August 29, 2017 by Casey Carr
By: Casey Carr
The Question: What are accurate predictors of neurologic recovery in comatose patients after cardiac arrest who have received targeted temperature management? What is the timeline for expected neurologic recovery in comatose patient’s after cardiac arrest who have received targeted temperature management?
The Guidelines: In 2006, the American Academy of Neurology produced guidelines which contained an algorithm for assessing the neurologic prognosis of patients after cardiac arrest. Keep in mind the studies these guidelines were based on were prior to targeted temperature management trials, and has not been reaffirmed since 2009
Most guidelines and approaches to the neurologic prognosis of the post arrest patient are based on studies prior to the wide spread utilization of targeted temperature management (TTM). TTM may be a potential source of interference in prognostication – it involves routine paralytics, sedatives, and hypothermia (which itself may reduce drug clearance) – all of which may depress clinical reactivity. TTM may reduce the prognostic value of circulating biomarkers of brain damage or the accuracy of somatosensory evoked potentials. The current evidence also suggests TTM improves neurologic outcomes, which again may alter prognosis after arrest. Additionally, most studies utilize CPC scores to define “poor”, with CPC 3-5 being poor. This is important to consider however whenever evaluating the literature, because CPC 3 includes a wide range of cerebral disabilities, from memory loss to minimally responsive states.
Timing: In a large TTM trial (Nielson 2013) comparing 33 to 36 degrees, prognostication of comatose patients occurred at a median of 118 hours. In a retrospective case study (Gold 2014) performed in patients after OHCA and TTM, the vast majority of patients who regained neurologic function did so in the first 48 hours after normothermia. However, 11% of patients who regained neurologic function did so after 72 hours; in these “late awakeners” the average time to awakening was 126 hours (the longest time to awakening in these patients was 259 hours). Lastly, in a cohort study (Mulder 2014), 32% of patients treated with TTM awoke and had a CPC score of 1-2 after 72 hours (after arrest).
- Absence of pupillary light reflex – after 72 hours from normothermia, false positive rate (FPR) approaches 0%
- Absent corneal reflex – FPR 5%
- Absent or extension motor response to pain – FPR 10-40%
- Somatosensory evoked potentials (SSEP) – 50% sensitive for predicting poor outcome after rewarming. 25% when used during hypothermia. However in two large prospective studies performed in patients treated with TTM, FPR was 0%. Notably, these studies were performed 72 hours after re-warming – SSEP has been shown to be prone to error when performed during TTM.
- EEG – In a retrospective study (Westhall 2016), highly malignant EEG findings were 100% specific for predicting poor outcomes when performed 72 hours after cardiac arrest – regardless of hypothermia. Highly malignant EEG findings was defined as “total suppression, suppression with periodic discharges, burst suppression”. Any EEG finding besides highly malignant was less accurate.
The Bottom Line:
While there are several clinical predictors and diagnostic maneuvers that are associated with poor neurologic recovery, no single test is perfectly able to predict prognosis. Current guidelines are based on prior studies that were performed prior to the widespread use of TTM. Based on recent data, similar predictors of poor outcome (lack of pupil reactivity, highly malignant EEG, lack of SSEP, early myoclonic status) seems to be comparable in patients who have received TTM – but only after 72 hours of rewarming. Time to awakening seems to be prolonged in patients who have undergone hypothermia, with a significant percentage of patients awakening after 72 hours. Prognosis after arrest with TTM should be performed using multiple modalities, and be performed 72 hours after re-warming.
Rossetti AO, Rabinstein AA, Oddo M. Neurological prognostication of outcome in patients in coma after cardiac arrest. The Lancet. Neurology. 2016; 15(6):597-609
Sandroni C, Cavallaro F, Callaway CW. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. Resuscitation. 2013; 84(10):1324-38
Nielsen N, Wetterslev J, Cronberg T. Targeted temperature management at 33°C versus 36°C after cardiac arrest. The New England journal of medicine. 2013; 369(23):2197-206. [pubmed]
- Westhall E, Rossetti AO, van Rootselaar AF. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest. Neurology. 2016; 86(16):1482-90.
- Gold B, Puertas L, Davis SP. Awakening after cardiac arrest and post resuscitation hypothermia: are we pulling the plug too early? Resuscitation. 2014; 85(2):211-4.
- Mulder M, Gibbs HG, Smith SW. Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors treated with therapeutic hypothermia*. Critical care medicine. 2014; 42(12):2493-9