Use of prophylactic antibiotic in preventing complications for blunt and penetrating chest trauma requiring chest drain insertion: a systematic review and meta-analysis.

BACKGROUND: Chest drain insertion after chest trauma is often associated with high rate of complications. The use of prophylactic antibiotics in patients with blunt and penetrating chest trauma to prevent empyema and pneumonia after chest drain insertion has been debated. OBJECTIVE: To analyze the effectiveness of prophylactic antibiotics versus placebo to prevent complications in patients with blunt and penetrating chest injuries who require the insertion of a chest drain. METHODS: Pubmed, Embase, and grey literature databases were searched during May 2017 for randomized clinical trails comparing prophylactic antibiotic versus placebo in patients with chest injuries requiring chest drain insertion. Good quality randomized studies which met the inclusion criteria were assessed using the Cochrane Collaboration tool for assessing risk of bias and then were included in the systematic review. A meta-analysis of the included studies was concluded using Stata to analyze the relative risk of empyema and pneumonia in these patients. RESULTS: The study identified 12 randomized studies that included 1263 patients with isolated blunt and penetrating chest trauma. The incidence of empyema after a chest drain insertion was 1% in the antibiotic group and 7.2% in the placebo group. The incidence of pneumonia after a chest drain insertion was 4.4% in the antibiotic group and 10.7% in the placebo group. The use prophylactic antibiotic in those patients was associated with a reduced risk of empyema (relative risk [RR] 0.25; 95% CI 0.13 to 0.49) and pneumonia (RR 0.41; 95% CI 0.24 to 0.71) after chest drain insertion when compared with placebo alone. CONCLUSION: Prophylactic antibiotic administration in patients with penetrating and blunt chest injuries requiring the insertion of a chest drain was associated with a reduced risk for post-traumatic empyema and pneumonia. Further studies should evaluate the optimal type, dose, and duration of antibiotic given to patients with chest trauma requiring chest drain insertion.

Activated Protein C Drives the Hyperfibrinolysis of Acute Traumatic Coagulopathy.

BACKGROUND: Major trauma is a leading cause of morbidity and mortality worldwide with hemorrhage accounting for 40% of deaths. Acute traumatic coagulopathy exacerbates bleeding, but controversy remains over the degree to which inhibition of procoagulant pathways (anticoagulation), fibrinogen loss, and fibrinolysis drive the pathologic process. Through a combination of experimental study in a murine model of trauma hemorrhage and human observation, the authors' objective was to determine the predominant pathophysiology of acute traumatic coagulopathy. METHODS: First, a prospective cohort study of 300 trauma patients admitted to a single level 1 trauma center with blood samples collected on arrival was performed. Second, a murine model of acute traumatic coagulopathy with suppressed protein C activation via genetic mutation of thrombomodulin was used. In both studies, analysis for coagulation screen, activated protein C levels, and rotational thromboelastometry (ROTEM) was performed. RESULTS: In patients with acute traumatic coagulopathy, the authors have demonstrated elevated activated protein C levels with profound fibrinolytic activity and early depletion of fibrinogen. Procoagulant pathways were only minimally inhibited with preservation of capacity to generate thrombin. Compared to factors V and VIII, proteases that do not undergo activated protein C-mediated cleavage were reduced but maintained within normal levels. In transgenic mice with reduced capacity to activate protein C, both fibrinolysis and fibrinogen depletion were significantly attenuated. Other recognized drivers of coagulopathy were associated with less significant perturbations of coagulation. CONCLUSIONS: Activated protein C-associated fibrinolysis and fibrinogenolysis, rather than inhibition of procoagulant pathways, predominate in acute traumatic coagulopathy. In combination, these findings suggest a central role for the protein C pathway in acute traumatic coagulopathy and provide new translational opportunities for management of major trauma hemorrhage.

Assessing the damage control resuscitation: development, drivers and direction.

Damage control resuscitation (DCR) has become a more widely adopted acute management strategy over the past decade. A cornerstone of this strategy is the performance of an initial limited surgical intervention for the control of active bleeding and contamination. This technique is indicated where significant physiological compromise exists and immediate surgical intervention is required. This damage control surgery itself is completed judiciously to allow a period of resuscitative stabilisation before later definitive surgical solutions. This discussion describes the three further principles of DCR and then explores the rationale and drivers behind the development of this approach.

Recurrent acute lower-limb ischemia with multiple organ infarctions secondary to acute myeloid leukaemia M1.

BACKGROUND: Acute myeloid leukemia (AML) is usually associated with coagulopathy and disorders of hemostasis, but cases of ischemic events have been reported. We present a case of AML with recurrent acute limb ischemia and multiple organ infarctions. METHODS AND RESULTS: A 57-year-old woman diagnosed with AML subtype M1 developed recurrent bilateral acute lower-limb ischemia refractory to multiple thromboembolectomies and bypass grafting. Histopathology revealed that thrombi were composed of leukemic blasts, and computed tomography angiogram incidentally revealed multiple infarctions. She demonstrated a response to chemotherapy, but died of an overwhelming sepsis 22 days after her acute admission. CONCLUSIONS: AML subtype M1 with acute lower-limb ischemia and multiple organ infarctions is associated with a poor prognosis. The role of emergency chemotherapy in reducing the tumour burden and possibly improving the results of vascular interventions needs to be defined. Limb-salvaging surgery should not be delayed but be administered immediately according to the degree of ischemia.

The pathophysiology of trauma-induced coagulopathy.

PURPOSE OF REVIEW: Transfusion paradigms and protocols have evolved at a rapid pace in the last few years to ameliorate the adverse effects of trauma-induced coagulopathy (TIC). This has occurred despite fragmented and inadequate knowledge of the underlying pathophysiology that they are supposed to treat. This review will collate and assimilate the most recent data about TIC in order to present our state-of-the-art understanding of this condition. RECENT FINDINGS: TIC was conventionally construed simply as depletion, dysfunction or dilution of procoagulant factors. However, contemporary understanding recognizes it as an imbalance of the dynamic equilibrium between procoagulant factors, anticoagulant factors, platelets, endothelium and fibrinolysis. The endogenous component of TIC (acute traumatic coagulopathy) is not merely a consumptive coagulopathy, but is characterized by isolated factor V inhibition, dysfibrinogenaemia, systemic anticoagulation, impaired platelet function and hyperfibrinolysis. Acute traumatic coagulopathy then becomes exacerbated by hypothermia, acidosis and resuscitation with hypocoagulable fluids. SUMMARY: Further improvement in the outcome from trauma-haemorrhage is possible with more refined and tailored haemostatic resuscitation. Achieving this will depend upon a better understanding of the haemostatic defects that develop after injury.

Acute traumatic coagulopathy.

PURPOSE OF REVIEW: Recent therapeutic and observational studies have demonstrated improved survival with better management of haemostasis early after injury. This review delineates our current understanding of the clinical importance, aetiology and pathophysiology of acute traumatic coagulopathy (ATC). RECENT FINDINGS: Trauma causes an acute disruption of the equilibrium between all components of haemostasis (coagulation, anticoagulation, fibrinolysis, platelets and endothelium). In patients with a combination of severe tissue damage and systemic hypoperfusion, this will progress rapidly to an endogenous coagulopathy that is independently associated with worse outcomes. New discoveries of the interactions between neurohormonal, vascular, and coagulation systems are beginning to explain how this haemostatic impairment develops and offer novel targets for therapeutic manipulation. Routine coagulation screening tests are ineffective for diagnosing ATC and guiding resuscitation in real-time. Viscoelastic coagulation tests (such as ROTEM or TEG) have emerged as practical, rapid and sensitive diagnostic modalities. Their role in therapeutic targeting requires further validation. SUMMARY: Conventional concepts of traumatic coagulopathy as a late occurring condition in response to iatrogenic haemodilution are redundant. ATC is an endogenous impairment of haemostasis that begins at the moment of injury. Further outcome improvements are possible with better understanding of the process by which this coagulopathy develops and how it may be inhibited.

Animal models of trauma-induced coagulopathy.

Resurgent study of trauma-induced coagulopathy (TIC) has delivered considerable improvements in survival after injury. Robust, valid and clinically relevant experimental models of TIC are essential to support the evolution of our knowledge and management of this condition. The aims of this study were to identify and analyze contemporary animal models of TIC with regard to their ability to accurately characterize known mechanisms of coagulopathy and/or to test the efficacy of therapeutic agents. A literature review was performed. Structured search of the indexed online database MEDLINE/PubMed in July 2010 identified 43 relevant articles containing 23 distinct animal models of TIC. The main aim of 26 studies was to test a therapeutic and the other 17 were conducted to investigate pathophysiology. A preponderance of porcine models was identified. Three new models demonstrating an endogenous acute traumatic coagulopathy (ATC) have offered new insights into the pathophysiology of TIC. Independent or combined effects of induced hypothermia and metabolic acidosis have been extensively evaluated. Recently, a pig model of TIC has been developed that features all major etiologies of TIC, although not in correct chronological order. This review identifies a general lack of experimental research to keep pace with clinical developments. Tissue injury and hemorrhagic shock are fundamental initiating events that prime the hemostatic system for subsequent iatrogenic insults. New animal models utilizing a variety of species that accurately simulate the natural clinical trajectory of trauma are urgently needed.

Sir Victor Horsley's 19th century operations at the National Hospital for Neurology and Neurosurgery, Queen Square.

Although he was not the first man to operate on the brain, Sir Victor Horsley was the world's first surgeon appointed to a hospital post to perform brain surgery, which happened in 1886 at the National Hospital for Neurology and Neurosurgery, Queen Square, London. The authors examined the patient records between 1886 and 1899 and found 151 operations performed by Sir Victor Horsley at the National Hospital, including craniotomies, laminectomies, and nerve divisions. The authors present the outcome data and case illustrations of cerebral tumor resections and laminectomies from the nineteenth century. Outcomes and notable pioneering achievements are highlighted.

The acute coagulopathy of trauma shock: clinical relevance.

Recent observational studies have identified an acute coagulopathy in trauma victims that is present on arrival in the emergency room. It has been associated with a four-fold increase in mortality and increased incidence of organ failure. Conventional trauma resuscitation and transfusion protocols are designed for dilutional coagulopathy and appear inadequate in the management of acute traumatic coagulopathy and massive transfusion. Acute Coagulopathy of Trauma Shock (ACoTS) is caused by a combination of tissue injury and shock, and may occur without significant fluid administration, clotting factor depletion or hypothermia. The mechanism through which acute coagulopathy develops is unclear but activation of the protein C pathway has been implicated. Standard coagulation tests do not identify cases in a timely fashion and ACoTS should be suspected in any trauma patient with a significant magnitude of injury and shock, as evidenced by an abnormal admission base deficit on blood gas. Development of point of care coagulometers and whole blood coagulation analysers, such as rotational thromboelastometry, may enable earlier laboratory identification of this group. Retrospective studies performed by the American military indicate that resuscitation of severely injured patients with higher ratios of plasma given early may improve outcome and reduce overall blood product use. The place of adjunctive pharmaceutical agents within this strategy remains unclear. There is an acute coagulopathy associated with trauma and shock that is an independent predictor of outcomes. Delineation of this entity, with directed management protocols should lead to a reduction in avoidable deaths from haemorrhage after trauma.

Increase in activated protein C mediates acute traumatic coagulopathy in mice.

In severely injured and hypoperfused trauma patients, endogenous acute coagulopathy (EAC) is associated with an increased morbidity and mortality. Recent human data correlate this coagulopathy with activation of the protein C pathway. To examine the mechanistic role of protein C in the development of EAC, we used a mouse model of trauma and hemorrhagic shock, characterized by the combination of tissue injury and severe metabolic acidosis. Mice were subjected to one of four treatment groups: 1) C, control; 2) T, trauma (laparotomy); 3) H, hemorrhage (MAP, 35 mmHg x 60 min); 4) TH, trauma + hemorrhage. After 60 min, blood was drawn for analysis. Compared with C mice, the TH mice had a significantly elevated activated partial thromboplastin time (23.3 vs. 34.5 s) and significantly increased levels of activated protein C (aPC; 2.30 vs. 13.58 ng/mL). In contrast, T and H mice did not develop an elevated activated partial thromboplastin time or increased aPC. Selective inhibition of the anticoagulant property of aPC prevented the coagulopathy seen in response to trauma/hemorrhage (23.5 vs. 38.6 s [inhibitory vs. control monoclonal antibody]) with no impact on survival during the shock period. However, complete blockade of both the anticoagulant and cytoprotective functions of aPC caused 100% mortality within 45 min of shock, with histopathology evidence of pulmonary thrombosis and perivascular hemorrhage. These results indicate that our unique mouse model of T/H shock mimics our previous observations in trauma patients and demonstrates that EAC is mediated by the activation of the protein C pathway. In addition, the cytoprotective effect of protein C activation seems to be necessary for survival of the initial shock injury.