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Plasminogen activation inhibitor concentrations in bronchoalveolar lavage fluid distinguishes ventilator-associated pneumonia from colonization in mechanically ventilated pediatric patients

Srinivasan, Ramya MD; Song, Yuanlin MD; Wiener-Kronish, Jeanine MD; Flori, Heidi R. MD

Pediatric Critical Care Medicine: January 2011 - Volume 12 - Issue 1 - p 21-27
doi: 10.1097/PCC.0b013e3181e2a352
Feature Articles

Objective: To compare the ability of four biomarkers to distinguish between those with ventilator-associated pneumonia (VAP) vs. lower respiratory tract bacterial colonization in mechanically ventilated intensive care unit (ICU) pediatric patients.

Design: Prospective, pilot cohort study.

Setting: Tertiary care children's hospital, pediatric ICU.

Patients: All pediatric ICU patients mechanically ventilated >48 hrs were eligible for enrollment between April 2006 to May 2007. Thirty-three patients were consecutively screened and enrolled after institutional consent process.

Interventions: None.

Measurements and Main Results: VAP was defined by both Centers for Disease and Prevention/National Nosocomial Infections Surveillance criteria and clinician diagnosis; those not meeting the criteria were considered to be colonized. Plasminogen activation inhibitor (PAI-1), soluble triggering receptor expressed on myeloid cells, receptor for advanced glycation end-products, and surfactant protein D levels were measured in bronchoalveolar lavage samples on average within 24 hrs of suspicion for VAP, i.e., a positive screening endotracheal Gram stain. Sixteen patients were diagnosed with VAP and 17 met the criteria for colonization. PAI-1 was associated with VAP independent of age, sex, race, acute lung injury/acute respiratory distress syndrome, Pediatric Risk of Mortality 3 score, pediatric logistic organ dysfunction score, and duration of intubation. The receiver operating characteristics for PAI-1 showed good discrimination with an area under the curve of 0.82. PAI-1 levels of ≥2.8 ng/mL had a sensitivity of 81.3%, specificity of 76.5%, and positive likelihood ratio of 3.5. Levels of soluble triggering receptor expressed on myeloid cells, receptor for advanced glycation end-products, and surfactant protein D were not significantly associated with VAP.

Conclusions: In mechanically ventilated pediatric ICU patients, PAI-1 is independently associated with the diagnosis of VAP. Real-time measurement of PAI-1 levels in bronchoalveolar lavage fluid may be of benefit in the early diagnosis and subsequent treatment of VAP in ICU patients.

From the University of California (RS, YS), San Francisco, San Francisco, CA; Massachusetts General Hospital (JW-K), Boston, MA; Children's Hospital & Research Center Oakland (HRF), Oakland, CA.

The work was performed at Children's Hospital & Research Center Oakland and University of California, San Francisco.

The research was funded, in part, by SCCOR HL74005 and HL69809, PCRC M01-RR01271, and in-kind donation of Combicath catheters from SRC Medical.

The authors have not disclosed any potential conflicts of interest.

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©2011The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies