Traumatic-induced coagulopathy (TIC) is a hemostatic disorder that is associated with significant bleeding, transfusion requirements, morbidity and mortality. A disorder similar or analogous to TIC was reported around 70 years ago in patients with shock, hemorrhage, burns, cardiac arrest or undergoing major surgery, and the condition was referred to as a "severe bleeding tendency," "defibrination syndrome," "consumptive disorder," and later by surgeons treating US Vietnam combat casualties as a "diffuse oozing coagulopathy." In 1982, Moore's group termed it the "bloody vicious cycle," others "the lethal triad," and in 2003 Brohi and colleagues introduced "acute traumatic coagulopathy" (ATC). Since that time, early TIC has been cloaked in many names and acronyms, including a "fibrinolytic form of disseminated intravascular coagulopathy (DIC)." A global consensus on naming is urgently required to avoid confusion. In our view, TIC is a dynamic entity that evolves over time and no single hypothesis adequately explains the different manifestations of the coagulopathy. However, early TIC is not DIC because an increased thrombin-generating potential in vitro does not imply a clinically relevant thrombotic state in vivo as early TIC is characterized by excessive bleeding, not thrombosis. DIC with its diffuse anatomopathologic fibrin deposition appears to be a latter phase progression of TIC associated with unchecked inflammation and multiple organ dysfunction.

Cardiac complication represents a major cause of morbidity and mortality after total joint arthroplasty, thus necessitating investigation into the associated risks in total hip arthroplasty and total knee arthroplasty. There remains a lack of clarity for many risk factors in the current literature. The aim of this systematic review is to assess the most recent published literature and identify the risk factors associated with cardiac complication in total hip arthroplasty and total knee arthroplasty. Scopus, PubMed, CINHAL, and Cochrane were searched to identify studies published since 2008 reporting on risk factors associated with cardiac complication in elective primary in total hip arthroplasty and total knee arthroplasty in patients ≥18 years old with osteoarthritis. Reported odds ratios, hazard ratios, and relative risk were the principal summary measures collected. The included studies were too heterogeneous to enable meta-analysis. Fifteen studies were included in this systematic review. Increasing age and history of cardiac disease were found by most studies to be positively associated with risk of cardiac complication. There was no strong association found between obesity and cardiac complication. The evidence for other risk factors was less clear in the examined literature, although there is suggestive evidence for male gender and cerebrovascular disease increasing risk. Increasing age and history of cardiac disease increases the risk of cardiac complication after total hip arthroplasty and total knee arthroplasty. Other risk factors commonly attributed to increased risk in non-cardiac surgery including hypertension and obesity require further evaluation in arthroplasty. A detailed protocol was published in the PROSPERO database (registration number CRD42018095887 ) for this systematic review.

Severe burn injury elicits a profound stress response with the potential for high morbidity and mortality. If polytrauma is present, patient outcomes appear to be worse. Sex-based comparisons indicate females have worse outcomes than males. There are few effective drug therapies to treat burn shock and secondary injury progression. The lack of effective drugs appears to arise from the current treat-as-you-go approach rather than a more integrated systems approach. In this review, we present a brief history of burns research and discuss its pathophysiology from a systems’ perspective. The severe burn injury phenotype appears to develop from a rapid and relentless barrage of damage-associated molecular patterns, pathogen-associated molecular patterns, and neural afferent signals, which leads to a state of hyperinflammation, immune dysfunction, coagulopathy, hypermetabolism, and intense pain. We propose that if the central nervous system control of cardiovascular function and endothelial-glycocalyx-mitochondrial coupling can be restored early, these secondary injury processes may be minimized. The therapeutic goal is to switch the injury phenotype to a healing phenotype by reducing fluid leak and maintaining tissue O₂ perfusion. Currently, no systems-based therapies exist to treat severe burns. We have been developing a small-volume fluid therapy comprising adenosine, lidocaine, and magnesium (ALM) to treat hemorrhagic shock, traumatic brain injury, and sepsis. Our early studies indicate that the ALM therapy holds some promise in supporting cardiovascular and pulmonary functions following severe burns. Future research will investigate the ability of ALM therapy to treat severe burns with polytrauma and sex disparities, and potential translation to humans.

New frontline drugs and therapies are urgently required to protect the body from primary and secondary injuries. We review more than 10 years of work on adenosine, lidocaine, and magnesium (ALM) and its possible significance to civilian and military medicine. Adenosine is an endogenous nucleoside involved in nucleotide production, adenosine triphosphate turnover, and restoration of supply and demand imbalances. Lidocaine is a local anesthetic and Class 1B antiarrhythmic, and magnesium is essential for ionic regulation and cellular bioenergetics. Individually, each plays important roles in metabolism, immunomodulation, inflammation, and coagulation. The original idea to combine all three was as a "polarizing" cardioplegia, an idea borrowed from natural hibernators. Two recent prospective, randomized human trials have demonstrated its safety and superiority in myocardial protection over high-potassium "depolarizing" solutions. The next idea came from witnessing how the human heart spontaneously reanimated after complex operations with little inotropic support. At high doses, ALM arrests the heart, and at lower doses, it resuscitates the heart. In rat and pig models, we have shown that ALM intravenous bolus and infusion "drip" protects against acute regional myocardial ischemia, lethal arrhythmias, cardiac arrest, compressible and noncompressible blood loss and shock, endotoxemia, and sepsis. Individually, adenosine, lidocaine, or magnesium fails to protect. Protection is afforded in part by reducing inflammation, correcting coagulopathy, and lowering energy demand. We propose a unifying hypothesis involving improved central, cardiovascular and endothelium coupling to maintain sufficient tissue oxygenation and reduce primary and secondary "hit" complications. As with any new drug innovation, translation into humans is challenging.