Autonomic Challenges From Mild Hypovolemia and Mechanical Ventilation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Low Central Volume and Intermittent Positive Pressure Ventilation on the Heart Rate Variability

Conditions
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Hypovolemia, Autonomic Nervous System Imbalance, Positive-Pressure Respiration

Intervention / Treatment
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* Other: Increase of central volume
* Other: Ventilation mode


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Studied subjects<br>Each subject will be studied during two sequential phases: before fluid challenge after fluid challenge During each phase, the subjects will be studied at: baseline - spontaneously breathing head down position - spontaneously breathing baseline - positive pressure ventilation head down position - positive pressure ventilation The sequence a-b-c-d will be randomized for each subject and for each phase | Other: Increase of central volume<br>* Mild hypovolemia will be induced in healthy volunteers by 12 hours fasting. Three conditions will be considered for the analysis, each of them both during spontaneous breathing and positive pressure ventilation: baseline after fluid shift induced by passive head down position at 15 degrees after fluid challenge with Ringer acetate 15ml*kg in head down position A total of six steps will be considered for the analysis<br>Other: Ventilation mode<br>* Each previous step will be done in two respiratory conditions: spontaneous breathing noninvasive ventilation via facial mask in pressure support mode at 8 cmH2O above positive end expiratory pressure of 5 cmH2O, inspiratory fraction of oxygen of 0.25 In both conditions respiratory rate will be set at 18 breaths per min following a metronome<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of increasing central blood volume on heart rate variability | The studied subjects will undergo to increase of central blood volume in two steps: passive head down tilt at -7 degrees intravenous infusion of ringer acetate of 15ml*kg body weight | 10 mins each step | 
| Effect of cyclic intrathoracic pressure oscillations on heart rate variability | The studied subject will undergo to two ventilatory modes: spontaneous breathing at 18 breaths per min positive pressure ventilation via face mask | 10 min each step | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of increasing central blood volume and of cyclic intrathoracic pressure oscillations on echographic cardiac function variables | At each step cardiac functionality assessment will be done by transthoracic echocardiography | 10 mins each step |