2IntroductionThe handling, preparation, administration and disposal of cytotoxic agents may constitute an occupational hazard. While it has not been established that handling cytotoxic agents is consistently linked with adverse health risks, handlers must be aware of the possibility. The implementation of suitable safety precautions reduces the possibility of adverse health effects to hospital employees
3Chemotherapy Preparation Admixture – leave to the professionalsAlways follow instructions provided from the manufacturermixing solutions and amountlight and temperature requirementsequipment requirements – glass syringesProtect self and environment – gloves, goggle, gown; always use a BSC to prepare/mix
4Pre-Administration Procedures Chemotherapy orders require a signature by an Attending Physician prior to administration.The patient's current height and weight must be recorded on the patient's chart.Body Surface Area (BSA) must be calculated on all patients.BSA = ht (cm) X wt (kg)3600
5Pre-Administration Procedures An Absolute Neutrophil Count (ANC) must be verified and documented on all patients by an RN.ANC = WBC X Neutrophil (or Segmenters)The patient's labs are reviewed, documented, and approved by the Attending Physicians.Verify the orders for any chemotherapy prerequisites (i.e. hydration, pre-medications, home medications, audiogram, etc.)Verify the patient's treatment plan as specific by the ordering physician or by protocol.Chemotherapy dose ordered must be within ten percent of the calculated dose unless otherwise noted by the physician.
6Cannulation Procedure: Careful choice of the vein into which cannula to be inserted is important and the first step in the avoidance of extravasation.The smallest size plastic cannula should be used, especially for irritant and vesicant drugs.All peripheral cannulas should be sited in a long straight vein. Avoid bony prominences and joints, such as the antecubital fossa and inner wrist.When the cannula is in situ a free flow of saline should be ensured.
7Cannulation Procedure: Cytotoxic Drugs must be administered into an existing cannula ( with the exception of patients receiving daily chemotherapy where the cannula is placed specifically for this purpose- usually for non vesicant drugs such as 5 FU or fludarabine).Dilatation techniques including warm water and heat are to be encouraged prior to siting a cannula in a patient with poor venous venous access.When a patient has a poor venous access, assessment should be made and their consultant should be notified so that consideration can be given to the placement of a long term intraveneous catheter e.g. P.I.C.C. line or tunelled central lines.
8Cannulation Procedure: When anti-emetics , such as metoclopromide are required intraveneously, they should be dministered last, can cause pain on injection, causing uncertainty of vein patency.Check vein patency. All vesicant drugs should be administerd first ( otherwise greater pressure is placed on vein walls, increasing the risk of extravasation.Vesicant drugs must be administered into a running infusion of sodium chloride 0.9% or glucose 5% to avoid high drug concentrations.
9Do’s and Don’t’s on Peripheral IV Insertion Use the most distal vein firstIf veins are small – dilate using warmth, gravity, gentle tapAvoid sites distal to recent venipuncturesIf vein has blown – do not re-stick it againUse the smallest gauge needle possibleAdvance the needle completely into the vein and anchor securely, leaving site visibleCaution patient to watch
10Do’s and Don’t’s on Peripheral IV Insertion Avoid areas of impaired lymphatic drainage, phlebitis, invading neoplasm, hematomas, sclerosed areas, impaired circulationDo not use lower extremities if possibleAvoid sites that have been irradiatedUse a new site for chemotherapy, especially for vesicants (unless VAD)Avoid sites of flexionAlternate arms whenever possible
11Types of infusion for cytotoxic agents Piggyback, or short-term, infusion1. Do not pinch the intravenous (IV) catheter to determine blood return and patency. Pinching causes a dramatic change in pressure that may rupture a vein. To check for blood return and IV patency:Use a suction check: Gently aspirate the line, using a syringe at the y-site closest to the patient while clamping or pinching off fluid from the bag.Use a gravity check: Remove the bag and tubing from the administration control device (the pump) and gently lower it to a point below the patient’s IV site.
12Types of infusion for cytotoxic agents Insert the connecting tubing into the appropriate primary tubing y-site; follow the drug manufacturer’s guidelines. Use a Luer-lock connection or some other locking device to prevent disconnection.Initiate flow rate in accordance with the physician’s orders or adjust the rate to administer the cytotoxic agent over a specified time.
13Types of infusion for cytotoxic agents If administering a vesicant in a peripheral vein:Administer the agent in a method that will decrease pressure on veins. For this reason, avoid the use of IV pumps.Monitor the patient frequently for extravasation during the infusion--ideally, every 5 min.Avoid hanging vesicant agents for extended periods, if possible.Upon completion of the infusion, check for vein patency; use a sterile, noncytotoxic IV solution to flush the line.
14Types of infusion for cytotoxic agents Continuous, or long-term, infusionCheck for blood return and IV patency; see guidelines for piggyback infusion.Connect the chemotherapeutic agent directly to the IV catheter or as a secondary infusion through a compatible maintenance solution.Secure the connection site by using a Luer-lock connection or some other locking device.Monitor the IV site throughout the infusion.
15Types of infusion for cytotoxic agents Check for blood return periodically during the infusion.If administering a vesicant:Do not use a peripheral IV for continuous vesicant administration.Use a central venous access catheter (CVC) or implanted access device to administer any vesicant infusion for longer than min.Check for blood return and patency periodically during infusion.Upon completion of the infusion, check for vein patency; use sterile, noncytotoxic IV solution to flush the line.
16Types of infusion for cytotoxic agents IV pushUse the push-pull technique to administer a vesicant to children: Push a very small amount, pull back on the syringe to obtain a blood return, and then push a small amount again; continue until the total amount has been administered.
17Types of infusion for cytotoxic agents Free-flow method.Check for IV patency by gently aspirating the line at the y-site closest to the patient.Allow IV solution to flow freely.Slowly administer the agent by means of an IV push, using a free-flowing flush solution. Unless otherwise indicated, administer the agent at 1-2 cubic centimeter (cc) per min. If administering a vesicant, gently aspirate the line every 2-3 cc to verify blood return.Upon completion of the infusion, check for vein patency; use sterile, noncytotoxic IV solution to flush the line.
18Types of infusion for cytotoxic agents Direct-push method:Establish patent IV access; use a syringe filled with sterile IV solution to flush the newly accessed line.Verify blood return and venous patency by aspirating the line gently.Detach the flush syringe; while maintaining sterile technique, attach the syringe containing the cytotoxic agent. Minimize blood loss.Slowly administer the agent; every 1-2 cc, monitor venous patency by using the syringe of cytotoxic agent to aspirate the line gently.
19Administration of Cytotoxic Agents via CVCs CVCs include percutaneous subclavian catheters, tunneled subclavian catheters, and peripherally inserted central catheters. (A midline catheter is considered a peripheral line because it ends in the middle of the upper arm.)Verify that the type of catheter and its placement are correct.Inspect exit site for evidence of leakage. Inspect ipsilateral chest for signs of venous thrombosis.Inspect exit site for evidence of erythema, swelling,drainage, etc.
20Administration of Cytotoxic Agents via CVCs Aspirate the line to ensure blood return. If blood return is not evident:Flush the catheter with saline, gently using the push-pull method. Avoid use of syringes less than 3 cc in size.Reposition the patient as appropriate. Ask the patient to cough.Explain to the patient why delaying therapy is necessary. Though the patient may indicate that not obtaining a blood return from his or her catheter is common and tells you to proceed, do not administer cytotoxic therapy. Remember that extravasation of a cytotoxic agent may have serious consequences.Obtain a physician’s order for a declotting procedureBefore administering a cytotoxic agent, use x-rays or dye studies to confirm proper CVC placement.
21Implanted portsImplanted ports are available that allow venous access, peritoneal access, arterial access, and epidural access. Ascertain which type is being used. Some patients have more than one type.Assess initial line placement by using the results of x-ray or fluoroscopic dye studies.Choose a noncoring, 90-degree needle whose length is appropriate to the:Depth of the port-Size of the patient (i.e., the amount of subcutaneous tissue or fat located above the port)Prepare the patient’s skin according to institution policy.Access the port, ensuring proper placement of the needle in the reservoir.
22Implanted portsEstablish blood return and patency for venous or arterial ports. Blood return is not expected with epidural or peritoneal access devices.Inspect the needle insertion site for needle dislodgement, leakage of IV fluid, drainage, or edema.Examine the ipsilateral chest for venous thrombosis.Apply an occlusive dressing to stabilize the needle. The dressing should be transparent, to allow a clear view of the insertion site. Experts disagree about other characteristics that are desirable.
23Oral Cytotoxic Drug Administration Care should be taken so that tablets and capsules are tipped from their container directly into a disposable medication cup.After the patient has taken the tablet/capsule, also without handling it, the medication cup should be discarded as cytotoxic waste.Many tablets and capsules may be dispersed in water, and the pharmacy will advise accordingly. It is best to contact the pharmacy if it is necessary to use oral cytotoxic agents to produce a mixture.After administration, gloves should be discarded as cytotoxic waste, and hands washed.
24Topical Cytotoxic Drug Administration WASH HANDS and put on PROTECTIVE CLOTHING(gown, protective glasses, respirator mask and 2 pairs of gloves)Apply a film of medication (use a disposable spatula)Dispose of gloves and spatula as cytotoxic wasteClean and launder other protective clothingThe patient should be advised not to wear clothing that may come in contact with the treated area, and to be careful not to accidentally touch the medication
26Side Effects of Chemotherapy a. MyelosuppressionNeutropeniaAnemiaThrombocytopeniab. GI and Mucosal Side EffectsNausea and VomitingDiarrheaMucositisAnorexiaConstipationPerirectal cellulitisAlopeciaFatigueCardiac toxicityPulmonary toxicityHemorrhagic cystitisHepatotoxicityNephrotoxicityNeurotoxicityAlterations in sexuality and reproductive functionCutaneous ReactionsAcral erythemaHyperpigmentationInflammation of keratosesNail changesNeutrophilic eccrine hydradenitisRadiation enhancementRadiation recallHand-and-foot syndromeOcular ToxicitySecondary Malignancies
27Classification of Chemotherapy Drug VESICANT – CAPABLE OF PRODUCING BLISTERSDactinomycinDoxorubicinEpirubicinIdarubicinMitomycinVinblastineVincristineVinorelbine
28Classification of Chemotherapy Drug NONVESICANT (Irritant)- CAPABLE OF PRODUCING PERI-VENOUS PAIN AT THE SITE OF INJECTION OR LONG THE VEIN INJECTION OR INFUSIONCisplatinDacarbazineDocetaxelEtoposideMesna (undiluted)MitoxantronePaclitaxelTeniposide
29Classification of Chemotherapy Drug NONVESICANT (None) AsparaginaseBCGBleomycinCarboplatinClodronateCyclophosphamideCytarabineFludarabineFluorouracilGemcitabineGoserelinIfosfamideInterferonIrinotecanLeucovorinLeuprolideMercaptopurineMesna (diluted)MethotrexateOcreotideOxaliplatinPamidronateRaltitrexedRituximab
30Vasospasms Symptoms pain at infusion site slowing of infusion rate loss of blood return in the lineManagementslow or stop infusionapply heat or warmthelevate extremity on a pillowre-start again at a later time, very slowlyIF NOT SURE – Start a new line
31Flare Reaction Painless Local reaction Along the Vein or Near the Intact Injection Symptomsblotches or streaks (histamine release phenomenon),symptoms usually subside with or without treatment min after the infusion is stopped, although they may last for 1-2 hours and rarely more than 24 hoursManagementStop chemotherapy and re-start laterRun IV fluidsIF NOT SURE – Start a new line
32Irritation no tissue necrosis or ulceration; classify a drug as irritant if it causes phlebitis and/or sclerosis of veins at intact injection site or along the veinSymptomsaching and tightness along the veinfull length of the vein may be reddened or darkenedblood return is usually present but may not beManagement:Stop chemotherapy; slow down IV rateApply heat and elevate extremitySlowly re-start chemotherapyIF NOT SURE – Start a new line
34Vesicants blistering, local or extensive tissue necrosis with or without ulceration Symptomspain, burning, and tinglingappearance of a bleb or erythema at IV site or along the vesselLoss of blood returnDecreased IV flow rate or increased resistance during IV push
36Procedure for the extravasation of a VESICANT At the time of extravasation:STOP the drug injection IMMEDIATELY.STOP the IV Infusion.Immediately aspirate and discard any residual drug and blood in the intravenous tubing, needle and suspected infiltration site. If applicable, instill the ordered antidote intravenously and then remove the IV catheter/needle.If unable to aspirate the residual drug from the intravenous tubing, remove the IV catheter/needle. Avoid excess pressure at the site.
37Procedure for the extravasation of a VESICANT Inject the antidote SC clockwise into the infiltrated area using G25 needle. Change and discard needle with each new injection. The number of injection needed depends upon the extent of the exravasated area.Avoid applying pressure to the suspected infiltration sites.Apply topical ointment as needed, if ordered.Elevate the arm.Apply warm or called compress as ordered.
38Procedure for the extravasation of a VESICANT Observe patient regularly for pain, erythema, induration, &/or necrosis, up to 14 days after the incident.Document interventions in the patient medical record. Include the following:Date, timePhysician notifiedDrug administered, amount of drug extravasatedCondition of patientAppearance of siteFollow-up measures
39Follow-up:Patients should be closely followed after suspected extravasation so that appropriate further action can be taken. Some extravasations, although painful, may heal without surgical intervention. This is particularly true of vinca alkaloids. Others, particularly those due to doxorubicin, other DNA binders and mechlorethamine, may recycle locally and produce progressive necrosis and slough requiring surgical intervention. Areas of extensive blistering or ulceration, progressive induration and erythema, or persistent severe pain, are indications for surgical assessment and possible excision of the injured tissue. Surgical intervention should not be delayed for long in the presence of progressive local injury. Analgesics should be given, as required, for pain.
40Assessment of Extravasation Versus Other Reactions Assessment ParameterExtravasationSpasm/Irritation of the VeinFlare ReactionImmediate Manifestations of ExtravasationDelayed Manifestations of ExtravasationPainSevere pain or burning that lasts minutes or hours and eventually subsides; usually occurs while the drug is being given and around the needle siteHours - 48Aching and tightness along the veinNo pain
41Assessment of Extravasation Versus Other Reactions Assessment ParameterExtravasationSpasm/Irritation of the VeinFlare ReactionImmediate Manifestations of ExtravasationDelayed Manifestations of ExtravasationRednessBlotchy redness around the needle site; it is not always present at time of extravasationHours - monthsThe full length of the vein may be reddened or darkenedImmediate blotches or streaks along the vein, which usually subside within 30 minutes with or without treatmentUlcerationDevelops insidiously; usually occurs hours laterHours – monthsNot usually
42Assessment of Extravasation Versus Other Reactions Assessment ParameterExtravasationSpasm/Irritation of the VeinFlare ReactionImmediate Manifestations of ExtravasationDelayed Manifestations of ExtravasationSwellingSevere swelling; usually occurs immediatelyHours – 48Not likelyNot likely; wheals may appear along the vein lineBlood returnInability to obtain blood returnGood blood return during drug administrationUsuallyOtherChange in the quality of infusionLocal tingling and sensory deficitsPossibly resistance felt on injectionUrticaria
43Doxorubicin and epirubicin Are particularly likely to cause a local wheal or red streaking (a histamine release phenomenon) which will subside but may take thirty minutes or more after the injection is stopped. Hydrocortisone injected into the IV line may hasten clearing of the reaction, and requires a physician's order. The injection may then be cautiously resumed.
44Thrombosis or Sclerosis Of veins may occur due to the local effect of chemotherapeutic agents on the endothelium. These can be managed conservatively with warm or cold compresses to the area plus an analgesic for pain, if required.
45Guidelines for the use of an antidote It is difficult to be certain that injection of antidotes into the area of extravasation is of benefit and reports are conflicting. Most small extravasations do not result in serious problems without injection of antidotes, so that injection of specific antidotes should likely be restricted to larger extravasations (>1-2 mL).
46Recommended Extravasation Antidotes Class / Specific AgentsLocal Antidote RecommendedAlkylating AgentsCisplatinMechlorehtamine HCL1/6 or 1/3 M sodium thiosulfateMitomycin-CDimethylsulfoxide 50% - 99% (w/v) solutionDNA intercalatorsDoxorubicin HCLDaunorubicin HCLAmsacrineCold CompressDimethylsulfoxide 50%-99% (w/v) solutionVinca alkaloidsVinblastineVincristineVinorelbineWarm compress, HyaluronidaseEpipodophyllotoxinsEtoposideTeniposideTaxanesIce compress, Hyaluronidase
47Target Therapy Never give as a bolus Slowly infuse over at least 30 minutesHave crash cart available (especially at the first time)Monitor vital signs (BP, P, RR and T) before, at 15 – 30 minutes into the infusion) and after the infusion; PRN before patient leaves the clinic
48Antineoplastic Agents: Who might be exposed to antineoplastic agents in hospitals? Hospital staff who work in areas where solutions of these agents (including agents prepared from crushing or breaking tablets) are prepared, administered, and disposed ofPharmacy personnel who prepare the solutionsHospital staff in oncology departments and infusion units who administer these solutionsHospital staff who dispose of feces, urine, etc. of patients treated with these agentsHospital staff who handle bed clothing of patients treated with these agents
49Antineoplastic:When are workers most likely to be exposed to antineoplastic agents in hospitals? by breathing themingesting them unintentionally, orhaving skin contact with them during the following procedures:Counting tablets poured from multidose bottlesCrushing or breaking tablets to be made into liquid preparations Preparing solutionsHandling solutionsAdministering solutionsDisposing of solutionsDisposing of used intravenous (IV) sets or other drug administration equipmentCleaning spillsDisposing of feces, urine, bed clothing, etc. of patients treated with these agentsHandling soiled bed clothing of patients treated with these agents
50Antineoplastic: How can I protect myself from exposure to antineoplastic agents? Prepare agents in a centralized area restricted to authorized personnel only.Prepare agents in a biological safety cabinet (BSC)—Class II Type B, or Class III. (A BSC with an outside exhaust must be vented away from outside fresh-air intake units.)Use syringes and IV sets with Luer-Lock-type fittings for preparing and administering these agents. Place these syringes and needles in chemotherapy waste containers designed to protect workers from injuries.Consider using closed-system drug transfer devices and needle less systems.
51Antineoplastic: How can I protect myself from exposure to antineoplastic agents? Avoid skin contact. Use a disposable gown made of a lint-free, low-permeability fabric. The gown should have a closed front, long sleeves, and elastic or knit closed cuffs. Use good quality, powder-free, disposable gloves that cover the gownUse two pairs of gloves.Change gloves periodically.Wear a plastic face shield or splash goggles to avoid contact of eyes, nose, or mouth with these agents whenever splashes, sprays, or aerosols are generated.Remove protective clothing carefully to avoid spreading contamination.
52Waste DisposalAll waste from the administration of cytotoxic drugs (IV tubing, bags, vials, etc.) will be placed in trash cans with cytotoxic waste liners or cytotoxic waste receptacles.Needles and syringes will be disposed of in the needle receptacles or in hard plastic cytotoxic waste receptacles.Patient care staff will place a cytotoxic waste receptacle in the room when a patient begins a course of chemotherapy administration.Housekeeping personnel will then change the trash can liners and keep the appropriate liners in place until the door tag has been removed. Each unit will determine its needs for special waste containers to be maintained at strategic areas.Any cytotoxic drug not administered to patients due to excess or contamination will be returned to Pharmacy for disposal.Only empty bags can be placed in the disposal containers.