Limitations
traumatic hemorrhagic shock, traumatic injuries, shock/resuscitation, hemorrhagic shock, ischemia/reperfusion injury, trauma
HEMORRHAGIC SHOCK
Despite a wealth of preclinical evidence pointing to the therapeutic effect of RIC in ischemia/reperfusion injury, translation to the clinical setting has been difficultThe nature of traumatic injuries and patient triage/transfer to our trauma centre affected our ability to precisely control the timing of initial RIC application across all patients as it relates to time after injury. Patients from our study had a median time of application at 2 h after injury, likely representing the post-resuscitative phase of injury. While there is no definitive clinical evidence to suggest the delayed application of RIC influences its protective effect, animal studies from our lab have shown that delaying RIC after shock/resuscitation in the early reperfusion period can diminish its protective effectThe heterogeneity in trauma patients results in a number of clinical characteristics that significantly differ between each patient. These include the number of blood products transfused, surgical procedures, and anesthesia regimens. Each of these variables can contribute to a different immunological responsePrevious studies in healthy volunteers that demonstrated the anti-inflammatory effect of RIC on leukocyte gene expression utilized the arm to conduct RICActivation of the vago-splenic axis has been shown by Lieder et al. to be causally involved in cardioprotection by RIC, implicating the spleen as a critical relay organ for its protective signalingIn summary, our study was the first trial to investigate the immunomodulatory effect of RIC in humans sustaining traumatic hemorrhagic shock. We demonstrate that post-trauma application of RIC in hemorrhagic shock patients is safe, feasible and not associated with adverse outcomes. Although RIC induced anti-inflammatory effects in neutrophils taken from healthy volunteers, this effect was not recapitulated in trauma patients, which may in part be due to confounding factors, including the timing of the intervention. However, RIC prevented the increase in Th2 cytokines that are associated with immunosuppression. Results from our preliminary study in trauma patients in hemorrhagic shock suggest further investigation into the possible immunomodulatory mechanisms of RIC on the post-trauma immuno-inflammatory response and its impact on clinical parameters.