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Optimisation of mitochondrial function as a novel target for resuscitation in haemorrhagic shock: a systematic review
  1. Laura Cottey1,
  2. J E Smith1,2 and
  3. S Watts3
  1. 1Academic Department of Military Emergency Medicine, Royal Centre for Defence Medicine, Birmingham, UK
  2. 2Emergency Department, University Hospitals Plymouth NHS Trust, Plymouth, UK
  3. 3Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory, Salisbury, UK
  1. Correspondence to Surg Lt Cdr Laura Cottey, Academic Department of Military Emergency Medicine, Royal Centre for Defence Medicine, Birmingham, BS15 2SQ, UK; laura.cottey{at}nhs.net

Abstract

Introduction Traumatic injury is one of the leading causes of death worldwide, and despite significant improvements in patient care, survival in the most severely injured patients remains unchanged. There is a crucial need for innovative approaches to improve trauma patient outcomes; this is particularly pertinent in remote or austere environments with prolonged evacuation times to definitive care. Studies suggest that maintenance of cellular homeostasis is a critical component of optimal trauma patient management, and as the cell powerhouse, it is likely that mitochondria play a pivotal role. As a result, therapies that optimise mitochondrial function could be an important future target for the treatment of critically ill trauma patients.

Methods A systematic review of the literature was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to determine the potential role of mitochondria in traumatic injury and haemorrhagic shock (HS) and to identify current evidence for mitochondrial optimisation therapies in trauma. Articles were included if they assessed a mitochondrial targeted therapy in comparison to a control group, used a model of traumatic injury and HS and reported a method to assess mitochondrial function.

Results The search returned 918 articles with 37 relevant studies relating to mitochondrial optimisation identified. Included studies exploring a range of therapies with potential utility in traumatic injury and HS. Therapies were categorised into the key mitochondrial pathways impacted following traumatic injury and HS: ATP levels, cell death, oxidative stress and reactive oxygen species.

Conclusion This systematic review provides an overview of the key cellular functions of the mitochondria following traumatic injury and HS and identifies why mitochondrial optimisation could be a viable and valuable target in optimising outcome in severely injured patients in the future.

  • TRAUMA MANAGEMENT
  • Adult intensive & critical care
  • ACCIDENT & EMERGENCY MEDICINE
  • THERAPEUTICS

Data availability statement

Data are available upon reasonable request. Data are available on reasonable request from the corresponding author.

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Data availability statement

Data are available upon reasonable request. Data are available on reasonable request from the corresponding author.

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Footnotes

  • Twitter @lauracottey, @DefProfEM

  • Contributors All authors were involved in the conception and design. LC undertook the search strategy, data extraction and is the guarantor for the publication. All authors were involved in the writing and final approval of the manuscript.

  • Funding This research was undertaken as part of a Ministry of Defence funded PhD.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.