ECMO and refractory Hypoxemia

Dr. Vinay Dhingra MD FRCPC Clinical Associate Professor of Medicine

Clinical Lead Critical Care BCPSQC Medical Director Quality VGH

Disclosures

ARDS

Lancet 1967; 2:319-323

Acute Phase

Acute lung injury: •hypoxemia •  risk factor •  Bilateral •  infiltrates •No left atrl. htn. •PaO2/FiO2 < 300

ARDS:

PaO2/FiO2 < 200

Acute Lung Injury and Acute Respiratory Distress

Syndrome PaO2/FiO2 201-300

Ventilator Induced/Associated Lung Injury

•  Barotrauma –  High pressure lung injury (pneumothorax etc)

•  Oxygen Toxicity •  Volutrauma

–  Damage by overdistention

•  Atelectotrauma –  Repeated recruitment and collapse. Shear injury

•  Biotrauma –  Inflammation release by injurious ventilation

Ventilator Induced Lung Injury Overdistention

Ventilator Induced Lung Injury: EM

Overdistention

Atelectotrauma

High Volume Ventilation Low Volume

Ventilation

⊕ Regional PEEP Overinflation (-) PEEP

Increased Surfactant ⊕ Microvascular Inactivation Permeability

Atelectasis Increased (-) Filtration PEEP ⊕

Pulmonary Edema ⊕ Alveolar Flooding PEEP

PEEP (-) Reduction in (-) Lung Distensible Repetitive Opening Volume and Closing of Distal Lung Units

Leukocyte Inflammation Activation and Infiltration

Distal Lung Tissue Damage

Mechanical Ventilation

Biochemical Injury Biophysical Injury � shear � overdistention � cyclic stretch � ↑ intrathoracic pressure

Cytokines, complement

prostanoids, leukotrienes

reactive oxygen species

bacteria •  ↑ alveolar-capillary permeability

•  ↓ cardiac output

•  ↓ organ perfusion

neutrophils Distal Organs •  tissue injury secondary to inflammatory mediators/cells

•  impaired oxygen delivery

•  bacteremia

MSOF

Mortality from ARDS

The  Berlin  Defini,on  

• Within  1  week  of  insult  Timing  

• Bilateral  opaci,es  consistent  with  pulmonary  oedema  on  CXR  or  CT  Imaging  

• Not  fully  explained  by  cardiac  failure/fluid  overload  • Echo  may  help  Origin  • Mild  -­‐  Pa/FiO2  <  300  • Moderate  -­‐  Pa/FiO2  <  200  • Severe  -­‐  Pa/FiO2  <  100  Categories  

Mortality and MV duration

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Dura%o

n  (Days)  

Mortality  (%

)  

Mortality  

MV  dura,on  

Refractory Hypoxemia Options

•  Esophageal Balloon (PEEP) •  Prone Positioning •  Inh NO •  NMB •  HFOV •  APRV

Berlin ARDS Definition 2013

What is ECMO?

ECMO Is Not CPB

Early Extracorporeal Circulation

•  Reached clinical application in mid to late 1950’s •  Use limited in duration due to activation of blood

components •  Due to early oxygenators with direct air-blood

interface •  Duration of use limited to few hours (Cardiac

Surgical Procedures)

Silicone membrane lung

•  Dimethylpolysilxane (DMPS, silicone) •  Discovered in 1957 •  By 1963 used in construction of

oxygenators suitable for long-term support •  Paved the way for long term

extracorporeal circulation

1972 Hill

1975 Bartlett

1996 •  First

Neonatal ECMO Patient celebrates her 21st Birthday

ECLS History Adult Respiratory Clinical Trials • 1979 NIH-ARDS randomized trial • 1986 Gattinoni ECCO2R cohort trial • 1986 Morris ECCO2R rdm trial • 2007 Peek CESAR randomized trial

NIH Adult ECMO Study Zapol WM et al JAMA 1979,242:20;2193-96

•  Prospective randomized study (9 Centres)

•  Acute respiratory failure (ARF)

•  90 adults selected by common

•  Entry criteria: FAST: PO2<50mmhg on FIO2=1,PEEP>5. SLOW: PO2<50 for>12hours onFIO2>0.6, PEEP >5,

•  48 conventional mechanical ventilation, 42 mechanical ventilation supplemented with partial venoarterial bypass

Insights into NIH Trial •  Little or no center

experience •  VA ECMO •  Antiquated (surgical)

cannulation •  High levels of

anticoagulation •  Excessive blood loss •  No concept of lung rest –

ventilators remained at same settings

Milan ECCO2R Trial

Morris ECCO2R-LFPPV Trial

PRIMARY HYPOTHESES For patients with severe but potentially reversible respiratory failure, ECMO: Will increase the rate of survival without severe disability by six months post randomisation. Will be cost effective, compared to conventional ventilatory support.

Inclusion Criteria ✦ Potentially reversible respiratory failure ✦ Murray score > 3.0 ✦ hypercapnoea pH <7.20 ✦ aged 18-65 years

Exclusion Criteria

1.  duration of high pressure and high FIO2 ventilation < 7 days

2.  no contra-indication to limited heparinisation

3.  no contra-indication to continuation of active treatment

Patients considered potentially eligible for trial (n=766)

Did not receive ECMO support (n=22)

Received ECMO support (n=68)

n=90 Information available for primary outcome n=87

Randomised (n=180)

Non-availability of ECMO bed (n=103) Murray score <3 or pH >7.2 (n=99) High pressure ventilation >7 days (n=86) Other* (n=298)

Not randomised (n=586)

Conventional Ventilation (n=90) ECMO (n=90)

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0.25

0.50

0.75

1.00

0 50 100 150 200Analysis time (days)

Conventional ECMO

Kaplan-Meier survival estimates, by allocation

TECHNOLOGICAL ADVANCES

Oxygenators Pump Systems Cannulation Techniques Heater- Cooling Devices Pressure Monitoring Capabilities Tubing Changes Flow and Blood Monitoring Anticoagulation Advances Gas Blenders

Oxygenators using Nanoporous Hollow Fiber

Nanoporous Oxygenator

•  Good long term •  Less platelet

aggregation •  Minimal

haemolysis •  Current Gold

Standard

Centrifugal Pump Designs

Cannulation Changes

ECMO v1, 1975-2008 •  It works BUT, very

complex •  It can fail suddenly

with blowout, air, clot •  Thrombogenic and

bleeding requiring ++ products

•  Vascular access complex

ECMO v2, 2008- •  New low resistance lungs can

be used with low pressure pumps, are less thrombogenic making it much safer

•  Inherently safe self regulating circuit

•  Safer easier vascular access •  Prevent ICU syndrome, more

awake, alert and ?mobile patients

ECMO Risk-Benefit

During swine flu 332 referrals

•  Data collected from SwiFT Study •  Web based study with data collected

from 192 acute hospitals throughout the UK

•  ECMO Patients matched by –  Individual Matching – Propensity Matching – GenMatch Matching

23.7% versus 52.5 % mortality

BC Guidelines: Veno-Venous (VV) Extra-Corporeal Life Support (Sept 2015)

Adult Indications: Severe Acute Respiratory Failure (ARDS): 1.  P/F ratio is < 50 mmHg when FiO2 = 1 for at least 3 hrs, despite

use of other protective ventilation strategies

2.  P/F ratio is < 80 mmHg when FiO2 = 1 for more than 6 hrs, despite use of other protective ventilation strategies

3.  Associated with use of protective ventilation strategies there is respiratory acidosis (pH < 7.20 for > 6 hrs)

4.  P/F < 100 with a trajectory of worsening hypoxemia despite optimization of ventilation and adjunct therapies.

Additional Considerations 1.  The use of VV-ECMO should only be considered if the underlying

process is potentially reversible

2.  The indications for ECLS must be based on a collective and multidisciplinary decision. The indications for ECLS should be discussed case-by-case

3.  There is no indication for veno-arterial (VA) ECLS in ARDS when respiratory failure is isolated

Contraindications A.  The impossibility of using anticoagulation treatment is a classic

contraindication to ECMO

B.  The risk-benefit ratio of ECMO in ARDS should be considered unfavorable in cases of:

1.  Hemorrhagic or potentially hemorrhagic intracranial lesions 2.  Coma following cardiac arrest 3.  ARDS in which the patient has already been mechanically

ventilated for more than seven days 4.  Immunocompromised 5.  Significant multisystem organ failure

ECMO: in BC •  Where do we perform

ECMO? •  Everywhere? •  Limited Hospitals

sites? •  Stabilize and

Transfer? •  Does size of program

matter?

Best Practices for ARF: Volumes and Critical Mass ECMOnet (2014)

•  Expected Volumes –  Occurrence of ARF severe to warrant consideration of

ECMO (Excluding Pandemics) •  5-10/million population

•  Critical Mass •  Better outcomes with increased volumes 25-30 cases/y

•  Learning Curve (to establish competency) –  Minimal 20 cases for start up for optimal results

•  Education requirements –  Ongoing CME/ ECMO training

ECMO and ARF Final Considerations

•  Overall significant technological changes leading to increased survivability

•  Gone from case reports to now true option for care in right patient

•  Early recognition and referral to ECMO centre is key to success

•  Potentially significant transport issues •  Increase in cases improves survivability