Age-dependent decrease in desflurane concentration for maintaining bispectral index below 50. 
Acta Anaesthesiologica Scandinavica 60 (2016) 177–182 doi: 10.1111/aas.12642

Presented by: Dr S Hale


Particularly since NAP5, the potential for awareness under anaesthesia is frequently discussed, and more anaesthetic departments are investing in depth of anaesthesia monitors. At the same time, more evidence now suggests an association between increased depth of anaesthesia and post-operative adverse neurological complications.

Design & Setting

The study hypothesised that the MACBIS50 would decrease with advancing age. Sixty patients requiring elective orthopaedic of GI surgery were enrolled into the trial. The investigators specifically looked at the MACBIS50 during the resting state, prior to knife to skin. Within each of the three age groups, they induced anaesthesia and intubated each patient with remifentanil and propofol (as desflurane is a respiratory irritant). A BIS monitor was attached prior to induction, and EEG measured for a set period. Desflurane was then started at a preset value once the BIS rose >60, using 8L/min driving gas.

After 10 minutes, a blinded observer monitored the BIS each minute. Within each age group, the starting Desflurane concentration was 4%. This was based on their unpublished preliminary study which showed that the MACBIS50/MAC ratio for sevoflurane was 0.6 for middle ages subjects. They applied the same ratio to the MAC of 6 for desflurane. If the patient had an average BIS < 50, they reduced the desflurane concentration by 0.5% for the next patient in that age group, or if it was >50%, then increased it by 0.5%.

The study was performed in Osaka City General Hospital, Japan.


Twenty subjects for each group: Young (20-30 years), middle aged (31-65 years) and elderly (65-80 years). All were ASA I or II. Patients with asthma, arrhythmias, psychiatric illness, neuromuscular disease, ischaemic heart disease, LVEF <40%, Blood pressure <80mmHg, or serum Na ≤135 of ≥148mEq/l were excluded.

All patients were of a similar height and weight. Other demographics such as smoking status and ethnicity were not mentioned.


The concentration of inspired desflurane was altered for each patient as described above. They then calculated the average desflurane used for each age group, using an up-down method and further logistical regression analysis. The two methods correlated relatively well.


The MACBIS50 did decrease with advancing age. The results were significantly significant using the up-down method. The MACBIS50 for the young was 4.25, middle ages 3.58, and elderly 2.75.


The authors state that the statistics within this study do provide the necessary information to prevent awareness under anaesthesia when using desflurane. However, given the study was performed during the resting state, it does not provide information regarding probability of movement in response to surgical stimulation. During our discussion, the group concluded that it would neither predict BIS values once surgical stimulation is applied, and can therefore the conclusions cannot necessarily be relied upon to avoid awareness.


The MACBIS50  during resting state did decrease with advancing age.


All of the 60 patients recruited completed the study. A preliminary study ensured adequate power of this study.

No patients reported awareness on questioning one day post operatively.


There are a number of weaknesses within the trial. By excluding patients with a range of common medical conditions, their study population does not necessarily reflect the average NHS cohort of patients. They did not fully justify why they used MACBIS50. We still don’t really know what BIS50 means, and it likely to be different between individuals. We don’t know at what BIS value an individual can be predicted to lose or regain consciousness. BIS values do not predict movement to stimulus, and the degree to which commonly used opioids effect BIS are unpredictable.

The study used average BIS, rather than highest and lowest values.

Implications & potential for impact

We know that MAC50 decreases by 6% for each decade of life and many modern anaesthetic machines will display MAC values adjusted for age.

Although this study supports current evidence, a knowledge of the values for MACBIS50 for three wide ranging age groups of patients not being surgically stimulated, is unlikely to change every day clinical practice.