(Circulation. 2001;103:2694.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Astroglial Protein S-100 Is an Early and Sensitive Marker of Hypoxic Brain Damage and Outcome After Cardiac Arrest in Humans
From the Departments of Anesthesiology and Sports Medicine (P.B.), University of Heidelberg, Heidelberg, Germany.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—The results of early conventional tests do not correlate with cerebral outcome after cardiac arrest. We investigated the serum levels of astroglial protein S-100 as an early marker of brain damage and outcome after cardiac arrest.
Methods and Results—In 66 patients undergoing cardiopulmonary resuscitation after nontraumatic cardiac arrest, blood samples for the evaluation of S-100 were drawn immediately after and 15, 30, 45, and 60 minutes; 2, 8, 24, 48, and 72 hours; and 7 days after initiation of cardiopulmonary resuscitation. Moreover, the serum levels of neuron-specific enolase were determined between 2 hours and 7 days. If patients survived for >48 hours, brain damage was assessed by a combination of neurological, cranial CT, and electrophysiological examinations. Overall, 343 blood samples were taken for the determination of S-100. Maximum S-100 levels within 2 hours after cardiac arrest were significantly higher in patients with documented brain damage (survivors and nonsurvivors, 3.70±0.77 µg/L) than in patients without brain damage (0.90±0.29 µg/L). Significant differences between these 2 groups were observed from 30 minutes until 7 days after cardiac arrest. In addition, the positive predictive value of the S-100 test at 24 hours for fatal outcome within 14 days was 87%, and the negative predictive value was 100% (P<0.001). With regard to neuron-specific enolase, significant differences between patients with documented brain damage and those with no brain damage were found at 24, 48, and 72 hours and 7 days.
Conclusions—Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and short-term outcome after cardiac arrest in humans.
Key Words: heart arrest • cardiopulmonary resuscitation • ischemia • brain • outcome
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Brain damage is one of the major causes of morbidity and mortality after cardiac arrest and cardiopulmonary resuscitation (CPR) in hospitalized patients.1 2 Early assessment of brain damage and prediction of cerebral outcome after cardiac arrest, therefore, may affect postarrest treatment strategies. Various attempts, including neurological evaluation, cranial CT, electroencephalogram, somatosensory evoked potentials, and measurement of cerebral oxygen consumption, have been made to assess brain damage in comatose patients soon after cardiac arrest.3 4 5 6 7 8 9 10 Early neurological and electrophysiological evaluations, however, do not predict cerebral outcome.11 A serum marker that reflects the severity of brain damage as accurately as biochemical markers do in myocardial injury,12 however, would improve early evaluation and quantification of post–cardiac arrest brain damage. Biochemical markers of hypoxic brain damage such as neuron-specific enolase (NSE), however, have also shown promising results only at later stages (ie, >24 hours after cardiac arrest).13 14 15 16 Recently, S-100 has been found to be a promising marker for central nervous system injury.17 18 19 20 21 22 23 24 Protein S-100 is part of a large family of calcium-binding proteins, and evidence exists that S-100 regulates calcium-dependent cellular signaling in neuronal differentiation, outgrowth, and apoptosis through different concentrations.25 26 27 28 29 Elevated serum levels of S-100 have been documented in patients suffering from different types of brain damage, including stroke, minor and severe head injury, and brain damage associated with extracorporeal circulation and later stages of global cerebral ischemia.17 18 19 20 21 22 23 24 No data are available, however, concerning serum levels of S-100 during the early phase after global cerebral ischemia from cardiocirculatory arrest in humans. In an attempt to find an early marker of hypoxic brain damage and outcome, we investigated the serum levels of astroglial protein S-100 during CPR and after restoration of spontaneous circulation (ROSC).
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients
After approval from the local Ethics Committee and informed consent from patients without brain damage or the relatives of patients with brain damage had been obtained, patients who had undergone CPR after nontraumatic cardiac arrest before admission to the hospital and who were covered by the local physician-staffed advanced cardiac life support system were studied. Venous blood samples were taken during CPR and after ROSC by an independent physician who was not responsible for the patient’s care. According to the recommendations of the Utstein Consensus Conference,30 patient survival was assessed with regard to ROSC and hospital admission (all patients were admitted to the same hospital). In addition, short-term outcome (14 days’ survival) was assessed, and patients were divided into 4 groups (as shown in Figure 1
): (1) no brain damage (patients discharged from the
hospital fully oriented and without any communication defects; ie,
cerebral performance
category31 CPC1), (2)
documented brain damage (ie, according to neurological, cranial CT, and
electrophysiological evaluations
systematically performed between 48 hours and 96 hours after cardiac
arrest; to focus on all patients, the data of surviving and
nonsurviving patients were combined here; see also
Table 1), (3) no ROSC, and (4) patients who died soon after
ROSC before assessment of brain damage.
|
|
Blood Samples and Biochemical Markers
For the evaluation of serum levels of S-100 (S-100
IRMA, AB Sangtec Medical; sensitivity, 0.2 µg/L), blood samples were
drawn immediately after and 15, 30, 45, and 60 minutes; 2, 8, 24, 48,
and 72 hours; and 7 days after CPR was initiated. Samples for the
determination of S-100 were put into specific tubes (Citrate Vacutainer
tubes, Boehringer Mannheim). After admission to the intensive
care unit, additional blood samples were drawn into EDTA tubes
(Vacutainer tubes, Boehringer Mannheim) for the determination
of NSE (Prolifigen R, AB Sangtec Medical; normal range <12.5 µg/L)
at 2, 8, 24, 48, and 72 hours and 7 days after CPR was initiated. In an
attempt to simplify blood sampling during CPR and in the prehospital
setting, NSE was not determined before 2 hours after cardiac
arrest.
In all patients, blood samples during CPR and immediately
after ROSC were drawn from the external jugular vein via a separate
12-gauge venous cannula inserted opposite to the infusion site. In each
case, the first 10 mL of blood was discarded. After admission to the
intensive care unit, blood samples were taken through a central venous
catheter after the first 10 mL of blood was discarded. Immediately
after sampling, the blood in the tubes was mixed, carefully avoiding
the formation of foam, and placed on a mixture of water and ice to
ensure a constant temperature of 
4°C, which was controlled by a
thermometer. The tubes were centrifuged within 1 hour of
collection at 1500g for 15
minutes (4°C). The plasma was then separated and stored as aliquots
in plastic tubes at -70°C until it was assayed. All assays were
performed in a blinded manner by an independent member of the
laboratory staff.
Statistical Analysis
ANOVA followed by the Scheffé test,
Wilcoxon test, and Fisher’s exact test were used for
statistical analysis. Data are mean±SEM; a probability value
of P<0.05 was considered
statistically significant. Because the duration of out-of-hospital
cardiac arrest can only be estimated, these data were excluded from
statistical analysis.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Astroglial Protein S-100
Overall, 66 patients (24 female, 42 male; mean age, 66 years [range, 25 to 91 years]; Figure 1
) were studied. The causes of cardiac arrest were
primary cardiogenic, including acute myocardial infarction and
pulmonary embolism (n=60); intoxication (n=3); status
asthmaticus (n=2); and subarachnoid hemorrhage (n=1).
According to the recommendations of the Utstein Consensus Conference,
the outcome in these patients is given in
Figure 1. Overall, 343 blood samples were taken. It was not
possible to obtain blood from each patient at every time
point.
Significant differences in the levels of S-100 between
patients surviving without brain damage (CPC1; n=9) and those with
documented brain damage (n=12, ie, 4 surviving and 8 nonsurviving
patients; see
Table 1) were observed during the entire study period. Even
very early during CPR, significant differences were observed between
the 2 groups
(Figure 2). Moreover, maximum S-100 levels within 2 hours
after cardiac arrest were significantly higher in patients with
documented brain damage (3.70±0.77 µg/L;
P<0.05) and in patients
without ROSC (3.44±0.58 µg/L;
P<0.05) than in patients with
no brain damage (0.90±0.29 µg/L), whereas patients who died before
assessment of brain damage showed intermediate levels (2.36±0.41
µg/L;
Figure 3). The odds ratio of having brain damage was 15
(95% CI, 2.02 to 111.22) if S-100 serum levels were elevated within 2
hours after cardiac arrest. At 48 hours after cardiac arrest, an S-100
serum level of >1.10 µg/L revealed a specificity of 100% for the
diagnosis of brain damage. The positive predictive value of the S-100
test at 2 hours for fatal outcome within 14 days was 79%, and the
negative predictive value was 100%
(P<0.01). At 24 hours, the
corresponding figures were 87% and 100%
(P<0.001), and at 48 hours,
they were 75% and 100%
(P<0.01), respectively
(Table 2).
|
|
|
Neuron-Specific Enolase
In 33 patients (9 female, 24 male; mean age, 67 years
[range, 34 to 85 years]), 137 blood samples were taken. Fourteen
patients died before assessment of brain damage (maximum NSE levels,
28.6±11.5 µg/L). Nine patients survived without neurological deficit
(CPC1), and 10 patients were shown to have suffered severe brain
damage. When the serum levels of NSE in patients without neurological
deficit (CPC1) and in those with documented brain damage were compared,
significant differences were observed at 24, 48, and 72 hours and 7
days
(Figure 4).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The present data demonstrate that there is a marked difference in S-100 levels after cardiac arrest between patients who had suffered brain damage and those who had not. By determining levels of astroglial protein S-100 in blood samples, differences between the 2 groups can be detected very soon after the initiation of CPR procedures. Interestingly, patients without ROSC also showed significantly elevated levels of S-100, suggesting that the duration of cardiac arrest and cerebral ischemia in these patients might have been longer than in those without brain damage. Patients who died soon after ROSC without neurological evaluation showed intermediate values, which was expected, because this group most likely represents a mixture of patients with and without brain damage. In addition to the association of S-100 levels with brain damage, S-100 levels between 2 hours and 48 hours predict short-term outcome after cardiac arrest.
Within the past few years, various attempts have been made
to assess brain damage in comatose patients soon after cardiac
arrest.3 4 5 6 7 8 9 10
Most of them, however, exhibit major limitations. A recent
meta-analysis of the clinical and
electrophysiological predictors of poor
outcome in anoxic-ischemic coma based on data from >4500
patients suggested that the absence of N20 components of somatosensory
evoked potentials in comatose patients with anoxic brain injury and the
absence of pain or pupillary responses at 72 hours after cardiac arrest
confirm that continuation of life support is
futile.11 The results of
early neurological and electrophysiological
evaluations, however, do not predict cerebral outcome in these
patients.11 Therefore, recent
attention focuses on biochemical markers of hypoxic brain
damage.13 14 15 16 22
To be an ideal marker for brain injury, the marker should be proved to
be released from neurons or glial cells in experimental settings, for
example cell cultures. Such proofs exist for
NSE32 but not for S-100. NSE,
however, also exists in platelets and in erythrocytes, and there is
a constant turnover of NSE in blood, making changes specifically
associated with brain damage in serum levels difficult to
evaluate.14 16
Moreover, it is well known that platelets are markedly
activated and hemolysis may occur during early reperfusion
after cardiac arrest.33
Therefore, even though at least a proportion of NSE is released from
neurons, the determination of NSE, particularly during early
reperfusion after cardiac arrest, may not be brain specific. This is in
line with the fact that NSE, as in the present study, has shown
promising results at later stages after cardiac
arrest.13 14 15 16
In contrast, release from blood cells in particular circumstances is
not the case with S-100. The presence of S-100 in serum indicates
cellular brain injury and damage to the blood-brain
barrier.25 26 27 28 29
S-100 is a protein with calcium-binding capacity. There are 19 S-100
proteins, of which S-100A1 and S-100B (formerly known as S-100
and
S-100ß, respectively) may represent a homodimer or
heterodimer.25 28 29
At least 4 of the possible subtypes are known to be
represented in human tissue: S-100A1 (striated muscles,
heart, and kidneys), S-100A1B (astroglial cells), S-100B (astroglial
and Schwann cells), and S-100BB (astroglial
cells).25 28 29
The test system used in the present study detects the ß-subunit
of S-100 and is therefore highly specific for the assessment of
astroglial injury. Astroglial cells are the most common cells in the
brain. They form a 3D network that constitutes a supporting framework
for neurons.28 29
Astroglial cells are known to be as sensitive as neurons to hypoxic
stress. Therefore, a marker for astroglial cell damage may indirectly
reflect neuronal
damage.17 18 19
Because of the estimated biological half-life of 
2
hours,23 constantly elevated
levels of S-100 in patients with documented brain damage, as observed
in the present study, may reflect a continuous release from damaged
tissue. At 48 hours after cardiac arrest, all patients with S-100
levels of >1.1 µg/L were subsequently diagnosed in the present
study as having brain damage. Interestingly, the positive and negative
predictive values of the S-100 test at 2 hours to 48 hours for fatal
outcome within 14 days were very high. This suggests that, in addition
to its association with brain damage, S-100 represents an early
marker of short-term outcome after cardiac arrest, which is in full
accordance with recent data presented by Rosen and
coworkers.22
In survivors without brain damage, the mean values of S-100 have also been found to be transiently increased during and in the early phase after CPR. Such a transient increase in S-100 serum levels can also be observed in cardiac surgical patients without cerebral symptoms during and early after extracorporeal circulation.19 20 21 At least 2 explanations for that finding exist: First, small amounts of S-100 may be released from tissue outside the brain (S-100 seems to be present, at least in a limited amount, in adipose and other tissue as well,25 28 29 and it cannot be ruled out that some early effects in other tissues can be a confounding factor). Second, temporary brain edema with blood-brain barrier dysfunction and/or minor brain damage induced by cardiac arrest and CPR may occur in patients without persistent neurological dysfunction.22 It has been demonstrated that after short periods of global cerebral ischemia due to cardiocirculatory arrest, minor patterns of brain damage can be observed. Predilection areas of minor brain damage are the selectively vulnerable areas of the brain, including the hippocampal CA1 sector, the striatum, and the thalamic reticular nucleus.34 35 In the present study, the absence of brain damage in survivors was assessed according to clinical criteria evaluated in previous studies (CPC1).1 2 31 Therefore, it cannot be excluded that minor neurological sequela like impaired memory, concentration problems, and other psycho-organic syndromes may have occurred in these patients.
The present data suggest that the determination of S-100 serum levels makes it possible to assess overall cerebral outcome and survival after cardiac arrest earlier than with any other method.11 From an ethical point of view, however, the significance of one single marker should not be overestimated. Low serum levels of S-100 after cardiac arrest should, however, prompt maximum therapeutic efforts even in patients in whom good neurological outcome is thought to be unlikely from a clinical point of view. Moreover, clinically relevant neurological impairment may not increase in a linear fashion with the amount of cell damage in the brain. Overall, the present data suggest that both biochemical markers of brain damage, NSE and S-100, could be of value in our diagnostic arsenal in difficult cases and enhance the ensemble of different diagnostic approaches.
In conclusion, astroglial protein S-100 is an early and sensitive marker of severe brain damage and short-term outcome after cardiac arrest in humans. Therefore, the determination of S-100 serum levels may help to assess comatose patients early after cardiac arrest.
|
Acknowledgments |
|---|
Dr Böttiger was supported by grants from the Medical Faculty of the University of Heidelberg and by the Deutsche Forschungsgemeinschaft (Bo 1686/1-1). The authors would like to thank the emergency staff of the German Red Cross (Heidelberg), the nursing staff of the cardiac intensive care unit (Department of Internal Medicine, University of Heidelberg), and all medical colleagues involved in the Heidelberg out-of-hospital emergency medical system (Departments of Anesthesiology and Surgery, University of Heidelberg) for their kind support. We also gratefully acknowledge the comments of 2 anonymous reviewers of the previous version of the manuscript. This article is dedicated to Prof Douglas Chamberlain on the occasion of his 70th birthday.
|
Footnotes |
|---|
Reprint requests to Bernd W. Böttiger, MD, DEAA, Associate Professor of Anesthesiology, Department of Anesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany.
Received January 25, 2001; revision received March 20, 2001; accepted March 21, 2001.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. 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.[Abstract]
2. Brain Resuscitation Clinical Trial II Study Group. A randomized clinical study of a calcium entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. N Engl J Med. 1991;324:1225–1231.[Abstract]
3.
Bassetti C, Bomio F,
Mathis J, et al. 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.
4.
Berek K, Lechleitner
P, Luef G, et al. Early determination of neurological outcome after
prehospital cardiopulmonary resuscitation.
Stroke. 1995;26:543–549.
5. Edgren E, Hedstrand U, Kelsey S, et al. Assessment of neurological prognosis in comatose survivors of cardiac arrest. BRCT I Study Group. Lancet. 1994;343:1055–1059.[Medline] [Order article via Infotrieve]
6.
Levy DE, Caronna JJ,
Singer BH, et al. Predicting outcome from hypoxic-ischemic
coma. JAMA. 1985;253:1420–1426.
7. Longstreth WT, Diehr P, Inui TS. Prediction of awakening after out-of-hospital cardiac arrest. N Engl J Med. 1983;308:1378–1382.[Abstract]
8. Madl C, Grimm G, Kramer L, et al. Early prediction of individual outcome after cardiopulmonary resuscitation. Lancet. 1993;341:855–858.[Medline] [Order article via Infotrieve]
9. Mullie A, Verstringe P, Buylaert W, et al. Predictive value of Glasgow Coma Score for awakening after out-of-hospital cardiac arrest. Cerebral Resuscitation Study Group of the Belgian Society for Intensive Care. Lancet. 1988;1:137–140.[Medline] [Order article via Infotrieve]
10. Saltuari L, Marosi M. Coma after cardiac arrest: will he recover all right? Lancet. 1994;343:1052–1053.[Medline] [Order article via Infotrieve]
11. Zandbergen EG, de Haan RJ, Stoutenbeek CP, et al. Systematic review of early prediction of poor outcome in anoxic-ischaemic coma. Lancet. 1998;352:1808–1812.[Medline] [Order article via Infotrieve]
12.
Adams JE, Bodor
GS, Davila-Roman VG, et al. Cardiac troponin I: a marker with high
specificity for cardiac injury.
Circulation. 1993;88:101–106.
13. Dauberschmidt R, Zinsmeyer J, Mrochen H, et al. Changes of neuron-specific enolase concentration in plasma after cardiac arrest and resuscitation. Mol Chem Neuropathol. 1991;14:237–245.[Medline] [Order article via Infotrieve]
14. 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.[Medline] [Order article via Infotrieve]
15. 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.[Medline] [Order article via Infotrieve]
16.
Roine RO, Somer H,
Kaste M, et al. Neurological outcome after out-of-hospital cardiac
arrest: prediction by cerebrospinal fluid enzyme analysis.
Arch Neurol. 1989;46:753–756.
17.
Herrmann M, Ebert
AD, Galazky I, et al. Neurobehavioral outcome prediction after cardiac
surgery: role of neurobiochemical markers of damage to neuronal and
glial brain tissue. Stroke. 2000;31:645–650.
18. Ingebrigtsen T, Waterloo K, Jacobsen EA, et al. Traumatic brain damage in minor head injury: relation of serum S-100 protein measurements to magnetic resonance imaging and neurobehavioral outcome. Neurosurgery. 1999;45:468–475.[Medline] [Order article via Infotrieve]
19.
Jonsson H,
Johnsson P, Alling C, et al. Significance of serum S100 release after
coronary artery bypass grafting.
Ann Thorac Surg. 1998;65:1639–1644.
20.
Kim JS, Yoon SS,
Kim YH, et al. Serial measurement of interleukin-6, transforming growth
factor-ß, and S-100 protein in patients with acute stroke.
Stroke. 1996;27:1553–1557.
21. Raabe A, Grolms C, Sorge O, et al. Serum S-100B protein in severe head injury. Neurosurgery. 1999;45:477–483.[Medline] [Order article via Infotrieve]
22.
Rosen H, Rosengren
L, Herlitz J, et al. Increased serum levels of the S-100 protein are
associated with hypoxic brain damage after cardiac arrest.
Stroke. 1998;29:473–477.
23.
Westaby S,
Johnsson P, Parry AJ, et al. Serum S100 protein: a potential marker for
cerebral events during cardiopulmonary bypass.
Ann Thorac Surg. 1996;61:88–92.
24.
Wunderlich MT,
Ebert AD, Kratz T, et al. Early neurobehavioral outcome after stroke is
related to release of neurobiochemical markers of brain damage.
Stroke. 1999;30:1190–1195.
25. Donato R. Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta. 1999;1450:191–231.[Medline] [Order article via Infotrieve]
26. Hu J, Ferreira A, Van Eldik LJ. S100beta induces neuronal cell death through nitric oxide release from astrocytes. J Neurochem. 1997;69:2294–2301.[Medline] [Order article via Infotrieve]
27. McAdory BS, Van Eldik LJ, Norden JJ. S100B, a neurotropic protein that modulates neuronal protein phosphorylation, is upregulated during lesion-induced collateral sprouting and reactive synaptogenesis. Brain Res. 1998;813:211–217.[Medline] [Order article via Infotrieve]
28. Schäfer BW, Heizmann CW. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci. 1996;21:134–140.[Medline] [Order article via Infotrieve]
29. Zimmer DB, Cornwall EH, Landar A, et al. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37:417–429.[Medline] [Order article via Infotrieve]
30.
Cummins RO,
Chamberlain DA, Abramson NS, et al. Recommended guidelines for uniform
reporting of data from out-of-hospital cardiac arrest: the Utstein
Style. A statement for health professionals from a task force of the
American Heart Association, the European Resuscitation Council, the
Heart and Stroke Foundation of Canada, and the Australian Resuscitation
Council. Circulation. 1991;84:960–975.
31. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975;1:480–484.[Medline] [Order article via Infotrieve]
32. Hans P, Bonhomme V, Collette J, et al. Neuron-specific enolase as a marker of in vitro neuronal damage, I: assessment of neuron-specific enolase as a quantitative and specific marker of neuronal damage. J Neurosurg Anesthesiol. 1993;5:111–116.[Medline] [Order article via Infotrieve]
33. Böttiger BW, Böhrer H, Böker T, et al. Platelet factor 4 release in patients undergoing cardiopulmonary resuscitation: can reperfusion be impaired by platelet activation? Acta Anaesthesiol Scand. 1996;40:631–635.[Medline] [Order article via Infotrieve]
34. Böttiger BW, Schmitz B, Wießner C, et al. Neuronal stress response and neuronal cell damage after cardiocirculatory arrest in rats. J Cereb Blood Flow Metab. 1998;18:1077–1087.[Medline] [Order article via Infotrieve]
35. Horn M, Schlote W. Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. Acta Neuropathol (Berl). 1992;85:79–87.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  J Ambrozic, M Bunc, J Osredkar, and M Brvar S100B protein in benzodiazepine overdose Emerg. Med. J., February 1, 2008; 25(2): 90 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Jauch, C. Lindsell, J. Broderick, S. C. Fagan, B. C. Tilley, S. R. Levine, and for the NINDS rt-PA Stroke Study Group Association of Serial Biochemical Markers With Acute Ischemic Stroke: The National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Stroke, October 1, 2006; 37(10): 2508 - 2513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.F.M. Wijdicks, A. Hijdra, G. B. Young, C. L. Bassetti, and S. Wiebe Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, July 25, 2006; 67(2): 203 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Part 4: Advanced Life Support Circulation, November 29, 2005; 112(22_suppl): III-25 - III-54. [Full Text] [PDF]
|
|
|
|
|
|
P Kaye Early prediction of individual outcome following cardiopulmonary resuscitation: systematic review Emerg. Med. J., October 1, 2005; 22(10): 700 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Plachky, S. Hofer, M. Volkmann, E. Martin, H. J. Bardenheuer, and M. A. Weigand Regional Cerebral Oxygen Saturation Is a Sensitive Marker of Cerebral Hypoperfusion During Orthotopic Liver Transplantation Anesth. Analg., August 1, 2004; 99(2): 344 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tiainen, R. O. Roine, V. Pettila, and O. Takkunen Serum Neuron-Specific Enolase and S-100B Protein in Cardiac Arrest Patients Treated With Hypothermia Stroke, December 1, 2003; 34(12): 2881 - 2886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Caputo, M. Yeatman, P. Narayan, G. Marchetto, R. Ascione, B. C. Reeves, and G. D. Angelini Effect of off-pump coronary surgery with right ventricular assist device on organ function and inflammatory response: a randomized controlled trial Ann. Thorac. Surg., December 1, 2002; 74(6): 2088 - 2095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Krieter, C. Denz, C. Janke, T. Bertsch, T. Luiz, K. Ellinger, and K. van Ackern Hypertonic-Hyperoncotic Solutions Reduce the Release of Cardiac Troponin I and S-100 After Successful Cardiopulmonary Resuscitation in Pigs Anesth. Analg., October 1, 2002; 95(4): 1031 - 1036. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||