The ability of bispectal index to detect intra-

operative wakefulness during total intravenous

anaesthesia compared with the isolated forearm

techniqueI.F Russell

Anaesthesia May 2013 68, 502-511

Background (1)TIVA – no direct method to measure drug

concentration in key body compartments? Is there more awareness when TIVA used“Awareness during anaesthesia” = patients in

post op period have recall of intra-operative events

“Wakefulness” = conscious during surgery but with no recall

Background (2)Most studies of anaesthesia brain monitoring

(ABM) focus on post op recall, but don’t tell us about intra-operative (un)consciousness

Studies so far of ABM using isolated forearm technique (IFT) to investigate intra-op consciousness during GA in presence of NMB show ABMs are unreliable at assessing patient’s level of consciousness at which they respond to commands

BIS (Bispectral index) – most commonly used ABM

Aim of studyTo use a manually adjusted target controlled

infusion of propofol for anaesthesia, titrated to a BIS index range of 55-60 to:

1.Observe the incidence of intra-op responsiveness to command as assessed by IFT

2.Evaluate the utility of BIS to predict/identify pt responses to commands

3.Compare BIS observed during intra-op responsiveness with that at eye opening to command at end of surgery

HypothesisIf BIS detected intra-op wakefulness appropriately,

its values would correspond to responses (if any) obtained using IFT

Methods (1)Ethical approval from Local Research Ethics

CommitteeWomen undergoing major gynaecological surgeryWritten consent obtained to undergo surgery using

BIS monitoring to guide administration of propofol, in association with clinical signs and the IFT

Exclusion criteria:Age >60 and <18Hearing difficultiesASA >2

Methods (2)Pre-op interview ascertained:

Name pt normally usedRight or left handedPt informed that anaesthetist would speak to her

during surgery and that she would be able to move hand to indicate she was awake

No mention of specific commands on minidisc player or content of recorded message

Methods (3)One minute recording consisting of following tracks

created to play continuously to patient through padded headphones during operation until it was switched off

1. Command (15 secs)2. Radiostatic (15 secs)3. Info for pt to remember (15 secs)4. Radiostatic (15 secs) Switched on at skin incision and switched off at

start of skin closure before TCI pump switched off

Methods (4)Command: “Name, name, this is Dr Russell

speaking. If you can hear me, open and close the fingers of your right/left hand, open and close the fingers of your right/left hand”

Info to remember: “Name, name, this is Dr Russell speaking. Here are some special words I want you to remember: green pear, sharp lemon, sour gooseberry”

From when TCI pumps switched off until a response was obtained, the patient was asked at 1 min intervals “Name, name, open your eyes” – BIS at eye opening noted

IFT (1) Tourniquet applied to dominant forearm ECG electrodes over ulnar and median nerves at elbow,

connected to nerve stimulator set at 60mA current Arm placed on armboard close to 90o from table so

forearm/hand observed at all times Hand restrained with strap around palm and armband After LOC, tourniquet inflated to 200mmHg and hand

response to nerve stimulation observed Atracurium 0.4mg/kg administered 20-30 mins post intubation the tourniquet deflated

IFT (2)NM integrity (TOF, short tetanic stimulus) assessed at

regular intervals to ensure adequate muscle powerIf further NMB needed during surgery, then cuff re-

inflated and IV bolus 0.2-0.3mg/kg atracurium given, then cuff deflated 20-30 mins later

If hand response noted during surgery, consciousness verified by speaking directly to pt and asking “Name, name, squeeze my fingers once”. If response then command to squeeze fingers twice given

Before speaking to pt directly minidisc player stopped and one ear piece eased from ear

Methods (5)Routine monitoring – ECG, NIBP (dominant upper

forearm), pulse oximetry (finger of non dominant hand)16G IV cannula (non dominant forearm)Low thoracic (~T10) epidural before induction of

anaesthesia if pt consented – 3ml 0.5% levobupivicaine test dose then further 7ml. Topped up with further 10ml increments of 0.5% levobupivicaine at 90-120 min intervals throughout surgery

Before induction of anaesthesia BIS electrodes applied

Methods (6)Anaesthesia induced and maintained using an

effect site TCI of propofol – initial target 4ug/mlAlso used effect site infusion of remifentanil (initial

target 2ng/ml)If consciousness was not lost at these target

concentrations (i.e. there was response to command “Name, open your eyes”) then target concentration of both drugs increased

Methods (7)Following intubation, TCI pumps manually

adjusted to maintain BIS in range 55-60If BIS >60 with no IFT response and stable clinical

signs then anaesthesia not deepenedRegardless of BIS value, if pt responded to

command the TCI propofol target increased until responding stopped (or not altered if command stopped spontaneously)

Methods (8)At end of surgery, following eye opening to

command, the ETT was removed and pt transferred to recovery

Pts interviewed in recovery by author using structured format to investigate implicit and explicit memory using info given via headphones

No follow up interviews on subsequent days

Methods (9)Definitions:

Consciousness = verified response to commandBIS index identifying consciousness in association

with pt response to command = BIS index >60 continuously for at least 60 secs within time period extending from 2 mins before to 2 mins after the pt IFT response

Interpreting BIS If BIS index rose >60 continuously in association with

hand movement response and then BIS index still >60 at time of subsequent movement response, then assumed that BIS had identified consciousness associated with this subsequent response

In absence of any pt response to command, a BIS index > 60 continuously for at least 60 secs was taken to indicate the mistaken prediction/identification of consciousness

Single BIS value <60 in the 1 min time intervals was ignored

Results22 women recruited1573 commands played to 22 ptsExcluding eye opening response at end of surgery,

16 (73%) women responded to commands during surgery In total these 16 women responded to command 80

times and of these the BIS monitor detected 47

Pts responded to command over wide range of BIS values

52% of the responses occurred in association with a BIS <60

BIS associated with eye opening to command after surgery vs BIS associated with response to intra-operative commands – STATISTICALLY SIGNIFICANT DIFFERENCE; BIS of 75 (IQR 70-78) vs 61 (IQR 52-67), P<0.001 – WHY??

No such difference in propofol concentrations when compare 2 groups at this point; 2.1 (IQR 1.7-2.8) ug/ml vs 2.0 (IQR 1.5-2.3) ug/ml, p value >0.05

BIS > 60 for 60 secs or more for median of 17% of time between tape on and tape off – no significant difference between responders and non-responders (17 vs 23%)

Median of time from when TCI pumps switched off until pts opened their eyes to command was 2.7 mins; no significant difference between responders and non-responders (2.4 vs 3.5 mins)

On direct questioning2/16 pts who responded during surgery had vague

memory about “squeezing fingers” and 1/6 pts in non-responding group remembered extubation

No other evidence of explicit/implicit memory in any pt, and no pt had recall of surgery

3 other women (1 responder, 2 non-responders) recalled dreaming, but not the content, apart from it being a good dream

NMB of isolated hand never compromised, TOF always 4 and tetanic stimulus well maintained

Discussion (1)Study does not support notion that manual

adjustment of TCI propofol in attempt to keep BIS 55-60 is an appropriate anaesthetic technique

Overall incidence of consciousness with recall in the patient group high (~10%)

Without concurrent use of IFT this incidence of consciousness could have been higher

Difficult to keep BIS in such narrow range of 55-60 (26% of time BIS >60; half of this time between 60-65)

Discussion (2)? Accuracy of BIS - sensitivity of BIS response (i.e.

> 60 for 60 secs) was only 59% If titrate propofol to this level then high possibility

that high proportion of pts are conscious during surgery

Even with IFT backup 2 women (10%) had recall of commands. ? How high could this have been without IFT

Discussion (3)Difficult to define a BIS response indicative of

consciousnessBIS dimensionless numberContinuum from fully conscious to isoelectric EEGBIS can only be associated with probability of pt

being consciousDespite this widely promoted “acceptable range” of

45-60 in which pts will be “unresponsive to verbal stimuli” i.e. unconscious

? Highest BIS value, ? change in BIS value, ? Average BIS value over a period

Discussion (4)Overlap of EEG and EMG frequencies in 35-47Hz

range can falsely elevate the BISEMG can raise due to wearing off of NMB or pt

waking up (without using IFT would not know whether to deepen anaesthesia or give further NMB drug)

If maintain near complete muscle paralysis can this be avoided?

BIS (black line); EMG (green line); propofol concentration (blue dotted line)

LimitationsOnly 22 patientsDefinition of consciousnessIf patients can move in response to command then

why don’t they move in response to surgical stimulus?Is BIS index of 55-60 too near the “margins of

consciousness”? though current guidance does say 45-60

Would further interviews later down the line have uncovered more recall?

SummaryStudy does not support notion that manual

adjustment of TCI propofol in attempt to keep BIS 55-60 is an appropriate anaesthetic technique

In presence of NMB drugs, ABMs like BIS are not able to identify the return of consciousness with any reliability

BIS correlates poorly with IFT when used as an indicator of consciousness during GA, with poor PPV and sensitivity