Intraoperative and Anesthesia Awareness

Issues of Concern

Risk Factors

Risk factors for AAGA may be broadly separated into those related to 1) technical application of anesthetics, 2) surgical procedure or context, and 3) inherent patient characteristics. 

Risk Factors Related to Anesthetic Technique 

Among the risk factors for anesthetic techniques, NMB is simultaneously the most significant and modifiable. The vast majority of self-reported cases of AAGA in the 5th National Audit Project for Awareness (NAP5) were associated with the use of NMBs (incidence 1:8200 with NMB vs. 1:135900 without NMB); this represents a more than 16-fold increase of reported instances where NMBs were used.[4] By disrupting the neuromuscular junction, NMBs deprive the practitioner of the most reliable indicator of insufficient or “light” anesthesia: patient movement. Furthermore, the experience of paralysis is novel to the patient and deeply distressing, adding profound psychological impact to episodes of auditory, tactile, or painful perception and recall. The significance of psychological distress in the context of awareness is recognized in the Michigan Awareness Classification Instrument, where such instances are notated with a “D” modifier.[2] 

Total intravenous anesthesia (TIVA) is also associated with an increased risk of AAGA compared to volatile-based anesthetics.[4][5] Contributing factors are rooted in the inherent mode of delivery of IV anesthetics, resulting in the absence of a reliable means to monitor anesthetic concentrations and the myriad opportunities for disruption of delivery of an intravenous infusion. Such examples include human error in pump programming, disconnected or unconnected infusion tubing, and unrecognized peripheral IV (PIV) site infiltration. Mechanical failure of drug delivery is often compounded by PIV sites that are tucked, draped, or otherwise obscured from the continuous view of the practitioner. Risk mitigation with TIVA may theoretically be achieved by target-controlled infusions (TCI). However, no evidence suggests that AAGA occurs at lower rates when TCI is utilized to deliver TIVA. Moreover, TCIs are not presently approved by the FDA for use in the United States. Processed electroencephalogram (EEG) monitoring (bispectral index or BIS) may significantly detect unintended consciousness during TIVA general anesthetics. As such, its use is recommended for cases where volatile concentrations are deemed insufficient to provide reliable unconsciousness and amnestic effects.[5][6]

Problems with the technical delivery of anesthetics contribute to AAGA, though human error is more often the culprit than the failure of a mechanical or electronic device.[7] Examples include failure to turn on or refill an empty vaporizer or errors in pump programming. 

Risk Factors Related to Surgical Procedure or Context 

Risk factors for AAGA related to surgical procedure or context are easily understood when one considers the common characteristics: urgent or emergent procedures, rapid pace from induction to surgical incision, and the attendant objectives that necessitate reduction of anesthetics in 1 form or another (eg, trauma, hypovolemia, depressed cardiac function.) Each of these characteristics is independent of and, in addition to the added risk when NMBs are employed, as described above. 

Emergency surgery, particularly trauma and cesarean section, poses relatively higher risks of AAGA due primarily to the reduction of anesthetic doses that are often required in these situations.[8][9] In the setting of emergent trauma, blood loss, and subsequent hemodynamic instability often preclude the delivery of anesthetics that are sufficient to prevent awareness and recall, as potent anesthetics are commonly associated with decreases in both myocardial contractility and systemic vascular resistance. Emergent cesarean delivery necessitates a rapid pace from identification of fetal or maternal distress to surgical delivery, resulting in scenarios where adequate anesthetic concentrations may not be achieved at the time of surgical incision. Additionally, anesthetics are often intentionally held during cesarean section to lower concentrations even when the interval between induction and delivery is longer, as anesthetics easily cross the placenta and may result in both respiratory and circulatory depression in the fetus.[9][10][11] 

Common to both the emergent trauma and obstetric populations, the potential for difficult airway placement introduces further opportunities for unintended awareness. Intravenous induction agents rapidly redistribute, resulting in lower blood and brain concentrations. At the same time, alveolar delivery of inhaled anesthetics is delayed by definitive airway placement, and necessary replacement with IV agents may be delayed amidst the focus on obtaining airway control.[11]

Cardiopulmonary bypass (CPB) also increases the risk of AAGA. This increase in risk may be related to the altered pharmacodynamics of bypass physiology.[12] Historically, open-heart surgery has been recognized to foster recall—though often painless—of intraoperative events due to the widespread use of opioid-based anesthetic techniques in favor of more hemodynamically compromising volatile-based techniques that have since become more common in recent decades.[13][14]

Patient-Related Risk Factors 

Patients reporting a history of intraoperative awareness may be at higher risk for subsequent AAGA, as reported by at least 1 observational study.[15]  Whether or not further studies validate an increased risk in this setting, patients who report a prior history of awareness deserve an appropriate and focused preoperative evaluation on discerning the context and nature of the episode where possible. Importantly, any planned risk-mitigation strategies that may lower the likelihood of similar patient experiences should be shared with the patient in advance to validate concerns and assuage any attendant anxiety. 

While not definitively proven or identified, genetic resistance to anesthetics may contribute to increased requirements and risk of AAGA.[16]

Chronic substance abuse may contribute to acquired resistance to anesthetics. Long-term use of commonly abused substances, including alcohol, opioids, and benzodiazepines, may increase anesthetic requirements, increasing the risk of AAGA.[17] Acute intoxication with the same substances may result in CNS depression, lowering anesthetic requirements. These counterbalancing effects must be considered when assessing the risk for AAGA. An extensive list of medications not typically associated with abuse and dependence may also raise anesthetic requirements by inducing cytochrome P450 3A.[18] Commonly encountered examples include barbiturates, phenytoin, carbamazepine, and glucocorticoids. 

AAGA is shown to be most common at induction and emergence from general anesthesia.[19] Difficult airway placement prolongs the induction phase, complicates and often delays the delivery of inhaled volatile anesthetics, and increases the likelihood of unintended awareness. Studies indicating a higher risk of AAGA in the obese population may stem from the related incidence of difficult airway management within this cohort.[20][21]

In addition to acute hemodynamic compromise, patients presenting with chronic cardiovascular conditions such as congestive heart failure or significant valvular disease are also shown to be at higher risk for AAGA, as dose reduction strategies are commonly employed to maintain hemodynamic stability in these settings.

Monitoring Depth of Anesthesia and Prevention of AAGA 

Monitoring for prevention of AAGA rests upon 3 primary axes of data: 1) end-tidal anesthetic concentration (ETAC), 2) blockade of the neuromuscular junction with NMB, and 3) brain monitoring with raw or processed EEG. Physiologic responses to surgical stimulation, including heart rate, blood pressure, and purposeful movement, are monitored as routine components of anesthetic care. However, the reliability of physiologic parameters as an indicator of AAGA is often compromised by variability in sympathetic responses, beta- or calcium-channel blockade, or, in the case of patient movement, NMB. 

Monitoring ETAC is a basic standard of modern anesthetic delivery.[22] Any given volatile agent's minimum alveolar concentration (MAC) prevents movement with a surgical stimulus in 50% of the population.[23] The MAC-awake or the MAC required to suppress consciousness is often lower than the concentration required to prevent movement, which inherently protects against AAGA when MAC levels are achieved.[24] MAC varies significantly across ages, comorbidities, and other patient and environmental factors.[25][26][27][28] Given this variability, the coadministration of NMB with volatile anesthetics may complicate the interpretation of safe MAC levels to prevent AAGA, as patient movement is abolished. MAC is only available in inhaled volatile anesthetics and, therefore, irrelevant when TIVA is utilized. 

Monitoring the depth of NMB is critical to avoid unnecessary intraoperative paralysis and adequate recovery of the neuromuscular junction (NMJ) at emergence from anesthesia. Most surgery may be performed with reasonable and intermittent use of NMB rather than a persistent state of complete paralysis.[29] Indeed, many surgeries do not require NMB at all. To minimize unnecessary use of NMBs, consideration for the requirement (or not) of NMB should occur before the patient's induction and include all perioperative team members. If paralysis is a surgical requirement, appropriate monitoring of the NMJ is essential to ensure that the minimal amount of NMB required is utilized to achieve surgical objectives. AAGA is known to occur as a byproduct of post-emergence neuromuscular weakness, further strengthening the case for adequate monitoring and reversal where NMBs are used.[29]

Processed EEG monitors are commonly employed to assess the level of consciousness under GA. One such common monitor, the BIS monitor, translates raw EEG data into frequency bands that reflect a numeric value from 0 to 100. One randomized study demonstrated that patients targeted between a BIS value of 40 and 60 were less likely to experience AAGA. Notably, no studies have shown an advantage of processed EEG monitoring over standard monitoring of ETAC concentration when available, including large meta-analyses.[30] Processed EEG suffers from several limitations, most significantly that values are not tightly correlated to ETAC concentration and that non-anesthetic agents may alter processed EEG values independent of the level of consciousness. NMB alone, by decreasing or eliminating the electrical signals generated by contracting muscles, has decreased BIS values when administered without any anesthetics.[31] Based on current evidence, processed EEG monitoring should not substitute for a holistic, comprehensive, and vigilant approach to patient monitoring for depth of consciousness using all available physiologic and anesthetic parameters. 

Raw EEG possesses a significant advantage over processed EEG when monitoring for depth of consciousness. EEG waveforms are altered consistently and reproducibly when anesthetics are present at clinically relevant concentrations.[32] However, the utility of raw EEG monitoring is significantly limited due to the relative inability of most practitioners to accurately interpret raw EEG data, thus creating a significant market for processed EEG monitors, however useful they may or may not be in detecting levels of consciousness.[30][33]

Clinical Significance

Management of AAGA 

When AAGA, or any form of awareness associated with patient distress, is suspected or confirmed, a prompt and multi-disciplinary proactive approach to management is the standard of care.[22] The ASA guidelines suggest immediate administration of a benzodiazepine if awareness is suspected during the procedure. While potentially helpful, it must be recognized that midazolam, lorazepam, and similar agents are unreliable in preventing retrograde recall.[34] Even when administered preoperatively or in advance of the event, the degree of pain, paralysis, or distress from other stimuli may be sufficient to outweigh the sole administration of a benzodiazepine. More important is the immediate deepening of anesthetic agents when clinical signs and symptoms suggest intraoperative AAGA. 

Postoperatively, patients with a suspected awareness event should be interviewed at several intervals to assess and minimize the downstream psychological impact of AAGA. Immediate assessment in the PACU, either in response to a patient report of awareness or when suspected by a clinician, should focus on an open-ended discussion whereby the patient can relate their experience in detail. Dismissal of related events or justification for awareness from the practitioner at this point is inadvisable, and it is paramount to validate the concerns raised by the patient early in their recovery. Expressing regret for unpleasant experiences is ethically sound and vital for patients to hear. Expression of regret for untoward outcomes, and in many states, even apologizing, cannot be used against a practitioner as evidence of negligence in a malpractice claim. 

Immediate post-operative interviews should occur in the presence of surgical and anesthesiology team members to ensure that all parties are informed of events and that a shared understanding and analysis of causative factors may be undertaken. A patient’s recognition of awareness may be delayed by hours or even days. In many cases, patients may hesitate to initiate conversations about unintended awareness until asked.[35] In such cases, specific and validated questions are essential tools to assess the likelihood of AAGA.

The Brice questionnaire, first described by Brice, Hetherington, and Utting in 1970, attempts to solicit experiences consistent with awareness by distinguishing explicit recall from dreaming and is open-ended in both format and syntax.[36] When employed on a routine basis postoperatively between days 28 and 30, this questionnaire is superior to standard quality assurance follow-ups currently used in surgical facilities. In 1 study capturing 18,836 patients, 19 cases of AAGA were revealed with the Brice questionnaire 1 month out from surgery, yielding a rate of awareness of 0.1%, consistent with previous studies.[37] 

In contrast, only 3 of those 19 individuals were captured on the basic post-operative quality assurance calls, demonstrating that commonly employed follow-up methods are insufficient tools to screen for AAGA. Directed interviews 1 month out for all surgical patients pose a logistical challenge for healthcare infrastructure, particularly in a depleted and overburdened workforce. Herein lies a considerable and persistent challenge in accurately detecting AAGA events. 

Effect of Accidental Awareness on Patients 

Awareness events are commonly associated with psychological sequela. Nightmares, depression, anxiety, and PTSD are reported at significant but variable rates after AAGA.[38][39][40][39] Avoidance of medical care is a common downstream consequence of significant awareness events and may lead to significant long-term health consequences. Of note, cases of AAGA involving paralysis have been shown to lead to more frequent long-term psychological distress.[41] Importantly, psychological sequelae are also common among self-reported cases of awareness after IV sedation or regional anesthetic techniques; despite that, a practitioner may anticipate and even plan for fluctuating levels of consciousness wherever general anesthesia is not employed.[39]

As such, it is of critical importance to perform a detailed and comprehensive informed consent for the planned anesthetic, including the possibility of awareness and explicit recall, even in the setting of routine preoperative benzodiazepine administration. Indeed, significant gaps in understanding among patients of commonly performed sedation and anesthetic techniques may be identified during a properly informed consent process, thus offering an opportunity to educate the patient and manage expectations for planned consciousness or the lack thereof. Psychiatric or psychologic referral and treatment are highly recommended after suspected or confirmed awareness events.[22][41] Appropriate evaluation and treatment by mental health professionals play a significant role in reducing long-term detrimental effects on the psychiatric and physical well-being of affected individuals.

Enhancing Healthcare Team Outcomes

An interprofessional team of anesthesiologists, nurse anesthetists, surgeons, and perioperative nurses must understand the patient and the anesthetic and procedural risk factors that predispose patients to accidental awareness. Risks can be mitigated through avoidance or judicious use of muscle relaxants, depth of consciousness monitoring, and administration of benzodiazepines when clinically appropriate. When patients experience accidental awareness, structured interviews should be performed, and referral for psychological support should be offered.