The Recovery Hypothesis states:
The Physiological marker of an uncomplicated recovery is a continually falling Acute Phase Response
The acute phase response (APR) is visualised in APEX v1 using the derivative of C Reactive Protein serum concentration time course. The rate of production of CRP depends on the acute phase trigger of protein synthesis in the liver: the rate of clearance is controlled by the half-life in the serum. The clearance half-life is reported to be 19 hrs under all conditions (Pepys MB, Hirschfield GM C-reactive protein: a critical update The Journal of Clinical Investigation 2003: 111; 1805-1812), although is presumably compromised during liver failure. The rate of change of CRP concentration in the serum depends on the rate of production and the rate of clearance for which the simplest differential equation may be written:
The numerical derivative of the interpolated CRP time course is added to the clearance rate, kC¬ determined by the serum half-life to produce the APR as follows:
During recovery, the APR rises to a maximum associated with surgical trauma or the peak of an infection marking the onset of physiological recovery, thereafter the APR falls continuously. Figure 1 shows a simulated recovery from a patient following an operation. The CRP time course and EWS score are conventional markers of recovery and the new markers and are shown on the patient dashboard along with the 4 new recovery markers.
Figure 1 Shows the App calculation of the CRP interpolated time course, the APR and the APEX score evolving in time. The 8-hr prediction is also shown at the end of the trace.
Any complications or secondary infection result in a second stimulus to the APR which begins to rise again which is indicated by an increasing APR and increasing APEX scores but not necessarily a rising CRP, at least in the early stages. The app will allow the new recovery markers to be compared with the CRP, EWS and the clinical assessment of recovery such as the Clavien-Dindo classification.