Transcript Conventional ventilation or ECMO for Severe ARDS

ECMO
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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
PATHOLOGY IS POTENTIALLY REVERSIBLE
PATHOLOGIES POTENTIALLY
TREATABLE BY ECMO
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Aspiration pneumonia
ARDS trauma
ARDS sepsis
ARDS obstetric
Pneumonia
– viral
– bacterial
– atypical
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Pancreatitis
Drowning
Burns - smoke
inhalation
Pulmonary embolus
Tricyclic Antidepressant
OD
Viral myocarditis
Post CPB failure to
wean
NORMAL LUNG
CONSOLIDATED LUNG
CONSOLIDATED LUNG
ARDS
Effects on the Lung
 Capillary
leak
 Hyaline membranes
 Surfactant depletion
 Collapse/consolidation
 VQ mismatch
 Reduced compliance
 Neutrophil infiltration and cytokine
release
HISTORY OF ECMO -1
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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
SILICONE - MEMBRANE LUNG
Dr & Mrs Gibbon
with their CPB
machine
HISTORY OF ECMO - 2
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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
2001 - 120 CENTRES WORLD WIDE
ECMO in Leicester UK
 Neonatal
~ 40 cases per year
 Paediatric ~ 20 cases per year
 Adult ~ 40 cases per year
 Cardiac (v.small number)
The Circuit
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
 Veno-venous
(v=28Fr ; a= 21 to 28Fr)
 Veno-arterial
 Percutaneous
 Open
 Semi-Seldinger
 Double
lumen
 Single lumen
21F percutaneous return cannula in
adult Rt femoral vein
VVAdvantages &
Disadvantages
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Pulmonary vasodilation
(corr. Of hypoxia and
acidosis
Myocardial oxygenation
Maintained pulmonary
blood flow
Minimally invasive
Not affected by PDA
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More difficult
Slower stabilisation
No circulatory support
Re-circulation
VA Advantages &
Disadvantages
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Easy to use
Circulatory support
Instant stabilisation
Huge experience
Right heart offloaded
and rested
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Carotid ligation
Jugular ligation
Raised LV afterload
Reduced pulmonary
blood flow
Hypoxic coronary
perfusion
Stun- high LV afterload
Duct
PT MANAGEMENT ON ECMO 1
LUNG REST
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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
FLUID BALANCE
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MULTIPLE TRANSFUSION
HYPOALBUMINAEMIC - SEPSIS, DILUTION
CAPILLARY LEAK SYDROME
RENAL FAILURE - SEPSIS
FLUID OVERLOAD FROM CIRCUIT PRIME
DIURESIS TO ‘DRY’ WEIGHT
 DOPAMINE
 FRUSEMIDE INFUSION
 AMINOPHYLLINE
 40% CVVHF
PATIENT MANAGEMENT ON ECMO -3
 Percutaneous
Veno-venous
Cannulation.
 Low range heparinisation; ACT 160-200
 Lung Rest (20/10, RR10, FIO2 30%).
 Normothermia.
 Diuresis to dry weight.
 Hb ~ 14g/dl.
DOES ECMO WORK
RCTs of ECLS in Adults
NIH Adult
ECMO Trial
Zapol et al JAMA 242:2193-96,1979
PCIRV
vs ECCO2R
Morris et al, Am J Respir Crit Care Med 1994;149:295-305.
Early Adult ECMO/ECCO2R Trials
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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
Little experience, varying technique in different centres
Early Adult ECMO/ECCO2R Trials
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Morris, et.al: Randomized Trial of PCIRV and
ECCO2R in ARDS. AJRCCM,1994;149:295-305
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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
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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
discontinuation of ECCO2R in 7/19 cases)
BOTH TRIALS HAVE LITTLE
RELEVANCE TO CURRENT ECMO
REGIMENS
OBSERVATIONAL STUDIES
Cohort studies of ECMO- Leicester
1997.
PaO2/FIO2 65mmhg
Murray Score=3.4
Diagnosis
N
Survival
Pneumonia
26
19
%
Survival.
73%
ARDS
20
13
65%
Other
4
1
25%
Total
50
33
66%
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)
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ECLS for 100 adult patients with severe
respiratory failure.PaO2/FiO2 = 55mmHg Kolla
S et al, Ann Surg 1997;226:544-64 (survival
54%)
OUTCOME IN ADULTS
WHEN ECMO IS
UNAVAILABLE
Results
 Conventional
patients
8/28 Survived (28.5%)
 ECMO patients
39/57 Survived (68.4%)
 p=0.001
However, time has passed and
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
 Michigan
 Leicester
 Berlin
 Vienna
- 66%
- 80%
-77%
-80%
The Sceptics’
Perspective
ADVANCED CONVENTIONAL ITU
TREATMENTS
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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
protective ventilatory strategies:
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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 nonsurvivors (65 first 50 adult VV ECMO Glenfield)
Recent improved survival in severe
ARDS
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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 kPa
(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
protective ventilatory strategies:
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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 failure in low PEEP high Vt (12 ml/kg) group
Improved survival in severe ARDS with
protective ventilatory strategies:
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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
No data on subgroup with paO2/FiO2 < 100)
Estimated mortality of most severe
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)
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Phone survey Glenfield/Heartlink ECMO
centre: ~ 72% mortality in patients referred
for but not receiving ECMO (no bed/staff)
VASILYEV (1995)
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
pts ie more like ECMO pts
We need another ECMO trial !
CRITERIA FOR ACCEPTANCE
 Age
<65 years
 Reasonable long term outlook
 No contraindication to anticoagulation
 IPPV < 7 days
 Reversible pathology
 Optimum conventional treatment tried
Inclusion Criteria
 Potentially
reversible
respiratory failure
 Murray score > 3.0
 hypercapnoea pH <7.20
 aged 18-65 years
Inclusion Criteria
 duration
of high pressure and high
FIO2 ventilation < 7 days
 no contra-indication to limited
heparinisation
 no contra-indication to continuation
of active treatment
Sample Size
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Assuming a 10% risk of severe disability
among survivors in both trial arms
a = 0.05 (2 sided test)
b = 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
Treatment
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“.. 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)
(Analogous to UK Neonatal ECMO trial)
CESAR Trial:
Outcome measures
 Primary:
death or severe disability at six
months
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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
(by methods adopted from neonatal ECMO trial)
CESAR TRIAL:
Potential Referring/conventional treatment
hospitals - so far: 28
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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
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Derby Royal Infirmary
Derby City
Milton Keynes General
Crosshouse, Kilmarnock
Pilgrim, Boston
Cheltenham
Queen’s, Burton-on Trent
Llandough, Penarth
Macclesfield
North Staffordshire, Stoke-onTrent
Wrexham Maelor
West Suffolk
Chase Farm, Enfield
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
treatment.
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
 PaO2/FIO2 138 + 64 vs. 134 + 58
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
RESULTS
 TV 6.2 + 0.8 vs. 11.8 + 0.8 ml/kg
 PIP 25 + 6 vs. 33 + 8 cm/H2O
 Mortality 31.0% vs. 39.8% (p=0.007)
 Days without organ failure also lower
(p=0.006)
Adult ECMO,
PATIENT STATUS AT REFERRAL.
 PaO2/FIO2
65mmhg
 Murray Score=3.4
 Time Vent=76.5 hrs
 Time on 100% O2=
14 hrs.
 PAP = 39.6 cmH2O.
 PEEP = 10 cmH2O.
 MV = 12.6 L/min.
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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
ECMO
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Median length of stay of adult ECMO pts is 14 days
(range 0-41days). ELSO recommend 2:1 specialist to
patient ratio
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Daily cost for conventional care for severe respiratory
failure is £1500 -£2300 (Sheffield Health care costing
system)
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Total cost per case £27000 - £63000
ECMO FOR CARDIAC
SUPPORT
Cardiac ECLS at Glenfield
40
pediatric cardiac
10 adult 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
 Post infarct VSD
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Cardiac ECLS at Glenfield
 Between
July 1991 and Sept 1998
 505 patients received ECMO
 152 adult respiratory
 182 neonatal respiratory
 121 pediatric respiratory
Adult Cardiac ECLS
10
patients, 5 survived
age 39.6 (19)
Run time 188 (220) hours
PaO2/FIO2 = 81 (20) mmHg
CESAR