Principle, management & monitoring of

patients on ECMO
Role of ECMO & ECCO2 R in ARDS

Kodati Rakesh
HISTORY
 ECLS (Extracorporeal life support)
• Encompasses all extracorporeal technologies and life
support components including oxygenation, carbon
dioxide removal, and haemodynamic support; renal
and liver support may also be incorporated

• ECMO ( VA & VV ECMO)

• ECPR
• ECCO2R
 History
• 1971 – first successfully treated case of ARDS
• 1975 – first neonatal case
• 1978 – first description of ECCO2R
• 1989 – foundation of ESLO (Extracorporeal
life support organisation)
• 2009 – renewed interest in ARDS (CESAR trial)
• 2009 – H1N1 pandemic, lead to widespread use
ECLS registry report 2016

RRThiagarajan et al, ELSO regitry,ASAIO Journal 2017

ECLS registry report 2016

RRThiagarajan et al, ELSO regitry,ASAIO Journal 2017

ECLS registry report 2016

RRThiagarajan et al, ELSO regitry,ASAIO Journal 2017

ECLS in respiratory failure

RRThiagarajan et al, ELSO regitry,ASAIO Journal 2017

BASIC PRINCIPLES
 Principles
• To provide cardiopulmonary support in cases
refractory to conventional management
• To correct gas exchange abnormalities not
maintained by conventional support
• Used to prevent ventilator associated lung injury
– Reducing the delivered volumes and
airway pressures
– Low FiO2 levels
 Principles
• Bridging therapy, not a cure
– Bridge to recovery – buying time for the patient to
recover
– Bridge to decision – temporary step till further
decision
– Bridge to transplant
 Different from CPB..

CPB (cardiopulmonary bypass) ECMO

Intraoperatively during cardiac sx Intensive care units

Few hours Longer duration of support

Low blood flow rates (2 l/min) Higher flow rates ( >4 l/min)

More anticoagulation Less anticoagulation

 Physiology - oxygenation
• Direct function of the blood flow
• Usual blood flow required is b/n 3 to 6 L/min
• Factors determining oxygenation
– Thickness of the blood film
– Fraction of inspired oxygen (FIO2)
– Hemoglobin concentration
– Oxygenation of the blood prior to membrane

Gattinoni et al. Critical Care 2011, 15:243

 Physiology – CO2 removal
• Direct function of ‘Sweep gas ’ flow rate
• Sweep flow – measure of gas flow across the
membrane oxygenator
• CO2 exchange is much more efficient than O2
exchange
• May necessitate adding CO2 to the sweep gas
to prevent excessive CO2 removal and
respiratory alkalosis in neonates

Gattinoni et al. Critical Care 2011, 15:243

Physiology - Artificial lung

Oxygenation CO2 removal

High
High sweep
extracorporeal
blood flow flow

Low sweep
Low blood flow
flow

Gattinoni et al. Critical Care 2011, 15:243

Physiology - Artificial lung

Murray Nadel Textbook of Respiratory Medicine, 6th Ed

 Modes of access
• Veno - venous (V-V)
– Isolated respiratory failure

• Veno - arterial (V-A)

– Isolated cardiac failure
– Cardiorespiratory failure
 Venovenous ECMO
• Blood is extracted from the vena cava or right
atrium and returned to the right atrium
• Provides respiratory support, but the patient is
dependent upon his or her own hemodynamics
• Systemic blood flow and pressure are the result of the
native cardiac function unrelated to the extracorporeal
flow
 Venovenous ECMO
• The PaO2 is determined by the mixing effect of
oxygenated blood returning from the ECMO circuit to
the right heart and deoxygenated blood returning from
the bronchial admixture, coronary sinus, and vena cava

• Connected in series with lungs and heart

 Venovenous ECMO

• Most frequently used

• Drainage though
femoral venous cannula
in IVC

• Infusion through IJV

cannula proximal to RA

Femoral vein (drainage)

Jugular vein (infusion)
 Venovenous ECMO
• Higher risk of recirculation

• Tip of the drainage

cannula at the level of L1–L2,
in order to receive the blood
contribution of the renal
veins

• Tip of the reimmission

cannula should be placed
close to the junction between
the IVC & RA
Femoral vein (drainage)
Femoral vein (infusion)
 Venovenous ECMO

• Cannula must cross the RA

with the tip in the IVC

• Blood is drained from

both the SVC & IVC

• Reinfusion occurs
through a separate lumen
into the RA just facing the
tricuspid valve

Single cannulation with

• Early mobilisation & less
double lumen need of sedatives
 Venoarterial ECMO
• Blood is extracted from the right atrium or vena
cava (for drainage), and returned to the arterial
system either through peripheral cannulations via
femoral, axillary or carotid arteries (for infusion)
• Connected in parallel with heart and lungs
 Venoarterial ECMO
• Systemic flow, PO2 and CO2 levels are determined by
combination of the blood added from the
extracorporeal circuit plus the amount of blood passing
through the native heart and lungs
 Venoarterial ECMO

Femoral vein (drainage) Femoral vein (drainage) Femoral vein (drainage)

Femoral artery Axillary artery Carotid artery
(infusion) (infusion) (infusion)
Central venoarterial ECMO

Right atrium (drainage)

Ascending aorta (infusion)

Post cardiotomy -
Cannulas of CPB are
transferred to the
ECMO circuit

Larger cannulas with

low resistance
 ECMO
V-V ECMO V-A ECMO

Does not provide cardiac support Provides cardiac support to assist

systemic circulation
Connected in series Connected in parallel
Low PaO2 achieved - Higher PaO2 achieved

• Blood with high oxygen saturation • artificially oxygenated blood mixes

reaches the PA, ↑ V/Q mismatch of the with arterial blood and directly perfuses
native lung due to the loss of hypoxic distal organs
vasoconstriction • no loss of hypoxic
• Recirculation of oxygenated blood vasoconstriction, in lungs
within the circuit

Less complications More complications

INDICATIONS &
CONTRAINDICATIONS
 Indications of ECLS
• Hypoxic respiratory failure due to any cause
– P/F ratio < 100 and/or Murray score ≥ 3
• Hypercapnic failure on MV despite high Pplat (pH
<7.2)
• Need for intubation in a patient on lung transplant list
• Immediate cardiac or respiratory collapse (PE,
blocked airway, unresponsive to optimal care)
• Refractory cardiogenic shock

ELSO General guidelinesVer 1.3 Dec 2013

 Contraindications
• Mechanical ventilation at high settings (FiO2 > 0.9, P-
plat > 30) for ≥ 7 days
• Major pharmacologic immunosuppression (absolute
neutrophil count <400/mm3)
• CNS hemorrhage that is recent or expanding
• Non recoverable co morbidity such as major
CNS damage or terminal malignancy
• Age: no specific age contraindication but
consider increasing risk with increasing age

ELSO General guidelinesVer 1.3 Dec 2013

ECMO CIRCUITRY &
COMPONENTS
ECMO circuitry
 Components
• Cannulas
• Pumps
• Oxygenator /Membrane lung
• Heat exchanger
• Tubings
 Components - Cannulas
• Best cannulation technique should be chosen on
the basis of patients and clinical settings
• Intrathoracic or extrathoracic
• Percutaneous or surgical
• Percutaneous approach is standard of care in VV ECMO
– Less risk of bleeding
– Short operative time
– Easier mobilization & nursing

Laurance Lequier et al; Pediatr Crit Care Med. 2013

 Components - Cannulas
• Cannula size
– Big enough to ensure adequate flow with relatively
low suction pressure
– Shouldn’t exceed 2/3 rd of vessel diameter

• Positioning
– Important to minimise recirculation
– Tip should be in a high flow vessel

Laurance Lequier et al; Pediatr Crit Care Med. 2013

 Components - Pumps
Roller pump Centrifugal pump
Compresses the circuit tubing and Driven by electromagnetic induction
pushes the blood through the raceway motors and uses the principles of
of the pump centrifugal force to generate a flow

Constant flow provided independent of Inability to maintain a set flow Back

circuit preload flow at low flow rates

Risk of cavitation and hemolysis Circuit Less risk of cavitation and air
disruption due to excessive pressure embolism
Reduced blood trauma

Laurance Lequier et al; Pediatr Crit Care Med. 2013

 Components - Oxygenator
• Blood and gas flow in counter-current directions within
the silicone lung and gas exchange occurs by diffusion
across the membrane
• Hollow fiber devices with polymethylpentene
surface (PMP) replaced silicone ones
– efficient at gas exchange
– minimal plasma leakage
– low resistance to blood flow

Laurance Lequier et al; Pediatr Crit Care Med. 2013

 Components – heat exchanger
• Principle is counter current flow
• A great deal of heat is lost while a patient is on ECMO as
a result of the large extracorporeal surface area to which
the patient’s blood is exposed
• The water is warmed to 37 ⁰C to 40 ⁰C to compensate for
the heat loss in the circuit
• Kept less than 42 ⁰C to prevent hemolysis and formation
of bubbles

Laurance Lequier et al; Pediatr Crit Care Med. 2013

 Components - Tubings
• Polyvinylchloride (PVC) – based plastic compound
• Minimal resistance to venous drainage
• Non-biologic surfaces of a circuit – activation of coagulation
pathway and the inflammatory response
• Blood flow and pressure monitors
• Continuous oxyhemoglobin saturation monitors
• Circuit access sites

Laurance Lequier et al; Pediatr Crit Care Med. 2013

 Components - Tubings
• Biocompatible lining to reduce the systemic
inflammatory response and risk of thrombosis
and bleeding
• Fewer the connectors and stopcocks – less is the
flow turbulence and blood stasis

Laurance Lequier et al; Pediatr Crit Care Med. 2013

 Components - Bridge
• Connection between the venous (drain) and
arterial (return) components of the
circuit
• Bypass to allow the isolation of the patient from
the circuit
• If adequate gas exchange and hemodynamics can
be maintained while flow continues through the
bridge after its opening
INITIATION & MAINTENANCE
hnique of ECMO

• Should only be performed by clinicians with training and

experience in its initiation, maintenance, and discontinuation
• The patient is anticoagulated with IV heparin
• Cannulae are inserted into the vessels
• Cannulae are connected to the limbs of circuit
• ECMO support is initiated after that

Gattinoni et al. Critical Care 20

S Allen et al; Journal of Intensive Car
 CIRCUIT INITIATION
• Flow rate: 50-80 cc/dry kg/min

• BF required during VV bypass for acceptable arterial

oxygenation is usually 3 to 6 L/min, partially depending on
the cardiac output of the patient, on hemoglobin
concentration and on saturation
• Maximum initially, then lowest flow to maintain
SaO2>80- 85% at rest vent settings in VV ECMO

Gattinoni et al. Critical Care 20

S Allen et al; Journal of Intensive Car
 Circuit initiation

• In contrast, the flow rate used during VA ECMO

*high enough to provide adequate perfusion pressure
and venous oxyhemoglobin saturation
*low enough to provide sufficient preload to maintain
left ventricular output

• Sweep gas flow is titrated to maintain PaCO2 at 40

mmHg

Gattinoni et al. Critical Care 20

S Allen et al; Journal of Intensive Car
 Titration & targets

• An arterial oxyhemoglobin saturation

– VA ECMO : > 90 % ;VV ECMO : 80-85%
• SvO2 25-30% less than SaO2, measured on the venous line
• Higher SaO2 targets would require high flows predisposing to
volume overload and hemolysis in VV bypass
• Adequate tissue perfusion, as determined by the ABP,
venous oxygen saturation, and blood lactate level

Gattinoni et al. Critical Care

S Allen et al; Journal of Intensive C
 Oxygenation monitoring

• If the FIO2 of the sweep gas is 1, the expected PO2 in the output
blood (PO2out) should be high (generally > 300 to 400 mm Hg)

• Drop in pO2 in post oxygenator

blood Oxygenator failure
Recirculation

Gattinoni et al. Critical Care 20

S Allen et al; Journal of Intensive Car
 Oxygenation monitoring

• Suspect recirculation

– SaO2 below 80 % with reasonable ECMO flows

– minimal improvement in saturation with higher flows

• Confirmed by decreased difference b/n pre and post
oxygenator blood saturations
• Decreased by distancing the inflow and outflow cannula
• Even after readjusting, it can occur secondary to
increased pulmonary vascular resistance leading to
preferential flow thru ECMO circuit

Gattinoni et al. Critical Care

S Allen et al; Journal of Intensive C
Pressure monitoring

Detect resistance in oxygenator (or )

post oxygenator circuit

Ensure excessive
suction is avoided
 Flow monitoring

Drop in flow at stable RPM

Decrease in preload Increase in after load

Hypovolemia / bleeding Kink in outflow cannula

Obstructive process – tamponade, Membrane oxygenator thrombus
tension PTX & Abd CS High SVR in VA circuit

Negative pressure – hemolysis -

chattering
M Chung et al, ScientificWorld Journal 2014
 MAP monitoring

• Essential in case of V A ECMO bypass - MAP > 65 mm Hg

• MAP should not exceed 90 mm Hg in order to limit the
afterload
• MAP can be increased by administering the volume or by
increasing the RPM
• Correction of volume status and vasopressor support as
indicated to maintain MAP

M Chung et al, ScientificWo

 LV monitoring - V A ECMO

VA ECMO

Decrease in preload to the heart Increase in after load

Decrease in volume work Increase in pressure work
 LV monitoring - V A ECMO

• Left ventricular output can be closely monitored by

pulsatility in the arterial line's waveform & frequent
echocardiography

• Insufficient unloading of the distended LV due to ongoing

blood flow to LV from the bronchial circulation and right
ventricle – pulmonary edema

M Chung et al, ScientificWo

 LV monitoring - V A ECMO

• Failing left ventricular contractility despite ECMO

– Inotropic support
– Intra aortic balloon pulsation

• Refractory LV depression
– LV decompression
– transatrial balloon septostomy or insertion of a left atrial or
ventricular drainage catheter

M Chung et al, ScientificWo

 Systemic anticoagulation

• Intended to prevent thrombotic complications

• UFH most commonly used
• Classical dose is b/n 20 and 70 IU/kg/hr
• Sensitivity of UFH depends on endogenous AT3 levels and
platelets
• If AT 3 deficiency, replace by FFP
 Systemic anticoagulation

• ACT (activated clotting time) - standard of monitoring

during heparin anticoagulation
• Target of ACT is 180 to 210 sec
• Target has to be individualised based on signs of hypo or
hypercoagulability and ECMO flow rates
• Alternatives of ACT

• PTT (1.5 times the baseline)

• anti-Factor Xa activity (anti Xa) levels
• thromboelastography (TEG)
 Systemic anticoagulation

• Systemic anticoagulation in VV ECMO

Systematic review, 18 studies including a total of 646 patients
Rate of major bleeds was 16%
Rate of clotting episodes was 53%

7 studies aPTT (n =199 ) studies ACT (n =37)

Major bleeding episodes - 37 (19%)Major bleeding episodes - 23 (62%)
Major thromboses - 53 (27%) Major thromboses - 23 (62%)

aPTT targets ≥ 60 seconds (n =43, 5 studies) reported 24 (56%) bleeds & 3

(7%) clot
aPTT target < 60 seconds(n = 156, 3 studies) reported 13 (8%) bleeds &
50 (32%) clots

Michael C Sklar et al, Annals

 Systemic anticoagulation

• Optimal therapeutic targets for anticoagulation during ECMO

are unclear
• Previously studies are retrospective, observational
design, small cohorts, and patient heterogeneity
• Clinical significance of reported thrombotic
complications is largely unknown
• Need for RCTs of anticoagulation strategies for patients
undergoing ECMO

Michael C Sklar et al, Annals

 MV - ECMO

• Significant knowledge gap in understanding the benefits and risks

of MV during ECMO
• Risk of VILI
– Limitation of the alveolar strain by decrease in Vt
– High PEEP with low Vt to prevent atelectrauma
– Avoid oxygen toxicity to the lung from a high FiO2 &
reabsorption atelectasis

Schmidt et al. Critical Care 20

 MV - ECMO

• Cardiovascular effects
– Increase in pulmonary vascular resistance, RV overload,
causing adverse effects in pts of RV failure
– Conversely, pts with predominately LV failure may develop
pulmonary edema requiring high PEEP
– ↓ lung perfusion may accelerate pulmonary vascular
thrombosis in severe lung injury

Schmidt et al. Critical Care 20

 MV - ECMO

• Most appropriate settings are unknown

• FiO2 <0.4
• Non damaging “rest settings (P plat<25 cm H2O)’’
• Tidal volumes are maintained below 4 ml/kg PBW
• Increased alveolar recruitment with PEEP to
maintain airway patency at low lung volumes

ELSO General guidelinesVer 1.3

 MV - ECMO

First 24 hrs 24 – 48 hrs After 48 hrs

Moderate to moderate to Minimal to no sedation

heavy minimal
sedati sedation
on
PCV 25/15 PCV 20/10 PCV as before
or take on PSV as the
I: E 2:1 I: E 2:1 condition improves

Rate 5/min Rate 5/min +

spontaneous
breaths
FiO2 0.5 FiO2 0.2 - 0.4

FiN2 50 % FiN2 60-80 %

ELSO General guidelinesVer 1.3

 MV - ECMO

European CESAR EOLIA

Network

Mode of MV Volume AC Pressure AC Volume AC /

APRV
PEEP ≥ 10 10 – 15 > 10

FIO2 0.3 – 0.5 0.3 0.3 – 0.6

Pressure limit ≤ 20 to 25 cm 20 to 25 cm 25 cm H20

H2O H2O

RR (/min) 6 – 20 10 10 - 30

Tidal volume Targeted to - Targeted to

above above
pressure pressure
* To what extent we should reduce both the tidal volume and the plateau
pressure to allow lung rest remains unknown
 Transfusion support

• The benefit of enhanced oxygen delivery must be weighed

against the potential harm of transfusion
• Many centers recommend transfusion who are receiving ECMO
until their hematocrit levels are in the normal range
• Lesser blood flows in the circuit are required if
hematocrit is maintained

Daniel Brodie NEJM 2011;36

 Transfusion support

• Platelets are continuously consumed during ECMO because

they are activated by exposure to the foreign surface area
• Platelet counts should be maintained greater than
50,000/microL, which may require platelet transfusion

Daniel Brodie NEJM 2011;36

 Weaning from ECMO

• Progressive reduction of the ECMO contribution to oxygenation

and CO2 removal as the gas exchange capability of the native
lung improves and the patient’s clinical conditions stabilize
• Requires regular monitoring the pts respiratory function
(gas exchange function, respiratory mechanics) and
hemodynamics

Steve Allen et al, Journal of Intensive Car

 Weaning from ECMO

• Respiratory failure
– when 50% to 80% of total gas exchange is by the native lungs
– when the patient’s lung compliance improves
– improving chest x-ray
• Cardiac failure
– Enhanced aortic pulsatility correlates with improved
left ventricular output
– Decrease in mixed-venous oxygenation saturation
– MAP> 60 mmHg in the absence of “high-dose” inopressors

Steve Allen et al, Journal of Intensive Car

 Weaning from ECMO

• VV ECMO trials
– Sweep low rate is slowly decreased
– Ventilator is placed on full support
– Successful weaning is confirmed if the patient remains
stable at a FGF of 0 L/min for a period of 4 to 24 hours

Steve Allen et al, Journal of Intensive Car

 Weaning from ECMO

• VA ECMO trials
– Require temporary clamping of both the drainage and
infusion lines, while allowing the ECMO circuit to
circulate through a bridge between the arterial and
venous limbs
– If the patient manifests signs of deterioration, the bridge is
clamped and flow is re-directed to the patient as before

Steve Allen et al, Journal of Intensive Car

COMPLICATIONS
 Complications ECLS
Circuit related complications
• Blood clots and thromboembolism
– Failure of the oxygenator
– Platelet consumption
– Pulmonary or systemic embolism

• Gas entrapment and embolism

• Circuit fractures
 Complications ECLS

Circuit related complications

• Recirculation – minimizing the oxygenation efficiency
• Shaking or ‘chatter’’ of the tubing - hypovolemia, cannula
malposition, pneumothorax, and pericardial tamponade
• Manifests as caused by excessive negative pressure (created by
the pump in the venous system) as well as a drop in pump
output
 Complications ECLS

Patient related complications

• Vascular access complications
– Perforation of posterior wall, hematoma
– Dissection of the vessel
– AV fistula or pseudo aneurysm
• Leg ischemia in femoral arterial cannulation
– Requires insertion of peripheral perfusion cannula
distally
 Complications ECLS

Patient related complications

• Bleeding – surgical site, GI, airway bleed
• Coagulopathy (TCP, HIT & DIC)
• Neurologic complications – intracranial hemorrhage
• Cardiac complications – insufficient unloading of the
distended LV due to ongoing blood flow to LV from the
bronchial circulation and right ventricle
• Sepsis
 Complications ECLS

RRThiagarajan et al, ELSO regitry,ASAIO

Journal 2017
ECMO - ARDS
 ECMO in ARDS

• Currently a salvage therapy for the most severe cases of

ARDS
• Benefit of ECMO as compared to conventional, standard of
care management for ARDS has yet to be demonstrated
• Increasing potential for ECMO to enhance the way ARDS is
managed

M Parekh et al; Ann Transl Me

 Benefit in ARDS

• Complete lung rest – Lung protective ventilation

• Complete avoidance of VILI
• Adequate gas exchange extracorporeally
• Decreases Oxygen toxicity to lung

M Parekh et al; Ann Transl Me

 Indications in ARDS

* Threshold for the initiation of ECMO varies considerably across studies

and guidelines
• Severe hypoxemia (P/F ratio <80, despite the application
of high PEEP) for at least 6 hr in patients with potentially
reversible respiratory failure
• Considered after a shorter interval if P/F ratio < 50
• Uncompensated hypercapnia with acidemia (pH <7.15)
• Murray score > 3.0

Daniel Brodie N Engl J Med 2011

 Contraindications in ARDS

• High-pressure ventilation (Pplat > 30 cm of water) or high Fio2

requirements (> 0.8) for >7 days
• Limited vascular access
• Any condition or organ dysfunction that would limit the likelihood of
overall benefit from ECMO, such as severe, irreversible brain
injury or untreatable metastatic cancer
• Any condition that precludes the use of anticoagulation therapy

Daniel Brodie N Engl J Med 2011

 ECMO

• First prospective randomised study in severe ARF

• 9 medical centres, 90 subjects
• Majority - acute bacterial or viral pneumonia (57%)
• Conventional MV (n=48) Vs MV + VA ECMO (42)
• MV before entry 7 days in control group vs 9.6 in test group
• 4 survived in each group

ZapolWM et al, JAMA 1979;242(2

 ECMO

Pts had significantly high PaO2, low

PaCO2 in study group Reduction of
FiO2 from 0.74 to 0.48 seen in
ECMO group High mean daily
transfusion support (1 to 2.5 L)
ECMO can support respiratory gas exchange but did not increase the
probability of
long-term survival in patients with severe ARF
 ECMO

• 122 ARDS pts (PaO2 ≤ 80 mm Hg on FiO2 ≥ 0.6)

• Followed a predefined clinical algorithm
• Initially treated with advanced non invasive Rx options (PCV
with PEEP, PHC, Reduction of pulmonary edema, optional
proning and iNO)
• Those who are not responding to advanced Rx were taken
onto VV ECMO by certain entry criteria

Lewandowski K et al, Intensive Care Med 1997

 ECMO

• 122 consecutive patients according to a predefined

treatment algorithm [(n=73), mean P/F 86] or to care
involving ECMO [(n=49), mean P/F 67]
• The overall survival rate was 75%
• 89% in the AT-sine ECMO group & 55% in the ECMO
treatment group (p < 0.001)
• Patients in the ECMO group were found to have higher severity
of illness scores and worse oxygenation at baseline

Lewandowski K et al, Intensive Care Med 1997

 ECMO

• Evidence from these studies suggested no definite

benefit of ECMO over conventional mechanical
ventilation
• Its usage was restricted to clinical trials and not got widely
implemented
• However these studies have little relevance now due to
changed ventilatory strategies, ECMO circuits, disease
management and increased experience with it
 H1 N1 Australia NZ report

• Retrospective study of ECMO receivers for H1 N1 ARDS in 15

ICUs from June to August 2009
• 68 patients were included
– 53 patients (78%) were PCR /viral culture positive
– 8 patients (12%) had serological evidence of recent
influenza A
– 7 patients (10%) had preceding symptoms of influenza
like illness

Andrew R Davies et al, JAMA, Nov 2009

17
H1 N1 Australia NZ report

Andrew R Davies et al, JAMA, Nov 2009;Vol 302, No.

H1 N1 Australia NZ report

48 (71 %)

14 (21 %)

Andrew R Davies et al, JAMA, Nov 2009;Vol 302, No.

 CESAR trial
Efficacy of conventional ventilatory support versus ECMO for severe
adult respiratory failure
Participants 180 adults of severe but potentially reversible respiratory failure
(Murray score ≥ 3.0 / pH < 7.2) despite optimal conventional Rx
Methods Randomised in 1 : 1 fashion
Conventional MV Vs Referral to consideration for ECMO
68/90 (75 %) received ECMO
Outcome measure Death or severe disability at 6 m of randomisation
Results Survival upto 6 months
63% (57/90) of ECMO Vs 47% (41/87) of conventional MV
RR of 0·69; 95% CI 0·05–0·97, p=0·03)
Conclusion Transfer of adult patients with severe but potentially reversible
respiratory failure to a centre with an ECMO-based management
protocol will significantly improve survival without severe disability

Giles J Peek et al;, Lancet 2009; 374: 1351–63

CESAR trial
CESAR trial

Giles J Peek et al; Lancet 2009; 374: 1351–63

 Limitations - CESAR trial
• No standardisation of Rx protocol
– 30% of the patients in control arm did not get LPV
– Steroid recipients more in study group

Giles J Peek et al; Lancet 2009; 374: 1351–63

 Limitations - CESAR trial
• Intervention in CESAR was referral to an ECMO center
not treatment with ECMO
 25 % of patients in ECMO referral group didnot receive
ECMO

• Two serious adverse events noted

– Mechanical failure of O2 supply during transport
– Vessel perforation during cannulation

Giles J Peek et al; Lancet 2009; 374: 1351–63

 Limitations - CESAR trial
• Three patients died before they could be transferred
and two died in transit
• Risk of death during transfer of such patients
• Exclusion of pts ventilated with high pressure
or high FiO₂ for more than 7 days
• Did improved care at the single ECMO hospital
lead to the relative risk observed??

Giles J Peek et al; CESAR trial, Lancet 2009; 374: 1351–63

 ECMO
• UK H1N1 2009-10
• H1N1-related ARDS transferred for ECMO Vs
matched patients who were not referred for ECMO
• Of 80 ECMO-referred patients, 69 received ECMO
(86.3%) and 22 died (27.5%) prior to discharge from
the hospital
• Survival to acute hospital discharge

Noah et al, JAMA 2011;306(15):1659-1668

 ECMO

*For patients with H1N1-related ARDS, referral and transfer to an

ECMO center was associated with lower hospital mortality compared to
matched ones

Noah et al, JAMA 2011;306(15):1659-1668

 ECLS – In hospital mortality
• 4 RCTs, 6 observational studies(496/1248)

Laveena Munshi et al, Annals ATS 2014

ECLS – In hospital mortality

Laveena Munshi et al, Annals ATS 2014

ECLS – complications

Laveena Munshi et al, Annals ATS 2014

 ECLS mortality
• Systematic review of 56 studies
• Mortality rates range from 36 to 56% in the studies
performed in the last 15 years and reporting outcomes
of >30 ECMO patients
• Mortality rates for H1N1 ARDS ranged from 14 to
64% in the 16 studies from 11 countries

Schmidt et al. Critical Care (2015) 19:99

 ECLS mortality
• Factors associated with poor outcomes after ECMO for
acute respiratory failure
– Older age
– More days of mechanical ventilation before ECMO
– More number of organ failures
– Low pre ECMO respiratory system compliance
– Immunosuppression

Schmidt et al. Critical Care (2015) 19:99

Respiratory ECMO survival prediction (RESP)

Schmidt et al, AJRCCM 2014

Respiratory ECMO survival prediction (RESP)
Derived from ELSO Registry (n =2355) 2000 to 2012

Schmidt et al, AJRCCM 2014

ECCO2 REMOVAL /
RESPIRATORY DIALYSIS
 ECCO2 removal
• Technique providing artificial respiratory support by
removal of CO2 from blood through an extracorporeal
gas exchanger
• Feature of other ECLS

• Low flowVV or AV devices – provide CO2 removal

without oxygenation
 History
• 1976 - Kolobow and Gattinoni explored the possibility of
treating severe respiratory failure using low frequency
PPV alongside ECCO2 removal in sheep
• 1986 – first clinical study on V-V ECCO2 removal
by Gattinoni et al
• 1997 – first clinical study on A-V ECCO2 removal
 Hypercapnia detrimental?

• Inhibition of cell membrane repair

• Suppression of innate immunity & host defence
• Uncoupling of RV & pulmonary circulation – RV failure
• Increase in intracranial pressure
• Depression of myocardial contractility

Morimont et al, Critical Care 2015, 19 : 117

 Benefits of ECCO2R
• Decreases the detrimental effects of hypercapnia
• Better oxygenation
– Increases the alveolar O2 concentration in
accordance with the alveolar gas equation
– By removing CO2, ECCO2R allows ventilation
strategies that are focused on oxygenation rather
than CO2 elimination
• “Rest lung” concept

Morimont et al, Critical Care 2015, 19 : 117

 Benefits of ECCO2R
• COPD
Obviates the need of intubation & IMV Facilitates
withdrawal of IMV & extubation

• Weaning from MV
• Bridge to lung transplantation

Morelli et al, Intensive Care Med 2017, 43 : 519-30

In ARDS...
• Decreases the ventilator induced lung injury (VILI)
by allowing to ventilate the lung at low volumes and
pressures
• Allows to continue low tidal volume ventilation (< 6
ml/kg IBW)
• Upto 50 % reduction in MV can be obtained while
maintaining normocarbia

Morimont et al, Critical Care 2015, 19 : 117

Morelli et al, Intensive Care Med 2017, 43 : 519-30
In ARDS...

Morimont et al. Critical care 2015, 19:117

V – V ECCO2
A – V ECCO2
Pumpless device
MAP of atleast 70 mm Hg
AV pressure gradient ≥ 60 mm Hg
Low resistance circuits

Higher cardiac index > 3 L/min

/m2 A proportion of CO doesn’t
affect the peripheral perfusion

Presence of hemodynamic instability /

heart failure limits the use of such
devices
 Various devices
• The Pump-Assisted Lung Protection
(PALP) (Maquet, Rastatt, Germany)
• The iLA Activve® (Novalung, Germany)
• The Hemolung® system (Alung
Technologies, Pittsburgh, USA)
• The Decap® system (Hemodec, Salerno, Italy)
 Complications of ECCO2 R
• Similar to ECMO
• Earlier had more complications in v/o large cannulas,
complex circuits, high anticoagulation requirements
• A-V devices – Limb ischemia (ensure that the
internal diameter of the artery is 1.5 times the
external diameter of the cannula)
• V- V devices – thrombosis of the circuit
 Evidence in ARDS
• Randomized controlled trial in 1994
• 40 patients of severe ARDS
• LFPPV - ECCO2 (21) vs conv MV (19)
• 30 day mortality
• No difference in survival in both {14/21(66.6%) vs
11/19 (57.9%)}
• 30% patients had severe hemorrhage

Morris et al, Am J Respir Crit Care Med 1994; 149:295-305

 Evidence in ARDS
• The high mortality of ECCO2R in the early use were
likely to be due to the complex extracorporeal systems
with high flow resistances and large surface areas
• Use of occlusive roller pumps (high haemolysis rate)
• Less biocompatible membrane requiring
high anticoagulation levels
• MV was in the pre-ARDSNet era and employed high
tidal volumes and peak pressures

Morris et al, Am J Respir Crit Care Med 1994; 149:295-305

 Evidence in ARDS
Tidal Volume Lower than 6 ml/kg Enhances Lung Protection
Participants Prospective study among 32 patients of ARDS who were ventilated ARDS
protocol for atleast 72 hrs
Intervention 10 patients 28 ≤ P plat ≤ 30 cm H2O were placed on V-V ECCO2 device
and progressive reduction in VT
VT was reduced from 6.3 ± 0.2 to 4.2 ± 0.3 ml/kg, and Pplat
decreased from 29.1 ± 1.2 to 25.0 ± 1.2 cm H2O (P < 0.001)
PEEP was increased to attenuate the reduction of P/F ratio
CT scan & BAL cytokine analysis was done before & after 72 hrs

Results 33.6 ± 6.3% reduction of PaCO2 (from 73.6 ± 1.1 to 48.5 ± 6.3 mmHg)
sufficient to normalize arterial pH (from 7.20 ± 0.02 to 7.38 ± 0.04)
Decrease in poorly aerated & hyper inflated areas of lungs on CT
B AL cytokines concentration significant reduction was seen

Terragni et al, Anaesthesiology 2009; 111:826–35

 Evidence in ARDS
• Use of VT lower than 6 ml/kg PBW was a/w
significant reduction of inflammatory and
morphological markers of VILI
• Only observational study
• No control group of patients who received usual care
without Lower ARDSNet/Carbon Dioxide Removal

Terragni et al, Anaesthesiology 2009; 111:826–35

 Evidence in ARDS
•
LTV Fanelli et al,+ AV
(3ml/kg) Critical Care (2016)
ECCO2R 20:36
Vs conventional LPV, XTRAVENT study
• Participants
Participants
• Prospective 79 patients
among of moderate/severe
15 patients of moderate ARDS
ARDS after 24 hrs stabilisation
study Period
• Intervention
Intervention Randomized to receive a low VT ventilation (3 ml/kg) + ECCO2
• VT was gradually reduced from 6 to
[or] ARDSNet a min value
strategy of 4 mL/kg by 0.5 mL/kg every
(6 ml/kg)
30 min & PEEP was increased
PEEP to target
following a Pplat‘high-PEEP/FIO2
ARDSNet between 23 and 25 cmH2O
’ table
• If arterial pH <7.25 with PaCO2
RR 10–25/min with>60
an mmHg,
I: E ratiodespite
of 1:1an increase in RR up to
was 35/min, R device was switched on
• ECCO2
Outcomes
Results 28-days and 60-days ventilator-free days (VFD)
• Initial reduction in VT, without
Results VFD’s within 60 days were not different between the study group
• resulted inECCO2R
gnificant respiratory acidosis (pH <7.25) in all
(33.2 ± 20) and the control group (29.2 ± 21,p = 0.469)
si duction in Pplat from 27.7 ± 1.6 to 23.9 ± 1
Mortality rate did not differ between groups
• significant recmH2O ays was 47 %, which was expected in
Mortality at 28moderate ARDS ither proning or ECMO for
d 1/3 rdrefractory hypoxia
Thomas Bein et al, Intensive Care Med (2013) 39:847–856
 Evidence in ARDS
LTV (3ml/kg) + AV ECCO2R Vs conventional LPV

Av ECCO2-R Control P
(n =40) (n =39)
VFD_28 days 10.0 ± 8 9.3 ± 9 0.779

VFD_60 days 33.2 ± 20 29.2 ± 21 0.469

LOS ICU (d) 31.3 ± 23 22.9 ± 11 0.144

LOS hospital (d) 46.7 ± 33 35.1 ± 17 0.113

In hospital mortality 7/40 (17.5 %) 6/39 (15.4 %) 1.000

Thomas Bein et al, Intensive Care Med (2013) 39:847–856

 Evidence in ARDS
• In a post hoc analysis, ARDS patients who were more
hypoxemic (P/F < 150 ) at baseline and who were
treated with the low VT strategy had a significantly
shorter ventilation period (28.2 ± 16.4 Vs 40.9 ±
12.8, p=0.033)
• No survival benefit was seen with LTV + ECCO2R

Thomas Bein et al, Intensive Care Med (2013) 39:847–856

 Evidence in ARDS
Fanelli et al, Critical Care (2016) 20:36

Participants Prospective study among 15 patients of moderate ARDS

Intervention VT was gradually reduced from 6 to a min value of 4 mL/kg by

0.5 mL/kg every 30 min & PEEP was increased to target a Pplat
between 23 and 25 cmH2O
If arterial pH was <7.25 with PaCO2 >60 mmHg, despite an
increase in RR up to 35/min, ECCO2R device was switched on

Results Initial reduction in VT, without ECCO2R

resulted in significant respiratory acidosis (pH <7.25) in all
significant reduction in Pplat from 27.7 ± 1.6 to 23.9 ± 1
cmH2O
Mortality at 28 days was 47 %, which was expected
1/3 rd required either proning or ECMO for refractory hypoxia
 Evidence in ARDS
• Systematic review
• 14 studies with 495 patients (two RCTs and 12
observational studies)
• No survival benefit seen in both RCTs
• More ventilator free days in P/F < 150 (Xtravent
study)
• No difference in ICU LOS

Fitzgerald et al, Critical Care 2014,18 : 22

 Evidence in ARDS
• All the studies showed reductions in tidal volume,
peak inspiratory pressure, arterial partial pressure of
carbon dioxide and increase in arterial pH
• Increased transfusion requirements were seen in
couple of studies
• Lack of robust data supporting the use of these
devices and their cost effectiveness

Fitzgerald et al, Critical Care 2014,18 : 22

 Awaited...
• SUPERNOVA trial, ECCO2 removal
combined with ultra low tidal volume MV in
ARDS
• EOLIA trial (ongoing RCT, France), ECMO
vs conventional MV for moderate to severe
ARDS
 Take home message
• Requires early & careful selection of patients with
reversible disease and without significant
comorbidities
• Rescue therapy for patients with severe ARDS
• Evidence of benefit in H1 N1 related ARDS
• VV ECMO – therapy of choice in ARDS
• ECCO2 R therapeutic adjunct in moderate to severe
ARDS