Erythropoietin in patients with aneurysmal subarachnoid haemorrhage: a double blind randomised clinical trial.
BACKGROUND
Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH.


METHODS
A larger scale clinical trial was planned but preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i.e. transcranial Doppler (TCD) flow velocity, symptomatic vasospasm, cerebral metabolism (microdialysis) and jugular venous oximetry, biochemical markers of brain damage (S-100beta and neuron specific enolase) and blood-brain barrier integrity.


RESULTS
The limited sample size precluded our primary hypotheses being verified and refuted. However, data from this study are important for any other study of SAH and as much raw data as possible are presented and can be included in future meta analyses. On admission the proportion of patients in a poor condition was higher in the EPO group compared with the placebo group but the difference was statistically insignificant. In the EPO-treated patients the CSF concentration of EPO increased 600-fold. Except for a higher extracelullar concentration of glycerol in the EPO group probably caused by the poorer clinical condition of these patients, there were no statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated.


CONCLUSIONS
Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted.
Springborg
J B
JB
Department of Neuroanaesthesia, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark. jacob.springborg@rh.hosp.dk
Møller
C
C
Gideon
P
P
Jørgensen
O S
OS
Juhler
M
M
Olsen
N V
NV
D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D001925:Brain Damage, Chronic; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D023261:Glasgow Outcome Scale; D006397:Hematinics / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D002532:Intracranial Aneurysm / Q000150:complications* / Q000401:mortality / Q000601:surgery; D008279:Magnetic Resonance Imaging; D008297:Male; D017551:Microdialysis; D008866:Microsurgery; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects; D011292:Premedication; D011994:Recombinant Proteins; D013345:Subarachnoid Hemorrhage / Q000175:diagnosis / Q000188:drug therapy*; D014057:Tomography, X-Ray Computed; D017585:Ultrasonography, Doppler, Transcranial
D006397:Hematinics; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa