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\begin{document}

\title{Successful use of veno-venous extracorporeal membrane oxygenation for
acute chest syndrome in a child with sickle cell disease and SARS-CoV-2}



\author[1]{Wonshill Koh}%
\author[1]{Punam Malik}%
\author[1]{Jason Whitehead}%
\author[1]{David Morales}%
\author[1]{Don Hayes}%
\affil[1]{Cincinnati Children's Hospital Medical Center}%


\vspace{-1em}



  
  \date{May 19, 2024}


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\selectlanguage{english}
\begin{abstract}
Children with sickle cell disease (SCD) are at increased risk for severe
illness due to severe acute respiratory syndrome Coronavirus 2
(SARS-CoV-2). We describe the successful native lung recovery of a child
with SCD referred for lung transplant (LTx) evaluation who was on
prolonged veno-venous extracorporeal membrane oxygenation (VV-ECMO). He
initially presented with acute chest syndrome complicated by SARS-CoV-2
infection that ultimately required dual-lumen, single bicaval VV-ECMO
cannulation for respiratory support. Despite increased risk of hemolysis
and thrombosis from SCD and SARS-CoV-2 infection, he was successfully
supported on VV-ECMO for 71 days without complications leading to native
lung recovery with meticulous management of his SCD therapy. This report
provides new insight on our approach to VV-ECMO support in a child with
SCD and SARS-CoV-2 infection. With a successful outcome, the patient has
returned home but still on mechanical ventilation with LTx still an
option if he is not eventually liberated from invasive respiratory
support.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Sickle cell disease (SCD), a hereditary recessive hemoglobinopathy,
disproportionately affects the African-American population and is
associated with vaso-occlusion, such as acute chest syndrome
(ACS).\textsuperscript{1} The severe acute respiratory syndrome
Coronavirus 2 (SARS-CoV-2) global pandemic has negatively impacted
children with SCD, leading to more intensive care unit admissions and
increased mortality.\textsuperscript{2} In children with acute
respiratory distress syndrome (ARDS) due to SARS-CoV-2, there is a
quickly rising need for extracorporeal mechanical oxygenation (ECMO)
support.\textsuperscript{3} Notably, ECMO in SARS-CoV-2 increases risk
of thromboembolism and coagulopathy, which is heightened in children
with SCD.\textsuperscript{4} The literature shows that ECMO use in the
SCD population is increasing, but a lingering degree of uncertainty
persists given their underlying propensity for hemolysis, stroke, and
thrombosis.\textsuperscript{5} In this correspondence, we report the
successful prolonged use of veno-venous ECMO (VV-ECMO) as a bridge to
recovery in a child with SCD who developed refractory ARDS due to
SARS-CoV-2.

\textbf{Case Description}

An 11-year-old, 40kg, boy with sickle cell anemia (HbSS), asthma, and
obstructive sleep apnea was transferred to our End-stage Lung Failure
Program for consideration for ECMO bridge to lung transplant (LTx). Upon
initial presentation at the local facility, he was diagnosed with ACS
due to SARS-CoV-2 and received supplemental oxygen, corticosteroids,
convalescent plasma, and remdesivir, but his hypoxemia worsened despite
the escalation of maximum conventional mechanical ventilation and
proning. His chest X-ray showed diffuse bilateral airspace opacities and
a large pneumomediastinum from the significantly high ventilator
pressures (Figure 1A). To sustain life, he underwent cannulation of the
right internal jugular with a 27 Fr dual-lumen, single bicaval catheter
on hospital day 15 for VV-ECMO. Over the next three weeks, there was no
evidence of lung recovery with multiple failed VV-ECMO weaning trials.
Therefore, he was transferred to our institution on ECMO day 43. To
maximize rehabilitation, a tracheostomy was placed for liberation from
sedation. While at our institution, a total of six exchange transfusions
were performed to strictly target a hemoglobin S (HbS) level [?]15\% to
minimize the effect of sickled red blood cells (RBCs) (Figure 2).
Routine transfusions were performed per our institutional ECMO protocol
with packed RBCs and Fresh frozen plasma (FFP) with extended blood group
matching for the E, Kell, and Duffy antigens to minimize the risk of
alloimmunization. His VV-ECMO course was uncomplicated without major
bleeding or thrombotic events. Surveillance echocardiograms showed
stable right ventricular pressure and function. The intensive physical
rehabilitation and maximal enteral nutrition via gastrostomy tube
significantly improved his deconditioning and allowed for weaning of
VV-ECMO support. He was successfully decannulated after 71 days of
VV-ECMO. On post-decannulation chest X-ray, he had bilateral patchy
airspace opacities but with marked improvement from his pre-ECMO
appearance (Figure 1B). Due to his complicated course, hydroxyurea
therapy was re-initiated while on ECMO and maximized with an increase of
fetal hemoglobin (HbF) levels from 0.3\% to 11.5\% during three months
of therapy. He was also transitioned to enoxaparin therapy for an
additional 2 weeks upon ECMO decannulation and then to apixaban during
hospitalization given an increased risk of thrombosis due to SCD and
SARS-CoV-2. After completing inpatient rehabilitation, he was ultimately
discharged home with chronic mechanical ventilation five months after
his initial presentation.

\textbf{Discussion}

ACS is one of the leading causes of mortality and morbidity in patients
with SCD.\textsuperscript{6} Given the propensity of pulmonary disease
in patients with SCD, any infectious process including SARS-CoV-2 can
exacerbate ACS and lead to life threatening refractory hypoxemic ARDS as
seen in our case through the sequestration of sickled RBCs. With limited
data detailing SARS-CoV-2 in children with SCD, our case illustrates key
elements that provide a treatment strategy for ECMO support which
allowed this patient to recover but also allowed for rehabilitation to
improve his candidacy for LTx.

As the ECMO circuit can exacerbate sickling and hemolysis, we believe
aggressive management of the HbS level maintaining a level [?]15\% while
on ECMO was critical in our management and contributed to the positive
outcome for this patient as we believe it prevented end organ damage
from vaso-occlusive events from further sickling. Pro-active and
pre-planned changes of oxygenator or circuit based on fibrin deposit
burden and the free plasma hemoglobin level also prevented further
hemolysis leading to end organ dysfunction or disastrous circuit
failure. We also maximized the hydroxyurea therapy to increase the level
of anti-sickling HbF level, in an attempt to minimize overall blood
transfusion requirements, thereby lowering risk of allosensitization,
should he later require LTx. The hydroxyurea-induced increase in HbF
level also allowed liberalization of his exchange transfusion
requirement to maintain HbS levels \textless{}30\% upon discharge. The
patient has returned home but continues to require chronic mechanical
ventilation and is only tolerating a very prolonged wean from mechanical
ventilation. He participates in physical rehabilitation without need for
re-hospitalization, which enhances his potential for full recovery or
makes his future candidacy for LTx more favorable as pre-transplant
hospitalizations is associated with increased morbidity and mortality
post-LTx.\textsuperscript{7}

\textbf{Conclusion}

At present, there is no consensus or published guidelines on ECMO
management in the sickle cell patient population; hence, there are no
recommendations for this patient population with SARS-CoV-2 infection.
With no immediate end in sight for the ongoing pandemic, any new
information that can shed a light on clinical management of sickle cell
patients with SARS-CoV-2 infection is greatly needed. Despite having SCD
and SARS-CoV-2, our patient was supported on VV-ECMO for 71 days with a
favorable outcome and without thrombosis, bleeding, pulmonary
hypertension, end organ dysfunction, or sepsis as a bridge to recovery
through a comprehensive multidisciplinary team effort.

\textbf{Conflicts of Interests}

The authors declare that there are no disclosures and no conflicts of
interests.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. \emph{N Engl J
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\item
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\item
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\item
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\item
  Kuo KW, Cornell TT, Shanley TP, et al. The use of extracorporeal
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\item
  Ruhl AP, Sadreameli SC, Allen JL, et al. Identifying Clinical and
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\item
  Rudym D, Benvenuto L, Costa J, et al. What Awaits on the Other Side:
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  Hospitalization. \emph{Ann Transplant} 2020;25:e922641.
\end{enumerate}\selectlanguage{english}
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