Autonomic Cardiovascular Control in Response to Blood Volume Reduction in Blood Donors

The function of the autonomic nervous system can be assessed using baroreflex sensitivity (BRS) and heart rate variability (HRV). Decreased HRV has been shown to be predictive of morbidity and mortality in diverse medical conditions such as acute myocardial infarction, aneurysmal subarachnoid haemorrhage, autoimmune diseases, sepsis and surgery.

The function of the autonomic nervous system has not yet been investigated in a "pure hypovolemia" model. The aim of the current study is therefore to investigate and describe the function of the autonomic nervous system prior to, during and after reduction of blood volume in healthy blood donors.

Study Overview

• Status: Completed
• Conditions: Blood Loss; Autonomic Dysfunction; Autonomic Imbalance
• Intervention / Treatment: Device: Monitoring of the autonomic nervous system

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2960
    • Hvidovre University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

Healthy male volonteers, aged 30-45, that are eligable for blood donation following the Danish legislation

Description

Inclusion Criteria:

• Volonteers eligable for blood donation following the Danish legislation
• Male
• Age 30-45
• Written informed consent
• Speak and understand Danish

Exclusion Criteria:

Volonteers not eligable for blood donation following the Danish legislation, among others due to:

• Alcohol and drug abuse
• Cognitive dysfunction
• Use of anxiolytic or antipsychotic drugs
• Arrhythmias or heart failure
• Diabetes mellitus type I
• Diabetes mellitus type II
• Use of opioids
• History of following diseases in the autonomic nervous system: Parkinson disease, multiple sclerosis, autonomic neuropathies
• History of cerebral apoplexy or transitory cerebral ischemia
• Dementia
• American Society of Anesthesiologists (ASA) score ≥ 4

Furthermore:

• History of orthostatic intolerance and/or orthostatic hypotension
• Use of following vasodilator antihypertensive drugs: beta-blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin 2 receptor blockers (ARBs), calcium channel blockers
• Use of loop diuretics, thiazid diuretics and potassium-sparing diuretics

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Blood donors; Healhy young male bloddonors, aged 30-45	Device: Monitoring of the autonomic nervous system; Monitoring of the autonomic nervous system using E-patch, LiDCO and Root-Massimo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in root mean square of successive NN-interval differences (RMSSD) during mobilisation	Measured in ms	15 minutes prior to and 15 minutes after blood donation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in root mean square of successive NN-interval differences (RMSSD) during sleep	Measured in ms	The night before and night after blood donation
Changes in standard deviation of N-N intervals (SDNN) during mobilisation	Measured in ms	15 minutes prior to and 15 minutes after blood donation
Changes in standard deviation of N-N intervals (SDNN) during sleep	Measured in ms	The night before and night after blood donation
Percentage of successive RR intervals that differ by more than 50 ms (pNN50) during mobilisation	Measured in %	15 minutes prior to and 15 minutes after blood donation
Percentage of successive RR intervals that differ by more than 50 ms (pNN50) during sleep	Measured in %	The night before and night after blood donation
Changes in low frequency (LF) power during mobilisation	Measured in ms^2	15 minutes prior to and 15 minutes after blood donation
Changes in low frequency (LF) power during sleep	Measured in ms^2	The night before and night after blood donation
Changes high frequency (HF) power during mobilisation	Measured in ms^2	15 minutes prior to and 15 minutes after blood donation
Changes high frequency (HF) power during sleep	Measured in ms^2	The night before and night after blood donation
Changes in ratio of LF-to-HF power during mobilisation	Measured in %	15 minutes prior to and 15 minutes after blood donation
Changes in ratio of LF-to-HF power during sleep	Measured in %	The night before and night after blood donation
Changes in S (area of the ellipse which represents total HRV) during mobilisation	Measured in ms	15 minutes prior to and 15 minutes after blood donation
Changes in S (area of the ellipse which represents total HRV) during sleep	Measured in ms	The night before and night after blood donation
Changes in SD1 (Poincaré plot standard deviation perpendicular the line of identity) during mobilisation	Measured in ms	15 minutes prior to and 15 minutes after blood donation
Changes in SD1 (Poincaré plot standard deviation perpendicular the line of identity) during sleep	Measured in ms	The night before and night after blood donation
Changes in SD2 (Poincaré plot standard deviation along the line of identity) during mobilisation	Measured in ms	15 minutes prior to and 15 minutes after blood donation
Changes in SD2 (Poincaré plot standard deviation along the line of identity) during sleep	Measured in ms	The night before and night after blood donation
Changes in SD1/SD2 ratio during mobilisation	Measured in ms	15 minutes prior to and 15 minutes after blood donation
Changes in SD1/SD2 ratio during sleep	Measured in ms	The night before and night after blood donation
Changes in systolic arterial pressure (SAP) during mobilization	Measured in mmHg by non-invasive LiDCO	15 minutes prior to and 15 minutes after blood donation
Changes in diastolic arterial pressure (DAP) during mobilization	Measured in mmHg by non-invasive LiDCO	15 minutes prior to and 15 minutes after blood donation
Changes in mean arterial pressure (MAP) during mobilization	Measured in mmHg by non-invasive LiDCO	15 minutes prior to and 15 minutes after blood donation
Changes in pulse pressure (PP) during mobilization	Measured in mmHg by non-invasive LiDCO	15 minutes prior to and 15 minutes after blood donation
Changes in heart rate (HR) during mobilisation	Measured in beats min-1 by non-invasive LiDCO	15 minutes prior to and 15 minutes after blood donation
Changes in cardiac output (CO) during mobilization	Measured in L/min by non-invasive LiDCO	15 minutes prior to and 15 minutes after blood donation
Changes in stroke volume (SV) during mobilization	Measured in mL by non-invasive LiDCO	15 minutes prior to and 15 minutes after blood donation
Changes in systemic vascular resistance (SVR) during mobilization	Measured in dynes s cm-5 by non-invasive LiDCO	15 minutes prior to and 15 minutes after blood donation
Changes in cerebral perfusion (ScO2) during mobilization	Measured in % by Root Masimo	15 minutes prior to and 15 minutes after blood donation
Changes in muscular perfusion (SmO2) during mobilization	Measured in % by Root Masimo	15 minutes prior to and 15 minutes after blood donation
Changes in peripheral index during mobilization	Measured in % by Root Masimo	15 minutes prior to and 15 minutes after blood donation
Concentration of C-reacitve protein	Measured in gr/dL	At time of blood donation
V-PLEX Biomarker 54.Plex Kit	54 key analytes that are important in inflammation response and immune system regulation as well as numerous other biological processes	Blood taken at time of blood donation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score	Measured by verbal rating scale (VRS) 0 - 10 (0 = no pain, 10 = worse pain imaginable) during mobilisation procedure	15 minutes prior to and 15 minutes after blood donation

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Investigators: Study Director: Henrik Kehlet, Professor, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 30, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Autonomic nervous system; Blood donors; Autonomic cardiovascular control; Heart rate variabilty; Baroreceptor sensitivity; Acute blood loss
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Hemorrhage; Primary Dysautonomias; Autonomic Nervous System Diseases
• Other Study ID Numbers: H-19069845

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No