1 Peninsula Medical School, ITTC Building, Tamar Science Park, Davy Road, Plymouth PL6 8BX, UK E-mail: robert.sneyd{at}pms.ac.uk
Intraoperative awareness is a terrifying experience, which patients fear and anaesthetists are anxious to avoid; any clinician who doubts this should read a first hand account.1 Since the early 1990s, the Bispectral Index (BIS) has been developed as a measure of hypnosis during anaesthesia and sedation. As BIS is a linearized and monotonic measure, clinicians have become comfortable with the idea that an increase in BIS may warn of actual or impending awareness. Although there are currently no substantial data proving that generalized use of the monitor would reduce the rate of awareness, the device has become popular, especially in the USA.
In this issue of the British Journal of Anaesthesia, Hoymork and colleagues2 report using BIS to guide the administration of i.v. anaesthesia. They found that measured plasma concentrations of propofol were poorly correlated with BIS and also observed wide discrepancies between predicted and measured concentrations of both propofol and remifentanil in some patients on some occasions.
Humans are unique and this is reflected in their responses to anaesthesia and surgery. This variability is visible during day-to-day clinical practice when one patient given a standardized anaesthetic recipe wakens promptly at the end of surgery and in another the recovery is significantly delayed. To an observer, it might appear that the anaesthetist has given a good anaesthetic in the first case and a bad one in the latter. The thinking clinician understands that giving the same dosage regimen to two patients produces different results because of pharmacokinetic and pharmacodynamic variability.
In practical terms, pharmacokinetic variability is evident when measuring blood concentrations during a fixed rate infusion. Even if the infusion rate is corrected for weight (i.e. mg kg1 h1 rather than mg h1), we will see a different concentration profile in every patient. The commercial TCI System for propofol (Diprifusor) expresses a predicted drug concentration, which is the output of a pharmacokinetic model based on previous patients. If we measure the actual rather than the predicted concentration, it is virtually never the same as that displayed and may be either higher or lower. It is therefore the case that we never know the actual concentration of any i.v. anaesthetic agent either in the blood or in the notional effect compartment.
Pharmacodynamic variability builds on the unstable foundation of pharmacokinetic variability. Even if we can achieve a constant drug concentration in individual patients their responses will be different, that is at a particular drug concentration one patient may be awake and another unconscious. Pharmacokinetic and pharmacodynamic information can be pooled and modelled3 and the effects of particular drug combinations predicted in detail.4
Given this fluctuating background, the search for a direct measure of drug effect, that is a depth of anaesthesia monitor, is attractive to clinicians and researchers alike. Various studies have shown that intraoperative BIS monitoring reduces drug administration and measured drug concentrations and reduces early recovery times, but has little impact on more important outcomes like readiness for discharge from hospital.57 Although superficially attractive in terms of reduced drug costs and slightly accelerated progress of patients through care pathways, it is possible that this monitoring may encourage risky anaesthetic practice with perilously light anaesthetics becoming the norm. Given current estimates of peroperative awareness (around one case in 600), then prospective studies to confirm whether BIS monitoring decreases, increases, or does not affect the rate of awareness, will be large and, therefore, costly.8
What should we be doing now? Despite vigorous commercial promotion, depth of anaesthesia monitoring is certainly not a care standard nor is it proven to improve patient safety. Using BIS to confirm that a patient is deeply anaesthetized may be reassuring but using it to skate on thin ice may lead both the anaesthetist and their patient into dangerous territory. Current marketing material from Aspect Medical Systems, the manufacturer of the BIS, includes as strap lines An extension of your expertise and The comfort of knowing. These anodyne phrases are seductive yet compatible with our present uncertainty. Only when large prospective studies have demonstrated that daily use of BIS by typical clinicians reduces the risk of awareness, can we state that the time of depth of anaesthesia monitoring has really come. Hoymork and colleagues2 have usefully reminded us that the relationships between predicted and measured drug concentration, indices of anaesthetic effect and actual anaesthesia are complex and, as yet, not fully characterized.
Declaration of interest. Professor Sneyd is an advisory board member for Organon Inc.
References
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2 Hoymork SC, Raeder J, Grimsmo B, Steen PA. Bispectral index, serum drug concentrations and emergence associated with individually adjusted target-controlled infusions of remifentanil and propofol for laparoscopic surgery. Br J Anaesth 2003; 91: 77380
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