ABSTRACT
Unfortunately, it remains a difficult task to predict with certainty which patients
will have a poor neurological outcome following cardiac arrest. Finding a quantitative
prognostic model of outcome has become the objective of many intensivists to assist
grieving families in making early difficult decisions regarding withdrawal of life
support. An ideal prognostic test should be readily available, easily reproducible,
and associated with a high degree of specificity for poor outcome. The goal is not
to define which patients may recover, but rather which patients have no likelihood
of meaningful neurological recovery at all to justify early withdrawal of support.
The literature and the role of biochemical markers in the blood and in the cerebrospinal
fluid will be evaluated as prognosticators following cardiac arrest. Radiological
indicators of anoxic cerebral damage are reviewed. Each serum or radiological marker
has its pros and cons. To accurately prognosticate following cardiac arrest, a multimodal
scale or algorithm that incorporates serum markers, radiological markers, and the
neurological exam is clearly needed. As these techniques are being evaluated more
closely and as imaging modalities increase in sensitivity and portability, physicians
will continue to assist families by providing some guidance as to which patients have
no chance of meaningful recovery.
KEYWORDS
Neuron-specific enolase - S-100 - cardiac arrest - radiological markers - serum markers
- prognostication
REFERENCES
- 1
Kouwenhoven W B, Jude J R, Knickerbocker G G.
Landmark article July 9, 1960: closed-chest cardiac massage. By W.B. Kouwenhoven,
James R. Jude, and G. Guy Knickerbocker.
JAMA.
1984;
251
3133-3136
- 2
Cummins R O, Eisenberg M S, Hallstrom A P, Litwin P E.
Survival of out-of-hospital cardiac arrest with early initiation of cardiopulmonary
resuscitation.
Am J Emerg Med.
1985;
3
114-119
- 3
Brain Resuscitation Clinical Trial I Study Group .
Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest.
N Engl J Med.
1986;
314
397-403
- 4
Levy D E, Bates D, Caronna J J et al..
Prognosis in nontraumatic coma.
Ann Intern Med.
1981;
94
293-301
- 5
Levy D E, Caronna J J, Singer B H, Lapinski R H, Frydman H, Plum F.
Predicting outcome from hypoxic-ischemic coma.
JAMA.
1985;
253
1420-1426
- 6
Longstreth Jr W T, Diehr P, Inui T S.
Prediction of awakening after out-of-hospital cardiac arrest.
N Engl J Med.
1983;
308
1378-1382
- 7
Jennett B, Bond M.
Assessment of outcome after severe brain damage.
Lancet.
1975;
1
480-484
- 8
Hamel M B, Goldman L, Teno J et al..
Identification of comatose patients at high risk for death or severe disability. SUPPORT
Investigators: Understand Prognoses and Preferences for Outcomes and Risks of Treatments.
JAMA.
1995;
273
1842-1848
- 9
Gueugniaud P Y, Garcia-Darennes F, Gaussorgues P, Bancalari G, Petit P, Robert D.
Prognostic significance of early intracranial and cerebral perfusion pressures in
post-cardiac arrest anoxic coma.
Intensive Care Med.
1991;
17
392-398
- 10
Gustafson I, Edgren E, Hulting J.
Brain-oriented intensive care after resuscitation from cardiac arrest [see comment].
Resuscitation.
1992;
24
245-261
- 11
Anastasiades K D, Mullins R E, Conn R B.
Neuron-specific enolase: assessment by ELISA in patients with small cell carcinoma
of the lung.
Am J Clin Pathol.
1987;
87
245-249
- 12
Hay E, Royds J A, Davies-Jones G A, Lewtas N A, Timperley W R, Taylor C B.
Cerebrospinal fluid enolase in stroke.
J Neurol Neurosurg Psychiatry.
1984;
47
724-729
- 13
Persson L, Hardemark H G, Gustafsson J et al..
S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers
of cell damage in human central nervous system.
Stroke.
1987;
18
911-918
- 14
Studahl M, Rosengren L, Gunther G, Hagberg L.
Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne
encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal
destruction.
J Neurol.
2000;
247
636-642
- 15
Royds J A, Timperley W R, Taylor C B.
Levels of enolase and other enzymes in the cerebrospinal fluid as indices of pathological
change.
J Neurol Neurosurg Psychiatry.
1981;
44
1129-1135
- 16
Correale J, Rabinowicz A L, Heck C N, Smith T D, Loskota W J, DeGiorgio C M.
Status epilepticus increases CSF levels of neuron-specific enolase and alters the
blood-brain barrier.
Neurology.
1998;
50
1388-1391
- 17
Roine R O, Somer H, Kaste M, Viinikka L, Karonen S L.
Neurological outcome after out-of-hospital cardiac arrest: prediction by cerebrospinal
fluid enzyme analysis.
Arch Neurol.
1989;
46
753-756
- 18
Schaarschmidt H, Prange H W, Reiber H.
Neuron-specific enolase concentrations in blood as a prognostic parameter in cerebrovascular
diseases.
Stroke.
1994;
25
558-565
- 19
Dauberschmidt R, Zinsmeyer J, Mrochen H, Meyer M.
Changes of neuron-specific enolase concentration in plasma after cardiac arrest and
resuscitation.
Mol Chem Neuropathol.
1991;
14
237-245
- 20
Fogel W, Krieger D, Veith M et al..
Serum neuron-specific enolase as early predictor of outcome after cardiac arrest.
Crit Care Med.
1997;
25
1133-1138
- 21
Martens P.
Serum neuron-specific enolase as a prognostic marker for irreversible brain damage
in comatose cardiac arrest survivors.
Acad Emerg Med.
1996;
3
126-131
- 22
Rosen H, Rosengren L, Herlitz J, Blomstrand C.
Increased serum levels of the S-100 protein are associated with hypoxic brain damage
after cardiac arrest.
Stroke.
1998;
29
473-477
- 23
Schoerkhuber W, Kittler H, Sterz F et al..
Time course of serum neuron-specific enolase: a predictor of neurological outcome
in patients resuscitated from cardiac arrest.
Stroke.
1999;
30
1598-1603
- 24
Meynaar I A, Straaten H M, van der Wetering J et al..
Serum neuron-specific enolase predicts outcome in post-anoxic coma: a prospective
cohort study.
Intensive Care Med.
2003;
29
189-195
- 25
Tiainen M, Roine R O, Pettila V, Takkunen O.
Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated
with hypothermia.
Stroke.
2003;
34
2881-2886
- 26
Martens P, Raabe A, Johnsson P.
Serum S-100 and neuron-specific enolase for prediction of regaining consciousness
after global cerebral ischemia.
Stroke.
1998;
29
2363-2366
- 27
Rosen H, Sunnerhagen K S, Herlitz J, Blomstrand C, Rosengren L.
Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome
after cardiac arrest.
Resuscitation.
2001;
49
183-191
- 28
Bottiger B W, Mobes S, Glatzer R et al..
Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage
and outcome after cardiac arrest in humans.
Circulation.
2001;
103
2694-2698
- 29
Heizmann C W.
Ca2 + -binding S100 proteins in the central nervous system.
Neurochem Res.
1999;
24
1097-1100
- 30
Donato R.
S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular
and extracellular functional roles.
Int J Biochem Cell Biol.
2001;
33
637-668
- 31
Li Y, Barger S W, Liu L, Mrak R E, Griffin W S.
S100beta induction of the proinflammatory cytokine interleukin-6 in neurons.
J Neurochem.
2000;
74
143-150
- 32
Hachimi-Idrissi S, Van der Auwera M, Schiettecatte J, Ebinger G, Michotte Y, Huyghens L.
S-100 protein as early predictor of regaining consciousness after out of hospital
cardiac arrest.
Resuscitation.
2002;
53
251-257
- 33
Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve
the neurologic outcome after cardiac arrest.
N Engl J Med.
2002;
346
549-556
- 34
Bernard S A, Gray T W, Buist M D et al..
Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.
N Engl J Med.
2002;
346
557-563
- 35
Calle P A, Buylaert W A, Vanhaute O A.
Glycemia in the post-resuscitation period. The Cerebral Resuscitation Study Group.
Resuscitation.
1989;
17(suppl)
S181-S188
, discussion S199-S206
- 36
Fang J F, Chen R J, Lin B C et al..
Prognosis in presumptive hypoxic-ischemic coma in nonneurologic trauma.
J Trauma.
1999;
47
1122-1125
- 37
Longstreth Jr W T, Diehr P, Cobb L A, Hanson R W, Blair A D.
Neurologic outcome and blood glucose levels during out-of-hospital cardiopulmonary
resuscitation.
Neurology.
1986;
36
1186-1191
- 38
Longstreth Jr W T, Inui T S, Cobb L A, Copass M K.
Neurologic recovery after out-of-hospital cardiac arrest.
Ann Intern Med.
1983;
98
588-592
- 39
Mullner M, Sterz F, Domanovits H, Behringer W, Binder M, Laggner A N.
The association between blood lactate concentration on admission, duration of cardiac
arrest, and functional neurological recovery in patients resuscitated from ventricular
fibrillation.
Intensive Care Med.
1997;
23
1138-1143
- 40
Edgren E, Hedstrand U, Nordin M, Rydin E, Ronquist G.
Prediction of outcome after cardiac arrest.
Crit Care Med.
1987;
15
820-825
- 41
Chandler W L, Clayson K J, Longstreth Jr W T, Fine J S.
Creatine kinase isoenzymes in human cerebrospinal fluid and brain.
Clin Chem.
1984;
30
1804-1806
- 42
Longstreth Jr W T, Clayson K J, Chandler W L, Sumi S M.
Cerebrospinal fluid creatine kinase activity and neurologic recovery after cardiac
arrest.
Neurology.
1984;
34
834-837
- 43
Goe M R, Massey T H.
Assessment of neurologic damage: creatine kinase-BB assay after cardiac arrest.
Heart Lung.
1988;
17
247-253
- 44 Osborn A.
Stroke. In: Osborn A, Maack J Diagnostic Neuroradiology. St. Louis; Mosby 1994: 330-398
- 45
Castillo M.
Imaging of cerebral infarction.
Curr Probl Diagn Radiol.
1998;
27
105-131
- 46
Singhal A B, Topcuoglu M A, Koroshetz W J.
Diffusion MRI in three types of anoxic encephalopathy.
J Neurol Sci.
2002;
196
37-40
- 47
Roine R O, Raininko R, Erkinjuntti T, Ylikoski A, Kaste M.
Magnetic resonance imaging findings associated with cardiac arrest.
Stroke.
1993;
24
1005-1014
- 48
Hossmann K A, Schuier F J.
Experimental brain infarcts in cats: I. Pathophysiological observations.
Stroke.
1980;
11
583-592
- 49
Iida K, Satoh H, Arita K, Nakahara T, Kurisu K, Ohtani M.
Delayed hyperemia causing intracranial hypertension after cardiopulmonary resuscitation.
Crit Care Med.
1997;
25
971-976
- 50
Schuier F J, Hossmann K A.
Experimental brain infarcts in cats: II. Ischemic brain edema.
Stroke.
1980;
11
593-601
- 51
Bell B A, Symon L, Branston N M.
CBF and time thresholds for the formation of ischemic cerebral edema, and effect of
reperfusion in baboons.
J Neurosurg.
1985;
62
31-41
- 52
Iannotti F, Hoff J T, Schielke G P.
Brain tissue pressure in focal cerebral ischemia.
J Neurosurg.
1985;
62
83-89
- 53
Hatashita S, Hoff J T.
Cortical tissue pressure gradients in early ischemic brain edema.
J Cereb Blood Flow Metab.
1986;
6
1-7
- 54
Han B K, Towbin R B, De Courten-Myers G, McLaurin R L, Ball Jr W S.
Reversal sign on CT: effect of anoxic/ischemic cerebral injury in children.
AJNR Am J Neuroradiol.
1989;
10
1191-1198
- 55
Torbey M T, Paydarfar D, Bigelow C, Recht L.
Loss of gray-white matter differentiation (GWMD) predicts poor patient outcome after
cardiac arrest.
Neurology.
1999;
52(suppl 2)
A61
- 56
Torbey M T, Selim M, Knorr J, Bigelow C, Recht L.
Quantitative analysis of the loss of distinction between gray and white matter in
comatose patients after cardiac arrest.
Stroke.
2000;
31
2163-2167
- 57
Nunes B, Pais J, Garcia R, Magalhaes Z, Granja C, Silva M C.
Cardiac arrest: long-term cognitive and imaging analysis.
Resuscitation.
2003;
57
287-297
- 58
Arbelaez A, Castillo M, Mukherji S K.
Diffusion-weighted MR imaging of global cerebral anoxia.
AJNR Am J Neuroradiol.
1999;
20
999-1007
- 59
Chalela J A, Wolf R L, Maldjian J A, Kasner S E.
MRI identification of early white matter injury in anoxic-ischemic encephalopathy
[see comment].
Neurology.
2001;
56
481-485
- 60
Wijdicks E F, Campeau N G, Miller G M.
MR imaging in comatose survivors of cardiac resuscitation [see comment].
AJNR Am J Neuroradiol.
2001;
22
1561-1565
- 61
Els T, Kassubek J, Kubalek R, Klisch J.
Diffusion-weighted MRI during early global cerebral hypoxia: a predictor for clinical
outcome?.
Acta Neurol Scand.
2004;
110
361-367
- 62
Rivkin M J, Volpe J J.
Hypoxic-ischemic brain injury in the newborn.
Semin Neurol.
1993;
13
30-39
- 63
Hossmann K A, Fischer M, Bockhorst K, Hoehn-Berlage M.
NMR imaging of the apparent diffusion coefficient (ADC) for the evaluation of metabolic
suppression and recovery after prolonged cerebral ischemia.
J Cereb Blood Flow Metab.
1994;
14
723-731
- 64
Knight R A, Dereski M O, Helpern J A, Ordidge R J, Chopp M.
Magnetic resonance imaging assessment of evolving focal cerebral ischemia: comparison
with histopathology in rats.
Stroke.
1994;
25
1252-1261
, discussion 1261-1262
- 65
Hossmann K A, Hoehn-Berlage M.
Diffusion and perfusion MR imaging of cerebral ischemia.
Cerebrovasc Brain Metab Rev.
1995;
7
187-217
- 66
Sontheimer H, Kettenmann H, Backus K H, Schachner M.
Glutamate opens Na + /K + channels in cultured astrocytes.
Glia.
1988;
1
328-336
- 67
Kuhn M J, Mikulis D J, Ayoub D M, Kosofsky B E, Davis K R, Taveras J M.
Wallerian degeneration after cerebral infarction: evaluation with sequential MR imaging.
Radiology.
1989;
172
179-182
- 68
Pantoni L, Garcia J H, Gutierrez J A.
Cerebral white matter is highly vulnerable to ischemia.
Stroke.
1996;
27
1641-1646
, discussion 1647
- 69
Hald J K, Brunberg J A, Dublin A B, Wootton-Gorges S L.
Delayed diffusion-weighted MR abnormality in a patient with an extensive acute cerebral
hypoxic injury.
Acta Radiol.
2003;
44
343-346
- 70
Zingler V C, Krumm B, Bertsch T, Fassbender K, Pohlmann-Eden B.
Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal
approach combining neurobiochemical and electrophysiological investigations may provide
high prognostic certainty in patients after cardiac arrest.
Eur Neurol.
2003;
49
79-84
- 71
Bassetti C, Bomio F, Mathis J, Hess C W.
Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological,
and biochemical study of 60 patients.
J Neurol Neurosurg Psychiatry.
1996;
61
610-615
- 72
Pfeifer R, Borner A, Krack A, Sigusch H H, Surber R, Figulla H R.
Outcome after cardiac arrest: predictive values and limitations of the neuroproteins
neuron-specific enolase and protein S-100 and the Glasgow Coma Scale.
Resuscitation.
2005;
65
49-55
- 73
Torbey M T, Geocadin R, Bhardwaj A.
Brain arrest neurological outcome scale (BrANOS): predicting mortality and severe
disability following cardiac arrest.
Resuscitation.
2004;
63
55-63
- 74
Kjos B O, Brant-Zawadzki M, Young R G.
Early CT findings of global central nervous system hypoperfusion.
AJR Am J Roentgenol.
1983;
141
1227-1232
- 75
Fujioka M, Okuchi K, Miyamoto S et al..
Changes in the basal ganglia and thalamus following reperfusion after complete cerebral
ischaemia.
Neuroradiology.
1994;
36
605-607
Michel T TorbeyM.D. M.P.H. F.A.H.A.
Director, Neurointensive Care Unit, Medical College of Wisconsin
9200 W. Wisconsin Avenue, Milwaukee, WI 53226