Adjuvant therapies for management of hemorrhagic shock: a narrative review

Abstract

Severe bleeding remains a leading cause of death in patients with major trauma, despite improvements in care during the acute phase, especially the application of damage control concepts. Death from hemorrhage occurs rapidly after the initial trauma, in most cases before the patient has had a chance to reach a hospital. Thus, the development of adjuvant drugs that would increase the survival of injured patients is necessary. Among the many avenues of research in this area, one is to improve cell survival during tissue hypoxia. During hemorrhagic shock, oxygen delivery to cells decreases and, despite increased oxygen extraction, anaerobic metabolism occurs, leading to acidosis, coagulopathy, apoptosis, and organ dysfunction. We selected six treatments that may help cells cope with this situation and could be used as adjuvant therapies during the initial resuscitation of severe trauma patients, including out-of-hospital settings: niacin, thiazolidinediones, prolyl hydroxylase domain inhibitors, O-GlcNAcylation stimulation, histone deacetylase inhibitors, and adenosine–lidocaine–magnesium solution. For each treatment, the biological mechanism involved and a systematic review of its interest in hemorrhagic shock (preclinical data and human clinical trials) are presented. Promising molecules, some of which are already used in humans for other indications, give us hope for human clinical trials in the field of hemorrhagic shock in the near future.