A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis. (Colman)

Carcillo JA, Sward K, Halstead ES, et al. A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis. Pediatr Crit Care Med. 2016 Dec 9. [Epub ahead of print]

OBJECTIVES: We tested the hypothesis that a C-reactive protein and ferritin-based systemic inflammation contingency table can track mortality risk in pediatric severe sepsis.

DESIGN: Prospective cohort study.

SETTING: Tertiary PICU.

PATIENTS: Children with 100 separate admission episodes of severe sepsis were enrolled.

INTERVENTIONS: Blood samples were attained on day 2 of sepsis and bi-weekly for biomarker batch analysis. A 2 × 2 contingency table using C-reactive protein and ferritin thresholds was developed.

MEASUREMENTS AND MAIN RESULTS: A C-reactive protein of 4.08 mg/dL and a ferritin of 1,980 ng/mL were found to be optimal cutoffs for outcome prediction at first sampling (n = 100) using the Youden index. PICU mortality was increased in the “high-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL category (6/13 [46.15%]) compared with the “intermediate-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin less than 1,980 ng/mL or C-reactive protein less than 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL categories (2/43 [4.65%]), and the “low-risk” C-reactive protein less than 4.08 mg/dL and ferritin less than 1,980 ng/mL category (0/44 [0%]) (odds ratio, 36.43 [95% CI, 6.16-215.21]). The high-risk category was also associated with the development of immunoparalysis (odds ratio, 4.47 [95% CI, 1.34-14.96]) and macrophage activation syndrome (odds ratio, 24.20 [95% CI, 5.50-106.54]). Sixty-three children underwent sequential blood sampling; those who were initially in the low-risk category (n = 24) and those who subsequently migrated (n = 19) to the low-risk category all survived, whereas those who remained in the “at-risk” categories had increased mortality (7/20 [35%]; p < 0.05).

CONCLUSIONS: A C-reactive protein- and ferritin-based contingency table effectively assessed mortality risk. Reduction in systemic inflammation below a combined threshold C-reactive protein of 4.08 mg/dL and ferritin of 1,980 ng/mL appeared to be a desired response in children with severe sepsis.

Use of time from fever onset improves the diagnostic accuracy of C-reactive protein in identifying bacterial infections. (Kamat)

Segal I, Ehrlichman M, Urbach J, Bar-Meir M. Use of time from fever onset
improves the diagnostic accuracy of C-reactive protein in identifying bacterial
infections. Arch Dis Child. 2014 May 15.

OBJECTIVE: To determine whether the input of time from fever onset will change the accuracy of C-reactive protein (CRP) in diagnosing bacterial infections in febrile children.

STUDY DESIGN: We performed a prospective observational study on febrile children presenting to the emergency department. The diagnostic performance of CRP at different time points from fever onset was compared using a receiver operating characteristic (ROC) curve.

RESULTS: Among 373 patients included, 103 (28%) had bacterial infection. The optimal cut-off for CRP suggesting bacterial infection changed with time from fever onset: 6 mg/dL for >12-24 h of fever; 10.7 and 12.6 mg/dL at >24-48 and >48 h of fever, respectively. The input of time from fever onset improved the area under the ROC curve from 0.83 (95% CI 0.78 to 0.88) for CRP overall to 0.87 (95% CI 0.77 to 0.96) and 0.90 (95% CI 0.84 to 0.97) at >24-48 and >48 h of fever, respectively. Duration of fever mostly affected the ability of CRP to correctly rule out bacterial infections. CRP level of 2 mg/dL obtained at ≤24 h of fever corresponds with a post-test probability for bacterial infection of 10%, whereas the same value obtained >24 h of fever reduces the risk to 2%.

CONCLUSIONS: Clinicians should apply different CRP cut-off values depending on whether they are trying to rule in or rule out bacterial infection, but also depending on fever duration at the time of CRP testing.

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Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. (Grunwell)

Oliveira CF, Botoni FA, Oliveira CR, Silva CB, Pereira HA, Serufo JC, Nobre V. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med. 2013 Oct;41(10):2336-43.

OBJECTIVE: We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis.

DESIGN: Randomized open clinical trial.

SETTING: Two university hospitals in Brazil.

PATIENTS: Patients with severe sepsis or septic shock.

INTERVENTIONS: Patients were randomized in two groups: the procalcitonin group and the C-reactive protein group. Antibiotic therapy was discontinued following a protocol based on serum levels of these markers, according to the allocation group. The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25% shorter than in the C-reactive protein group. For both groups, at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and/or bacteremia at inclusion, and patients with evident resolution of the infectious process had antibiotics stopped after 7 days, despite biomarkers levels.

MEASUREMENTS AND MAIN RESULTS: Ninety-four patients were randomized: 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group. The mean age was 59.8 (SD, 16.8) years. The median duration of antibiotic therapy for the first episode of infection was 7.0 (Q1-Q3, 6.0-8.5) days in the procalcitonin group and 6.0 (Q1-Q3, 5.0-7.0) days in the C-reactive protein group (p = 0.13), with a hazard ratio of 1.206 (95% CI, 0.774-1.3; p = 0.13). Overall, protocol overruling occurred in only 13 (13.8%) patients. Twenty-one patients died in each group (p = 0.836).

CONCLUSIONS: C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients, causing no apparent harm.

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