Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage.
OBJECTIVE
To investigate whether accurate prognostic rules can be derived from the combined results of studies concerning prediction of poor prognosis in anoxic-ischaemic coma with biochemical markers of brain damage in cerebrospinal fluid (CSF) or serum.


METHODS
A meta-analysis of prognostic studies in anoxic-ischaemic coma, selected from Medline and EMBASE databases, according to predefined criteria.


METHODS
Twenty-eight studies, with a total of 802 unselected, consecutive patients, in which tests, sampling time and outcome measures were described unequivocally and results were described using clear cut-off values or raw data.


METHODS
Poor outcome, defined as death or vegetative state, versus good outcome, defined as any other outcome state.


METHODS
The overall prognostic accuracy of these variables was expressed as the 95% CIs of the pooled false-positive test rate and the pooled positive-likelihood ratios.


RESULTS
Only markers in CSF (creatine kinase isoenzyme (CKBB) >204 U/l, neuron specific enolase (NSE) >33 ng/ml, lactate dehydrogenase (LDH) >82 U/l and glutamate oxaloacetate (GOT) >62 U/l) reached a 0% false-positive rate. However, due to small sample sizes, the confidence limits were wide. The accuracy of prediction of poor outcome seemed acceptably high for CSF-CKBB (pooled false-positive rate 0% [95% CI 0-2.3%]; pooled positive-likelihood ratio 33.2 [95% CI 4.8-230.2]), but this result was based on two retrospective studies without blinding of the treating physicians for the test result.


CONCLUSIONS
Because of small numbers of patients studied and methodological limitations the combined results are not sufficiently accurate to provide a solid basis for non-treatment decisions.
Zandbergen
E G
EG
Department of Neurology and Clinical Neurophysiology, Academic Medical Centre/University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
de Haan
R J
RJ
Hijdra
A
A
D001219:Aspartate Aminotransferases / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D002545:Brain Ischemia / Q000150:complications*; D003128:Coma / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality; D003402:Creatine Kinase / Q000097:blood / Q000134:cerebrospinal fluid; D052276:Creatine Kinase, BB Form; D005189:False Positive Reactions; D006801:Humans; D002534:Hypoxia, Brain / Q000150:complications*; D007527:Isoenzymes / Q000097:blood / Q000134:cerebrospinal fluid; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000134:cerebrospinal fluid; D016013:Likelihood Functions; D010751:Phosphopyruvate Hydratase / Q000097:blood / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards; D018401:Sample Size; D013997:Time Factors
D015415:Biomarkers; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D052276:Creatine Kinase, BB Form; D010751:Phosphopyruvate Hydratase