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Brian was diagnosed with stage three, diffuse large B- cell lymphoma, which is the commonest type of Non- Hodgkins Lymphoma Dotan, Aggarwal and Smith 2010. To treat diffuse large B- cell lymphoma effectively, a combination regime is usually used (Flowers, Sinha & Vose 2010). The most widely used combination regime used in previous years was the CHOP regime which includes cyclophosphamide, doxorubicin, vincristine and prednisolone (Coiffier et al 2010). However in more recent years the R-CHOP regime seems to have become more popular as a front line therapy, due to emerging evidence that the rituximab given at the begging of the CHOP regime is more effective against B- cell lymphoma than CHOP alone (Wöhrer et al 2004, Coiffier et al 2002). Consequently R-CHOP is currently considered the gold standard ACDT regime for diffuse Large B- cell NHL(Coiffier et al 2007), and is recommended for use by NICE (2003). Brian was put on the R-CHOP regime for eight cycles and he attended the unit every three weeks.
Chemotherapy regimens are designed the way they are by looking at the individual cancer at a cellular level, and deciding where and how it will be most easily attacked. Each ACDT drug works on the cell cycle in a different way and it is important to understand how it works at a cellular level to be able to kill as many of the specific cancerous cells as possible. Therefore a combination of different drugs is used as it is likely to kill more cells than a single agent alone (Shah & Schwartz 2001).
The first drug in the R-CHOP regime is classed a monoclonial antibody, specific for the CD20 antigen on B- lymphocytes (Cang et al 2012). The drug Rituximab attaches itself to the antigen CD20 and induces apoptosis (Jaglowski et al 2010). Rituximab has been found to be very effective against Large B- cell NHL's mainly due to the CD20 antigen being present on 95% of their cells (Boye 2003). Rituximab is therefore very specific in the way it acts, and because it only binds itself to the CD20 antigen which is only present on B cells, there are no ill effects on normal cells in the body (Dotan, Aggarwal and Smith 2010). Never the less, not all drugs in the regime are so specific.
Cyclophosphamide, is unlike rituximab as it is less specific in the cells that it targets. Cyclophosphamide is known as an alkylating agent (Chu & DeVita 2013), and works by damaging the Deoxyribonucleic acid (DNA), by reacting with its proteins which make up the double helix structure (Prendergast & Jaffee 2007). Hence if the DNA is damaged, cells will not be able to divide and may die. Cyclophosphamide can work at anytime during the cell cycle, and is known as non cell specific (Chang 2006). However because cyclophosphamide is less specific, it can also affect normal cells, and this can sometimes cause unwanted side effects.
Doxorubicin the next drug in the regime also interacts with DNA and is non- cycle specific (Skeel 2003). Doxorubicin is an anthracycline antibiotic (Perry 2008). It specifically inhibits the action of the enzyme topoisomerase II (Kik 2009), and prevents the DNA helix from being released, preventing replication of the DNA strand. If the DNA cannot replicate, cell division is halted resulting in apoptosis (Yokochi & Robertson 2004). Safa et al (2010) suggests that Doxorubicin induces the binding of DNA to the p53 gene, inducing apoptosis. However there are contradictory reports regarding this link (Gariboldi et al 2003), and researchers are still working to find out the full extent on how anthracyclines interfere with DNA.
Vincristine, unlike the previous drugs I have discussed is cell cycle specific (Morgan 2003). It is known as a plant alkaloid and it causes cancer cells to arrest in the M (mitotic) stage of the cell cycle. Vincristine is found to inhibit mitosis by preventing the microtubules from forming spindles across the centre of the nucleus in metaphase, and thus halting cell division and possibly causing apoptosis (Burke, Wilkes and Ingwersen 2001). Vincristine therefore slows down the growth of cancer cells by stopping their rapid cell division.
The final drug in the R-CHOP regime is prednisolone. Brian received 5 days worth to take home after each cycle, and was instructed to take 100mg a day. Prednislone is a steroid, and it is thought that alongside the R-CHOP regime, it produces ACDT effects by inhibiting anti inflammatory agents in the body, which have been involved in the growth of cancers (Rayburn et al 2009). Nevertheless, the full action of prednisolone at a cellular level is still greatly unknown.
Brian' s R-CHOP chemotherapy is given every 3 weeks in cycles. This means during Brian's rest periods, his body will have time to rebuild his normal healthy cells. However in allowing some of the healthy cells to grow back, we are allowing some of the cancerous cells to grow back. Therefore another cycle of chemotherapy is given to kill another fraction of cancerous cells in Brian's body. Brian is intended to complete a total of 8 cycles, and the hope is at the end of each cycle we see a reduction in the number of cancerous cells, and finally by the end of the eighth cycle we hope to have killed all cancerous cells. This is why chemotherapy is given in cycles. It is known as the cell kill hypothesis (Skipper et al 1965). Although this is an old hypothesis it is still relevant today.
There are several ways in which chemotherapy drugs can be administered. The most common routes of administration are orally, intravenously and subcutaneously. However there are several other ways such as intramusculy, intrathecally and topical. The mode of administration is only determined through rigorous testing and clinical trials. It is extremely important that ACDT's are given the correct route, as drugs given the wrong route can cause catastrophic consequences. As reported by the National Patients Safety Agency (2007).
However there are policies and guidance that exist to prevent the associated risks of incidences occurring (Department of Health 2008; NGAG 2009), and in addition guidance for reporting a patient's death (NCEPOD 2008). To prevent error chemotherapy is always checked by two chemotherapy trained nurses before administration. Nurses checking and administering chemotherapy should have a thorough knowledge of the Guidance for the Administration of ACDT's, and also be familiar with the local medicines policy in their particular area (NMC 2008b).
In relation to Brian's ACDT regime, his chemotherapy drugs are all given intravenously through a peripheral cannula. However the R-CHOP regime can also be given through a PICC line or central line. There are advantages and disadvantages to having chemotherapy through a peripheral cannula. The main advantage of a cannula is that they are easily inserted, and they can be removed after treatment (Royal College of Nursing 2005). However there are quite a few major disadvantages, such as chemotherapy becoming irritant to the veins, and making it increasingly more difficult to cannulate (Summerhayes and Daniels 2003). However the biggest risk is extravasation.
To prevent the risk of an extravasation chemotherapy nurses are taught to cannulate in a particular way, to limit the chances of an extravasation from occurring. Careful assessment of the most appropriate vein for cannulation should be sought before insertion. Veins near a joint such as the antecubital fossa should be avoided to prevent the chances of the cannula becoming dislodged (Dougherty and Watson 2008). Veins in the forearm are preferable due to the soft tissue in the arm. A new cannula should be inserted before starting any chemotherapy regime such as R-CHOP, especially if the regime contains vesicant drugs (Hadway 2007).
Other aspects to consider when cannulating a patient such as Brian are what size cannula to use. To abide by my local trust policy (NHS TRUST POLICY- name withheld 2010), I cannulate using a small non ported cannula. However there is some controversy on whether small gauge needles are better than large gauge needles in the administration of ACDT's. Some believe that large bore needles provide more rapid access to general circulation and decrease the potential for vein irritation (Burke, Wilkes and Ingwersen 2001). On the other hand smaller cannulas are believed to be less likely to cause vein perforation, and provide greater blood flow around the tip of the cannula, allowing for greater dilution (Dougherty 2008). Accordingly the majority of trusts use the smallest cannula in the largest vein possible.
Once a cannula is in place it is important that it is fixed securely in place with a clear film dressing so that the cannula cannot move but you can easily see the cannula insertion site for any signs of extravasation. When observing a cannula sight you should observe the sight for swelling, leakage, redness and absence of blood return. When Brian is receiving his R-CHOP, I make sure that he is aware that he should report any pain, burning, stinging or discomfort that he may feel around the site, especially when receiving doxorubicin and vincristine as these are vesicants. Never the less, there are other conditions such as flare reactions that may resemble an extravasation. Therefore it is important that full careful assessments are done.
If an extravasation is suspected the early detection and treatment is vital to minimize any damage. Nonetheless, damage of the extravasated drug may only become apparent one to four weeks following the incident (European Oncology Nursing Society 2007). Therefore it is important that nursing staff abide the guidelines set by their individual trust policy on how to minimize the risk of an extravasation occurring in their area. The manual for cancer services (Department of Health 2004) now requires every area administering chemotherapy to have an agreed extravasation policy. Never the less, policies may vary.
My trust policy outlines several ways that an extravasation can be minimized when administering an ACDT. One crucial way is by administering the most vesicant drug first when there is more than one agent like in the R-CHOP regime. This is done so that the most vesicant drug is given when the vein is at its best and less irritated. In addition the nurses assessment of vein patency and patient awareness of changes have shown to be more accurate at the start of treatment (Hyde & Dougherty 2008) and therefore any changes are more likely to be noticed. Hence, when Brian is receiving the CHOP part of his chemotherapy regime he is usually given the drugs in the following order Doxorubicin, Vincristine and then Cyclophosiphamide. Consequently, Brian must be observed at all times at the start of his treatment (NHS TRUST POLICY- name withheld 2010), so any signs of extravasation can be recognized straight away, and the infusion stopped immediately.
Once an extravasation is confirmed action should be taken immediately preferably within the first 24hrs of recognition. Extravasation should be treated as a medical emergency. Never the less management of extravasation is a controversial one because of limited evidence of efficiency due to the lack of clinical studies in this area. However, immediate management of any extravasated drug through a peripheral cannula is to stop the infusion, and aspirate as much of the drug as possible from the cannula. Much of the literature I have read around the management of extravasation supports this notion (Dougherty 2010). However Goolsby and Lombardo (2006) disagree and feel that this may be of little benefit and may cause unnecessary pain and discomfort to the patient.
Extravasation kits should be collected from your area and should contain all the relevant equipment needed to deal with an extravasation. Ideally all clinical areas where vesicant drugs are being administered should have an extravasation kit at hand (Gabriel 2008). Furthermore the availability of extravasation kits has now been recommended by the Department of Health (2004) in all NHS hospitals where cytotoxic agents are used to treat oncology patients.
Part of the immediate action also includes the removal of the cannula. However there are conflicting views on this and some researchers believe that the cannula is best left in to instill the relevant antidote into the cannula (Stanley 2002). Never the less to abide by my local trust policy (NHS TRUST- name withheld 2010) I would remove the cannula to prevent any further solution being injected through the cannula into the affected area.
Following these first line management actions the second line actions greatly depend on the drug which has extravated as how to manage the extravasated area. Never the less when vesicant chemotherapy drugs have extravated, treatment whether it is to 'disperse and dilute' or 'localize and neutralize' should start as soon as possible to prevent tissue damage (Schulmeister 2011).
As well as the ACDT's in Brians' R-CHOP regime having the potential to cause very nasty extravasations they also have the potential to cause allergic, hypersensitive or even anaphylactic reactions. These reactions are when the immune system is over exaggerated by a foreign substance (Linton and Watson 2010). The most severe allergic reaction is anaphylaxis. Virtually all the chemotherapy drugs in Brian's chemotherapy have the potential to initiate a reaction, therefore it is very important that he is monitored throughout. Although severe reactions are not common some ACDT's are known have a higher risk than others, such as the monoclonial antibody rituximab.
When Brian first started his ACDT regime his rituximab was started at a rate of 50ml/hr, and observations were done every half an hour and the rate increased in 50ml increments to a maximum of 400ml/hr. Patients are often started on a slower rate as it has been shown that people are more likely to react on their first dose (Dotan, Charu and Smith 2010). As Brian had no reaction to the first infusion his rituximab was commenced at 100mls/hr on following cycles and went up in 100ml increments to a maximum of 400ml/hr. To reduce the risk of an anaphylactic reaction Brian is given hydrocortisone, chlorphenamine, and paracetamol 30 minutes prior his rituximab. I also informed Brian that rituximab can cause severe to mild reactions and he must report any new symptoms.
Even though precautions are taken when giving drugs such as rituximab, they may not stop an anaphylaxis from occurring, therefore nurses must be vigilant for any signs of an anaphylaxis. Despite this Jevon (2004) warns that symptoms may not always be consistent. However potentially, anaphylaxis could present with breathing difficulties, tachycardia, hypotension, cyanosis, loss of consciousness, and possible death (Finney and Rushton 2007). Consequently chemotherapy induced anaphylaxis is a medical emergency, and the management should follow the ABCDE approach, as recommended by the United Kingdom Resuscitation Council (2008). Furthermore if patient death occurs within 30 days of receiving an ACDT this must be reported (NCEPOD 2008).
Anaphylaxis is a life- threatening side effect of ACDT's, however there are many other side effects which are not so life-threatening. One very common side effect and one which Brian suffered with as a result of his R-CHOP regime is peripheral neuropathy, which is an associated toxicity with the drug vincristine. Although peripheral neuropathy is not life threatening, a high incidence is associated with regimes such as the R-CHOP and it can be very troublesome to the patient and if not monitored can cause long lasting damage. Therefore, it is important that healthcare professionals review patient's side effects before each cycle of chemotherapy, and record any significant toxicity experienced by the patient (NCAG 2009).
Brian's side effects were assessed prior to every cycle of R-CHOP using a chemotherapy toxicity assessment tool (NHS TRUST- name withheld 2011a). This tool goes into great detail into each side effect, and the grading. An advantage of my trusts assessment tool is it states what action is needed, following the grading of that particular side effect. Brian's peripheral neuropathy was graded at a 2 using my trusts tool. Therefore the action would be to carry on with treatment and review and assess at the next cycle. However, despite this other hospitals might grade Brian's peripheral neuropathy differently. For instance, toxicity assessment tool (NHS TRUST- name withheld 2011b), scores patients on a scale of 0- 5, and Brian's peripheral neuropathy may be scored at a 3 at this hospital. This may make their management slightly different. However there assessment tool is much smaller and does look straight forward and easier to use. Never the less this tool has no action needed column, and I would argue the point that an action column is needed to direct the nurse on what to do next. However, despite such different toxicity tools, both trusts use the ECOG performance status by Oken et al (1982), scale to assess the functional status of their patients. Even though this is an old tool it is still used in many NHS hospitals today. However it is unclear precisely how many hospitals are choosing to use this assessment tool.
What has become clear is that ACDT's play a huge role in the treatment of cancers such as NHL. This reflective case study has highlighted the need for nurses administering ACDT's to have the relevant knowledge and skills to be able to administer these potentially harmful drugs in a safe and controlled environment. A thorough knowledge of how each individual drug works on the cell cycle, how to prevent and manage anaphylaxis and extravasations, and side effects and toxicities of the ACDT are all essential for the chemotherapy nurse. Throughout this case study several government policies have also been highlighted, and from this I can see how much they have shaped cancer services today.
Completing this reflective case study has really made me think before administering ACDT's, and I feel it has made me become more vigilant in my clinical practice. I hope to continue to gain knowledge in ACDT's, and I am determined to keep my knowledge current and up to date in this area.