Abstract: Systems, devices, and methods to measure interstitial concentration of selected compounds over time to provide early detection of shock are described. In an example method, interstitial fluid is obtained from a subject. Analytes are detected in the interstitial fluid. At least one of the analytes corresponds to hypoxia of a tissue of the subject and at least one other analyte corresponds to vascular permeability of the subject. The example method further includes determining whether the subject is in shock based on a computing model and the detected analytes and generating an alert based on whether the subject is in shock. Treatments can be administered following the alert generation.