The Effect of Phenylephrine and Ephedrine on Microvascular Blood Flow

Recruiting

Phase N/A Results N/A

Trial Description

During operations to treat abdominal problems the blood pressure can fall, resulting in falls in blood flow to the vital organs. This fall can be treated by the administration of drugs that cause constriction of blood vessels. Although these drugs correct falls in blood pressure, it is unclear what effect they have on blood flow from the heart and to the vital organs.
In this study of healthy volunteers we aim to better understand the changes in blood flow in both small and large vessels that occur in response to administration of these drugs. To do this we will use two different techniques of ultrasound imaging. A narrow (4-5mm) ultrasound probe will be inserted into the oesophagus via a nostril to measure blood flow in a major blood vessel. A second probe will rest on the abdomen and will record changes in blood flow in small vessels of the liver. Two drugs which raise the blood pressure via different mechanisms will be administered and the changes in flow from the heart and to vital organs will be measured and compared.

Detailed Description

Optimising the cardiac output is essential to ensure adequate organ perfusion in patients who are undergoing major surgery. To enable this cardiac output (CO) is frequently monitored during operations using a variety of techniques; one such technique is trans-oesophageal Doppler ultrasound also known as oesophageal Doppler monitoring (ODM). ODM measurement of CO 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 and CO is advantageous for visceral organs, in marrying demands for oxygen and nutrients to their delivery. Major surgery and the attendant requirement for general anaesthesia can result in dramatic changes in blood pressure (BP) and CO. These changes can be corrected by the administration of vasoactive drugs such as phenylephrine and ephedrine, although it is unclear what effects these drugs have on microvascular blood flow (MVBF) to the intra-abdominal viscera. Whilst they correct falls in BP, and hence may increase visceral flow, this increased BP is partially mediated via splanchnic vasoconstriction, which may result in decreased blood flow. A greater appreciation of the effect of these vasoactive drugs on the CO and MVBF may help with the development of more refined algorithms for their use in the clinical setting. In our clinical physiology laboratories we regularly employ contrast-enhanced ultrasound (CEUS) using a Phillips iU22, to measure MVBF in healthy males 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 MVBF and CO following vasoactive drug administration. Transference of this investigative approach to a clinical setting has the potential to greatly improve the care of the surgical patient under anaesthesia.

Conditions

Interventions

  • Administration of phenylephrine Drug
    Intervention Desc: Intravenous phenylephrine will be administered in 50-100 microgram increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 1mg has been administered.
    ARM 1: Kind: Experimental
    Label: Group 1
    Description: Healthy volunteers
  • Measurement of stroke volume Other
    Intervention Desc: The measurement of stroke volume will be performed using an Oesophageal Doppler Monitor
    ARM 1: Kind: Experimental
    Label: Group 1
    Description: Healthy volunteers
  • Contrast enhanced ultrasound scan Other
    Intervention Desc: Microvascular blood flow will be measured using a contrast enhanced ultrasound scan
    ARM 1: Kind: Experimental
    Label: Group 1
    Description: Healthy volunteers
  • Administration of ephedrine Drug
    Intervention Desc: Intravenous ephedrine will be administered in 3-6mg increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 30mg has been administered.
    ARM 1: Kind: Experimental
    Label: Group 1
    Description: Healthy volunteers

Trial Design

  • Perspective: Prospective
  • Sampling: Non-Probability Sample

Trial Population

Healthy male volunteers

Outcomes

Type Measure Time Frame Safety Issue
Primary Change in microvascular blood flow 30 minutes No
Secondary Change in stroke volume 30 mins No

Sponsors