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Conventional ventilation or ecmo for severe ARDS

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ECMO

ECMO

EXTRA CORPOREAL MEMBRANE OXGENATIONPROVIDES PROLONGED RESPIRATORY AND

CARDIAC SUPPORT

DOES NOT TREAT UNDERLYING PATHOLOGYALLOWS SUPPORT WHILST DISEASE

RESOLVES OR REVERSES

ONLY APPROPRIATE IF UNDERLYING

(2)

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

(3)
(4)
(5)

NORMAL LUNG

(6)

CONSOLIDATED LUNG

(7)

CONSOLIDATED LUNG

(8)

ARDS

ARDS

Effects on the Lung

Effects on the Lung

Capillary leak

Hyaline membranes

Surfactant depletion

Collapse/consolidation

VQ mismatch

Reduced compliance

(9)

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 CPB1956 - CLOWES - INVENTED MENBRANE

OXGENATOR

1957 - KAMMERMEYER - INVENTED

(10)

Dr & Mrs Gibbon

with their CPB

(11)

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

(12)
(13)
(14)
(15)
(16)

ECMO in Leicester UK

ECMO in Leicester UK

Neonatal ~ 40 cases per year

Paediatric ~ 20 cases per year

Adult ~ 40 cases per year

(17)

The Circuit

(18)

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

(19)

TECHNICAL ASPECTS

(20)

Cannulation

Cannulation

Veno-venous (v=28Fr ; a= 21 to 28Fr)

Veno-arterial

Percutaneous

Open

Semi-Seldinger

Double lumen

Single lumen

(21)
(22)
(23)
(24)

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

(25)

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

(26)

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

(27)

PATIENT MANAGMENT ON ECMO 2

PATIENT MANAGMENT ON ECMO 2

FLUID BALANCE

FLUID BALANCE

MULTIPLE TRANSFUSION

HYPOALBUMINAEMIC - SEPSIS, DILUTIONCAPILLARY LEAK SYDROME

RENAL FAILURE - SEPSIS

FLUID OVERLOAD FROM CIRCUIT PRIME

DIURESIS TO ‘DRY’ WEIGHTDOPAMINE

FRUSEMIDE INFUSIONAMINOPHYLLINE

(28)

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

2

30%).

Normothermia.

Diuresis to dry weight.

Hb ~ 14g/dl.

(29)

DOES ECMO WORK

(30)

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

(31)

Early Adult ECMO/ECCO

Early Adult ECMO/ECCO

22

R 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 - 77Survival < 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

(32)

Early Adult ECMO/ECCO

Early Adult ECMO/ECCO

22

R 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 + LFPPV42% survival in 19 patients PCIRV

P = 0.8, no significant difference

Little previous experience in centre with technique in humansHigh pressure ventilation before and DURING ECCO2R (PEEP >

20, Peak 45 - 55 cmH2)

Frequent severe bleeding complications (leading to

(33)

BOTH TRIALS HAVE LITTLE

RELEVANCE TO CURRENT ECMO

REGIMENS

(34)

OBSERVATIONAL STUDIES

(35)

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%

(36)

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%)

(37)

OUTCOME IN ADULTS

OUTCOME IN ADULTS

WHEN ECMO IS

WHEN ECMO IS

UNAVAILABLE

UNAVAILABLE

(38)

Results

Results

Conventional patients

8/28 Survived

(28.5%)

ECMO patients

39/57 Survived

(68.4%)

p=0.001

(39)
(40)

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

(41)

Survival for ARDS with ECMO

Survival for ARDS with ECMO

Michigan

- 66%

Leicester

- 80%

Berlin

-77%

(42)

The Sceptics’

The Sceptics’

Perspective

(43)

ADVANCED CONVENTIONAL ITU

ADVANCED CONVENTIONAL ITU

TREATMENTS

TREATMENTS

HF JET VENTILATION - Romand 1995HF OSCILLATING - Moller 1995

INHALED NITIC OXIDE - Gerlach 1993

NEBULISED PROSTACYCLIN - Zwissler 1996PCIRV - Morris 1994

PERMISSIVE HYPERCAPNOEA - Gentilello 1995

(91%n=11, survival in trauma pts )

PRONE VENTILATION - Stoller 1990; Pappert 1994LIQUID VENTILATION - still experimental

(44)

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

(45)

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)

(46)

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

(47)

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

(48)

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)

(49)

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

(50)

We need another ECMO trial !

(51)
(52)

CRITERIA FOR ACCEPTANCE

CRITERIA FOR ACCEPTANCE

Age <65 years

Reasonable long term outlook

No contraindication to anticoagulation

IPPV < 7 days

Reversible pathology

(53)

Inclusion Criteria

Inclusion Criteria

Potentially reversible

respiratory failure

Murray score > 3.0

hypercapnoea pH <7.20

aged 18-65 years

(54)

Inclusion Criteria

Inclusion Criteria

duration of high pressure and high

FIO

2

ventilation < 7 days

no contra-indication to limited

heparinisation

no contra-indication to continuation

(55)

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%

(56)

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)

(57)

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

(58)

CESAR TRIAL:

CESAR TRIAL:

Potential Referring/conventional treatment

Potential Referring/conventional treatment

hospitals - so far: 28

hospitals - so far: 28

Bristol Royal InfirmarySt James Leeds

Royal Liverpool University Hospitals (3)

University of WalesCardiffSouth Manchester

Royal Infirmary, EdinburghMorriston, Swansea

North Devon District Gloucester RoyalWalsgrave

Queen Elizabeth, GatesheadRoyal Chesterfield

Derby Royal InfirmaryDerby City

Milton Keynes General Crosshouse, KilmarnockPilgrim, Boston

Cheltenham

Queen’s, Burton-on TrentLlandough, Penarth

Macclesfield

North Staffordshire,

Stoke-on-Trent

Wrexham MaelorWest Suffolk

(59)

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

(60)

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

(61)

RESULTS

TV 6.2 + 0.8 vs. 11.8 + 0.8 ml/kg

PIP 25 + 6 vs. 33 + 8 cm/H

2

O

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

(62)

Adult ECMO,

PATIENT STATUS AT REFERRAL.

PaO

2

/FIO

2

65mmhg

Murray Score=3.4

Time Vent=76.5 hrs

Time on 100% O

2

=

14 hrs.

PAP = 39.6 cmH

2

O.

PEEP = 10 cmH

2

O.

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.

(63)

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)

(64)

ECMO FOR CARDIAC

ECMO FOR CARDIAC

SUPPORT

(65)

Cardiac ECLS at Glenfield

Cardiac ECLS at Glenfield

40 pediatric cardiac

(66)

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

(67)

Cardiac ECLS at Glenfield

Between July 1991 and Sept 1998

505 patients received ECMO

152 adult respiratory

182 neonatal respiratory

121 pediatric respiratory

(68)

Adult Cardiac ECLS

10 patients, 5 survived

age 39.6 (19)

Run time 188 (220) hours

(69)

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