Erythropoietin
Erythropoietin (EPO) is a glycoprotein hormone that primarily controls red blood cell production. Interest in utilizing this pharmaceutical agent to treat acute SCI stems from one of its most commonly studied secondary functions, the prevention of neuronal apoptosis in the presence of ischemia (Siren et al. 2001). Even less well understood, EPO has been shown to elicit anti-inflammatory properties, minimize lipid peroxidation, scavenge free radicals, regenerate axons, and reduce calcium ions and influx of glutamate in in vitro and in vivo animal studies (Matis & Birbilis 2009). Experimental SCI studies in animal models to date have shown that EPO elicits a neuroprotective benefit that contributes to neurological recovery (Hong et al. 2011; Okutan et al. 2007). To date, there are four studies that have evaluated EPO for possible neuroprotection after SCI in humans.
| Author Year
Country Research Design PEDro Sample Size |
Methods | Outcomes |
| Alibai et al. 2015
Iran RCT PEDro= 8 Ninitial= 27, Nfinal= 20 |
Population: Mean age= 40.1±9.5yr; Gender: male= 90%, female= 10%; Level of injury: cervical; Severity of injury: complete= 60%, incomplete= 40%
Treatment: Patients were first administered methylprednisolone per standard protocol. Patients were then randomly assigned to receive erythropoietin or placebo. The EPO dosage was 500 IU/mL immediately and 24 hours later. Outcome Measures: Assessed baseline, 1, 6, and 12 months post-injury: ASIA sensory and motor scores. Chronicity: Individuals were studied within 8 hr of sustaining injury. |
|
| Costa et al. 2015
Italy RCT PEDro= 7 Ninitial= 19, Nfinal= 19 |
Population: Mean age= 27.67y Gender: male= 94.7%, female= 5.3%; Level of injury: cervical, thoracic; Severity of injury: AIS A or B
Treatment: Participants were randomized to receive either methylprednisolone or erythropoietin treatment groups for 48 hours. Outcome Measures: ASIA motor and sensory, MAS, Penn Score, VAS, SCIM. Evaluated at baseline, day 3, 7, 14, 30, 60, and 90. Chronicity: Screened and enrolled within 8 hours of sustaining injury. |
|
| Alibai et al. 2014
Iran RCT PEDro=6 N=30 |
Population: Age range=18-65 yr; Gender: male=77%, female=23%; Level of injury: cervical-thoracic; Severity of injury: complete=47%, incomplete=53%.
Treatment: Patients were randomly assigned to receive either recombinant human erythropoietin (rhEPO) + methylprednisolone sodium succinate (MPSS; 500 unit/kg of rhEPO) or placebo + MPSS. MPSS was administered according to National Acute Spinal Cord Injury Study (NASCIS) III guidelines. Outcome Measures: The following after 1 week, 1 month, and 6 months: neurological recovery using the AIS. The following after 6 months: sexual dysfunction. Chronicity: Individuals studied were admitted to hospital within less than 6 hr after trauma. |
|
| Xiong et al. 2011
China Prospective Control Trial N=63 |
Population: Mean age=53 yr; Gender: male=62%, female=38%; Level of injury: cervical-thoracic; Severity of injury: complete=14%, incomplete=86%.
Treatment: Patients who developed ischemia-reperfusion injuries during spinal decompression surgery received either erythropoietin (EPO) + methylprednisolone (MP) or MP alone. MP was delivered intravenously according to National Acute Spinal Cord Injury Study (NASCIS) II guidelines. EPO was injected intramuscularly three times a week (3000U/vial) for 8 weeks. Outcome Measures: The following after 1 week, 1 year, and 2 years: neurological recovery using ASIA score (motor function and sensory function), activities of daily living (ADLs), and adverse event outcomes. Chronicity: Individuals were studied at 1 week, 1 year and 2 years post spinal surgery. |
|
Discussion
Although two early unblinded studies showed promising results for EPO in treating acute SCI (Alibai et al. 2014, Xiong et al. 2011), two subsequent, blinded studies failed to demonstrate benefit to EPO for neurologic outcomes post-SCI. It is important to note that all studies had very small sample sizes (n<70) and that in the positive trials, participants were neither blinded nor randomized. Both studies using randomized double-blind (Alibai et al. 2015) or single-blind (Costa et al. 2015) methodology did not detect a statistically significant difference between EPO and control, although sample sizes were small (n<30) and may have been underpowered to detect a difference. Large-scale blinded RCTs are warranted to determine the effectiveness of EPO in treating acute SCI. At present, there are no guidelines that recommend the use of EPO for neuroprotection in the acute phase of SCI.
Conclusion
There is level 1a evidence (from one double-blind RCT: Alibai et al. 2015; and one single-blind RCT: Costa et al. 2015) that acute administration of erythropoietin does not improve neurological outcomes post-SCI.
There is level 1b evidence (from one RCT: Alibai et al. 2014; and one prospective controlled trial: Xiong et al. 2011) that erythropoietin is effective in promoting neurological recovery in acute SCI individuals.
