ASAIO Journal 2024 Adult Circulatory Support

Venopulmonary Artery Extracorporeal Life Support (VPa

ECMO): A Novel Strategy for Refractory Hypoxemia
Complicating VV ECMO
Leonardo Alberto Salazar Rojas,* Dafna Isvevia García Gómez,* Yuri Valentina Pinzon Martinez,*
Julie Pauline Lasso Perdomo,* Juan Carlos Soto Ramirez,* Tamar Gorgadze ,† Mary Alejandra Mendoza Monsalve,*
Raul Fernando Vasquez Rincon,* Mario Alberto Castillo Blanco,* Camilo Ernesto Pizarro Gomez,* and
Anderson Bermon Angarita ‡

Refractory hypoxemia (RH) during venovenous extracorpo- as a rescue therapy in patients with severe ARDS.1,2 During
real membrane oxygenation (VV ECMO) support is a complex the coronavirus disease 2019 (COVID-19) pandemic, its use
problem that limits the benefit of this therapy. The need for increased exponentially, although the mortality rate is still
sustained deep sedation and delays in active rehabilitation are around 50%.3 A common problem in VV ECMO patients is the
considered as a direct consequence of RH. Changing from VV development of hypoxemia when sedation is decreased. This
ECMO to a configuration that returns the flow to pulmonary problem limits active rehabilitation and can lead to longer hos-
artery, such as venopulmonary extracorporeal membrane pitalization and worse outcomes.4,5
oxygenation (VPa ECMO) may decrease recirculation and The treatment of hypoxemia in ECMO is challenging and
improve systemic oxygen delivery. We present a retrospective although there are many alternatives, there is uncertainty about
report that describes the impact of VPa ECMO on oxygen- how to address this problem.6 The interventions described
ation during sedation withdrawal in 41 patients who received to deal with hypoxemia focus on two strategies4,7,8: the first
VV ECMO for coronavirus disease 2019 (COVID-19). We evi- is to improve the oxygen supply through the ECMO circuit;
denced that arterial oxygen pressure (PaO2) increased from increasing blood flow, oxygen transport capacity, and decreas-
68 to 112.3 mm Hg (p = 0.001) with a reduction of ECMO ing recirculation by changing the number or position of the
flow (5.7–4.8 L/m; p = 0.001). Other findings included lower cannulas.9 The second strategy is directed to decrease oxygen
rates of depth sedation (Richmond Agitation Sedation Scale consumption by increasing sedation, associating muscle relax-
[RASS] ≤3, 37–63%; p = 0.007) and lower requirement ino- ation, inducing hypothermia, or decreasing cardiac output
tropic support assessed by LVIS score (4.7–1.1; p = 0.005). with β-blockers.10 Although these measures are theoretically
Discharge survival was 54% with a sustained benefit until day and physiologically supported, there is no evidence about its
79. This cannulation strategy improved effectively PaO2 in this benefit.11
cohort, it may be an alternative in patients with RH in VV Venopulmonary extracorporeal membrane oxygenation
ECMO. ASAIO Journal 2023; XX:XX–XX (VPa ECMO) is a novel configuration12 that has been described
in different scenarios of acute heart failure as right ventricular
Key Words: extracorporeal membrane oxygenation, COVID- support,13–15 even in the management of patients with severe
19, outcome and process assessment health care, survival acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infec-
analysis, cardiac surgical procedures tion.16 This configuration potentially decreases recirculation,
increases support efficiency, and could be an alternative in the
From the CESAR and EOLIA studies, venovenous extracor- management of refractory hypoxemia (RH) in VV ECMO.
The aim of this study is to evaluate the impact on arterial
poreal membrane oxygenation (VV ECMO) was established
oxygenation, support efficiency, hemodynamic performance,
and sedation weaning in patients with configuration change
From the *ECMO and VAD program, Fundación Cardiovascular from the VV ECMO configuration to a VPa ECMO.
de Colombia, Floridablanca, Santander, Colombia; †Catheterization
laboratory, Chief medical officer IC-HIC, Fundación Cardiovascular
de Colombia, Floridablanca, Santander, Colombia; ‡Research Center, Materials and Methods
Fundación Cardiovascular de Colombia, Piedecuesta, Santander,
Colombia.
Submitted for consideration April 2023; accepted for publication in Design
revised from December 2023.
Disclosure: The authors have no conflicts of interest to report. Retrospective longitudinal observational study, conducted in
Supplemental digital content is available for this article. Direct URL a hospital in Bucaramanga, Colombia from April 1, 2021, to
citations appear in the printed text, and links to the digital files are June 30, 2022. This study was approved by the ethics commit-
provided in the HTML and PDF versions of this article on the journal’s tee of the Fundación Cardiovascular de Colombia (FCV).
Web site (www.asaiojournal.com).
Correspondence: Anderson Bermon Angarita, Fundacion
Cardiovascular de Colombia—(FCV), Centro Internacional de Patient Population
Especialistas, Office 521s. Valle de Menzuly Km 7, Piedecuesta,
Santander, Colombia. Email: andersonbermon@fcv.org. Patients older than 18 years with a confirmed diagnosis of
Copyright © ASAIO 2024 SARS-CoV-2, managed with VV ECMO (venous femoral can-
DOI: 10.1097/MAT.0000000000002125 nula for extraction and internal jugular cannula for return in all

1
Copyright © ASAIO 2024
2 SALAZAR ROJAS ET AL.

cases) and who presented episodes of hypoxemia when seda- approach to improve oxygenation. However, as we gained
tion was decreased and received a change of configuration to confidence in this strategy, it was offered earlier to patients
VPa ECMO were included in the study. with RH. Therefore, the change of configuration took longer
Due to a lack of supplies during the pandemic, ECMO cir- at the beginning of the pandemic. Currently, conversion to
cuit was built using different consoles, pumps, oxygenators, VPa is indicated for patients who experience desaturation on
and cannulas according to availability. During the analysis awakening, despite an increase in flow and hematocrit.
period, 111 patients with COVID-19 were admitted to VV
ECMO. Seventy-three COVID-19 patients required a change
Technical Details of Recannulation
from VV to VPa ECMO due to RH. Extracorporeal membrane
oxygenation flow reinfusion in pulmonary artery was possible The VPa ECMO cannulation procedure was performed in the
in 41 patients. In these patients, we used percutaneous venous Cath-Lab under general anesthesia. Venovenous ECMO support
cannulas with only side holes near the tip. In the remaining was maintained during the procedure. Seven French catheter
patients (n = 32), bi-caval cannulas with both proximal and dis- was inserted into the left or right subclavian vein under ultra-
tal holes were used. In this case, part of the reinfusion ECMO sound guidance. Venography was performed to assess vessel
flow was delivered in the right atrium. Double-lumen cannulas size and anatomy. If the anatomical structure was normal, a 5
were not used in any patient. Venopulmonary patients were Fr multipurpose catheter and a Teflon-coated diagnostic guide-
defined as those with blood reinfusion exclusively in the pul- wire were inserted into an inferior branch of the right pulmo-
monary artery (Figure 1). nary artery. Over the multipurpose catheter, the diagnostic
The weaning from sedation started in the first 72 hours. wire was exchanged for a high-support Amplatz Super Stiff
Extracorporeal membrane oxygenation and fresh gas flow (Boston Scientific, Malborough, MA) wire. The catheter was
were modified according to the patient’s metabolic activity removed, and the 7 Fr was introduced. Progressive dilations
to obtain an oxygen saturation greater than 90%, without were performed to a diameter of 20 Fr and a venous cannula
dyspnea or respiratory acidosis. The hemoglobin transfusion was advanced with only distal fenestrations while heart rate and
threshold was 8 g/dl; if the patient increased work of breath- hemodynamic stability were assessed. The tip of the cannula was
ing or decreased saturation below 90% despite changes in advanced into the pulmonary artery and an angiography was
ECMO flow this threshold was increased to 10 g/dl. If the performed through the cannula verifying bilateral lung perfusion
desaturation episodes limited the rehabilitation process, cir- meaning that all the fenestrae were above the pulmonary valve.
cuit configuration was changed to provide up to 7 L of ECMO The ECMO return was connected to the pulmonary cannula and
flow. Finally, if this was insufficient, the configuration was the right jugular cannula was removed. After the 24 hours post-
changed to VPa ECMO. Early in the pandemic, it was observed cannulation, a control echocardiogram was performed to rule
that certain types of patients (such as those with morbid obe- out procedure complications (all the procedure is presented in
sity) undergoing VV ECMO struggled to achieve oxygen- the Supplemental Material, Supplemental Digital Content, http://
ation goals despite the mentioned strategies. Therefore, the links.lww.com/ASAIO/B183). The oxygenator was only replaced
indication for conversion to VPa was proposed as the final during the configuration change in five patients (12.2%).

Figure 1. Flow diagram. None of the patients were cannulated with double lumen cannula because they were not available in the country.
VPa ECMO, venopulmonary artery extracorporeal membrane oxygenation; VV ECMO, venovenous extracorporeal membrane oxygenation.

Copyright © ASAIO 2024

 VPA CANNULATION FOR HYPOXEMIA IN VV ECMO 3

Complications inotropic support. The change of configuration to the VPa

ECMO was performed an average of 14 days after the initial
Complications following the procedure were defined as
ECMO cannulation (Table 1).
those that required intervention or resulted in death and could
On the first day after the change of configuration to VPa
be attributed to the procedure itself.
ECMO, PaO2 increased by a mean of 44 mm Hg. Before
Data were collected in RedCap (RM) from clinical records.
the intervention, 73% of patients had a PaO2 below 80 mm
Double entry was performed with blinding of both parties, and
Hg; this value decreased to 31%. The ECMO flow, the cen-
data were captured at three different moments: 1 day before
trifugal pump revolutions, and the sweep gas flow dropped
and 2 days after the intervention.
significantly after the change to VPa ECMO, as shown in
Recorded data included sex, age, body mass index (BMI),
Table 2.
mechanical ventilation before ECMO cannulation, precan-
In patients with membrane change (n = 5) during the switch
nulation ventilatory parameters, days on ECMO before the
of configuration, PaO2 on the first day was 127 mm Hg (IQR:
change of configuration. Richmond Agitation Sedation Scale
123–128) vs. 105.8 mm Hg (IQR: 69.3–174.3) in patients
(RASS), ECMO parameters, arterial blood gases, and inotropic
without membrane change (n = 36). Adjusted linear regres-
support were evaluated 1 day before and 2 days after the inter-
sion analysis revealed that the improvement in PaO2 associ-
vention. Survival to hospital discharge was reported.
ated with the configuration change was not explained by the
membrane change.
Statistical Analysis Moderate to high support was defined as an LVIS score
greater than 10. On the day before the VPa configuration, seven
A descriptive analysis of the data was carried out, report-
patients had LVIS greater than 10; at 2 days of VPa ECMO, only
ing percentages for the categorical variables and medians, and
one patient required moderate to high support. Absolute LVIS
their interquartile range (IQR) was described for continuous
also decreased significantly (Figure 2).
variables. Bivariate analysis was performed according to the
Patients with deep sedation assessed as RASS ≤−3 decreased
normality. The differences between the results obtained were
in the first 2 days after switching to ECMO VPa (26/41 to 13/41
performed using the Mann-Whitney U and bivariate logistic
patients) (Table 2, Figure 2).
(RASS ≤3; arterial pressure of oxygen (PaO2) <80) or linear
Four patients required interventions for procedure-related
(pump flow; Levosimendan Vasopressor Inotropic Score [LVIS])
complications. One patient died due to cardiac tamponade
regression. To assess the effect of membrane change during VPa
and hemothorax, requiring emergency pericardiocentesis,
configuration on arterial oxygen pressure (PaO2) levels the day
thoracostomy, and conversion to VA ECMO. One patient pre-
after, a linear regression was also performed. Finally, the sur-
sented a right subclavian artery lesion, with a pseudoaneurysm
vival and condition of the patients at hospital discharge were
that required placement of a covered self-expanding stent. Two
described by means of an actuarial table.
patients presented atrial fibrillation managed with intravenous
antiarrhythmic (amiodarone).
Results The patients required ECMO support on average 79 days
During the study period, 111 patients with ARDS due to (minimum 15 days and maximum 214 days). Survival to hospi-
SARS-CoV-2 infection required VV ECMO, 36.2% (41 patients) tal discharge was 54% (Figure 3).
received a cannulation with exclusive return to VPa ECMO
(Figure 1). Most were male with a median age of 51 years. Discussion
Before ECMO cannulation, they presented severe hypoxemia, There are few data about the use of pulmonary artery can-
high ventilator parameters, and nearly half of them needed nulation associated with ECMO. It has been used mainly for

Table 1. Sociodemographic Characteristics and Pre-VV ECMO Cannulation Characteristics of the Study Population

Data
Characteristics n (%)

Sex (male)* 29 (70.7%)

Age (years)† 51 (45–62)
Days on mechanical ventilation before VV ECMO† 6 (3–9)
Body mass index† 29.1 (27.7–33.1)
Arterial pH† 7.41 (7.39–7.44)
PaO2 (mm Hg)† 72.7 (65.5–77.9)
PaCO2 (mm Hg)† 45.8 (40.5–48.2)
PaFi† 71 (60–85)
Driving pressure (cm H2O)† 19.5 (15.5–25)
Respiratory rate (breaths per minute)† 20 (20–24)
Peak pressure (cm H2O)† 31 (27.5–36.5)
Patients with inotropic support* 20 (48.7%)
VV ECMO before VPa ECMO cannulation (days)† 9 (5–14)

*n (%).
†Median (interquartile range).
PaCO2, arterial carbon dioxide pressure; PaFi, arterial oxygen pressure/fraction of inspired oxygen; PaO2, arterial oxygen pressure; VPa
ECMO, venopulmonary artery extracorporeal membrane oxygenation; VV ECMO, venovenous extracorporeal membrane oxygenation.

Copyright © ASAIO 2024

4 SALAZAR ROJAS ET AL.

Table 2. Hemodynamic Parameters, Arterial Blood Gases, and Inotropic Support

1 Day Before 1 Day After 2 Days After

RASS ≤−3* 26 (63.4%) 21 (51.2%) 17 (41.5%)

ECMO revolutions† 3,150 (3,000–3,280) 2,930 (2,700–3,090) 2,945 (2,715–3,123)
Blood flow rate (LPM)† 5.7 (5.2–6.05) 4.8 (4.5–5.4) 5 (4.3–5.4)
Sweep gas flow (LPM)† 10 (7–13) 6 (5–12) 7.5 (5–11)
PaO2 (mm Hg)† 68.5 (57.1–79.1) 112.3 (70.5–173) 95.7 (74.5–149.6)
Patients PaO2 <80* 30 (73.2%) 13 (31.7%) 12 (29.3%)
PaCO2 (mm Hg)† 44.2 (40.8–47.5) 44 (38.7–50.7) 46 (46.1–149.6)
Patients with inotropic support* 15 (36.6%) 11 (26.8%) 7 (17.1%)
LVIS‡ 4.7 (8.9) 2.8 (8.3) 1.1 (3.1)
Patients with LVIS >10* 7 (17.1%) 3 (7.3%) 1 (2.4%)
FiO2 (ventilator)† 70% (50–100%) 50% (50–100%) 50% (50–80%)
PEEP† 10 (8–10) 10 (8–10) 10 (8–10)
Neuromuscular blockers 2 (4.9%) 4 (9.8%) 1 (2.4%)

*n (%).
†Median (interquartile range).
‡Mean (standard deviation).
ECMO, extracorporeal membrane oxygenation; FiO2, fraction of inspired oxygen; LVIS, Levosimendan Vasopressor Inotropic Score; PaO2,
arterial pressure of oxygen; PaCO2, arterial pressure of carbon dioxide; PEEP, Positive end-expiratory pressure; RASS, Richmond Agitation
Sedation Scale.

Figure 2. Significance of variables over time. *A longitudinal analysis was performed, using bivariate logistic regression comparing the
number of patients who 1 day before VPa had RASS ≤3 or >3 with patients who had RASS ≤3 or >3 one and two days after VPa. Likewise,
the number of patients who had pO2 <80 or PO2 >80 one day before VPa was compared with those who had pO2 <80 or PO2 >80 one day
and two days after VPa. For these comparisons, the dependent variables were RASS and PaO2. For the quantitative variables, bivariate linear
regressions were performed, comparing the LVIS score 1 day before vs. 1 and 2 days after VPa and pump flow 1 day before vs. 1 and 2 days
after VPa. For these comparisons, the dependent variables were LVIS and pump flow. CI, confidence interval; Coef, linear regression coef-
ficient; LVIS, Levosimendan Vasopressor Inotropic Score; PaO2, arterial pressure of oxygen; RASS, Richmond Agitation Sedation Scale; RR,
relative risk; VPa, venopulmonary artery.

hemodynamic support in right ventricular failure. We describe The ELSO registry shows a 90 day mortality between 36.9%
the results of 41 patients between April 1, 2021, and June 30, and 51.9%, reflecting great variability, according to the ECMO
2022, who received VPa ECMO as a treatment for RH on VV center, and the cohort assessed.3,17 The mortality at hospital
ECMO. discharge in our cohort was 46%.

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 VPA CANNULATION FOR HYPOXEMIA IN VV ECMO 5

Figure 3. Actuarial survival, discharge from ECMO, and discharge from the ICU. ECMO, extracorporeal membrane oxygenation; ICU,
intensive care unit.

The survival reported in patients with VPa ECMO is appar- ECMO cannulation.10,19,20 In patients with ARDS and hemody-
ently better than that obtained with VV ECMO.18 However, these namic instability due to right ventricular dysfunction, VPa can-
reports are case series with few patients and a follow-up of less nulation has shown a significant decrease in inotropic support
than 60 days. Badu et al.14 reported experience in the use of VPa and central venous pressure.14 In our cohort, VPa configuration
ECMO with ProtekDuo cannula for the treatment of right ven- was associated with a significant decrease in inotropic support.
tricular failure in three subgroups of patients, one of these cohorts It is possible that the need of high support was secondary to
had associated respiratory failure. In-hospital mortality at 40 days right ventricular failure, however, we did not evaluate system-
in 10 patients with ARDS was 32.5%. Subsequently, he described atically the right ventricular function in these patients due to
early use of the VPa cannula in 18 patients with ARDS by SARS- personnel limitations triggered by the pandemic.
CoV-2, with significantly lower 30 day mortality compared to The technique described for VPa ECMO uses a double-
patients managed exclusively with mechanical ventilation (11% lumen cannula designed for this position (Protekduo), which
vs. 52.4%; p = 0.008).16 We present a final outcome in a cohort is not available in our country. Therefore, we use a double
of patients who developed RH on VV ECMO with survival to dis- cannulation technique with an extraction cannula in the right
charge similar to that reported in COVID-19 ECMO patients. atrium and, out of label, a straight return cannula in the pul-
Refractory hypoxemia in VV ECMO patients limits the sur- monary artery.21,22 The ProtekDuo cannula may provide around
vival benefit of this therapy.6 Increased work of breathing usu- 4, 5 L of blood flow per minute.21,22 In contrast, in our cohort
ally leads to deepening sedation delaying the onset of active with the two cannula VPa configuration, flow rates up to 5. 5 L
rehabilitation.4 The intervention proposed for the treatment were achieved.23
of hypoxemia related to sedation weaning was the change of When the pulmonary artery cannula was advanced into a
configuration to an exclusive pulmonary artery return cannula. pulmonary artery branch, the angiography revealed preferen-
This intervention was associated with an increase in PaO2 tial flow. Selective pulmonary artery branch cannulation may
and a decrease in the number of patients with PaO2 <80 mm produce unilateral pulmonary edema and should be avoided.
Hg. This improvement in oxygenation was accompanied by a High-flow VPa ECMO can lead to cardiogenic pulmonary
decrease in the need for ECMO flow, which reflects a higher edema in patients with left ventricular failure. Our recom-
efficacy of support. This effect may be explained by the reduc- mendation is to assess the impact of this configuration on the
tion in recirculation. left ventricle diameter and ejection fraction, as well as its fill-
The aim of our intervention was to ensure better oxygenation ing pattern. Venopulmonary artery ECMO should be avoided
when oxygen consumption increases, for example, during the in patients with decreased left ventricular function or mitral
decrease of sedation and the start of rehabilitation. After the stenosis.
initiation of ECMO VPa, it was possible to significantly reduce The placement of venous cannula in the pulmonary artery
the level of sedation assessed by the RASS scale. The impact of has the potential to lead to life-threatening complications. In
VPa ECMO in rehabilitation progress needs to be assessed by our cohort, vascular and cardiac complications occurred in
further studies. the first cases, in the latest cases, we have not experienced
Right ventricular dysfunction is common in patients with any of these technical problems. A multidisciplinary team
ARDS. This dysfunction persists even after conventional VV integrated by ECMO intensivist, interventional cardiologist,

Copyright © ASAIO 2024

6 SALAZAR ROJAS ET AL.

and cardiovascular surgeon may reduce the risk of procedure- support versus extracorporeal membrane oxygenation for
related complications. The use of multimodality imaging for severe adult respiratory failure (CESAR): A multicentre ran-
domised controlled trial. Lancet 374: 1351–1363, 2009.
vascular access, dilations, and cannula advancement is key for 3. Barbaro RP, MacLaren G, Boonstra PS, et al; Extracorporeal Life
a safe procedure. Support Organization: Extracorporeal membrane oxygenation
In our cohort, change of configuration was offered only to for COVID-19: Evolving outcomes from the international
patients who experienced RH during sedation weaning. This Extracorporeal Life Support Organization Registry. Lancet 398:
was associated with an increase in the spontaneous respiratory 1230–1238, 2021.
4. Montisci A, Maj G, Zangrillo A, Winterton D, Pappalardo F:
effort that might worsen lung injury. The use of this strategy Management of refractory hypoxemia during venovenous
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should be evaluated in the future. 227–236, 2015.
Although the duration of VV ECMO in patients with COVID- 5. Haji JY, Mehra S, Doraiswamy P: Awake ECMO and mobilizing
patients on ECMO. Indian J Thorac Cardiovasc Surg 37: 309–
19 is longer than that reported for influenza ARDS,19 the dura- 318, 2021.
tion of VPa ECMO support in our cohort is longer than that 6. Nunes LB, Mendes PV, Hirota AS, et al; ECMO Group: Severe
reported in the ELSO registry in COVID.17 We do not know hypoxemia during veno-venous extracorporeal membrane oxy-
whether this strategy may be associated with this outcome. genation: Exploring the limits of extracorporeal respiratory sup-
port. Clinics (Sao Paulo) 69: 173–178, 2014.
7. Messai E, Bouguerra A, Guarracino F, Bonacchi M: Low blood
Limitations arterial oxygenation during venovenous extracorporeal mem-
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This is a single-center retrospective study, with data obtained management. J Intensive Care Med 31: 553–560, 2016.
from electronic medical records. We do not have consistent 8. Patel B, Arcaro M, Chatterjee S: Bedside troubleshooting during
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Thorac Dis 11: S1698–S1707, 2019.
or serial recirculation measurements that could provide addi- 9. Conrad SA, Wang D: Evaluation of recirculation during venove-
tional information on the physiologic impact of this strategy. nous extracorporeal membrane oxygenation using computa-
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10. Bunge JJH, Diaby S, Valle AL, et al: Safety and efficacy of beta-
stress and a shortage of ECMO supplies during the pandemic. blockers to improve oxygenation in patients on veno-venous
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Conclusions nulation ECMO. Extracorporeal Membrane Oxygenation:
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The change of configuration from VV ECMO to VPA MS., 2016.
ECMO settings in patients who develop hypoxemia during 13. Lorusso R, Raffa GM, Heuts S, et al: Pulmonary artery cannulation
to enhance extracorporeal membrane oxygenation manage-
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reported literature of this intervention is the reduction in ino- monary artery cannulation to treat acute secondary right heart
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associated with the procedure and a survival to hospital dis- genation. ASAIO J 68: 1483–1489, 2022.
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Acknowledgment Brewer JM: The ProtekDuo in ECMO configuration for ARDS
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Nathalia Andrea Rodríguez-Álvarez, Andrés Felipe Pimiento-Macías, tion in patients with COVID-19: A systematic review and meta-
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