Vm Ranieri

The Use of CO2 Removal Devices in Patients Awaiting Lung Transplantation: An Initial Experience

BACKGROUND Lung transplantation is the treatment of choice for patients with end-stage lung failure. Limitations are presented by the shortage of donors and the long waiting list periods. New techniques, such as extracorporeal membrane ventilator devices with or without pump support, have been developed as bridges to transplantation for patients with severe, unresponsive respiratory insufficiency. METHODS Between November 2005 and September 2009, 12 patients (7 males and 5 females), of overall mean age of 43.3 +/- 15.5 years underwent decapneization with extracorporeal devices. In 6 cases, a NovaLung system was used; in the remaining 6 patients, it was a Decap device. Causes of respiratory failure that led to implantation of such devices were cystic fibrosis (n = 6), pulmonary emphysema (n = 5), and chronic rejection of a previous double lung transplant (n = 1). RESULTS Mean time on extracorporeal decapneization was 13.5 +/- 14.2 days. Eight patients died on the device. Three patients were bridged to lung transplantation; 1 recovered and was weaned from the device after 11 days. Mean PaCO(2) on the extracorporeal gas exchanger was significantly lower for both the devices at 24, 48, and 72 hours after implantation (P < .05). No significant difference was observed for the 2 systems. CONCLUSION In our initial experience, decapneization devices have been simple, efficient methods to support patients with mild hypoxia and severe hypercapnia that is refractory to mechanical ventilation. This could represent a valid bridge to lung transplantation in these patients.

The RacGAP ArhGAP15 is a master negative regulator of neutrophil functions.

In phagocytes, GTPases of the Rac family control crucial antimicrobial functions. The RacGAP ArhGAP15 negatively modulates Rac activity in leukocytes, but its in vivo role in innate immunity remains largely unknown. Here we show that neutrophils and macrophages derived from mice lacking ArhGAP15 presented higher Rac activity but distinct phenotypes. In macrophages, the loss of ArhGAP15 induced increased cellular elongation and membrane protrusions but did not modify chemotactic responses. Conversely, the lack of ArhGAP15 in neutrophils affected critical Rac-dependent antimicrobial functions, specifically causing enhanced chemotactic responses, straighter directional migration, amplified reactive oxygen species production, increased phagocytosis, and improved bacterial killing. In vivo, in a model of severe abdominal sepsis, these effects contributed to increase neutrophil recruitment to the site of infection, thereby limiting bacterial growth, controlling infection spread, reducing systemic inflammation, and ultimately improving survival in ArhGAP15-null mice. Altogether, these results demonstrate the relevance of ArhGAP15 in the selective regulation of multiple neutrophil functions, suggesting that ArhGAP15 targeting might be beneficial in specific pathologic settings like severe sepsis.

Protective ventilation for lung transplantation.

Purpose of review Lung transplantation has been one of the great medical advances as the last option for the treatment of end-stage pulmonary disease. Optimal pulmonary care of potential donors and recipients can definitely increase the number of successful lung retrievals and reduce the incidence of complications. Recent findings The use of a lung-protective ventilatory strategy, associated with recruitment maneuvers, has a profound clinical impact, doubling the number of lungs available for transplant. Postoperatively, it is important to use a lung-protective ventilation strategy, whereas for patients with life-threatening reperfusion injury, extracorporeal membrane oxygenation can ensure a survival rate between 50 and 80%. Pumpless extracorporeal carbon dioxide removal system allows the maintenance of normal gas exchange and can be maintained in the perioperative period. Summary Perioperative ventilatory care of the transplanted patient still represents a challenge for the ICU clinician. The lung-protective strategy and the early application of carbon dioxide removal systems can increase the number of lung donor eligibility. Further studies are needed to increase the viability of other organs and to develop new strategies that reduce the risk of ischemia–reperfusion injury, which still represents the most common complication in the postoperative period.

Extracorporeal support for severe acute respiratory failure.

Extracorporeal membrane oxygenation (ECMO) and extracorporeal CO(2) removal (ECCO(2)R) techniques have increasingly been applied in patients with severe acute lung injury refractory to conventional mechanical ventilatory support. The objectives of this article are to review current concepts of extracorporeal life support techniques (ECMO and ECCO(2)R systems) and provide the rationale for their application in patients with acute respiratory distress syndrome, chronic obstruction pulmonary disease, and as adjunctive therapy for bridging patients to lung transplantation.

Ventilator-Associated Lung Injury

Since its introduction into clinical practice as life-sustaining therapy in the polio epidemic, mechanical ventilation has proved to be an important tool for the treatment of the respiratory failure. One of the main reasons for a patient’s admission into the intensive care unit (ICU) is to receive ventilator support [1]. According to a recent review by Esteban and co-workers [2], 66% of patients who require mechanical ventilation suffer from acute respiratory failure, including acute respiratory distress syndrome (ARDS), heart failure, pneumonia, sepsis, complications of surgery and trauma. The remaining indications include coma (15%), acute exacerbation of chronic obstructive pulmonary disease (13%) and neuromuscular disorders (5%). The aims of mechanical ventilation are primarily to decrease the work of breathing and to reverse life-threatening hypoxaemia or acute progressive respiratory acidosis. However, over the last two decades, research in a number of animal models has shown that mechanical ventilation itself can produce acute lung injury (ALI) [3]. The classical form of iatrogenic lung injury, recognised clinically for many decades, is the well-known barotrauma, defined as radiological evidence of extra-alveolar air [4]. The extraalveolar accumulation of air has several manifestations, of which the most threatening is tension pneumothorax.

Lipopolysaccharide is required for leukocyte adhesion to Toraymyxin ® filters used in the treatment of sepsis

Extracorporeal hemoperfusion with polymyxin B is a novel septic treatment, shown to improve hemodynamics, organ dysfunction, and mortality through the removal of circulating lipopolysaccharide (LPS). This therapy can also remove activated leukocytes, which likely contributes to reduced inflammation and improved patient outcome; however, the mechanistic role of LPS in the removal of leukocytes remains unclear.

Postregistration trials: Should we? How do we?

Postregistration trials or postmarketing or phase IV trials are tools to investigate any treatment that is already approved and is, therefore, available for prescription use. The main objectives of these trials are typical effectiveness, more structured surveillance for uncommon or rare side effects, and the potential development of new indications. Several issues need to be addressed in the postregistration phase of the evaluation of a therapeutic treatment. Among those we will focus on two ethical challenges: reporting bias from industry-sponsored research and use of placebo as one of the arms in controlled studies where proven treatment already exists. The review of this topic is particularly relevant in the field of critical care because it is ongoing in the debate about the opportunity to perform a new placebo-controlled study with the recombinant human activated protein C (activated drotrecogin alfa—activated protein C). In fact, despite the approval of activated protein C for treatment of patients with severe sepsis and high risk of death, several issues regarding the efficacy and safety of its administration have been recognized by several investigators to the point that the European Medicines Agency asked for a new placebo-controlled study to further clarify the benefit/risk profile of activated protein C.