To our knowledge, this is the largest pool of cases systematically evaluated for adverse event data related to anesthetic AWR. Additionally, our use of electronic anesthesia records allowed for a more accurate assessment of important data including BIS numbers, end-tidal volatile concentrations, and vitals would be inherently limited in any review of paper records, as demonstrated previously . Even using conservative estimates for the incidences of AWR (0.01%), one might anticipate ~65 cases from a dataset of over 647,000 general anesthesia records. However, our actual results were an order of magnitude lower, consistent with lower estimates using some other non-prospective identification methodologies [9-11]. We strongly suspect that our health system’s EAR adverse event data significantly underestimates the true incidence of AWR in our patient population. Thus, our case cohort is a potentially biased sample of early-presenting AWR cases, and we recognize that our identified cases have significant limitations in their predicitive ability for AWR. Nonetheless, we are presenting the series of seven general anesthetic cases identified and have recognized some themes that are worthy of discussion.
Most well-known risk factors for AWR are based on descriptive data or case reports [21, 22]. The occurrence of AWR during cardiac, obstetric, and trauma surgical cases, seems intuitive, as these are situations in which it is likely to deliver lower anesthetic doses. Some patient-related risk factors are also not surprising, as they would predispose to anesthetic-resistance, including obesity and chronic alcohol or sedative use. Notably, most of these case- or patient- related risk factors did not emerge in our cohort, except that 4/7 were obese. In fact, all but one (case 3) were elective patients admitted from home.
Several risk factors for AWR related to medication choices have been variably reported in the literature. Relevant to our case series, the use of neuromuscular blocking drugs can mask patient movement that would likely provide an early clinical sign of light anesthesia. Correlation between pharmacologic paralysis and AWR has been suggested [23, 24], as well as increased distress of AWR patients who were unable to move during the awareness event . It is notable that paralysis was used in all seven of our identified cases, substantiating this correlation. The pre-induction administration of benzodiazepines intuitively should be protective against AWR, by providing amnesia. In some studies, their administration has been anti-correlated to AWR risk [25, 26]. However, similar to larger studies , our series demonstrate that AWR can certainly still occur despite benzodiazepine premedication, as these were part of the anesthetic in all but case 4.
The use of TIVA has been correlated to AWR . It makes intuitive sense that the use of TIVA may increase the risk, for two reasons related to specific favorable properties of volatile anesthetics. First, end-tidal gas monitoring allows breath to breath measurement of the dose of anesthetic delivered. If used in combination with processed EEG monitoring, expired anesthetic concentration provides potentially synergistic information that can be used to ensure an adequate dose and depth of anesthesia. Second, IV failure can cause an occult disruption of anesthetic delivery, and this is much more likely to go unrecognized than a breathing circuit disconnect. Only one case of IV infiltration was identified within the cohort of general anesthetics. However, it is worthy of note that one of the three sedation cases with AWR that were identified by our initial query also had IV infiltration noted as the suspected etiology. This highlights the importance of particular vigilance in assuring IV patency during TIVA cases to avoid AWR. Further, It has been previously demonstrated that lower-dose propofol TIVA with neuromuscular blockade and alfentanil, with or without midazolam premedication, resulted in a high incidence of AWR . A TIVA technique with propofol ≤ 100 mcg/kg/min was used in cases 4, 5 and 7. Though cases 5 and 7 employed midazolam premedication, the lower propofol dosing strategy may have contributed to AWR in these three cases.
Improper or no use of depth of consciousness monitoring could play a role in AWR. The utility of processed EEG monitoring in preventing awareness has been shown not superior to end-tidal anesthetic gas concentration alarms, but is better than clinical signs alone . It is also worthy of note that the previously-cited study on AWR with propofol TIVA  relied on clinical assessment to titrate anesthetic depth. This could seem to suggest that processed EEG monitoring should be applied in TIVA cases, whenever possible. However, notably the ASA’s practice advisory only recommends that their use be considered on a case-by-case basis . It does, however, stand to reason that, if a processed EEG monitor is employed, the anesthetic should be modified if index values are consistent with light anesthesia. In our series, cases 1 and 2 did not employ BIS monitoring, likely due to field avoidance concerns, but these cases did employ volatile anesthesia. Cases 4 and 6 (both TIVA) employed BIS monitoring, but index values were elevated ≥ 60 during most of the case. Though retrospective and anecdotal, this does raise the question as to whether additional or multimodal anesthetics would have both reduced the BIS index and/or prevented AWR. Case 3 illustrates the situation of reassuring BIS index, but a low anesthetic gas concentration. This suggests that clinicians should consider ensuring both adequate empiric anesthetic dose and reassuring depth of consciousness index values.
The timeline within the case in which AWR seemed to occur in our case series is also worthy of note. Cases 1, 4, and 5 document specific recall of events near the end of their surgical experiences. Case 1 recalled waking up prone. Case 4 recalled waking up with the endotracheal tube in place. Case 5 reported feeling stiches, which presumably was during wound closure (though documentation is not totally clear). These examples serve as a reminder that AWR most often occurs with light anesthesia, and patients are most likely to experience light anesthesia during emergence. Providers must balance the desire for a timely wake-up against the risk of a patient becoming aware while still experiencing noxious stimulation. Though not suggested by events in our case series, this can also be an issue in cases with a prolonged time between IV induction and initiation of the maintenance anesthetic, as with difficult airway management. The administration of additional anesthetic should be considered during this initial period, as appropriate.
Finally, patients with a history of AWR are at 5-fold increased propensity for experiencing AWR again - even when they are enrolled in an AWR-prevention trial . This seems to suggest that a subset of the population might show anesthetic resistance, even in the setting of reassuring depth of consciousness monitoring and clinical signs. This is illustrated by case 5, where the BIS index and vital signs were consistent with the appearance of adequate general anesthesia. An interesting population-based measure of this phenomenon is illustrated by the spread of data in the first figure of Aranake’s previous study on AWR . The top of the figure shows many data points with BIS indices above 60, despite being in a range of age-adjusted MAC that should be clinically adequate to ensure unconsciousness and amnesia. This unusual discordance in EEG response to anesthetics may be an area for future neuroscience investigation, to provide better, more personalized, anesthetic care for patients.
This case series has several limitations. The retrospective nature of the study was not able to discern clinical decision-making details that may have been involved in each case, and this limits the ability to specifically determine causative factors for each AWR event. We also do not have long-term psychiatric follow-up documented for any of the patients. The design was also limited in ability to identify cases, relying on self-reporting by providers marking an event flag in the EAR. This inherently restricted the time window for identifying and reporting AWR to the immediate post-operative period. Previous studies have suggested that up to 2/3 of cases present only after PACU discharge . These factors likely contributed to our lower incidence, compared to previous studies that employed longer follow-up periods in their methodology.
We are implementing system-wide provider education surrounding anesthetic awareness prevention to reduce the occurrence of these potentially devastating events, including highlighting some of the important themes suggested by these cases. We are also reviewing our event reporting system, in general, with an aim to improve the capture rate of AWR and other rare, but important adverse events. Finally, the lack of specificity in documentation surrounding this series of AWR events suggests the need for a structured form to be used when both collecting data and offering follow-up to patients after an AWR event.