A Systematic Review of Neuroprotective Strategies during Hypovolemia and Hemorrhagic Shock

Int J Mol Sci. 2017 Oct 26;18(11):2247. doi: 10.3390/ijms18112247.


Severe trauma constitutes a major cause of death and disability, especially in younger patients. The cerebral autoregulatory capacity only protects the brain to a certain extent in states of hypovolemia; thereafter, neurological deficits and apoptosis occurs. We therefore set out to investigate neuroprotective strategies during haemorrhagic shock. This review was performed in accordance to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Before the start of the search, a review protocol was entered into the PROSPERO database. A systematic literature search of Pubmed, Web of Science and CENTRAL was performed in August 2017. Results were screened and evaluated by two researchers based on a previously prepared inclusion protocol. Risk of bias was determined by use of SYRCLE's risk of bias tool. The retrieved results were qualitatively analysed. Of 9093 results, 119 were assessed in full-text form, 16 of them ultimately adhered to the inclusion criteria and were qualitatively analyzed. We identified three subsets of results: (1) hypothermia; (2) fluid therapy and/or vasopressors; and (3) other neuroprotective strategies (piracetam, NHE1-inhibition, aprotinin, human mesenchymal stem cells, remote ischemic preconditioning and sevoflurane). Overall, risk of bias according to SYRCLE's tool was medium; generally, animal experimental models require more rigorous adherence to the reporting of bias-free study design (randomization, etc.). While the individual study results are promising, the retrieved neuroprotective strategies have to be evaluated within the current scientific context-by doing so, it becomes clear that specific promising neuroprotective strategies during states of haemorrhagic shock remain sparse. This important topic therefore requires more in-depth research.

Keywords: bleeding; brain damage; haemorrhage; hypovolemia; neuroprotection; neuroprotective strategies; resuscitation; shock.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Epinephrine / therapeutic use
  • Fluid Therapy / methods
  • Humans
  • Hypothermia, Induced / methods
  • Hypovolemia / physiopathology
  • Hypovolemia / therapy*
  • Ischemic Preconditioning / methods
  • Mesenchymal Stem Cell Transplantation / methods
  • Resuscitation / methods
  • Shock, Hemorrhagic / physiopathology
  • Shock, Hemorrhagic / therapy*
  • Treatment Outcome
  • Vasopressins / therapeutic use


  • Vasopressins
  • Epinephrine