Practice Advisory for Intraoperative Awareness and Brain Function Monitoring

Abstract

PRACTICE advisories are systematically developed reports that are intended to assist decision making in areas of patient care. Advisories provide a synthesis and analysis of expert opinion, clinical feasibility data, open forum commentary, and consensus surveys. Advisories are not intended as standards, guidelines, or absolute requirements. They may be adopted, modified, or rejected according to clinical needs and constraints.The use of practice advisories cannot guarantee any specific outcome. Practice advisories summarize the state of the literature and report opinions derived from a synthesis of task force members, expert consultants, open forums, and public commentary. Practice advisories are not supported by scientific literature to the same degree as are standards or guidelines because sufficient numbers of adequately controlled studies are lacking. Practice advisories are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.Intraoperative awareness under general anesthesia is a rare occurrence, with a reported incidence of 0.1–0.2%.1–4Significant psychological sequelae (e.g. , post–traumatic stress disorder) may occur after an episode of intraoperative awareness, and affected patients may remain severely disabled for extended periods of time.5However, in some circumstances, intraoperative awareness may be unavoidable to achieve other critically important anesthetic goals.The following terms or concepts discussed in this Advisory include: consciousness, general anesthesia, depth of anesthesia or depth of hypnosis, recall, amnesia, intraoperative awareness, and brain function monitors. Consistent definitions for these terms are not available in the literature. For purposes of this Advisory, these terms are operationally defined or identified as follows:Consciousness is a state in which a patient is able to process information from his or her surroundings. Consciousness is assessed by observing a patient’s purposeful responses to various stimuli. Identifiers of purposeful responses include organized movements following voice commands or noxious/painful stimuli.*For example, opening of the eyes is one of several possible identifiers or markers of consciousness. Purposeful responses may be absent when paralysis is present as a consequence of neurologic disease or the administration of a neuromuscular blocking drug.General anesthesia is defined as a drug-induced loss of consciousness during which patients are not arousable, even by painful stimulation.†The ability to maintain ventilatory function independently is often impaired. Patients often require assistance in maintaining a patent airway, and positive-pressure ventilation may be required because of depressed spontaneous ventilation or drug-induced depression of neuromuscular function. Cardiovascular function may be impaired.Depth of anesthesia or depth of hypnosis refers to a continuum of progressive central nervous system depression and decreased responsiveness to stimulation.For the purpose of this Advisory, recall is the patient’s ability to retrieve stored memories. Recall is assessed by a patient’s report of previous events, in particular, events that occurred during general anesthesia. Explicit memory is assessed by the patient’s ability to recall specific events that took place during general anesthesia. Implicit memory is assessed by changes in performance or behavior without the ability to recall specific events that took place during general anesthesia that led to those changes.6A report of recall may be spontaneous or it may only be elicited in a structured interview or questionnaire. This Advisory does not address implicit memory.Amnesia is the absence of recall. Many anesthetic drugs produce amnesia at concentrations well below those necessary for suppression of consciousness. Anterograde amnesia is intended when a drug with amnestic properties is administered before induction of anesthesia. Retrograde amnesia is intended when a drug such as a benzodiazepine is administered after an event that may have caused or been associated with intraoperative consciousness in the hope that it will suppress memory formation and “rescue” from recall.Intraoperative awareness occurs when a patient becomes conscious during a procedure performed under general anesthesia and subsequently has recall of these events. For the purpose of this Advisory, recall is limited to explicit memory and does not include the time before general anesthesia is fully induced or the time of emergence from general anesthesia, when arousal and return of consciousness are intended. Dreaming is not considered intraoperative awareness.Brain function monitors are devices that record or process brain electrical activity and convert these signals mathematically into a continuous measure typically scaled from 0 to 100. In addition to monitoring spontaneous cortical electrical activity (electroencephalogram [EEG]), these devices may also record and process evoked cortical and subcortical activity (auditory evoked potentials [AEPs]) as well as electromyographic (EMG) activity from scalp muscles. For the purpose of this Advisory, only monitors purported to measure depth of anesthesia or hypnosis will be considered. Other, non-EEG, non-AEP, non-EMG devices are also available but are not addressed by this Advisory.Intraoperative awareness under general anesthesia is an important clinical problem that clearly is within the foundation of training and continuing medical education in anesthesiology. The purposes of this Advisory are to identify risk factors that may be associated with intraoperative awareness, provide decision tools that may enable the clinician to reduce the frequency of unintended intraoperative awareness, stimulate the pursuit and evaluation of strategies that may prevent or reduce the frequency of intraoperative awareness, and provide guidance for the intraoperative use of brain function monitors as they relate to intraoperative awareness.This Advisory focuses on the perioperative treatment of patients who are undergoing a procedure during which general anesthesia is administered. This Advisory is not intended for the perioperative management of minimal, moderate, or deep sedation in the operating room or intensive care unit; regional or local anesthesia without general anesthesia; monitored anesthesia care; tracheal intubation of patients or those undergoing resuscitation in emergency trauma after the administration of a neuromuscular block, or intentional intraoperative wake-up testing (e.g. , for the purposes of assessing intraoperative neurologic function). In addition, this Advisory is not intended to address the perioperative treatment of pediatric patients.This Advisory is intended for use by anesthesiologists, other physicians who supervise the administration of general anesthesia, and all other individuals who administer general anesthesia. The Advisory may also serve as a resource for other physicians and healthcare professionals who are involved in the perioperative management of patients receiving general anesthesia.The American Society of Anesthesiologists (ASA) appointed this Task Force of 10 members to (1) review and assess the currently available scientific literature on intraoperative awareness, (2) obtain expert consensus and public opinion, and (3) develop a practice advisory. The Task Force is comprised of anesthesiologists from various geographic areas of the United States, an anesthesiologist from The Netherlands, and two methodologists from the ASA Committee on Practice Parameters.The ASA appointed the 10 members to the Task Force because of their knowledge or expertise in the medical specialty of anesthesiology, and the development of practice parameters. The members include but are not limited to anesthesiologists with specialized knowledge or expertise in the area of neuroanesthesiology. Two of the 10 members disclosed receipt of funds from or a financial interest in a company developing or manufacturing brain function monitors; these companies have a direct financial interest in the expanded use of such monitors. Task Force members may also have received funds from or have a financial interest in other companies, such as developers or manufacturers of anesthetics, that may be indirectly affected by the expanded use of brain function monitors. The Task Force did not request for its members to disclose such interests because they were deemed too remote and speculative to present conflicts of interest.The Task Force, in turn, sought input from consultants, many of whom who had particularized knowledge, expertise, and/or interest in intraoperative awareness and brain function monitors. Such knowledge or expertise is based in part in some cases on research or investigational activities funded by a company developing or manufacturing brain function monitors. Fifty-four percent of the consultants disclosed receipt of funds from or a financial interest in a company developing or manufacturing brain function monitors. Consultants also may have received funds from or have a financial interest in other companies that may be indirectly affected by the use of brain function monitors. The Task Force did not request for its consultants to disclose such interests because they were deemed too remote and speculative to present conflicts of interest.The Task Force used a six-step process. First, the members reached consensus on the criteria for evidence of effective perioperative interventions for the prevention of intraoperative awareness. Second, they evaluated original articles published in peer-reviewed journals relevant to this issue. Third, consultants who had expertise or interest in intraoperative awareness and who practiced or worked in diverse settings (e.g. , scientists and/or physicians in academic and private practice) were asked to participate in opinion surveys on the effectiveness of various perioperative management strategies and to review and comment on a draft of the Advisory developed by the Task Force. Fourth, additional opinions were solicited from a random sample of active members of the ASA. Fifth, the Task Force held open forums at three national and international anesthesia meetings to solicit input on the key concepts of this Advisory. Sixth, all available information was used to build consensus within the Task Force on the Advisory.The draft document was made available for review on the ASA Web site, and commentary was invited via e-mail announcement to all ASA members. All submitted comments were considered by the Task Force in preparing the final draft.Practice advisories are developed by a protocol similar to that of an ASA evidence-based practice guideline, including a systematic search and evaluation of the literature. However, practice advisories lack the support of a sufficient number of adequately controlled studies to permit aggregate analyses of data with rigorous statistical techniques such as meta-analysis. Nonetheless, literature-based evidence from case reports and other descriptive studies are considered during the development of the Advisory. This literature often permits the identification of recurring patterns of clinical practice.As with a practice guideline, formal survey information is collected from consultants and members of the ASA. The following terms describe survey responses for any specified issue. Responses are solicited on a five-point scale, ranging from 1 (strongly disagree) to 5 (strongly agree), with a score of 3 being equivocal. Survey responses are summarized based on median values as follows:Strongly Agree: Median score of 5 (at least 50% of the responses are 5)Agree: Median score of 4 (at least 50% of the responses are 4 or 4 and 5)Equivocal: Median score of 3 (at least 50% of the responses are 3, or no other response category or combination of similar categories contain at least 50% of the responses)Disagree: Median score of 2 (at least 50% of responses are 2 or 1 and 2)Strongly Disagree: Median score of 1 (at least 50% of responses are 1)Additional information is obtained from open forum presentations and other invited and public sources. The advisory statements contained in this document represent a distillation of the current spectrum of clinical opinion and literature-based findings (appendix 1).A preoperative evaluation includes (1) obtaining a focused history (i.e. , medical records, laboratory reports, patient or patient-and-family interview), (2) conducting a physical examination, (3) identifying patients at risk for intraoperative awareness (e.g. , planned anesthetics, type of surgery), and (4) informing selected patients of the possibility of intraoperative awareness.Descriptive studies and case reports suggest that certain patient characteristics may be associated with intraoperative awareness, including age, sex, ASA physical status, and drug resistance or tolerance.4,7–11Descriptive studies and case reports suggest that certain procedures (e.g. , cesarean delivery, cardiac surgery, trauma surgery)4,8,12–29as well as anesthetic techniques (e.g. , rapid-sequence induction, reduced anesthetic doses with or without the presence of paralysis)2,3,9,13,16,21,23,30–33may be associated with an increased risk of intraoperative awareness. No studies were found that examined the clinical impact of informing the patient before surgery of the possibility of intraoperative awareness.The consultants and ASA members agree that a preoperative evaluation may be helpful in identifying patients at risk for intraoperative awareness (appendix 2). In addition, they agree that a focused preoperative evaluation to identify patients at risk of intraoperative awareness should include review of a patient’s medical record, a thorough physical examination, and a patient or patient-and-family interview. They agree that patient characteristics that may place a patient at risk for intraoperative awareness include substance use or abuse, limited hemodynamic reserve, and ASA physical status of IV or V. The consultants strongly agree and the ASA members agree that a history of intraoperative awareness may place a patient at risk. The consultants disagree and the ASA members are equivocal regarding whether all patients should be informed of the possibility of intraoperative awareness. The consultants and ASA members agree that only patients considered to be at elevated risk of intraoperative awareness should be informed of the possibility of intraoperative awareness. Finally, the consultants and the ASA members disagree that informing the patient preoperatively of the risk of intraoperative awareness increases the actual risk of intraoperative awareness.The Task Force believes that some components of the preoperative evaluation may be useful in identifying a patient at increased risk for awareness. An evaluation should include, if possible, a review of a patient’s medical records for previous occurrences of awareness or other potential risk factors, a patient interview to assess level of anxiety or previous experiences with anesthesia, and a physical examination. Potential risk factors to consider for patients undergoing general anesthesia include substance use or abuse (e.g. , opioids, benzodiazepines, cocaine), a history of awareness, a history of difficult intubation or anticipated difficult intubation, chronic pain patients using high doses of opioids, cardiac surgery, cesarean delivery, trauma and emergency surgery, reduced anesthetic doses in the presence of paralysis, planned use of muscle relaxants during the maintenance phase of general anesthesia, total intravenous anesthesia, the planned use of nitrous oxide-opioid anesthesia, ASA physical status of IV or V, and limited hemodynamic reserve. The consensus of the Task Force is that patients whom the individual clinician considers to be at substantially increased risk of intraoperative awareness should be informed of the possibility of intraoperative awareness when circumstances permit.Issues regarding the preinduction phase of anesthesia related to the prevention of intraoperative awareness include checking the functioning of anesthesia delivery systems, and the prophylactic administration of benzodiazepines.Although checking the functioning of anesthesia delivery systems is standard practice, some cases of intraoperative awareness have resulted from too-low concentrations of inspired volatile anesthetics or drug errors, including drug delivery errors.8,34–39One double-blind randomized clinical trial evaluated the efficacy of the prophylactic administration of midazolam as an anesthetic adjuvant during ambulatory procedures under total intravenous anesthesia and reported a lower frequency of intraoperative awareness in the midazolam groups compared with the placebo group.40Two randomized clinical trials examined anterograde amnesia by providing pictures as stimuli after administration of midazolam but before induction of general anesthesia. Although these studies reported reduced recall in patients administered midazolam, the presence of consciousness during general anesthesia and subsequent intraoperative awareness was not examined.41,42The consultants and ASA members strongly agree that the functioning of anesthesia delivery systems (e.g. , vaporizers, infusion pumps, fresh gas flow, intravenous lines) should be checked to reduce the risk of intraoperative awareness. The consultants disagree and the ASA members are equivocal that a benzodiazepine or scopolamine should be used as a component of the anesthetic to reduce the risk of intraoperative awareness for all patients. The consultants agree that a benzodiazepine or scopolamine should be used for patients requiring smaller dosages of anesthetics, patients undergoing cardiac surgery, and patients undergoing trauma surgery. They are equivocal regarding patients undergoing cesarean delivery, emergency surgery, and total intravenous anesthesia. The ASA members agree that a benzodiazepine or scopolamine should be used for patients requiring smaller dosages of anesthetics and patients undergoing cardiac surgery, emergency surgery, trauma surgery, and total intravenous anesthesia. They are equivocal regarding patients undergoing cesarean delivery.Because intraoperative awareness may be caused by equipment malfunction or misuse, the Task Force believes that there should be adherence to a checklist protocol for anesthesia machines and equipment to assure that the desired anesthetic drugs and doses will be delivered. These procedures should be extended to include verification of the proper functioning of intravenous access, infusion pumps, and their connections. The Task Force consensus is that the decision to administer a benzodiazepine prophylactically should be made on a case-by-case basis for selected patients (e.g. , patients requiring smaller dosages of anesthetics). The Task Force cautions that delayed emergence may accompany the use of benzodiazepines.Intraoperative awareness cannot be measured during the intraoperative phase of general anesthesia, because the recall component of awareness can only be determined postoperatively by obtaining information directly from the patient. Therefore, the primary issue regarding intraoperative monitoring addressed by this Advisory is whether the use of clinical techniques, conventional monitoring systems, or brain function monitors reduces the occurrence of intraoperative awareness.The majority of literature obtained during the search and review process did not directly address whether these techniques, systems, or monitors reduce the frequency of intraoperative awareness. However, many studies were found that report intraoperative measures or index values from monitoring activities. This literature, although not directly assessing the impact of an intervention on awareness, often reported patterns or values that occurred at identifiable times during the perioperative period with the intention of describing or predicting variations in the depth of anesthesia. Commonly reported findings from this literature are summarized below.The literature for each intervention is presented in the following order: (1) randomized clinical trials, (2) nonrandomized comparative studies (e.g. , quasi-experimental, prospective cohort studies), (3) correlational studies (e.g. , correlations of index values with end-tidal concentrations of hypnotic drugs or with movement in response to noxious stimuli), (4) descriptive reports of monitored index values at particular times during a procedure, and (5) case reports of unusual or unintended benefits or harms occurring during a monitoring activity. Correlational studies often report a measure of association between two continuous variables (e.g. , the correlation between index values and anesthetic drug concentrations). Other correlational measures include a prediction probability (Pk) value that provides a measure of how well a monitor or technique can differentiate between two different clinical states (e.g. , response vs. no response to verbal command).43A Pk value of 1.0 indicates perfect association between an index value and a clinical state, whereas a Pk value of 0.50 indicates a prediction probability equal to chance.Among the clinical techniques used to assess intraoperative consciousness are checking for movement, response to commands, opened eyes, eyelash reflex, pupillary responses or diameters, perspiration, and tearing. Conventional monitoring systems include ASA standard monitoring‡as well as the end-tidal anesthetic analyzer.No clinical trials or other comparative studies were found that examine the effect of clinical techniques or conventional monitoring on the incidence of intraoperative awareness. Correlational studies reported Pk values ranging from 0.74 to 0.76 for the association between reflex or purposeful movement and indicators for depth of anesthesia.44One study reported a significant association between response to command and memory when continuous infusions of propofol were used as the induction anesthetic.45Pk values for mean arterial pressure (MAP) ranged from 0.68 to 0.94 for distinguishing a responsive state from an unresponsive state and from 0.81 to 0.89 for distinguishing an anesthetized state from emergence after anesthesia (i.e. , first response). Pk values for heart rate (HR) ranged from 0.50 to 0.82 for distinguishing a responsive state from an unresponsive state and from 0.54 to 0.67 for emergence.46–48Wide ranges of mean MAP and HR values were reported during various intraoperative times. Studies reported ranges of mean MAP values as follows: before induction or baseline, 90–103 mmHg; at induction, 58.4–88 mmHg; during surgery, 78–102 mmHg; at emergence or end of surgery, 58.7–97 mmHg; and during postoperative recovery, 86–104 mmHg. Mean HR ranges were reported as follows: before induction or baseline, 61–82 beats/min; at induction, 55–67 beats/min; during surgery, 74–82 beats/min; at emergence or end of surgery, 59–92 beats/min; and during postoperative recovery, 82–89 beats/min.49–56Awareness has been reported to occur in the absence of tachycardia or hypertension.8,23,24The consultants and ASA members agree that clinical techniques (e.g. , checking for purposeful or reflex movement) are valuable and should be used to assess intraoperative consciousness. In addition, the consultants and ASA members agree that conventional monitoring systems (e.g. , electrocardiogram, blood pressure, HR, end-tidal anesthetic analyzer, capnography) are valuable and should be used to help assess intraoperative consciousness.Most of the devices designed to monitor brain electrical activity for the purpose of assessing anesthetic effect record electroencephalographic activity from electrodes placed on the forehead. Systems can be subdivided into those that process spontaneous electroencephalographic and electromyographic activity and those that acquire evoked responses to auditory stimuli (AEPs). After amplification and conversion of the analog electroencephalographic signal to the digital domain, various signal processing algorithms are applied to the frequency, amplitude, latency, and/or phase relationship data derived from the raw EEG or AEP to generate a single number, often referred to as an “index,” typically scaled between 0 and 100. This index represents the progression of clinical states of consciousness (“awake,”“sedated,”“light anesthesia,”“deep anesthesia”), with a value of 100 being associated with the awake state and values of 0 occurring with an isoelectric EEG (or absent middle latency AEP). These processing algorithms may either be published and in the public domain or proprietary. Detailed descriptions of the various approaches to electroencephalographic signal processing, including bispectral analysis, may be found elsewhere.57Artifact recognition algorithms intended to avoid contaminated and therefore spurious “index” values are an important component of the software in most monitors.Although electromyographic activity from scalp muscles can be considered an artifact from the viewpoint of pure electroencephalographic analysis, it may be an important source of clinically relevant information. Sudden appearance of frontal (forehead) electromyographic activity suggests somatic response to noxious stimulation resulting from inadequate analgesia and may give warning of impending arousal. For this reason, some monitors separately provide information on the level of electromyographic activity.Bispectral Index. The Bispectral Index (BIS) is a proprietary algorithm (Aspect Medical Systems, Natick, MA) that converts a single channel of frontal electroencephalograph into an index of hypnotic level (BIS). BIS is available either as a separate device (BIS® monitor; Aspect Medical Systems) or incorporated, under license from Aspect Medical Systems, in “BIS modules” made by various anesthesia equipment manufacturers. To compute the BIS, several variables derived from the electroencephalographic time domain (burst-suppression analysis), frequency domain (power spectrum, bispectrum: interfrequency phase relationships) are combined into a single index of hypnotic level. BIS values are scaled from 0 to 100, with specific ranges (e.g. , 40–60) reported to reflect a low probability of consciousness under general anesthesia. The weight factors for the various components in the multivariate model that generates the BIS were empirically derived from a prospectively collected database of more than 1,500 anesthetics. The BIS® model accounts for the nonlinear stages of electroencephalographic activity by allowing different parameters to dominate the resulting BIS as the electroencephalographic changes its character with increasing plasma concentrations of various anesthetics, resulting in a linear decrease in BIS. As more data have become available and as methods and algorithms to suppress artifacts have been improved, revised iterations of the algorithm and optimized hardware have been released.Several randomized controlled trials (RCTs) have compared outcomes with BIS-guided anesthetic administration versus standard clinical practice without BIS. In one RCT that enrolled 2,500 patients at high risk of intraoperative awareness, explicit recall occurred in 0.17% of patients when BIS monitors were used and in 0.91% of patients treated by routine clinical practice (P < 0.02).58A small (n = 30), single-blinded RCT (i.e. , the anesthesiologists were blinded to the recorded BIS values) compared BIS monitoring with clinical signs during cardiac surgery and reported one episode of recall in the clinical signs group compared with no episodes in the BIS-monitored group (P > 0.50).59In other RCTs, times to awakening, first response, or eye opening and consumption of anesthetic drugs were reduced with the use of BIS.8,60–68One nonrandomized comparison of the use of BIS monitoring versus a cohort of historic controls (n = 12,771) found explicit recall occurring in 0.04% of the BIS-monitored patients versus 0.18% of the historic controls (P < 0.038).69Another prospective nonrandomized cohort study (n = 19,575) designed to establish the incidence of awareness with recall during routine general anesthesia and to determine BIS values associated with intraoperative awareness events reported no statistically significant difference when BIS was used (0.18% of patients) compared with when BIS was not used (0.10% of patients).4Other nonrandomized comparative studies reported higher index values on arrival in the postanesthesia care unit, shorter recovery times, and lower anesthetic use among patients monitored with BIS compared with patients not monitored with BIS.70,71Numerous correlational studies reported Pk values for BIS ranging from 0.72 to 1.00 for awake versus loss of response after induction with propofol (with or without opioids) and from 0.79 to 0.97 for anesthetized versus first response.46–48,72–78One study reported a Pk value of 0.86 for movement from electrical stimulation.44Wide ranges of mean BIS values have been reported during various intraoperative times. Ranges of mean BIS values were as follows: before induction or baseline, 80–98; at or after induction, 37–70; during surgery, 20–58; at emergence or end of surgery, 42–96; and during postoperative recovery, 64–96.50,51,54-56,79-110Several case reports indicate that intraoperative events unrelated to titration of anesthetic agents can produce rapid changes in BIS values (e.g. , cerebral ischemia or hypoperfusion, gas embolism, unrecognized hemorrhage, inadvertent blockage of anesthesia drug delivery).111–119Other case reports suggest that routine intraoperative events (e.g. , administration of depolarizing muscle relaxants, activation of electromagnetic equipment or devices, patient warming or planned hypothermia) may interfere with BIS