Autonomic Challenges From Mild Hypovolemia and Mechanical Ventilation

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

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.

Study Overview

• Status: Completed
• Conditions: Hypovolemia; Autonomic Nervous System Imbalance; Positive-Pressure Respiration
• Intervention / Treatment: Other: Increase of central volume; Other: Ventilation mode

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20157
    • ASST Fatebenefratelli Sacco, Luigi Sacco Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Studied subjects; 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; 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; Other: Ventilation mode; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ASST Fatebenefratelli Sacco

Publications and helpful links

General Publications

• 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.
• 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
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2019
• Primary Completion (Actual): July 30, 2019
• Study Completion (Actual): July 30, 2019

Study Registration Dates

• First Submitted: August 5, 2017
• First Submitted That Met QC Criteria: August 5, 2017
• First Posted (Actual): August 10, 2017

Study Record Updates

• Last Update Posted (Actual): October 14, 2019
• Last Update Submitted That Met QC Criteria: October 10, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hypovolemia
• Other Study ID Numbers: HRV2017_Healthy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No