Transplanted-like Heart in Critical Ill Patients
Condition: Autonomic Nervous System Dysfunction in Critically Ill
MeSH terms: Critical Illness
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Gravitational sympathetic stimulus
Intervention type(s): Other
Intervention description(s): Autonomic nervous system (ANS) activity is assessed by means of HRV, SAP variability and baroreflex control analysis daily from day 1 to discharge from ICU or day 28.
Analysis is performed (i)at rest in supine position with bed at zero degrees of inclination (ii) during modified tilt (MTILT) and (iii) recovery from MTILT in supine position at zero degrees. In a subgroup of patients motor sympathetic nervous activity (MSNA) is recorded at day 1,2 and 7.
MTILT consists in elevating head and trunk of patients at 60 degrees and lowering legs at 15 degree with a standard critical care bed. MSNA is recorded from the external peroneal nerve with microneurographic technique.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Heart Rate Variability; Multiple Organ Dysfunction Syndrome; Critically Ill