The Relationship Between Cardiac Output and Microvascular Visceral Blood Flow

Healthy Volunteers Clinical Trial

Official title:

Investigation of the Relationship Between Oesophageal Doppler Assessed Increases in Cardiac Output and Microvascular Visceral Blood Flow in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02167178
• Other study ID #: A12012012
• Status: Completed
• Phase: N/A
• First received: June 16, 2014
• Last updated: January 26, 2015
• Start date: January 2013
• Est. completion date: August 2014

Study information

• Verified date: January 2015
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Councils UK
• Study type: Observational

Clinical Trial Summary

Although major surgery is often required to treat abdominal problems, there is a significant risk of death or complication following these operations. By using ultrasound the amount and timing of fluid patients receive during operations can be optimised and the risk of surgery reduced. However, little is known about the exact changes in blood flow in the small vessels of the body in response to fluid. A greater understanding of this may allow for more appropriate care of patients undergoing this type of surgery in the future.

In this study of healthy volunteers we will attempt to better understand how fluid administration guided by ultrasound effects blood flow in large and small vessels, by using two different techniques of ultrasound imaging. A narrow bore (approximately 4-5mm diameter) ultrasound probe will be passed through the nostril and mouth to rest within the oesophagus allowing measurement of blood flow in the main artery, while a second probe will be rested on the volunteer's abdomen and used to record changes in blood flow in small liver blood vessels. Comparison of these two techniques during the administration of fluid will allow us to better understand the relationship between large and small vessel blood flow.

Because different types of fluid may behave in different ways, we will test the effect of two types of fluid commonly used in clinical practice; `normal` saline solution and gelofusine.

Description:

Optimizing intravascular volume and cardiac output are essential to ensure adequate organ perfusion in patients who are undergoing major surgery. To enable this cardiac output is frequently monitored during operation using a variety of techniques; one such technique is trans-oesophageal Doppler ultrasound also known as oesophageal Doppler monitoring (ODM). ODM measurement of cardiac output is a less invasive technique than many currently used methods, and has recently been recommended by NICE for adoption in clinical practice.

The matching of microvascular blood flow, cardiac output and fluid administration is advantageous for visceral organs, in marrying demands for oxygen and nutrients to their delivery. However, although there is evidence to suggest that intraoperative ODM directed fluid administration can improve outcomes in the perioperative period, reducing hospital stay and complications, there is little direct evidence that optimization of cardiac output via ODM improves the microvascular blood flow to the visceral organs which are frequently compromised by major surgical interventions. A greater appreciation of the effect of ODM guided fluid replacement on the delivery of blood and hence oxygen and nutrients to these vital organs could help with the development of more refined algorithms for fluid administration in a clinical setting in the future. In our clinical physiology laboratories we regularly employ contrast-enhanced ultrasound (CEUS) using a Phillips iU22, to visualize microvascular blood flow in healthy young and elderly men following a variety of physiological challenges. This minimally invasive ultrasound based imaging technique is ideal for gaining an insight into the effect various physiological interventions have on tissue blood flow and could be readily used to chart changes in visceral microvascular flow following ODM guided fluid optimization. Transference of this investigative approach to a clinical setting has the potential to greatly improve the care of the surgical patient requiring fluid resuscitation.

Different types of intravenous fluids are used in clinical practice. These are primarily crystalloid solutions, such as 0.9% sodium chloride (`normal` saline), or colloidal suspensions, such as gelofusine. There is good experimental evidence that the colloid gelofusine produces a greater effect on cardiac output than an equivalent volume of of saline, but it is unclear if this effect is replicated in the microvasculature.

We will test the hypotheses: (1) cardiac output and stroke volume as measured by ODM are determinants of visceral microvascular blood flow (2) visceral microvascular blood flow in elderly individuals is more closely determined by stroke volume (3) gelofusine produces a greater increase in microvascular blood flow than the same volume of normal saline.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• male

• age 18-80 years

• body mass index 20-30kg/m2

Exclusion Criteria:

• BMI < 20 or > 30 kg/m2.

• Active cardiovascular disease: uncontrolled hypertension (BP > 160/100), angina, heart failure (class III/IV), arhythmias , right to left cardiac shunt or recent cardiac event.

• Individuals taking beta-adrenergic blocking agents.

• Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial)..

• Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, types 1 or 2 diabetes.

• Active inflammatory bowel disease, or renal disease,

• Malignancy

• Clotting dysfunction

• Previous oesophageal surgery

• Individuals with a known history of oesophageal varices

• Individuals with a known history of epistaxis

• Family history of early (<55y) death from cardiovascular disease.

• Known sensitivity to SonoVue

• Known sensitivity to gelofusine

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Other:
• Administration of 0.9% NaCl solution
Volunteers administered 0.9% NaCl solution in 250ml boluses
• Measurement of stroke volume
The measurement of stroke volume will be performed using an Oesophageal Doppler Monitor.
• Measurement of microvascular blood flow
Microvascular blood flow will be measured using a contrast enhanced ultrasound scan.
• Administration of gelofusine
Volunteers administered gelofusine in 250ml boluses

Locations

Country	Name	City	State
United Kingdom	University of Nottingham, School of Medicine, Division of Medical Sciences and Graduate Entry Medicine	Derby	Derbyshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in microvascular visceral blood flow	Microvascular visceral blood flow is assessed using contrast enhanced ultrasound scanning, following stroke volume optimisation.	30 minutes	No
Secondary	Change in stroke volume	The change in stroke volume will be assessed using an Oesophageal Doppler Monitor, and will be assessed pre- and post-intravenous fluid administration.	30 minutes	No
Secondary	Change in haematocrit	The change in the haematocrit will be measured pre- and post-intravenous fluid administration.	60 minutes	No