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Etre les premiers pour vous
HôpitauxUniversitairesde Genève
INCOMPATIBILITY
OF IV DRUGS :
SOME CLINICAL
HIGHLIGHTS
Dre Caroline Fonzo-Christe
Pharmacie des HUG
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FACULTY DISCLOSURE
No, nothing to disclose
x Yes, please specify:
Company NameHonoraria/
Expenses
Consulting/
Advisory
Board
Funded
Research
Royalties/
Patent
Stock
Options
Ownership
/ Equity
Position
EmployeeOther
(please specify)
Doran InternationalInvited
speaker
Pall companyInvited
speaker
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WHAT ARE WE TALKING ABOUT?
Addition of midazolam
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WHAT ARE WE TALKING ABOUT?
Addition of midazolam
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WHAT ARE WE TALKING ABOUT?
B.Braun, KIK 2.1 2002 and Drug incompatibility 2011 www.safeinfusiontherapy.com
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HUG
caspofungine + heparine
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SOME QUESTIONS
• A theoretical problem?
• An old stuff?
• What are the clinical consequences?
• A pharmacist issue?
• What can we do? Can YOU do something
for this issue?
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CONTEXT
Environment
• Temperature
• Light
Material
• PVC (DEHP)
• Silicone
•…
Drug A
Solvent +
excipients
Drug B
Factors
• Concentration
• Contact time
Solvent +
excipients
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TYPE OF REACTIONS
Physico- chemical
• Acid-base reactions (pH)
• Solubility
• Emulsion cracking
• Oxydo-reduction
• …
Consequences
• Precipitates (visible)
• Colour change (visible)
• Gaz production (visible)
• pH change (invisible)
• concentration (invisible)
• Catheter occlusion
• Renal and pulmonary embolism
• therapeutic effect
• Toxic effects (peroxides) patient
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ACIDS AND BASES
From: KIK 2.1,
BBraun, 2002
Acid drug molecule basic drug solution
Basic drug molecule acidic drug solution
Don’t mix or infuse
on Y-site
acidic with basic
drug solutions!
Molecule Drug
solution
Molecule Drug
solution
Furosemide (acid) pH 9 Furosemide (acid) pH 9
Vancomycin (base) pH 3 Midazolam (base) pH 4
From: KIK 2.1, BBraun, 2002
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SOLVENT (DILUENT)
Furosemide in Glucose 5% From: KIK 2.1, BBraun, 2002
Glucose 5%-20% pH = 3.5 - 6.5 amiodarone, amphotericine B
NaCl 0.9% pH = 5.0 - 7.0 aciclovir, phenytoin
Solvent pH Appropriate for
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LIPID EMULSION
reversible
irreversible
Coalescence :
pH
conc. AA
Electrolytes with
high valence (Ca2+,
Mg2+, PO43-)
Lipid emulsion is
not water!
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SOLUBILITY
“Pastis effect”
drug excipient
amiodarone Cordarone® polysorbate (tween)
paracetamol Perfalgan® mannitol, phosphate, NaOH
esomeprazole Nexium® NaOH, EDTA
phenytoin Phenhydan® glycofurol-75, EDTA
clonazepam Rivotril® propylene glycol, acetic acid
Co-solvent and/or adjusting pH
can increase the solubility of
drugs in solution
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CLINICAL INCIDENTS
Knowles JB et al. JPEN 1989;13:209-13
Hill SE et al. JPEN 1996;20:81-87 McNearney T et al. Dig Dis Sci 2003;48:1352-4
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CALCIUM COMPLEXATION
Insoluble
Ceftriaxone – Calcium
Complex
Bradley JS et al. Pediatrics 2009;123:609-13
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RECENT DATA: DRUG - DRUG
Kalikstad B et al. Arch Dis Child 2010;95:745-748
Zhao B et al. Am J Health-Syst Pharm 2014;71:901-902
Lack of DATA
in NICU
Case-reports of
catheter
occlusion
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RECENT DATA: DRUG - SOLVENT
Christensen RD et al. Arch Dis Child Fetal Neonatal 2012;97:F3
Stark MJ et al. Arch Dis Child Fetal Neonatal 2012;97:F62-64
Blood always
alone
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SOME QUESTIONS
• A theoretical problem?
• An old stuff?
• What are the clinical
consequences?
• Not only, also a real one
• Yes, well known problem
since the eighties, but still
a current problem in the
practice
• May lead to precipitates
and renal and pulmonaryembolism
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AIR POLLUTION
Visible range:
> 50 m
Erythrocytes:
about 7.5 m
Capillary:
8-10 m
Brook RD. Clinical Science 2008;115:175–187
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CLINICAL CONSEQUENCES
Mechanical local
endothelial
damage
Thrombotic and
inflammatory
response
Brook RD. Clinical Science 2008;115:175–187
S.I.R.S
Predisposition
to SIRS?
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IN-LINE FILTRATION AND SIRS
Jack T et al. Intensive Care Med 2012;38:1008–1016
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COSTS
Jack T. et al Intensive Care Med 2012;38:1008–1016
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IN PRACTICE
Austr Prescr 2008;31:98-101
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IN VITRO TESTING
Bouchoud L et al. JPEN J Parenter Enteral Nutr. 2013;37:416-24
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TPN: CALCIUM/PHOSPHATE
Bouchoud L et al. JPEN J Parenter Enteral Nutr. 2010;4:542-5
• Phocytan ® (Glucose-1-phosphate Na)
• Glycophos ® (Glycerophosphate Na)
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TOOLS
http://pharmacie.hug-ge.ch/infomedic/utilismedic/HUG_CompatAdm_DCI.pdf
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I-TOOLS, DATA-BASES
http://fr.appbrain.com/app/injectable-medicines/air.coim, http://www.ahfsdruginformation.com,
http://www.theriaque.org, http://www.kik-service.de, http://www.stabilis.org, https://www.kingguide.com
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HUG: IN-LINE FILTERS
http://pharmacie.hug-ge.ch/infomedic/utilismedic/filtres_USI.pdf
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CHRU LILLE (FRANCE)
Foinard A et al. Anesth Analg 2013;116:101-6
Perez M. CHRU Lille
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SOME QUESTIONS
• A pharmacist issue?
• What can we do? Can
YOU do something for this
issue?
• Yes, it is– In vitro testing
– Drug incompatibility charts
– Bedside teaching
But also…• Multidisciplinary team
working– Infusion material: In-line
filters, new devices
– Clinical pharmacist
physician
pharmacist
nurse
biomedical,
technicians…
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ARE YOU READY TO INVEST?
Thank you
for your
attention