Delayed Awakening After Cardiac Arrest: Prognostic Implications and Recovery Potential

Navigating Neurological Recovery After Cardiac Arrest

For clinicians managing patients resuscitated from out-of-hospital cardiac arrest (OHCA), predicting neurological outcome is a persistent challenge in critical care [1, 2]. Despite modern interventions like targeted temperature management, a substantial number of survivors sustain hypoxic-ischemic brain injury [3, 4]. Decisions regarding the withdrawal of life-sustaining therapy (WLST) often occur within the first week and depend heavily on multimodal prognostication [2, 5]. This process is frequently confounded by deep sedation, a common and necessary practice that can mask or delay the return of consciousness [6, 7]. The resulting diagnostic ambiguity forces clinicians to weigh the potential for meaningful recovery against the risks of prolonging suffering, creating an urgent need for clearer guidance on interpreting neurological signs in the post-arrest period.

Defining Delayed Awakening: A Clinical Conundrum

The presence of delayed awakening in patients after out-of-hospital cardiac arrest (OHCA) significantly complicates neuroprognostication. This clinical uncertainty can contribute to premature decisions to withdraw life-sustaining therapy (WLST) based on an incomplete picture of a patient's recovery potential. To clarify this issue, a recent scoping review sought to synthesize the available evidence on the definitions, determinants, and outcomes associated with delayed awakening. Researchers conducted a comprehensive search of Medline via PubMed, Embase, and Scopus for all relevant literature published through February 22, 2026. The review included studies that described delayed awakening in resuscitated adult OHCA patients, with the authors performing a risk of bias assessment and a descriptive synthesis of the collective findings.

Variability in Definitions and Study Contexts

The review synthesized data from 19 studies (17 observational, 2 randomized trials) encompassing 5441 patients, all from high-income countries. The reported incidence of delayed awakening varied widely, from 11% to 52% of patients. However, the clinical context of this evidence is critical: 18 of the 19 studies were conducted before the latest International Liaison Committee on Resuscitation (ILCOR) recommendations, suggesting the data reflect older care protocols. Furthermore, only two studies were performed in settings without WLST, a factor that significantly confounds the interpretation of true neurological outcomes. A primary obstacle identified was the lack of a consistent definition for delayed awakening. The researchers uncovered nine distinct definitions across the literature. These definitions differed on three key parameters: the time threshold for awakening (ranging from 48 hours to 7 days), the reference point for measurement (post-resuscitation, post-rewarming, or post-sedation withdrawal), and the clinical criterion for awakening (using measures like the Glasgow Coma Score, ability to follow commands, or the Richmond Agitation-Sedation Scale). This definitional chaos makes it difficult to compare study results and apply them consistently in clinical practice.

Treatment-Related Factors and Neurological Outcomes

The analysis revealed that delayed awakening was most consistently associated with iatrogenic factors. Specifically, therapeutic hypothermia, the use of longer-acting sedatives, and prolonged sedation were the most common treatment-related determinants. While patients who awakened later generally had worse outcomes than those who awakened promptly, the findings challenge the assumption that a delay invariably signals a poor prognosis. A crucial finding was that a substantial portion of these patients went on to have favorable outcomes. Across four patient cohorts in the review, 51% to 94% of patients with delayed awakening achieved good neurological recovery at discharge. Although these individuals tended to report a worse long-term quality of life, the data demonstrate that delayed awakening, often driven by treatment variables, does not preclude meaningful neurological recovery. This suggests that early pessimism based solely on a delayed return of consciousness may be unwarranted.

Addressing Bias and Future Directions

The review underscores two major limitations that temper the conclusions of existing research. First, nearly all available evidence reflects outdated temperature management practices, limiting its direct applicability to contemporary critical care. Second, and more critically, the findings were heavily confounded by a self-fulfilling prophecy bias related to WLST. This bias occurs when an early, pessimistic prognosis leads to the withdrawal of care, which in turn prevents the patient from having the chance to recover, thereby confirming the initial negative prediction. The authors note this confounding factor severely limits any conclusions regarding the true, unadulterated outcomes for this patient population. To move forward, the study highlights two urgent needs. First, a standardized definition for delayed awakening is essential to ensure consistency across research and clinical settings. Second, studies must be designed to be free of WLST-driven bias to accurately determine the true recovery potential of these patients. Such research would provide clinicians with more reliable prognostic information, helping to prevent the premature withdrawal of life-sustaining therapy in patients who might otherwise achieve a meaningful recovery.

References

1. Sandroni C, D’Arrigo S, Cacciola S, et al. Prediction of good neurological outcome in comatose survivors of cardiac arrest: a systematic review. Intensive Care Medicine. 2022. doi:10.1007/s00134-022-06618-z

2. Sandroni C, D’Arrigo S, Cacciola S, et al. Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review. Intensive Care Medicine. 2020. doi:10.1007/s00134-020-06198-w

3. Minini A, Annoni F, Peluso L, Bogossian EG, Créteur J, Taccone FS. Which Target Temperature for Post-Anoxic Brain Injury? A Systematic Review from “Real Life” Studies. Brain Sciences. 2021. doi:10.3390/brainsci11020186

4. Persson O, Valeriánová A, Bělohlávek J, et al. Hypothermia After Cardiac Arrest in Large Animals (HACA-LA): Study protocol of a randomized controlled experimental trial. Resuscitation Plus. 2024. doi:10.1016/j.resplu.2024.100704

5. Monk A, Patil S. Infrared pupillometry to help predict neurological outcome for patients achieving return of spontaneous circulation following cardiac arrest: a systematic review protocol. Systematic Reviews. 2019. doi:10.1186/s13643-019-1209-z

6. Ceric A, Holgersson J, May T, et al. Level of sedation in critically ill adult patients: a protocol for a systematic review with meta-analysis and trial sequential analysis. BMJ Open. 2022. doi:10.1136/bmjopen-2022-061806

7. Ceric A, Dankiewicz J, Hästbacka J, et al. Continuous deep sedation versus minimal sedation after cardiac arrest and resuscitation (SED‐CARE): A protocol for a randomized clinical trial. Acta Anaesthesiologica Scandinavica. 2025. doi:10.1111/aas.70022