Optimisation of mitochondrial function as a novel target for resuscitation in haemorrhagic shock: a systematic review

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.

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.

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.

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.