Does bispectral index monitoring optimize

intravenous anaesthetic drug delivery?

Jaap Vuyk

Deparment of Anaesthesiology

Leiden University Medical Center

2300 AA, Leiden, The Netherlands

Email: j.vuyk@lumc.nl

The bispectral index monitor has been ongoing developed since 1992 with the premarket approval by the FDA in 1996 (Aspect Medical Systems, Inc., Natick, MA). The bispectral analysis is a further computation of time domain and frequency domain parameters. The bispectral analysis considers the relationship between the sinusoids at two frequencies ƒ1 and ƒ2 and a modulation of these two ƒ1+ ƒ2. For this set of three frequency components the bispectrum can be calculated on the basis of the phase information or bicoherence (BIC ƒ1,ƒ2) and the sum of the magnitude of the 3 members known as the real triplet product (RTP ƒ1,ƒ2). Finally, the bispectral index then is composed of time domain, frequency domain and higher order spectral parameters. An important feature in the calculation of the bispectral index is that the weight of any of these 4 subparameters (BSR, QUAZI, β-ratio and SyncFastSlow) changes with the level of sedation. The β-ratio weighs heavier in the final computation of BIS at levels of light sedation, the SyncFastSlow parameter dominates at excitation and surgical levels of hypnosis and the BSR and QUAZI are more important in the BIS calculation at the most deep levels of EEG depression. The specific weight of the various subparameters of BIS at various clinical states has been determined, during the development of the BIS by Aspect Medical Systems, on the basis of a body of data gathered from a group of patients that received various anesthetics while EEG and behavioral data were collected. In the end the BIS is determined as a running average of 15-30 seconds of EEG signal collection and visualized as a dimensionless nonlinear parameter between 0-100. With 0 equaling no electrical activity and with 100 defining the awake state. In general, the Bispectral Index Scale (BIS) reflects the awake state at values exceeding 95, a state of sedation at BIS values of 65-85, an arousal state depression suited for general anesthesia at BIS values of 40-65 and burst suppression patterns become evident at BIS levels below 40.

The effect of various anesthetic agents on the bispectral index scale appears to be agent specific. In general, hypnotic agents like propofol, midazolam or thiopental have a strong depressant effect on BIS, inhalational anesthetic agents propagate an intermediate depressant effect on BIS whereas the opioids have little or no influence on the BIS at clinically relevant concentrations. Lastly, nitrous oxide and ketamine appear to have paradoxical effects on the BIS. Altogether, this may be interpreted as BIS relating well to sedation and hypnosis levels but not properly reflecting the level of analgesia or depth of anesthesia.

The most promising application of the bispectral index monitor may be as a monitor of consciousness-sedation-unconsciousness levels. In the absence of central nervous system monitoring hypnotic agents are often administered on the basis of prescribed dosing regimens (12-10-8 mg/kg/h step-down propofol infusion scheme) that may be adjusted to the response of the individual patient. The prescribed dosing regimens do not take into account the pharmacokinetic variability of + 70% or the pharmacodynamic variability of + 300-400% in between patients. This huge interindividual PK/PD variability next to the sometimes poor predictability of the surrogate measures of sedation and anesthesia (haemodynamic parameters, movement responses etc.) are the cause of the frequent over- and under dosing of individual patients during sedation and general anesthesia. The BIS probably is most easily interpreted and may relate best to the actual level of sedation during sedation with a single agent in the absence of painful stimuli. Although no single BIS value exists that will assure an adequate hypnotic level in every patient in the presence of any possible anesthetic agent combination or type of stimulation, the BIS has proven acceptably reliable as a measure of hypnosis during sedation and general anesthesia with most anesthetic agents. Clinically, the optimized focusing of drug administration to the specific needs of the patient with BIS monitoring may result in a reduced agent administration and increased speed of return of consciousness and recovery.

Because the BIS very closely correlates with the level of (un)consciousness it is very tentative to state that the use of bispectral index analysis will reduce or prevent the occurrence of awareness. However, because the incidence of awareness is relatively low and because awareness has been reported in the presence of BIS monitoring, showing that the efficiency of awareness prevention by the BIS is not 100%, to get absolute prove that BIS monitoring would reduce the risk of awareness it would take great numbers of patients.

During the development of the bispectral index monitor agent versus behavioral data have been used to optimize the BIS algorithm. Consequently, when new anesthetic agents arise new data have to be entered and probably the BIS monitor adjusted to enable use with the new agent. As already mentioned some agents like nitrous oxide and ketamine induce their effects by mechanisms that the BIS monitor apparently is unable to track. Adding ketamine or nitrous oxide deepens the anesthetic level but increases the BIS. In the presence of these agents the BIS monitor therefore should not be used.

Electrocautery will make the BIS disappear or increase; pacemakers have been described to increase the BIS as well. EMG activity has been claimed to increase the BIS, but later versions like the recent XP version may be less susceptible to this. Lastly, hypothermia decreases the BIS by 1.12 units per degree Celsius decline in body temperature.

Conclusion.

Bispectral index monitoring is useful for the intraoperative tracking of the level of unconsciousness especially during high hypnotic-low opioid anesthesia. It allows for an improved titration of hypnotic agent requirement and may lead to a reduced agent use and improved recovery. No data yet provide sufficient prove that BIS may predict anesthetic depth or may be used to predict patient responses to noxious stimulation. BIS monitoring may be useful for guidance of sedation e.g. in the ICU but more data are required to judge its value in this setting. Lastly, no data yet provide sufficient proof that bispectral index monitoring reduces the incidence of awareness.

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