Autonomic Challenges From Mild Hypovolemia and Mechanical Ventilation
Primary Purpose
Autonomic Nervous System Imbalance, Hypovolemia, Positive-Pressure Respiration
Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Increase of central volume
Ventilation mode
Sponsored by
About this trial
This is an interventional basic science trial for Autonomic Nervous System Imbalance
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
Sites / Locations
- ASST Fatebenefratelli Sacco, Luigi Sacco Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Studied subjects
Arm Description
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
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
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
Full Information
NCT ID
NCT03244891
First Posted
August 5, 2017
Last Updated
October 10, 2019
Sponsor
ASST Fatebenefratelli Sacco
1. Study Identification
Unique Protocol Identification Number
NCT03244891
Brief Title
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
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
June 15, 2019 (Actual)
Primary Completion Date
July 30, 2019 (Actual)
Study Completion Date
July 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
ASST Fatebenefratelli Sacco
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autonomic Nervous System Imbalance, Hypovolemia, Positive-Pressure Respiration
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Studied subjects
Arm Type
Experimental
Arm Description
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
Intervention Type
Other
Intervention Name(s)
Increase of central volume
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Ventilation mode
Intervention Description
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
Primary Outcome Measure Information:
Title
Effects of increasing central blood volume on heart rate variability
Description
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
Time Frame
10 mins each step
Title
Effect of cyclic intrathoracic pressure oscillations on heart rate variability
Description
The studied subject will undergo to two ventilatory modes:
spontaneous breathing at 18 breaths per min
positive pressure ventilation via face mask
Time Frame
10 min each step
Secondary Outcome Measure Information:
Title
Effects of increasing central blood volume and of cyclic intrathoracic pressure oscillations on echographic cardiac function variables
Description
At each step cardiac functionality assessment will be done by transthoracic echocardiography
Time Frame
10 mins each step
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
ASST Fatebenefratelli Sacco, Luigi Sacco Hospital
City
Milan
ZIP/Postal Code
20157
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
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
Results Reference
background
PubMed Identifier
6166045
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.
Results Reference
background
PubMed Identifier
25793464
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.
Results Reference
background
PubMed Identifier
9602579
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.
Results Reference
background
PubMed Identifier
16540963
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.
Results Reference
background
PubMed Identifier
8598068
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.
Results Reference
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Autonomic Challenges From Mild Hypovolemia and Mechanical Ventilation
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