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Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis.

ABSTRACT: Among surgical intensive care unit (SICU) patients, it is difficult to distinguish bacterial sepsis from other causes of systemic inflammatory response syndrome (SIRS). Biomarkers have proven useful to identify the presence of bacterial infection. We enrolled a prospective cohort of 69 SICU patients with suspected sepsis and assayed the concentrations of 9 biomarkers (?-2 macroglobulin [A2M], C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amyloid P, and tissue plasminogen activator) at baseline, 24, 48, and 72hours. Forty-two patients (61%) had bacterial sepsis by chart review. A2M concentrations were significantly lower, and PCT concentrations were significantly higher in subjects with bacterial sepsis at 3 of 4 time points. Using optimal cutoff values, the combination of baseline A2M and 72-hour PCT achieved a negative predictive value of 75% (95% confidence interval, 54-96%). The combination of A2M and PCT discriminated bacterial sepsis from other SIRS among SICU patients with suspected sepsis.

SUBMITTER: Kelly BJ

PROVIDER: S-EPMC4841711 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis.

Kelly Brendan J BJ Lautenbach Ebbing E Nachamkin Irving I Coffin Susan E SE Gerber Jeffrey S JS Fuchs Barry D BD Garrigan Charles C Han Xiaoyan X Bilker Warren B WB Wise Jacqueleen J Tolomeo Pam P Han Jennifer H JH

Diagnostic microbiology and infectious disease 20160108 1

Among surgical intensive care unit (SICU) patients, it is difficult to distinguish bacterial sepsis from other causes of systemic inflammatory response syndrome (SIRS). Biomarkers have proven useful to identify the presence of bacterial infection. We enrolled a prospective cohort of 69 SICU patients with suspected sepsis and assayed the concentrations of 9 biomarkers (α-2 macroglobulin [A2M], C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amylo ...[more]

PMID: 26971636

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Project description:OBJECTIVES:Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. DESIGN:Cohort study. SETTING:The medical and surgical ICUs at an academic medical center. SUBJECTS:We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy. INTERVENTIONS:We assayed nine biomarkers (?-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve. MEASUREMENTS AND MAIN RESULTS:Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ? 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve > 0.76 for 14-d and 0.74 for total mortality). CONCLUSIONS:Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.

Project description:BACKGROUND:A growing number of patients survive sepsis but remain chronically critically ill. We sought to define clinical outcomes and incidence of chronic critical illness (CCI) after sepsis and to determine whether selected biomarkers of inflammation, immunosuppression, and catabolism differ between these patients and those that rapidly recover (RAP). METHODS:This 3-year prospective observational cohort study (NCT02276417) evaluated 145 surgical intensive care unit patients with sepsis for the development of CCI (?14 days of intensive care unit resource utilization with persistent organ dysfunction). Patient clinical demographics, outcomes, and serial serum/urine samples were collected for plasma protein and urinary metabolite analyses. RESULTS:Of 145 sepsis patients enrolled, 19 (13%) died during their hospitalization and 71 (49%) developed CCI. The CCI patients were significantly older (mean, 63 ± 15 vs. 58 ± 13 years, p = 0.006) and more likely to be discharged to long-term acute care facilities (32% vs. 3%, p < 0.0001), whereas those with RAP were more often discharged to home or a rehabilitation facility. Six-month mortality was significantly higher in CCI as compared with RAP cohort (37% vs. 2%; p < 0.01). Multivariate logistic regression modeling revealed delayed onset sepsis (>48 hours after admission; odds ratio [OR], 10.93; 95% confidence interval [CI], 4.15-28.82]), interfacility transfer (OR, 3.58; 95% CI, 1.43-8.96), vasopressor-dependent septic shock (OR, 3.75; 95% CI, 1.47-9.54), and Sequential Organ Failure Assessment score of 5 or greater at 72 hours (OR, 5.03; 95% CI, 2.00-12.62) as independent risk factors for the development of CCI. The CCI patients also demonstrated greater elevations in inflammatory cytokines (IL-6, IL-8, IL-10), and biomarker profiles are consistent with persistent immunosuppression (absolute lymphocyte count and soluble programmed death ligand 1) and catabolism (plasma insulin-like growth factor binding protein 3 and urinary 3-methylhistidine excretion). CONCLUSION:The development of CCI has become the predominant clinical trajectory in critically ill surgical patients with sepsis. These patients exhibit biomarker profiles consistent with an immunocatabolic phenotype of persistent inflammation, immunosuppression, and catabolism. LEVEL OF EVIDENCE:Prognostic, level II.

Project description:ImportanceHigh health care costs encourage initiatives that avoid overuse of resources and identify opportunities to promote appropriate care.ObjectiveTo investigate the causes of potentially avoidable surgical intensive care unit (SICU) admissions and disposition delays to determine whether targeted interventions could decrease these stays.Design, setting, and participantsThis prospective, observational study focused on potentially avoidable SICU days, as determined by observers with input from the rounding intensivists at a 24-bed open SICU at an urban, academic hospital. The preintervention phase occurred from April 6 through June 21, 2015; after implementation of targeted interventions, the postintervention phase occurred from April 4 through June 28, 2016. Data collected included demographic characteristics, reason for admission, and length of stay. All patients admitted to the SICU during the preintervention and postintervention phases were included in the analysis.InterventionsBased on results collected in the preintervention phase, targeted interventions were designed and implemented from July 1, 2015, through March 31, 2016, including (1) reducing SICU care for minor traumatic brain injury, (2) optimizing postoperative airway management, (3) enhancing communication between services regarding transfers to the SICU, (4) identifying and facilitating more timely end-of-life conversations and supportive care consultations, and (5) encouraging early disposition of patients to floor beds.Main outcomes and measuresChanges in the proportion of potentially avoidable SICU days owing to potentially avoidable admissions and/or disposition delays.ResultsA total of 459 patients (253 men [55.1%] and 206 women [44.9%]; median age, 62 years [interquartile range, 46-75 years]) were admitted during the preintervention and postintervention phases. Of 261 patients admitted during the preintervention period and 245 during the postintervention period, median SICU and hospital length of stay remained unchanged. A reduction was noted in the percentage of postintervention SICU days owing to potentially avoidable admissions (152 of 1168 days [13%] vs 118 of 1338 days [8.8%]; P?=?.001) and disposition delays (138 of 1168 days [11.8%] vs 97 of 1338 days [7.2%]; P?<?.001). During the postintervention period, decreases were noted in the SICU days related to the most common sources of potentially avoidable admissions (SICU stay ?24 hours, airway concerns, and somnolence) and disposition delays (end-of-life decisions and floor bed unavailable) as well as in the overall rate of potentially avoidable days (269 of 1168 days [23%] vs 205 of 1338 days [15.3%]; P?<?.001).Conclusions and relevanceNearly one-fourth of SICU days could be categorized as potentially avoidable. Targeted interventions resulted in a significant reduction of potentially avoidable SICU days.

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Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis.

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Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis.

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