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\begin{document}

\title{Post-Cardiotomy Extracorporeal Membrane Oxygenator: No Longer a Bridge
to No Where?}



\author[1]{HelenMari Merritt Genore}%
\author[1]{Michael Schwabe}%
\author[2]{Abel Luksan}%
\author[1]{Timothy Ryan}%
\author[3]{Elizabeth Lyden}%
\author[3]{Michael Moulton}%
\affil[1]{University of Nebraska Medical Center College of Medicine}%
\affil[2]{Mary Lanning Memorial Hospital}%
\affil[3]{University of Nebraska Medical Center}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background Post-Cardiotomy ECMO (PC-ECMO) represents a unique subset of
critically ill patients, with a paucity of data regarding long-term
survival, and characteristics correlated with short and long-term
outcomes. We present a retrospective cohort PC patients supported with
ECMO at a single institution, with outcomes at 1 and 3-year follow-up.
Methods Data was collected retrospectively for all patients requiring
ECMO within 72 hours of index cardiac operation, excluding assist
devices and heart transplantation. Operative data, frozen mediastinum
status, cannulation site, postoperative hemorrhage, and timing of
cannulation (immediate versus delayed) were all collected and examined.
Primary outcomes were ability to wean from ECMO, hospital survival, and
long-term survival. Results 33 patients required PC ECMO, representing a
total of 179 days of ECMO support. Overall survival data were: ability
to wean 61\%, hospital survival 55\%, one month survival 45\%. The
estimated 12 and 36 month survival for all PC ECMO patients was 40\% and
33\% respectively. Twelve and 36 month survival for all hospital
survivors was 66\% and 60\% respectively. Operative times, type of
operation performed, open chest status, reoperation for hemorrhage and
cannulation location (central/peripheral) were all compared. There were
no statistically significant relationships of these variables short or
long-term survival. Conclusions Overall 12 month survival for PC-ECMO
patients was 40\%, and was 33\% at 36 months. For hospital survivors, 1
year survival was 66\%, and was 60\% at 36 months. These data support
PC-ECMO as a reasonable salvage strategy, with mid-term survival
comparable to other surgically treated diseases.%
\end{abstract}%



\sloppy


\textbf{Title:} Post-Cardiotomy Extracorporeal Membrane Oxygenator- No
Longer a Bridge to No Where?

\textbf{Running Head:} Post-Cardiotomy ECMO

\textbf{Authors:} HelenMari Merritt-Genore\textsuperscript{1,5}, Michael
Schwabe\textsuperscript{2}, Abel Luksan\textsuperscript{3}, Timothy
Ryan\textsuperscript{1}, Elizabeth Lyden\textsuperscript{4} and Michael
Moulton \textsuperscript{1}

\begin{enumerate}
\tightlist
\item
  University of Nebraska Medical Center, College of Medicine; Omaha, NE,
  USA
\item
  University of Nebraska Medical School; Omaha, NE, USA
\item
  Mary Lanning Healthcare, Department of Pulmonary Medicine; Hastings,
  NE, USA
\item
  University of Nebraska Medical Center, Biostatistics; Omaha, NE, USA
\item
  Methodist Health System; Omaha, NE, USA
\end{enumerate}

\textbf{Word Count:} 3451

\textbf{Keywords:} Perfusion, Extracorporeal Membrane Oxygenator;
Post-Cardiotomy Shock; Cardiogenic Shock

\textbf{Presentations:} This abstract has been presented at the 2020 STS
Annual Meeting, and was selected as a finalist in the poster
competition.

\textbf{Corresponding Author:}

HelenMari Merritt-Genore

Email: helenmari.merritt@gmail.com

Address: 982315 Nebraska Medical Center

Omaha, NE 68198

Phone: 402-559-2239

\textbf{Abstract}

\textbf{Background}

Post-Cardiotomy ECMO (PC-ECMO) represents a unique subset of critically
ill patients, with a paucity of data regarding long-term survival, and
characteristics correlated with short and long-term outcomes. We present
a retrospective cohort PC~patients supported with ECMO at a single
institution, with outcomes at 1 and 3-year follow-up.

\textbf{Methods}

Data was collected retrospectively for all patients requiring ECMO
within 72 hours of index cardiac operation, excluding assist devices and
heart transplantation. Operative data, frozen mediastinum status,
cannulation site, postoperative hemorrhage, and timing of cannulation
(immediate versus delayed) were all collected and examined. Primary
outcomes were ability to wean from ECMO, hospital survival, and
long-term survival.

\textbf{Results}

33 patients required PC ECMO, representing a total of 179 days of ECMO
support. Overall survival data were: ability to wean 61\%, hospital
survival 55\%, one month survival 45\%. The estimated 12 and 36 month
survival for all PC ECMO patients was 40\% and 33\% respectively. Twelve
and 36 month survival for all hospital survivors was 66\% and 60\%
respectively Operative times, type of operation performed, open chest
status, reoperation for hemorrhage and cannulation location
(central/peripheral) were all compared. There were no statistically
significant relationships of these variables short or long-term
survival.

\textbf{Conclusions}

Overall 12 month survival for PC-ECMO patients was 40\%, and was 33\% at
36 months. For hospital survivors, 1 year survival was 66\%, and was
60\% at 36 months. These data support PC-ECMO as a reasonable salvage
strategy, with mid-term survival comparable to other surgically treated
diseases.

\textbf{Introduction}

Extra-corporeal membrane oxygenation (ECMO) therapy has been growing in
use over the last several decades. In 1990, there were 1,644 ECMO runs
performed at 83 centers, which has increased to 10,423 cases among 391
centers in 2018\textsuperscript{{[}1{]}}. Much of this growth has been
due to an increase in the number of ECMO runs performed on adult cardiac
patients \textsuperscript{{[}1{]}}. According to the 2018
Extra-Corporeal Life Support Organization (ELSO) registry data, 59\% of
all adult cardiac patients were able to be successfully weaned from
extra-corporeal life support, with 42\% of these patients surviving to
hospital discharge\textsuperscript{{[}1{]}}.

Post-Cardiotomy ECMO (PC-ECMO) represents a unique subset of critically
ill patients following cardiac surgery. One of the feared complications
following open heart surgery is refractory post-cardiotomy cardiogenic
shock (PCS), which occurs in between 0.5-1.5\% of adult cardiac surgical
patients \textsuperscript{{[}2-3{]}}. There is a paucity of data
regarding long-term survival of PC-ECMO patients, and even less
regarding which patient characteristics are correlated with better short
and long-term survival in this cohort. Survival to hospital discharge,
which has been the most frequently reported outcome, has varied
significantly. Early studies demonstrated rates of hospital-survival of
25-30\%\textsuperscript{{[}3-4{]}}, with more recent data showing 50\%
of patients may be successfully weaned from ECMO and short-term (6
months or less) survival ranging from
37\%-42\%\textsuperscript{{[}5-6{]}}. The few studies that have reported
longer-term survival have shown overall 2-year survival to be around
37\%\textsuperscript{{[}6{]}} for PC-ECMO patients.

Given the relative lack of data related to long-term survival in
PC-ECMO, we present a retrospective cohort series of post-cardiotomy
patients supported with ECMO at our institution.

\textbf{Methodology}

The Nebraska ECMO Research Database (NERD) is a collection of data
points for all ECMO patients at our institution since 2006, with data
collected in a retrospective fashion. After institutional review board
at the University of Nebraska Medical Center approved this study, data
was collected from NERD for ECMO patients supported between 2006-2017.
PC-ECMO support was defined as ECMO instituted within 72 hours of
cardiotomy. Patients who were status post orthotopic heart transplant or
left ventricular assist device placement were excluded. The type of
support was defined as either veno-arterial (VA) or veno-venous (VV)
ECMO, with subgroup analysis performed between these cohorts. The VV
ECMO group included the temporary percutaneous right ventricular assist
device configuration with an in-line oxygenator. Basic demographic
information was collected. Operative data including type of operation
performed, overall time in the operating room, cross-clamp (XC) and
cardiopulmonary bypass (CPB) times, and red blood cell transfusions
during the index operation were recorded. Frozen mediastinum status was
defined as prior cardiac surgery or mediastinal radiation. Cannulation
site (peripheral or central), time to cannulation (immediately versus
delayed by up to 72 hours), and reoperation for hemorrhage were all
examined.

Primary outcomes were ability to wean from ECMO and hospital survival.
Secondary outcomes included hospital and intensive care lengths of stay
and long-term survival status. Fisher's exact test or the Mann-Whitney
test, as appropriate to the data, was used to compare patient
characteristics and outcomes between subsets of patients. Overall
survival for patients discharged from the hospital was defined as the
time from discharge to death from any cause and was determined by the
Kaplan-Meier method. Comparisons of survival curves was done using the
log-rank test All analyses were done using SAS Version 9.4 and a p-value
\textless{} 0.05 was considered statistically significant.

\textbf{Results}

Of 246 patients in the review, 33 (13\%) were PC-ECMO patients. This
cohort were supported on ECMO a total of 179 days. The median age was 66
years old, and 73\% of patients were male. The most common operations
were coronary artery bypass (30\%), followed by combination of major
cardiac procedures (i.e.: CABG/AVR, AVR/MVR, etc.) cases (21\%) and
aortic surgery (18\%). VA ECMO represented 82\% of cases (n 27), with
the remaining six cases (18\%) of cases being VV support. The median
duration of ECMO support was 4 days and median length of stay was 23
days. Median operative (OR) time was 478 (range 192-1262) minutes,
median CPB time was 233 (range 102-899) minutes, and median XC time was
125 (range 34-388) minutes. On average, patients went back on pump one
time before transitioning to ECMO (range 0-6 times) and received a
median of 2 units of red blood cells (range 0-20 units) in the operating
room. ECMO was initiated immediately in the operating room in 22
patients (66\%), and 11 patients (34\%) had ECMO initiated later, at a
median of 18 hours postoperatively (range 1-71). This data included four
patients who were transferred to our institution following their index
operation.

Overall survival data were as follows: overall ability to wean from ECMO
61\%, hospital survival 55\%. One-month survival was 45\%. Long term
survival was captured for all patients who were discharged, representing
a total of 15,068 days of follow up data. The median follow up time for
surviving patients was 1071 days {[}Range: 640-1996 days{]} or 35.2
months after discharge. The estimated 12 month survival for all PC-ECMO
patients was 40\%, and was 33\% for both 24 and 36 months. The estimated
12 month survival for patients surviving their index hospitalization was
66\% (95\%CI: 40\%, 83\%), and survival was 60\% at both 24 and 36
months (95\% CI: 33\%, 78\%). Survival data are further described via
Figure 1 below.

Data was examined in multiple ways to determine differences between
groups. Discussion will focus on both pertinent positives and negatives
of our investigation. Basic demographic information was examined to
determine if any effect on survival or ability to wean from ECMO
existed. There was a borderline, statistically significant difference in
age for 30-day survivors versus those who expired (median 60 versus 71
years old, p 0.053) but otherwise there were no differences in the basic
demographics collected (Figures 2-4).

Operative, CPB, and XC times were all examined for impact on length of
stay, duration of support, ability to wean from ECMO and hospital
survival. Total OR time includes all time in the OR from ``wheels in to
wheels out'' including induction of anesthesia, line placement and all
associated activities prior to and after surgery. Operative time is the
``skin to skin'' time of the actual procedure performed. Interestingly,
longer CPB and XC times were associated with increased ability to wean
from ECMO (Figure 2) though this did not translate into hospital or
30-day survival differences (Figures 3-4).

The type of operation was also examined to determine if this played a
role in survival outcomes. There was no difference in the types of
operations performed when compared to ability to wean from ECMO (p
0.27), hospital survival (p 0.16) or 30 day survival (p 0.59). Likewise
we compared open chest status, reoperation for postoperative hemorrhage
and cannulation location (central versus peripheral). In terms of how
patients were placed on ECMO, 36\% remained with central cannulation,
and 64\% were cannulated via peripheral technique. More patients in the
centrally cannulated group were also able to wean from ECMO (central =
83\% versus peripheral = 48\%; p 0.07). This trend did continue through
30 day survival after hospital discharge (central = 67\% versus
peripheral = 33\%; p 0.08) but did not reach statistical significance
(Figures 3-4).

The chest was left open following surgery in 39\% of cases, with a
primary closure performed in the remainder of cases. Twelve patients
were taken back to the operating room specifically for hemorrhage or
tamponade and this did not correlate with initial open chest status or
site of cannulation (p 0.14). A hemorrhagic event was interestingly
associated with an increased chance of weaning from ECMO (92\% versus
43\%, p 0.01), and longer length of stay (18 versus 30 days, p 0.026)
though this difference did not translate to a statistically significant
difference in hospital survival or 30 day survival (p 0.15, p 0.08
respectively) (Figures 3-4).

Subgroup analysis was performed on several groups of interest: the
frozen mediastinum patients, patients with immediate versus delayed ECMO
initiation and patients supported with VA versus VV ECMO.

Of the 33 patients reviewed, there were 16 patients (48\%) who met
criteria for frozen mediastinum which included 14 patients with prior
sternotomy and 2 patients with chest radiation in the past.

As one might expect, those patients with a frozen mediastinum status
required more time for the operative procedure, but their ability to
wean from ECMO and survival was not affected (Figure 5).The type of ECMO
support required (VV versus VA), and location of cannulation site
(peripheral versus central) was similar between these two groups (p
0.65, 0.28 respectively). There was also no difference in rates of
re-operation for hemorrhage or for open chest status (p 1.00 and 0.48
respectively). These patients did not require more units of RBCs in the
operating room (p 0.13) contrary to what one might suspect.

Long-term survival of patients who were discharged from the hospital was
not significantly altered for patients with frozen mediastinum versus
normal chest (55\% versus 65\% p 0.55).

Outcomes were compared to determine if a survival benefit might exist
for patients who were placed on ECMO earlier in their PC course versus
at some point after leaving the OR. We compared the same values with the
results summarized in Figure 6. If ECMO was not initiated immediately in
the operating room following the index procedure, the median time to
ECMO was 18 hours (range 1-71 hours).

Patients who were placed on ECMO immediately spent more time in the
operating room and more time on pump. They also required more RBC
transfusions during the case. Patients who were placed on ECMO
immediately were more likely to have an open chest at the end of the
operation (59\% versus 0\%, p 0.002) and were also more likely to return
to the operating room for hemorrhage (50\% versus 9\%, p 0.03). They
were also more likely to be cannulated centrally compared to the delayed
group (50\% versus 9\%, p 0.27). There was not a difference in type of
support required, with VA representing the vast majority of patients in
both groups (86\% versus 73\%, p 0.38).

There was no difference in ability to wean from ECMO, hospital or 30-day
survival between the immediate or delayed ECMO groups. Likewise, there
was not a statistically significant difference in long-term survival
(immediate 50\%, delayed 85\% p 0.24).

Patients supported with VA versus VV ECMO were compared. There were six
patients included in this study who required VV support within 72 hours
of cardiac surgery. Four of the six patients were supported with an RVAD
with in-line oxygenation for profound right ventricular dysfunction
following surgery, and two were purely VV support. All of the above
analysis were performed both including and excluding the six VV patients
and the results were nearly identical. Of all of the comparisons made
between the VA versus VV cohorts, there were no statistically
significant findings (likely related to sample size) other than number
of units of RBCs in the OR with the VA group requiring more blood
(median 2.5 units versus 0 units, p 0.01). The remainder of the findings
are summarized in Figure 7.

There was no difference in type of surgery performed, rates of
reoperation for hemorrhage, site of cannulation, open chest status, or
amount of time to ECMO initiation.

Thirty-six month follow up for hospital survivors was 75\% for VV and
55\% for VA, and did not reach statistical significance for variation (p
0.29), again likely due to a small sample size.

\textbf{Discussion}

ECMO technology, patient selection and its implementation has improved
dramatically since the early studies. This has occurred due to better
circuits, improved oxygenator technology, more experienced teams, and
more informed decision-making regarding timing of implementation. This
increase in the deployment of ECMO is evident in ELSO reporting, with
studies increasing regarding factors impacting survival in different
subsets of ECMO populations.

Interestingly, our data has shown no correlation between survival, and
several factors that had previously been thought to contribute to
mortality; the type of operation, operative times (including cross-clamp
and cardiopulmonary bypass times), open chest status, reoperation for
bleeding, the presence of frozen mediastinum and the timing of
cannulation. Our data has shown that patients who are centrally
cannulated may have a trend toward ability to wean from ECMO, with a
non-significant trend toward short and long-term survival as well. One
possible consideration may be more efficient venous drainage and cardiac
offloading via central cannulation, as the timing of cannulation was not
a key factor in survival based on our analysis.

One critique of the study could be the inclusion of VV patients with a
VA ECMO cohort. We included these patients as they represented severe
organ impairment in the postoperative period, and the majority of these
patients were supported with RVAD with in-line oxygenator representing
RV failure, a known indicator of mortality in postcardiotomy
patients\textsuperscript{{[}7{]}}. Though a small sample size, no
statistical significance was noted between groups. Of note, analysis was
also conducted for every comparison with and without the VV cohort
included and there were no noted statistically significant differences
in the data at short or long-term follow-up.

The use of ECMO in the post-cardiotomy population has been reported to
have high morbidity and mortality with ability to wean from ECMO
\textless{}50\% and hospital survival ranging between 25-40\%, and
minimal data on long-term outcomes available. Our experience has
demonstrated that PC-ECMO utilization may be associated with a
reasonable rate of long-term survival. Overall survival data in our
PC-ECMO group was: 61\% were weaned, 55\% survived hospitalization, and
45\% were alive one month after discharge. This compares favorably to
data from the ELSO registry (59\% weaned, 43\% discharged), and
superiorly to ECPR support (41\% weaned, 29\% discharged).

This data also offers a glimpse into long-term survival for PC-ECMO
patients. At 12 months, 40\% of PC-ECMO patients were still alive, and
at almost 3 years after discharge, 33\% of patients were still alive.
The estimated 12 month survival for patients surviving their index
hospitalization was 66\%, and survival was 60\% at both 24 and 36
months, indicating a reasonable prognosis for long-term survival if
patients reach hospital discharge. For reference, in renal failure
patients receiving hemodialysis, the median survival at 3 years is
approximately 57\%\textsuperscript{{[}8-9{]}}. Data exists for many
chronic medical processes with five-year survival rates to use as a
comparison (Figure 8). Heart failure, gastric and esophageal cancer,
lung cancer and pancreatic carcinoma all have median survival at 5 years
\textless{}30\%\textsuperscript{{[}10{]}}. More specifically, localized
pancreatic adenocarcinoma carries a median 5-year survival of 34\%,
which is comparable to the overall survival of our PC-ECMO
cohort\textsuperscript{{[}10{]}}. Certainly, medical and surgical
oncologists may advocate for the surgical resection of localized
pancreatic adenocarcinoma, provided that the patient is otherwise an
appropriate surgical candidate\textsuperscript{{[}11{]}}.

More robust data is needed to determine predictors for quality of life
following PC-ECMO, which may yield improved decision-making strategies
for ECMO implementation based on these individual patient
characteristics, allowing physicians to predict which patients stand to
benefit the most from ECMO cannulation from a quality of life
standpoint.

In closing, our results demonstrate that PC-ECMO is a reasonable
strategy to salvage patients who experience refractory post-cardiotomy
cardiogenic shock, and has a 1-year and 3-year survival comparable to
other surgically-treated diseases. Further data is needed to help
characterize which patients may benefit most from ECMO implementation,
but our experience has shown that post-cardiotomy ECMO support is no
longer a bridge to nowhere.

\textbf{FIGURE LEGEND:}

Figure 1: Kaplan Meyer demonstration of survival for patients who were
able to be weaned from ECMO and discharged from the hospital.

Figure 2: Table comparing demographics and perioperative details for
patients who were able to be weaned from ECMO support, versus those who
expired on ECMO.

Figure 3: Table comparing demographics and perioperative details for
patients who were discharged successfully from the hospital, versus
those who expired during their index hospitalization.

Figure 4: Table comparing demographics and perioperative details for
patients who were discharged from the hospital and still alive at 30
days postop, versus non-survivors.

Figure 5: Table comparing demographics and perioperative details for
patients who underwent operation with ``frozen mediastinum'' (either
prior chest radiation or reoperation status) versus those with virgin
chest.

Figure 6: Table comparing demographics and perioperative details for
patients who were cannulated for ECMO during their index operation,
versus those who were not immediately cannulated (median time to
cannulation 18 hours postoperatively).

Figure 7: Table comparing demographics and perioperative details between
VA or VV Postcardiotomy ECMO patients. VV patients included RVAD support
with inline oxygenator.

Figure 8: Comparison of other medically and surgically treated disease
to survival for Postcardiotomy ECMO patients.

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https://www.nccn.org/professionals/physician\_gls/pdf/bone.pdf\selectlanguage{english}
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\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/PC-Figure-6/PC-Figure-6}

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\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/PC-Figure-7/PC-Figure-7}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/PC-Figure-8/PC-Figure-8}

\end{center}
\end{figure}

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