Primary Graft Dysfunction and Mortality Following Lung Transplantation: A Role for Proadrenomedullin Plasma Levels

Abstract

Primary graft dysfunction (PGD) after lung transplantation (LT) is a heterogeneous syndrome that comprises clinical presentations with diverse grades of severity. Proadrenomedullin (proADM) levels may be associated with PGD and may enhance its relationship with outcomes. We prospectively included 100 LT recipients. Plasma levels of proADM were measured at 24, 48 and 72 h after admission to the intensive care unit (ICU). We assessed their relationship with PGD grade and ICU mortality. Fifty patients (50%) presented grade 3 PGD at ICU admission. Twenty‐two patients (22%) developed grade 3 PGD at 72 h, the only grade associated with higher mortality (odds ratio 6.84, 95% confidence interval [CI] 1.47–38.44). ProADM levels measured at 24 h (3.25 vs. 1.61 nmol/L; p = 0.016) and 72 h (2.17 vs. 1.35 nmol/L; p = 0.011) were higher in these patients than the rest of the population. When we added the individual predictive utility of grade 3 PGD at 72 h for ICU mortality (area under the curve [AUC] 0.72, 95% CI 0.53–0.90) to that of ProADM at 72 h, the predictive value of the model improved (AUC 0.81, 95% CI 0.65–0.97). Higher levels of proADM measured following LT are associated with grade 3 PGD at 72 h. ProADM enhances the association of this entity with mortality.

The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial

“…Mid-regional proadrenomedullin (MR-proADM) is a peptide generated by multiple tissues in order to stabilise the microcirculation and protect against endothelial permeability [ 6 – 11 ], both of which are widely acknowledged to play a significant role in the pathophysiological host response to sepsis [ 12 , 13 ]. Indeed, MR-proADM levels are rapidly induced during the initial stages of sepsis development following burns [ 14 ] and neurological disorders [ 15 ], in response to invasive fungal infections in patients with septic shock [ 16 ], and in other conditions such as lower respiratory tract infections [ 17 – 19 ], lung transplantation [ 20 ] and thoracic surgery [ 21 ]. Thus, MR-proADM may be of significant clinical utility in the early risk stratification of patients with sepsis.…”

Pneumonia versus graft dysfunction as the cause of acute respiratory failure after lung transplant: a 4-year multicentre prospective study in 153 adults requiring intensive care admission

“…Overall, the MIC50 to meropenem was >16 μg•mL −1 and the MIC90 was >32 μg•mL −1 . Improved diagnostic strategies, including new biomarkers [33,34] in blood and BAL, should be implemented. Moreover, our findings emphasise the need for new antibiotics such as ceftolozane-tazobactam, due to the spread of carbapenem-resistant P. aeruginosa, in which early adequate treatment (mostly with colistin and aminoglycosides) does not seem to be associated with improved prognosis.…”

Chronic Obstructive Pulmonary Disease and Lung Transplantation

“…87 Recent research has highlighted preemptive biomarkers, such as raised procalcitonin and proadrenomedullin levels at 24 hours, could accurately predict PGD-3 at 72 hours. 88,89 Management focuses on prevention and supportive measures, with fluid volume management and oxygenation being central. Depending on clinical circumstances, data for high-flow oxygen therapy, noninvasive ventilation, and reintubation with early tracheostomy and weaning have all been advocated.…”