Blood Isoflurane Concentration and the Oxygenator

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.