Textbook outcome in lung transplantation: Planned venoarterial extracorporeal membrane oxygenation versus off-pump support for patients without pulmonary hypertension

Several reports have demonstrated higher rates of grade 3 primary graft dysfunction among patients who underwent BOLT with versus without ECMO support.

“While VA ECMO offers hemodynamic stability and adequate gas exchange, and facilitates controlled allograft reperfusion,3,8,18,28 several reports have demonstrated higher rates of grade 3 PGD among patients who underwent BOLT with versus without ECMO support.9,10,13”

• cites [9] Hoetzenecker, 2017, Intraoperative extracorporeal membrane oxygenation and the possibility of postoperative prolongation improve survival in bilateral lung transplantation, J Thorac Cardiovasc Surg sourceDisputed

  The PGD results (p. 2198) report grade 3 PGD at 72 hours in 0% of both the intraoperative-ECMO and no-ECMO groups after propensity-score matching—not a higher rate with ECMO. The paper also reports a trend toward less grade 2 or 3 PGD with intraoperative ECMO. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [10] Ius, 2016, Five-year experience with intraoperative extracorporeal membrane oxygenation in lung transplantation: Indications and midterm results, J Heart Lung Transplant sourcePartly supported

  Table 3 (p. 5) reports higher rates of combined grade 2–3 primary graft dysfunction at 24 and 48 hours in the ECMO groups than in the no-ECMO group. It does not report grade 3 separately, and the comparison includes some single-lung transplant recipients rather than only patients who underwent BOLT. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [13] Ius, 2020, Long-term outcomes after intraoperative extracorporeal membrane oxygenation during lung transplantation, J Heart Lung Transplant sourcePartly supported

  The PGD results (p. 3) report higher grade 3 PGD rates at 24, 48, and 72 hours with intraoperative ECMO than without it. However, the comparison covers isolated lung transplants as a group, including some single-lung transplants (Table 2, p. 5); the paper does not report this PGD comparison specifically for BOLT patients. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Sequential BOLT performed off-pump using single-lung ventilation has long been the standard planned intraoperative support strategy for BOLT recipients without pulmonary hypertension at many institutions, including ours.

“Sequential BOLT performed off-pump using single-lung ventilation has long represented the standard planned intraoperative support strategy for BOLT recipients without PH at many institutions, including ours.4,6”

• cites [4] Van Raemdonck, 2017, Report of the ISHLT Working Group on primary lung graft dysfunction Part IV: prevention and treatment: A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation, J Heart Lung Transplant sourceNot checked — no full text of the source
• cites [6] Coster, 2021, Extracorporeal life support during lung transplantation, Indian J Thorac Cardiovasc Surg sourcePartly supported

  The section “The trend towards using ECMO” describes a Toronto group's usual practice of starting bilateral sequential transplantation off-pump, with primary pulmonary hypertension as an exception. The “Off-pump lung transplantation” section says the operation can proceed without extracorporeal support when single-lung ventilation is tolerated. The paper does not establish that this has long been the standard planned strategy at many institutions, including the citing authors’ institution; page numbers are unavailable in our copy. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Use of VA ECMO may increase the risk of bleeding complications due to cannulation, hemodilution, external circulation, and anticoagulation that are absent with off-pump support.

“Use of VA ECMO may also increase the risk of bleeding complications due to the combination of cannulation, hemodilution, external circulation, and anticoagulation that is absent with off-pump support.3,28”

• cites [3] Schaheen, 2018, Extracorporeal membrane oxygenation in lung transplantation: no longer a four-letter word, J Thorac Cardiovasc Surg sourcePartly supported

  The discussion of intraoperative support options (labeled Abstract; page unavailable) says off-pump transplantation avoids anticoagulation, whereas ECMO requires some. It does not state that VA ECMO increases bleeding risk relative to off-pump support or identify cannulation, hemodilution, and external circulation as causes of bleeding. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [28] Ohsumi, 2021, Perioperative circulatory support for lung transplantation, General Thorac Cardiovasc Surg sourcePartly supported

  In the V-V versus V-A ECMO section (page not provided), the review reports bleeding at peripheral cannulation sites. The Comparison with off-pump section and Table 1 (pages not provided) associate off-pump support with less bleeding and no anticoagulation, while ECMO generally uses heparin. The copy does not identify hemodilution as a cause of VA ECMO bleeding, and its discussion of circuit-related bleeding concerns cardiopulmonary bypass rather than ECMO. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Previously reported associations between planned VA ECMO and increased grade 3 primary graft dysfunction are likely confounded by differences in underlying physiology and illness severity between planned support groups.

“In this context, our findings suggest that previously reported associations between planned VA ECMO and increased grade 3 PGD are likely confounded by differences in underlying physiology and illness severity between planned support strata.”

• cites [9] Hoetzenecker, 2017, Intraoperative extracorporeal membrane oxygenation and the possibility of postoperative prolongation improve survival in bilateral lung transplantation, J Thorac Cardiovasc Surg sourcePartly supported

  The Discussion says an earlier ECMO comparison included more complex patients in its ECMO groups and did not adjust for baseline differences. The Propensity Score Matching section likewise identifies substantial differences between this paper’s support groups. But the paper does not report the claimed prior association between planned VA ECMO and increased grade 3 PGD; its own matched comparison found grade 3 PGD at 0% in both groups (p. 2198). (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [10] Ius, 2016, Five-year experience with intraoperative extracorporeal membrane oxygenation in lung transplantation: Indications and midterm results, J Heart Lung Transplant sourcePartly supported

  Table 3 (p. 5) reports more grade 2–3 PGD in the planned-ECMO group than in the no-ECMO group, and the Discussion (p. 6) notes that ECMO recipients had higher pre-operative risk and that complications could reflect either recipient risk or ECMO itself. The paper does not isolate grade 3 PGD or planned VA ECMO, nor does it conclude that their association is likely confounded by differences between support groups. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [13] Ius, 2020, Long-term outcomes after intraoperative extracorporeal membrane oxygenation during lung transplantation, J Heart Lung Transplant sourcePartly supported

  The PGD section (p. 3) reports more grade 3 PGD after intraoperative ECMO than without ECMO, and the Results (p. 1) describe higher pre-transplant risk among ECMO recipients. The paper does not establish that the association is confounded by differences between planned VA ECMO support groups; its comparison is intraoperative ECMO versus no intraoperative support. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Planned VA ECMO patients were more likely than planned off-pump patients to receive donation after circulatory death donor lungs (22.1% vs 11.2%, p=0.03).

“Planned VA ECMO patients were also more likely than planned off-pump patients to receive donation after circulatory death (DCD) donor lungs (22.1% vs 11.2%, p=0.03) (Table 2).”

Among complications occurring at rates above 5%, planned VA ECMO patients were less likely to remain intubated beyond 48 hours post-transplant than planned off-pump patients.

“Among events that occurred at rates >5%, planned VA ECMO patients were less likely to remain intubated >48 hours post-transplant, less likely to experience acute rejection within 30 days, and more likely to require reintervention within 30 days than planned off-pump patients (Table 5).”

In a sensitivity analysis excluding patients who needed unanticipated escalations of intraoperative mechanical circulatory support (N=199), planned VA ECMO remained associated with higher odds of textbook outcome than planned off-pump support (aOR 4.40, 95% CI 1.71-11.95, p=0.003).

“In a sensitivity analysis restricted to patients who did not require unanticipated escalations of intraoperative MCS (N=199), planned VA ECMO remained associated with higher odds of TO achievement than planned off-pump support (aOR 4.40, 95% CI 1.71-11.95, p=0.003) (Table 4A).”

In a multivariable model adjusting for prior lung transplant, lung allocation score, ischemic time, and intraoperative transfusions, planned VA ECMO was linked to greater odds of achieving textbook outcome compared with planned off-pump support (aOR 3.89, 95% CI 1.58-9.90, p=0.004).

“After adjustment for prior BOLT, lung allocation score, ischemic time, and intraoperative transfusions, planned VA ECMO was associated with higher odds of textbook outcome than planned off-pump support (odds ratio 3.89, 95% confidence interval 1.58-9.90, p=0.004).”

• Also stated in: § Achievement of textbook outcome · plain

  “On adjusted analysis, planned VA ECMO was independently associated with higher odds of TO achievement than planned off-pump support (adjusted odds ratio [aOR] 3.89, 95% confidence interval [CI] 1.58-9.90, p=0.004) (Table 3).”

• Also stated in: § CONCLUSIONS: · plain

  “At our institution, planned VA ECMO for isolated BOLT was associated with higher odds of textbook outcome than planned off-pump support among patients without pulmonary hypertension.”

Planned VA ECMO patients were less likely than planned off-pump patients to require unanticipated escalations of intraoperative mechanical circulatory support (4.4% vs 20.7%, p=0.002).

“Compared to planned off-pump patients, planned VA ECMO patients were less likely to require escalations of intraoperative MCS (4.4% vs 20.7%, p=0.002).”

In this study, rates of grade 3 primary graft dysfunction at 48 or 72 hours were similar between planned VA ECMO and off-pump groups.

“In our study of patients without PH, rates of grade 3 PGD at 48 or 72 hours were similar between planned VA ECMO and off-pump strata.”

Most patients experienced multiple complications (planned off-pump: 59.7%; planned VA ECMO: 55.9%).

“Although any single complication was sufficient to determine TO failure, most patients experienced multiple complications (planned off-pump: 59.7%; planned VA ECMO: 55.9%) (Figure S2).”

Patients who underwent BOLT with planned VA ECMO were more likely to require reintervention within 30 days than those who underwent planned off-pump BOLT.

“In the present study, patients who underwent BOLT with planned VA ECMO required more intraoperative transfusions and were more likely to require reintervention within 30 days than those who underwent planned off-pump BOLT”

• Also stated in: § Reasons for textbook outcome failure · plain

  “Among events that occurred at rates >5%, planned VA ECMO patients were less likely to remain intubated >48 hours post-transplant, less likely to experience acute rejection within 30 days, and more likely to require reintervention within 30 days than planned off-pump patients (Table 5).”

Patients who underwent BOLT with planned VA ECMO required more intraoperative transfusions than those who underwent planned off-pump BOLT.

“In the present study, patients who underwent BOLT with planned VA ECMO required more intraoperative transfusions and were more likely to require reintervention within 30 days than those who underwent planned off-pump BOLT”

Postoperative ECMO was used more frequently among patients who underwent BOLT with planned VA ECMO than among those with off-pump support.

“In our study, postoperative ECMO was used more frequently among patients who underwent BOLT with planned VA ECMO versus off-pump support.”

Planned VA ECMO patients were more likely than planned off-pump patients to have had a prior lung transplant (13.2% vs 5.3%, p=0.04).

“Compared to planned off-pump patients, planned VA ECMO patients were more likely to have undergone prior LTx (13.2% vs 5.3%, p=0.04).”

Among primary BOLT recipients (N=219), planned VA ECMO was also associated with higher odds of textbook outcome than planned off-pump support (aOR 4.02, 95% CI 1.57-10.76, p=0.004).

“Among primary BOLT recipients (N=219), planned VA ECMO was also associated with higher odds of TO achievement than planned off-pump support (aOR 4.02, 95% CI 1.57-10.76, p=0.004) (Table 4B).”

Among complications occurring at rates above 5%, planned VA ECMO patients were less likely to experience acute rejection within 30 days than planned off-pump patients.

“Among events that occurred at rates >5%, planned VA ECMO patients were less likely to remain intubated >48 hours post-transplant, less likely to experience acute rejection within 30 days, and more likely to require reintervention within 30 days than planned off-pump patients (Table 5).”

The findings support broader use of VA ECMO as the standard planned intraoperative support strategy during BOLT.

“These findings suggest that planned VA ECMO may be superior to planned off-pump support for BOLT recipients without PH and support broader use of VA ECMO as the standard planned intraoperative support strategy during BOLT.”

The findings support broader use of planned VA ECMO for BOLT recipients without pulmonary hypertension.

“Accordingly, our findings support broader use of planned VA ECMO for BOLT recipients without PH and motivate further application of TO as a means to identify avenues to optimize the multifaceted management of these patients to improve post-transplant outcomes and quality of care moving forward.”

The findings suggest that planned VA ECMO may be superior to planned off-pump support for BOLT recipients without pulmonary hypertension.

“These findings suggest that planned VA ECMO may be superior to planned off-pump support for BOLT recipients without PH and support broader use of VA ECMO as the standard planned intraoperative support strategy during BOLT.”

Planned VA ECMO may increase the odds of achieving an overall optimal perioperative outcome, free of multiple interconnected complications that may compromise long-term post-transplant survival.

“However, in the context of improved odds of TO among planned VA ECMO patients, our findings suggest that planned VA ECMO may increase odds of achieving an overall optimal perioperative outcome, free of multiple, interconnected complications that may compromise long-term post-transplant survival.”

• cites [22] Krischak, 2022, Textbook surgical outcome in lung transplantation: analysis of a US national registry, Clin Transplant sourceNot checked — no full text of the source
• cites [23] Halpern, 2021, Textbook outcome: definition and analysis of a novel quality measure in lung transplantation, Ann Surg sourceNot checked — no full text of the source

DCD lung transplantation was previously found by our group to be associated with failure to achieve textbook outcome.

“Our group previously found that DCD LTx was associated with failure to achieve TO.22,23”

• cites [22] Krischak, 2022, Textbook surgical outcome in lung transplantation: analysis of a US national registry, Clin Transplant sourceNot checked — no full text of the source
• cites [23] Halpern, 2021, Textbook outcome: definition and analysis of a novel quality measure in lung transplantation, Ann Surg sourceNot checked — no full text of the source

Non-selective use of planned VA ECMO does not increase the risk of severe primary graft dysfunction among patients who have traditionally undergone BOLT without mechanical circulatory support.

“Accordingly, our study expands upon prior findings by providing promising evidence to suggest that non-selective use of planned VA ECMO does not increase the risk of severe PGD among patients who have traditionally undergone BOLT without MCS.”

Textbook outcome effectively predicts post-transplant prognosis.

“However, TO effectively predicts post-transplant prognosis,22,23 and thus represents a robust, multidimensional metric through which to investigate the safety and utility of planned VA ECMO for BOLT recipients without PH.”

• cites [22] Krischak, 2022, Textbook surgical outcome in lung transplantation: analysis of a US national registry, Clin Transplant sourceNot checked — no full text of the source
• cites [23] Halpern, 2021, Textbook outcome: definition and analysis of a novel quality measure in lung transplantation, Ann Surg sourceNot checked — no full text of the source

Planned use of VA ECMO represents one means to reduce complications and improve outcomes for recipients of donation after circulatory death donor lungs.

“Our findings suggest that planned use of VA ECMO represents one means to reduce complications and improve outcomes for recipients of DCD donor lungs.”

Residual confounding may exist despite inclusion of an overall risk index (lung allocation score) in the model.

“Given our cohort size, we are likely underpowered to detect small but potentially meaningful between-group differences in risk factors; although we included an overall risk index (LAS) in our model, residual confounding may exist.”

The single-center, high-volume institutional experience may not generalize to other programs.

“As we examined a series of BOLTs performed at a single, high-volume institution, our experience may not generalize to other programs.”

The cohort size likely left the study underpowered to detect small but potentially meaningful between-group differences in risk factors.

“Given our cohort size, we are likely underpowered to detect small but potentially meaningful between-group differences in risk factors; although we included an overall risk index (LAS) in our model, residual confounding may exist.”