired bloodstream infection with severe sepsis and septic shock

Purpose

The purpose of the study was to determine the independent risk factors on mortality in patients with community-acquired severe sepsis and septic shock.

Methods

A single-site prospective cohort study was carried out in a medical-surgical intensive care unit in an academic tertiary care center. One hundred twelve patients with community-acquired bloodstream infection with severe sepsis and septic shock were identified. Clinical, microbiologic, and laboratory parameters were compared between hospital survivors and hospital deaths.

Results

One-hundred twelve patients were included. The global mortality rate was 41.9%, 44.5% in septic shock and 34.4% in severe sepsis. One or more comorbidities were present in 66% of patients. The most commonly identified bloodstream pathogens were Escherichia coli (25%) and Staphylococcus aureus (21.4%). The proportion of patients receiving inadequate antimicrobial treatment was 8.9%. By univariate analysis, age, Acute Physiology and Chronic Health Evaluation II score, at least 3 organ dysfunctions, and albumin, but neither microbiologic characteristics nor site of infection, differed significantly between survivors and nonsurvivors. Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.13; 95% confidence interval, 1.06-1.21) and albumin (odds ratio, 0.34; 95% confidence interval, 0.15-0.76) were independent risk factors associated with global mortality in logistic regression analysis.

Conclusion

In addition to the severity of illness, hypoalbuminemia was identified as the most important prognostic factor in community-acquired bloodstream infection with severe sepsis and septic shock.     

Multi-drug resistance,inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study

Introduction

The impact of in vitro resistance on initially appropriate antibiotic therapy (IAAT) remains unclear. We elucidated the relationship between non-IAAT and mortality, and between IAAT and multi-drug resistance (MDR) in sepsis due to Gram-negative bacteremia (GNS).

Methods

We conducted a single-center retrospective cohort study of adult intensive care unit patients with bacteremia and severe sepsis/septic shock caused by a gram-negative (GN) organism. We identified the following MDR pathogens: MDR P. aeruginosa, extended spectrum beta-lactamase and carbapenemase-producing organisms. IAAT was defined as exposure within 24 hours of infection onset to antibiotics active against identified pathogens based on in vitro susceptibility testing. We derived logistic regression models to examine a) predictors of hospital mortality and b) impact of MDR on non-IAAT. Proportions are presented for categorical variables, and median values with interquartile ranges (IQR) for continuous.

Results

Out of 1,064 patients with GNS, 351 (29.2%) did not survive hospitalization. Non-survivors were older (66.5 (55, 73.5) versus 63 (53, 72) years, P = 0.036), sicker (Acute Physiology and Chronic Health Evaluation II (19 (15, 25) versus 16 (12, 19), P <0.001), and more likely to be on pressors (odds ratio (OR) 2.79, 95% confidence interval (CI) 2.12 to 3.68), mechanically ventilated (OR 3.06, 95% CI 2.29 to 4.10) have MDR (10.0% versus 4.0%, P <0.001) and receive non-IAAT (43.4% versus 14.6%, P <0.001). In a logistic regression model, non-IAAT was an independent predictor of hospital mortality (adjusted OR 3.87, 95% CI 2.77 to 5.41). In a separate model, MDR was strongly associated with the receipt of non-IAAT (adjusted OR 13.05, 95% CI 7.00 to 24.31).

Conclusions

MDR, an important determinant of non-IAAT, is associated with a three-fold increase in the risk of hospital mortality. Given the paucity of therapies to cover GN MDRs, prevention and development of new agents are critical.     

Increased colorectal permeability in patients with severe sepsis and septic shock

Objective To develop a method for the assessment of colorectal permeability in septic patients.Design and setting Observational study in ICUs at two university hospitals.Participants Nine patients with septic shock and abdominal focus of infection, 7 with severe sepsis and pulmonary focus and 8 healthy subjects.Measurements and results Colorectal permeability was assessed as the initial appearance rate of ^99mTc-DTPA in plasma after instillation into the rectal lumen and as the cumulative systemic recovery at 1 h. To calculate the latter, volume of distribution and renal clearance of ^99mTc-DTPA was estimated by an i. v. bolus of ⁵¹Cr-EDTA. The initial rate of permeability was increased in patients with septic shock and severe sepsis compared with controls [29.0 (3.7–83.3), 20.6 (3.6–65.5) and 6.0 (2.2–9.6) cpm ml⁻¹ min⁻¹, respectively, p < 0.05)] with a positive linear trend (r ² = 0.27, p = 0.01) and correlated to L-lactate concentrations in the rectal lumen (r ² = 0.39, p < 0.05). The cumulative permeability was also increased in patients with septic shock and severe sepsis compared with controls [2.07 (0.05–15.7), 0.32 (0.01–1.2) and 0.03 (0.01–0.06)‰, respectively, p < 0.01] and correlated to the initial permeability rate (r ² = 0.26, p = 0.01).Conclusions In septic patients, the systemic recovery of a luminally applied marker of paracellular permeability was increased and related to the luminal concentrations of L-lactate and possibly to disease severity. This suggests that the assessment of colorectal permeability by systemic recovery of ^99mTc-DTPA is valid and that metabolic dysfunction of the mucosa contributes to increased permeability of the large bowel in patients with severe sepsis and septic shock.     

Performance of the Mortality in Emergency Department Sepsis score for predicting hospital mortality among patients with severe sepsis and septic shock

Objective

The aim of the study was to test if the Mortality in Emergency Department Sepsis (MEDS) score accurately predicts death among emergency department (ED) patients with severe sepsis and septic shock.

Methods

This study was a preplanned secondary analysis of a before-and-after interventional study conducted at a large urban ED. Inclusion criteria were suspected infection, 2 or more criteria for systemic inflammation, and either systolic blood pressure of less than 90 mm Hg after a fluid bolus or lactate 4 mmol/L or higher. Exclusion criteria were: age of less than 18 years, no aggressive care desired, or need for immediate surgery. Clinical and outcomes data were prospectively collected on consecutive eligible patients for 1 year before and 1 year after implementing early goal-directed therapy (EGDT). The MEDS scores and probabilities of in-hospital death were calculated. The main outcome was in-hospital mortality. The area under the receiver operating characteristic curve was used to evaluate score performance.

Results

One hundred forty-three patients, 79 pre-EGDT and 64 post-EGDT, were included. The mean age was 58 ± 17 years, and pneumonia was the source of infection in 37%. The in-hospital mortality rate was 23%. The area under the receiver operating characteristic curve for MEDS to predict mortality was 0.61 (95% confidence interval [CI], 0.50-0.72) overall, 0.69 (95% CI, 0.56-0.82) in pre-EGDT patients, and 0.53 (95% CI, 0.33-0.74) in post-EGDT patients.

Conclusions

The MEDS score performed with poor accuracy for predicting mortality in ED patients with sepsis. These results suggest the need for further validation of the MEDS score before widespread clinical use.     

降低严重感染与感染性休克的病死率:机遇与挑战并存

严重感染(severe sepsis)与感染性休克(septic shock)是一种高患病率、高病死率、高治疗费用的临床综合征。虽然经过了多年的研究与实践探索,但严重感染与感染性休克的病死率一直居高不下,可高达40%左右,仍然是重症加强治疗病房(ICU)患者的首要致死原因。因此,目前在国际上,包括各级政府、医学专业组织和临床工作者已越来越重视这一问题。     

Pharmacokinetics of moxifloxacin in patients with severe sepsis or septic shock

Purpose  

To investigate the steady-state pharmacokinetics of moxifloxacin in critically ill patients after intravenous administration of the 400 mg fixed dose.     

糖皮质激素在严重感染和感染性休克中的应用

复杂的生命过程中，各种来源的刺激(包括寒冷、疼痛、感染、创伤以及低血压等)超过一定阈值时，都将激活机体产生应激反应，出现下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal．HPA)轴的激活，使促肾上腺皮质激素(adrenocorticotrophic hormone，ACTH)的释放以及血中皮质醇水平增高，这是机体适应和抵御疾病、维持内环境稳态和各系统器官功能正常的重要保证。     

Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study

Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock.

Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study.

Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50?nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p?=?0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p?p?p?>?0.9; and <25?nmol/L: HR 0.44 (95% CI: 0.22–0.87), p?=?0.018).

Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock.

• Key messages

• In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality.

• Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury.