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How to
deal with
antibiotics
and fluids?
Harlinde Peperstraete, MD
Ghent University Hospital
Harlinde.peperstraete@ugent.be
Patients receive...
• Sedatives
• Analgesics
• Antibiotics
• Anticoagulants
• Vasoactive medications
• Fluids
• Feeding
Pharmacokinetics & ECMO
SIRS, CO↑
• Drug clearance↑
Haemodilution &
fluid shifts
• Volume of
distribution ↑
Drug
sequestra...
Pharmacokinetics & ECMO
SIRS, CO↑
• Drug clearance↑
Haemodilution &
fluid shifts
• Volume of
distribution ↑
Drug
sequestra...
ECMO & drug
sequestration
Circuit
factors
Drug
factors
Circuit factors
• LARGE surface area
• Drugs can be
trapped
• Drugs can be
released
Oxygenators (PMP):
small losses of fen...
Circuit factors
Conduit tubing (PVC):
lorazepam, fentanyl and
morphine losses
• Older circuits have
higher drug losses
Circuit factors
priming: ↑ circulating volume
Electrolytes, pH, temperature
Cristalloid- vs bloodprimed:
affects proteinbi...
Cristalloid-
vs blood-
primed
Mehta et al
(2007)
Cristalloid-primed
 71% ampicilline
 17% fosphenytoin
 33% heparin
 8...
Drug
factors
Shekar et
al.,
Wildshut
et al.
High degree of
lipophilicity: highly
extracted by the circuit (ex
vivo)
• Morp...
ECMO &
Increased
Volume of
distribution
(Vd)
↑Vd of hydrophylic drugs
• Drug sequestration
• Priming and haemodilution of
...
ECMO &
Drug
Clearance
♥: Initially ↑ CO (fluids & inotropes),
often myocardial depression => end
organ failure
Renal dysfu...
ECMO & infections
• Longer ECMO
duration
• Longer post-
ECMO ventilator
support
• Higher
prevalence of
mortality
• Subopti...
Beta-lactams
• Need 4-5x MIC for extended
periods: extended infusions
• Different studies: altered pK to
not altered PK
• ...
Vancomycin
• Glycopeptide
• Relatively hydrophilic
• Through concentration of 15-
20mg/L to prevent adverse effects
• Load...
Aminoglycosides
• Vd ↑? Clearance ↓?
• Old studies
• => TDM as in non-ECMO patients
Quinolones
• Not-lipophilic
• Relatively low protein binding
• => no dosing adjustments
Linezolid - De Rosa
FG et al., Minichmayr
IK et al
• Methicillin-resistant S. aureus
• MIC ≤ 1mg/L : standard dosing:
600m...
PK & ECMO safest option : TDM
PK & ECMO safest option : TDM
Fluids & ECMO
SIRS
• Vascular
permeability↑
ECMO is preload
dependent
• Large fluid
amounts to
prevent suction
events
Mult...
Fluids & ECMO
SIRS
• Vascular
permeability↑
ECMO is preload
dependent
• Large fluid
amounts to
prevent suction
events
Mult...
Reducing
fluid
overload
To optimize lung condition
To reduce right ventricular
filling pressures
To improve longterm outco...
Achieving
negative
fluid
balance
CRRT with
ultrafiltration
•Better sodium
removal per unit
volume
Diuretics
CRRT & ECMO
•UZ Ghent: CVVH
"Countercurrent": from
post-oxygenator to pre-
oxygenator
•Idealy: post CF pump
(pos pressures)
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5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 1 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 2 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 3 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 4 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 5 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 6 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 7 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 8 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 9 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 10 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 11 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 12 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 13 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 14 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 15 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 16 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 17 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 18 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 19 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 20 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 21 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 22 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 23 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 24 5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete) Slide 25
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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.

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5. how to deal with ab and fluids on ecmo #beach2019 (peperstraete)

  1. 1. How to deal with antibiotics and fluids? Harlinde Peperstraete, MD Ghent University Hospital Harlinde.peperstraete@ugent.be
  2. 2. Patients receive... • Sedatives • Analgesics • Antibiotics • Anticoagulants • Vasoactive medications • Fluids • Feeding
  3. 3. Pharmacokinetics & ECMO SIRS, CO↑ • Drug clearance↑ Haemodilution & fluid shifts • Volume of distribution ↑ Drug sequestration • Volume of distribution ↑ Organ dysfunction • Drug clearance ↓
  4. 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. 5. ECMO & drug sequestration Circuit factors Drug factors
  6. 6. Circuit factors • LARGE surface area • Drugs can be trapped • Drugs can be released Oxygenators (PMP): small losses of fentanyl and morphine
  7. 7. Circuit factors Conduit tubing (PVC): lorazepam, fentanyl and morphine losses • Older circuits have higher drug losses
  8. 8. Circuit factors priming: ↑ circulating volume Electrolytes, pH, temperature Cristalloid- vs bloodprimed: affects proteinbinding, adsorption on tubings Haemodilution: ↑volume of distribution (hydrophylic drugs)
  9. 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. 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. 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. 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. 13. ECMO & infections • Longer ECMO duration • Longer post- ECMO ventilator support • Higher prevalence of mortality • Suboptimal dosing => bacterial resistance
  14. 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. 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. 16. Aminoglycosides • Vd ↑? Clearance ↓? • Old studies • => TDM as in non-ECMO patients
  17. 17. Quinolones • Not-lipophilic • Relatively low protein binding • => no dosing adjustments
  18. 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. 19. PK & ECMO safest option : TDM
  20. 20. PK & ECMO safest option : TDM
  21. 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. 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. 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. 24. Achieving negative fluid balance CRRT with ultrafiltration •Better sodium removal per unit volume Diuretics
  25. 25. CRRT & ECMO •UZ Ghent: CVVH "Countercurrent": from post-oxygenator to pre- oxygenator •Idealy: post CF pump (pos pressures)

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.

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