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Continuous Renal Replacement Therapy Based Dose Adjustments - Adult - Inpatient

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Continuous Renal Replacement Therapy
Based Dose Adjustments - Adult - Inpatient
Clinical Practice Guideline


Note: Active Table of Contents – Click to follow link
Table of Contents
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ...................................................................................................................................... 4
METHODOLOGY ...................................................................................................................... 5
DEFINITIONS ............................................................................................................................ 6
INTRODUCTION ....................................................................................................................... 6
RECOMMENDATIONS .............................................................................................................. 7
UW HEALTH IMPLEMENTATION ............................................................................................. 7
REFERENCES .......................................................................................................................... 8
APPENDIX A ............................................................................................................................. 8





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CPG Contact for Content:
Name: Jeff Fish, PharmD, BCCCP - Pharmacy
Phone Number: (608) 263-1290
Email Address:jfish@uwhealth.org

Name: Cindy Gaston PharmD, BCPS- Pharmacy
Phone Number: (608) 265-8161
Email Address:cgaston@uwhealth.org

CPG Contact for Changes:
Name: Philip J Trapskin, PharmD, BCPS – Drug Policy Program Manager
Phone Number: (608) 263-1328
Email Address: ptrapskin@uwhealth.org

Guideline Author(s):
Jeff Fish, PharmD, BCCCP
Ryan Draheim, PharmD
Chris Viesselmann, PharmD

Coordinating Team Members:
J. Fish, PharmD, BCCCP

Review Individuals/Bodies:
A.Yevzlin, MD; L. Schulz, PharmD, BCPS; Cindy Gaston, PharmD, BCPS

Committee Approvals/Dates:
Antimicrobial Use Subcommittee 12/10/2015
Pharmacy and Therapeutics Committee 12/17/2015

Release Date: May 2009 (original); December 2015

Next Review Date: December 2018











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Executive Summary
Guideline Overview
These clinical practice guidelines are intended to guide pharmacists in the dosing of
medications in adult intensive care unit (ICU) patients receiving continuous renal
replacement therapy (CRRT).

Key Practice Recommendations
1. The CRRT dose adjustment table should be used in adult ICU’s at UW Health to
guide medication dosing for patients receiving CRRT (CVVH or CVVHD) to
maximize drug therapy, ensure appropriate drug dosing, and standardize CRRT
based dose adjustments (Appendix A). (Class I, Level C)
2. Medication dose adjustments should be performed by the clinical pharmacist
according to the “Continuous Renal Replacement Therapy (CRRT)-Based Dose
Adjustments Delegation Protocol – Adult – Inpatient” (Class I, Level C)

Companion Documents
1. UW Health Renal Function-Based Dose Adjustment -Adult – Inpatient/Ambulatory
Clinical Practice Guideline

Pertinent UW Health Policies & Procedures
1. Continuous Renal Replacement Therapy (CRRT)-Based Dose Adjustments
Delegation – Adult – Inpatient Protocol
2. Renal Function-Based Dose Adjustments - Adult – Inpatient/Ambulatory Protocol




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Scope
Clinical Specialty:
This guideline may be used by any prescriber or pharmacist treating an adult patient
undergoing CRRT in an ICU to identify appropriate dosing of medications based on
ultrafiltration rate and patient weight.

Intended Users:
Physicians, pharmacists, mid-level providers, and nurses

Objective(s):
The objective of this guideline is to facilitate the appropriate dosing of medications in
adult ICU patients receiving CRRT based on patient and therapy-specific
pharmacokinetic calculations.

Target Population:
Critically ill adult patients receiving CRRT therapy in an ICU

Interventions and Practices Considered:
This guideline provides patient and therapy-specific dosing recommendations based on
each medication’s unique pharmacokinetic parameters, ultrafiltration rate and patient
weight.

Major Outcomes Considered:
The major outcome considered in this guideline is the appropriate dosing of medications
in patients receiving CRRT. Efficacy is measured by the rate of clinical cure of infection
for antimicrobials and drug efficacy for other medications. Safety is measured as the
rate of clinical failure and the occurrence of adverse events due to medications.

Guideline Metrics:
Literature will be periodically reviewed to determine new recommendations for dosing
medications in CRRT. Patient Safety Net events (PSNs) related to medication therapy
in patients receiving CRRT are reviewed throughout the year.
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Methodology
Methods Used to Collect/Select the Evidence:
Completed a comprehensive literature search of electronic databases (Micromedex,
LexiComp, eFacts); conducted an in-depth review of relevant abstracts and articles;
conducted a thoughtful discussion and interpretation of findings; ranked strength of
evidence underlying the current recommendations that have been provided.

Rating Scheme for the Strength of the Evidence and
Recommendations:
A modified Grading of Recommendations Assessment, Development, and Evaluation
(GRADE) developed by the American Heart Association and American College of
Cardiology was used to assess the Quality and Strength of Evidence in this Clinical
Practice Guideline.1



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Methods Used to Formulate the Recommendations:
Recommendations were based on strength of evidence and clinical expert consensus.
Definitions
1. Slow continuous ultrafiltration (SCUF): a type of CRRT used to remove excess fluid
in fluid overloaded patients. Fluid is removed via ultrafiltration and no replacement
or dialysis fluids are utilized.
2. Continuous venovenous hemofiltration (CVVH): a type of CRRT that utilizes
convection for fluid and solute removal. Replacement fluids are utilized in CVVH.
3. Continuous venovenous hemodialysis (CVVHD): a type of CRRT that utilizes
diffusion for fluid and solute removal. Dialysis fluids are utilized in CVVHD.
4. Equations and formulas2
4.1.
4.1.1. TBC = total body clearance
4.1.2. CLNR = clearance (non-renal)
4.1.3. CLCRRT = clearance via CRRT = renal clearance for anuric patients on
CRRT
4.2.
4.2.1. S = sieving coefficient = concentration of drug in ultrafiltrate divided by the
concentration of drug in the blood (may be estimated by fraction of drug
unbound)
4.2.2. UFR = ultrafiltrate flowrate of CRRT machine
4.3.
4.3.1. Vd = volume of distribution (in dialysis patients if available)
4.3.2. KHD = elimination rate constant in dialysis patients
4.4.
4.4.1. frCRRT = fraction of drug removed by CRRT
4.5.
4.5.1. MDMF = maintenance dose multiplication factor
4.6.
Introduction
Continuous renal replacement therapy (CRRT) is a dialysis mode common in ICUs, for
its use in patients with severe hemodynamic instability.3 Periods of volume overload and
depletion, which are likely with intermittent hemodialysis, are minimized with CRRT due
to the continuous regulation of fluid and nutrition, both enteral and parenteral.
Appropriate dosing of medications in patients receiving CRRT is difficult to determine
due to limited number of studies, small heterogeneous study populations and differing
modes of CRRT and ultrafiltration rates in the studies. However, reliable dose
adjustments can be made with the use of pharmacokinetic principles.4

A CRRT dose adjustment table was developed in Microsoft Excel at UW Health to
assist providers with dose adjustments in patients receiving CRRT. The patient’s weight
and ultrafiltration rates are entered into the Excel spreadsheet to make the dose
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adjustments patient specific. Adjustments may be made to the dose or dosing interval
based on whether the drug has time dependent or concentration dependent
pharmacodynamics. Pharmacokinetic parameters and recommended dosing regimens
for CRRT were obtained from medication databases, clinical dosing markers, and/or
published primary literature.5-10
Recommendations
3. The CRRT dose adjustment table should be used in adult ICU’s at UW Health to
guide medication dosing for patients receiving CRRT (CVVH or CVVHD) to
maximize drug therapy, ensure appropriate drug dosing, and standardize CRRT
based dose adjustments (Appendix A). (Class I, Level C)
4. Medication dose adjustments should be performed by the clinical pharmacist
according to the “Continuous Renal Replacement Therapy (CRRT)-Based Dose
Adjustments Delegation Protocol – Adult – Inpatient” (Class I, Level C)
4.1. )

UW Health Implementation
Potential Benefits:
1. Appropriately dosing antibiotics in ICU patients will improve patient outcomes.
2. Standardizing dosing of medications in ICU patients will provide consistency in
patient treatment.

Potential Harms:
None anticipated

Implementation Plan/Tools
1. Guideline will be housed on U-Connect in a dedicated folder for CPGs.
2. Release of the guideline will be advertised in the Clinical Knowledge Management
Corner within the Best Practice newsletter.
3. Links to this guideline will be updated in Health Link.
4. Critical care pharmacists will be trained on correct use of the CRRT dose adjustment
table.
5. The guideline will be operationalized by pharmacists through a delegation protocol.

Disclaimer
CPGs are described to assist clinicians by providing a framework for the evaluation and
treatment of patients. This Clinical Practice Guideline outlines the preferred approach
for most patients. It is not intended to replace a clinician’s judgment or to establish a
protocol for all patients. It is understood that some patients will not fit the clinical
condition contemplated by a guideline and that a guideline will rarely establish the only
appropriate approach to a problem.

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References
1. Jacobs AK, Kushner FG, Ettinger SM, et al. ACCF/AHA clinical practice guideline
methodology summit report: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines.
Journal of the American College of Cardiology. 2013;61(2):213-265.
2. Schetz M, Ferdinande P, Van den Berghe G, Verwaest C, Lauwers P.
Pharmacokinetics of continuous renal replacement therapy. Intensive Care Med.
1995;21(7):612-620.
3. John S, Eckardt KU. Renal replacement strategies in the ICU. Chest.
2007;132(4):1379-1388.
4. Bouman CS, van Kan HJ, Koopmans RP, Korevaar JC, Schultz MJ, Vroom MB.
Discrepancies between observed and predicted continuous venovenous
hemofiltration removal of antimicrobial agents in critically ill patients and the
effects on dosing. Intensive Care Med. 2006;32(12):2013-2019.
5. Wooley M, Miller B, Krishna G, Hershberger E, Chandorkar G. Impact of renal
function on the pharmacokinetics and safety of ceftolozane-tazobactam.
Antimicrob Agents Chemother. 2014;58(4):2249-2255.
6. Vossen MG, Gattringer KB, Jager W, Kraff S, Thalhammer F. Single-dose
pharmacokinetics of cidofovir in continuous venovenous hemofiltration.
Antimicrob Agents Chemother. 2014;58(4):1952-1955.
7. Leighton A, Gottlieb AB, Dorr MB, et al. Tolerability, pharmacokinetics, and
serum bactericidal activity of intravenous dalbavancin in healthy volunteers.
Antimicrob Agents Chemother. 2004;48(3):940-945.
8. Ulldemolins M, Soy D, Llaurado-Serra M, et al. Meropenem population
pharmacokinetics in critically ill patients with septic shock and continuous renal
replacement therapy: influence of residual diuresis on dose requirements.
Antimicrob Agents Chemother. 2015;59(9):5520-5528.
9. Scheetz MH, Griffith MM, Ghossein C, Hollister AS, Ison MG. Pharmacokinetic
assessment of peramivir in a hospitalized adult undergoing continuous
venovenous hemofiltration. Ann Pharmacother. 2011;45(12):e64.
10. Awissi DK, Beauchamp A, Hebert E, et al. Pharmacokinetics of an extended 4-
hour infusion of piperacillin-tazobactam in critically ill patients undergoing
continuous renal replacement therapy. Pharmacotherapy. 2015;35(6):600-607.

Appendix A
Table 1. CRRT Dosing Table

UW Health CRRT
table .xls

Copyright © 2015 University of Wisconsin Hospitals and Clinics Authority, University of Wisconsin Medical Foundation, Inc, UW-Madison