In Search of a Reliable Awareness Monitor

The term anesthesia originally meant “the state in which a patient is insensible to the trauma of surgery.” Although, the science of anesthesiology has advanced rapidly, defining, measuring, and understanding depth of anesthesia has moved ahead slowly. Indeed, we are yet to define properly the phenomenon that we use in our everyday practice to render patients insensitive to the trauma of surgery. Prys-Roberts ⁽¹⁾ defined anesthesia as the state in which, as a result of drug-induced unconsciousness, the patient neither perceives nor recalls noxious stimuli. He further stated that analgesia, muscle relaxation, and suppression of autonomic activity are not the components of anesthesia, but should be considered as desirable supplements to the state of anesthesia as a means to enable surgery to be performed. Although awareness during surgery was not unknown before the use of muscle relaxants, the use of small concentrations of anesthetic with muscle relaxants resulted in some patients being aware during surgery. The incidence of awareness during anesthesia and surgery is variable and depends on the type of surgery, the anesthetics used, and the timing of and technique for, evaluating awareness and recall. In two large series of patients, the incidence of awareness has been reported to be 0.2%⁽²⁾ and 0.16%(³⁾ and a more frequent incidence ranging from 1.1% to 1.5% during cardiac surgery ^(4,5).

Awareness during general anesthesia can be a horrifying experience and may cause acute psychological trauma ⁽⁶⁾. It may also have medico-legal implications. Therefore, Eich et al. ⁽⁷⁾ believe that recall indicates a failure to anesthetize. A reliable indicator that would confirm that the level of anesthesia is adequate to ensure lack of awareness is obviously desirable. Initially, the hemodynamic response to laryngoscopy, endotracheal intubation and/or skin incision was used to assess the depth of anesthesia. Subsequently, electroencephalography (EEG) and processed EEG were used to relate drug concentration and clinical depth of anesthesia. However, application of these measures to assess clinical depth of anesthesia has not been very successful.

The Bispectral index (BIS) is a variable derived from mathematical analysis of the EEG signal that estimates phase difference. It measures the hypnotic component of the anesthetic and is a potentially useful adjunct for monitoring the depth of anesthesia. The BIS is a dimensionless number that varies from 0 to 100. The monitor assigns the BIS number based on a database of prior recordings and the expert opinion of the anesthesiologist during those recordings regarding the anesthetic depth of the patient. In the awake state the BIS is close to 100 and the number decreases with increasing sedation and hypnosis. A BIS value of <60 is often regarded as the criterion for adequate anesthesia, whereas a value of more than 70 is frequently seen during awakening ⁽⁸⁾. Its utility as a monitor having high probability of correctly predicting absence of consciousness during general anesthesia ^(9–11) and degree of sedation in intensive care patients ⁽¹²⁾ has been recognized. Therefore it has been proposed to be a useful monitor for anesthetic depth during cardiac surgery with cardiopulmonary bypass (CPB) ⁽¹³⁾, when the usual clinical markers of anesthetic depth, such as hemodynamic responses and sweating, are less dependable.

The use of words “awareness,” “memory,” or “recall” in an interchangeable fashion has caused considerable confusion, and there is a need to distinguish “awareness” and “memory.”⁽¹⁴⁾ However, irrespective of the definitions of general anesthesia, conscious recall of events should not occur during general anesthesia. Unfortunately, despite best efforts, awareness with explicit recall of events with or without pain still occur, and are often reported by victims as the worst experience of their lives.

Advances in cardiac surgery, such as off-pump coronary artery bypass grafting, where the patient is generally expected to awaken at the end of surgery, and minimizing the extubation times in patients undergoing conventional on-pump coronary artery bypass grafting demand a high degree of precision and add to the pressure on the cardiac anesthesiologist. He/she is expected to provide a perfect anesthetic that causes the least hemodynamic disturbance and allows recovery as soon as possible. While these objectives are being accomplished the patient should not suffer from awareness. The cardiac anesthesiologist is thus expected to maintain a depth of anesthesia that is commensurate with the level of surgical stimulus (that may vary from time to time) and also ensure that the effect wears off as soon as possible after the surgery. The newer more potent and shorter-acting anesthetics (e.g., remifentanil, propofol, sevoflurane, desflurane) have certainly helped a great deal in achieving these goals. However, the precise concentration of the anesthetic required to guarantee lack of recall is unknown and reliance on clinical signs is certainly not enough, especially with the use of muscle relaxants that abolish two of the most valuable indicators of depth of anesthesia, respiration and movement in response to surgery. The last few years have seen a changing trend from large-dose opioid technique to a drastic reduction in the doses of the opioids and benzodiazepines or use of shorter-acting drugs in infusion forms with or without inhaled anesthetics. In general, the incidence of awareness is associated with smaller doses of anesthetics ^(15,16) So, is the incidence of awareness increasing with modern day cardiac anesthesia practice? Perhaps not; the incidence of awareness in a large series of patients undergoing fast-track cardiac anesthesia was as small as 0.3%⁽¹⁷⁾. This may be attributed to the continuous use of either isoflurane or propofol infusions during the entire surgical procedure, as well as to monitoring of end-tidal anesthetic gas concentration.

Nevertheless, in the current scenario of cardiac anesthesia, the need for a reliable monitor that ensures unconsciousness is highly desirable. It may be more appropriate to call it an “awareness monitor,” as it would be expected to track a patient’s arousal levels and warn of impending awareness. Can BIS be called a reliable monitor? Large-scale studies confirming the utility of BIS as an anesthetic depth monitor in patients undergoing cardiac surgery are not available. However, a few studies using BIS in patients undergoing cardiac surgery have revealed conflicting results ^(18–20). The BIS values also decrease almost linearly from a median value of 95.3 to 45.5 with end-tidal sevoflurane concentration increasing from 0.2 to 1.4%⁽⁸⁾. The BIS and sevoflurane end-tidal concentration correlated closely with the clinical sedation scores of the patients. The case report in this issue of Anesthesia & Analgesia by Mychaskiw et al. ⁽²¹⁾ demonstrates the failure of BIS as a monitor of depth of anesthesia, as the patient experienced explicit recall of intraoperative events at a BIS of 47 with nitrous oxide and sevoflurane anesthesia. BIS in the range of 50 to 60 appears to be the therapeutic window associated with a high probability of unconsciousness ⁽²²⁾ and such a small BIS number with inhaled anesthetic has not been previously associated with recall. We understand that monitoring of hypnosis by BIS is a probability function, and therefore it can be expected that recall may occur despite a relatively small displayed value. In this respect, it is not totally wrong to expect similar reports of awareness at BIS as low as 47 or even lower, albeit at a very small incidence.

One study has suggested that BIS is not an accurate measure of the depth of anesthesia when fentanyl and midazolam were used during coronary artery bypass grafting ⁽¹⁸⁾. In this study, implicit recall was absent in all the patients, but BIS varied widely and values that are usually related to excessively light anesthesia or wakefulness were occasionally observed. A few more studies have demonstrated that a small percentage of patients can respond to verbal command with BIS value as small as 55 during recovery from anesthesia ^(23–25) when there was no or minimal surgical stimulus (indicating that BIS is not totally reliable when the patient is waking). Because depth of anesthesia is a balance between two antagonizing factors—the anesthetic and the surgical stimulus—is it possible that in the presence of surgical stimulus (as was present in the case) some patients can respond at BIS values smaller than 55? Perhaps yes, but the patients are usually amnesic as a result of the effects of anesthetics and, therefore, these events do not add to the instances of explicit awareness. In the present case, however, sevoflurane (end-tidal anesthetic gas concentration of 2%) administration along with 67% nitrous oxide was insufficient to provide requisite anesthesia as well as amnesia. It has also been suggested that an abrupt increase in BIS usually indicates that some form of change in awareness has just taken place ⁽²³⁾. It is not clear from the report of Mychaskiw et al. ⁽²¹⁾ if such an abrupt increase in BIS occurred in their patient after sternotomy.

This case proves yet again that some patients are not fully unconscious, even when adequately anesthetized by accepted criteria, and also highlights the need for a monitor that is capable of assessing just such instances of awareness. It is also in agreement with the general experience that auditory stimuli in particular can be perceived intraoperatively and recalled postoperatively, suggesting that auditory modality is apparently the most receptive sensory channel for perception during general anesthesia ⁽²⁶⁾. Preservation of early cortical potentials of midlatency auditory evoked potential during general anesthesia allows auditory information to be processed and remembered postoperatively ⁽²⁶⁾ and it has been suggested that drugs that suppress midlatency auditory evoked potential (volatile anesthetics and propofol) should be included in the anesthetic technique ⁽²⁷⁾. Although, changes in midlatency auditory evoked potential can reliably reflect the level of anesthesia, the AEP waves are not easy to analyze in the clinical situation and therefore the AEP_Index has been investigated as a means of assessment of depth of anesthesia ⁽²⁸⁾. Recently it has been shown ⁽²⁹⁾ that AEP_Index and BIS appear to be capable of distinguishing the awake and the anesthetized state, but AEP_Index appeared to indicate more accurately the transition from the unconscious to conscious state.

It may not be easy to answer why BIS should fail to detect inadequate depth of anesthesia in this patient. Is it because of changes in neurotransmitter levels in the brain? Is it related to the peripheral vascular disease that might have interfered with cerebral blood flow? Is there an artifactual electromyographic interference produced by vibrations of the sternal saw? Artifacts induced by pacemaker ⁽³⁰⁾ and warming blanket ⁽³¹⁾ in the BIS (BIS increasing) have been reported. Could it be merely the electrical interference of the sternal saw (if an electrical saw was used)? Or is it a result of the interaction between nitrous oxide and sevoflurane on BIS? The interaction between nitrous oxide and other anesthetics on BIS has not been well studied. Nitrous oxide alone does not alter BIS ⁽³²⁾, but BIS values were larger when isoflurane was used in combination with nitrous oxide, as compared with when isoflurane was used alone, without nitrous oxide ⁽³³⁾. Even if we accept the failure of BIS to detect the inadequate depth of anesthesia, the problem is not solved; what is more worrying is that the anesthetic (consisting essentially of nitrous oxide and volatile anesthetic at a total concentration of more than 1 minimum alveolar concentration that had been maintained for at least 30 min before recall occurred) was not sufficient to anesthetize the patient adequately. Some patients may be more resistant to the effects of anesthetics than others. Young age, tobacco smoking, and long-term use of certain drugs (alcohol, opiates, or amphetamines) may increase the anesthetic dose required to produce unconsciousness ⁽¹⁴⁾. Can a young age and smoking (as other factors were eliminated) lead to an increased anesthetic requirement of this patient leading to awareness? The explanation is unlikely to be straightforward.

Use of intrathecal morphine in as small a dose as 5 μg/kg along with total elimination of preoperative and intraoperative IV opioids and benzodiazepines (as done in the present case), is debatable, with many of us inclined to use at least a little dose of these drugs. The theory put forth by Mychaskiw et al. ⁽²¹⁾ that cerebral edema resulting from CPB may decrease the postoperative analgesic requirement needs to be investigated further, and it is perhaps too early to draw any conclusions. These changing trends in our practice reflect the efforts to realize the combined benefits of early extubation of the trachea and satisfactory pain control. In any case, we have to accept (albeit reluctantly) that the issues regarding level of consciousness that occur during general anesthesia are complex and poorly understood and that there are no reliable means (having zero percent failure) to determine the state of consciousness in an anesthetized patient. It also means that intraoperative awareness during cardiac anesthesia may not be totally abolished and the cardiac anesthesiologist must accept that awareness is a distinct possibility in a handful of patients even after eliminating cases caused by failure of anesthesia equipment, the anesthetist’s insufficient knowledge, and lack of vigilance. This is because large doses of anesthetics cannot be administered in patients with poor cardiac reserve to avoid greater morbidity and mortality from deep levels of anesthesia. Some cardiac anesthesiologists have even gone to the extent of saying that neuromuscular blockers should be totally avoided during cardiac surgery so that movement response can warn the anesthesiologist of the awareness ⁽³⁴⁾.

Finally, like any other clinician, the cardiac anesthesiologist should be concerned about offering the patient care of the highest order. If you ask an anesthesiologist “when would you like to awaken after cardiac surgery?” the usual answer is “don’t worry about when I wake up but give me enough medications to ensure that I am not awake during the surgery.” It is therefore imperative to consider all instances of awareness with explicit recall as “inadequate anesthesia” and it is essential that our anesthetic practice safeguards the patient against such apparently escapable suffering. Many arguments supporting the use of depth of anesthesia monitoring are based on cost savings, by reducing either the level of anesthesia or length of stay in the recovery room. No doubt these are welcome and important aspects of our practice, but if by changing practice there is even a slight increase in the possibility of awareness, the purpose will be defeated. The primary aim should therefore be to improve patient care, and if other benefits such as cost savings are achieved in doing so, they should be welcome.

With this perspective, it seems that there is a need to redefine the role of BIS monitoring as well as laying threshold values for BIS at various stages of cardiac anesthesia, such as incision, intubation, and sternotomy. According to a report of 617 patients, incidence of awareness during fast-track cardiac anesthesia has been 0.3% without the use of monitors of depth of anesthesia ⁽¹⁷⁾. To prove that the use of monitors of depth of anesthesia (BIS or AEP_Index) can reduce the incidence of awareness, a randomized controlled study of a large magnitude is necessary; 50,000 patients would be needed to show a significant reduction in incidence from 0.2% to 0.1%⁽³⁾. Such a trial is not impossible and could be completed in 1 yr if 50 cardiac centers doing 1000 cardiac operations per year participate. The differences in the anesthetic techniques should not be a matter of concern, as the ideal monitor of depth of anesthesia is supposed to provide a single yardstick for measuring the performance of all anesthetics. Should we look for the reduction in the incidence of awareness that is statistically significant? Perhaps not, because the incidence of awareness should be reduced to as low a level as possible and any decrease should be considered clinically important because in the case of awareness there is always the risk of development of posttraumatic neurosis ⁽⁶⁾. What could be the acceptable financial repercussions of this philosophy? This can only be determined if we are able to define the acceptable price for patient comfort. Future work using BIS with various anesthetics and their combinations is necessary and we hope that a combined effort by a group of anesthesiologists, psychologists, and others will resolve some of the mysteries surrounding the subject.