Extracorporeal Therapy - Dr. Samir kamal MNDU 8

1. Extrac0rporeal
therapy
NON-RENALUSES
r: SamirKamal

2. Corpus = Body
Extracorporeal therapy = ttt
comes from outside the body
Objective : Extracorporeal
circulator therapy

3. Lecture Outline
• RRT:
• Hemoperfusion
• Apheresis
• (ECMO) and ECLS
• ECLSS
• Others e.g. Heart-lung machine, LVADs
….

4. Renal Replacement Therapy
machines for Extracoeporeal
therapy

5. Types of RRT
• Intermittent Hemodialysis (IHD)
• Continuous Dialysis (CRRT)
– Continuous veno-venous hemo-dialysis/
-filtration/ -diafiltration (CVVHD, CVVHF,
CVVHDF)
– Sustained low-efficiency daily dialysis
(SLEDD)

6. Principles of Dialysis: Diffusion
Compartment #1 Compartment #2
Hydrostatic pressure (Ph) = Hydrostatic
pressure (Ph)
Concentration [x] > Concentration [x]

7. Principles of Dialysis:
Convection
Compartment #1 Compartment #2
Ph > Ph
[x] ≈ [x]
solvent drag

8. Diffusion With Convection
Compartment #1 Compartment #2
Ph > Ph
[x] > [x]

9. Dialysis Setup
Blood (QB) Dialysate (QD)
From patient
To patient
To drain
Inflow
Hemodialyzer

10. SCUF
Slow Continuous
Ultrafiltration
Maximum Pt. Fluid removal rate = 2000 ml/h
Therapy options

11. CVVH
Continuous
Veno-Venous
Hemofiltration
Maximum Pt. Fluid removal rate = 1000 ml/h
Therapy options

12. CVVHD
Continuous
Veno-Venous
Hemodialysis
Maximum Pt. fluid removal rate = 1000 ml/h
Therapy Options

13. CVVHDF
Continuous
Veno-Venous
Hemodiafiltration
Maximum Pt. Fluid removal rate = 1000 ml/h
Therapy options
Replacement

14. Indications of RRT
Non-renal:
Systemic inflammatory
response syndrome and
Sepsis
Acute respiratory distress
syndrome
Congestive heart failure
Cardiopulmonary bypass
Crush injury
Inborn errors of
metabolism
Tumor lysis syndromes
Lactic acidosis

15. Hemofiltration and sepsis:
From the few well-designed and
documented studies that we have so far, it
is safe to say that optimalization
of delivered dose in renal
replacement therapy has
a proven positive effect.
An ultrafiltration rate between 35 and 45
ml/kg/h, with adjustment for predilution and
down time, can be recommended for the
septic patient until other data are available.
The results of further dose outcome
studies with higher ultrafiltration rates will
likely be the stepping stone to further
improvements in daily clinical practice.

16. Hemofiltration and sepsis:
The underlying hypothesis is that hemofiltration
removes inflammatory mediators from the
circulation and thereby dampens the systemic inflammatory
response
With the exception of endotoxin and the biologically active
form of tumor necrosis factor (TNF), which is a trimer with
molecular weight of 54,000 Da, the molecular weight of
most inflammatory mediators is compatible with
convective removal through high-flux membranes
Another explanation is binding of the circulating
mediators either to each other or to other
substances

17. Hemofiltration and ARDS:
Elimination of inflammatory
mediators and fluid removal
with reduction of extra-
vascular lung water (EVLW)
are mechanisms by which
hemofiltration may be
beneficial in ARDS

18. RRT and Congestive cardiac
failure:
CONCLUSION:
Ultrafiltration removed fluid
overload in diuretic-resistant,
severe, CHF in our single-center
experience. Six months after
ultrafiltration, hospitalization
rates were reduced by 36%
and furosemide dose was
50% lower, compared to the
previous 6 months. Worsened
renal function was the most
common complication (14% of
patients).

19. RRT and Cardiopulmonary
bypass:

20. RRT and Crush injury:
Because the molecular
weight of myoglobin is
17,000 Da and thus
compatible with convective
removal, hemofiltration
might represent a means
to prevent renal failure in
crush injury and other
causes of rhabdomyolysis
and myoglobin gaining
access to the circulation.
The presence of myoglobin
in the filtrate has indeed
been demonstrated
Crush syndrome is the clinicalCrush syndrome is the clinical
condition caused by compressioncondition caused by compression
of muscle with subsequentof muscle with subsequent
rhabdomyolysis which can thenrhabdomyolysis which can then
cause the complications ofcause the complications of
electrolyte disturbances, fluidelectrolyte disturbances, fluid
sequestration, & myoglobinuria.sequestration, & myoglobinuria.
Another :Another :
"A form of traumatic"A form of traumatic
rhabdomyolysis that occurs afterrhabdomyolysis that occurs after
prolonged continuous pressure &prolonged continuous pressure &
is characterized by systemicis characterized by systemic
involvement".involvement".

21. RRT and Tumor lysis
syndrome:
The prospective use of CVVH could potentially decrease the
morbidity and mortality associated with induction
chemotherapy in very high-risk patients with a large tumor
burden
Both uric acid and phosphate
are small molecules that
require a highly diffusive
clearance, and conventional
dialysis is certainly more
effective than the continuous
techniques
However, CRRT can be used
in unstable patients or in
combination with intermittent
dialysis

22. RRT and Inborn errors of
metabolism:
(CVVHD) are rapidly effective in clearing these low molecular
weight toxic metabolites, allowing the patients to recover their
neurological status
Children with maple
syrup urine disease,
urea cycle disorders,
and organic acidemia
can produce high
levels of branched-
chain amino acids and
hyperammonemia,
inducing irreversible
damage, especially in
the central nervous
system.

23. RRT and Lactic acidosis:
Causes of lactic acidosis
Type A:
Acute hypoxia
Anemia
Carbon monoxide poisoning
Cardiogenic shock
Hemorrhagic shock
Septic shock
Type B
Systemic diseaseLiver failure
Malignancy
Drugs or toxinsMetformin
Cyanide
Salicylate, ethylene glycol, methanol,
propylene glycol
Linezolid
Propofol
Stavudine, didanosine
Isoniazid
Hereditary enzyme deficiency.
CRRT or IHD should only be considered in
treatment of patients with severe lactic
acidosis if the patient has other indications
for initiation of dialysis such as volume
overload, metabolic disturbances.
Filtered lactate clearance by high-volume CRRT is
small compared with overproduction of lactic acid in
septic shock. Therefore, lactic acidosis alone
should not be the sole indication for initiation of
CRRT.

24. What is hemoperfusion?
- the passage of blood through a column containing adsorbent particles
- The particles are typically activated charcoal or resin
Muirhead, EE, Reid, AF. Resin artificial kidney. Lab Clin Med 1948; 33:841.

25. Hemoperfusion
Uses hemodialysis machine - but runs blood directly through a charcoal-
or sorbent-containing filter
Blood
from
patient
ARTERY
or
VEIN
VEIN
Return
to
patient

26. The Charcoal Hemoperfusion
Filter:
Brochure from the “Adsorba C” range by Gambro, for the Prismaflex machines
- Canister with 300g of
activated charcoal
- Blood flow though the
canister is driven by a
normal dialysis machine
- There is no ultrafiltration,
no fluid removal,
no dialysis.

27. Activated charcoal
Botella et.al. Adsorption in hemodialysis. Kidney International (2000) 58, S60–S6
Winchester, JF, Boldur, A, Oleru, C, Kitiyakara, C. Use of dialysis and hemoperfusion in treatment of poisoning.
In: Handbook of Dialysis, 4th ed, Daugirdas, JT, Blake, PG, Ing, TS (Eds), Lippincott Willliams & Wilkins,
- Starts life as coconut shell
- Controlled combustion in superheated O2
- Fine granules, ~ 0.1mm
- Massive surface area in one 300g cartridge
- 40 m2
external surface
- 300,000m2
internally (pores)
- Small diffusion distance

28. The principle of Charcoal
Hemoperfusion:
Botella et.al. Adsorption in hemodialysis. Kidney International (2000) 58, S60–S6
Winchester, JF, Boldur, A, Oleru, C, Kitiyakara, C. Use of dialysis and hemoperfusion in treatment of poisoning. In: Handbook of
Dialysis, 4th ed, Daugirdas, JT, Blake, PG, Ing, TS (Eds), Lippincott Willliams & Wilkins, Philadelphia 2007. p. 300.
Replacement of renal function by dialysis: a textbook of dialysis By John Francis Maher, the 20th
chapter by james F.
Winchester (pp 439)
- ADsorption vs ABsorption:
- Absorption is when atoms molecules or
ions diffuse into a bulky volume
- Adsorption is when the atoms molecules
or ions settle on a surface
- Charcoal or resin in the cartridge
will compete with plasma proteins
for the drug molecules; these
molecules will adsorb onto the
charcoal surface

29. The principle of Charcoal
Hemoperfusion:
Botella et.al. Adsorption in hemodialysis. Kidney International (2000) 58, S60–S6
Winchester, JF, Boldur, A, Oleru, C, Kitiyakara, C. Use of dialysis and hemoperfusion in treatment of poisoning. In: Handbook of
Dialysis, 4th ed, Daugirdas, JT, Blake, PG, Ing, TS (Eds), Lippincott Willliams & Wilkins, Philadelphia 2007. p. 300.
Replacement of renal function by dialysis: a textbook of dialysis By John Francis Maher, the 20th
chapter by james F.
Winchester (pp 439)
- Hemoperfusion is effective at clearing protein-
bound and lipid-soluble drugs (not just water
soluble molecules)
- Hemoperfusion has variable effectiveness at
removing small water-soluble molecules,
- Clearance of any given molecule depens not only
on its size but also on the affinity of the charcoal
or resin for that molecule

30. Preventing the clotting of the filter
Dunea G. et al, Experience with the Yatzidis charcoal artificial kidney Trans Am Soc Artif Intern Organs 11:178, 1965
Botella et.al. Adsorption in hemodialysis. Kidney International (2000) 58, S60–S6
Winchester, JF, Boldur, A, Oleru, C, Kitiyakara, C. Use of dialysis and hemoperfusion in treatment of poisoning. In: Handbook of
Dialysis, 4th ed, Daugirdas, JT, Blake, PG, Ing, TS (Eds), Lippincott Willliams & Wilkins, Philadelphia 2007. p. 300.
Replacement of renal function by dialysis: a textbook of dialysis By John Francis Maher, the 20th
chapter by james F.
- Blood must come in direct contact with the adsorption surface
- The surface needs to be biocompatible, or terrible things will happen
- Initial attempts were frustrated by the degradation of blood components
- Subsequently, biopolymer coating was introduced to reduce platelet
aggregation and fibrin adsorption – cellulose nitrate was the first.
- High flows are used, and heparin or prostacyclin
- Textbooks recommend anticoagulation to increase intra-circuit
whole blood clotting time to ~ 30 minutes!

31. Charcoal Hemoperfusion vs.
Hemodiafiltration:
Botella et.al. Adsorption in hemodialysis. Kidney International (2000) 58, S60–S6
Replacement of renal function by dialysis: a textbook of dialysis By John Francis Maher, the 20th
chapter by james F. Winchester (pp 439)
- Hemoperfusion is more effective at clearing protein-bound drugs
- Hemoperfusion is also more efficient than hemodialysis at clearing
lipid-soluble drugs
- Hemodialysis and hemodiafiltration are more efficient at clearing readily
water-soluble substances and small molecules
- If a substance is equally well removed by either hemodialysis or
hemoperfusion, then hemodialysis is the modality of choice, because it
has fewer complications.

32. Complications of Charcoal
Hemoperfusion
Dunea G. et al, Experience with the Yatzidis charcoal artificial kidney Trans Am Soc Artif Intern Organs 11:178, 1965
EARLY PROBLEMS
-Particle embolization in filters with uncontrolled granule diameter
-Profound platelet depletion with uncoated filters
-Anaphylactic reactions to dirty coconut charcoal
-Deposition of hydrocarbons into the patient by treated charcoal
PROBLEMS REMAINING
-Some platelet depletion with coated filters
-Fibrinogen depletion
-Decreased WCC: complement is activated even by coated filters, and
this results in leucocyte margination and thus WCC is observed to fall
-Hypotension: likely due to platelet activation in the filter, and resulting
massive release of vasoactive amines
-Removal of calcium
-Removal of glucose
-Removal of hormones, coagulation factors and trace elements

33. History of Hemoperfusion:
Muirhead et al, Resin artifical kidney J lab Clin Med 33:841 1948
Schreiner et al, the role of hemodialysis in acute poisoning Arch Intern Med 102:896 1958
Yatzidis et al, Treatment of severe barbiturate poisoning lancet 2: 216 1963
Chang et al, Serum middle molecule levels in uremia during long term intermittent hemopefusion with ACAD (coated charcoal) microcapsule artficial kidney
Trans Am Soc Irtif int Organs 20:364, 1974
Replacement of renal function by dialysis: a textbook of dialysis By John Francis Maher, the 20th
chapter by james F. Winchester (pp 439)
- In 1948, Muirhead and Reid killed several lab animals
- Cation and anion exchange resin filters shown to
remove 3.5 G urea
- 1958: Schreiner removed a useful
amount of pentobarbital out of an
overdose patient with 2 x 15-minute
sessions on a lactated anion resin column.
Massive hemolysis, electrolyte derangement and death
quoted
as the main obstacle to therapy

34. History of Hemoperfusion:
Muirhead et al, Resin artifical kidney J lab Clin Med 33:841 1948
Schreiner et al, the role of hemodialysis in acute poisoning Arch Intern Med 102:896 1958
Yatzidis et al, Treatment of severe barbiturate poisoning lancet 2: 216 1963
Chang et al, Serum middle molecule levels in uremia during long term intermittent hemopefusion with ACAD (coated charcoal) microcapsule artficial kidney
Trans Am Soc Irtif int Organs 20:364, 1974
Replacement of renal function by dialysis: a textbook of dialysis By John Francis Maher, the 20th
chapter by james F. Winchester (pp 439)
-1964, Yatzidis et al treated barbiturate overdoses with
coconut shell charcoal
- both patients regained consciousness.
- Anaphylactoid side effects eg facial flushing and wheezy
dyspnoea
- 50% platelet count drop following 5 x 1 hr sessions
-1973, Chang et al demonstrate that though uremic toxin
removal is greater with hemoperfusion than with
hemodialysis, urea itself could not be removed in clinically
useful quantities.

35. Hemoperfusion in
Overdose
Replacement of renal function by dialysis: a textbook of dialysis By John Francis Maher, the 20th
chapter by james F. Winchester (pp 439)
Notable drugs:
-Theophylline
-Barbiturates
-Tricyclics (incl. Carbamazepine)
-Digoxin
-Salicylates
-Paraquat
-Organophosphates

36. WELL ESTABLISHED INDICATIONS
for hemoperfusion
Holubek et al, Use of hemodialysis and hemoperfusion in poisoned patients idney International (2008) 74, 1327–1334;
Winchester, JF, Boldur, A, Oleru, C, Kitiyakara, C. Use of dialysis and hemoperfusion in treatment of poisoning. In: Handbook of
Dialysis, 4th ed, Daugirdas, JT, Blake, PG, Ing, TS (Eds), Lippincott Willliams & Wilkins, Philadelphia 2007. p. 300.
Replacement of renal function by dialysis: a textbook of dialysis
PARAQUAT
- Near-continuous charcoal hemoperfusion
prevents progression to pulmonary fibrosis and
improves mortality
ORGANOPHOSPHATES
- Indicated in SEVERE massive overdose
- less beneficial in mild overdose
CARBAMAZEPINE
- Indicated in SEVERE massive overdose
THEOPHYLLINE
-Charcoal hemoperfusion decreases progression to seizures
and improves mortality

37. LESS WELL ETABLISHED APPLICATIONS
of hemoperfusion
Licari, Elisa MD; Calzavacca, Paolo MD; Warrillow, Stephen J. MD; Bellomo, Rinaldo MD Life-threatening sodium valproate overdose: A
comparison of two approaches to treatment. Critical Care Medicine: December 2009 - Volume 37 - Issue 12 - pp 3161-3164
- Methotrexate
- Better with uncoated charcoal
- Diltiazem
- Especially sustained release
- Phenytoin
- Half life reduced from 100 to 7 hrs
- Valproate
- Chloramphenicol in children
- Muscarine (from Amanita Muscaria)

38. Charcoal Hemoperfusion
in Hepatic Encephalopathy
in 1972, Chang et al first reported the use of charcoal hemoperfusion in an
encephalopathic woman. (She survived)
- In theory, the mercaptans and ammonia are adsorbed more easily than they are dialysed
- The idea is to intervene BEFORE Stage IV coma by West Haven Criteria
(i.e. before unresponsiveness, when cerebral oedema is irreversibly established)
Exactly when to intervene?
Nobody agrees.
Some useful things may also be removed.

39. NON-STANDARD APPLICATIONS OF
HEMOPERFUSION
1976, McEwoy et al
Psoriasis improved during dialysis. Effect was not sustained in RCT.
1977, Wagemaker and Cade:
“dramatic” improvement in delusions and paranoid ideation in 5 out of the 6
chronic schizophrenics , attributed to the hemoperfusion removal of leucine-
endorphin.
Not supported by subsequent series.
2009, EUPHAS trial:
Significant reduction in mortality following hemoperfusion with Polymyxin-B containing
column, in 64 surgical patients with severe septic shock.
Trial terminated: unethical to withhold lifesaving polymyxin.
Wagemaker, Cade ; the use of hemodialysis in chronic schizophrenia. Am J Psychiatr 134: 684 1977.
McEwoy et al, psoriatic clearance during hemodialysis Ulster Med J 76: 1976
Cruz DN, Antonelli M, Fumagalli R, et al. Early Use of Polymyxin B Hemoperfusion in Abdominal Septic
Shock: The EUPHAS Randomized Controlled Trial JAMA. 2009;301:2445-2452

40. When is hemodialysis better:
Botella et.al. Adsorption in hemodialysis. Kidney International (2000) 58, S60–S6
- Hemodialysis is much better at correcting acidosis
- Thus, hemodialysis is better at treating overdose with a substance
that causes acidosis, such as ethylene glycol, methanol or salicylates
- Hemodialysis is better in ethanol poisoning, because charcoal is
rapidly saturated by ethanol
- If a substance is equally well removed by either hemodialysis or
hemoperfusion, then hemodialysis is the modality of choice,
because it has fewer complications.

41. Aphersis
• Therapeutic apheresis refers to an extracorporeal
procedure in which blood separator technology is
used to remove abnormal blood cells and plasma
constituents.
• The terms plasmapheresis, leukapheresis,
erythrocytapheresis and thrombocytapheresis
describe the specific blood element that is removed.
• In plasmapheresis or therapeutic plasma exchange
large quantities of plasma are removed from a patient
and replaced with fresh frozen plasma, albumin
solution and saline

42. Plasmaphersis
• Plasma is removed from the
blood by a cell separator.
• Two procedures are
commonly used to separate
the plasma from the blood
cells, with each method
having its own advantages
and disadvantages.
• There are membrane
separator and centrifuge
separator

44. Membrane vs. Centrifugation
• In the US, most TPE is performed by
centrifugation.  One machine can do
all apheresis procedures.
• Double filtration method: first
membrane separates plasma from
cellular portion and second membrane
separates globulin from albumin.

45. Blood Components Separated by Centrifugation

46. Plasma Exchange

47. Double Filtration Plasmapheresis

48. Plasma adsorption & Immunadsorption

49. Efficiency of removal is greatest early in the procedure and
diminishes progressively during the exchange

50. Plasma Volume Exchange
Plasma Volume
Exchange
Percent Removed
0.5 39.3%
1.0 63.2%
1.5 77.7%
2.0 86.5%
2.5 91.8%
3.0 95.0%

51. Small vs. Large Volume
Exchange
• 1.0 plasma volume exchange: minimizes
time required for each procedure but may
need more frequent procedures.
• 2.0 – 3.0 plasma volume exchange:
greater initial diminution of pathologic
substance but requiring considerably more
time to perform the procedure.

52. Rationale of Plasma
Exchange
• The existence of a known pathogenic
substance in the plasma.
– IgG, IgM, phytanic acid, cytokines (?)
• The possibility of removing this
substance more rapidly than it can be
renewed in the body.

53. Mechanical Removal of Antibodies
• When antibody is rapidly and massively
decreased by TPE, antibody synthesis
increases rapidly.
• This rebound response complicates
treatment of autoimmune diseases.
• It is usually combined with immune
suppressive therapy.

54. Indication for TPE

55. Indication for TPE
Category 1: Standard acceptable
therapy
• Chronic idiopathic demyelinating polyneuropathy
(CIDP)
• Cryoglobulinemia
• Goodpasture syndrome
• Guillain-Barre syndrome
• Recurrent FSGS
• Myasthenia gravis
• Post transfusion purpura
• Refsum’s disease
• TTP

56. Indication for TPE
Category 2: Sufficient evidence to suggest
efficacy as adjunctive therapy
• ABO incompatible organ transplant
• bullous pemphigoid
• coagulation factor inhibitors
• drug overdose and poisoning (protein bound)
• Eaton-Lambert syndrome
• HUS
• monoclonal gammopathy with neuropathy
• Sydenham’s chorea
• RPGN
• Systemic vasculitis

57. Indication for TPE
Category 3: Inconclusive evidence of efficacy
or uncertain risk/benefit ratio.
TPE can be considered for the following occasions:
1. Standard therapies have failed.
2. Disease is active or progressive.
3. There is a marker to follow.
4. It is agreed that it is a trial of TPE and when to stop.
5. Possibility of no efficacy is understood by the patient.

58. Indication for TPE
Category 4: Lack of efficacy in controlled
trials.
• Examples: AIDS, amyotrophic lateral
sclerosis, lupus nephritis, psoriasis,
schizophrenia, rheumatoid arthritis

59. Thrombotic Syndromes
• TTP-HUS complex
• Sepsis
• Malignancy
• Drugs
• Pancreatitis
• Pregnancy

60. Effect of DFPP on various plasma
components
• IgG, IgA, IgM, albumin,
and fibrinogen are
removed by DFPP. IgG
is sub-optimally
removed whereas IgA,
IgM, and fibrinogen are
substantially removed
Year : 2017 | Volume : 27 | Issue : 5 | Page : 377-38
Effect of double filtration plasmapheresis on various plasma components and patient
safety: A prospective observational cohort study
K Jagdish, etal.,

61. TPE in Sepsis
• Significant debate over the risks/benefits
of TPE in sepsis and MODS
• Could this be of benefit in prothrombotic
forms of sepsis and MODS?
• The risk of the increased
immunosuppressive effect
• What parameter to follow?

62. TPE in Sepsis
Conclusions
Plasmapheresis may be an
important adjuvant to
conventional treatment to
reduce mortality in patients
with severe sepsis or
septic shock.
Plasmapheresis is a safe
procedure in the treatment
of septic patients.

63. TPE in Sepsis

64. TPE in Sepsis
Conclusions
Insufficient evidence exists to
recommend plasma exchange as
an adjunctive therapy for patients
with sepsis or septic shock.
Rigorous randomized controlled
trials evaluating clinically relevant
patient-centered outcomes are
required to evaluate the impact of
plasma exchange in this condition

65. Comparison of IVIg & Plex in
Myth Gravis
Barth, et al Neurology 2011;76
• 84 pts to IVIg 1g/kg/d x 2 days
– Or PE x 5
• QMG > 10.5 and “worsening”
Improved: 69% IVIg
and 65% PE
Conc: IVIg & PE
both effective Rx

66. Comparison PE& DFPP in
GBS
•The rationale for therapeutic apheresis in the treatment of acute GBS is based
on removal of circulating factors causing the autoimmune neuropathy
•No significant difference between the two
modalities

67. Leucocytapheresis in ttt of IBD
Conclusion
GCAP therapy is safe and effective in inducing and
maintaining clinical remission both in SD and in SR patients affected by
either UC or CD

68. LDL apheresis
LDL apheresis is
indicated for the
treatment of familial
hypercholesterolemia,
which is an autosomal
dominant disease caused
by a mutation in the LDL
receptor. This procedure
selectively removes
apolipoprotein B100-
containing lipoproteins
LDL and lipoprotein (a).

69. Erthrocytapheresis
Erythrocytapheresis (automated RBC exchange transfusion
[arbx]) has been increasingly used for chronic
transfusion therapy (CTT)

70. Extracorporeal Photopheresis
Indication
1. Cutaneous T-Cell
Lymphoma
2. Chronic GVHD
3. Acute GVHD
4. Lung
Transplantation

71. Extracorporeal CO2 removal

72. What’s it?
• ECCO2R
– Lower flow need
• CO2 mainly carried by
plasma (dissolved
bicarbonate)
• Linear kinetics without
saturation
• 1 L blood carry > 500 ml
CO2
– CO2 removal rate < 1
L/min blood flow
• CO2 diffuses more readily
than O2 across
extracorporeal membrane

73. Indications
• ARDS with lung protective ventilation (LPV)
– Tidal volume ~6 ml/kg*,
– Evidence ~< 4 ml/kg (ultra protective ventilation)#
even better than 6 ml/kg
– Hypercapnia (Permissive hypercapnia)
• Raised ICP
• R heart failure
• Immunosuppression
• Impaired pulmonary epithelial repair
• COPD exacerbation or Status Asthmaticus
• Bridge to lung transplant
* The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000, 342:1301-1308
#
Terragni PP et al, Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon
dioxide removal. Anesthesiology 2009, 111:826-835.

74. Membrane Lung
• Past: coiled silicon rubber, low efficiency
and high resistance
• Present: hollow fibre membrane
– Microporous polypropylene – plasma leak
– Nonporous poly-4-methyl-1-pentene (PMP)
• No plasma leak
• Efficient with superior gas exchange
• inc. biocompatibility

75. Membrane Lung
blood

76. ExtraCorporeal Membrane
Oxgenation (ECMO)
blood

77. History of usage of ECMO
In general Neonatal Pediatric Adults
1970s CI for sepsis 1976: first neonatal ECMO
For resp failure
For resp failure 1972:first adult ECMO
For resp failure
1990s Could be
lifesaving in
neonatal and
pediatric
septic shock
UK Collaborative ECMO Trial Group. UK
collaborative randomised
trial of neonatal ECMO. Lancet
1996; 348: 75-82.
Overall survival 80% (90% survival for
meconium aspiration syndrome, lower in
congenital diaphragmatic
hernias)
Expected survival not higher
than 50%
Not to be used
Poor outcomes
21st
century
to date
Standard
indication for
refractory
septic shock
in neonates
Cost-effectiveness data available
Bennett CC, Johnson A, Field DJ, et al. UK
collaborative randomised
trial of neonatal ECMO: follow-up to age 4
years. Lancet 2001; 357: 1094-6.
ELSO and U Michigan survival rate: around
80%
Surviving Sepsis Campaign
2012: Consider ECMO for
refractory pediatric septic
shock and resp failure (Grade
2C(
With high flow, central ECMO
with modern circuitry, survival
approaching 75%
CESAR Study of overall
benefit
Isolated case reports of
efficacy in sepsis, but
definite outcome data
not available, survival
worse than neonates
and paediatrics
Ref: Dellinger RP, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and
septic shock: 2012. Crit Care Med. 2013; 41:580-637

78. From this…
TO THIS!!

79. Ref: ELSO Registry, accessed Dec 2014
ELSO Diagnoses (<1986 – 2013)
ELSO Definition of sepsis:
The presence of pathogenic
microorganisms or their toxins in the
blood or other tissues. It may be
diagnosed clinically by symptomatic
evidence of infection, or by laboratory
studies. It may also be diagnosed by
a documented positive culture.
ELSO definition of survival was
successful separation from ECMO.

80. Bréchot, N, et al. Critical care medicine 2013
N = 14 adults with sepsis-associated cardiac failure
All femoro-femoral VA ECMO
Blood flow 4 to 5 LPM
Venoarterial extracorporeal membrane oxygenation support
for refractory cardiovascular dysfunction during severe
bacterial septic shock

81. Outcomes
Bréchot, N, et al. Critical care medicine 2013

82. Others:-
Liver-albumin dialysis
Ventricular Assisted Devices
Heart-lung machine
blood

83. Artificial Liver Support
Systems
• Cell-based
1- Hepatassist
2- Extracorporeal Liver
Assist Device
3- Bioartificial Liver
Support System
4- Amsterdam Medical
Center Bioartificial Liver
5- Modular
Extracorporeal liver
support
• Non cell-based
1- MARS
2- Fractionated Plasma
Separation and
adsorption (Prometheus)
3- SPAD
4- Selective Plasma
Separation Therapy

84. Extracorporeal Liver Support
Systems
MARS (Molecular adsorption
recirculation system)
SPAD (Continuous venovenous
Single Pass Albumin
hemoDiafiltration)

85. Extracorporeal Liver Support
Systems
MARS (Molecular adsorption
recirculation system)
ECLAD (Extracorporeal liver
assist device

86. Extracorporeal Liver Support
Systems
Extracorporeal hepatic
perfusion
MELS ( Modular Extracorporeal
Liver Support)

87. LV assisted devices

88. TandemHeart pVAD
• Used for LV support; not
appropriate in RV failure
• Cannulas are inserted
percutaneously through the
femoral vein and advanced
across the intraatrial
septum into the left atrium
• The pump withdraws
oxygenated blood from the
left atrium and returns it to
the femoral arteries via
arterial cannulas
• Provides up to 5L/min of
flow
• Can be used for up to 14
days

89. CentriMag
• Can be used for
LV and/or RV
support
• Cannula are
typically inserted
via a midline
sternotomy
• Capable of
delivering flows up
to 9.9 L/min
• Can be used for
up to 30 days

90. Conclusions and Home
message …….
1. We can produce a lot for the critically ill
patients by EC therapies
2. HD machine can produce a job beyond
RRT
3. Every ICU should have a multifiltration
machine not only to treat renal failure

92. No further questions, please.