Early goal-directed therapy in the treatment of severe sepsis and septic shock

Summary Background Procalcitonin is a promising marker for identification of bacterial infections. We assessed the accuracy and clinical value of procalcitonin for diagnosis of sepsis in critically ill patients. Methods We searched Medline, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, and Science Direct, from inception to Feb 21, 2012, and reference lists of identified primary studies. We included articles written in English, German, or French that investigated procalcitonin for differentiation of septic patients—those with sepsis, severe sepsis, or septic shock—from those with a systemic inflammatory response syndrome of non-infectious origin. Studies of healthy people, patients without probable infection, and children younger than 28 days were excluded. Two independent investigators extracted patient and study characteristics; discrepancies were resolved by consensus. We calculated individual and pooled sensitivities and specificities. We used I 2 to test heterogeneity and investigated the source of heterogeneity by metaregression. Findings Our search returned 3487 reports, of which 30 fulfilled the inclusion criteria, accounting for 3244 patients. Bivariate analysis yielded a mean sensitivity of 0·77 (95% CI 0·72–0·81) and specificity of 0·79 (95% CI 0·74–0·84). The area under the receiver operating characteristic curve was 0·85 (95% CI 0·81–0·88). The studies had substantial heterogeneity ( I 2 =96%, 95% CI 94–99). None of the subgroups investigated—population, admission category, assay used, severity of disease, and description and masking of the reference standard—could account for the heterogeneity. Interpretation Procalcitonin is a helpful biomarker for early diagnosis of sepsis in critically ill patients. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, physical examination, and microbiological assessment. Funding Ministry of Education and Research, the Deutsche Forschungsgemeinschaft, Thuringian Ministry for Education, Science and Culture, the Thuringian Foundation for Technology, Innovation and Research, and the German Sepsis Society.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(12)70323-7.pdf

Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis

Procalcitonin is widely reported as a useful biochemical marker to diff erentiate sepsis from other non-infectious causes of systemic infl ammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specifi city being 71% (95% CI 67–76) and an area under the summary receiver operator characteristic curve of 0·78 (95% CI 0·73–0·83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes’ classifi cation. Phase 2 studies had a low pooled diagnostic odds ratio of 7·79 (95% CI 5·86–10·35). Phase 3 studies showed signifi cant heterogeneity because of variability in sample size (meta-regression coeffi cient –0·592, p=0·017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null eff ect in larger studies. Procalcitonin cannot reliably diff erentiate sepsis from other non-infectious causes of systemic infl ammatory response syndrome in critically ill adult patients. The fi ndings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.

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Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis

Mortality in sepsis remains unacceptably high and attempts to modulate the inflammatory response failed to improve survival. Previous reports postulated that the sepsis-triggered immunological cascade is multimodal: initial systemic inflammatory response syndrome (SIRS; excessive pro-, but no/low anti-inflammatory plasma mediators), intermediate homeostasis with a mixed anti-inflammatory response syndrome (MARS; both pro- and anti-inflammatory mediators) and final compensatory anti-inflammatory response syndrome (CARS; excessive anti-, but no/low proinflammatory mediators). To verify this, we examined the evolution of the inflammatory response during the early phase of murine sepsis by repetitive blood sampling of septic animals. Increased plasma concentrations of proinflammatory (IL-6, TNF, IL-1beta, KC, MIP-2, MCP-1, and eotaxin) and anti-inflammatory (TNF soluble receptors, IL-10, IL-1 receptor antagonist) cytokines were observed in early deaths (days 1-5). These elevations occurred simultaneously for both the pro- and anti-inflammatory mediators. Plasma levels of IL-6 (26 ng/ml), TNF-alpha (12 ng/ml), KC (33 ng/ml), MIP-2 (14 ng/ml), IL-1 receptor antagonist (65 ng/ml), TNF soluble receptor I (3 ng/ml), and TNF soluble receptor II (14 ng/ml) accurately predicted mortality within 24 h. In contrast, these parameters were not elevated in either the late-deaths (day 6-28) or survivors. Surprisingly, either pro- or anti-inflammatory cytokines were also reliable in predicting mortality up to 48 h before outcome. These data demonstrate that the initial inflammatory response directly correlates to early but not late sepsis mortality. This multifaceted response questions the use of a simple proinflammatory cytokine measurement for classifying the inflammatory status during sepsis.

/pdf/circulating-cytokine-inhibitor-profiles-reshape-the-43mnmic3am.pdf

Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality

The systemic inflammatory response syndrome.

Background Patients who undergo major surgery for cancer are at high risk of postoperative sepsis. Early markers of septic complications would be useful for diagnosis and therapeutic management in patients with postoperative sepsis. The aim of this study was to investigate the association between early (first postoperative day) changes in interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) serum concentrations and the occurrence of subsequent septic complications after major surgery. Methods Serial blood samples were collected from 50 consecutive patients for determination of IL-6, PCT and CRP serum levels. Blood samples were obtained on the morning of surgery and on the morning of the first postoperative day. Results Sixteen patients developed septic complications during the first five postoperative days (group 1), and 34 patients developed no septic complications (group 2). On day 1, PCT and IL-6 levels were significantly higher in group 1 (P-values of 0.003 and 0.006, respectively) but CRP levels were similar. An IL-6 cut-off point set at 310 pg ml−1 yielded a sensitivity of 90% and a specificity of 58% to differentiate group 1 patients from group 2 patients. When associated with the occurrence of SIRS on day 1 these values reached 100% and 79%, respectively. A PCT cut-off point set at 1.1 ng ml−1 yielded a sensitivity of 81% and a specificity of 72%. When associated with the occurrence of SIRS on day 1, these values reached 100% and 86%, respectively. Conclusions PCT and IL-6 appear to be early markers of subsequent postoperative sepsis in patients undergoing major surgery for cancer. These findings could allow identification of postoperative septic complications.

Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery

Background Early identification of high-risk patients undergoing major surgery can result in an aggressive management affecting the outcome. Methods We designed a prospective cohort study of 93 adult patients undergoing major oncological surgery to identify the predictive risk factors for developing postoperative severe sepsis. Results Nineteen of 93 patients developed a severe sepsis after surgery; seven of the septic patients died in intensive care unit. Multivariate analysis discriminated preoperative and postoperative (first and second day after surgery) predictive risk factors. The postoperative severe sepsis was independently associated with preoperative factors like male gender (OR 4.7, 95% CI between 1.5 and 15.5, P Conclusion We have shown that some of the markers that can be easily collected in the preoperative or postoperative visits can be used to screen the patients at high risk for developing severe sepsis after major surgery.

A Sannini

Papers

Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery

Predictive perioperative factors for developing severe sepsis after major surgery

A reappraisal of preoperative chemoradiation for localized pancreatic head ductal adenocarcinoma in a 5-year single-institution experience.