Evaluation of the Diagnostic Accuracy of Exhaled Nitric Oxide as a Marker of Infection and Sepsis in Emergency Department Patients.

Abstract

Background: Early identification of septic patients in the ED is important, but high patient volumes and lengthy wait times often delay workups, and typically used noninvasive triage screening tools such as vital signs and qSOFA have poor sensitivity. Nitric oxide (NO) is a molecule in the blood that has been found to be upregulated in sepsis. Since it has a very short half-life in blood, its measurement can be challenging. We aimed to determine if exhaled NO could be used to help predict bacterial infection and sepsis. Methods: Emergency department patients with concern for infection were assessed for enrollment. Patients were included if blood cultures were ordered by the ED provider. The exhaled breath NO levels of enrolled subjects were measured. A score (vital signs and nitric oxide [VSNO]) was then created that included triage vital signs and NO level. Results: 104 patients (41 female) were enrolled. The median exhaled NO level was 9.8 parts per billion (ppb) (IQR: 5.6-17.0). Sixty-two (60%) patients were diagnosed with bacterial infection, and of those, 54 (52%) patients were diagnosed with sepsis. Using cut points of < 7 or > 12 ppb, the VSNO score demonstrated a sensitivity of 0.89 (95% CI: 0.77-0.96) and a specificity of 0.48 (95% CI: 0.34-0.63) for predicting sepsis. The score showed a sensitivity of 0.82 (95% CI: 0.70-0.91) and a specificity of 0.45 (95% CI: 0.30-0.64) for predicting bacterial infection. Conclusions: Exhaled NO measurement combined with vital signs has a high sensitivity for the detection of bacterial infection and sepsis. In a clinical setting, this score would be immediately available at the point of patient triage and would help to direct downstream evaluation and care. Further research is warranted.