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.
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
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
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
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
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
25. CRRT & ECMO
•UZ Ghent: CVVH
"Countercurrent": from
post-oxygenator to pre-
oxygenator
•Idealy: post CF pump
(pos pressures)
Notas do Editor
Paediatrics: priming volume and surface area of tubings is much greater relative to patient size including the ciculating blood and axtracellular volume
Non-pulsatile flow is associated with decreased GFR (glomerular fltration rate)
The influence of ECMO on PK of piperacilline tazobactam en meropenem did not appear to be significant.... unlike in vitro studies
Both for this outmost critical ill population therapeutic drug monitoring
In this publication of Bouglé, they performed TDM of all AB that were possible to quantify and you can see that in only 3 AB the dosing was adequte