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. Design: A meta-analysis of prognostic studies in anoxic-ischaemic coma, selected from Medline and EMBASE databases, according to predefined criteria. Subjects: 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. Main outcome measures: Poor outcome, defined as death or vegetative state, versus good outcome, defined as any other outcome state. Analyses: 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 nontreatment decisions.