Chapter 20 Intrathecal Preparations By the end of this chapter, you will be able to: l Describe the specific risks with intrathecal cytotoxic products l List five checks that need to be carried out on Intrathecal products l Explain the transportation and storage methods of Intrathecal products l 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. Chapter 20: Intrathecal Preparations 1
Aseptic Processing What is an intrathecal injection and why is it so special? 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 What are Intrathecal chemotherapy drugs? Intrathecal products include both intrathecal and intraventricular preparations. 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. 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). 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. Indications for Intrathecal preparations Leukaemia, lymphoma, and tumour cells can be found in the cerebro-spinal fluid. 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. How are Intrathecal preparations administered? 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). How do we prepare Intrathecal preparations? 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). 2 Chapter 20: Intrathecal Preparations
Chapter 20 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 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. 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. Chapter 20: Intrathecal Preparations 3
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: 4 Chapter 20: Intrathecal Preparations
Chapter 20 Intrathecal Preparations 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 Product Segregation Actions To reduce the risk of errors associated with the incorrect administration of intrathecal cytotoxic chemotherapy, procedures must be in place to ensure that: l requests for intrathecal cyctotoxics are on a designated intrathecal prescription. l during assembly, preparation and labelling, intrathecal preparations are kept separate from all other cytotoxics l packaging for transportation ensures that no other products are packed in the same bags/containers l storage is in designated lockable refrigerators or containers Chapter 20: Intrathecal Preparations 5
Aseptic Processing Production Stage Documentation Actions 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. 6 Chapter 20: Intrathecal Preparations
Chapter 20 Intrathecal Preparations Production Stage Setup/Assembly Actions 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. Chapter 20: Intrathecal Preparations 7
Aseptic Processing Production Stage Checks Actions 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. Reconciliation All other details on the label should be checked. 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. 8 Chapter 20: Intrathecal Preparations
Chapter 20 Intrathecal Preparations Production Stage Pass out finished products Actions 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. Packaging 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). 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. Chapter 20: Intrathecal Preparations 9
Aseptic Processing 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 Risk assessment Issue Intrathecal drug chart Checking Timing Packaging All staff involved in an Intrathecal service must be on a register. Trusts must undertake regular risk assessment of the service they provide, especially if they are high or low volume providers of intrathecal chemotherapy. Staff must be appropriately trained, competent and on the register to be allowed to prescribe intrathecal chemotherapy A specific Intrathecal chemotherapy drug chart or a specific intrathecal section on a general chemotherapy chart must be used. Abbreviations must not be used. Only staff on the intrathecal register can perform checks involving the prescribing, aseptic preparation dispensing, issuing and administration of intrathecal chemotherapy. 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. 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. 10 Chapter 20: Intrathecal Preparations
Chapter 20 Intrathecal Preparations Storage Transportation 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. 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) Department of Health Publication NPSA Rapid Response Report (RRR) Ref: HSC 2008/001 Updated National Guidelines on the safe administration of Intrathecal chemotherapy www.dh.gov.uk Ref: An organisation with a memory, Chapter 2, Point 2.9 Case Studies www.dh.gov.uk/en/publicationsandstatistics Ref: NPSA/2008/RRR004 Using Vinca alkaloid mini-bags www.npsa.nhs.uk Chapter 20: Intrathecal Preparations 11
Aseptic Processing Intrathecal Methotrexate Syringes The following images show intrathecal Methotrexate syringes being prepared in an isolator. l A number of 2 ml Methotrexate vials are needed to prepare the required quantity of syringes. l The tops of the vials are swabbed with alcohol and allowed to dry. l Using a filter to regulate the pressure in the vials the contents of the vials are drawn up into a large syringe. l 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. l The syringes and vials will be checked before passing out of the isolator to be labelled and packaged. 12 Chapter 20: Intrathecal Preparations
Chapter 20 Intrathecal Preparations Risks Risks to patients Risk Prescription errors Product assembly errors Microbial contamination Incorrect Administration Route Incorrect Patient administration Administration area Information and Actions Each prescription should be clinically checked by a pharmacist on the intrathecal register for accuracy following local procedures. 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. 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 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) 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. 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. Chapter 20: Intrathecal Preparations 13
Aseptic Processing Risk to products Risk Incorrect product reconstitution Use of Negative Pressure Isolators Leakage /damage or defects Particles Incorrect transportation and storage Information and Actions 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. 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. 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. 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. The correct protocol for transportation and storage of intrathecal cytotoxic preparations should be followed at all times. 14 Chapter 20: Intrathecal Preparations
Chapter 20 Intrathecal Preparations Risks to operators Risk Contamination Toxicity Equipment Isolators Gloves Information and Actions 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. 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. Appropriate personal protection equipment (PPE) should be used at all times. 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. 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 15
Aseptic Processing Risks to operators (continued) Risk Needlestick injury Upper limb disorders; ULDs (Repetitive strain injuries) Cuts Cleaning Occupational Exposure MARCH Guidelines Chapter 19 Cytotoxics Information and Actions 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. 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 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. 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. 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. Read MARCH Guidelines for further information on Management and Awareness of Risks of Cytotoxic Handling www.marchguidelines.com For more detailed information on handling cytotoxic compounds please refer to details in this chapter. 16 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 17
Aseptic Processing 1. Q3 List six of the checks that should be carried out when producing intrathecal preparations 2. 3. 4. 5. 6. 18 Chapter 20: Intrathecal Preparations
Chapter 20 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 Chapter 20: Intrathecal Preparations 19
Aseptic Processing 20 Chapter 20: Intrathecal Preparations