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Anti-Infective Lock Therapy – Adult/
Pediatric – Inpatient/Ambulatory –
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
Table of Contents
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ...................................................................................................................................... 4
METHODOLOGY ...................................................................................................................... 5
DEFINITIONS ............................................................................................................................ 5
TABLE 1. VENOUS ACCESS DEVICES ................................................................................... 6
TABLE 2. CENTRAL VENOUS CATHETER TYPE AND CAPACITANCE ............................... 7
INTRODUCTION ....................................................................................................................... 8
RECOMMENDATIONS .............................................................................................................. 8
BENEFITS/HARMS OF IMPLEMENTATION ...........................................................................11
IMPLEMENTATION TOOLS/PLAN ..........................................................................................11
REFERENCES .........................................................................................................................11
APPENDIX 1. NON-HEMODIALYSIS ALT PREPARATIONS AVAILABLE AT UWHC ..........13
APPENDIX 2. HEMODIALYSIS (HD) ALT PREPARATIONS AVAILABLE AT UWHC ...........14
APPENDIX 3. ALT PREPARATIONS AVAILABLE FROM CHARTWELL MIDWEST
WISCONSIN HOME INFUSION SERVICES FOR CENTRAL LINES .......................................15
CPG Contact for Changes: CPG Contact for Content:
Name: Philip Trapskin, PharmD, BCPS Name: Lucas Schulz, PharmD, BCPS
Phone Number: 608-263-1328 Phone Number: 608-263-1328
Email Address: ptrapskin@uwhealth.org Email Address: ptrapskin@uwhealth.org
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Guideline Author(s):
Marie H. Pietruszka, PharmD; Rohan Pradhan PharmD; Megan Bauer PharmD, Philip
Trapskin, PharmD; Joshua Vanderloo, PharmD
Coordinating Team Members:
Joshua Vanderloo, PharmD; Philip Trapskin, PharmD
Review Individuals/Bodies:
Christopher Crinch, MD; Nasia Safdar, MD; Sheryl Henderson, MD; Barry Fox, MD; Dennis
Maki, MD; Laura Maursetter, DO; Alexander Yevzlin, MD; Caitlin Curtis, PharmD; Susan
Luskin, PharmD: Nicole Lubcke, PharmD; Gretchen Manthei, PharmD (Chartwell Midwest
Wisconsin); Luke Schulz, PharmD
Committee Approvals/Dates
Lab Practice Committee, April 2015
Antimicrobial Use Subcommittee, June 2015
Pharmacy and Therapeutics Committee, July 2015
ξ Interim update: September 2015
Release Date: July 2015
Next Review Date: July 2018
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Executive Summary
Guideline Overview
The guideline provides recommendations on the use of anti-infective lock technique (ALT)
including: indications for use, ordering, preparing, and monitoring.
Target Population
Patients at risk for developing, and/or diagnosed with a catheter-related bloodstream infection
(CRBSI)
Key Practice Recommendations
This guideline provides recommendations on antiinfective lock technique selection and
administration for patients receiving antiinfective lock technique.
Companion Documents
1. Flushing/Locking of Venous Access Devices – Adult/Pediatric – Inpatient/Ambulatory
–Clinical Practice Guideline
2. Central Venous Access Device Occlusion – Adult/Pediatric/Neonatal –
ED/Inpatient/Ambulatory – Clinical Practice Guideline
Pertinent UW Health Policies & Procedures
1. UWHC Policy #13.26: Insertion and Maintenance of Central Venous Catheters for
Prevention of Central Line-Associated Bloodstream Infection (CLABSI)
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Scope
Disease/Condition(s):
1. Adult and pediatric patients with long-term central venous catheters at-risk for and with
central-line-associated bloodstream infections (CLABSI).
2. Low birth weight infants and neonates requiring central venous catheters at-risk for and
with CLABSI are NOT INCLUDED in the scope of this guideline.
Clinical Specialties/Intended Users
Physicians, Advanced Practice Providers, Nurses, and Pharmacists
CPG objective
To provide an evidence-based resource that will maximize the safe, efficacious and efficient use
of anti-infective lock therapy
Target Population:
Patients at risk for developing, and/or diagnosed with a catheter-related bloodstream infection
(CRBSI)
Interventions and Practices Considered:
The use of ALT for the prevention or treatment of CRBSI
Major Outcomes Considered:
1. Sterility and stability of anti-infective lock therapy preparations
2. Catheter salvage rates
Guideline Implementation Metrics:
1. Availability of clinical decision support (order sets, medication record) build to promote
adherence to the guidelines
2. Adherence of prescribed anti-infective lock regimens to the CPG
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Methodology
A modified Grading of Recommendations Assessment, Development and Evaluation (GRADE)
developed by the American Heart Association and American College of Cardiology has been
used to assess the quality and strength of the evidence in this Clinical Practice G uideline.1
Definitions
1. Anti-infective lock technique (ALT)2: the installation of a highly concentrated anti-
infective solution into a catheter lumen and allowing the solution to dwell for a specified
period for the purpose of sterilizing the lumen.
2. Catheter-related blood stream infection (CRBSI)3: Defines the catheter as the cause
of a blood stream infection. CRBSI is a clinical definition used when diagnosing or
treating patients. Criteria for CRBSI include the following: Presence of bacteremia or
fungemia in a patient who has an intravascular catheter; AND at least 1 positive blood
culture obtained peripherally; AND clinical signs of infection (fever, chills, or
hypotension); AND absence of infection at another site; AND one of the following: (a)
Positive semiquantitative [>15 colony forming units (CFU) per catheter segment] or
quantitative [>102 CFU per catheter segment] catheter tip culture, (b) Quantitative blood
culture with a ratio >3:1 CFU/mL (catheter vs peripheral), (c) Differential time to positivity
(blood culture from catheter is detected at least 2 hours before detection of peripheral
blood culture).
3. Central-line associated blood stream infection (CLABSI)3: Describes a blood stream
infection in a patient who had a recent central catheter. Used by the National Healthcare
Safety Network (NHSN) for surveillance. Criteria for CLABSI include: Presence of
bacteremia or fungemia (a single positive blood culture is required for most organisms,
whereas 2 positive blood cultures are required for skin flora organisms), AND presence
of central line within 48 hours, AND absence of an infection at a different site.
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4. Catheter volume: the intraluminal volume of the catheter
4.1. French (Fr) scale4 - describes the external diameter of the catheter (1Fr = 1/3mm)
using an ascending scale (i.e., higher Fr size indicates larger catheter diameter)
4.2. Gauge - describes both inner and outer diameter using a descending scale (i.e.
higher gauge indicates smaller catheter diameter)
5. Catheter overfill: a specified volume in addition to the catheter volume that ensures that
the ALT solution totally fills the catheter, including the portion closest to the blood
interface
5.1. For patient weighing fewer than 15 kg, the overfill volume is 0.1 mL.5
5.2. For patient weighing 15 kg or greater, the overfill volume is 0.2 mL.5
Table 1. Venous access devices (from Flushing/Locking of Venous Access Devices
– Adult/Pediatric – Inpatient/Ambulatory Clinical Practice Guideline) 6-8
Type of Device
Common
Catheter
Length
Insertion Location When to Use
Umbilical
Venous and
Arterial
Catheter
(UVC/UAC)
< 5 cm
Inserted through the umbilical vein
and joins the left portal vein or
umbilical artery and joins arteries
either at the thoracic or lumbar
vertebral bodies
Short-term access up to 7
days after birth
Peripheral (PIV) < 3 in
Terminates in a vein of the forearm
or hand; location may vary in
pediatric patients
Short-term access < 1 week
Midline 3 – 8 in
Peripheral device terminating in the
basilic, cephalic, or brachial vein
distal to the shoulder
Access needed for < 1 month,
not appropriate for vesicant
administration
Non-Tunneled
Central ≥ 8 cm
Percutaneous device terminating in
the superior or inferior vena cava
Short term access when
peripheral not suitable, ex.
resuscitation and central
venous pressure monitoring
Peripherally
Inserted Central
(PICC)
≥ 20 cm Peripheral device terminating in the
superior or inferior vena cava
Medium-term (up to 6 months)
access
Tunneled
Central ≥ 8 cm
Implanted into the subclavian,
internal jugular, or femoral veins
Frequent medium-term (up to
6 months) access and a PICC
line is contraindicated
Implanted
Central (Port) ≥ 8 cm
Tunneled under skin with port
accessed by needle; implanted in
subclavian or internal jugular vein
terminating in the superior vena cava
Infrequent long-term (> 6
months) access
Dialysis and
Apheresis ≥ 15 cm
Non-cuffed catheter placed in the
neck or chest terminating in the
superior or inferior vena cava
Long or short term access for
the maintenance of dialysis
therapy
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Table 2. Central venous catheter type and capacitance (from Central Venous Access
Device Occlusion – Adult/Pediatric/Neonatal – ED/Inpatient/Ambulatory – Clinical Practice)
Guideline) Catheter Type Adult Capacity Pediatric Capacity Neonatal Capacity
PICC 1 mL 1 mL or less 0.1 mL (1.9 Fr)
Tunneled Cuff Catheter
(ex. Hickman) 2 mL 1 mL or less
Tunneled Cuff Catheter
(ex. Groshong) 1 mL 1 mL or less
Implanted Venous Port 2 mL 1 mL or less
Dialysis-Pheresis Catheters Volume on
catheter lumen 1 mL or less
Non-tunneled Triple Lumen
(ex. Arrow) 1 mL 1 mL or less
Umbilical Catheters (Double
and Single Lumen 3.5 and 5 Fr) 0.5 mL or less
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Introduction
ALT is used for the prevention or treatment of device-related bacteremias or fungemias resulting
from the colonization of bacteria or fungi within the lumen of an intravascular device. ALT as
developed to allow a concentrated anti-infective solution to dwell within the catheter lumen for
an extended period of time in order to eradicate infectious pathogens.
The most commonly reported CLABSI pathogens are coagulase-negative staphylococci,
Staphylococcus aureus, enterococci, Candida species, and Gram-negative bacilli.9 Important
pathogenic determinants of CRBSI include: (1) device material; (2) formation of fibrin sheaths
around the catheter; (3) intrinsic virulence factors of the infecting organism (extracellular
polymeric substance production, biofilm formation).9 The formation of a biofilm within a catheter
lumen limits the penetration of solution. Bacteria within a biofilm require a 100 to 1000 times
greater anti-infective concentration to achieve killing versus planktonic bacteria. 10 Standard
intravenous therapy does not reach a sufficient concentration in the catheter lumen to reduce
microorganism burden within the biofilm of the catheter. One report concluded that, in
hemodialysis patients with dialysis catheter-related infection, systemic vancomycin
administration produces a therapeutic plasma concentration; however, during the intradialytic
period, the diffusion of the vancomycin from the plasma into the catheter lumen was negligible.11
Additionally, the success of ALT is dependent on the stability and compatibility of the ALT
solution.12 The stability and compatibility of ALT solutions is dependent on a number of factors
including: temperature, dwell time, syringe materials, pH, device materials, and anti-infective
concentrations.12
Recommendations
1. ALT for the prevention of CRBSI
1.1. Routine use of ALT in general patient populations is not recommended.2 (Class III,
Level B)
1.2. Use of ALT is beneficial when vascular access device use is required for a long-
term/indefinite duration and cannot easily be replaced in patients with a history of
CRBSI despite maximal adherence to aseptic technique.2 (Class I, Level A)
1.3. Selection of the ALT solution should consider the following: (Class I, Level C)
1.3.1. Catheter indication (e.g., hemodialysis, non-hemodialysis)
1.3.2. Catheter composition and compatibility with ALT solution(s) (e.g., prolonged
exposure to ethanol can affect the integrity of certain catheter materials)13
1.3.3. History of CRBSIs and previous culture/sensitivity results
1.3.4. History of previous ALT use/failure
1.3.5. Need for anticoagulant as part of ALT therapy
1.3.6. Medication allergies or adverse drug reactions
1.3.7. Risk of systemic exposure and adverse effects associated with ALT (e.g.
ethanol intoxication in pediatric population)5
1.3.8. Targeted microorganism(s)
1.3.9. Patient age (neonate, pediatric, adult)
1.3.10. Risks of adverse effects from ALT systemic exposure
1.3.11. Regimens available at UW Health (see Appendix 1 and Appendix 2)
2. ALT catheter salvage
2.1. ALT can be beneficial for patients with CRBSI involving long-term catheters with no
signs of exit site or tunnel infection for whom catheter salvage is the goal.10 (Class IIa,
Level B)
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2.2. For CRBSI, antibiotic lock should not be used alone; instead, it is reasonable to be
used in conjunction with systemic antimicrobial therapy.10 (Class IIa, Level B)
2.3. Dwell times for ALT solutions generally should not exceed 48 hours before
reinstallation of lock solution. Reinstallation is probably indicated every 24 hours for
ambulatory patients with femoral catheters.14 (Class IIa, Level B)
2.3.1. For patients who are undergoing hemodialysis, the lock solution can be
renewed after every dialysis session.10 (Class IIa, Level B)
2.4. Catheter removal is probably recommended for CRBSI due to S. aureus and Candida
species, instead of treatment with ALT and catheter retention, unless there are
unusual extenuating circumstances (e.g., no alternative catheter insertion site).10
(Class IIa, Level A)
2.5. For patients with multiple positive catheter-drawn blood cultures that grow coagulase-
negative staphylococci or Gram-negative bacilli and concurrent negative peripheral
blood cultures, antibiotic lock therapy may be considered without systemic therapy for
ten to fourteen days.10 (Class IIb, Level B)
2.6. Long-term catheter removal is probably indicated in patients with CRBSI associated
with any of the following conditions: severe sepsis; suppurative thrombophlebitis;
endocarditis; bloodstream infection that continues despite 72 hours of antimicrobial
therapy to which the infecting microbes are susceptible; or infections due to S. aureus,
P. aeruginosa, fungi, or mycobacteria.10 (Class IIa, Level A)
2.7. Short-term catheter removal is probably indicated in patients with CRBSI due to Gram-
negative bacilli, S. aureus, enterococci, fungi, or mycobacteria.10 (Class IIa, Level A)
2.8. In patients with CRBSI for whom catheter salvage is attempted, additional blood
cultures are reasonable. Catheter removal is probably indicated if peripheral blood
culture results (e.g., two sets of blood cultures obtained on a given day;) remain
positive when blood samples are obtained 72 hours after the initiation of appropriate
therapy.10 (Class IIa, Level B)
3. ALT pathogen-specific salvage recommendations.
3.1. An infectious diseases consult should be considered for the determination of CRBSI
catheter-salvage recommendations. (Class IIb, Level C)
4. ALT dwell times
4.1. Dwell times should be specified as part of the ALT orders.10 (Class I, Level C)
4.2. Dwell times for ALT solutions generally should not exceed 48 hours before
reinstallation of lock solution. Reinstallation is probably indicated every 24 hours for
ambulatory patients with femoral catheters.10 (Class IIa, Level B)
4.2.1. For patients who are undergoing hemodialysis, the lock solution can be
renewed after every dialysis session.10 (Class IIa, Level B)
4.3. Flushing of the instilled ALT solution through the catheter into the systemic circulation
is not recommended as to reduce the risk adverse effects and the emergence of
microorganism resistance. (Class III, Level C)
5. Determining catheter volume
5.1. The volumes of common catheters currently used at UW Health are specified in the
Flushing/Locking of Venous Access Devices – Adult/Pediatric – Inpatient/
Ambulatory Clinical Practice Guideline and Central Venous Access Device
Occlusion – Adult/Pediatric/Neonatal – ED/Inpatient/Ambulatory – Clinical Practice
Guideline.
6. ALT solution-specific precautions and considerations
6.1. Stability and compatibility
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6.1.1. The stability and compatibility of the ALT solution should be considered
when ordering ALT for prophylaxis or treatment. ALT solutions without
documented stability or compatibility should not be used.2,12 (Class III, Level
B)
6.1.2. Temperature, dwell time, and solution concentration can influence stability
and compatibility. Also, stability may be altered by manufacturer changes
that are not reflected in the published stability studies. ALT solutions should
be examined for evidence of physical incompatibility (discoloration or
precipitation) prior to instillation into the catheter. (Class I, Level C)
6.1.3. ALT solutions may be stable for short durations and require admixture in the
clinical care area instead of the pharmacy. In these scenarios, it is
reasonable for the pharmacy servicing the ambulatory site to supply the
necessary supplies and instructions for admixture of the ALT solution. (Class
III, Level C)
6.2. Ciprofloxacin
6.2.1. In clinical trials, admixed solution was allowed to dwell for at least 12 hours
and was changed daily.15 Some references cite ciprofloxacin is compatible
with heparin, however, experience at UWHealth has shown ciprofloxacin
and heparin have variable compatibility. Therefore, ciprofloxacin lock
solutions should not include heparin. (Class III, Level C)
6.3. Daptomycin
6.3.1. Daptomycin has a unique mechanism of action involving a calcium-
dependent dissipation of membrane potential, leading to the release of
intracellular ions from the cell and the killing of bacteria. Daptomycin ALT
solution requires the addition of calcium for antimicrobial activity. The
addition of Lactated Ringer’s to the daptomycin ALT provides 3.6 mEq/L of
calcium ions.16
6.4. Ethanol and other alcohol-containing solutions
6.4.1. Ethanol compatibility with heparin and trisodium citrate is variable.12 Ethanol
should not be considered compatible with heparin or trisodium citrate and
neither heparin nor trisodium citrate should be used with ethanol in ALT.
(Class III, Level C)
6.4.2. When ethanol lock solutions are considered, the effect of ethanol on the
mechanical and structural integrity of the catheter should be considered.13
(Class IIa, Level B)
6.4.3. It is reasonable to restrict use of ethanol ALT to silicone and carbathane
catheters until sufficient data are available to ensure that ethanol has no
effect on catheter integrity of non-silicone catheters (e.g. polyurethane
catheters).13,17 (Class IIa, Level C)
6.4.4. It is reasonable to aspirate and discard ethanol ALT from the catheter lumen
and at the end of the dwell, and catheter should be flushed with 0.9%
sodium chloride.13,17 (Class IIa, Level C)
6.5. Gentamicin
6.5.1. Gentamicin precipitates at a concentration of 10mg/mL or higher when
mixed with heparin.18
6.6. Vancomycin
6.6.1. In vancomycin ALT solution, it is reasonable that the vancomycin
concentration be at least 1000 times greater than the MIC of the
microorganism involved.10 (Class IIa, Level B)
7. ALT Preparation
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11
7.1. To maximize the sterility and stability of the ALT, it is reasonable to prepare all ALT
aseptically in a pharmacy when feasible.10 (Class IIa, Level A)
Benefits/Harms of Implementation
1. Potential benefits of use of anti-infective lock therapy in appropriately selected patients
include improved patient outcomes and decreased healthcare costs by reducing
infectious complications associated with intravascular catheter use and the need to for
catheter replacement.9,10
2. Potential harms include the potential for adverse drug events and the emergence of
microbial resistance.9,10
Implementation Tools/Plan
1. Development and build of medication records (ERx) and an order set to facilitate
ordering, dispensing and administration for common ALT regimens.
2. CPG will be hyperlinked to ALT solution medication records (ERx).
Disclaimer
This Clinical Practice Guideline provides an evidence-based approach for use of anti-infective
lock therapy for the prevention and treatment of catheter-related infections. It is understood that
occasionally patients will not match the conditions considered in the guideline.
References
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sodium citrate stored in dialysis catheters at 37 degrees C. Hemodial Int. Jul 2010;14(3):322-326.
33. Battistella M, Walker S, Law S, Lok C. Antibiotic lock: in vitro stability of vancomycin and four
percent sodium citrate stored in dialysis catheters at 37 degrees C. Hemodial Int. Jul
2009;13(3):322-328.
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 07/2015CCKM@uwhealth.org

13
Appendix 1. Non-hemodialysis ALT preparations available at UWHC
Lock Base Solution Record Number in HealthLink Notes
Ciprofloxacin 2 mg/mL15, A D5W 760332
Ceftazidime 2 mg/mL and heparin 100 units/mL12,19 Normal saline 760299
Daptomycin 1 mg/mL and heparin 100 units/mL20, A Lactated Ringers 760356
Daptomycin 5 mg/mL16,21 Lactated Ringers N/A
ξ Not available at
UWHC
ξ Available for
ambulatory through
Chartwell Midwest
Wisconsin
Ethanol 50% (v/v)5,17,22-28 Sterile water 760301
ξ Do not use with
polyurethane
catheters
ξ Incompatible with
heparin and sodium
citrate
Ethanol 70% (v/v)5,17,22-28 Sterile water 760352
Vancomycin 2 mg/mL and heparin 100 units/mL15 Normal saline 760303
Vancomycin 2 mg/mL and heparin 20 units/mL15 Normal saline 760304
A
Note: not available through Chartwell Midwest Wisconsin home infusion services
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 07/2015CCKM@uwhealth.org

14
Appendix 2. Hemodialysis (HD) ALT preparations available at UWHC A, B
Lock Base Solution Record Number in HealthLink
Ceftazidime 10 mg/mL and heparin 5000 units/mL (HD)12,31 Normal saline 760298
Daptomycin 1 mg/mL and heparin 1000 units/mL (HD)20 Lactated Ringers 760355
Gentamicin 1 mg/mL and heparin 2500 units/mL (HD)18 Normal Saline 760302
Gentamicin 2.5 mg/mL and 4% sodium citrate (40 mg/mL) (HD)32 No base 760334
Vancomycin 2.5 mg/mL and heparin 2500 units/mL (HD)18 Normal Saline 760305
Vancomycin 3 mg/mL and 4% mg sodium citrate(40 mgmL) (HD)33 No base 760336
A
Note: Chartwell Midwest Wisconsin does not provide any HD ALT preparations
B ALT for HD include anticoagulant of high-dose heparin (1000 units/mL or greater) or sodium citrate (40 mg/mL)
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 07/2015CCKM@uwhealth.org

15
Appendix 3. ALT preparations available from Chartwell Midwest Wisconsin home infusion services for central lines
(May 2015)
Lock Base Solution
Cefazolin 0.5 mg/mL and heparin 100 units/mL Normal saline
Cefazolin 10 mg/mL and heparin 10 units/mL Normal saline
Ceftazidime 0.5 mg/mL and heparin 100 units/mL Normal saline
Ceftazidime 2 mg/mL and heparin 100 units/mL Normal saline
Ciprofloxacin 0.125 mg/mL and heparin 100 units/mL Normal saline
Daptomycin 5 mg/mL Lactated Ringers
Daptomycin 5 mg/mL and heparin 100 units/mL or heparin 10 units/mL Lactated Ringers
Ethanol 50% Sterile water
Ethanol 70% Sterile water
Vancomycin 25 mcg/mL, ciprofloxacin 0.002 mg/mL and heparin 10 units/mL Normal saline
Vancomycin 50 mcg/mL, ciprofloxacin 0.002 mg/mL and heparin 10 units/mL Normal saline
Vancomycin 0.5 mg/mL and heparin 100 units/mL 0.45% saline
Vancomycin 25 mcg/mL and heparin 10 units/mL Normal saline
Vancomycin 2 mg/mL and heparin 10 units/mL Normal saline
Vancomycin 2 mg/mL and heparin 100 units/mL Normal saline
Vancomycin 2 mg/mL and heparin 20 units/mL Normal saline
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 07/2015CCKM@uwhealth.org