Blood Isoflurane Concentration and the Oxygenator

Does the Type of Oxygenator Influence Arterial Blood Concentration of Isoflurane During Cardiopulmonary Bypass?

This study compares two oxygenators commonly in use to establish whether they effect the amount of isoflurane in the patient's blood. Half of the patients will be placed in a group using the Sorin Inspire oxygenator and half into the group using the Medtronic Affinity Fusion oxygenator.

Study Overview

• Status: Unknown
• Conditions: Cardiopulmonary Bypass
• Intervention / Treatment: Device: Sorin Inspire Oxygenator; Device: Medtronic Affinity Fusion

Detailed Description

Cardiopulmonary bypass (CPB) is the keystone of most of these surgeries, as it allows for the maintenance of patient circulation without the requirement for a beating heart or breathing lungs. However, in doing so, CPB creates a unique set of difficulties associated with administering and maintaining anaesthesia. Firstly, the usual route of administration of inhalational anaesthetics, such as isoflurane, via the lungs is impossible. Secondly, clinical signs used to assess depth of anaesthesia, such as heart rate and systemic arterial blood pressure, are obscured by the mechanical support of the circulation. As a consequence, maintaining and assessing the depth of anaesthesia achieved during CBP provides challenges for the anaesthetists.

One common approach to administering anaesthesia during CBP involves the delivery of an inhalational anaesthetic agent, such as isoflurane, into the sweep gas supply to the oxygenator. Whilst classic terminology describes agents such as isoflurane as inhalational, in CPB this may cause confusion due to the delivery of the agent through the oxygenator as opposed to the lungs. Therefore, the alternative name of volatile anaesthetic agents is utilised in this protocol. Isoflurane concentrations ranging between 1% and 2.5% have been used by several anaesthetists at the Royal Infirmary of Edinburgh (RIE) for many years. This pragmatic approach has been found to produce clinically adequate depth of anaesthesia when either of the two oxygenators in routine use at the RIE are employed. Indeed, it has been shown using an electro-encephalographic (EEG) technique of assessing depth of anaesthesia, known as the Bispectral Index (BIS), that administering 2.5% isoflurane produces a more than adequate depth of anaesthesia. However, as discussed below, the interpretation of this finding is limited by the profound effect of hypothermia, which is commonly induced on CPB, has on BIS.

BIS is frequently utilised by anaesthetists to monitor anaesthetic depth. It involves real-time monitoring brain electrical waves using an EEG to produce a dimensionless number between 0 (no cortical brain activity) and 100 (awake), with 40 to 60 being widely accepted as a score suitable for general anaesthesia. Whilst BIS is frequently used in practice, as it has been shown to reduce anaesthetic awareness and increase emergence time, it is not without controversy as there is conflicting evidence regarding its reliability, particularly during CPB as low body temperature is known to affect its readings.

Considering the limitations of BIS, other methods can be employed to estimate depth of anaesthesia. The arterial blood concentration of the volatile agent is a good surrogate, as the concentration of agent in the brain will equilibrate with that of the blood.

Whilst this measurement provides a definitive value of how much anaesthetic agent is reaching the brain, it is impractical for clinical use because of the long duration and complexity of laboratory analysis that is required. Therefore, another approach can use the concentration of the volatile agent in the gases exhausted from the oxygenator in order to estimate the arterial blood concentration. This approach is analogous to using the end-tidal concentration that is expired from the lungs during routine general anaesthesia. Oxygenator exhaust, unlike arterial blood concentration, would be practical in a clinical scenario as the oxygenator exhaust from CPB can be attached to a standard anaesthetic gas monitor. Indeed, there is evidence that suggests measuring the oxygenator exhaust concentration of volatile anaesthetic agent is a good surrogate of arterial blood levels.

The oxygenator acts as the key interface between the patient's blood and volatile anaesthetic agent, and their availability is essential for CPB to go ahead. The RIE stock and routinely use two makes of oxygenator in case of manufacture supply problems - in which event the perfusionist would be familiar with using both. Both oxygenators are membrane in nature, consisting of microporous polypropylene hollow fibres. One is the Medtronic Affinity Fusion ('Fusion') and the other is Sorin Inspire ('Inspire'), with the choice of which is used being at the discretion of the perfusionist. Both oxygenators possess a similar design, with the patient's blood flowing over the fibers and a mixture of air and oxygen passing through them, allowing for gas exchange to occur, and crucially allowing the passage of volatile anaesthetic agent into the patient's blood. As the manufacture and design of various oxygenators are different, each possesses a unique set of transfer characteristics, which has been shown in bench tests to affect the uptake and elimination of isoflurane. The combined experience of the anaesthetists at the RIE indicates there is no clinical difference between the two different oxygenators in routine use or the resulting anaesthesia, however these bench tests suggest there may be some difference in transfer characteristics which may be established by small differences measured in the arterial blood level of isoflurane.

It also follows that if there are differences in arterial blood levels, other methods of measuring depth of anaesthesia, such as BIS and oxygen exhaust concentration of anaesthetic agent, may also show differences dependent on the oxygenator used. This is because they are measuring the same end-point, and should theoretically be related if they are accurately doing so.

Regardless of which of the two routine oxygenators is used during CPB, it has anecdotally been seen that no clinical difference in anaesthetic depth is observed. However, small differences may be detected by measuring the arterial blood concentration of isoflurane. If a difference exists, it suggests that anaesthetists should take the oxygenator transfer characteristics into account when deciding on which isoflurane concentration is to be used. If no difference is established, it will reassure anaesthetists that their interpretation of depth of anaesthesia in the clinical environment is correct.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Alston; Phone Number: (44) 131 242 3180,; Email: peter.alston@ed.ac.uk

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom, EH16 4SA
    • Recruiting
    • Royal Infirmary Edinburgh
    • Contact: Peter Alston; Phone Number: (44) 131 242 3180,; Email: peter.alston@ed.ac.uk
    • Sub-Investigator: Cathy Kitchen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged 18 years or older
• who have given their consent to participate
• scheduled for elective cardiac surgery requiring CPB

Exclusion Criteria:• younger than 18 years' old

• unwilling or unable to provide informed consent
• presenting for emergency surgery
• undergoing cardiac surgery without CPB
• in whom total intravenous anaesthesia (TIVA) is being used

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sorin Inspire Oxygenator; Sorin Inspire Oxygenator is used on the cardiopulmonary bypass machine	Device: Sorin Inspire Oxygenator; This is an oxygenator manufactured by the Sorin group. It is a hollow fibre polypropylene oxygenator.
Active Comparator: Medtronic Affinity Fusion Oxygenator; Medtronic Affinity Fusion Oxygenator is used on the cardiopulmonary bypass machine	Device: Medtronic Affinity Fusion; This is an oxygenator manufactured by the Medtronic group. It is a hollow fibre polypropylene oxygenator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial blood concentration of isoflurane	6ml sample of blood will be taken at three time points during an operation requiring cardiopulmonary bypass. This blood will be analysed using gas chromatography and mass spectrometry in order to quantify isoflurane concentrations. Mean values will be calculated for each participant, and then an overall mean will be produced for each oxygenator. This will then be compared using independent-samples t-test.	Application of aortic cross clamp, 20 minutes after application, removal of aortic cross clamp.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bispectral Index Score (BIS)	A five-electrode BIS monitor will be placed on the forehead at the beginning of surgery. This will display a BIS Score on the Mindray monitor.	Application of aortic cross clamp, 20 minutes after application, removal of aortic cross clamp.
Change in arterial temperature	Arterial temperature is measured by the cardiopulmonary bypass machine and displayed continuously on the perfusionist's monitors. It will be read directly from these monitors.	Application of aortic cross clamp, 20 minutes after application, removal of aortic cross clamp.
Change in exhaust isoflurane concentration	The cardiopulmonary bypass exhaust output will be analysed by infrared gas analysis, which will be displayed as a reading on the Mindray monitor throughout the operation.	Application of aortic cross clamp, 20 minutes after application, removal of aortic cross clamp.

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian
• Investigators: Principal Investigator: Peter Alston, Honorary Clinical Senior Lecturer and Consultant Anaesthetist

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2017
• Primary Completion (Anticipated): June 30, 2017
• Study Completion (Anticipated): July 31, 2017

Study Registration Dates

• First Submitted: April 6, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): May 10, 2017
• Last Update Submitted That Met QC Criteria: May 5, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: AC16130

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