ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO
Transcript of ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO
![Page 1: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/1.jpg)
ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO
Department of
Intensive Care Medicine
Royal Brisbane Hospital
University of Queensland
Professor Jeffrey Lipman
![Page 2: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/2.jpg)
NO CONFLICT
OF INTERESTS
![Page 3: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/3.jpg)
Important concept
Recommended dosages are obtained from healthy volunteers and possibly (ward)
“sick” patients
![Page 4: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/4.jpg)
Clinical pharmacology:
drug development
Antibiotic regimens are derived from non-critically ill volunteers. Their haemodynamic system is normal, as is their liver and kidney blood flow. They have not leaky capillaries nor have they drips and pipes in every orifice.
![Page 5: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/5.jpg)
![Page 6: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/6.jpg)
Blot S et al. Diagnostic Microbiology and Infectious Disease 2014;79:77–84
The kidney and antibiotics
![Page 7: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/7.jpg)
Cmax Peak Concentration
Cmin Trough Concentration
t1/2 Half-life
V (or VD) Volume of distribution
AUC Area under curve
Cl Clearance
Protein binding
Antibiotic related IMPORTANT
pharmacokinetic parameters
![Page 8: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/8.jpg)
Capillary lead and fluid administration
![Page 9: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/9.jpg)
Marik PE Anaesthesia and Intensive Care 1993;21:172-3.
![Page 10: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/10.jpg)
….we have found that higher-than-recommended loading and daily doses of vancomycin seem to be necessary to rapidly achieve therapeutic serum concentrations.
35mg/kg loading 35mg/kg/day
![Page 11: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/11.jpg)
Antibiotics that stay in extravascular and
extracellular space ie that don’t penetrate
“solid” organs, (hydrophilic tendencies)
namely AMINOGLYCOSIDES
GLYCOPEPTIDES
β-LACTAMS (to a lesser extent)
COLISTIN
VOLUME OF DISTRIBUTION
ALTERATIONS IN ICU
![Page 12: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/12.jpg)
LOADING DOSE vs
CLEARANCES
Fundamental concept Loading dose is INDEPENDENT of
clearances
EVEN IN RENAL FAILURE (without
clearance) YOU MUST GIVE
LOADING DOSE
![Page 13: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/13.jpg)
LOW EXPOSURE TO ANTIBIOTICS ENABLES
DEVELOPMENT OF RESISTANCE
Critical Care Medicine August 2008;36:2433-40
![Page 14: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/14.jpg)
Sepsis changes PK
Extracorporeal circuits
Altered CL and Increased Vd cf AKI
? Plasma concentrations
![Page 15: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/15.jpg)
Kidney Filter
Ultrafiltrate Dialysate
FLOW
FLOW
Semi-permeable Membrane
(C)RRT
(Continuous) Renal
Replacement Therapy
![Page 16: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/16.jpg)
Ultrafiltrate
FLOW
Semi-permeable
Membrane
CRRT Effects on Electrolytes and Water
..…and Drugs.
+/- Dialysate
Ur Cr
K Ca PO4
Ur Cr Cr
Cr Cr
Ur Ur
K Ca PO4
H2O H2O
FLOW
![Page 17: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/17.jpg)
Then it’s easy!
If you know
1. Membrane Pore Size
2. Drug Size
3. Sieving Coefficient
DRUG CLEARANCE
![Page 18: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/18.jpg)
Then it’s easy!
If you know
1. Membrane Pore Size
2. Drug Size
3. Sieving Coefficient
DRUG CLEARANCE
![Page 19: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/19.jpg)
CRRT Continuous Renal Replacement Therapy
Access (Pre- Filter)
From Patient
Return (Post Filter)
To Patient
Kidney Filter
Ultrafiltrate Dialysate
FLOW
FLOW
Semi-permeable Membrane
![Page 20: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/20.jpg)
Access (Pre- Filter)
From Patient
Return (Post Filter)
To Patient
Kidney Filter
Ultrafiltrate Dialysate
FLOW
FLOW
Semi-permeable Membrane
CVVHD Continuous Veno-Venous HeamoDialysis
NO Replacement Fluid.
![Page 21: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/21.jpg)
Effluent
FLOW
Semi-permeable
Membrane
CVVHD Removal of urea, toxins, electrolytes
& DRUGS (small molecules)
Dialysate
Ur Cr
K Ca PO4
Ur Cr Cr
Cr Cr
Ur Ur
K Ca PO4
FLOW
![Page 22: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/22.jpg)
CVVHD
Sd = [Antibiotic] dialysate
[Antibiotic] plasma
![Page 23: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/23.jpg)
CVVHD
ClCVVHD ≈ Qd x Sd
![Page 24: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/24.jpg)
Ultrafiltrate
FLOW
Semi-permeable
Membrane
Ur Cr
K Ca PO4
Ur Cr Cr
Cr Cr
Ur Ur
K Ca PO4
H2O H2O
CVVH Removal of H2O, urea, toxins, electrolytes
& DRUGS (small + middle molecules)
H2O
H2O H2O
H2O
H2O
H2O
H2O
![Page 25: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/25.jpg)
Access (Pre- Filter)
From Patient
Return (Post Filter)
To Patient
Kidney Filter
Ultrafiltrate
FLOW
FLOW
Semi-permeable Membrane
CVVH Continuous Veno-Venous Heamofiltration
Replacement Fluid can be either
Pre- Filter or Post Filter.
NO Dialysate
![Page 26: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/26.jpg)
[Antibiotic] ultrafiltrate
[Antibiotic] plasma Sc =
CVVH
![Page 27: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/27.jpg)
Cl CVVH(pre) = Qf x Sc x CF
where CF = Qb
Qb + Q pre
CVVH
![Page 28: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/28.jpg)
Access (Pre- Filter)
From Patient
Return (Post Filter)
To Patient Kidney Filter
Ultrafiltrate
FLOW
FLOW
Semi-permeable Membrane
CVVHDF Continuous Veno-Venous HeamoDiaFiltration
Dialysate
Replacement Fluid can be either
Pre- Filter or Post Filter.
![Page 29: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/29.jpg)
SLEDD as an alternative
And then there is SLEDD
Slow Low Efficiency Daily Dialysis, Extended Daily Dialysis
A “Hybrid” of CRRT + IHD
Minimal antibiotic clearance data published
![Page 30: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/30.jpg)
Roberts, Lipman. (Editorial) Crit Care Med 2011;39:602-3
Crit Care Med 2011;39:560–70
Nine original research articles plus a few case reports
![Page 31: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/31.jpg)
Therapeutic Options of
RRT Differ
CVVH
CVVHD
CVVHDF
SCUF
SLEDD
![Page 32: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/32.jpg)
Tables and equations
![Page 33: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/33.jpg)
Then it’s easy!
If you know
1. Membrane Pore Size
2. Drug Size
3. Sieving Coefficient
![Page 34: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/34.jpg)
Then it’s easy!
If you know
1. Membrane Pore Size
2. Drug Size
3. Sieving Coefficient
Convection
Diffusion
Protein binding
Volume of distribution
Membrane characteristics
![Page 35: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/35.jpg)
HOW DO WE DOSE
AT MY HOSPITAL?
![Page 36: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/36.jpg)
Roberts JA et al. Int J Antimicrob Agents 2010;36:332-0
Roberts JA, Hope WW, Lipman J. Int J Antimicrob Agents 2010;35:419-20
![Page 37: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/37.jpg)
BEST WE HAVE
Choi et al Crit Care Med 2009;37:2268-82
![Page 38: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/38.jpg)
CRRT and MEROPENEM
Jamal et al Crit Care Med 2014:42:1640-50
![Page 39: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/39.jpg)
CRRT and PIPTAZO
Jamal et al Crit Care Med 2014:42:1640-50
![Page 40: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/40.jpg)
CRRT and VANC
Jamal et al Crit Care Med 2014:42:1640-50
![Page 41: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/41.jpg)
ONE WAY
Choi et al Crit Care Med 2009;37:2268-82
![Page 42: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/42.jpg)
Advantages
Individualized
CRRT
MIC
Takes PK/PD relationships into account
Choi G et al. Crit Care Med 2009; 37: 2268-82
Choi G et al. Blood Purif 2010; 30: 195-212
![Page 43: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/43.jpg)
Alternatively
Choose a PK article that most closely
resembles the form of CRRT you use
Use their clearances – see if it seems
a reasonable estimate of your
clearances
Dose accordingly
![Page 44: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/44.jpg)
RECENTLY ACCEPTED REVIEW
Jamal JA, Mueller BA, Choi GYS, Lipman J, Roberts JA
How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?
Diagnostic Microbiology and Infectious Disease
![Page 45: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/45.jpg)
RECENTLY ACCEPTED REVIEW
Jamal JA, Mueller BA, Choi GYS, Lipman J, Roberts JA
How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?
Diagnostic Microbiology and Infectious Disease
TABLE 1: Pharmacokinetic parameters of different class of antibiotics in critically ill patients receiving variable types of renal replacement therapy modalities
![Page 46: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/46.jpg)
IMPORTANT BEDSIDE
PRACTICAL POINT…..
You may prescribe Continuous RRT….
but is it continuous? How often do you
come on morning ward round to here
the “kidney” was off for xxx hours? How
often do you do rounds to here “Oh we
are changing the filter”……
Do you factor in for the “down time”?
![Page 47: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/47.jpg)
IMPORTANT BEDSIDE
PRACTICAL POINT…..
What do you do when you want to
cease RRT. We say “leave the filter off
for awhile to see if pt passes urine…”
And often forget to change dose of drugs…..
Do you factor in for the “down time”?
![Page 48: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/48.jpg)
Conclusions:
This matched cohort study confirms an increase in Vd and a decrease in CL
for meropenem in adult patients receiving ECMO. In patients receiving
meropenem on ECMO, standard dosing does not always result in optimal
drug concentrations because of the significant PK changes in the setting of
critical illness, ECMO and RRT. Therapeutic drug monitoring where
possible is recommended until robust dosing guidelines become available.
CRITICAL CARE
Therapeutic drug monitoring
![Page 49: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/49.jpg)
DEFINITION
Therapeutic Drug Monitoring (TDM)
refers to analysis and subsequent
interpretation of drug concentrations in biological fluids
![Page 50: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/50.jpg)
PLACE
TDM should be used to
maximise efficacy
minimize toxicity
To personalise dosing for high probability of
therapeutic success, prevent development of
resistance, provide low probability of toxicity
![Page 51: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/51.jpg)
BETA-LACTAMS
Safe drugs
Large therapeutic range
TDM should be used to
maximise efficacy minimize toxicity
![Page 52: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/52.jpg)
J Chromatogr B 2010;878:2039-2043
![Page 53: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/53.jpg)
CONCLUSION
For various reasons therapeutic drug
monitoring (TDM) of most antibiotics is
difficult if not impossible. We have set up
a TDM service for all our beta-lactam use
and have (not surprisingly ) shown that in
more than half of our ICU patients we are
dose adjusting once receiving back a drug
level!
![Page 55: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/55.jpg)
![Page 56: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/56.jpg)
ONE WAY
Choi et al Crit Care Med 2009;37:2268-82
![Page 57: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/57.jpg)
Time above threshold
concentration Cmax:MIC & AUC24:MIC
Cmax:MIC ratio
Loading dose=Desired concentration x Vd
Calculate CRRT clearance based on mode of CRRT, formulae & published values
Pharmacokinetic
target?
Calculate elimination rate
= concentration x Cltot
Total clearance (Cltot) =calculated CRRT clearance+non-CRRT clearance
Maintenance infusion rate=
elimination rate
Calculate half-life
= 0.693 x Vd / Cltot
Calculate time to reach
target trough concentration
Repeat loading dose at
calculated time
Calculate target mean
concentration
= target AUC24/24
Calculate dosing interval
= Dose/(Cp x Cltot )
Repeat loading dose at
calculated dosing interval
![Page 58: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/58.jpg)
Time above threshold
concentration Cmax:MIC & AUC24:MIC
Cmax:MIC ratio
Loading dose=Desired concentration x Vd
Calculate CRRT clearance based on mode of CRRT, formulae & published values
Pharmacokinetic
target?
Calculate elimination rate
= concentration x Cltot
Total clearance (Cltot) =calculated CRRT clearance+non-CRRT clearance
Maintenance infusion rate=
elimination rate
Calculate half-life
= 0.693 x Vd / Cltot
Calculate time to reach
target trough concentration
Repeat loading dose at
calculated time
Calculate target mean
concentration
= target AUC24/24
Calculate dosing interval
= Dose/(Cp x Cltot )
Repeat loading dose at
calculated dosing interval
Loading dose=Desired concentration x Vd (28 l)
Desired concentration = 5 x MIC = 20 mg/l
Loading dose = 20 x 28 500 mg
![Page 59: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/59.jpg)
Time above threshold
concentration Cmax:MIC & AUC24:MIC
Cmax:MIC ratio
Loading dose=Desired concentration x Vd
Calculate CRRT clearance based on mode of CRRT, formulae & published values
Pharmacokinetic
target?
Calculate elimination rate
= concentration x Cltot
Total clearance (Cltot) =calculated CRRT clearance+non-CRRT clearance
Maintenance infusion rate=
elimination rate
Calculate half-life
= 0.693 x Vd / Cltot
Calculate time to reach
target trough concentration
Repeat loading dose at
calculated time
Calculate target mean
concentration
= target AUC24/24
Calculate dosing interval
= Dose/(Cp x Cltot )
Repeat loading dose at
calculated dosing interval
Calculate CRRT clearance based on mode of CRRT
& published Sc or Sd values
ClCVVH (post) = Qf x Sc
= 2450 x 0.95 = 2327 ml/h = 39 ml/min
![Page 60: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/60.jpg)
Time above threshold
concentration Cmax:MIC & AUC24:MIC
Cmax:MIC ratio
Loading dose=Desired concentration x Vd
Calculate CRRT clearance based on mode of CRRT, formulae & published values
Pharmacokinetic
target?
Calculate elimination rate
= concentration x Cltot
Total clearance (Cltot) =calculated CRRT clearance+non-CRRT clearance
Maintenance infusion rate=
elimination rate
Calculate half-life
= 0.693 x Vd / Cltot
Calculate time to reach
target trough concentration
Repeat loading dose at
calculated time
Calculate target mean
concentration
= target AUC24/24
Calculate dosing interval
= Dose/(Cp x Cltot )
Repeat loading dose at
calculated dosing interval
Total clearance (Cltot) =calculated CRRT clearance+non-CRRT clearance
= 39 + 60 100 ml/min = 0.1 l/min
![Page 61: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/61.jpg)
Time above threshold
concentration Cmax:MIC & AUC24:MIC
Cmax:MIC ratio
Loading dose=Desired concentration x Vd
Calculate CRRT clearance based on mode of CRRT, formulae & published values
Pharmacokinetic
target?
Calculate elimination rate
= concentration x Cltot
Total clearance (Cltot) =calculated CRRT clearance+non-CRRT clearance
Maintenance infusion rate=
elimination rate
Calculate half-life
= 0.693 x Vd / Cltot
Calculate time to reach
target trough concentration
Repeat loading dose at
calculated time
Calculate target mean
concentration
= target AUC24/24
Calculate dosing interval
= Dose/(Cp x Cltot )
Repeat loading dose at
calculated dosing interval
Calculate elimination rate
= concentration x Cltot
= 20 x 0.1 = 2 mg/min
![Page 62: ANTIBIOTIC DOSE AND DOSE INTERVALS IN RRT and ECMO](https://reader031.fdocuments.us/reader031/viewer/2022012407/616a274c11a7b741a34f61de/html5/thumbnails/62.jpg)
Time above threshold
concentration Cmax:MIC & AUC24:MIC
Cmax:MIC ratio
Loading dose=Desired concentration x Vd
Calculate CRRT clearance based on mode of CRRT, formulae & published values
Pharmacokinetic
target?
Calculate elimination rate
= concentration x Cltot
Total clearance (Cltot) =calculated CRRT clearance+non-CRRT clearance
Maintenance infusion rate=
elimination rate
Calculate half-life
= 0.693 x Vd / Cltot
Calculate time to reach
target trough concentration
Repeat loading dose at
calculated time
Calculate target mean
concentration
= target AUC24/24
Calculate dosing interval
= Dose/(Cp x Cltot )
Repeat loading dose at
calculated dosing interval
Maintenance infusion rate
= elimination rate
= 2 mg/min