Autonomic Challenges From Mild Hypovolemia and Mechanical Ventilation

NCT ID: NCT03244891

Last Updated: 2019-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-15
• Study Completion Date: 2019-07-30

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.

Conditions

Autonomic Nervous System Imbalance; Hypovolemia; Positive-Pressure Respiration

Study Design

• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Studied subjects

Each subject will be studied during two sequential phases:

1. before fluid challenge

2. after fluid challenge

During each phase, the subjects will be studied at:

1. baseline - spontaneously breathing

2. head down position - spontaneously breathing

3. baseline - positive pressure ventilation

4. head down position - positive pressure ventilation The sequence a-b-c-d will be randomized for each subject and for each phase

Group Type: EXPERIMENTAL

Increase of central volume

Intervention Type: OTHER

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:

1. baseline

2. after fluid shift induced by passive head down position at 15 degrees

3. after fluid challenge with Ringer acetate 15ml*kg in head down position

A total of six steps will be considered for the analysis

Ventilation mode

Intervention Type: OTHER

Each previous step will be done in two respiratory conditions:

1. spontaneous breathing

2. 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

Interventions

Increase of central volume

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:

1. baseline

2. after fluid shift induced by passive head down position at 15 degrees

3. 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

Ventilation mode

Each previous step will be done in two respiratory conditions:

1. spontaneous breathing

2. 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

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ASST Fatebenefratelli Sacco

OTHER

Sponsor Role: lead

Responsible Party

Riccardo Colombo

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

ASST Fatebenefratelli Sacco, Luigi Sacco Hospital

Milan, , Italy

Countries

Italy

References

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 6166045 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25793464 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9602579 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16540963 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8598068 (View on PubMed)

Other Identifiers

HRV2017_Healthy

Identifier Type: -

Identifier Source: org_study_id