Cytotoxic and Biotherapies Credentialing Programme ‐ Module 7 1. Hypersensitivity Reactions 2. Tumour Lysis Syndrome 3. Chemotherapy related Nausea and Vomiting 4. Chemotherapy related Diarrhoea 5. Chemotherapy related Myelosuppression At the completion of this module the RN will • Manage a hypersensitivity reaction effectively • Discuss tumour lysis syndrome • Demonstrate comprehensive knowledge of chemotherapy induced nausea and vomiting and be able to formulate an individualised antiemetic plan for each patient they treat • Identify the risk of chemotherapy related diarrhoea and understand the management of this condition • Detail the implications of immunosuppression REFERENCES Haematology Department. (n.d.). Haematology Red Book. Retrieved 2011, from CDHB Intranet. McGraw, B. (2008). At an Increased Risk: Tumour Lysis Syndrome. Clinical Journal of Oncology Nursing, 12(4), 563‐565. Oncology Nursing Society. Chemotherapy & Biotherapy Guidelines and Recommendations for Practice (2nd ed.). Pittsburgh, PA: ONS. Understanding & Managing Oncology Emergencies. (n.d.). Retrieved from Cancer Therapy Evaluation Programme. 2010, from http://ctep.cancer.gov/protocoldevelopment/electronic applications/docs/ctcaev3.pdf
Transcript
Cytotoxic and Biotherapies Credentialing Programme ‐ Module 7
1. Hypersensitivity Reactions 2. Tumour Lysis Syndrome 3. Chemotherapy related Nausea and Vomiting 4. Chemotherapy related Diarrhoea 5. Chemotherapy related Myelosuppression At the completion of this module the RN will • Manage a hypersensitivity reaction effectively • Discuss tumour lysis syndrome • Demonstrate comprehensive knowledge of chemotherapy induced nausea and vomiting
and be able to formulate an individualised antiemetic plan for each patient they treat • Identify the risk of chemotherapy related diarrhoea and understand the management of
this condition • Detail the implications of immunosuppression
REFERENCES
Haematology Department. (n.d.). Haematology Red Book. Retrieved 2011, from CDHB Intranet.
McGraw, B. (2008). At an Increased Risk: Tumour Lysis Syndrome. Clinical Journal of Oncology Nursing, 12(4), 563‐565. Oncology Nursing Society. Chemotherapy & Biotherapy Guidelines and Recommendations for Practice (2nd ed.). Pittsburgh, PA: ONS.
Understanding & Managing Oncology Emergencies. (n.d.). Retrieved from Cancer Therapy Evaluation Programme. 2010, from http://ctep.cancer.gov/protocoldevelopment/electronic applications/docs/ctcaev3.pdf
Hypersensitivity and anaphylactic reactions related to chemotherapy agents are mediated by the immune system. These reactions may be triggered by the drug or the diluent. A reaction may occur at any time during the delivery of the medication and sometimes hours after the infusion (delayed or biphasic reactions). Reactions can also occur with repeated exposure to the drug. Pathophysiology of anaphylaxis This is not clearly understood but immunoglobulin E is implicated. The National Cancer Institute CTCAE defines anaphylaxis as an acute inflammatory reaction caused by the release of histamine and related substances that trigger a hypersensitivity reaction immune response and may lead to significant symptoms or death.
Anaphylaxis is differentiated from other reactions by the severity and that it most often occurs during the infusion and usually early on.
Hypersensitivity Reactions Hypersensitivity is an exaggerated or inappropriate immune response that may be localised or systemic. It can occur at any time during an infusion and some hours later. This is known as a biphasic reaction. Biotherapy’s such as monoclonal antibodies are most commonly known to cause infusion related hypersensitivity reactions. These reactions are related to antibody‐antigen interaction and/or the release of cytokines.
The reactions are usually manageable with pharmacologic interventions such as steroids and antihistamines and adjustment of the infusion rate. These reactions can occur within minutes to several hours after the start of administration of the antibody. Many centres administer a premedication before starting the drug infusion. Common hypersensitivity reaction symptoms include: agitation, tightness in the chest, shortness of breath, wheeziness, stridor, hypotension, urticaria, abdominal cramping, diarrhoea, nausea and vomiting, rash, itchiness, periorbital or facial oedema, light headedness or dizziness. Nursing Management • Review the patients’ allergy history and reports of any previous hypersensitivity. • Obtain and record baseline observations. • Administer pre‐medications as charted. • Ensure emergency equipment is available. • Instruct the patient to report any hypersensitivity symptoms as detailed above. • When administering the drug, infuse it slowly to start with and observe the patient
closely for signs and symptoms of a reaction. • Obtain observations regularly throughout the infusion. They may be every 15 to 30
minutes for an hour then hourly until the end of the infusion.
If the patient reports any signs of hypersensitivity • Stop the infusion immediately. • Maintain ABC as required. • Obtain the patients observations. • Seek medical assistance/advice. • Administer further medications as prescribed. • Restart the infusion as medically directed. • Document the hypersensitivity reaction in the clinical notes. If the patient has an anaphylaxis reaction • Stop the infusion immediately. • Maintain ABC as required. • Obtain the emergency drug trolley. • Prepare for the administration of emergency drugs for example, adrenaline. • Seek medical assistance/advice.
• Obtain the patients observations • Ensure the reaction is clearly documented and the patient’s sensitivity record is
recorded in the medical records.
Now complete the workbook section on hypersensitivity
Tumour lysis syndrome (TLS) is a group of metabolic complications that can occur due to the treatment of cancer. These complications are caused by the break‐down of tumour cells and the kidneys inability to clear the by products that are released into the blood. This can be a rapidly developing oncological emergency that can be life threatening if not identified and treated early. Clinical consequences include acute renal failure needing dialysis, cardiac failure and other multisystem organ failure and death. Pathophysiology TLS occurs from the rapid release of intracellular components during cell death. Cancer cells have an abnormally high amount of potassium, phosphorus, and nucleic acid. When cancer cells are destroyed by chemotherapy or radiation, they spill their intracellular components into the bloodstream, causing an influx of potassium, phosphorus, and nucleic acid which the kidneys are not able to efficiently excrete, leading to hyperuricemia, hyperphosphatemia, hypocalcemia, and hyperkalemia. Hyperuricemia occurs when the liver converts nucleic acids into uric acid and hypocalcemia develops when serum calcium binds to elevated amounts of phosphorus within the bloodstream
At risk patients • Those with a high tumour burden • High grade lymphomas/Acute leukaemia • Patients presenting with hepatomegaly or splenomegaly • Patients with poor renal function • Patients who are dehydrated • Highly chemo‐sensitive tumours People are the most at risk of developing TLS at initial diagnosis and at relapse but it potentially can occur any time throughout the treatment. Clinical signs • Hyperkalemia (high potassium). This can cause cardiac issues plus severe muscle
weakness. • Hyperphosphatemia (high phosphate) • Hypocalcaemia (low calcium). This is because of the inverse relationship that phosphate
has with calcium. • Elevated creatinine • Elevated urea • Elevated uric acid • Poor urine output • Weight gain/oedema Hyperkalemia generally is the first electrolyte imbalance, followed by hyperphosphatemia, and leads to hypocalcemia and hyperuricemia. TLS has the ability to affect the renal, gastrointestinal, cardiac, and neuromuscular systems. Renal Hyperuricemia occurs when uric acid crystals and calcium phosphate salts obstruct renal flow, causing renal failure. Patients will have increased uric acid and creatinine levels, indicating renal failure. Physical symptoms consist of flank pain, gross haematuria, cloudy urine, oliguria, lethargy, nausea, and vomiting. Weight gain and oedema also may be present. Gastrointestinal Hyperkalemia causes nausea, vomiting, and diarrhoea. Anorexia, abdominal cramping, and pain also may occur because of the elevated potassium. Decreased levels of serum calcium may cause intestinal cramping and increased bowel activity. Cardiac High serum potassium levels may cause irregular heart rhythms and hypotension. Often the dysrhythmias are atrial in origin. Hyperkalemia causes electrocardiogram changes such as tall T waves, flattened P waves, prolonged PR intervals, widened QRS complexes, and depressed ST segments. The presence of a prolonged QT interval may indicate hypocalcemia.
Neuromuscular Hyperkalemia causes neuromuscular irritability, muscle weakness, or paralysis, and hypocalcemia causes neuromuscular excitability. A decreased level of serum calcium also may cause seizures. Management To prevent morbidity and mortality, early recognition and management of TLS is the key. Patients at increased risk for TLS should be identified early and preventive measures should be initiated prior to beginning treatment. The goals of preventative strategies are to prevent renal failure and severe electrolyte imbalances. Preventive measures Before treatment begins, patients are given oral allopurinol to prevent uric acid formation. Aggressive hydration and the addition of diuretics are commenced to enhance urinary excretion. IV solutions containing sodium bicarbonate help alkalinize urine, increasing uric acid solubility and, therefore, decreasing precipitation in the renal tubules and electrolyte monitoring is essential once treatment has begun. Electrolyte monitoring should begin prior to treatment initiation and then every 6–12 hours for early TLS identification. Although symptoms of TLS may occur up to seven days after initial treatment, patients are at greatest risk during the first 6–48 hours. Treatment measures Depending on the severity of the electrolyte imbalance, medical management will begin and treatment options initiated. Hyperkalemia is managed with the use of Resonium, diuretics, IV glucose and insulin infusions, IV calcium gluconate. Hyperphosphatemia and hypocalcemia can be treated with IV calcium gluconate, Management of hyperuricemia consists of aggressive hydration with or without sodium bicarbonate for urinary alkalinization (keep the urine pH at 7–7.5), diuretics, allopurinol orally, or IV rasburicase (Rasburicase converts uric acid into allantoin, which is more soluble in urine and easily excreted through the kidneys). Dialysis would be required if electrolyte imbalances continued and renal failure was imminent. Nursing management Identifying and initiating preventative measures prior to the first course of treatment for high‐risk patients will help avoid TLS. Continued monitoring for side effects related to TLS is essential. Maintenance of IV fluids, strict intake and output monitoring, daily weights, and continued assessment for fluid overload is required. Nurses should also be familiar with the signs and symptoms of hyperuricemia, hyperphosphatemia, hypocalcemia, hyperkalemia and the signs and symptoms of renal insufficiency. The most important factor in managing high‐risk patients is anticipation of problems, accurate fluid balance monitoring, and prompt early intervention.
Now complete the workbook section on tumour lysis syndrome
Nausea and Vomiting ________________________________________________________ Nausea and vomiting is one of the most common side effects of having chemotherapy. It is the one side effect that people often fear. It can impact greatly on the way they cope with their illness. Prevention of nausea and vomiting is the key to successful treatment and symptom management. Nausea and vomiting can be described as anticipatory, acute or delayed. Many cytotoxic agents cause nausea and vomiting due to the sensitivity of the epithelial cells in the GI tract. The rate of cell division in this part of the body is only slightly lower than that of bone marrow cells. A short time after treatment microvilli mitosis stops resulting in a loss of mucosal cells, which leads to nausea and vomiting. This usually starts 4 hours after treatment and may persist for a few days to a week. Mechanism of vomiting Vomiting is mediated through a complex series of multi‐afferent neural pathways involving the neurotransmitters ‐ 5HT3, serotonin, dopamine, histamine and acetylcholine. Drugs that block these receptors have useful antiemetic properties. Antagonists of histamine and acetylcholine have proved more useful in controlling vomiting associated with motion sickness, whereas serotonin receptor antagonists (ondansetron) and dopamine receptor antagonists (metoclopramide/domperidone) have proved more useful in controlling chemotherapy induced emesis. Additional drugs such as corticosteroids, whose mode of action is uncertain, are highly effective when used in conjunction with ondansetron and improve success by a further 15‐25%. The diagram below shows the neuronal pathways involved with chemotherapy induced nausea and vomitin
This diagram shows the drug pathways to minimise chemotherapy induced nausea and vomiting
Each cytotoxic drug has been given an emetogenic potential. This refers to the risk of nausea and vomiting that can occur with the administration of a particular drug without any antiemetics. This needs to be taken into account when deciding what antiemetic best suit the regimen. Management Assessment at baseline for associated risk factors Regular constant assessment during and after treatment Administration of antiemetics prophylactically, not just after the problem has occurred Monitor diet and fluid intake, output as necessary (dependent on regimen). Consider non‐pharmacological/dietary interventions as well as medication.
Now complete the workbook section on chemotherapy related nausea and vomiting
Treatment related Diarrhoea _______________________________________________________
Diarrhoea = loose watery stools A number of chemotherapy drugs are associated with this toxicity. If left untreated or inadequately treated chemotherapy induced diarrhoea (CID) can lead to dehydration, hospitalisation, chemotherapy delays and dose reductions and potentially death. Most commonly implicated are the fluoropyrimidines (5FU, Capecitabine) and Irinotecan. Other drugs associated with diarrhoea also include: high‐dose methotrexate, oxaliplatin, and docetaxel. The
incidence of diarrhoea can be influenced by a number of factors – dose and regimen schedule, route of administration, women vs. men, cultural differences. With 5FU in particular a small number of people are deficient in the enzyme Dihydropyrimidine dehydrogenase (DPD) which is required for metabolising 5FU and therefore produces severe toxicity which can be potentially fatal; testing for DPD is controversial and not widely practised. The most common mechanisms involved in CID are osmotic, secretory and exudative. • Osmotic – related to injury to gut, diet factors or problems with digestion. • Secretory – related to infection and inflammation of the gut, damage to the gut caused
by chemotherapy, radiation or GVHD or some endocrine tumours. • Exudative – caused by alterations in mucosal integrity, epithelial loss and enzyme
destruction The specific drug, dose, schedule and combination of therapy all influence the severity of CID. Management • alert the patient of the likelihood of this side effect • assess the patients baseline bowel habit prior to commencement of treatment • a prophylactic prescription of Loperamide should be offered for the patient to take
when diarrhoea starts – instruct the patient on how to do this • encourage the patient to report diarrhoea that remains excessive (>4‐6 motions/day
above baseline) – medical assessment will be required and treatment may be stopped temporarily
• admission and adjunctive care may be required Refer to local policy and procedure on the cytotoxic website for more information on managing CID
Now complete the workbook section on chemotherapy related diarrhoea
Colitis and intestinal perforation ____________________________________________________ Three types of chemotherapy related colitis are known: neutropenic colitis, ischemic colitis and C. Difficile associated colitis. Neutropenic enterocolitis is a form of necrotizing enterocolitis or typhilitis. C. Difficile colitis is a common problem mostly due to high rate of antibiotic use and hospitalisation in patients with cancer. This is a rare side effect of treatment which is associated more often with antiangiogenic agents such as Bevacizumab. However it is not unique to targeted agents as perforation may be seen with tumours of the GI tract which respond rapidly to conventional chemotherapy e.g. GI lymphoma.
Chemotherapy related Myelosuppression _______________________________________________
Myelosuppression is defined as a decrease in the number of circulating blood cells from the myeloid cell line. This affects the neutrophils, thrombocytes and erythrocytes. These haemopoietic cells normally divide rapidly therefore are sensitive to the effects of chemotherapy. It is the most common dose limiting toxicity of chemotherapy. It can also be life threatening. Haemopoietic Cascade
All blood cells develop from one cell called the stem cell. This stem cell is found in the bone marrow of most bones but in particular, it is found in the long bones, iliac crests of the hip and sternum. Most chemotherapy agents cause some degree of myelosuppression. There are some drugs that can cause more severe myelosuppression. This is because they affect both the actively dividing cells and the resting cells. Examples of this are alkylating agents like cyclophosphamide, cisplatin and melphalan. Myelosuppression causes leucopenia/neutropenia, anaemia and thrombocytopenia. Patient education is the key to managing this side effect. Immunity There are two ways in which the body responds to invading pathogens. One is a non‐specific response involving the white blood cells (basophils, monocytes and neutrophils) and the other is a cell mediated response involving the B and T lymphocytes which produce antibodies. The white blood cells and in particular the neutrophils are the body’s first line of defence. They are attracted to the invading pathogen by chemotaxis and engulf and destroy the pathogen by phagocytosis. Neutrophils are particularly responsive to invading bacteria. Leucopenia Is defined as a lower than normal circulating total white blood count. The normal value is 4 – 11 x10(9)/L.
Neutropenia Is a lower than normal circulating blood neutrophil count. The normal value is 1.9‐7.5 x10(9)/L. The life span of a neutrophil is 6 to 8 hours once it has entered the blood stream. Because the life span of a neutrophil is very short the bone marrow needs to continually reproduce these cells. The impact of the chemotherapy on the bone marrow results in suppression of the stem cell therefore the number of circulating neutrophils falls rapidly exposing the body to the risk of infection. Because of this the body is unable to mount a normal inflammatory response to infection therefore it is unlikely that you will see redness, heat or swelling at the site of infection or the collection of pus. Often the only sign of infection will be a fever and a rise in the blood C‐Reactive protein (CRP, inflammatory marker). When the neutrophil count reaches its lowest point it is called the NADIR. For most drugs this occurs 7‐14 days from the start of chemotherapy administration. Recovery of the neutrophil count will depend on the chemotherapy cycle but will usually occur 7‐14 days after this.
Neutropenia has been graded by the Common Terminology Criteria for Adverse Events (CTCAE) • Grade 1 = <1.5 x10(9)/L. • Grade 2 = <1.5 – 1.0 x10(9)/L. • Grade 3 = <1.0 – 0.5 x10(9)/L. • Grade 4 = <0.5 x10(9)/L. (profound neutropenia) Patient/Family education prior to discharge includes the following • Avoidance of people with coughs and colds or who are unwell • Protective Isolation diet/Food safety education • Regular mouth cares • Good personal hygiene and environment • If the patient is unwell at home, shivery or their temperature is above 38, they should
contact their local treatment centre and/or follow the immunosuppression pathway using the immunosuppression card.
• Educate patient to assess their central venous access device for signs of infection • Educate the patient on other early signs of infection including cough, cold, dyspnoea,
sore throat, dysuria, malodorous or cloudy urine and haematuria, headache • Avoid activities that will put you at risk of infection like gardening • Avoid constipation • Avoid dehydration • Prophylactic medication may be prescribed i.e. acyclovir, fluconazole, cotrimoxazole Nursing assessment of the neutropenic patient • Patients may be admitted to hospital if their neutrophil count is low. • The patients temperature should be monitored at least four hourly. This includes
assessment using the Early Warning Score and observing for changes in the patients condition.
• Patients who have a central venous access device (CVAD) will need their line assessed for signs of infection 4 ‐8 hourly. Careful hand washing prior to using the CVAD is crucial in ensuring it remains infection free.
• Assess for signs of infection like a cough, sore throat, dysuria, diarrhoea, perianal discomfort or tender areas.
• Ask the patient about any skin lesions, sores, redness or discomfort. • Ask the patient about any mouth discomfort, sores, blisters, white patches. • Avoid any unnecessary invasive procedures like urinary catheterisation. • Avoid per rectal medications or examinations. This reduces both the risk of trauma and
infection. The well neutropenic patient can have • A neutrophil count less than 2.0 • No abnormal temperature • No signs of infection • The patient feels well
The febrile neutropenic patient can have • An abnormal temperature • The source of infection may be unidentified or identified • The patient can feel unwell but is haemo‐dynamically stable Management of the febrile neutropenic patient • Monitor vital signs at least 4 hourly • Reportable parameters are – BP < 100 systolic, P >90, RR >20, temp >38 or < 36 • If temperature rises above 38 degrees or below 36 degree take central and peripheral
blood cultures, CRP and electrolytes, swab any areas of concern and take urine/stool/ sputum/drainage samples if needed.
• Commence IV antibiotics • IV fluids if needed • Observe for signs of sepsis and shock
• Administer GCSF as directed. Gram negative sepsis (E‐coli, pseudomonas, Klebsiella) usually presents with a low temperature ie below 36oC. The patient feels unwell. This can progress to sepsis and shock within hours if left untreated. Sepsis Is a systemic inflammatory response to pathogens and toxins in the blood. Due to bone marrow suppression the body is unable to mount a sufficient immunological response which puts them at greater risk. Generally presents with two or more of the following • Temp >38 • Pulse >90 • RR >20 • BP – Systolic below 100 • There may also be signs of organ dysfunction, hypotension or hypo perfusion which
would demonstrate severe sepsis. Septic shock Is defined as, an uncontrolled inflammatory response to bacterial toxins, which leads to severe hypotension and hypo perfusion of organs. The patient is haemo‐dynamic ally unstable despite aggressive fluid resuscitation. This is because of vasodilatation within the vascular system that results in hypotension and tachycardia. Septic shock is characterised by fever, chills, tachycardia, tachypnoea, mental state changes, hypotension/hypo perfusion. Other signs and symptoms include cold, clammy skin, cyanosis, and a decreased urine output.
Other nursing management would include • Monitoring vital signs on a frequent basis. One of the earliest signs of septic shock is
tachypnoea with dyspnea • Observe for other signs of septic shock as documented above • Appropriate and timely medical review • Initiate any treatment urgently • Assess urine output ‐ catheterise if needed • Administer oxygen as directed • Fluid resuscitation • Think ahead ‐ ? ICU, discuss patient with ICU Out Reach In summary, early detection and treatment of infection in immunocompromised patients ensures the best possible outcome for them. The patient needs to demonstrate bone marrow recovery before they receive their next cycle of chemotherapy. Anaemia Red blood cells normally circulate in the blood for 120 days. In patients with cancer their life span is reduced to 60‐90 days. These cells are responsible for carrying oxygen and carbon dioxide around the body. Normal values depend on the gender of the patient but generally are between 120 – 180 g/l. Because of their longer life span, compared to other blood cells, symptoms of anaemia may not present until a couple of months into treatment. Common symptoms include lack of energy, lethargy, constipation, pallor, dizziness.
Management • Provide written and verbal information to the patient and relatives about this side
effect. • Educate the patient and family about the symptoms of anaemia
• Assess for signs of anaemia. Evaluate level of fatigue, shortness of breath, heart palpitations, heart rate, and respiratory rate.
• Encourage the patient to have more time for rest.
• Assess haemoglobin blood level between, and just prior, to each chemotherapy cycle.
• Find out at what level the patient’s haemoglobin should be before chemotherapy is administered and a blood transfusion be administered (usually less than 80, unless symptomatic).
• Administer blood transfusion as per local policy. Thrombocytopenia Thrombocytopenia is a decrease in the platelet count. Again, this is due to the effects of the chemotherapy on the bone marrow. It has the potential to result in haemorrhage or bruising. Normal values are 150 – 400 x10(9)/L. They circulate in the blood for around 9‐10 days. Patient who are undergoing treatment for haematological malignancies or stem cell transplants are more at risk of thrombocytopenia When thrombocytopenia is present the most frequent sites of bleeding are • The mucous membranes (bleeding gums, epistaxis) • Skin on lower limbs and trunk (bruising, petechiae) • GI tract (gastritis, haematemesis, and malaena) • Respiratory system (haemoptysis) • Genitourinary system (haematuria, prolonged menstrual loss) • Intracranial haemorrhage (headache, blurred vision, falls, change in mental • status) Management • Inform the patient and carer of this side effect, and the signs and symptoms associated
with minor and serious bleeding. Emphasise the importance of reporting these to medical and nursing staff.
• Assess patient regularly for signs of minor bleeding such as: petechiae, conjunctival haemorrhages, epistaxis, bleeding gums, urinalysis for haematuria, bleeding at puncture sites.
• Assess the patient regularly for signs and symptoms of serious bleeding such as: headache and changes in neurological signs, haemoptysis, haematuria, malaena, hypotension, tachycardia, and dizziness.
• Avoid unnecessary invasive and non‐invasive procedures that may increase the possibility of bleeding: prevent constipation, avoid frequent blood pressures, minimise venepuncture and apply firm pressure for 3 – 5 minutes afterwards, avoid injections and any per rectal medications or procedures, relieve nausea and vomiting, prevent menstruation by administering hormone therapy.
• Educate patient to prevent bleeding: • use a soft toothbrush but no floss or toothpicks • use an electric shaver and not a razor blade razor • use gloves when doing work that is likely to injure the hands • don’t take aspirin or other drugs/creams that contain aspirin • avoid contact sports • if bleeding occurs, apply direct pressure until bleeding stops, then contact your local
treatment area • avoid hard or abrasive foods • advise dentist, if you need dental treatment • Know the acceptable platelet levels in your area and transfuse with platelets as
necessary following local policy.
Now complete the workbook section on chemotherapy related myelosuppression
