The Relationship Between Cardiac Output and Microvascular Visceral Blood Flow
Condition: Healthy Volunteers
Study type: Observational

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.
    

Detailed 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.
    

Intervention name(s): Administration of 0.9% NaCl solution; Measurement of stroke volume; Measurement of microvascular blood flow; Administration of gelofusine
Intervention type(s): Other; Other; Other; Other
Intervention description(s): Volunteers administered 0.9% NaCl solution in 250ml boluses; The measurement of stroke volume will be performed using an Oesophageal Doppler Monitor.; Microvascular blood flow will be measured using a contrast enhanced ultrasound scan.; Volunteers administered gelofusine in 250ml boluses
Other intervention name(s): Normal saline; Saline; CEUS; Contrast enhanced ultrasound scan; SonoVue.
Intervention MeSH terms: Polygeline
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Healthy male volunteers, aged 18-80.