ECMO
ECMO
EXTRA CORPOREAL MEMBRANE OXGENATION PROVIDES PROLONGED RESPIRATORY AND
CARDIAC SUPPORT
DOES NOT TREAT UNDERLYING PATHOLOGY ALLOWS SUPPORT WHILST DISEASE
RESOLVES OR REVERSES
ONLY APPROPRIATE IF UNDERLYING
PATHOLOGIES POTENTIALLY
PATHOLOGIES POTENTIALLY
TREATABLE BY ECMO
TREATABLE BY ECMO
Aspiration pneumonia ARDS trauma ARDS sepsis ARDS obstetric Pneumonia – viral – bacterial – atypical Pancreatitis Drowning Burns - smoke inhalation Pulmonary embolus Tricyclic Antidepressant OD Viral myocarditis Post CPB failure to wean
NORMAL LUNG
CONSOLIDATED LUNG
CONSOLIDATED LUNG
ARDS
ARDS
Effects on the Lung
Effects on the Lung
Capillary leak
Hyaline membranes
Surfactant depletion
Collapse/consolidation
VQ mismatch
Reduced compliance
HISTORY OF ECMO -1
HISTORY OF ECMO -1
1916 - MACLEAN - HEPARIN (JH) 1930 - JOHN GIBBON - FIRST
INVESTIGATION INTO ECLS
1944 - KOLFF AND BERK - BLOOD
OXYGENATION IN CELLOPHANE CHAMBERS OF ARTIFICIAL KIDNEY
1950 - EARLY DEVELOPEMENTS OF CPB 1956 - CLOWES - INVENTED MENBRANE
OXGENATOR
1957 - KAMMERMEYER - INVENTED
Dr & Mrs Gibbon
with their CPB
HISTORY OF ECMO - 2
HISTORY OF ECMO - 2
1960 - EXPERIMENTS INTO PROLONGED CPB
1972 - HILL - FIRST ADULT ECMO - AORTIC
RUPTURE
1975 - BARTLETT - FIRST SUCCESSFUL
NEONATAL ECMO
1986 - USA 18 CENTRES ECMO
1986 - GATTINONI - 50% SURVIVAL IN ADULT
ECCO2R
1989 - ELSO REGISTRY
ECMO in Leicester UK
ECMO in Leicester UK
Neonatal ~ 40 cases per year
Paediatric ~ 20 cases per year
Adult ~ 40 cases per year
The Circuit
DIFFERENCES WITH CPB
DIFFERENCES WITH CPB
– NO RESERVOIR; BLADDER SERVOREGULATOR – NO CENTRIFUGAL PUMP (haemolysis)
– NO MICROPROUS OXYGENATOR
– VENO-VENOUS PREFERRED WITH ADEQUATE
CARDIAC FUNCTION
– NORMOTHERMIA
– HEPARIN ACT 160-200 NOT 500+ – NO ARTERIAL FILTER
– NOT HAEMODILUTED HB 14g/dl;HCT @ 40 – NO AUTOTRANSFUSION
TECHNICAL ASPECTS
Cannulation
Cannulation
Veno-venous (v=28Fr ; a= 21 to 28Fr)
Veno-arterial
Percutaneous
Open
Semi-Seldinger
Double lumen
Single lumen
VVAdvantages &
VVAdvantages &
Disadvantages
Disadvantages
Pulmonary vasodilation
(corr. Of hypoxia and acidosis
Myocardial oxygenation Maintained pulmonary
blood flow
Minimally invasive Not affected by PDA
More difficult
Slower stabilisation No circulatory support Re-circulation
VA Advantages &
VA Advantages &
Disadvantages
Disadvantages
Easy to use Circulatory support Instant stabilisation Huge experience Right heart offloaded
and rested Carotid ligation Jugular ligation Raised LV afterload Reduced pulmonary blood flow Hypoxic coronary perfusion
Stun- high LV afterload Duct
PT MANAGEMENT ON ECMO 1
PT MANAGEMENT ON ECMO 1
LUNG REST
LUNG REST
FIO2 - 0.3 PEEP 10cm H20 PEAK INSPIRATORY PRESSURE 20cm H2O RATE 5- 10/min THEREFORE REDUCE: – BAROTRAUMA – VOLUTRAUMA – OXYGEN TOXICITY – MYOCARDIAL DEPRESSION
PATIENT MANAGMENT ON ECMO 2
PATIENT MANAGMENT ON ECMO 2
FLUID BALANCE
FLUID BALANCE
MULTIPLE TRANSFUSION HYPOALBUMINAEMIC - SEPSIS, DILUTION CAPILLARY LEAK SYDROME
RENAL FAILURE - SEPSIS
FLUID OVERLOAD FROM CIRCUIT PRIME
DIURESIS TO ‘DRY’ WEIGHT DOPAMINE
FRUSEMIDE INFUSION AMINOPHYLLINE
PATIENT MANAGEMENT ON ECMO -3
PATIENT MANAGEMENT ON ECMO -3
Percutaneous Veno-venous
Cannulation.
Low range heparinisation; ACT 160-200
Lung Rest (20/10, RR10, FIO
230%).
Normothermia.
Diuresis to dry weight.
Hb ~ 14g/dl.
DOES ECMO WORK
RCTs of ECLS in Adults
RCTs of ECLS in Adults
NIH Adult ECMO Trial
Zapol et al JAMA 242:2193-96,1979
PCIRV vs ECCO2R
Early Adult ECMO/ECCO
Early Adult ECMO/ECCO
22R Trials
R Trials
Zapol, : (NIH Trial) (VA ECMO +ventilation and
ventilation only) Severe ARF. A Randomized Prospective Study. JAMA 1979:242:2193-6)
90 patients, 9 US centres, 1974 - 77 Survival < 10% in both arms
Criticism:
– 1. VA ECMO used (prone to microthrombi in lungs) – 2. High anticoagulation and bleeding complications – 3. High pressure ventilation used even DURING ECMO – 4. Mean duration of ventilation prior to ECMO was 9
days
Early Adult ECMO/ECCO
Early Adult ECMO/ECCO
22R Trials
R Trials
Morris, et.al: Randomized Trial of PCIRV and
ECCO2R in ARDS. AJRCCM,1994;149:295-305
40 patients, severe ARDS (paO2/FiO2 63 mmHg) in one US
centre
33% survival in 21 patients ECCO2R + LFPPV 42% survival in 19 patients PCIRV
P = 0.8, no significant difference
Little previous experience in centre with technique in humans High pressure ventilation before and DURING ECCO2R (PEEP >
20, Peak 45 - 55 cmH2)
Frequent severe bleeding complications (leading to
BOTH TRIALS HAVE LITTLE
RELEVANCE TO CURRENT ECMO
REGIMENS
OBSERVATIONAL STUDIES
Cohort studies of ECMO- Leicester
Cohort studies of ECMO- Leicester
1997.
1997.
PaO2/FIO2 65mmhg Murray Score=3.4 Diagnosis N Survival % Survival. Pneumonia 26 19 73% ARDS 20 13 65% Other 4 1 25% Total 50 33 66%Cohort Studies of ECLS - Other
Cohort Studies of ECLS - Other
LFPPV with ECCO2R in severe acute
respiratory failure, Gattinoni L et al, JAMA
1986 256;7:881-6 (50% survival)
ECLS for 100 adult patients with severe
respiratory failure.PaO
2/FiO
2= 55mmHg Kolla
S et al, Ann Surg 1997;226:544-64 (survival
54%)
OUTCOME IN ADULTS
OUTCOME IN ADULTS
WHEN ECMO IS
WHEN ECMO IS
UNAVAILABLE
UNAVAILABLE
Results
Results
Conventional patients
8/28 Survived
(28.5%)
ECMO patients
39/57 Survived
(68.4%)
p=0.001
However, time has passed and
However, time has passed and
things have changed since ...
things have changed since ...
Some centres in the US and Europe have
been quite successful at providing ECMO
for severe adult respiratory failure
(Ann Arbor, Michigan, Berlin, Marburg,
Munich, Glenfield Hospital, Leicester etc.)
ECMO has become ‘standard’ treatment
for severe Neonatal Respiratory Failure
and Persistent Pulmonary Hypertension of
the Newborn
Survival for ARDS with ECMO
Survival for ARDS with ECMO
Michigan
- 66%
Leicester
- 80%
Berlin
-77%
The Sceptics’
The Sceptics’
Perspective
ADVANCED CONVENTIONAL ITU
ADVANCED CONVENTIONAL ITU
TREATMENTS
TREATMENTS
HF JET VENTILATION - Romand 1995 HF OSCILLATING - Moller 1995
INHALED NITIC OXIDE - Gerlach 1993
NEBULISED PROSTACYCLIN - Zwissler 1996 PCIRV - Morris 1994
PERMISSIVE HYPERCAPNOEA - Gentilello 1995
(91%n=11, survival in trauma pts )
PRONE VENTILATION - Stoller 1990; Pappert 1994 LIQUID VENTILATION - still experimental
Improved survival in severe ARDS with
Improved survival in severe ARDS with
protective ventilatory strategies:
protective ventilatory strategies:
Hickling, Walsh, Henderson, Jackson:
Low mortality rate in adult respiratory distress syndrome using low-volume, pressure
limited ventilation with permissive hypercapnia: A prospective study.Crit Care
Med1994,22:1568-78
74 % survival (= 40 of 53 patients with severe
ARDS, ie. Murray Lung Injury score > 2.5,
paO2/FiO2 < 150 mmHg), 1988 - 1992, one centre
Mean Murray score 3.1 survivors,
3.2 non-survivors (3.4 first 50 adult VV ECMO Glenfield)
Mean PaO2/FiO2: 91+/-29 survivors, 81+/- 46
Recent improved survival in severe
Recent improved survival in severe
ARDS
ARDS
Abel, Finney, Brett, Keogh, Morgan, Evans:
Reduced mortality in association with ARDS.
Thorax 1998; 53: 292 - 294
66% survival in moderate to severe ARDS
78 patients 1993-97 at Brompton Hospital (vs 34% survival in 41 patients 1990-93)
mean Murray score 2.8, mean PaO2/FiO2 90 mmHg/12 kPamean Murray score 2.8, mean PaO2/FiO2 90 mmHg
(First 50 adult VV ECMO patients Glenfield Hospital, Leicester,
1989 - 1995: Murray lung injury score 3.4, PaO2/FiO2 65 mmHg, (66% survival)
Improved survival in severe ARDS with
Improved survival in severe ARDS with
protective ventilatory strategies:
protective ventilatory strategies:
Amato, Barbas, Medeiros et al: Effect
of a Protective-Ventilation Strategy on Mortality in ARDS. NEJM;1998;338:347-54
53 patients, two ICU’s in Brazil, 1990 - 1995, early
ARDS + 2 - 3 extrapulmonary organ failures
62% 28 day survival with protective ventilation (n =
29, mean PaO2/FiO2 112, mean LIS 3.4) mean PEEP 16 >> 13, Vt < 6 ml/kg (360-390 ml), pressure limited ventilation with peak pressure < 30 cmH2O,
permissive hypercapnoea
vs 29% survival and more deaths from progressive respiratory vs 29% survival and more deaths from progressive respiratory
failure in low PEEP high Vt (12 ml/kg) group
Improved survival in severe ARDS with
Improved survival in severe ARDS with
protective ventilatory strategies:
protective ventilatory strategies:
The ARDS Network: Ventilation with Lower Tidal
Volumes as Compared with Traditional Tidal
Volumes for Acute Lung Injury and ARDS. NEJM 4 May 2000;342:1301-8
861 patients in 10 US university centres
ALI/ARDS, ie. paO2/FiO2 < 300 mmHg, 80% < 200, mean 136
69% survival and less ventilator days with 6ml/kg
tidal volume (mean paO2/FiO2
60% survival with 12 ml/kg Vt
22% mortality difference, P = 0.007
Estimated mortality of most severe
Estimated mortality of most severe
ARDS (paO2/FiO2 < 100 mmHg):
ARDS (paO2/FiO2 < 100 mmHg):
US: NIH ARDSnet database: 70 %
UK:
Intensive Care National Audit &
Research Centre (ICNARC): 62%
(1506 patients with paO2/FiO2 < 100 mmHg)
Phone survey Glenfield/Heartlink ECMO
centre: ~ 72% mortality in patients referred
for but not receiving ECMO (no bed/staff)
VASILYEV (1995)
VASILYEV (1995)
Chest 1995;107:1083-8
Chest 1995;107:1083-8
International multicentre prospecttive study of
hospital survival in acute respiratory
failure
defn /Fio2 0.5 for >24hrs
1426 patients from 25 centres (USA11;
Europe 14)
Overall survival 55%
Survival only 33% in hypoxic and hypercarbic
We need another ECMO trial !
CRITERIA FOR ACCEPTANCE
CRITERIA FOR ACCEPTANCE
Age <65 years
Reasonable long term outlook
No contraindication to anticoagulation
IPPV < 7 days
Reversible pathology
Inclusion Criteria
Inclusion Criteria
Potentially reversible
respiratory failure
Murray score > 3.0
hypercapnoea pH <7.20
aged 18-65 years
Inclusion Criteria
Inclusion Criteria
duration of high pressure and high
FIO
2ventilation < 7 days
no contra-indication to limited
heparinisation
no contra-indication to continuation
Sample Size
Sample Size
Assuming a 10% risk of severe disability
among survivors in both trial arms
= 0.05 (2 sided test)
= 0.2
Sample size of 120 patients in each group
would be required to detect a reduction in the
rate of primary outcome from 73% to 55%
CESAR Trial: Conventional
CESAR Trial: Conventional
Treatment
Treatment
“.. Any treatment which relies on the patient’s
lungs to provide gas exchange…”
Can include any treatment modality thought
appropriate by patient’s intensivist, eg prone, NO, HFOV
Low (6ml/kg) tidal volume strategy (as in
ARDSnet trial) and PIP < 40 cmH2O recommended, but not mandatory
Not standardized (no consensus)
CESAR Trial:
CESAR Trial:
Outcome measures
Outcome measures
Primary: death or severe disability at six
months
Secondary:
- Nature and duration of ventilation and other organ system support
- Length of ICU and hospital stay - Blood product use
- Cost/cost effectiveness to health and social services, patients and their families
CESAR TRIAL:
CESAR TRIAL:
Potential Referring/conventional treatment
Potential Referring/conventional treatment
hospitals - so far: 28
hospitals - so far: 28
Bristol Royal Infirmary St James Leeds
Royal Liverpool University Hospitals (3)
University of WalesCardiff South Manchester
Royal Infirmary, Edinburgh Morriston, Swansea
North Devon District Gloucester Royal Walsgrave
Queen Elizabeth, Gateshead Royal Chesterfield
Derby Royal Infirmary Derby City
Milton Keynes General Crosshouse, Kilmarnock Pilgrim, Boston
Cheltenham
Queen’s, Burton-on Trent Llandough, Penarth
Macclesfield
North Staffordshire,
Stoke-on-Trent
Wrexham Maelor West Suffolk
CONCLUSIONS
CONCLUSIONS
.
.
ECMO with lung rest is a rational
treatment.
Survival with conventional treatment
remains poor in most centres.
Only an RCT can determine the best
Ventilation with lower tidal volumes for acute lung
injury and the acute respiratory distress syndrome
The Acute Respiratory Distress Syndrome Network
N Engl J Med 2000;342:1301-8
6ml/Kg (PIP<30) vs. 12ml/Kg (PIP<50)
861 patients
Age 51 + 17 vs. 52 + 18
RESULTS
TV 6.2 + 0.8 vs. 11.8 + 0.8 ml/kg
PIP 25 + 6 vs. 33 + 8 cm/H
2O
Mortality 31.0% vs. 39.8% (p=0.007)
Days without organ failure also lower
(p=0.006)
Ventilation with lower tidal volumes for acute lung
injury and the acute respiratory distress syndrome
The Acute Respiratory Distress Syndrome Network
Adult ECMO,
PATIENT STATUS AT REFERRAL.
PaO
2/FIO
265mmhg
Murray Score=3.4
Time Vent=76.5 hrs
Time on 100% O
2=
14 hrs.
PAP = 39.6 cmH
2O.
PEEP = 10 cmH
2O.
MV = 12.6 L/min.
MAP = 82 mmHg. MPAP = 29 mmHg. CVP = 12 mmHg. PAWP = 12 mmHg. CO = 127 ml/kg/min. UO = 1.4 ml/kg/hr. Age = 30.1 yrs. Wt = 71.9 Kg. Hb = 10.8 Kg.COST IMPLICATIONS OF
COST IMPLICATIONS OF
ECMO
ECMO
Median length of stay of adult ECMO pts is 14 days
(range 0-41days). ELSO recommend 2:1 specialist to patient ratio
Daily cost for conventional care for severe respiratory
failure is £1500 -£2300 (Sheffield Health care costing system)
ECMO FOR CARDIAC
ECMO FOR CARDIAC
SUPPORT
Cardiac ECLS at Glenfield
Cardiac ECLS at Glenfield
40 pediatric cardiac
Adult Cardiac ECLS
DIAGNOSES
Post op MVR
Pulmonary Emboli
(2)
Loefflers syndrome
CABG (2)
Viral Myocarditis
Pericardectomy
septic shock post
removal of infected
pacing wire /
vegative mass
Cardiac ECLS at Glenfield
Between July 1991 and Sept 1998
505 patients received ECMO
152 adult respiratory