Introduction:
Chronic lung diseases are difficult to treat. Diseases like chronic obstructive pulmonary disease, cystic fibrosis, interstitial lung diseases, and idiopathic pulmonary fibrosis (IPF) cause progressive degradation of lung structures. In most cases, such conditions are beyond the scope of traditional treatment options. In such conditions, lung transplantation can be a useful method to save the life of the patient. Patients with lung transplantation have shown around a 55 percent survival rate after five years.
But in most cases, often patients suffer from lots of complications after lung transplantation. One of the most common immediate complications of lung transplantation is primary graft dysfunction. Around 10 to 25 percent of patients undergoing lung transplantation experience such complications. Primary graft dysfunction is also responsible for early mortality in lung transplantation patients.
What Is Primary Graft Dysfunction?
Primary graft dysfunction is a severe complication of lung transplantation. This complication usually arises within 72 hours of lung transplantation. This is characterized by profuse pulmonary edema (fluid inside the lung) and alveoli damage. The clinical features of primary graft dysfunctions are:
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Decreased oxygenation in the body and the lungs.
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The radiograph of the lung shows multiple diffuse opposites in the lung structure.
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Decreased in the change in the lung volume and decreased expandability of the lungs.
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Increased resistance of the pulmonary vessels can be seen. Along with this, the incidence of a mixture of arterial and venous blood can be observed.
On the basis of the above factors, primary graft dysfunction can be categorized into several stages. These are:
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Primary Graft Dysfunction Grade 0: Involvement of the lung tissues and presence of the opacities are not observed bilaterally. The P/F ratio (index to identify oxygenation in the blood) is more than 300.
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Primary Graft Dysfunction Grade 1: P/F ratio is more than 300, but the involvement of the lung tissues and the presence of diffuse, gourd glass-type opacities can be seen in the radiographs.
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Primary Graft Dysfunction Grade 2: In this condition, the P/F ratio is between 200 to 300. Also, bilateral involvement of the lung tissues and opacities can be seen.
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Primary Graft Dysfunction Grade 3: The P/F ratio is below 200 in this condition. Profuse involvement of the lung tissues and multiple bilateral radio opacities can be seen.
What Are the Pathophysiology of Primary Graft Dysfunctions?
The process of primary graft dysfunction starts with the activation of the neutrophils. These polymorphonuclear neutrophils cross the blood circulation and accumulated in the airway. Damaged and dead lung tissues release substances like CXCL8 and damage-associated molecular patterns (DAMPs) that attracts neutrophils. One of the most common factors associated with the release of such chemicals is ischemia-reperfusion injury (IRI). This is associated with donor-related factors which result in the accumulation of inflammatory cells in the donor's lungs. These lymphocytes and macrophages present in the donor's lungs are responsible for the attraction of the neutrophils. Also, sudden re-establishment of the blood flow after interruption leads to cell depolarization and chase in the cellular environment.
Another factor that is associated with primary graft dysfunction is the release of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin beta. These factors cause the up-regulation of the adhesion molecules and recruitment of leucocytes. This causes the production of the reactive oxygen species which are responsible for lung damage. In the later period, CD4+ T lymphocytes are involved in this process. All these factors lead to significant lung damage and accumulation of fluid in the lungs.
What Are the Risk Factors?
The potential risk factors for the development of primary graft dysfunction are:
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Age of the Donor: Donor age is closely related to the development of primary graft dysfunction. Ideally, 32 to 45 years of age is considered as ideal age group for a donor in lung transplant cases. Donor age of more than 45 years has been associated with an increased risk of primary graft dysfunction. Along with this, gender factors like the female and African-American ethnicity of the donor are related to the increased incidence of primary graft dysfunction.
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Physical State of the Donor: Physical condition and physical state of the donor is correlated with the development of primary graft dysfunction. Conditions like brain death and prolonged mechanical ventilation are associated with graft dysfunctions. Broncho-aspiration (aspiration of gastric substance), pneumonia (a type of lung infection), underlying trauma, and excessive blood transfusion also increase the incidence of graft dysfunction. Fat embolism (the presence of fat droplets in the blood vessels) is one of the greatest risk factors for the development of primary graft dysfunctions. Smoking and effect of the pollution increase the prevalence of primary graft dysfunctions. Disorders like hypertension, pulmonary hypertension, and sarcoidosis are related tho graft dysfunctions.
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Recipient-Related Risk Factors: Factors related recipient is very much related to primary graft dysfunctions. Increased age, increased BMI, and usage of drugs like (steroid drugs, and inotropic drugs) is associated with primary graft discussion. Disorders like lung fibrosis, left-sided heart disorders, and pulmonary hypertension increase the incidence of such complications post-transplantations.
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Surgery-Related Risk Factors: Single or double lung transfusion does not increase the incidence of primary graft dysfunctions. But other operative factors like more than four units of blood transfusion, extracorporeal membrane oxygenation (ECMO) after surgery, sepsis, infections, re-transplantation, and repeated intensive care are very much related to the increased prevalence of primary graft dysfunctions.
What Are the Preventive Methods?
Several Protective measures can be taken to reduce lung injury caused by primary graft dysfunction. These methods are:
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Several cytoprotective substances like prostaglandins, nitric oxide, surfactants, and adenosine can be used to reduce the amount of pro-inflammatory mediators and free radicals.
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An Ischemia period of more than eight hours can be associated with primary graft dysfunctions. Alterations in the temperature and duration of the cold ischemia can be fruitful in preventing post-transplantation lung injury.
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The establishment of the reperfusion should be done slowly and gradually. The blood flow should be released gradually (time should be more than 10 minutes) and slowly.
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Mechanical ventilation is provided to the lung allograft (tissue sample transfer between two species) sample before transplantation. This increases the chance of lung injury and complications after transplantations. Methods like the use of high tidal volume and low positive end-expiratory pressure (PEEP) increase the chance of primary graft dysfunctions.
What Are the Treatment Options?
The treatment option for primary graft dysfunctions are:
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Inhalation of nitric oxide is helpful in the reduction of inflammation and pulmonary artery pressure. The side effect of this therapy is methemoglobinemia (reduced oxygen caring capacity of the hemoglobin).
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Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) has proved to be the most important treatment option in such conditions. This is used mainly for the treatment of reduced oxygenation caused by lung tissue destruction.
Conclusion:
Lung transplantation is a useful method to save the life of a person with a defective lung. Primary graft dysfunction is one of the common and earliest complications of lung transplantation. Such complications may cause death also. Donor condition, nature of the surgery, and recipient factors are involved in such conditions. Care selection of the donor, allograft preparation, and proper techniques can be useful in preventing such complications.
