This workshop will outline the basic principles of extracorporeal life support made easy by key-experts in the field. During the course delegates will gain a good understanding of ECMO in the following areas: Theoretical concepts, basic physiology and pathophysiology, cardiac and respiratory support and monitoring, alarm settings and monitoring, role of cardiac ultrasound during ECMO, newest technologies, circuits and devices, practical hands-on sessions and simulations.

1. How to
deal with
antibiotics
and fluids?
Harlinde Peperstraete, MD
Ghent University Hospital
Harlinde.peperstraete@ugent.be

2. Patients receive...
• Sedatives
• Analgesics
• Antibiotics
• Anticoagulants
• Vasoactive medications
• Fluids
• Feeding

3. Pharmacokinetics & ECMO
SIRS, CO↑
• Drug clearance↑
Haemodilution &
fluid shifts
• Volume of
distribution ↑
Drug
sequestration
• Volume
of distribution ↑
Organ dysfunction
• Drug
clearance ↓

4. Pharmacokinetics & ECMO
SIRS, CO↑
• Drug clearance↑
Haemodilution &
fluid shifts
• Volume of
distribution ↑
Drug
sequestration
• Volume
of distribution ↑
Organ dysfunction
• Drug
clearance ↓
Low drug
concentration
High drug
concentration
Therapeutic failure
Antibiotic resistance
Drug toxicity

5. ECMO & drug
sequestration
Circuit
factors
Drug
factors

6. Circuit factors
• LARGE surface area
• Drugs can be
trapped
• Drugs can be
released
Oxygenators (PMP):
small losses of fentanyl
and morphine

7. Circuit factors
Conduit tubing (PVC):
lorazepam, fentanyl and
morphine losses
• Older circuits have
higher drug losses

8. Circuit factors
priming: ↑ circulating volume
Electrolytes, pH, temperature
Cristalloid- vs bloodprimed:
affects proteinbinding,
adsorption on tubings
Haemodilution: ↑volume of
distribution (hydrophylic drugs)

9. Cristalloid-
vs blood-
primed
Mehta et al
(2007)
Cristalloid-primed
 71% ampicilline
 17% fosphenytoin
 33% heparin
 87% fentanyl
Were lost (ex vivo)
Blood-primed
 15% ampicilline
 31% fosphenytoin
 53% heparin
 100% fentanyl
Were lost (ex vivo)
Priming related alterations in PK will be greatest in paediatrics

10. Drug
factors
Shekar et
al.,
Wildshut
et al.
High degree of
lipophilicity: highly
extracted by the circuit (ex
vivo)
• Morphine <<< midazolam < Fentanyl
Degree of protein binding ~
drug loss (ex-vivo)
• Ciprofloxacin is 20-40% PB: 4% lost in
the circuit

11. ECMO &
Increased
Volume of
distribution
(Vd)
↑Vd of hydrophylic drugs
• Drug sequestration
• Priming and haemodilution of
critical illness: SIRS and fluid shifts
pH disturbances => alterations
in protein binding and drug
distribution
Activated RAS: ↑Vd by ↑
circulating bloodvolume

12. ECMO &
Drug
Clearance
♥: Initially ↑ CO (fluids & inotropes),
often myocardial depression => end
organ failure
Renal dysfunction: 32% in VV & 47%
in VA
Hepatic dysfunction
RRT: 50%in VV& 41% in VA:
importance of therapeutic drug
monitoring
Likelihood of toxicity

13. ECMO & infections
• Longer ECMO
duration
• Longer post-
ECMO ventilator
support
• Higher
prevalence of
mortality
• Suboptimal
dosing =>
bacterial
resistance

14. Beta-lactams
• Need 4-5x MIC for extended
periods: extended infusions
• Different studies: altered pK to
not altered PK
• Distribution volume is higher,
Clearance is lower
• P. aeruginosa: high doses
• Regular dosing aided with
therapeutic drug monitoring

15. Vancomycin
• Glycopeptide
• Relatively hydrophilic
• Through concentration of 15-
20mg/L to prevent adverse effects
• Loading dose of 25-30mg/kg
• Followed by 30-40mg/kg/day

16. Aminoglycosides
• Vd ↑? Clearance ↓?
• Old studies
• => TDM as in non-ECMO patients

17. Quinolones
• Not-lipophilic
• Relatively low protein binding
• => no dosing adjustments

18. Linezolid - De Rosa
FG et al., Minichmayr
IK et al
• Methicillin-resistant S. aureus
• MIC ≤ 1mg/L : standard dosing:
600mg /12h
• MIC > 1mg/L: 600mg single dose,
followed by continuous
infusion 1200mg/24h
• Highly variable pharmacokinetics
in severely ill
• => TDM

19. PK & ECMO safest option : TDM

20. PK & ECMO safest option : TDM

21. Fluids & ECMO
SIRS
• Vascular
permeability↑
ECMO is preload
dependent
• Large fluid
amounts to
prevent suction
events
Multiple drug
infusions
• Large amounts
of fluids
Organ
dysfunction
• AKI with oliguria
or anuria,
electrolyte and
pH disturbances

22. Fluids & ECMO
SIRS
• Vascular
permeability↑
ECMO is preload
dependent
• Large fluid
amounts to
prevent suction
events
Multiple drug
infusions
• Large amounts
of fluids
Organ
dysfunction
• AKI with oliguria
or anuria,
electrolyte and
pH disturbances
FLUID OVERLOAD
Prolonged use of ECMO, weaning failure
INCREASED MORTALITY

23. Reducing
fluid
overload
To optimize lung condition
To reduce right ventricular
filling pressures
To improve longterm outcome
To prevent abdominal
compartment syndrome
To facilitate nutrition

24. Achieving
negative
fluid
balance
CRRT with
ultrafiltration
•Better sodium
removal per unit
volume
Diuretics

25. CRRT & ECMO
•UZ Ghent: CVVH
"Countercurrent": from
post-oxygenator to pre-
oxygenator
•Idealy: post CF pump
(pos pressures)