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Chapter 20
Intrathecal
Preparations
By the end of this chapter,
you will be able to:
l
l
l
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Describe the specific risks with
intrathecal cytotoxic products
List five checks that need to
be carried out on Intrathecal
products
Explain the transportation
and storage methods of
Intrathecal products
Identify who should be on the
Trust Intrathecal Register
Introduction
This chapter examines the preparation of
Intrathecal cytotoxic chemotherapy. We
will look at some examples of its uses and
indications. Specific risks are associated with
the administration of Intrathecal cytotoxic
preparations. Patients are also at risk from product
contamination, incorrect dose and calculation.
There are risks to products from incorrect
preparation and storage, and specific risks to
operators from cytotoxic contamination and injury.
It also looks at steps taken to reduce those risks.
This chapter will provide information on the
special administration and prevention of errors
needed in the preparation of Intrathecal products.
Remember: Cytotoxic drugs may be fatal
if administered by the incorrect route.
Confusion over Intravenous/Intrathecal
administration has lead to paralysis and
death of a number of patients worldwide.
The techniques, equipment and risks
associated with handling cytotoxics are
covered in the Cytotoxic preparations
chapter. Make sure you have read and
understood Chapter 19 Cytotoxics.
Reference to the Aseptic Technique chapter
and the Preparation of Central Intravenous
Additive Service chapter will also be useful.
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What is an intrathecal injection
and why is it so special?
Indications for Intrathecal
preparations
It is an injection into the spinal fluid which
surrounds the nerves in the spinal column. It
is not connected to the blood so there are no
white blood cells to fight infection. If we get it
wrong paralysis or death may follow
Leukaemia, lymphoma, and tumour cells can
be found in the cerebro-spinal fluid.
What are Intrathecal
chemotherapy drugs?
Chemotherapy drugs given intravenously and
orally don’t pass into the cerebro-spinal fluid
so can’t be used in these types of cancer.
Intrathecal preparations are also given to prevent
cancer spreading to the cerebro-spinal fluid.
Intrathecal products include both intrathecal
and intraventricular preparations.
How are Intrathecal
preparations administered?
An intrathecal injection is one that is made
into the subarachnoid space that surrounds
the spinal cord (directly into the cerebro-spinal
fluid via a lumber puncture). Cerebro-spinal
fluid is the fluid that surrounds the brain and
spinal column.
A lumbar puncture procedure is performed
where a needle is inserted between the bones
of the lower back and into the cerebro-spinal
fluid. Intrathecal preparations are presented
in syringes and usually contain very small
volumes (from 0.5 ml to 5 ml).
An intraventricular injection is the introduction
of materials for diffusion throughout the
ventricular and subarachnoid space by means
of ventricular puncture (injection into the brain).
How do we prepare
Intrathecal preparations?
Methotrexate, Cytarabine and Hydrocortisone
are all used as intrathecal drugs.
Hydrocortisone is not licensed (has not been
approved) for this indication but is usually
given in conjunction with other drugs.
Only specific products from certain
manufacturers are licensed for intrathecal
administration.
Intrathecal chemotherapy is aseptically
prepared in the same way as any cytotoxic
drug, using specialised aseptic techniques and
personal protective equipment.
However a number of special precautions
must be in place when dealing with the
provision of an Intrathecal Chemotherapy
Service, from receiving a prescription into the
pharmacy through to delivery to the clinical
area for administration to the patient.
These special precautions have been put in
place following a number of patient deaths
from incorrect administration of chemotherapy
products intended for intravenous
administration (see detailed information on The
Intrathecal Register in the following section).
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Intrathecal Preparations
The Intrathecal Register
Why do we have a register?
The Department of Health introduced
guidelines for all NHS Trusts providing an
Intrathecal Chemotherapy Service (and also
guidelines for Trusts who do not normally
provide this service).
The guidelines were necessary to reduce and
prevent death and serious harm to patients
from the incorrect administration of certain
types and presentations of chemotherapy.
The major errors have been where vinca
alkaloids (vincristine, vinblastine, vindesine
and vinorelbine) were injected intrathecally
(via spinal or intraventricular injections)
instead of intravenously.
When injected intrathecally vinca alkaloids
cause paralysis usually followed by death.
The Government agreed a target to reduce
the number of deaths or paralysis of patients
by incorrect administration to zero by the
end of 2001.
The Department of Health have implemented
and updated guidelines and have set
minimum standards, which all NHS Trusts
must follow when providing an Intrathecal
Chemotherapy Service. This is available as a
Health Service Circular (HSC) and available
from www.dh.gov.uk
Who is on the register?
Anyone involved in the prescribing,
preparation, dispensing, delivery and
administration of intrathecal cytotoxic drugs
must be trained and assessed as competent
and entered on the Trust intrathecal register.
A record of staff activity should also be kept
and those who do not actively take part may
be removed from this register. They must
keep a minimum level of involvement with
intrathecal cytotoxic drugs in order to remain
on the register.
Staff are required to be certificated, with a date
expiring certificate. They must be re-trained
and re-assessed annually.
Key Facts when handling
and working with Intrathecal
cytotoxic preparations
Administration Timing
A designated pharmacist must check
that any IV drugs due that day have been
given before dispensing/handing over the
intrathecal drug for administration.
Important! Intrathecal chemotherapy must
always be issued at a different time from
intravenous chemotherapy.
Intravenous medicines should be given first
and then Intrathecal, ideally on a different day.
Ref: HSC 2008/001 Updated National
Guidelines on the safe administration of
Intrathecal chemotherapy
Included in these guidelines is the necessity
for all NHS Trusts to establish and maintain
a register which lists those members of staff
who have been trained and are competent to
provide an intrathecal service.
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Aseptic Processing
Action
Using the information from the Updated National Guidelines on the Safe Administration of
Intrathecal Chemotherapy and local standard operating procedures (SOPs) read the sections
on timing and issuing of drugs and make some notes below
Notes:
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Prevention of errors during production
Here are some important actions that must be implemented at each stage of the production
process in order to prevent mistakes and to keep patients safe.
Production Stage
Actions
Product
Segregation
To reduce the risk of errors associated with the incorrect administration
of intrathecal cytotoxic chemotherapy, procedures must be in place to
ensure that:
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requests for intrathecal cyctotoxics are on a designated intrathecal
prescription.
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during assembly, preparation and labelling, intrathecal preparations
are kept separate from all other cytotoxics
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packaging for transportation ensures that no other products are
packed in the same bags/containers
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storage is in designated lockable refrigerators or containers
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Aseptic Processing
Production Stage
Actions
Documentation
Intrathecal drugs are prescribed for individual patients on a designated
prescription by a doctor named on the intrathecal register.
The correct intrathecal worksheet should be selected.
On delivery, the drug must be handed directly to the administering
doctor and the chart signed by the delivering pharmacist or technician
and the administering doctor.
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Production Stage
Actions
Setup/Assembly
Assembly of ingredients and equipment for intrathecal products can
only be carried out by staff on the intrathecal register.
A 0.2 micron filter must be used to filter all intrathecal chemotherapy drugs
The starting material manufacturer to be used should be specified on
the worksheet.
The starting material should be checked by a person on the register to
ensure that it is suitable for intrathecal injection. Not all versions of the
same drug are suitable.
All ingredients must be preservative-free and suitable for intrathecal
administration.
Only two cytotoxic drugs have a licence for intrathecal administration:
Methotrexate 5mg in 2ml and Cytarabine 20mg in 1ml.
Hydrocortisone Sodium Succinate, a steroid, is also given intrathecally but
the available products are not licenced for this route of administration.
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Aseptic Processing
Production Stage
Actions
Checks
Intrathecal prescriptions are clinically checked and signed by a
designated pharmacist.
The drug doses should be checked to ensure that they are calculated
appropriately.
The diluents should be checked for compatibility and the correct volume
written up – intrathecal injections are usually small volumes (0.5 to 5ml).
The stability data and storage conditions should be clear on the
prepared label – usually a maximum of 24 hours due to high risk from
contamination.
The route of administration must be clear.
All other details on the label should be checked.
Reconciliation
The route of administration makes the product a very high risk.
Expiry of intrathecals is usually 24 hours, as the drug is preservative free.
Check the expiry of ingredients again in the isolator before
preparation/disposal.
Check again that the correct product has been used.
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Production Stage
Actions
Pass out finished
products
The original vial should be checked by a competent member of staff (i.e.
trained and on the Trust intrathecal register) before passing the syringe
out of the isolator.
The vial should be checked against the worksheet to ensure the drug
and concentration are correct.
The final volume of the prepared medicine should be checked against
the worksheet. Check also that it has been filtered through a 0.2 micron
filter (refer to local guidelines).
Packaging
Intrathecal chemotherapy must be packaged following the procedures
for cytotoxic preparations i.e. in sealed heavy-duty polythene bags with
yellow cytotoxic notice and protected from light when necessary.
Storage
Intrathecal chemotherapy drugs must be kept in a dedicated lockable
container/refrigerator between dispensing and issuing, and between
issuing and administration.
Intrathecal drugs should be transported and packed separately from any
other items.
They should be transported in a distinctive bag or container that is not
used for any other purpose.
They must be transported from the pharmacy by the administering
doctor or the pharmacy staff on the register of designated people.
The member of pharmacy staff should sign the release of the drugs and
sign to say that they have gone to the administering doctor or have been
locked in a designated container.
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Prevention of errors checklist
Here is a reminder of some of the important factors taken by all staff involved in the provision of
intrathecal chemotherapy in order to prevent mistakes and to keep patients safe.
The Register
All staff involved in an Intrathecal service must be on a register.
Risk assessment
Trusts must undertake regular risk assessment of the service they
provide, especially if they are high or low volume providers of intrathecal
chemotherapy.
Issue
Staff must be appropriately trained, competent and on the register to be
allowed to prescribe intrathecal chemotherapy
Intrathecal
drug chart
A specific Intrathecal chemotherapy drug chart or a specific intrathecal
section on a general chemotherapy chart must be used.
Abbreviations must not be used.
Checking
Only staff on the intrathecal register can perform checks involving the
prescribing, aseptic preparation dispensing, issuing and administration
of intrathecal chemotherapy.
Timing
Intrathecal chemotherapy should be issued at a different time from
drugs for intravenous therapy-preferably on a different day. Intravenous
drugs must be issued first.
Packaging
Intrathecal chemotherapy must be packed separately from all other
treatments for all other administration routes.
Labelling
Route of administration should be clear and printed in the largest font
size possible in bold e.g. FOR INTRATHECAL INJECTION
Negative labelling should be avoided.
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Storage
In the pharmacy department intrathecal chemotherapy should be kept in
a dedicated lockable refrigerator/container between preparation and issue.
On the wards it should be kept in a dedicated lockable refrigerator/
container between issue and administration.
Transportation
Transported separately from treatments for other administration routes.
Transported in a distinctive bag or container that is not used for any
other purpose.
Delivery
Only staff on the register can collect, deliver, issue and sign for
intrathecal chemotherapy.
If delivered from pharmacy it must be delivered by a pharmacist or
pharmacy technician on the register to the ward and issued directly to
the doctor administering the treatment, or delivered to and stored in a
designated container/refrigerator.
The member of pharmacy should sign the release of the drugs.
If collected from pharmacy it must be by the administering doctor on
the register.
Important Reading
Department
of Health
Health Service
Circular (HSC)
Ref: HSC 2008/001 Updated National Guidelines on the safe
administration of Intrathecal chemotherapy www.dh.gov.uk
Department of
Health Publication
Ref: An organisation with a memory, Chapter 2, Point 2.9 Case Studies
NPSA Rapid
Response Report
(RRR)
Ref: NPSA/2008/RRR004 Using Vinca alkaloid mini-bags
www.dh.gov.uk/en/Publicationsandstatistics
www.npsa.nhs.uk
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Aseptic Processing
Intrathecal Methotrexate Syringes
The following images show intrathecal Methotrexate syringes being prepared in an isolator.
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A number of 2 ml Methotrexate vials are needed to prepare the required quantity of syringes.
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The tops of the vials are swabbed with alcohol and allowed to dry.
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Using a filter to regulate the pressure in the vials the contents of the vials are drawn up into a
large syringe.
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Using a 0.2 micron filter to filter the Methotrexate solution, the required quantity of
Methotrexate is transferred from the larger syringe into a number of smaller syringes using a
luer lock transfer device.
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The syringes and vials will be checked before passing out of the isolator to be labelled and packaged.
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Risks
Risks to patients
Risk
Information and Actions
Prescription errors
Each prescription should be clinically checked by a pharmacist on the
intrathecal register for accuracy following local procedures.
Product
assembly errors
Intrathecal chemotherapy can only be dispensed using medicines
that are specifically licensed for intrathecal use. Check your local
Intrathecal Standard Operating Procedures for up to date drugs, drug
manufacturers and drug strengths that can be used.
Only chemotherapeutic drugs that have FOR INTRATHECAL USE
specified on the label should be used.
Microbial
contamination
The presence of micro-organisms in an aseptic product can have fatal
consequences.
All ingredients for intrathecal administration are preservative free which
means a higher risk of product contamination.
Use of a negative pressure Isolator provides less protection for
the product.
Leaks occurring in the isolator body, or in the glove or sleeve system,
may cause microbial contamination of a product.
Refer to Chapter 3 Basic Microbiology, for information on sources and
control of contamination. Refer to Chapter 6 Work Zones, for more
information on working in an isolator
Incorrect
Administration
– Route
Remember-Cytotoxic drugs may be fatal if administered by the
incorrect route.
Confusion over Intravenous/Intrathecal administration has lead to
paralysis and death of a number of patients worldwide.
Check your local standard operating procedures (SOPs)
See documents listed in Important Reading section (above)
Incorrect Patient
administration
Patients should be allowed to check the name, dose and route of
administration of the preparation against their drug chart if they wish to
minimise risk of administration to the wrong patient.
Administration area
A designated location for the administration of intrathecal cytotoxics
should be available-this should be a separate room.
No other chemotherapy should be administered or stored in this room.
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Aseptic Processing
Risk to products
Risk
Information and Actions
Incorrect product
reconstitution
It is of paramount importance that the correct drug, diluent and dosage
is prepared and that the worksheet instructions are followed.
All equipment must be suitable for purpose and available to staff.
See local SOPs for receipt and checking of intrathecal cytotoxic
prescriptions.
Use of Negative
Pressure Isolators
Negative pressure isolators operate with an internal pressure below that
of the room. This protects the user from any aerosols of drug generated
inside. However, if a leak occurs in the isolator body, or in the glove /
sleeve system, air may enter the isolator from the room. The risk of
producing a microbially contaminated product is therefore greater than
with a positive pressure isolator.
Leakage /damage
or defects
Leaks or cracks can occur as a result of inappropriate storage or as
a result of faulty equipment which has not been checked properly.
Products should be inspected before and after preparation, and before
issue to patient.
Particles
Products should be inspected for particles before and after preparation.
If particles are visible then the affected container(s) must be rejected
by attaching label with reject written on and separating it from any other
containers that are satisfactory.
Incorrect
transportation
and storage
The correct protocol for transportation and storage of intrathecal
cytotoxic preparations should be followed at all times.
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Risks to operators
Risk
Information and Actions
Contamination
A study to investigate the cytotoxic contamination of preparation areas
in simulated preparation scenarios has demonstrated significant
contamination occurs within the isolator.
Several scientific studies have shown that there may be high levels of
cytotoxic residues on the outside of vials from manufacturers.
Toxicity
Cytotoxics are:
Mutagenic – have ability to cause genetic mutation
Carcinogenic – have the ability to cause cancer
Teratogenic – have ability to cause physical defects in developing embryos
Operators have the potential for occupational exposure to toxic
substances, so safe handling and preparation techniques are required
at all times. Studies have shown that good working practices such as
those described in this manual significantly reduce the risk for operators.
Regular staff training is essential.
Equipment
Appropriate personal protection equipment (PPE) should be used at all times.
Isolators
Negative pressure isolators operate with an internal pressure below that
of the room. This protects the user from any aerosols of drug generated
inside. However, if a leak occurs in the isolator body, or in the glove
/ sleeve system, air may enter the isolator from the room. The risk of
producing a microbially contaminated product is therefore greater than
with a positive pressure isolator.
Gloves
Operators should make sure their gloves are intact at all times. This
means that you must check your gloves regularly. Operators should always
ensure they are wearing the correct gloves for the task and that they offer
appropriate protection from cytotoxic chemicals. Nitrile and Neoprene
gloves often offer more protection but users should always check
supplier information. Double gloving is recommended when preparing
chemotherapy i.e. operator is wearing gloves inside the isolator gloves.
For further information on suitable glove material see local SOPs, MARCH
guidelines on PPE Selection and Use at www.marchguidelines.com, HSE
Information Sheet MISC615 at www.hse.gov.uk
Chapter 20: Intrathecal Preparations
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Aseptic Processing
Risks to operators (continued)
Risk
Information and Actions
Needlestick injury
This is any injury from a needle. Needlestick
injuries can be harmful to the operator and
also to patients as there is an increased risk
of contamination.
Correct operating procedures and practices
should be followed at all times to avoid the
incidence of needlestick injuries. See your
local operating procedures for action to take in the event of a needlestick
injury. This is particularly important when handling chemotherapy.
Needlestick injuries should be reported and documented.
When re-sheathing needle use “drop on” technique to apply needle cap.
Upper limb
disorders; ULDs
(Repetitive strain
injuries)
This is caused by continued repetitive movements. To reduce the risk of harm
operators should take adequate short breaks and reduce resistance and force
employed during manipulations. Rotation of activities can also help.
For more information on ULDs visit http://www.hse.gov.uk
Ref: HSG60 Upper Limb Disorders in the workplace
Cuts
Operators are at risk of cuts from glass shards or ampoule tops. This poses
a risk not only to the operator, but also to the product as it increases the
chances of contamination.
Cleaning
Operators often work with highly toxic substances every day, so it’s vital to have
an appropriate cleaning schedule in place for both before and after preparation.
It is important that appropriate Personal Protection Equipment (PPE) is
worn for cleaning areas where cytotoxics are handled.
Occupational
Exposure
Safe handling of cytotoxic drugs should not cause any problems with the
health of staff.
However in some hospitals additional steps are taken by the Pharmacy
Department and the Occupational Health Department to monitor staff
health. All members of staff are given a medical questionnaire and/or
routine medical on employment. This determines the basic level of health
of all new staff members.
Details of any needlestick injuries and any spillages should be documented
both on a handling record form and on a Trust Incident Record.
MARCH Guidelines
Read MARCH Guidelines for further information on Management and
Awareness of Risks of Cytotoxic Handling
www.marchguidelines.com
Chapter 19
Cytotoxics
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For more detailed information on handling cytotoxic compounds please refer
to details in this chapter.
Chapter 20: Intrathecal Preparations
Chapter 20
Intrathecal Preparations
Questions
Q1
What information must be kept on the Trust Intrathecal Register?
Why is this information important?
Q2
Why are preservatives not allowed when producing intrathecal drugs?
What effect does this have on the preparations shelf life?
Chapter 20: Intrathecal Preparations
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Aseptic Processing
Q3
List six of the checks that should be carried out when producing intrathecal preparations
1.
2.
3.
4.
5.
6.
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Intrathecal Preparations
Q4
How should intrathecal chemotherapy preparations be stored between:
a. dispensing and issuing
b. issuing and administration
(2)
Q5
Explain why the timing and order of intrathecal chemotherapy is so important.
Give some examples of the actions taken to prevent errors of administration
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Aseptic Processing
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Chapter 20: Intrathecal Preparations