Pulse Photoplethysmography as an Early Tool for the Diagnosis of Sepsis

Sepsis is a life-threatening syndrome and the most common cause of death nowadays. This syndrome develops as a result of the dysregulated host response to an infectious insult. As such the mainstay of treatment is the early administration of antimicrobials leading to early eradication of the offending pathogen. However, in this statement the key-feature is the definition of what "early" means. Using the retrospective analysis of data associating final outcome from septic shock with the delay in start of antimicrobials from the start of vasopressors in 2713 patients with septic shock, it was found that 79.1% of patients in which this delay was less than one hour survived. Every further hour of delay in start of antibiotics led to 7.6% increase of the risk for unfavorable outcome. These findings were later confirmed from two other analyses. These findings generate two thoughts: a) the above results are based on early recognition of hospital-acquired sepsis that was achievable only because these studies were done in an Intensive Care Unit (ICU) environment in patients under close monitoring. However, early sepsis recognition for a newly admitted patient remains an unmet need; b) all the above results are coming from patients with septic shock where diagnosis had already been established since patients were already on vasopressors.

It is reasonable to hypothesize that if sepsis had been recognized even earlier final outcome would have been even better. Sanmina have developed a non-invasive technique for the measurement of endothelial released nitric oxide (NO) through customized pulse photoplethysmography (PPG). Since NO is released by the vascular endothelium early in the pathogenesis of sepsis it is reasonable to hypothesize that PPG is a technique that can early inform on the risk for a patient with suspicion of an infection to develop sepsis. The time of measurement is less than two minutes. Preliminary data show that the reading of a healthy subject of eight consecutive minutes cannot trace any increase of NO; in sepsis a peak of more than 200 units is shown within the first 40 seconds of measurement.

The development of PPG as a tool for the early diagnosis of sepsis requires a two-stage approach. The first stage is based on the association of PPG readings with the change of the SOFA (sequential organ failure assessment) score and vital signs to define if among patients who eventually develop sepsis, PPG changes will be produced earlier than changes of SOFA scores and of vital signs.