Sensitivity analysis
Patients with an underlying diagnosis of COPD, emphysema,
bronchiectasis, lymphangioleiomyomatosis and pulmonary hypertension (n =
107) were excluded, since none of them was placed on VV-ECMO (to avoid
aliasing between diagnosis and ECMO support), resulting in 21 BTT and
169 non-BTT patients in the sensitivity analysis (Table 5).
Perioperative characteristics (Table 5) and postoperative outcomes
(Table 6) in BTT and non-BTT patients were similar to those in the
entire cohort. After matching, both subgroups were well-balanced with
respect to the age, low platelet count, serum creatinine and prevalence
of CF, while imbalance remained regarding the proportion of men, BMI,
and preoperative hemoglobin levels (Table 7). Intraoperatively, CPB was
used less often, while the use of ECMO was considerably higher in BTT
compared with non-BTT patients (Table 7). Need for postoperative ECMO
(62.0% vs. 8.7%), delayed chest closure (16.5% vs. 5.6%),
tracheostomy (50.8% vs. 34.4%), chest infection (60.8% vs. 41.2%)
and AKI requiring RRT (45.7% vs. 30.5%) were more common in BTT than
in non-BTT patients, while the two subgroups were similar in respect to
30-day mortality, surgical re-exploration, chest drainage within 24
hours, sepsis, stroke and 1-year mortality (Table 7). With further
adjustment for the unbalanced covariates (gender, BMI and hemoglobin
level), VV-ECMO as a BTT was associated with 12.8-fold higher odds of
need for postoperative ECMO and with 6-fold higher odds of tracheostomy,
but it did not appear associated with any other early and mid-term
outcome (Table 8).
DISCUSSION
The use of VV-ECMO as a BTT can allow patients with decompensated
end-stage lung disease to remain eligible for LTx and offer a viable
strategy for improving their post-transplant survival outcomes. In this
study, we reported our single-center experience with 297 transplanted
patients, 21 (7.1%) of whom were bridged to LTx with VV-ECMO. The most
common diagnosis in both BTT and non-BTT recipients was CF. One of the
reasons is that there is a well-established CF Unit in our institution
which attracts tertiary referrals from the whole country. In the primary
analysis, both 30-day and 1-year posttransplant mortality were
considerably higher in patients requiring VV-ECMO as a BTT than in
non-BTT patients. In addition, the incidence of the most important early
postoperative complications, including need for ECMO, delayed chest
closure, surgical re-exploration and AKI requiring RRT, was
significantly increased in the bridged patients.
To minimize potential effects of selection bias and decrease variability
of both groups, we performed further analysis comparing matched groups
which were well-balanced in terms of preoperative recipients’ baseline
characteristics. Importantly, after matching, we observed a similar
30-day mortality between the BTT and non-BTT patients (4.6% vs. 6.6%,p =0.083) despite a higher incidence of early postoperative
complications (need for ECMO, delayed chest closure, AKI requiring RRT),
while the 1-year mortality was even lower in the BTT patients (8.0% vs.
15.6%, p =0.238). Furthermore, when evaluating the effect of
preoperative VV-ECMO on postoperative outcomes, it did not appear
associated with 30-day or 1-year mortality. Moreover, in the sensitivity
analysis, the two subgroups were similar in respect to 30-day (BTT 7.8%
vs. 6.5%, p =0.048) and 1-year mortality (12.5% vs. 18%,p =0.154). The clinical condition of patients who were bridged to
LTx with VV-ECMO is usually more critical than that among the rest of
the patients who were not bridged, and this may negatively influence
their outcomes. However, in our experience, post-transplant survival in
bridged patients was comparable to that in patients who did not have
pre-transplant VV-ECMO. Therefore, VV-ECMO has been demonstrated to be a
valuable supportive strategy to prolong life in these critically ill
patients while increasing the waiting period for suitable organs. Our
early and mid-term results are in general consistent with previous
reports that have shown no significant difference in post-transplant
survival among BTT and non-BTT patients, especially in high-volume
centers.4,10-12,24-29 Surprisingly, we have found that
1-year mortality was even lower in the BTT group but this might be
related to several other factors. One of the reasons could be that the
average duration of pre-transplant support with VV-ECMO in our cohort
was relatively short (8 days) and this could positively affect the
outcomes. As recently reported by Crotti et al. , patients who
underwent LTx after a waiting period longer than 14 days had
significantly higher rates of post-transplant mortality and
morbidity.30 Furthermore, shorter waiting times after
urgent listing have likely contributed to these favorable outcomes. In
addition, we have observed more commonly intraoperative ECMO than CPB
among BTT patients when compared to the non-BTT group, and it is well
known that the intraoperative use of ECMO might have several
advantages.31,32 We believe that the improved survival
among BTT patients can be also related to an increased experience with
this strategy, early ambulation of these patients, advancement in the
perioperative care, and development of an experienced ECMO and
multidisciplinary team.
On the other hand, Schechter et al. have reported a decreased
1-year post-transplant survival among patients requiring preoperative
support including ECMO with MV.3 However, they have
demonstrated in a multivariable analysis that ECMO alone was not
associated with decreased 1-year survival.3 In our
study, 38.1% of patients were supported using both VV-ECMO and MV
before LTx, but the sample size was too small to perform a further
analysis whether MV could have had any effect on postoperative outcomes.
Furthermore, Mason et al. have reported that survival after LTx
is markedly worse (1-month and 1-year post-transplantation survival were
72% and 50%, respectively) when preoperative mechanical support is
necessary, although they suggested that additional risk factors for
mortality should be considered when selecting patients for LTx in order
to improve survival.2 In addition, Fischer et
al. have reported that the perioperative mortality of LTx after
preoperative ECMO can be even up to 60%.9
As expected, need for postoperative ECMO, delayed chest closure,
tracheostomy, chest infection, and AKI requiring RRT were more common
among BTT patients. This can be related to the common and well-known
risks related to the use of ECMO such as bleeding complications,
systemic inflammatory response, acute kidney injury and thromboembolic
complications.33-35 However, the rate of these
complications was lower than in some of the previous reports that
demonstrated an incidence of tracheostomy in up to
77%36, delayed chest closure in
50%37 and stroke in 8%36 of
recipients. Still, in our study it seems that both 30-day and 1-year
survival have not been negatively affected by the increased incidence of
early postoperative complications.
The strength of this study is the comparison of two cohorts of patients
(BTT and non-BTT) that were matched. However, we acknowledge several
study limitations. First, the analysis was performed retrospectively and
designed as a single-center study, although the study period was up to 7
years and included moderate sample size with 1-year follow-up. The
present study also lacks donor data as we were not able to collect these
data for the whole study period. In addition, it would be interesting to
expand the research and study primary graft dysfunction and rejection
rate as we did not have this data. Further studies with long-term
follow-up would be useful in order to analyze occurrence of late
complications. Lastly, we were not able to extend our analysis including
patients bridged with other devices (VA-ECMO, Novalung) due to a small
sample size and different clinical characteristics some of these
patients.