Heart rate variability in human endotoxemia as potential marker for immune response using a practical wearable device.

Author(s):
Mats Koeneman; Rebecca Koch; Matthijs Kox; Harry Van Goor; Sebastian Bredie

Background:

Researchers in the Radboudumc developed trials to learn about human endotoxemia. For example, they proved with intravenous bacterial lipopolysaccharide (LPS) challenges in healthy volunteers the development of endotoxin tolerance, exemplified by a severely blunted immune response upon a second LPS challenge. In a follow-up trial one secondary research question was if theimmune response of the LPS could also be detected by changes in heart rate variability measured with a wearable device and whether this preceded the symptoms, haemodynamic responses and possible even the cytokine levels.

Hypothesis:

Given the immune response after administration op LPS and the effect of the parasympathetic nervous system on HRV. An increase in LF:HF ratio could be used as a marker for the immune response in human endotoxemia.

Methods:

Healthy participants received either bacterial endotoxin [Escherichia coli-derived lipopolysaccharide (LPS)] or placebo intravenously. Flu-like symptoms were scored every 30 min resulting in a total score of 0–25. TNF-α, IL-6, and IL-10 were measured in plasma samples using a simultaneous Luminex assay. Next to the regular bedside monitoring HRV was calculated using a continuously single-lead HealthPatch ECG recording.

Results:

LPS administration resulted in increased plasma cytokine levels. Preliminary results in the HRV measurements show significant increase in LH:HF ratio and decrease in RMSSD in the intervention group. Whether these changes occur before the onset of symptoms, haemodynamic or cytokine responses will be tested next. An example of a response of HRV compared to the TNF-α and symptom score is given in Figure 1.

Conclusions:

Changes in HRV after LPS administration can be detected with a straightforward wearable device. If the sensitivity and speed of these changes are high enough to be useful in clinical practice remains to be seen. Single results show potential in early detection of an immune response in human endotoxemia.