Risk Factors Associated with Intraoperative Awareness

Accidental awareness during general anesthesia presents a substantial risk of posttraumatic stress disorder in patients who experience it. Recent large-scale audits and randomized trials have clarified both the incidence and the risk factors associated with intraoperative awareness, offering clinicians a clearer picture of which patients and practices warrant heightened vigilance.

The 5th National Audit Project (NAP5) in the UK remains the most comprehensive dataset on this topic, estimating an overall incidence of patient-reported intraoperative awareness of approximately 1 in 19,600 general anesthetics (Pandit et al., 2014). However, this figure masks marked variation by technique and surgical subspecialty. The use of neuromuscular blocking drugs (NMBDs) was the single strongest modifiable risk factor identified: incidence rose to roughly 1 in 8,200 when NMBDs were used, compared with 1 in 135,900 when they were not. Total intravenous anesthesia combined with neuromuscular blockade carried an almost fourfold increased risk relative to volatile-based techniques. Obstetric anesthesia, particularly Caesarean section, was disproportionately represented, with an incidence of 1 in 670, likely reflecting the influence of rapid sequence induction and frequent emergency, out-of-hours operating. Cardiothoracic surgery was similarly overrepresented, most likely attributable to intentionally light anesthesia in hemodynamically unstable patients. Additional risk factors identified in NAP5 included female sex, younger adult age, obesity, junior anesthetist involvement, and a prior history of awareness. Notably, ASA physical status, race, and nitrous oxide use were not associated with increased risk.

Other research has also identified prior history of intraoperative awareness as a risk factor for future incidence. A matched cohort analysis drawn from three major awareness-prevention trials found that patients with a self-reported history of AWR had a fivefold increased risk of recurrence compared with matched controls (relative risk 5.0; 95% CI, 1.3–19.9), despite no measurable difference in anesthetic management between groups. Patients with a prior history also demonstrated an altered relationship between bispectral index (BIS) values and end-tidal anesthetic concentration, suggesting a possible pharmacodynamic component to their vulnerability, though the authors caution that this finding does not fully explain the elevated risk.

Several strategies have been developed and tested to better titrate anesthetic depth, such as BIS monitoring. The BAG-RECALL trial examined whether using BIS monitoring reduced the incidence of intraoperative awareness in high-risk populations (patients undergoing planned open-heart surgery, those with aortic stenosis, pulmonary hypertension, reduced ejection fraction, end-stage lung disease, or marginal exercise tolerance, as well as regular users of opiates, benzodiazepines, anticonvulsants, or alcohol). Researchers found no superiority of BIS-guided anesthesia over end-tidal anesthetic concentration monitoring in reducing awareness, and a substantial proportion of both definite and possible awareness events occurred despite BIS or ETAC values remaining within recommended targets (Avidan et al., 2011).

Pharmacologic strategy also appears relevant to risk mitigation, with benzodiazepines like midazolam often being incorporated to induce anterograde amnesia. A systematic review and meta-analysis found that perioperative benzodiazepine administration was associated with a reduced risk of intraoperative awareness, although the certainty of this evidence was rated very low and the absolute risk reduction was modest when non-events were considered.

Collectively, these data highlight key risk factors for intraoperative awareness: neuromuscular blockade without adequate depth-of-anesthesia assurance, obstetric and cardiac surgery, hemodynamic instability prompting deliberate anesthetic underdosing, and prior awareness history. Clinicians managing patients in these situations should maintain heightened vigilance, consider multimodal monitoring, and discuss individualized risks with the patient.