Efficacy and safety of erythropoietin in patients with traumatic brain injury: A systematic review and meta-analysis

Lee, Juncheol; Cho, Youngsuk; Choi, Kyu Sun; Kim, Wonhee; Jang, Bo‐Hyoung; Shin, Hyungoo; Ahn, Chiwon; Lim, Tae Ho; Yi, Hyeong Joong

doi:10.1016/j.ajem.2018.08.072

Cited by 14 publications

(9 citation statements)

References 27 publications

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“…The RR for erythropoietin was similar to progesterone yet did not reach significance, which could indicate a power problem. This negative finding corroborates a previous meta-analysis by Lee et al including three RCTs 48 , who did show that the use of EPO may prevent death following TBI. The study by Li et al was the only positive erythropoietin study in our meta-analysis, with a large effect size of 1.89 34 .…”

Section: Discussionsupporting

confidence: 91%

Drugs with anti-inflammatory effects to improve outcome of traumatic brain injury: a meta-analysis

Begemann

Leon

Horn

et al. 2020

Sci Rep

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Outcome after traumatic brain injury (TBI) varies largely and degree of immune activation is an important determinant factor. This meta-analysis evaluates the efficacy of drugs with anti-inflammatory properties in improving neurological and functional outcome. The systematic search following PRISMA guidelines resulted in 15 randomized placebo-controlled trials (3734 patients), evaluating progesterone, erythropoietin and cyclosporine. The meta-analysis (15 studies) showed that TBI patients receiving a drug with anti-inflammatory effects had a higher chance of a favorable outcome compared to those receiving placebo (RR = 1.15; 95% CI 1.01–1.32, p = 0.041). However, publication bias was indicated together with heterogeneity (I2 = 76.59%). Stratified analysis showed that positive effects were mainly observed in patients receiving this treatment within 8 h after injury. Subanalyses by drug type showed efficacy for progesterone (8 studies, RR 1.22; 95% CI 1.01–1.47, p = 0.040), again heterogeneity was high (I2 = 62.92%) and publication bias could not be ruled out. The positive effect of progesterone covaried with younger age and was mainly observed when administered intramuscularly and not intravenously. Erythropoietin (4 studies, RR 1.20; p = 0.110; I2 = 76.59%) and cyclosporine (3 studies, RR 0.75; p = 0.189, I2 = 0%) did not show favorable significant effects. While negative findings for erythropoietin may reflect insufficient power, cyclosporine did not show better outcome at all. Current results do not allow firm conclusions on the efficacy of drugs with anti-inflammatory properties in TBI patients. Included trials showed heterogeneity in methodological and sample parameters. At present, only progesterone showed positive results and early administration via intramuscular administration may be most effective, especially in young people. The anti-inflammatory component of progesterone is relatively weak and other mechanisms than mitigating overall immune response may be more important.

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Section: Discussionsupporting

confidence: 91%

Drugs with anti-inflammatory effects to improve outcome of traumatic brain injury: a meta-analysis

Begemann

Leon

Horn

et al. 2020

Sci Rep

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“…A metaanalysis of 6 RCTs with 1041 patients (up to January 2017) looking at outcomes of EPO-treated patients vs untreated patients following acute (moderate-to-severe) TBI showed that EPO significantly reduced mortality but did not reduce rates of poor functional outcome. There were no significant differences in complication rates including deep venous thrombosis between the treatment groups [63]. Further welldesigned prospective work is required to clarify these findings and determine optimum dosage and treatment timing.…”

Section: Erythropoietinmentioning

confidence: 82%

Recent advances in traumatic brain injury

2019

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Traumatic brain injury (TBI) is the most common cause of death and disability in those aged under 40 years in the UK. Higher rates of morbidity and mortality are seen in low-income and middle-income countries making it a global health challenge. There has been a secular trend towards reduced incidence of severe TBI in the first world, driven by public health interventions such as seatbelt legislation, helmet use, and workplace health and safety regulations. This has paralleled improved outcomes following TBI delivered in a large part by the widespread establishment of specialised neurointensive care. This update will focus on three key areas of advances in TBI management and research in moderate and severe TBI: refining neurointensive care protocolized therapies, the recent evidence base for decompressive craniectomy and novel pharmacological therapies. In each section, we review the developing evidence base as well as exploring future trajectories of TBI research.

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“…With a primary role in erythroid development and maturation during hematopoiesis, EPO is now well-known for additional effects on the central nervous system, ranging from stimulation of neurogenesis through to prevention of oxidative stress, inflammation and cell death (84,85). Recent meta-analyses of EPO in clinical trials have reported that EPO may prevent mortality after TBI; however, whether EPO treatment can improve neurological and functional outcomes remains unclear (86)(87)(88). To our knowledge, no pre-clinical studies have considered the effect of EPO administration on social behavior outcomes after TBI.…”

Section: Modulating Secondary Injury Processes: Neuroinflammation and Oxidative Stressmentioning

confidence: 99%

A Pro-social Pill? The Potential of Pharmacological Treatments to Improve Social Outcomes After Pediatric Traumatic Brain Injury

Semple

Raghupathi

2021

Front. Neurol.

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Traumatic brain injury (TBI) is a leading cause of injury-induced disability in young children worldwide, and social behavior impairments in this population are a significant challenge for affected patients and their families. The protracted trajectory of secondary injury processes triggered by a TBI during early life—alongside ongoing developmental maturation—offers an extended time window when therapeutic interventions may yield functional benefits. This mini-review explores the scarce but promising pre-clinical literature to date demonstrating that social behavior impairments after early life brain injuries can be modified by drug therapies. Compounds that provide broad neuroprotection, such as those targeting neuroinflammation, oxidative stress, axonal injury and/or myelination, may prevent social behavior impairments by reducing secondary neuropathology. Alternatively, targeted treatments that promote affiliative behaviors, exemplified by the neuropeptide oxytocin, may reduce the impact of social dysfunction after pediatric TBI. Complementary literature from other early life neurodevelopmental conditions such as hypoxic ischemic encephalopathy also provides avenues for future research in neurotrauma. Knowledge gaps in this emerging field are highlighted throughout, toward the goal of accelerating translational research to support optimal social functioning after a TBI during early childhood.

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Efficacy and safety of erythropoietin in patients with traumatic brain injury: A systematic review and meta-analysis

Cited by 14 publications

References 27 publications

Drugs with anti-inflammatory effects to improve outcome of traumatic brain injury: a meta-analysis

Drugs with anti-inflammatory effects to improve outcome of traumatic brain injury: a meta-analysis

Recent advances in traumatic brain injury

A Pro-social Pill? The Potential of Pharmacological Treatments to Improve Social Outcomes After Pediatric Traumatic Brain Injury

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