Chapter 1: ECMO

History and development:

Gibbon discovered the benefits of a disk-oxygenator in the mid-1950s, thus, he
provided an important tool for prolonged cardiac operations. Accordingly, extra-
corporeal oxygenation was developed to support patients who had severe
cardiopulmonary dysfunction. Since then, Callaghan et al. documented the first
animal ECMO experiment on preterm neonate dogs with acute respiratory distress
syndrome (ARDS) in 1961 and in 1979, 90% mortality had been reported in a
randomized control study of adult patients with ARDS. With the advanced
technological development of the silicon oxygenator and dialyzer, improved
monitoring and control of gas and blood flow, and a better under-standing of
ECMO physiology, survival rates had dramatically improved, as illustrated in
several studies, during the H1N1 influenza pandemic. According to the
Extracorporeal Life Support Organization (ELSO), about 100,000 ECMO runs had
been reported worldwide at more than 300 centers, with 68 percent ECMO
survivors and 56 percent surviving to discharge.

ECMO system and cannulations:

The use of Extracorporeal membrane oxygenation is to bypass the
cardiopulmonary system, mainly in in-tractable conditions where all other therapy
options fail or are unfeasible. The idea of bypassing the heart and lungs is to
supply oxygenated blood directly to the body tissues independently, which gives
the heart and lungs enough time to recover.
The decision of whether to connect a patient to veno-arterial (VA) or veno-venous
(VV) ECMO depends on the patient’s illness and situation. This system provides
short-term mechanical circulatory support in varied acute life-threatening
conditions, and it also provides proper and effective body tissue oxygenation in
cases of respiratory failure such as ARDS. In such cases, VV ECMO bypasses the
failing lungs and also provides circulatory and hemodynamic sup-port in cases of
cardiac failure like in post-myocardial infarction and cardiogenic shock. In such
cases, VA ECMO is used to bypass the heart–lung system.
Veno-arterial ECMO cannulation is done by introducing a large venous cannula to
the venous system and a smaller arterial cannula to the arterial system. Blood that
exits the body is driven by gravity and the low negative pressure generated by the
centrifugal pump, it passes through the silicon heparin-coated tubes to the
centrifugal pump, then through the polymethyl pentene hollow fiber membrane
oxygenator where gas exchange takes place, before returning the now oxygenated
blood to the arterial system.
In VV ECMO, two large venous cannulas are introduced to the venous system; one
pulls the blood from the vena cava system to the ECMO circulation, while the
other drives the oxygenated blood back to the right atrium.
Multiple modes of ECMO system cannulation are described involving different
arterio-venous combinations and cannulation sites, depending on the situation. The
combinations most commonly used are the veno-venous-arterial (VVA) and the
veno-arterial-venous (VAV) cannulations. The VVA initially functions as a VV,
with an arterial line added as needed, while the VAV is initially a VA with the
venous line added as needed. Those combinations allow physicians to better
control the blood outflow distribution, pressures, and, ultimately, the
hemodynamics. These so-called “hybrid ECMO modes” are used mainly for
dynamic ECMO patients where the site of cannulations or the blood flow and
distributions need to be modified in accordance with the patient’s situation.

Indications and contraindications:

Despite ECMO being a life-saving procedure, it is dangerous and risky. Hence
careful and proper patient selection as well as following appropriate and well-
established implant procedure techniques is of vital importance. Patients eligible
for ECMO are usually critically ill with progressing cardiopulmonary condition;
timing is crucial, and a decision whether to connect these patients to ECMO must
be made quickly and accurately. While examining the patient, ECMO physicians
usually rapidly examine the patients, considering some indications and ruling out
some contraindications before making decisions.
The most common indications for VV ECMO are hypoxic respiratory failure and
ARDS. According to ELSO, ECMO ought to be considered if the mortality risk is
50% and is indicated if the mortality risk is 80% despite optimal mechanical
ventilation. Treating such conditions with ECMO is done only after all other
therapeutic options for the failing lungs have been exhausted, such as ideal
mechanical ventilation, nitric oxide, prone positioning, and other lung recruitment
maneuvers. Other indications could be CO2 retention on optimal mechanical
ventilation, severe air leak syndrome, need for intubation in a patient on the lung
transplant list, and immediate respiratory collapses like in pulmonary embolism or
blocked airway.
As for VA ECMO, the indications are conditions that lead to cardiac insult and
consequently cardiogenic shock and heart failure, such as myocardial infarction,
myocarditis, cardiomyopathies, and others. Other indications for VA ECMO can
be failure to wean from cardiopulmonary bypass machine in open-heart surgery,
refractory cardiopulmonary resuscitation (CPR), or as a bridge to assist device or
heart transplant.
According to ELSO, there aren’t any absolute contra-indications for ECMO use;
the physician calculates the risks and benefits for each patient individually and
decides whether or not to initiate ECMO. However, some conditions may predict
worse outcome due to poor prognosis despite ECMO and are considered relative
contraindications, for example, pro-longed (>7 days) high ventilation settings,
prior conditions with poor prognosis (e.g. malignancies, major bleedings, and in
the elderly, even though there is no specific age contraindication).

Complications of ECMO:
Bleeding and thromboembolism are the major complications.
Bleeding — Bleeding occurs in 30 to 50% of patients who receive ECMO and can
be life-threatening. It happens because of both the continuous anticoagulation and
platelet dysfunction. Meticulous surgical technique, maintaining platelet counts
greater than 50,000/mm3, and maintaining the target activated clotting time (ACT)
reduce the likelihood of bleeding.
Intervention is essential when major bleeding occurs. Bleeding resulted from
surgical wounds often requires prompt exploration with liberal use of
electrocautery. Hemorrhage into body cavities (eg, abdomen, pleural space) could
require surgical exploration to achieve hemostasis, after which vacuum-assisted
closure is recommended as it allows removal and measurement of the blood.
Plasminogen inhibitors (eg, aminocaproic acid) can be infused or heparin can be
discontinued for several hours, but these actions could increase the risk of circuit
thrombosis. Infusion of activated factor VII has been reported with mixed results
and should only be considered for life-threatening hemorrhage after all other
options failed.
The target ACT is generally reduced once bleeding occurs and infusions of
anticoagulant are reduced or held. For example, the target ACT may become 170
to 190 seconds, instead of 210 to 230 seconds. With the use of modern devices the
anticoagulation can be stopped altogether for days if bleeding is a problem.
Recombinant factor VIIa had been administered to some cases of refractory
bleeding.
Thromboembolism — Systemic thromboembolism because of thrombus
formation within the extracorporeal circuit is a complication that can be
devastating with one report suggesting rates of pulmonary embolism as high as 16
percent; rates of deep venous thrombosis may be higher (up to 70 percent) and
could be associated with cannulation, especially femorofemoral cannula. Its impact
is much bigger with venoarterial (VA) ECMO than venovenous (VV) ECMO
because infusion is into the systemic circulation. Anticoagulation that achieves its
target ACT and vigilant observation of the circuit for signs of clot formation
successfully prevents thromboembolism in most of the patients.
The observation of the circuit for signs of clot formation includes routine
inspection of all connectors and monitoring the pressure gradient across the
oxygenator. Sudden change in the pressure gradient suggests that a thrombus had
developed. Immediate circuit or component exchange is required with large or
mobile clots. Primed circuits are generally kept at the bedside if the target ACT has
been reduced due to bleeding because the risk of thrombus formation is greatest in
this situation. Having a primed circuit available facilitates urgent exchange, if
needed.
Neurological — The incidence of neurologic injury in adult respiratory failure
patients recorded in the Extracorporeal Life Support Organization (ELSO) registry
and others is approximately 10%. The incidence in cardiac failure and for those
whom ECMO is administered during cardiopulmonary resuscitation is 50%
Cannulation-related — A variety of complications may occur during cannulation,
including vessel perforation with hemorrhage, arterial dissection, distal ischemia,
and incorrect location (eg, venous cannula within the artery). These complications
are considered rare (<5%). A skilled and experienced surgeon is important to avoid
or address these complications.
Heparin-induced thrombocytopenia — Heparin-induced thrombocytopenia
(HIT) can occur in patients who receive ECMO. In case HIT is proven, the heparin
infusion should be replaced by a non-heparin anticoagulant. Argatroban is favored
because its half-life is short and a similar ACT target range is effective.

Evaluation of ECMO in Egypt:

Extracorporeal membrane oxygenation (ECMO) isn’t a newly discovered
technique. The main goal of ECMO development was trying to maintain tissue
oxygenation through bypassing the lungs when other strategies fail. The theory
was to develop a membrane lung that could withstand hydrostatic pressure and is
permeable to gas exchange.
The alveolar filling affects proper oxygenation in addition to carbon dioxide
removal in severe forms. According to the degree of hypoxemia, ARDS was
categorized with correlation to mortality (Table 1).

Table 1: ECMO cases.

VV ECMO cases Indications MV MURRA Resp. PaO2/ ECMO Hospital Survival
before Y score FiO2 run LOS
ECMO score duration
H1N1 Refractory 3 3.75 5 70 21 44 Survived
hypoxia
Vasculitis Refractory a
hypoxia
3 NA -3 70 13 22 Died
Bacterial Refractory 14 3.75 -8 20 22 27 Died
pneumonia hypoxia and
(4 cases) hypercapnia 4 3.75 -1 70 23 33 Died
4 3.7 5 80 14 20 Survived
4 3.25 5 50 7 30 Survived
Traumatic lung (2 Refractory 1 3.5 1 60 9 39 Survived
cases) hypoxia
3 3.75 2 60 12 27 Survived
Organophosphorus Refractory 3 3.75 3 70 6 28 Survived
hypoxia
Undiagnosed Refractory 2 3.75 6 50 3 26 Survived
hypoxia

This study included all the patients connected to ECMO from January 2014 till
September 2015. The initial ECMO set up was in a single room in the department
with an air fluidized bed.
Upon our arrival to the center all patients were subjected to detailed history of
comorbidities, current illness including onset, duration, progression, investigations
and treatments received. Murray lung injury score (LIS) for the patients was
calculated using four parameters: number of quadrants with consolidation in chest
X-ray, PaO2/FiO2 in mmHg, Positive end expiratory pressure in cm H2O, and
Compliance in ml/cm. The score ranged from 1 to 4, and score above 3 represented
severe ARDS with expected high mortality.

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