Pharmacology during ECMO and CRRT

1
Pharmacology during ECMO and CRRT
Jonas Lindholm
2
Neonate on ECMO and CRRT RSV CMV virus
Candida pneumonia led to PHT
3
Neonatal ECMO Centrifugal system and CRRT
CRRT
4
Neonate on ECMO Roller system and CRRT Total
blood volume !
CRRT
5
CRRT on ECMO 2010 Jan 2012 Dec L.Mitander,
K.Albo, G.Frisén 42 Neonatal patients Gambro
HF20 filter 34 Pediatric patients Gambro M60
filter Before 2010 the Gambro M10 filter was
used Over 90 of Adult patients is treated with
CRRT during ECMO using Gambro ST150 or Oxiris
filters
6
You are on ECMO You connected your CRRT It runs
perfect! What about your treatment?
7
(No Transcript)
8
Pharmacology during ECMO and CRRT
Calculate the approx total blood volume For
dosing (Albumin, AntithrombinIII,
Fibrinogen) Use the best possible access The
ECMO circuit Its important with CRRT functioning
24 hrs a day to keep your treatment in a steady
state and for control of fluid balance. Frequent
starts and stops are dangerous due to measuring
problems in CRRT equipment and circulating volume
can rapidly change! What is eliminated due to
CRRT? Drugs and proteins may be
eliminated. Protein binding effect? Second
compartments? Monitoring or guessing?
9
Erytropoietin and CRRT Case Jehovas witness Hb
5.5 g/dL   S-Erytropoeitin 184 E/L (norm 3.7
25 E/L)   Waste bag sample Erytropoeitin 5.3 E/L
10
Vancomycin concentrations during ECMO and
CRRT J.Lindholm, L.Mitander, S.Eksborg
Total blood volume patient ECMO circuit
CRRT circuit Treatment goal Vancomycin plasma
conc 20-25 microg/ml high PBP flow 0 dialysate /
high dialysate 0 PBP / Combo normal
flows Patient Blood volume Filter
Daily dose Plasma concentration 1.7kg
532ml HF20 80mg
20-22 microg/ml 5.2kg 747ml
HF20 276mg 29-34
microg/ml 18kg 1630ml
ST60 720mg 20-24 microg/ml
110kg 8163ml ST150
3240mg 30-32 microg/ml Adults normal
dose Vancomycin 1-2.5g/day, Meropenem 4-6 g/day
11
(No Transcript)
12
Boluses vs Infusion Bolus When peak
concentration is wanted Constant infusion Easy
to adjust the daily dose in relation to
concentrations Samples can be withdrawn at any
time Avoid time lt MIC Avoid high peak
concentrations
13
Infections at ECMO center 2010 77 patients
J.Lindholm, L.Falk, C.Hoel, H.Hanberger
Blood cultures 290 cultures 12 positive 10 Stf
epidermidis No antibiotic resistance
BAL cultures 295 cultures 71 positive 11 Stf
epidermidis 3 Vancomycin R, treated with
Linezolid 19 Candida albicans 4 Pseudomonas
aeruginosa 3 develop resistance during treatment
14
Infections at ECMO center 2010 Pos cultures
found in 10 of patients. Pos culture say there
is an infection Neg culture say ? do NOT
say there is no infection the treatment
might be working sensitivity might not be
good enough
15
Monitor your treatment Enough
to get effect? Treatment not
working? Toxic levels?
16
Antibiotics Give more! Not less! Increase the
dose on CRRT Decrease dose when off CRRT Correct
high dose may reduce risk for resistance
17
(No Transcript)
18
Celebrating 20th birthday with Champagne Jan 2012
19
Pediatr Nephrol. 2013 May28(5)819-22. doi
10.1007/s00467-012-2394-3. Epub 2013 Jan 11. Use
of HF20 membrane in critically ill unstable
low-body-weight infants on inotropic support.
Liu ID, Ng KH, Lau PY, Yeo WS, Koh PL, Yap HK.
Shaw-NKF-NUH Children's Kidney Center,
KTP-National University Children's Medical
Institute, National University Hospital,
Singapore, Singapore. BACKGROUND Initiating
continuous renal replacement therapy (CRRT) in
infants exposes them to the dual hemodynamic
challenges of high circuit extracorporeal volumes
and potential membrane reactions, in the case of
acrylonitrile AN69 membranes. The use of the new
Prismaflex HF20 membrane in hemodynamically
unstable low-body-weight infants on inotropic
support has not been reported. TREATMENT We
describe the use of the HF20 membrane in four
low-body-weight infants (2.3 to 5.4 kg) with
multi-organ dysfunction syndrome who were
critically ill in the Pediatric Intensive Care
Unit (PICU), hemodynamically unstable, and on
inotropes. xxxxxxxxxx there was no adverse
reaction with the polyarylethersulfone (PAES)
membrane. CONCLUSIONS CRRT using the HF20
membrane is safe and hemodynamically well
tolerated in high-risk, unstable low-body-weight
infants with cardiac dysfunction on multiple
inotropes.
20
Vancomycin Bioavailabiliy and Distribution

• Distribution
• Vd 0.5 1.0 L/kg
• 30-55 protein bound
• Diffuse well into pleural, pericardial, synovial
  and ascitic fluid
• Penetration into CSF is not reliable or
  predictable, therapeutic concentrations may be
  reached in patients with a acute meningitis
• Poor penetration into solid organs, 20-30
  vancomycin serum concentration is achieved in
  lung tissue
• High dose vancomycin aiming for trough of more
  than 20mg/L has been advocated. (Jason A.
  Roberts Jeffrey Lipman, Antibacterial Dosing in
  Intensive Care Clinical Pharmacokinetics 2006
  45(8)

21
Amphotericin B C47H73NO17 molecular weight
924.09 Contains true liposomes that are less than
100 nm in diameter. Metabolic pathways of
amphotericin B after administration of AmBisome
are not known. Clearance at steady state was
independent of dose. The excretion of AmBisome
has not been studied. Due to the size of the
liposomes, there is no glomerular filtration and
renal elimination of AmBisome, thus avoiding
interaction of amphotericin B with the cells of
the distal tubuli and reducing the potential for
nephrotoxicity seen with conventional
amphotericin B
22
AN-69
50 microm
23
DIALYSATE eliminates small particles, urea, ions
and antibiotics due to differences in
concentrations
Diffusion
Baxter
24
Convection
High flow over the membrane creates drag for
molecules. PRE / POST DILUTION
Baxter
25
Flow of water to control the fluid balance and
contributes to convection. FLUID WITHDRAW
Ultrafiltration
Baxter
26
Adsorption occur within first hour . SPECIFIC
MEMBRANE
Adsorption
Baxter
27
Pharmacology and CRRT
PBP pre blood pump dilution Decreased
concentration prefilter, decreased diffusion
effect Increased Ultrafiltration and
Convection Post filter dilution High dialysate
effect Increased Ultrafiltration and
Convection Non-Protein bound part can be removed
by CRRT VD Volume of distribution total amount
of molecules Redistribution from other
compartments into blood stream Time to target
28
Adult ECMO and CRRT
29
(No Transcript)
30
20th birthday and 60th day on ECMO