ECMOECMO

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 PATHOLOGIES POTENTIALLY TREATABLE BY ECMOTREATABLE 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 LUNGNORMAL LUNG

CONSOLIDATED LUNGCONSOLIDATED LUNG

CONSOLIDATED LUNGCONSOLIDATED LUNG

ARDSARDSEffects on the LungEffects on the Lung

Capillary leak Hyaline membranes Surfactant depletion Collapse/consolidation VQ mismatch Reduced compliance Neutrophil infiltration and cytokine release

HISTORY OF ECMO -1HISTORY 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

SILICONE - MEMBRANE LUNG

Dr & Mrs Gibbon with their CPB

machine

HISTORY OF ECMO - 2HISTORY 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 2001 - 120 CENTRES WORLD WIDE

ECMO in Leicester UKECMO in Leicester UK

Neonatal ~ 40 cases per year Paediatric ~ 20 cases per year Adult ~ 40 cases per year Cardiac (v.small number)

The CircuitThe Circuit

DIFFERENCES WITH CPBDIFFERENCES 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 ASPECTSTECHNICAL ASPECTS

CannulationCannulation

Veno-venous (v=28Fr ; a= 21 to 28Fr) Veno-arterial Percutaneous Open Semi-Seldinger Double lumen Single lumen

VVAdvantages & VVAdvantages & DisadvantagesDisadvantages

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 & DisadvantagesDisadvantages

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 1PT MANAGEMENT ON ECMO 1LUNG RESTLUNG 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 2PATIENT MANAGMENT ON ECMO 2FLUID BALANCEFLUID 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 40% CVVHF

PATIENT MANAGEMENT ON ECMO -3PATIENT 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 WORKDOES ECMO WORK

RCTs of ECLS in AdultsRCTs 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/ECCOEarly Adult ECMO/ECCO22R TrialsR 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 Little experience, varying technique in different centres

Early Adult ECMO/ECCOEarly Adult ECMO/ECCO22R TrialsR 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

discontinuation of ECCO2R in 7/19 cases)

BOTH TRIALS HAVE LITTLE RELEVANCE TO CURRENT ECMO

REGIMENS

OBSERVATIONAL STUDIESOBSERVATIONAL STUDIES

Cohort studies of ECMO- Leicester Cohort studies of ECMO- Leicester 1997.1997.

PaO2/FIO2 65mmhgMurray 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 - OtherCohort 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.PaO2/FiO2 = 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 UNAVAILABLEUNAVAILABLE

ResultsResults

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 ECMOSurvival for ARDS with ECMO

Michigan - 66% Leicester - 80% Berlin -77% Vienna -80%

The Sceptics’ The Sceptics’ PerspectivePerspective

ADVANCED CONVENTIONAL ITU ADVANCED CONVENTIONAL ITU TREATMENTSTREATMENTS

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 non-survivors (65 first 50 adult VV ECMO Glenfield)

Recent improved survival in severe Recent improved survival in severe ARDSARDS

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 mmHgmean 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 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 vs 29% survival and more deaths from progressive respiratory failure in low PEEP high Vt (12 ml/kg) grouprespiratory 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 No data on subgroup with paO2/FiO2 < 100)

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;107:1083-8Chest 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 !We need another ECMO trial !

CRITERIA FOR ACCEPTANCECRITERIA FOR ACCEPTANCE

Age <65 years Reasonable long term outlook No contraindication to anticoagulation IPPV < 7 days Reversible pathology Optimum conventional treatment tried

Inclusion CriteriaInclusion Criteria

Potentially reversible respiratory failure

Murray score > 3.0 hypercapnoea pH <7.20 aged 18-65 years

Inclusion CriteriaInclusion 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 SizeSample 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 TreatmentTreatment

“.. 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: CESAR Trial: Outcome measuresOutcome 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

(by methods adopted from neonatal ECMO trial)

CESAR TRIAL: CESAR TRIAL: Potential Referring/conventional treatment Potential Referring/conventional treatment

hospitals - so far: 28hospitals - 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 Chase Farm, Enfield

CONCLUSIONSCONCLUSIONS..

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 NetworkN 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

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)

Ventilation with lower tidal volumes for acute lung injury and the acute respiratory distress syndrome

The Acute Respiratory Distress Syndrome NetworkN Engl J Med 2000;342:1301-8

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.

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 ECMOECMO

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)

Total cost per case £27000 - £63000

ECMO FOR CARDIAC ECMO FOR CARDIAC SUPPORTSUPPORT

Cardiac ECLS at GlenfieldCardiac ECLS at Glenfield

40 pediatric cardiac 10 adult cardiac

Adult Cardiac ECLSDIAGNOSES

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

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