The practice of neurological prognostication in comatose CA
patients
As shown in table 3, a formalized prognostic protocol is only available
in 6.8% respondents. Compared with clinical examination (85.4%),
neuroimaging (65.6%) and biomarkers (30.1%), electrophysiological
measurement (21.9%) is less used. Among stem reflexes, pupillary reflex
(91.9%) and corneal reflex (68.1%) was used by most respondents.
67.9% respondents had used brain CT for predicting outcome, but 18.4%
for MRI. Among biomarkers, NSE was a little more widely used than
S-100β. However, only 4.4% respondents had performed SSEP and 11.4%
had performed EEG for prognostication in CA patients.
This survey serves as the first nation-wide analysis of neurological
prognostication in survivors after CA in China and can serve as a
baseline for future work. The main finding is that post CA neurological
assessment has not been well understood and performed by emergency
physicians who are more likely to take care of such patients in China.
In practice, they were more likely to use clinical evaluation rather
than other objective prognostic tools.
Clinical examination is the most commonly used method to predict outcome
after CA in our study. However, the details were not well understood.
Assessment of brainstem reflexes, motor responses to pain, and myoclonus
represent the standard test in clinical
examination.5,6 But in our survey, only 50%
recognized that brainstem reflexes and motor responses to pain
correlated with outcome. Corneal reflex was significantly less performed
than pupillary reflex despite of its easy use. 62.7% confirmed the
progGnostic value of myoclonus. In fact, myoclonus is variably
associated with outcome. Myoclonic jerk is not consistently associated
with poor outcome and status myoclonus starting within 48h from ROSC is
highly predictive of poor outcome.7,8 This was partly
explained by the lack of developed post-CA care centers in China.
Moreover, the lack of special training in neurological prognostication,
together with limited attendance of emergency physicians contributed to
the insufficient understanding of clinical evaluation.
Guidelines suggest EEG for prognostication after CA. Certain EEG
patterns such as electrocerebral silence, burst suppression, absence of
reactivity and status epilepticus, was associated with a high rate of
poor outcome, though not uniformly.9-11 The other
patterns (including low-voltage, seizures alone and discontinuous
background) were less reliable because of limited
evidence.12 But epileptiform, burst suppression,
isoelectric was considered to predict poor outcome by only 35.0%,
27.4%, 33.3% respondents respectively in our survey. Only 11.4% had
performed EEG in routine practice in this study. However, recent surveys
showed that EEG was widely used.13,14 Friberg et al
reported that 74% of members from European Society of Emergency
Medicine had used intermittent EEG or continuous EEG for CA patients in
practice.14 The low level utility of EEG in China is
likely due to several causes. One primary reason is lack of national
recommendations and formalized SOP for neurological prognosis in CA
patients which can improve the practice and makes the assessment less
physician and/or hospital-dependent. However, national recommendation
was not available until 2018 one year after our
study.15 A written SOP is only available in 6.8%
respondents in present study, which is far behind that of European
countries. 3 In addition, there also exist barriers to
access EEG services in timely manner even at developed
university-affiliated hospitals in China.
Among evoked potentials, somatosensory evoked potentials (SSEP) are best
studied after CA. Bilateral absence of SSEP N20 response is strongly
associated with poor outcomes.5,6 Surprisingly, the
present study showed that only 7.3% respondents knew the predictive
value of SSEP N20 and only 4.4% had performed SSEP for CA patients in
practice. There was still a huge gap with that in European countries. It
was reported that more than half of respondents or ICUs had used SSEP in
post CA patients.3,14 In addition to the lack of
national guidelines and local protocols, the need for special skill and
experience is one of the main reasons why SSEP is less used.
Despite the evidences of neuroimaging for prognostication were limited
and its use only in combination with other predictors was recommended in
guidelines, our survey showed that next to clinical examination, brain
CT was the most widely used methods to predict outcome after CA which is
in line with previous studies.14-16 This was likely
related to the extensive use of brain CT to exclude brain hemorrhage or
infarction after CA and to the fact that this technique is easily
available. When it comes to details, however, only 30% of respondents
know that a marked reduction of the grey matter/white matter ratio was
associated with poor outcome.17,18 MRI has a high
sensitivity for identifying ischemic brain injury and was considered to
be an even more accurate tool for prognostication, however, its use can
be problematic in the most clinically unstable
patients.19 This partly explained the finding that the
use of brain MRI for predicting outcome was reported by only 18.8%
respondents in our survey.
Biomarkers were more commonly used than EEG and SSEP in present study,
mainly because of their simplicity, independence from sedation and low
cost. Although a wide range of proteins have been identified as
indicators of brain injury, only NSE and S-100β have been extensively
studied.20,21 S-100β is less well documented than NSE.
However, there is a great variability in thresholds due to
heterogeneity. The cut off levels varied in different studies and at
different time point.20-22 Furthermore, the threshold
of NSE in TTM-patients might be higher than in those without cooling as
hypothermia may significantly reduce NSE levels.23 So
no optimal threshold of NSE or S-100βwas established to predict poor
neurological outcome with a false positive rate of 0%.
No single test can accurately predict the prognosis of patients
following CA. A multimodal approach combining clinical examination, EEG,
biomarkers and brain imaging was recommended to increase the certainty
of prognostication. Combining any of two or more tools improved
prognostic performance compared to either each individual
method.24,25 Ji Hoon Kim and his college reported a
stepwise model combining brain CT and MRI, NSE, EEG, SSEPs and pupil
light reflex predicted poor outcomes with a 0% false positive
rate.25 But in our study, the low utility of EEG, SSEP
and biomarkers illustrated that multimodal approach was not well
performed in practice.
The optimal time of neurological evaluation is under discussion. The
current advisory suggests that multimodal modalities should not be
performed before 72h from ROSC, especially in the ear of
TTM.6,26 Previous studies had shown that TTM and the
related pharmacological sedation may influence the neurological
examination and also modify the predictive value of NSE or the accuracy
of SSEPs.27 So prolonging clinical observation after
rewarming, usually beyond 72h from ROSC, may be suggested when
interference from residual effects of drugs is
suspected.28 But our survey reported only a few
respondents knew that neurological prognostication should be performed
later than 72h from CA either in TTM or non-TTM patients. This
misunderstanding may cause premature decisions to withdrawal of life
support in practice.