Clinical trial NCT01930669: Transplanted-like Heart in Critical Ill Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autonomic Nervous System Dysfunction in Critically Ill
Keywords: Heart Rate Variability
Multiple Organ Dysfunction Syndrome
Critically Ill
Lead sponsor: ASST Fatebenefratelli Sacco
Sponsor class: OTHER
Collaborators: name: Regione Lombardia
First posted: 2013-08-29
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: Inclusion Criteria:

Patients admitted in ICU with

* age between 18 and 75 years
* expected length of stay in ICU \>24 hours
* sinus rhythm on ECG
* ectopic heart beats \<5% of all heart beats
* no contraindications of any kind to head-up 60 degrees position

Exclusion Criteria:

* age \<18 and \>75 years
* elective postoperative patients
* non sinusal rhythm of ECG
* ectopic heart beats \>5% of all heart beats
* spinal or head injury
* suspected or documented intracranial hypertension
* contraindications of any kind to head up 60 degrees position

Primary outcomes:
measure: Incidence of autonomic nervous system dysfunction in critical ill patients
timeFrame: from day 1 to day 28
Secondary outcomes:
measure: to measure the occurrence of ANS failure in subgroups
timeFrame: from day 1 to day 28
measure: Length of stay in ICU and in Hospital
timeFrame: 8 months
measure: mortality
timeFrame: 8 months
measure: days free from mechanical ventilation
timeFrame: 28 days
Other outcomes:
measure: to define ANS dysfunction and failure in response to MTILT
timeFrame: 28 days
Locations:
city: Milan
country: Italy
facility: Azienda Ospedaliera "Luigi Sacco" - Polo Universitario - University of Milan
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
Study officials:
affiliation: Azienda Ospedaliera "L.Sacco"
name: Ferdinando Raimondi, Director
role: STUDY_CHAIR
affiliation: Azienda Ospedaliera "L.Sacco"
name: Riccardo Colombo, Consultant
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera "L.Sacco"
name: Stefano Guzzetti, Director
role: STUDY_DIRECTOR
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