Annual Update in Intensive Care and Emergency Medicine 2011

In summary, in comatose resuscitated patients who have not been treated with
therapeutic hypothermia, clinical examination allows accurate prediction of poor
outcome as early as 24 hours from cardiac arrest. Status myoclonus and pupillary
and corneal reflexes appear more reliable, having the narrowest confidence intervals.
The major limitation of clinical examination is that its findings may be influenced
by pathological factors, such as circulatory or metabolic derangements,
and by the effects of treatments, e.g., sedatives and muscle relaxants. Patient stabilization
and removal of any possible interference are necessary to avoid incorrect
prognostication.
Biochemical Markers
Prediction of Neurological Outcome after Cardiac Arrest 657
In the last 20 years, a series of biochemical markers of brain damage obtained
from peripheral blood and cerebrospinal fluid (CSF) have been investigated as
predictors of functional outcome after CPR. Since blood samples are much easier
and less dangerous to obtain than CSF, serum markers have been more extensively
investigated and are considered more suitable for routine clinical practice.
The serum marker which has so far demonstrated the best accuracy to predict
poor outcome is neuron-specific enolase (NSE). NSE is the neuronal form of the
cytoplasmic glycolytic enzyme enolase and it is found in neurons and neuroendocrine
cells. NSE is released in blood and in CSF after neuronal ischemia and its
serum concentrations correlate with the extent of brain damage [24]. Several
studies showed that serum NSE in the first days after cardiac arrest could predict
poor outcome with a 0 % false positive rate and narrow 95 % CIs, but the cut-off
levels varied greatly. The largest study [15] which included 407 comatose patients,
showed that serum NSE concentrations > 33 ` g/l drawn between 24 and 72 h
after CPR predicted persistent vegetative state or death with a false positive rate
of 0 % (95 % CI 0–3). However, in two other studies [25, 26], serum concentrationsashighas60
` g/l and 90.9 ` g/l in the first 36 and 72 hours, respectively,
were needed to achieve a 0 % false positive rate. Finally, in a study from Pfeifer et
al. [27] NSE levels higher than 65 ` g/l at 72 hours were still compatible with neurologicalrecovery(falsepositiverate4%).Sensitivityfortheabovecitedstudies
ranged from 33 to 77 %.
Protein S100B is a calcium-binding protein secreted from glial and Schwann
cells and released after cerebral ischemia. In the largest study conducted so far
[15], 72/207 patients had serum levels of S100B greater than 0.7 ` g/l at 72 hours
from cardiac arrest. All of these patients died or survived in a persistent vegetativestate(falsepositiverate0%;95%CI0–5).Smallerstudiesconfirmeda0%
false positive rate at 72 h for serum S100B with cut-offs ranging from 0.20 to 2.76
` g/l [9, 26, 28, 29]. However, in another study [27], among 25 patients with serum
levels above a threshold of 1.5 ` g/l one survived with good neurological outcome
(false positive rate 4 %). The sensitivity of S100B in the above studies ranged
from 40 to 75 %.
In summary, in most studies, measurement of serum levels of NSE and S100B
allowed prediction of poor neurological outcome with a zero false positive rate,
but cut-offs varied considerably. Moreover, in at least one study, high levels of
both these biomarkers were still compatible with a good outcome. At present,
there is still insufficient evidence to recommend a specific serum level of NSE or
S100B for a 100 % accurate prediction of poor outcome.
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