Active clinical trials for "Primary Graft Dysfunction"

This study is being done to determine if parenterally administered ascorbic acid (Vitamin C) given at the time of lung transplant is safe. Vitamin C may be an effective intervention towards primary graft dysfunction (PGD). The study will enroll 69 participants who consent to the intervention. Participants who do not consent to the intervention will be treated according to standard-of-care, but may choose to be consented to have their data retrospectively reviewed. Based on our consent rate, this group may include 40-70 participants. Participants will be on study for up to 12 months.

The recent introduction of ex-vivo lung perfusion (EVLP) as a tool to evaluate and recondition lungs from marginal donors has opened a new era in the field of lung transplantation.

Working Hypothesis: The purpose of the trial is to study the effect of exogenous calf surfactant (calfactant) on the prevention of primary graft failure due to ischemic-reperfusion lung injury in lung transplant patients. Aims of the Study: The purpose of the trial is to study the effect of exogenous calf surfactant (calfactant) on the prevention of primary graft failure due to ischemic-reperfusion lung injury in lung transplant patients.

Pulmonary transplantation is a very demanding surgical procedure, often accompanied by coagulopathy and severe perioperative bleeding. The most common complication that develops within the first 72 hours after surgery is primary graft dysfunction (PGD), up to 30% in the most severe form. The etiology of PGD is multifactorial. One of the causes may be the amount of perioperative blood loss. Intravascular volume is normally maintained by the administration of crystalloid and colloid solutions and fresh frozen plasma, which is also used to treat coagulopathy, however it is administered at the discretion of the anaesthetist and his experience, practically meaning ,,blindly". In the field of the allogeneous ischemic organ, these substitution solutions essentially become another allogeneous material and can cause undesired immunomodulation and contribute to the development of PGD. In our prospective randomized trial (120 patients), two patient groups will be investigated. In the first group, the coagulopathy and perioperative blood loss will be treated by the current standard approach, by ,,blind" administration of fresh frozen plasma, crystalloids and colloids. In the second group, the cause of coagulopathy will be diagnosed and treated according to the point-of-care (POC) results of ROTEM, PFA 200 and Multiplate. A colloidal solution of 5% albumin will be used to replace the circulating volume and maintain the oncotic pressure. Investigators assume that the POC management of coagulopathy and bleeding in the second group will lead to a reduction in perioperative bleeding, to reduced administration of infusion solutions, and thus to a reduction of the incidence of PGD.

Primary graft dysfunction, a form of reperfusion pulmonary edema that occurs early after lung transplantation, shares key clinical and pathological features with acute lung injury and its more severe form, the acute respiratory distress syndrome. However, in contrast to acute lung injury/acute respiratory distress syndrome, in which biomarkers in plasma, urine and lung edema fluid have prognostic and pathogenetic value, the role of biomarkers in primary graft dysfunction has been less thoroughly explored. We will try in this study de determine the rule of pneumoproteins in the donor organ on the pulmonary edema in the recipient.

Primary graft dysfunction (PGD) is the most common cause of early morbidity and mortality following lung transplant and is characterized by acute lung injury and capillary leak leading to an increase in extravascular lung water index (ELWI) and impaired graft function. PGD has many features in common with acute respiratory distress syndrome (ARDS). PGD may be life-threatening and can also lead to impaired long term lung function. In ARDS, a restrictive fluid strategy has been associated with an improvement in lung function and outcomes. Accurate methods of evaluating, quantifying and guiding the hemodynamic / fluid management and limiting the extent of ELWI that accumulates in the setting of PGD are lacking. Using transpulmonary thermodilution to estimate ELWI and the pulmonary permeability index (PPI) represents a novel approach to fluid management, which has been used in patients with ARDS, but to date not in the transplant setting. To determine if these measurements may better guide the management of lung transplant patients, the investigators first wish to establish whether these methods are able to predict the onset of clinical pulmonary edema earlier, whether they correlated with traditional markers of PGD, and whether they may be useful for predicting outcomes. AIM 1: The investigators will evaluate the correlation between ELWI and current surrogates of pulmonary edema in lung transplant patients with and without Primary Graft Dysfunction (PGD) AIM 2: The investigators will correlate the use of ELWI and PPI to determine the presence and severity of PGD. AIM 3: a) The investigators will determine whether early measurements of ELWI and PPI can predict the onset of PGD. b) Across different strata of PGD, the investigators will determine whether ELWI and PPI have a differential effect on duration of mechanical ventilation. The results of the study will be used for the following: Provide the rationale for routine monitoring of ELWI to detect PGD if found to be more discriminatory and have a stronger association with outcome compared to the current gold standard. Provide the means of early identification of those as risk of developing PGD in order to guide management decisions or future therapeutic interventions aimed at preventing or treating PGD. Provide the requisite groundwork for a clinical trial comparing the effects of an ELWI-driven protocol versus usual care on ICU outcomes in lung transplant recipients.

Among the complications of heart transplant, primary dysfunction of the graft (PDG) is the most feared with a net impact on early morbidity and mortality. The all-cause mortality rate at the international level is 10% at 30 days and 34% at one year. Mortality at 30 days is secondary in 66% of cases with DPG or multi-organ failure. The treatment of choice for the more severe PDG remains ECMO-type circulatory mechanical assistance or ventricular assistance. According to several studies, this could reduce early mortality. Early placement and short-term (<30 days) of support appear to improve survival in the first year after transplantation. The haemodynamic parameters revealing this DPG are not clearly described in the literature. hypothesis of this research is that: DPG risk factors in strasbourg's hospital center are comparable to other European and international centers. Simple hemodynamic parameters can be used to detect PDG earlier in order to set up assistance more quickly.

The validity of several functional parameters, which could be included in a new PGD scoring system, will be tested in a prospective pilot study of 80 consecutive bilateral lung transplant recipients in high volume lung transplant centers. Functional parameters will be collected at different time points within the first 72hrs after lung transplantation and their accuracy in predicting clinical outcome as well as their correlation with lung water content (measured by PiCCO) will be tested. Insights will serve to generate a hypothesis (a novel PGD score), which can then be tested in future prospective trials.

Primary graft dysfunction (PGD or lung reperfusion edema) complicates 10 to 20% of lung transplantations and leads to severe early and late postoperative complications. Its pathophysiology remains unclear but may involve graft ischemia-reperfusion, increased vascular permeability, pneumocyte dysfunction and finally alveolar flooding that impair gas exchange and blood oxygenation.Its substrate, namely extravascular lung water (EVLW), can now be clinically measured with minimally invasive Intensive Care Unit monitors (PiCCO2®, Pulsion Medical Systems) that also provides a physical estimate of pulmonary vascular permeability (PVPI). Similarly, biochemical correlates of vascular permeability (ICAM-1) and pneumocyte dysfunction (RAGE) can now be measured in plasma samples. Our study aims at quantifying physical and biochemical markers of PGD and assess their diagnosis and prognosis values.