Editors Note: Potential Conflict of Interest: Dr. Mathews has received speaking honoraria and research support from Aspect Medical Systems within the past five years.

s anesthesiologists we spend our days trying to avoid myriad adverse outcomes for our patients. One particular adverse outcome, postoperative recall of intraoperative consciousness — or, more colloquially, anesthesia awareness (AA) — is different and more troubling than most others. While other adverse outcomes may force a patient to adapt to a decreased level of physical functioning, AA, especially when it leads to post-traumatic stress disorder (PTSD), may actually change the patient’s psychological and emotional functioning. Patients can be significantly altered: they may have mood swings, panic attacks and personality changes, which usually lead to withdrawal and isolation, all from the experience of consciousness during surgery. Some patients benefit from the care of mental health professionals; others are irreversibly changed.

The following suggestions should not be considered a comprehensive review of the topic, which is available in the literature,¹ nor a thorough discussion of the preoperative, intraoperative and postoperative issues involved, which may be found in a report of the ASA Task Force on Intraoperative Awareness at www.ASAhq.org/publicationsAndServices/AwareAdvisoryFinalOct05.pdf.² Rather, it should be considered a series of suggestions from a practitioner who has carefully considered the pertinent scientific information and has made a commitment to try to eliminate AA in his practice.

Premedication: For AA to occur, a patient must both experience intraoperative consciousness and also maintain memory of the intraoperative consciousness. There are data to suggest that AA is only “the tip of the iceberg” in that the incidence of intraoperative consciousness is significantly greater than that of AA. For example, Kersens et al. demonstrated that 37 of 56 patients deeply sedated with propofol had unequivocal responses to verbal command; only nine, however, had postoperative recall of those commands.³ Why only a percentage of intraoperative consciousness is subsequently recalled is not clear; it may be a function of the duration of consciousness and the emotional context (e.g., pain, fear, anxiety).

Benzodiazepines have amnesic properties — they prevent anterograde memory formation. The old adage that “an ounce of prevention is worth a pound of cure” is particularly pertinent when considering benzodiazepines. In a prospective study, preoperative administration of midazolam 30 to 45 micrograms per kilogram prevented AA compared with control patients.⁴ Added benefits of preinduction midazolam administration include decreased propofol requirements and increased satisfaction with anesthetic induction.^5,6 Most studies of doses in this range find no significant prolongation of recovery milestones.⁷ While preinduction administration has efficacy, there is no information about what plasma levels need to be maintained during longer operations to continue to provide effective prevention of memory formation during intraoperative consciousness. The author administers midazolam 40 to 50 micrograms per kilogram prior to induction and administers 25 micrograms per kilogram each hour for longer procedures.

Induction and intubation: Data from the ASA Closed Claims Project database⁸ and other collections of AA cases⁹ reveal that the time of anesthesia induction is a period of risk. Such risks include inadequate hypnotic agent administration, mislabeled syringes, administration of muscle relaxants prior to hypnotic agent, lack of one-way valves in the I.V. set allowing hypnotic agents to flow upstream, and difficult intubations. In fact, three of four patients in two studies who experienced AA while being monitored with brain activity monitors experienced AA during induction and intubation.^10,11

It is easy to understand how the environment of a difficult intubation can lead to AA. Caregivers are focused on maintaining oxygenation and securing the airway and attention to the hypnotic state of the patient takes lesser priority. One effective strategy is to assign a member of the operating room team the task of watching the clock and readministering half the induction dose of propofol every three to three and one-half minutes. Pharmacokinetic modeling demonstrates that with this strategy, the effect-site concentration of propofol is maintained near the level of the initial induction dose.

Maintenance of Anesthesia: Empty vaporizers are a reoccurring cause of AA. Desflurane is a particularly attractive agent as its vaporizer is alarmed. While the study has not been performed, it is very likely that the use of desflurane, compared with other agents, results in less intraoperative consciousness secondary to empty vaporizers. With most monitoring systems, it is possible to graphically display the inspired and end-tidal concentrations of a volatile agent, and further, to set an alarm for low end-tidal concentration. These actions should better allow the caregiver to detect an empty vaporizer and augment vigilance to this issue.

Failure to deliver appropriate intravenous agents also can lead to AA. One strategy is to place the bags of intravenous fluid within the same field of vision as the monitors so that it is more likely that an empty bag will be detected in a timely manner. It is controversial whether total intravenous anesthesia (TIVA) with propofol is associated with an increased risk of AA compared with volatile anesthetics. Empty syringes, broken or misaligned stopcocks and I.V. disconnections can lead to AA. One way to limit AA with TIVA is to choose to utilize it only if there is continuous intraoperative access to the entire pathway from the propofol reservoir to the I.V. insertion site.

Muscle Relaxants: Muscle relaxants play a significant role in AA. In the ASA Closed Claims Project database, the relative risk of AA is increased by 2.28-fold with their utilization.⁸

The implication of this association needs to be carefully considered. When used appropriately, these agents contribute to the overall patient conditions that allow our surgical colleagues to effectively function. When used inappropriately, they are used simply to prevent patient movement and can mask an otherwise inadequate anesthetic state. There is a seeming paradox here: we know from animal studies that most patient movement is probably due to spinal reflexes and does not necessarily reflect consciousness. Information from patient anecdote shows, however, that when conscious, patients attempt to signal to their caregiver through movement. When completely paralyzed, they are unable to so communicate. Indeed a repeated and tragic episode reported from patient experience is the attempt to signal consciousness by moving, only to be given additional muscle relaxants. It is impossible for a caregiver to detect, in real time, whether patient movement is due to spinal reflexes or due to purposeful patient movement; either condition, however, represents an inadequate anesthetic state and should never be treated with muscle relaxants alone. In addition to administering additional anesthetic agents, the compassionate caregiver will consider that movement may be due to intraoperative consciousness and will speak with the patient and let him/her know that movement was observed and that additional anesthetic agents are being administered.

Each practitioner needs to carefully consider his/her administration of muscle relaxants. What is the goal of the use of these agents? It is extremely rare that a patient needs to be completely paralyzed for a surgeon to function. Proper use of these agents mandates use of a train-of-four neuromuscular twitch monitor. Maintaining at least one twitch in the train-of-four allows the possibility of patient communication of consciousness while providing the surgeon with excellent relaxation. If a surgeon requests or demands further relaxation, a discussion should ensue that further administration of these agents will increase the risk of AA. Often the surgeon will decide that conditions are acceptable after all. For a particularly recalcitrant surgeon, administration of 20 or 30 mg of propofol often improves surgical conditions.

While overexuberant muscle relaxant administration is a significant cause of AA, it can occur without muscle relaxants. In the prospective study of Sandin et al., the overall incidence of awareness was 0.15 percent; 0.18 percent when muscle relaxants were utilized and 0.10 percent when they were not.¹² The use of muscle relaxants was associated with negative psychological outcome; however, in the nonparalyzed patients with awareness, none had found the intra-operative experience traumatic or distressing nor did they have immediate or delayed PTSD reactions. In contrast, 11 of the 14 paralyzed patients reported intraoperative trauma and anxiety. Persistent postoperative psychological symptoms were associated with those who, during the operation, did not understand why they were wakeful and why they were paralyzed. Often the psychological trauma comes from the conscious patient’s intraoperative assumption that the paralysis is due to a catastrophic event such as the surgeon cutting the spinal cord. It is frequently the intraoperative misconception that the state of paralysis is irreversible, which causes acute psychological trauma (Michael Wang, Ph.D., F.B.Ps.S., personal communication, December 20, 2006).

Brain Function Monitoring (BFM): The need for brain function monitoring is currently very controversial, particularly the issue of the utility for preventing AA. Two studies, one prospective in patients at high risk¹⁰ and one retrospective in patients at average risk,¹¹ demonstrated that use of the bispectral index monitor (BIS, Aspect Medical System, Newton, Massachusetts) significantly decreased the incidence of AA by about 80 percent. The ASA Task Force on Intraoperative Awareness considered this information and the state of opinion of both consultants and randomly selected ASA members in issuing the following advisory statement about the utility of BFM and AA: “The decision to use a brain function monitor should be made on a case-by-case basis by the individual practitioner for selected patients (e.g., light anesthesia).”² While this statement may accurately reflect the state of knowledge and opinion, it is possible that a practitioner could interpret this statement as meaning that since they would never choose to use this type of monitoring for any patient, they can entirely ignore the technology and the debate. Hoping to avoid this issue altogether will not prove to be an effective strategy.

This is an area in which change is expected. Indeed ASA Past President Eugene P. Sinclair, M.D., stated:

“This is a dynamic and relatively young area of science in which knowledge and understanding are rapidly and continually expanding…you will see an ever-increasing volume of literature on this subject. ASA policy has been to revisit practice parameters every five years. The pace of new publications on this subject suggests that this advisory might have to be revisited monthly to remain current.”¹³

Survey data were collected by the task force in late 2004 and early 2005. At that time, a majority of both consultants and ASA members agreed that “brain function monitors are valuable and should be used to decrease the risk of intraoperative awareness … for patients with conditions that may place them at risk for intraoperative awareness … [and] for patients requiring smaller doses of general anesthetics.” Other high-risk situations received a majority of agreement by consultants (cesarean section, trauma, TIVA) or by ASA members (cardiac surgery). It is possible that a survey conducted today would lead to a stronger statement by the task force, particularly in the high-risk patient.

In addition the practitioner should consider the implications of choosing not to become familiar with BFM. Consider what one would do with a patient with previous awareness who would like to have monitoring utilized or if the president of the hospital board of trustees asks for its use on a family member. Are monitors available at the practitioner’s facility? Are there enough available so that several patients can be monitored at the same time? Does the practitioner know how to interpret the information from the monitor? It makes as much sense to use BFM on a high-risk patient for AA without familiarity as is does to use a fiberoptic bronchoscope for the first time on a difficult airway.

It behooves all practitioners to acquire a working familiarity with this technology. While the BIS monitor is the only device with Food and Drug Administration approval to be marketed with the indication of preventing AA, it is certainly logical that other commercially available monitors will become so as well. Acquire a monitoring system, learn the basics of its function and, at a minimum, monitor a series of patients using your routine anesthetic so you can learn what to expect during your usual care. You will then be prepared to utilize BFM should you choose to do so.

The practice of the author is to use BFM for all patients receiving general anesthesia. This is from personal experience in which monitoring may have prevented awareness¹⁴ and also from a determination that other monitoring modalities (e.g., somatic signs, autonomic nervous system, lack of patient movement) are insufficient and have allowed an incidence of AA of 0.1 to 0.2 percent, or as Peter S. Sebel, M.B., Ph.D., calculates, 100 Americans per anesthesia work day.¹⁵

References:
1. Ghoneim MM. Awareness during anesthesia. Anesthesiology. 2000; 92:597-602.
2. American Society of Anesthesiologists Task Force on Intraoperative Awareness. Practice advisory for intraoperative awareness and brain function monitoring. Anesthesiology. 2006; 104:847-64.
3. Kerssens C, Klein J, Bonke B. Awareness: Monitoring versus remembering what happened. Anesthesiology. 2003; 99:570-5.
4. Miller DR, Blew PG, Martineau RJ, Hull KA. Midazolam and awareness with recall during total intravenous anaesthesia. Can J Anaesth. 1996; 43:946-53.
5. Tighe KE, Warner JA. The effect of co-induction with midazolam upon recovery from propofol infusion anaesthesia. Anaesthesia. 1997; 52:1000-4.
6. Ong LB, Plummer JL, Waldow WC, Owen H: Timing of midazolam and propofol administration for co-induction of anaesthesia. Anaesth Intensive Care. 2000; 28:527-31.
7. Smith AF, Pittaway AJ. Premedication for anxiety in adult day surgery (Cochrane Review). The Cochrane Library, Issue 1,2003. Oxford: Update Software.
8. Domino KB, Posner KL, Caplan RA, Cheney FW. Awareness during anesthesia: a closed claims analysis. Anesthesiology. 1999; 90:1053-61.
9. Bergman IJ, Kluger MT, Short TG. Awareness during general anaesthesia: a review of 81 cases from the Anaesthetic Incident Monitoring Study. Anaesthesia. 2002; 57:549-56.
10. Myles PS, Leslie K, McNeil J, Forbes A, Chan MT. Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial. Lancet. 2004; 363:1757-63.
11. Ekman A, Lindholm ML, Lennmarken C, Sandin R. Reduction in the incidence of awareness using BIS monitoring. Acta Anaesthesiol Scand. 2004; 48:20-6.
12. Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet. 2000 ; 355:707-11.
13. Sinclair EP. Awareness-a personal viewpoint. President’s Update Vol. 8 No.1, July 12,2005.
14. Mathews DM, Rahman SS, Cirullo PM, Malik RJ. Increases in bispectral index lead to interventions that prevent possible intraoperative awareness. Br J Anaesth. 2005; 95:193-6.
15. Sebel PS, Bowdle TA, Ghoneim MM, Rampil IJ, Padilla RE, Gan TJ, Domino K. The Incidence of Awareness During Anesthesia: A Multicenter United States Study. Anesth Analg. 2004; 99:833-9.

Donald M. Mathews, M.D., is Program Director of the anesthesiology residency and Associate Chair for Academic Affairs at St. Vincent Catholic Medical Centers-St. Vincent's Manhattan, and Associate Professor of Clinical Anesthesiology, New York Medical College, Valhalla, New York.