The Effect of Primary Graft Dysfunction on Survival after Lung Transplantation

Christie, Jason D.; Kotloff, Robert M.; Ahya, Vivek N.; Tino, Gregory; Pochettino, Alberto; Gaughan, Christina; Demissie, Ejigayehu; Kimmel, Stephen E.

doi:10.1164/rccm.200409-1243oc

Cited by 308 publications

(225 citation statements)

References 23 publications

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“…Twenty-eight patients were excluded because of missing mPAP is primary graft dysfunction (PGD), a severe, acute lung injury occurring early after lung transplantation that is responsible for significant morbidity and mortality. [11][12][13][14][15][16][17][18][19][20] While previous studies have demonstrated that primary PAH is known to be a risk factor for PGD, [14][15][16]21 the role of secondary PAH in PGD risk is incompletely understood. The purpose of this study was to evaluate the association between mPAP and the development of severe PGD in patients with IPF who underwent lung transplantation.…”

Section: Resultsmentioning

confidence: 99%

Elevated Pulmonary Artery Pressure Is a Risk Factor for Primary Graft Dysfunction Following Lung Transplantation for Idiopathic Pulmonary Fibrosis

Fang

Studer

Kawut

et al. 2011

Chest

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Idiopathic pulmonary fibrosis (IPF) is a fatal and chronically progressive diffuse parenchymal lung disease that is characterized by varying degrees of fi brosis of the lung parenchyma. 1 Currently, there are few proven, standardized therapies for IPF 2 ; the only viable treatment that has shown survival benefi t for patients with advanced stages of IPF is lung transplantation. [3][4][5][6][7] Nonetheless, the survival benefi t for lung transplantation in patients with IPF is still complicated by signifi cant early mortality rates, especially within the fi rst year (approximately 28%). The 10-year survival rate after lung transplantation is worse for patients with IPF when compared with other diseases, such as idiopathic pulmonary arterial hypertension (PAH), cystic fi brosis, and a 1 -antitrypsin-defi ciency emphysema. 8 Elevated mean pulmonary arterial pressure (mPAP) in patients with IPF has been associated with decreased exercise capacity and worse survival. 9 Higher mPAP was also associated with increased mortality following lung transplantation in a large registry study. 10 One possible explanation for the link between PAH and early mortality after lung transplantation

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Section: Resultsmentioning

confidence: 99%

Elevated Pulmonary Artery Pressure Is a Risk Factor for Primary Graft Dysfunction Following Lung Transplantation for Idiopathic Pulmonary Fibrosis

Fang

Studer

Kawut

et al. 2011

Chest

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“…The main reason for PGD is ischaemia/reperfusion (I/R) injury, clinically manifesting within a spectrum from mild acute lung injury (ALI) to severe acute respiratory distress syndrome (ARDS). I/R injury is associated with increased short-and long-term morbidity and mortality [1,3,4]. During I/R injury, the graft organ develops structural damage, such as interstitial and intraalveolar oedema formation and loss of integrity of the blood-air barrier [5,6].…”

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confidence: 99%

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion

Mühlfeld¹,

Schaefer²,

Becker³

et al. 2008

Eur Respir J

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The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model.Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4uC, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included ''worst case'' without Perfadex and surfactant (5), ''no injury'' without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood-air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (Ppa) were determined during reperfusion in groups 1 to 4.Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood-air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4. Ppa did not differ between the groups.In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood-air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.

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“…However, primary graft dysfunction (PGD), infection, and rejection remain as important contributors to mortality after lung transplantation. PGD is the most common postoperative complication, occurring in 25% of recipients [10,11]. The treatment of PGD varies with the severity of lung injury, with general supportive care in low grade forms.…”

Section: Harefield Hospitalmentioning

confidence: 99%

Mechanical ventilation after lung transplantation

Thakuria

Romano

Carby

et al. 2016

Journal of Critical Care

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IntroductionTo explore the hypothesis that early ventilation strategies influence clinical outcomes in lung transplantation, we have examined our routine ventilation practices in terms of tidal volumes (Vt) and inflation pressures.Methods 124 bilateral lung transplants between 2010 and 2013 were retrospectively assigned to low (<6ml/kg), medium (6-8ml/kg) and high (>8ml/kg) Vt groups based on ventilation characteristics during the first 6 hours after surgery. Those same 124 patients were also stratified to low-pressure (<25cm H2O) and high-pressure (≥25cm H2O) groups. ResultsEighty per cent of patients were ventilated using pressure control mode. Low, medium and high tidal volumes were applied to 10%, 43%, and 47% of patients respectively. After correcting for patients requiring extracorporeal support, there was no difference in short to mid-term outcomes among the different Vt groups. Low inflation pressures were applied to 61% of patients, who had a shorter length of ICU stay (5 vs. 12 days; p=0.012), higher FEV1 at 3 months (77.8% vs. 60.3%; p<0.001), and increased 6-month survival rate (95% vs. 77%; p=0.008). ConclusionLow Vt ventilation has not been fully adopted in our practice. Ventilation with higher inflation pressures, but not tidal volumes, were significantly associated with poorer outcomes after lung transplantation.Response to Reviewers: Dear Prof. Lumb, Article ID: JCRC-D-15-00340 -Mechanical ventilation following lung transplantationWe are most grateful to the reviewers for taking the time and care to appraise this manuscript, and for your constructive critique. We have addressed all of the points that were raised and have amended the manuscript accordingly. We feel that your suggestions has significantly improved the original manuscript.Responses to Reviewer #1 Reviewer #1: "The manuscript does not add anything new to the literature. It has been known for a very long time that excessive tidal volume and/or inflation pressures adversely affect patient outcome."Author response: We are grateful that you have taken the time to review our manuscript, although we are disappointed by your conclusions. We have made detailed arguments in both the introduction and discussion that highlight the need for this work within lung transplantation, combined with our unique approach to this clinical problem. Your statement is in direct opposition with the views of the other reviewers, who have helpfully pointed out the potential importance of our study within this field. Your critique also fails to acknowledge the major ongoing debate regarding the special importance of driving pressures, and the relative roles of tidal volumes and pressures in acute lung injury. As a rebuttal, we would respectfully suggest that our manuscript does add to the existing body of knowledge on this topic. As stated in the manuscript, we believe that our manuscript fills an important gap within the literature on VALI by providing new observations on lung ventilation practices in lung transplant recipients, a population that was...

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The Effect of Primary Graft Dysfunction on Survival after Lung Transplantation

Cited by 308 publications

References 23 publications

Elevated Pulmonary Artery Pressure Is a Risk Factor for Primary Graft Dysfunction Following Lung Transplantation for Idiopathic Pulmonary Fibrosis

Elevated Pulmonary Artery Pressure Is a Risk Factor for Primary Graft Dysfunction Following Lung Transplantation for Idiopathic Pulmonary Fibrosis

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion

Mechanical ventilation after lung transplantation

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