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In patients with severe sepsis, ADAMTS-13 may be one of the key players in altered endothelial function and procoagulant activity. Because the methods for detection of an altered vWF-biofunctionality as well as the proteolytic activity of ADAMTS-13 are complex and elaborate there is need for the development of rapid and reliable methods to detect the presence of ULvWF multimers in human plasma.

The potential beneficial effects of protease supplementation appear to result from at least two distinct properties: reconstitution of ULvWF multimer proteolysis may prevent formation of vWF-rich platelet aggregates and lower the tethering and rolling of leukocytes via platelet-decorated vWF-strings. Future studies are needed to elucidate to what extent these properties of ADAMTS-13 are associated with a potential benefit in patients with severe sepsis.

The pathophysiology of coagulopathy in the trauma patient is complex and multifactorial. The term ‘DIC’ is incorrectly used to define trauma-related coagulopathy. Although the routine laboratory results resemble those of DIC because they detect activation of coagulation and fibrinolysis and consumption of platelets and coagulation factors, the pathophysiology of the coagulopathy is quite different. While DIC reflects a hypercoagulable state with loss of localization of the coagulation process, leading to diffuse deposition of fibrin, trauma-related coagulopathy is a hypocoagulable state with fibrin deposition limited to the site of injury. The use of the right terms is not only a semantic issue but has major implications for treatment. In fact this was the main reason for the delay in introduction of rFVIIa to trauma patients a few years after its introduction to hemophilia and bleeding disorders: The use of agents markedly enhancing hemostasis, such as rFVIIa, in patients already suffering from a hypercoagulable state seemed to be risky. Much of the early data in the literature are not applicable due to the change of blood components and transfusion policy in the modern area of trauma patient resuscitation. A multidisciplinary approach involving anesthesiologists, transfusion specialists, hematologists, laboratory specialists and surgeons is required for the diagnosis and treatment of traumatic bleeding.

Hemorrhage in blunt trauma usually derives from many contemporary bleeding sites, which may be stopped with surgery or interventional radiology. Protocol-driven management of specific injuries is mandatory to achieve the best results when a multi-disciplinary team is at work. However, a significant amount of blood loss may derive from small interrupted vessels, not amenable to surgical or angiographic control, especially in the case of traumatic coagulopathy. A pharmacological approach may be indicated to stop this so-called non-mechanical bleeding. Based on available data and on our experience, rFVIIa is a safe and useful adjunctive treatment to standard therapies in the management of critical hemorrhage in a selected trauma population. The drug is extremely expensive, but if it works and if we consider potential reduction of ICU days and, ultimately, life preservation, it may become a cost-effective treatment. However, large, prospective randomized, phase 3 trials are needed to answer some unresolved questions including optimal timing of administration, dosing and number of doses.

The resuscitation of patients with trauma and hemorrhagic shock has improved over recent years but there is still a need to control bleeding that cannot be corrected surgically, particularly coagulopathic bleeding, in order to reduce the morbidity and mortality associated with major trauma.

Although blood component therapy remains the mainstay of management for coagulopathic bleeding, and RBC transfusion can be life-saving, many patients remain at risk of exsanguination, and there are well-documented post-injury problems associated with high rates of RBC transfusion in trauma. Hemostatic agents may offer effective adjunctive control in cases of coagulopathic bleeding, helping to reduce the reliance on transfusion and potentially decreasing the morbidity and mortality burden.

Blood transfusion therapy is unlikely to be replaced completely, but the role of new agents capable of improving bleeding control in emergency settings clearly warrants close consideration and further study.

Component therapy is useful for the majority of patients when blood requirements are minimal and there is no associated coagulopathy. Of concern are requirements for massive transfusion and resuscitation that absorb resources and create a short-fall for patients whose injuries are less severe. Additionally, the conventional massive transfusion model of packed RBCs, plasma and platelets actually further dilutes the patient compared to the blood he or she has lost and thus is not the ideal fluid for patients who require this massive transfusion of products. Fresh whole blood has three vital properties: oxygen carrying capacity, volume, and hemostatic effect. In the austere environment of combat the practice of fresh whole blood transfusion has proven beneficial to patients who are coagulopathic and require massive transfusion. Appropriate use following established guidelines can be beneficial and may even be superior to packed RBCs. A fluid containing the vital properties of fresh whole blood would serve as a bridge to allow a patient to be resuscitated without initiating the ‘bloody cycle of death’ that is seen all too often in our current paradigm of massive resuscitation.

All plasma expanding solutions have effects on the coagulation system. These effects may go beyond simple dilution of coagulation factor concentration. Most plasma substitutes cause a decrease in von Willebrand factor, with or without an associated reduction in factor VIII plasma levels, and may, thereby, also cause effects on thrombin generation. If large amounts of plasma substitutes are given to patients with an already compromised coagulation status, the anti-hemostatic effects of these agents may become clinically significant, although marked differences between various plasma substitutes may exist.

The last several years have seen an accumulation of evidence that TRALI is an important complication of blood transfusion and is likely occurring much more frequently than previously estimated. Most data support a causal relationship though there are admittedly confounders given the prevalence of this disorder in patients with other predispositions to ALI/ARDS, including sepsis, shock, trauma and aspiration. Both massive and submassive transfusion have been implicated as risk factors. It is apparent from the studies to date that each additional unit likely increases a patient’s risk in an additive fashion thus mitigating any false reassurances if no reaction is witnessed after the first few units are transfused.

The implications of this disorder are far and wide given the regular and wide-spread use of blood transfusions around the world. While most attention in the past has focused on the risk of transmitting infectious diseases, it is imperative that some of the light now be shifted to better defining and understanding the true prevalence of TRALI. The moral, ethical and financial issues of potentially preventive strategies (screening or deferral of particular donors, decrease in storage time and pre-storage leukoreduction) are substantial.

Desialylation of the RBC membrane by neuraminidase may alter RBC shape, RBC capacity for deformability, and RBC biochemistry. Some of these alterations are observed early in clinical situations. These RBC modifications are reproduced within a few hours. Moreover, desialylation could facilitate uptake by the reticuloendothelial system, as observed in the senescent process. Further studies including the measurement of neuraminidase activity are needed to understand the process of RBC sialic acid decrease in critically ill patients. As a potential consequence, blockade of neuraminidase activity could represent an interesting therapeutic option to limit anemia and improve RBC rheology in critically ill patients.

The diagnosis of pulmonary infection caused by and , and different species of , is often long and challenging although they are the major etiologic agents of pneumonia. For this reason, the treatment of these infections remains probabilistic. Advances in new diagnostic techniques, such as PCR sequencing, show the relative predominance of atypical organisms and serves to identify emerging pathogenic agents. Moreover, these techniques should clarify the correlation between common and atypical pathogens.

This chapter describes cardiocerebral resuscitation, a new approach to out-of-hospital witnessed arrest in adults due to VF or pulseless ventricular tachycardia. We have reviewed the studies that led us to institute this new methodology for witnessed unexpected sudden cardiac arrest in adults. It is dramatically different from Guidelines 2000 and in all probability significantly different from Guidelines 2005. Guidelines 2005 had not been published when this chapter was due for submission.

Compared to historical controls where Guidelines 2000 CPR was used, cardiocerebral resuscitation resulted in dramatic improvements in neurologically normal survival in patients with witnessed out-of-hospital cardiac arrest and shockable arrhythmias (personal communication Kellum). While these finding were in an observational study, they were so dramatic and in accordance with our animal research studies, that we recommend this approach for all out-of-hospital cardiac arrests with a shockable rhythm until a different protocol is proven to be better.