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Chemical Contamination
Risk Prevention in Infusion Therapy
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Chemical Contamination
Definition
Causes
Definition
The term chemical contamination is defined as the
unintended exposure of a healthcare professional
to hazardous drugs.
The American National Institute for Occupational Safety and Health
(NIOSH) defines a hazardous drug as any drug identified by at least
one of the following criteria: carcinogenicity, teratogenicity or
developmental toxicity, reproductive toxicity in humans, organ
toxicity at low doses in humans or animals, genotoxicity, or new
drugs that mimic existing hazardous drugs in structure or toxicity
[NIOSH 2004]. 136 hazardous drugs are listed, including:
n Chemotherapy/cytotoxic agents
n Antibiotics/Antivirals
Bioengineered drugs
n
Monoclonal antibodies
n
Gene & hormone agents
n
Other miscellaneous drugs
n
Causes
This brochure will give an outline on the causes of chemical
contamination.
Kromhout and others have noted that the exact cause or pathway
of this exposure is unclear [Kromhout et al. 2000], but two primary routes can be found in the literature: a dermal [Valanis et al.
1993a, b] and an aerosol route [Kromhout et al. 2000].
Dermal contamination
There are many areas where contamination has been found and
which have been identified as leading to dermal, or ‘touch’, contamination. These include:
n the surface of vials [Mason et al. 2003],
n the surface of drug boxes [Schmaus et al. 2002],
n preparation of drugs such as cyclophosphamide
[Fransman et al. 2004]
n and handling bodily fluids of patients undergoing cytostatic
treatment [Fransman et al. 2004, Kromhout et al. 2000].
The presence of contamination in these areas suggests that preparing cytostatics as well as handling vials, boxes and bodily fluids is a
cause of contamination.
Other causes of contamination, discussed by regulatory bodies such
as the NIOSH, are poorly decontaminated spills, the priming of IV
sets, handling outside of the pharmacy and poor product choice
[NIOSH 2004].
Fig. 1: Contamination caused by priming of IV sets
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“The results show that pharmacy technicians and oncology
nurses were dermally exposed to cyclophosphamide”.
[Fransman et al. 2004]
Aerosol contamination
Aerosol contamination during preparation and delivery is accepted by bodies such as NIOSH and can be found in the literature
[Neal et al. 1983, NIOSH 2004, Sessink 1994]. Certain studies,
however find no evidence for aerosol contamination but it has
been suggested that this is due to inadequate detection limits
[Larson et al. 2003].
Risks
Skin contact during:
n
Contact with vial surfaces
n
Contact with packaging surfaces
n
Handling bodily fluids of patients
n
Spills
n
Priming IV sets
Aerosol contact during:
n
Preparation of drugs
n
Administration of drugs
Fig. 2: Contamination caused during preparation
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Chemical Contamination
Consequences
The consequences of chemical contamination depend on the drug
in question. For this reason, a differentiation between toxic and
non-toxic contamination seems appropriate.
Non-toxic contamination
Exposure to non-toxic medications such as certain antibiotics is not
without consequences and has been shown to lead to dermatitis
[Gielen and Goossens 2001] and hypersensitivity [AFS 2005] which
can reduce working efficiency.
Toxic contamination
1. Acute symptoms
Drug SPCs are the principle source of information regarding
undesirable effects and should be consulated regulary.
Paclitaxel, for example, is said to lead to acute symptoms such as
nausea, alopecia (hair loss) and bradycardia [Paclitaxel SmPC 2010].
Studies show a significant increase in similar acute symptoms
between control cases and cases exposed to antineoplastic agents
(e.g. diarrhea, throat irritation, skin rashes) [McDiarmid et al.
1988, Valanis et al. 1993a]. However, the main acute symptom is
mutagenicity. Studies have found various mutagenicity indicators
such as sister chromatid exchange or aberrations [Falck et al. 1979,
Sarto et al. 1990]. Since chromosomal mutagenicity following exposure is stochastic in nature [Health Counsel 1994], as little as one
molecule could cause a mutation. For this reason, regulatory bodies
do not quote threshold levels under which exposure is acceptable.
“The results showed that nurses exposed to antineoplastic agents
at work were significantly more likely to have urinary mutagenicity, as compared to nonexposed nurses … A significantly higher
proportion of untoward pregnancy outcomes occurred in pregnancies with exposure to antineoplastic agents.” [Rogers and
Emmett 1987]
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2. Chronic symptoms
Carcinogenicity
Mutagenicity, while being an acute symptom in itself, can lead to
the chronic disease cancer. The link between exposure to high dose
cytotoxic medication and secondary malignant neoplasia has also
been shown, and has led to the International Agency for Research
on Cancer (IARC) classifying many antineoplastic drugs as group 1
(carcinogenic to humans) compounds [IARC]. The stochastic nature
of carcinogenicity makes even low doses, such as those found during
a contamination, a risk. Studies showing such a link are subject to
certain statistical challenges due to the low occurrence of cancer
in the population and limited sample sizes. However, Sessink calculated that the theoretical lifetime risk that a healthcare worker
suffers from leukemia was 95-475 per million [Sessink et al. 1995].
Skov shows an increased risk of leukemia and non-Hodgkin’s lymphoma in hospital workers [Skov et al. 1992].
Reproductive effects
Studies show an increased occurrence of fetal loss [Selevan et al. 1985,
Stücker et al. 1990, Valanis et al. 1999] as well as teratogenicity
[Hemminki et al. 1985].
Other chronic effects
As further possible consequences, Sotaniemi showed chronic liver
damage and fibrosis [Sotaniemi et al. 1983] as a result of exposure to
toxic drugs.
“A statistically significant association was observed between
fetal loss and occupational exposure to antineoplastic drugs
during the first trimester of pregnancy.” [Selevan et al. 1985]
Fig. 3: Causes of chemical contamination and their potential consequences.
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Chemical Contamination
Consequences
The costs factors here will be split into the cost to society and the
cost to the healthcare institutions which will be discussed below
(see Fig. 4).
Cost for the hospital
Common standard operating procedures (SOPs) in hospitals as well
as published guidelines dictate that healthcare workers exposed to
contamination must thoroughly rinse the exposed area with water
for ten minutes. If the eyes are contaminated, an ophthalmologist
is to be consulted [QuapoS 2003]. Added to this lost productivity,
there are some hardware costs for washes, ointments, bandages
and medication to ease the symptoms of any acute consequences
such as diarrhea.
The dermatitis and hypersensitivity caused by repeated exposure
to medication has not been investigated with regard to cost, but
Mälkönen found that healthcare workers with an occupational skin
disease had to take sick leave (21 %) or were forced to change
occupation (21 %) [Mälkönen 2009]. The reduction of the working
efficiency of staff who stay, and the training of new staff to replace
those who leave, are two cost factors that must not be forgotten.
Another case where a complication leads to loss of productivity is
cancer; for example, in the UK, patients are allocated up to 28 weeks
statutory sick leave with a sick pay of 79.15 £ (90 €) per day
[Macmillan cancer support 2010].
In a similar way, hospital costs associated with the reproductive
complications such as fetal loss, are caused when compassionate sick
leave is granted to the healthcare worker. While this will certainly
vary significantly, the legal minimum leave for the loss of a 1st degree relative for many industries in Germany is 2 days [IGBCE 2000].
Depending on the country one can imagine, that if any of these
health problems can be traced back to poor safety procedures,
there may be costly legal consequences for a healthcare institution.
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Fig. 4: Estimation of possible additional costs as a consequence of complications caused by chemical contamination.
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Chemical Contamination
Preventive
strategies
Fig. 5:
Centralized pharmacy
preparation
Fig. 6:
Safety devices
Fig. 7:
Protective coverings
in use in a laminar air
flow cabinet
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Preventive strategies
Preventative strategies are often recommended
by national bodies (see box) and focus on reducing
exposure. The pictures (left) illustrate the main
precautions, namely:
n Prevent contamination caused by handling
errors by centralizing preparation [QuapoS 2003].
This allows medication to be handled by specially
trained personnel (Fig. 5).
n Prevent release of toxic contamination by using
“safety” devices [NIOSH 2004]. These aim to
reduce aerosol contamination (e.g. aerosol filters)
as well as drip contamination (e.g. needle free
devices) (Fig. 6).
Some causes of contamination such as the vial surface, however, are difficult to prevent and so must be
contained (Fig. 7):
n Any aerosol contamination which is formed is
contained by using laminar air flow (LAF) or
isolator cabinets [Nguyen et al. 1982,
Crauste-Manciet et al. 2005].
n Any drip contamination which is formed is prevented from being absorbed by use of protective
coverings such as gowns, masks and gloves
[ASTM 2005].
Regulatory bodies
The following bodies (among others) publish recommendations for the prevention of chemical
contamination:
n
n
n
n
n
The National Institute for Occupational Safety
and Health (NIOSH), USA
Centers for Disease Control and Prevention
(CDC), USA
International Society of Pharmacovigilance (ISOP)
German Society for Oncology Pharmacy (DGOP),
Germany
Swedish Work Environment Authority (AFS),
Sweden
In addition, regular controls such as blood tests are
recommended in order to monitor exposure levels
[QuapoS 2003]. If systematic protective measures are
put in place, exposure can be reduced [Ündeger et al.
1999, Skov et al. 1992].
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Chemical Contamination
Riskprevention
Mini-Spike® Chemo V
Vented dispensing pin for safe and convenient fluid transfer
with syringes.
n Air vent includes inbuilt filter to prevent toxic aerosols
from escaping.
n Two-way valve prevents drips and spills.
Cyto-Set® Mix
The complete system solution for safe and easy toxic preparations
n Allows needle free admixture into infusion container.
n Optimal system compatibility with Cytoset.
Ecoflac® plus
The state of the art IV solution container that offers safe and
convenient application of all IV procedures from drug admixture
to drug delivery.
n Superior properties of the resealable port membrane prevent
drips.
n Innovative cap design allows a safe and easy drug admixture
process and secure spiking.
Safeflow / Ultrasite®
Valves for safe and convenient access to the infusion line.
The valve ensures the system remains closed.
n B. Braun’s needle-free infusion systems reduce the risk of drip
contamination and reduce use of needles.
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Ecoflac® Connect
Closed system transfer cap for single dose drug admixture.
n The closed system of Ecoflac® Connect, ensures
that there is no contact with the external environment.
n This closed system reduces exposure of healthcare
professional to the medication.
Intrafix® SafeSet
IV set for safe and convenient infusions.
n Automated, drip free priming through innovative
Prime Stop membrane built into the end cap.
Cyto-Set®
The complete system solution for safe and easy toxic
infusions.
n Toxic drips prevented by allowing simple pre- and
post-filling of the line with neutral solution.
n Design prevents need for re-spiking.
Discofix® C
The unique stopcock for premium safety.
n A special material prevents toxic drips out of system by
eliminating stress cracks.
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Chemical Contamination
Literature
Literature
AFS Cytostatics and other medications with permanent toxic effects [translation] Swedish Work Environment Agency 2005: 5
ASTM. D6978-05: Standard Practice for Assessment of Resistance
of Medical Gloves to Permeation by Chemotherapy Drugs, American
Society for Testing and Materials 2005
January 1, 2006, Using Different Tumor Inclusion Criteria. Accessed
at http://seer.cancer.gov/csr/1975_2006/results_single/sect_01_
table.21_2pgs.pdf on September 3, 2009
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans - Overall Evaluations of Carcinogenicity: An Updating of IARC
Monographs 1987. Supplement 7; Volumes 1-42
Crauste-Manciet S, Sessink PMJ, Ferrari S, Jomier JY, Brossard D. Environmental Contamination with Cytotoxic Drugs in Healthcare Using
Positive Air Pressure Isolators. Ann Occup Hyg 2005; 49(7): 619–628
IGBCE. Manteltarifvertrag 2000
Falck K, Gröhn P, Sorsa M, Vainio H, Heinonen E, Holsti LR. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1979;
1(8128): 1250–1251
Kromhout H, Hoek F, Uitterhoeve R, Hui­jbers R, Overmars RF,
Anzion R, Vermeulen R. Postulating a dermal pathway for exposure
to antineoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace sur­veys. Ann Occup
Hyg 2000; 44(7): 551–560
Flintoff JP. Thalidomide: the battle for compensation goes on. The
Sunday Times. March 23, 2008
Fransman W, Vermeulen R, Kromhout H. Occupational dermal exposure to cyclophosphamide in Dutch hospitals: a pi­lot study. Ann
Occup Hyg 2004; 48(3): 237–244
Gielen K, Goossens A. Occupational allergic contact dermatitis from
drugs in healthcare workers. Contact Dermatitis 2001; 45: 273–279
Health Counsel of the Neatherlands. Risk assessment of carcinogenic chemicals in the Neatherlands. Regul Toxicol Pharmacol
1994; 19: 14-30
Hemminki K, Kyyrönen P, Lindbohm M-L. Spontaneous abortions
and malformation in the offspring of nurses exposed to anaesthetic
gases, cytostatic drugs, and other potential hazards in hospitals,
based on registered information of outcome. J Epidemiol Community Health 1985; 39: 141-147
Horner MJ, Ries LAG, Krapcho M, et al (eds). SEER Cancer Statistics
Review, 1975-2006, National Cancer Institute. Bethesda, Md, based
on November 2008 SEER data submission, posted to the SEER web
site, 2009. Table I-21, US Prevalence Counts, Invasive Cancers Only,
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Larson RR, Khazaeli MB, Dillon HK. A New Monitoring Method Using Solid Sorbent Media for Evaluation of Airborne Cyclophosphamide and Other Antineoplastic Agents. Appl Occup Environ Hyg
2003; 18(2): 120-131
Macmillan cancer support website. A guide to benefits and financial help for people affected by cancer. http://www.cancer.gov/
aboutnci/servingpeople/CostOfCancer. Accessed Feb. 2010
Mälkönen T, Jolanki R, Alanko K, Luukkonen R, Aalto-Korte K, Lauerma A, Susitaival P. A 6-month follow-up study of 1048 patients diagnosed with an occupational skin disease. Contact Dermatitis
2009; 61(5): 261-8
Mason HJ, Morton J, Garfitt SJ, Iqbal S, Jones K. Cytotoxic drug
contami­nation on the outside of vials delivered to a hospital pharmacy. Ann Occup Hyg 2003; 47(8): 681–685
McDiarmid MA, Egan T. Acute occupational exposure to antineoplastic agents. J Occup Med 1988; 30(12): 984–987
National Cancer Institute website (USA). http://www.cancer.gov/
aboutnci/servingpeople/CostOfCancer. Accessed Feb. 2010
Neal AdW, Wadden RA, Chiou WL. Exposure of hospital workers to
airborne antineoplastic agents. Am J Hosp Pharm 1983; 40(4): 597601
Nguyen TV, Theiss JC, Matney TS. Exposure of pharmacy personnel
to mutagenic antineoplastic drugs. Cancer Res 1982; 42: 4792–
4796
NHS Careers website. www.nhscareers.nhs.uk. Accessed Feb. 2010
NIOSH Alert: Preventing occupational exposures to antineoplastic
and other hazardous drugs in health care settings. U.S. Department
of Health and Human Services, Public Health Service, Centers for
Disease Control and Prevention, National Institute for Occupational
Safety and Health, DHHS (NIOSH) 2004. Publication No. 2004-165
Sessink PJM, Van De Kerkhof MCA, Anzion RBM, Noordhoek J, Bos
RP. Environmental contamination and assessment of exposure to
antineoplastic agents by determination of cyclophosphamide in
urine of exposed pharmacy technicians: is skin absorption an important exposure route? Arch Environ Health 1994; 49(3): 165–169
Sessink PJM, Kroese ED, van Kranen HJ, Bos RP. Cancer risk assessment for health care workers occupationally exposed to cyclophosphamide. Int Arch Occup Environ Health 1995; 67: 317-323
Skov T, Maarup B, Olsen J, Rørth M, Winthereik H, Lynge E. Leukaemia and reproductive outcome among nurses handling antineoplastic drugs. Br J Ind Med 1992; 49: 855–861
Paclitaxel SmPC. BMS 2010
Sotaniemi EA, Sutinen S, Arranto AJ, Sutinen S, Sotaniemi KA,
Lehtola J, Pelkonen RO. Liver Damage in Nurses Handling Cytostatic
Agents. Acta Med Scand 1983; 214: 181-9
QuapoS 3 Quality Standard for the Oncology Pharmacy Service with
Commentary. Institute for Applied Healthcare Sciences (IFAHS e.V.)
for the German Society of Oncology Pharmacy (DGOP e.V.). 2003
Stücker I, Caillard J-F, Collin R, Gout M, Poyen D, Hémon D. Risk of
spontaneous abortion among nurses handling antineoplastic drugs.
Scand J Work Environ Health 1990; 16: 102–107
Rogers B, Emmett EA. Handling anti-neoplastic agents: urine mutagenicity in nurses. J Nurs Scholarsh 1987; 19: 108–113
Ündeger Ü, Baþaran N, Kars A, Güç D. Assessment of DNA damage
in nurses handling antineoplastic drugs by the alkaline COMET assay. Mutat Res 1999; 439: 277–285
Sarto F, Trevisan A, Tomanin R, Canova A, Fiorentino M. Chromosomal Aberrations, Sister Chromatid Exchanges, and Urinary
Thioethers in Nurses Handling Antineoplastic Drugs. Am J Ind Med
1990; 18: 689495
Schmaus G, Schierl R, Funck S. Monitoring surface contamination
by anti-neoplastic drugs using gas chromatography-mass spectrometry and voltammetry. Am J Health Syst Pharm 2002; 59: 956–
961
Selevan SG, Lindbohm M-L, Hornung RW, Hemminki K. A study of
occupational exposure to antineoplastic drugs and fetal loss in
nurses. N Engl J Med 1985; 313(19): 1173–1178
Valanis BG, Vollmer WM, Labuhn KT, Glass AG. Acute symptoms associated with antineoplastic drug handling among nurses. Cancer
Nurs 1993a; 16(4): 288–295
Valanis BG, Vollmer WM, Labuhn KT, Glass AG. Association of antineoplastic drug handling with acute adverse effects in pharmacy
personnel. Am J Hosp Pharm 1993b; 50: 455–462
Valanis B, Vollmer WM, Steele P. Occupational exposure to antineoplastic agents: self-reported miscarriages and stillbirths among
nurses and pharmacists. J Occup Environ Med 1999; 41(8): 632–638
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Chemical Contamination
Notes
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The summarized scientific information in this document has been prepared for healthcare professionals. It is based on an analysis of
public literature and guidelines. The intention is to give an introduction to the risks commonly associated with infusion therapy and to
increase the awareness of healthcare workers to these kinds of problems. Due to its summary nature, this text is limited to an overview
and does not take into account all types of local conditions. B. Braun does not assume responsibility for any consequences that may
result from therapeutical interventions based on this overview.
B. Braun Melsungen AG | Hospital Care | 34209 Melsungen | Germany
Tel. +49 5661 71-0 | www.bbraun.com | www.safeinfusiontherapy.com
Nr. 6069097 Edition: 03/2011