Extra-corporeal membrane oxygenation for
paediatric respiratory failure
G J Peek and A W Sosnowski
Heartltnk ECMO Centre, Department of Cardtothoracic Surgery, Glenfield Hospital, Leicester, UK
Extracorporeal membrane oxygenation (ECMO) uses modified cardiopulmonary
bypass technology to provide prolonged respiratory or cardiorespiratory support
for patients of all ages who have failed conventional intensive care management.
The use of ECMO for neonatal respiratory failure is now evidence-based following
the publication of the randomised UK Collaborative Trial. ECMO use in children
remains more controversial, but overall survival of 71% is possible in a group of
moribund patients whose mean PaO2/FIO2 ratio of 61 mmHg accurately predicts
death in studies of conventional ventilation.Common diagnoses for children
requiring ECMO support are pneumonia and the acute respiratory distress
syndrome (ARDS).
Extracorporeal membrane oxygenation (ECMO) uses modified cardiopulmonary bypass technology to provide prolonged cardiorespiratory
support in the intensive care unit. ECMO is usually considered when a
patient has an estimated mortality of 80% despite maximal treatment.
Survival rate with ECMO is 50-95% depending on diagnosis and age
group. We will discuss the principles of ECMO for paediatric respiratory
failure, based on the Extracorporeal Life Support Organisation (ELSO)
registry, published literature and our own experience.
History
Correspondence to
Dr AW Sosnowski,
Director,
Heartltnk ECMO Centre,
Department of
Cardiothoracic Surgery,
Glenfield Hospital,
Leicester LE3 9QP, UK
The concept of using a pump for 'life support' is not new. Richardson
first experimented with such a system in 18651, but was hampered by the
coagulation of the blood. The discovery of heparin in 1916 by McLean2
was a necessary pre-condition to the successful development of
extracorporeal circulation. However, it was the death of a young
woman from pulmonary embolism witnessed by Gibbon that inspired
the development of cardiopulmonary bypass3. Film oxygenators were
not suitable for prolonged perfusion as severe haemolysis occurred after
a few hours4, but they did allow intra-cardiac surgery, demonstrated by
the first successful clinical use of the pump oxygenator by Gibbon to
close an atrial septal defect in 19535. It was the development of the
Bnhih Medico/ Bulletin 1997;53 (No 4) 745-756
© T I M British Council1997
Transplantation
silicone rubber membrane oxygenator by Kolff6, Bramson7 and
Kolobow8 in the late 1950s and early 1960s that allowed prolonged
circulatory support, as the separation of the blood and gas phases greatly
reduced the blood damage. The first ECMO success was in 19729, when
Hill et al used femoro-femoral veno-artenal ECMO to support a 24 year
old man who developed ARDS following a road accident; he was
supported on ECMO for 75 h.
Hill's success generated wide interest in adult ECMO leading to the US
National Institutes of Health (NIH) study in the mid 1970s10'11. This was a
national multi-centre trial in which patients with severe respiratory failure
who fulfilled certain 'ECMO criteria' (fast entry — PaO2 <50mmHg
with FIO2 1 cmH 2 O and PEEP > 5 cmH 2 O: slow entry —PaO 2
<50mmHg for > 12 h with FIO2 >0.6 cmH2O and PEEP > 5 cmH2O
and shunt fraction >30%) were randomised to either receive ECMO or
continue on conventional treatment. The trial was curtailed because of
high mortality in both groups (91.7% conventional and 86.4% ECMO).
Although interest in ECMO waned considerably after the publication
of the NIH study, two groups of researchers, Gattinoni et al in Italy, and
Bartlett et al in the US believed that the fundamental principle of ECMO
was correct and that greater understanding could result in better
outcomes. Gattinoni, in collaboration with Kolobow, developed a low
flow veno-venous system to provide extracorporeal carbon dioxide
removal (ECCO2R) to adult patients. Survivals of 48.8%12 were recorded
which he attributed to use of low pressure and low frequency ventilation
minimising barotrauma. Bartlett held similar beliefs about the importance
of lung rest, but also believed that the neonatal lung had greater
recuperative power than the adult. He reported the first series of successful
neonatal ECMO patients in 198213. Following this lead, other groups
began to experiment with neonatal respiratory ECMO. By the mid 1980s
it was accepted practice for severe neonatal respiratory failure in the US.
Following two modified design trials in the US14-15 and a fully randomised
UK trial16, it is now accepted therapy in this age group in the UK. Bartlett
and other workers also began to extend their practice to include paediatric
patients and, tentatively, adults, using the lessons learnt from the neonatal
age group, namely low level heparinisation, avoidance of haemorrhage,
lung rest and selecting patients with potentially reversible pathology. The
use of veno-venous perfusion became accepted as the mode of choice for
isolated respiratory failure17-18.
Indications and contra-indications
Patients may benefit from ECMO if they have developed severe
respiratory failure refractory to maximal conventional treatment,
746
flnhsh
Madical Bullehn 1997,33 (No A)
Paediatric ECMO
providing that the underlying disease process is potentially reversible.
Contra-indications fall into three main groups concerning: (i) the
reversibility of the disease; (ii) the projected functional status and quality
of life for the patient should they survive; and (iii) contra-indications to
prolonged heparinisation. Conventional treatment can be considered to
have failed when a-A oxygen gradient exceeds 450 mmHg for over 24 h;
this level predicting death most accurately19. Common diagnoses include
pneumonia and the acute respiratory distress syndrome (ARDS).
Pneumonia may be bacterial, atypical or viral (especially respiratory
syncitial virus, RSV). ARDS may follow sepsis, massive transfusion,
smoke inhalation or trauma. Often patients with sepsis present in multiorgan failure with impaired tissue oxygen delivery despite inotropic
support: these patients may benefit from veno-arterial (VA) ECMO.
Absolute contra-indications are irreversible ventilator lung injury and
intra-cranial haemorrhage. Irreversible ventilator lung in]ury due to
barotrauma, volutrauma and oxygen toxicity occurs after approximately
7-9 days depending on age: younger children are more resilient. Intracranial bleeding is more difficult to diagnose after the fontanelles have
closed. However, if a high index of suspicion is present, for example in
the child with a head injury, intra-cranial bleeding should be excluded
radiologically prior to ECMO. Other contra-indications include the
presence of a disease incompatible with a reasonable quality of life, such
as severe broncho-pulmonary dysplasia, cystic fibrosis, or other
irreversible diseases, such as disseminated tumours. Extra-cranial
bleeding sources are usually amenable to surgical treatment.
Results of patients treated with ECMO
Results from the Extracorporeal Life Support Organisation Registry
(ELSO, Ann Arbor, MI, USA) and at Glenfield Hospital are given in
Tables 1 and 2, respectively.
ECMO patient management
Personnel
It is essential that there is a member of staff (the 'ECMO Specialist') at
the patient's bedside 24 h per day who is not only competent in
managing the ECMO circuit, but can also perform emergency repairs if/
when it malfunctions. The specialist is usually an experienced intensive
care nurse who has received additional training. Other staff include a
Bnhsh Medico/ Bu/Jef/n 1997,53 (No 4)
747
Transplantation
Table 1
Overall results to end 1995
ELSO
Group
n
Neonatal respiratory
Poedkitric respiratory
Cardiac support (poediatnc)
Adult
Table 2
Glenfield Hospital
% survival
n
% survival
11,011
80%
97
72%
1067
53%
59
71%
1650
43%
26
61%
246
46%
65
63%
Paediatnc respiratory results at Glenfield Hospital to end of 1996
Diagnosis
n
Age (months)
Run (h)
%Vono-venous PoO2/FIO2(mmHg)
% Survivors
Viral pneumonia
17
22 4
261
59%
58
76%
RSV
24
59
169
71%
53
92%
Bactend pneumonia
9
71 7
196
89%
49
89%
Aspiration pneumonia
3
12
274
100%
42
100%
Miscellaneous pneumonia
2
98 3
58
100%
61
50%
ARDS sepsis
8
63%
ARDS trauma
2
ARDS miscellaneous
7
Near drowning
Miscellaneous
Total
197
75%
54
222
50%
68
0%
60.1
223
88%
61
75%
4
54
107
25%
141
50%
5
44
51
40%
64
60%
191
68%
61
77%
81
53 4
106
34.8
co-ordinator, the medical director and medical team. It is important that
the director retains clinical control to ensure continuity of care. Many
different skills are required to perform ECMO safely, and it is sensible to
have a core team of doctors from different specialities such as
cardiothoracic surgery, anaesthesia and paediatrics to provide these
diverse abilities. Close liaison with other teams such as cardiology and
blood transfusion is also essential.
Cannulation
Patients must be anaesthetised and paralysed to reduce the risk of air
embolism. Once the target vessels have been either exposed or initial
vascular access obtained (if percutaneous cannulation is being used) a
loading dose of heparin (50 U/kg) is given.
Veno-venous cannulation Veno-venous or W ECMO is the mode of
choice for respiratory failure. In children weighing <6kg, the double
lumen cannula can be used. Cannulation is via the right internal jugular
vein using the semi-Seldinger technique20, which does not require
748
Brihsh Medical Bullahn 1997,53 (No. 4)
Paediatric ECMO
ligation of the vein, and obviates the need for re-exploration of the neck
for de-cannulation.
Advantages of non-ligation of the jugular vein include the drainage of
de-oxygenated blood down the ipsilateral jugular vein and directly into
the cannula, thereby reducing recirculation, and possibly a reduction in
intracranial venous pressure which may have important advantages in
terms of further reducing the incidence of intra-cerebral haemorrhage21.
Patients larger than 6 kg who have not started walking yet will require
VA cannulation, as their femoral vessels will be too small to allow W
ECMO via two cannulae.
In two cannula W or VA ECMO, the total flow rate in the circuit is
determined by the size of the venous cannula and the height of the
venous syphon (height of the bed). The best venous drainage can be
obtained by the most direct route, i.e. the right internal jugular vein,
which will allow the insertion of the largest and shortest drainage
cannula possible. The return cannula can be inserted in either femoral
vein.
There are certain facets of the Seldinger technique22 which become
crucial if large cannulae are to be placed safely. Initial cannulation of the
vein with a small cannula and confirmation of venous placement by
pressure transduction removes the risk of inadvertent arterial cannulation. When dilating the track over the guidewire, great care must be
taken to prevent the guidewire kinking, ensuring that the guidewire and
dilator/cannula can move independently at all times. When initiating W
ECMO, low flow should be used until mixing of the patients blood and
prime has occurred, otherwise infusion of large amounts of hyperkalaemic, citrated blood prime will result in hypotension or hypocalcaemic, hyperkalaemic cardiac arrest.
Veno-arterial cannulation Veno-arterial (VA) support is indicated in
the presence of haemodynamic instability for cardiac support, or when
W cannulation is not technically possible.
The right carotid artery and jugular vein are the vessels of choice
although other routes have also been described23. The vessels are
exposed using the same approach as for the double lumen cannula
above. The jugular vein and carotid artery are encircled with ligatures
proximally and distally, and heparin is given. The cephalad ligature on
the artery is now tied and the cannula is inserted via an arrowhead
arteriotomy. The cannula is secured with the ligatures. The tip of the
cannula should lie at the orifice of the innominate artery, and not in the
arch or ascending aorta. The venous cannula is inserted in exactly the
same manner so that the cannula tip and side holes lie in the right
atrium.
Bnhi/i Medical Bulletin 1997;53 (No 4)
749
Transplantation
Because the carotid is not an end artery it is possible to tie it off
without any short term sequelae in the majority of cases16-24. When
lesions do occur following carotid ligation they are more likely to be
right sided25. Risk factors for such a lesion include cardiac arrest, severe
hypoxia and hypotension at the time of cannulation25 which results in a
loss of cerebral autoregulation26 allowing infarction during the 3-5 min
that it takes for cerebral perfusion to be re-established from the left
side27, thus the majority of right sided lesions could be avoided28, except
for approximately 10% of patients who do not have a complete circle of
Willis29.
Opinion regarding carotid and jugular reconstruction is divided30'31. It
is our practice to primarily re-construct only those vessels which look
healthy and non-friable at the time of de-cannulation, most vessels are
hgated. Jugular ligation may be more dangerous than carotid ligation21
as high venous pressures are thought to contribute to cerebral ischaemia
by decreasing cerebral perfusion pressure. When initiating ECMO,
hypercarbia should be corrected slowly, over several hours, otherwise
severe cerebral vaso-constriction will result32.
Advantages and disadvantages Advantages of VA ECMO include the
ability to provide circulatory as well as respiratory support, and the
absence of recirculation.
Disadvantages of VA ECMO are physiological and those related to
the cannulation discussed above. When the majority of the venous return
is drained from the patient into the pump, right atnal pressure, right
ventricular preload, pulmonary blood flow and right ventricular
afterload are reduced. Reduced pulmonary blood flow leads to reduced
left atrial return and low left ventricular pre-load. However, the arterial
cannula is pumping blood back into the aortic arch at systemic arterial
pressure and, therefore, the left ventricular afterload is high. Gradually,
the left ventricle will fill from the small amount of pulmonary venous
return, and veni-cordi minimi, until it has sufficient end diastolic volume
to eject against the raised after-load imposed by the pump. Problems
may arise, however, if left ventricular contraction is impaired, i.e. by
myocarditis, as the heart will not be able to eject against the raised left
ventricular afterload, and then the left ventricle will become distended
with blood causing further damage. This can be prevented by venting.
VA ECMO is probably the only practical method of circulatory assist for
small children.
Myocardial stun is a reversible impairment of left ventricular function
related to VA ECMO33~36. A combination of high afterload, distension
and myocardial hypoxia is probably to blame. Myocardial hypoxia, as a
potential cause of stun, may seem paradoxical as oxygenated blood is
being pumped into the aorta. However, whilst on VA ECMO, coronary
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Bnhsh Medical Bullttm 1997,53 (No 4)
Paediatric ECMO
blood flow comes largely from the left ventricle37. As there is little
underlying lung function this blood will be poorly oxygenated38. Low
pulmonary blood flow may also to be responsible for the pulmonary
infarcts and fibrosis seen in the post mortem material in the NIH ECMO
study10.
The presence of a large ductus arteriosus may cause problems on VA
ECMO once the patient starts to recover and the pulmonary vascular
resistance falls. High pulmonary blood flow through a large duct results
in severe pulmonary oedema.
In spite of all these problems, VA ECMO remains the method of
choice for inexperienced users and unstable patients particularly if
circulatory support is required. VA ECMO is especially good for right
sided cardiac problems. Veno-venous ECMO is the mode of choice for
respiratory failure. It provides no circulatory support but can, nevertheless, still be used when there is moderate inotrope requirement (up to
approximately 10 mcg/kg/min of dopamine or dobutamine).
ECMO circuit design, equipment and priming
ECMO circuits vary but most centres use occlusive roller pumps, usually
Stockert, servoregulated with a Seabrook bladder box, Avecor silicone
membrane oxygenators and Tygon S-65-HL tubing. Pressure measurement pre- and post-oxygenator is essential. Circuits are first flushed with
CO2, then washed with albumin and clear primed with Plasmalyte-A and
100 U heparin. The clear prime is displaced with blood prior to initiation
of ECMO.
Oxygen delivery, ventillation and lung management on ECMO
The key to respiratory ECMO is the ability to maintain normal blood
gases whilst resting the lungs, preventing further barotrauma. This is
achieved by gentle ('rest') ventilator settings whilst on ECMO, i.e 20/
10cmH2O, 30% O2 and 10 breaths per minute. The high PEEP has been
shown to prevent alveolar collapse allowing faster weaning39. In the
presence of severe barotrauma and air leaks, the lungs can be maintained
static on CPAP until air leaks resolve. Blood gas tensions are controlled
on ECMO by increasing extra-corporeal flow to provide more
oxygenation, and increasing sweep gas flow to remove more CO2.
Bnhi/i Medico/ Bulletin 1997;53 (No 4)
751
Transplantation
Fluid balance during ECMO
Pulmonary oedema reduces gas exchange, and fluid restriction improves
both gas exchange and outcome in a number of lung diseases40"42. Many
patients referred for ECMO have received large volume infusions during
resuscitation, and may be oedematous. This is compounded by the
capillary leak syndrome40 and low serum albumin concentration due to
illness, catabolism and haemodilution. Diuresis is an important part of
lung management. If haemofiltration is required, the haemofiltration
circuit is attached to the ECMO circuit, avoiding the risk of dialysis
catheter insertion in a heparinised patient.
Anti-coagulation and haematology during ECMO
Bleeding is a constant risk during ECMO, and must be prevented.
Invasive procedures such as intra-muscular injections and central line
insertion are avoided. Central lines, umbilical artery catheters, chest
drains, etc., that are present when the patient is cannulated for ECMO
are left in situ. The level of heparinisation during ECMO is much lower
than during cardiopulmonary bypass (CPB). Whilst on ECMO, the ACT
is kept between 160-200 s with hourly or half-hourly adjustment of
hepann infusion rate, normal range 30-60 U/kg/h.
The bleeding encountered in previous reported studies of adult
ECMO10'12-43 can be almost eliminated by tight hepann control and
percutaneous cannulation. This reduces the need for red cell transfusion
unless surgery is required.
When the extracorporeal circuit is exposed to the patient's blood for
the first time, plasma proteins and inflammatory cells adhere to the
surface and become activated44. Pre-washing the circuit with 20%
human albumin solution decreases this tendency, acting to passivate the
circuit to some degree45-46. This process occurs for 2-3 days until an
equilibrium is reached.
We aim to keep our patients' platelet counts over 100,000/ml in order
to reduce the risk of haemorrhage16. Other factors may also contribute
to thrombocytopenia (apart from activation by the circuit), such as
heparin associated thrombocytopenia (HAT)47, anti-platelet antibodies48'49, and disseminated intra-vascular coagulation (DIC). A DIC like
picture may result from a failing oxygenator, rather than sepsis, which is
more likely if the pressure gradient is increasing or the post oxygenator
gases are deteriorating.
Platelet function may be preserved to some degree by infusion of the
serine protease inhibitor aprotinin. Whilst aprotinin is extremely useful
752
Bnhsh Medical Bulletin 1997,53 (No A)
Paediatric ECMO
to control and prevent haemorrhage during ECMO, especially if surgery
is required, it makes heparin management very difficult50"52.
The maintenance of normothermia is essential. All coagulation assays,
including the ACT, are conducted at 37°C and thus have little bearing on
the function of the coagulation cascade at lower temperatures. Centres
advocating hypothermic cardiac ECMO have yet to document acceptable outcome data.
Weaning from ECMO
Patients are ready to be weaned from ECMO when their lung
compliance, and chest X-ray, have improved, and when they have good
blood gases on rest ventilator settings and minimum flow. Minimum
flow on W is 50 ml/kg/min and VA 30 ml/kg/min (with a lower limit of
lOrpm, or 130ml/min for 0.25 inch tubing). At this point, the patient
can be 'trialled off ECMO for 2 h, prior to decannulation.
Conclusions
The efficacy of ECMO for neonatal respiratory failure is now proven,
but there is still widespread scepticism about paediatric and adult
ECMO. A randomised trial or a case control study may eventually
resolve this issue. However, until that time, it is reasonable to offer
ECMO to moribund patients with potentially reversible disease if
conventional treatment is failing. The disease pattern and management
of paediatric respiratory patients resembles that of adult ECMO rather
than neonatal practice. Patients should be treated in experienced ECMO
units as the outcome is likely to be improved, compared to ECMO
provided by inexperienced users. Mobile ECMO units are now available
which means that almost any patient can be transferred to a suitable
unit.
Key points for clinical practice
ECMO should be considered to salvage children with severe, but
potentially reversible, respiratory failure who are not responding to
maximal intensive care. Contra-indications are intracranial haemorrhage and duration of ventilation longer than 7-9 days depending on
age. Use of ECMO in experienced centres has resulted in survival of
Bnfii/i Medico/BuHehn 1997,53 (No. 4)
753
Transplantation
71% of patients, almost all of whom would be expected to die by
objective criteria.
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