Effect of mode of intraoperative support on primary graft dysfunction after lung transplant

Loor, Gabriel; Huddleston, Stephen J.; Hartwig, Matthew G.; Bottiger, Brandi; Daoud, Daoud; Wei, Qi; Zhang, Qianzi; Ius, F.; Warnecke, G.; Villavicencio, Mauricio A.; Tirabassi, Briana; Machuca, Tiago; Raemdonck, Dirk Van; Frick, Anna Elisabeth; Neyrinck, Arne; Toyoda, Yoshiya; Kashem, Mohammed A.; Landeweer, M.; Chandrashekaran, S.

doi:10.1016/j.jtcvs.2021.10.076

Cited by 42 publications

(25 citation statements)

References 23 publications

(46 reference statements)

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“…The higher rates in our study may be due to the use of the updated 2016 ISHLT scoring guidelines, which increase detection of PGD, particularly in extubated patients 5 . However, our PGD rates were not entirely different from those in a recent international multicenter cohort 25 . Finally, caution should be taken when analyzing baseline biomarkers and their effects on PGD as we have previously reported; although potentially informative, these relationships can be heavily influenced by confounding variables 5 .…”

Section: Discussioncontrasting

confidence: 92%

“…Since the early biomarker studies from the LTOG consortium, the PGD scoring system has been revised to improve consistency and sensitivity 4,5 . Additionally, perioperative practices in lung transplantation have evolved, including greater use of ECLS and EVLP [25][26][27] . Although these perioperative practices could confound our results, it is almost impossible to study biomarkers associated with PGD in the current era without including them.…”

Section: Discussionmentioning

confidence: 99%

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Plasma protein biomarkers for primary graft dysfunction after lung transplantation: a single-center cohort analysis

Chacon‐Alberty

Kanchi

et al. 2022

Sci Rep

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The clinical use of circulating biomarkers for primary graft dysfunction (PGD) after lung transplantation has been limited. In a prospective single-center cohort, we examined the use of plasma protein biomarkers as indicators of PGD severity and duration after lung transplantation. The study comprised 40 consecutive lung transplant patients who consented to blood sample collection immediately pretransplant and at 6, 24, 48, and 72 h after lung transplant. An expert grader determined the severity and duration of PGD and scored PGD at T0 (6 h after reperfusion), T24, T48, and T72 h post-reperfusion using the 2016 ISHLT consensus guidelines. A bead-based multiplex assay was used to measure 27 plasma proteins including cytokines, growth factors, and chemokines. Enzyme-linked immunoassay was used to measure cell injury markers including M30, M65, soluble receptor of advanced glycation end-products (sRAGE), and plasminogen activator inhibitor-1 (PAI-1). A pairwise comparisons analysis was used to assess differences in protein levels between PGD severity scores (1, 2, and 3) at T0, T24, T48, and T72 h. Sensitivity and temporal analyses were used to explore the association of protein expression patterns and PGD3 at T48–72 h (the most severe, persistent form of PGD). We used the Benjamini–Hochberg method to adjust for multiple testing. Of the 40 patients, 22 (55%) had PGD3 at some point post-transplant from T0 to T72 h; 12 (30%) had PGD3 at T48–72 h. In the pairwise comparison, we identified a robust plasma protein expression signature for PGD severity. In the sensitivity analysis, using a linear model for microarray data, we found that differential perioperative expression of IP-10, MIP1B, RANTES, IL-8, IL-1Ra, G-CSF, and PDGF-BB correlated with PGD3 development at T48–72 h (FDR < 0.1 and p < 0.05). In the temporal analysis, using linear mixed modeling with overlap weighting, we identified unique protein patterns in patients who did or did not develop PGD3 at T48–72 h. Our findings suggest that unique inflammatory protein expression patterns may be informative of PGD severity and duration. PGD biomarker panels may improve early detection of PGD, predict its clinical course, and help monitor treatment efficacy in the current era of lung transplantation.

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Section: Discussioncontrasting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Plasma protein biomarkers for primary graft dysfunction after lung transplantation: a single-center cohort analysis

Chacon‐Alberty

Kanchi

et al. 2022

Sci Rep

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“…In the recent literature, the best io management of LT is still matter of debate, despite an increasing number of investigations reporting promising results in favour of a ‘routine’ use of VA ECMO compared to cardio-pulmonary bypass (CPB). In contrast, data are unclear about the potential superiority of io VA ECMO in relation to ‘off-pump’-group [ 3 , 24 , 33 ]. In fact, the use of CPB during LT has been abandoned due to its well-known adverse effects, such as the need for full heparinization, severe bleeding complications, higher po PGD values and more frequent renal dysfunction [ 24 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…The following variables were collected from electronic health records: (i) demographic data (age, gender, body mass index (BMI)); (ii) therapies at home (i.e., corticosteroids or O 2 -therapy); (iii) diabetes or chronic kidney injury; (iv) Oto score [ 22 ]; (v) lung-allocation score (LAS) [ 23 ]; (vi) underlying diseases leading to LT (see full description in Table 1 ); (vii) pre-existing recipient-related Gram-negative (GN) colonization; (viii) provenience (hospital, home); (ix) surgical characteristics (time of LT, time of graft ischemia, io fluid support and peri/po surgical revisions, bleeding needing surgery and thromboembolic/ischemic events); (x) io use of ‘prophylactic’, ‘rescue’ or ‘prolonged’ ECMO [ 1 , 5 , 6 , 20 ]; (xi) immunosuppressive therapy; (xii) length of invasive mechanical ventilation; (xiii) Clavien-Dindo score [ 24 , 25 ]; and (xiv) short- and mid-term outcomes of interest (72-h PGD), perioperative blood units (transfused within 72–96 h after LT), ICU length of stay (LOS), re-tracheal intubation and/or tracheostomy, AKI (only stage 2 or 3, according to the KDIGO guidelines) and/or renal replacement therapy, multi-drug resistant (MDR)/extended-beta lactamases (ESBL) gram-negative bacteria, acute cellular rejection within 30 days after LT (according to the International Society for Heart and Lung Transplantation criteria), and hospital (H) LOS and mortality [ 14 , 15 , 24 , 25 , 26 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

The Impact of New Treatments on Short- and MID-Term Outcomes in Bilateral Lung Transplant: A Propensity Score Study

Boscolo

Amore

Pettenuzzo

et al. 2022

JCM

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Background: Despite many efforts to improve organ preservation and recipient survival, overall lung transplant (LT) mortality is still high. We aimed to investigate the impact of ‘prophylactic’ veno-arterial extracorporeal membrane oxygenation (VA ECMO) and tacrolimus on 72-h primary graft dysfunction (PGD) and 30-day acute cellular rejection, respectively. Methods: All consecutive LT patients admitted to the Intensive Care Unit of the Padua University Hospital (February, 2016–2022) were screened. Only adult patients undergoing first bilateral LT and not requiring cardio-pulmonary bypass, invasive mechanical ventilation, and/or ECMO before LT, were included. A propensity score weighting analysis was employed to account for the non-random allocation of the subjects to different treatments. Results: A total of 128 LT recipients were enrolled. Compared to the ‘off-pump’-group (n.47, 37%), ‘prophylactic’ VA ECMO (n.51,40%) recorded similar 72-h PGD values, perioperative blood products and lower acute kidney dysfunction. Compared with cyclosporine (n.86, 67%), tacrolimus (n.42, 33%) recorded a lower risk of 30-day cellular rejection, kidney dysfunction, and bacteria isolation. Conclusions: ‘Prophylactic’ VA ECMO recorded 72-h PGD values comparable to the ‘off-pump’-group; while tacrolimus showed a lower incidence of 30-day acute cellular rejection.

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“…Patients requiring CPB can easily be converted back to V-A or V-V ECMO at the end of the procedure if further support is needed. Patients with severe pulmonary hypertension are best approached using CPB as the risk of bleeding is quite high while dissection of the enlarged PA's can be challenging (25).…”

Section: Intra-operative Ecmo Configuration Strategymentioning

confidence: 99%

ECMO in lung transplant: pre, intra and post-operative utilization—a narrative review

García¹,

Ashworth²,

Hage³

2023

Curr Chall Thorac Surg

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Objective: The goal of this chapter is to evaluate the use of Extracorporeal Membrane Oxygenation (ECMO) in the lung transplant patient. ECMO will be evaluated pre, intra and post-operative lung transplant with discussion on cannulation, benefits and risks that can affect patient outcomes.Background: Patients with end-stage lung disease (ESLD) unresponsive to medical therapy will succumb to their disease unless they undergo lung transplantation which remains the gold standard for treatment.Unfortunately, there are not enough donors to meet the demand of the UNOS waitlist. Due to donor shortage and long wait times, some patients will not survive to transplant. The introduction of the current allocation system for lungs in 2005 was aimed to improve donor organ allocation and outcomes by determining disease burden and risk factors allowing for transplantation of the sickest patients first. ECMO is a form of temporary mechanical support that removes CO 2 and oxygenates the blood and can also provide hemodynamic support if needed. ECMO technology has rapidly expanded over the last 15 years and is now being used to support patients as a bridge-totransplant (BTT), intraoperative pulmonary and/or cardiac support and post-operative support in patients with severe graft dysfunction. Early results utilizing pre-operative ECMO support were not promising before 2010.Methods: Systematic review of the available literature to investigate ECMO in pre, intra and post-operative lung transplant patients. A systematic review of available research articles was reviewed from 1990 to 2021 to evaluate ECMO as a bridge to transplant. Focusing on the use of ECMO preoperatively, intraoperatively, and post operatively including the risk and benefits to the patient.Conclusions: Recent studies have shown survival outcomes in ECMO supported recipients comparable to non-ECMO recipients in appropriately selected patients, such as younger patients with single system failure. Intra-operatively, it is increasingly being used for hemodynamic support, especially in patients with fibrotic disease undergoing double lung transplantation via an anterior approach. Hybrid circuits allow for conversion from ECMO to full cardiopulmonary bypass (CPB) and back to ECMO easily. Current reports have also shown a decrease incidence of primary graft dysfunction in double lung transplants that are supported by intra-operative ECMO. With the improvements in ECMO technology and better patient management protocols, we can expect increasing use of this technology in lung transplantation.

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Effect of mode of intraoperative support on primary graft dysfunction after lung transplant

Cited by 42 publications

References 23 publications

Plasma protein biomarkers for primary graft dysfunction after lung transplantation: a single-center cohort analysis

Plasma protein biomarkers for primary graft dysfunction after lung transplantation: a single-center cohort analysis

The Impact of New Treatments on Short- and MID-Term Outcomes in Bilateral Lung Transplant: A Propensity Score Study

ECMO in lung transplant: pre, intra and post-operative utilization—a narrative review

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