Autonomic Nervous System Dysfunction in Critically Ill Clinical Trial
The purpose of this study is to measure the dysfunction of the autonomic nervous system in modulating the heart rate variability and baroreflex control in critically ill.
Autonomic nervous system (ANS) is able to change both heart beat-to-beat interval and
peripheral muscle vascular tone in response to different stimuli. Unfortunately the direct
measure of the sympathetic and vagal activity appears not feasible in a clinical setting.
ANS modulation is studied non-invasively by means of heart rate variability (HRV) and
baroreflex sensitivity. Decreased HRV has been found in critical ill patients with multiple
organ dysfunction syndrome (MODS) and sepsis, thus it has been supposed being a sign of
autonomic dysfunction. Frequently, in mechanically ventilated critical ill patients the HRV
does not show any oscillatory pattern, as well as it appears in the early months after heart
transplantation. Under these circumstances the heart seems to lack the neuro-modulatory
control by ANS and it seems to respond exclusively to the preload and afterload laws. This
could have implications for outcome because autonomic dysfunction is associated with
increasing severity of illness and mortality. Since the ANS modulation is a dynamic process
that implies a central integration of a complex variety of afferent stimuli (from carotid
sinus, cardiopulmonary receptors, pain,…) and efferences through sympathetic and vagal
branches, up to the present it is unclear if in critically ill a reduced HRV at rest
reflects a state of low requirement of ANS modulation or truly a failure of the ANS. To
provide new insights into this important topic we study the changes of ANS modulation in
response to a orthostatic sympathetic stimulus daily from the day of ICU admission until day
28, or the day of discharge from ICU if it occurs before the day 28.
Measurements. Beat-to-beat intervals are computed detecting the QRS complex on the
electrocardiogram and locating the R-apex using parabolic interpolation. The maximum
arterial pressure within each R-to-R interval is taken as systolic arterial pressure (SAP).
Sequences of 300 values are randomly selected inside each experimental condition. The power
spectrum is estimated according to a univariate parametric approach fitting the series to an
autoregressive model. Autoregressive spectral density is factorized into components each of
them characterized by a central frequency. A spectral component is labeled as low frequency
(LF) if its central frequency is between 0.04 and 0.15 Hz, while it is classified as high
frequency (HF) if its central frequency is between 0.15 and 0.4 Hz. The HF power of R-to-R
series is utilized as a marker of vagal modulation directed to the heart , while the LF
power of SAP series is utilized as a marker of sympathetic modulation directed to vessels.
The ratio of the LF power to the HF power assessed from R-to-R series is taken as an
indicator sympatho-vagal balance directed to the heart. Baroreflex control in the low
frequencies is computed as the square root of the ratio of LF(RR) to LF(SAP). In the same
way baroreflex control in the high frequencies is defined as the square root of the ratio of
HF(RR) to HF(SAP).
The experimental condition is a sequence of three time point each lasting 10 min: (i) rest,
with patient in supine position at zero degree; (ii) modified tilt; (iii) recovery, with the
patient supine.
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Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science