Late Awakening in Survivors of Postanoxic Coma: Early Neurophysiologic Predictors and Association With ICU and Long-Term Neurologic Recovery

Abstract

Objectives: To examine neurophysiologic predictors and outcomes of patients with late awakening following cardiac arrest. Design: Observational cohort study. Setting: Academic ICU. Patients: Adult comatose cardiac arrest patients treated with targeted temperature management and sedation. Interventions: None. Measurement and Main Results: Time to awakening was calculated starting from initial sedation stop following targeted temperature management and rewarming (median 34 hr from ICU admission). Two-hundred twenty-eight of 402 patients (57%) awoke: late awakening (> 48 hr from sedation stop; median time to awakening 5 days [range, 3–23 d]) was observed in 78 subjects (34%). When considering single neurophysiologic tests, late awakening was associated with a higher proportion of discontinuous electroencephalography (21% vs 6% of early awakeners), absent motor and brainstem responses (38% vs 11%; 23 vs 4%, respectively), and serum neuron specific enolase greater than 33 ng/mL (23% vs 8%; all p < 0.01): no patient had greater than 2 unfavorable tests. By multivariable analysis—adjusting for cardiac arrest duration, Sequential Organ Failure Assessment score, and type of sedation—discontinuous electroencephalography and absent neurologic responses were independently associated with late awakening. Late awakening was more frequent with midazolam (58% vs 45%) and was associated with higher rates of delirium (62% vs 39%) and unfavorable 3-months outcome (27% vs 12%; all p = 0.005). Conclusions: Late awakening is frequent after cardiac arrest, despite early unfavorable neurophysiologic signs and is associated with greater neurologic complications. Limiting benzodiazepines during targeted temperature management may accelerate awakening. Postcardiac arrest patients with late awakening had a high rate of favorable outcome, thereby supporting prognostication strategies relying on multiple rather than single tests and that allow sufficient time for outcome prediction.

European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post-resuscitation care

“…Treatment with sedatives and conventional antiepileptic drugs in high doses may delay awakening, prolong the need for mechanical ventilation, and increase critical care length of stay. 204 Consider that generalised myoclonus in combination with epileptiform discharges may be early signs of Lance-Adams syndrome which is compatible with awakening and a good outcome. 181,184 In such cases, aggressive treatment may confound the clinical examination and lead to overly pessimistic prognostication.…”

Postreanimationsbehandlung

“…Organfunktionsstörungen, wie z. B. ein Postreanimationsschock-oder Nierenversagen [207,308], und die Verwendung von Midazolam anstelle von Propofol zur Sedierung [207,268] [267].…”

“…Bei reanimierten Patienten, die komatös bleiben, nimmt die Wahrscheinlichkeit des Erwachens mit der Zeit allerdings progressiv ab. Vergleicht man die Zeiträume des Wachwerdens, sind die Raten für ein gutes neurologisches Ergebnis im Allgemeinen umso niedriger, je später die Patienten wach werden [207,308,418].…”

Targeted temperature management for postcardiac arrest syndrome

“…One study showed that patients undergoing TTM ( ≤ 33°C) recovered consciousness in a mean of 3.8 days, with approximately 20% awakening after 5 days postarrest [64]. Recently, Rey et al [65] reported that increased utilization of midazolam during the TTM phase correlates with late awakening (median time to awakening 5 days; range, 3 to 23 days from sedation stop).…”

“…Midazolam results in less hemodynamic instability than propofol, but it prolongs the duration of mechanical ventilation and length of ICU stay [70]; furthermore, it may prolong the time to awakening and reduce the accuracy of the clinical examination, because the half-life of midazolam is prolonged by hypothermia [65,71]. During TTM, low continuous infusions of midazolam are preferred.…”