Clinical trial NCT03244891: Autonomic Challenges From Mild Hypovolemia and Mechanical Ventilation
Official title: Effects of Low Central Volume and Intermittent Positive Pressure Ventilation on the Heart Rate Variability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autonomic Nervous System Imbalance
Hypovolemia
Positive-Pressure Respiration
Lead sponsor: ASST Fatebenefratelli Sacco
Sponsor class: OTHER
First posted: 2017-08-10
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: Heart Rate Variability (HRV) analysis has been studied in the critically ill patients although it is affected by several uncontrolled variables in the clinical conditions. The aim of this trial is to measure the effects of mildly reduced central volume and cyclic variation of intrathoracic pressure on the variables frequently used to describe the HRV.

Detailed description: Twelve healthy volunteers will be studied. Mild hypovolemia will be induced by 12 hours fasting from food and drinks. At 8.30 AM the study protocol will start. The studied subjects will lie calm supine in a ICU bed able to provide passive head up and head down tilt. They will be connected to a Siemens SC9000 monitor showing their ECG waves and to a Nexfin (BMEYE) monitor for continuous noninvasive blood pressure (NBP) assessment. Both waves (ECG and NBP) will be recorded on a laptop PC through analogic/digital input/output converter (PowerLab 8/35, ADinstruments). The studied subjects will undergo to a sequence of (1) spontaneous breathing at 10 degrees head up, (2) spontaneous breathing at 7 degrees head down, (3) noninvasive ventilation at 10 degrees head up, and (4) noninvasive ventilation at 7 degrees head down. The sequence 1-2-3-4 will be randomized. After this four phases, a fluid challenge of ringer acetate 15ml\*kg will be intravenously administered and the a sequence 1-2-3-4 will be repeated after a new randomization. Noninvasive ventilation will be provided with a facial mask with ventilatory setting: Psupp 8 cmH2O, PEEP 5 cmH2O, FiO2 0.28. Psupp will be decreased by 2 cmH2O steps if the inspiratory tidal volume will be \>10ml\*kg. During both spontaneous breathing and noninvasive ventilation the subjects will breathe following a metronome at 18bpm.

HRV analysis will be conducted following the recommendation of the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (see reference).

Furthermore, the healthy volunteers will be studied by trans-thoracic ultrasound assessment with a Philips EPIQ7 sonographer, during each study phase.

Eligibility criteria: Inclusion Criteria:

* healthy volunteers

Exclusion Criteria:

* history of cardiac, metabolic, respiratory, renal, neurological or hematologic disease of any kind
* chronically assuming drugs of any kind
* non sinus cardiac rhythm
* ectopic beats \>5% of all cardiac beats
* claustrophobia or unable to tolerate noninvasive ventilation via facial mask

Primary outcomes:
measure: Effects of increasing central blood volume on heart rate variability
timeFrame: 10 mins each step
measure: Effect of cyclic intrathoracic pressure oscillations on heart rate variability
timeFrame: 10 min each step
Secondary outcomes:
measure: Effects of increasing central blood volume and of cyclic intrathoracic pressure oscillations on echographic cardiac function variables
timeFrame: 10 mins each step
Other outcomes:
Locations:
city: Milan
country: Italy
facility: ASST Fatebenefratelli Sacco, Luigi Sacco Hospital
Study officials:
References:
citation: Guyton JE, Arthur C. The Autonomic Nervous System and The Adrenal Medulla, in Textbook of Medical Physiology, 12th ed., Saunders Elsevier, Ed. Philadelphia, 2011, pp. 738-739
citation: Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981 Jul 10;213(4504):220-2. doi: 10.1126/science.6166045.
citation: Ferrario M, Moissl U, Garzotto F, Cruz DN, Tetta C, Signorini MG, Ronco C, Grassmann A, Cerutti S, Guzzetti S. The forgotten role of central volume in low frequency oscillations of heart rate variability. PLoS One. 2015 Mar 20;10(3):e0120167. doi: 10.1371/journal.pone.0120167. eCollection 2015.
citation: Galletly DC, Larsen PD. Relationship between cardioventilatory coupling and respiratory sinus arrhythmia. Br J Anaesth. 1998 Feb;80(2):164-8. doi: 10.1093/bja/80.2.164.
citation: Monnet X, Rienzo M, Osman D, Anguel N, Richard C, Pinsky MR, Teboul JL. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med. 2006 May;34(5):1402-7. doi: 10.1097/01.CCM.0000215453.11735.06.
citation: Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.