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NURSING MANAGEMENT OF CLIENTS WITH DISTURBANCES IN CELLULAR FUNCTIONING LEARNING OBJECTIVES: At the end of the discussion, the students

will be able to: 1. Summarize the nursing roles and opportunities in cancer prevention, detection, diagnosis and treatment of cancer 2. Enumerates the case finding and early detection methods of cancer. 3. Explains the major health problems of client with cancer and its specific nursing diagnosis with interventions. 4. Identify the psychosocial implications of cancer. 5. Differentiate the modes of treatment for cancer and its specific nursing responsibilities. 6. Discuss the nursing management for oncologic emergencies. CANCER y CANCER affects every age group. y The incidence of cancer is higher in men than in women and higher in industrialized sectors and nations y Refers to class of diseases or disorders characterized by the development of abnormal cells that divide uncontrollably and have the ability to infiltrate and destroy normal body tissue WARNING SIGNS OF CANCER C - Change in bowel or bladder habits A - Sore that does not heal U - Unusual bleeding T - Thickening or lump I - Persistent indigestion O - Obvious change in warts or mole N - Nagging cough or persistenthoarseness A - Anemia L - Loss of appetite DETECTION AND PREVENTION OF CANCER y PRIMARY PREVENTION Acquisition of knowledge and skills necessary to educate client, community about cancer risk.

SECONDARY PREVENTION Cancer screening programs for individuals who are found to be at high risk for cancer

NURSING RESPONSIBILITIES IN EARLY DETECTION OF CANCER STEPS TO REDUCE CANCER RISK When teaching individual patients or groups, nurses can recommend the following cancer prevention strategies: 1. Increase consumption of fresh vegetables (especially those of the cabbage family.) 2. Increase fiber intake. 3. Increase intake of Vitamin A. 4. Increase intake of foods rich in Vitamin C. 5. Practice weight control. 6. Reduce intake of dietary fat. 7. Practice moderation in consumption of salt-cured, smoked and nitrate-cured foods. 8. Stop smoking cigarettes and cigars. 9. Reduce alcohol intake. 10. Avoid overexposure to sun. RECOMMENDATION FOR EARLY DETECTION OF CANCER BREAST CANCER Risk Factors Menarche before age 11 Menopause after age 50 Family history of breast cancer especially mother or sister History of uterine cancer Nulliparity or birth of first child after age 30 History of uterine cancer Link with obesity, diabetes and hypertension Presence of benign breast cyst. Screening Breast Self-Examination Regular mammograms (screen all middle aged woman) COLORECTAL CANCER  COLORECTAL means colon and rectum combined  Highest for people older than 85 years of age  High for people with family history of colon cancer, polyps adenomatous, of inflammatory bowel disease, high fat, high protein (with high intake of beef), low fiber diet, genital or breast cancer in women

Diagnostic Procedure 1. Colonoscopy an insertion of fiber optic scope through the rectum for direct visualization of the colon. 2. Digital Rectal Examination PROSTATE CANCER Risk Factors Increasing age, after age 50 Having father or brother with prostate cancer doubles the risk of relatives A diet high in red meat increase risk Difficulty and frequent urination, urinary retention, decreased size and force of the urinary stream Every man older than 40 should have DRE ( Digital rectal exam ) as part of regular check up The more advanced lesion, it becomes stony hard and fixed DIAGNOSTIC PROCEDURE  Digital Rectal Examination  Prostate Specific Antigen TESTICULAR CANCER Primarily affect young to middle-aged men (20 to 35 years old) Most testicular tumors originate in gonadal cells. Signs:  Early sign firm painless, smooth testicular mass varying in size  Late sign ureteral obstruction, abdominal mass, shortness of breath Screening: Testicular Self-Examination(TSE) CERVICAL CANCER Refers to the cancer of the neck of the uterus. Assessment:  Painless vaginal bleeding post-menstrual and post-coital  Foul-smelling or serosanguinous vaginal discharge  Pelvic, lower back, leg or groin pain Diagnostic Procedure 1. Pap s Smear THYROID CANCER

- Lesions that are single, hard, & fixed on palpation or associated with cervical lymphadenopathy, suggest malignancy. SCREENING: Use of fine or large bore needle biopsy, Ultrasound, MRI, CT Scan & Thyroid Scan LUNG CANCER  Most common from cigarette smoking.  Genetic, underlying respiratory diseases, COPD, TB  most common symptom is a cough or change in cough  Repeated unresolved URTI Diagnostic Examination: Chest x ray - is performed to search for pulmonary density, a solitary peripheral nodule (coin lesion), atelectasis and infection. NURSING PROCESS: THE PATIENT WITH CANCER I. ASSESSMENT Regardless of type of cancer treatment or prognosis many patients with cancer are susceptible to the following problems and complications. An important role of the oncology nurse is to assess the patient for these problems and complications 1. Infection A. Assess factors that promotes infection:  Impaired skin & mucus membrane integrity  Chemotherapy  Radiation Therapy  Biologic Response Modifiers  Malignancy  Malnutrition  Urinary Catheter, Intravenous Catheter  Other Invasive Procedures  Contaminated Equipment  Age  Chronic Illness  Prolonged Hospitalization B. Monitoring laboratory studies to detect early changes in WBC count Leukopenia Granulocytopenia Neutropenia

C. Chest x- ray 2. Bleeding A. Assess factors that contribute to bleeding Bone marrow suppression from radiation Chemotherapy Medications that interfere with coagulation and platelet functioning B. Common bleeding sites: Skin and mucous membranes Intestinal Genito-Urinary Tract Respiratory tract Brain C. Signs of bleeding Gross hemorrhage Blood in the stools, urine, sputum, or vomitus Oozing at injection sites Bruising (ecchymosis) Petechiae Changes in mental status 3. Skin Problems Assess predisposing factors and other risk factors 4. Hair Loss Assess also the psychological impact of this side effect on the patient and the family 5. Nutritional Concerns COMMON NUTRITIONAL PROBLEMS 1. Anorexia 2. Mal-absorption 3. Cachexia A. Impaired nutritional status may contribute to:  Disease progression  Immune incompetence  Increased incidence of infection  Delayed tissue repair  Diminished functional ability  Decreased capacity to continue chemotherapy B.Physical signs of weight loss and cachexia are secondary to decreased protein and caloric intake, metabolic, mechanical effects of cancer and systemic disease, side effects of the treatment or emotional status of the patient. 3

C. Determine diet history, any episodes of anorexia, changes in appetite, altered taste, nausea, diarrhea, situation and foods that aggravate or relieve anorexia and medication history D. Clinical and laboratory data useful in assessing Patient s nutritional status o o o o o o 6. Pain A. Related factors causing pain:  Underlying disease  Pressure exerted by tumor  Diagnostic procedures  Cancer treatment B. Assess site of pain, pain perception, pain scales C. Give emphasis not only to physical pain but psychosocial as well. 7. Fatigue  Fatigue has been recognized as one of the significant and frequent symptoms experienced by patients receiving cancer therapy.  Assess for feelings of weariness, weakness, lack of energy, inability to carry out ADL, lack of motivation, and inability to concentrate  Assess for physiologic and psychological stressors that contribute to fatigue, (pain, nausea, constipation, fear, anxiety) 8. Psychosocial Status 9. Body Image and Self-Esteem II. Nursing Diagnosis Risk for infection related to altered immunologic response Impaired skin integrity: erythematous and wet desquamation reaction to radiation therapy. Impaired oral mucous membranes related to stomatitis. Imbalanced nutrition: less than body requirements related to nausea and vomiting. Anthropometrical measurements Serum protein levels Serum electrolytes Skin response to intradermal injection Hemoglobin and hematocrit levels Serum Iron Levels

Fluid and electrolyte imbalance related to anorexia, nausea & vomiting, altered taste, diarrhea Anticipatory grieving related to loss of body parts and altered role functioning Disturbed body image and situational low selfesteem related to changes in appearance, function and roles Self care deficit due to fatigue, malaise, and protective isolation Anxiety due to knowledge deficit and uncertain future Disturbed body image r/t changes in appearance, function and roles Grieving r/t anticipatory loss and altered role functioning Potential for spiritual distress Deficient knowledge about disease process, treatment, complication management, and selfcare measures

Assisting Patients to cope with Alopecia: o Provide information about hair loss, support patient and family in coping with disturbing effects of therapy. o Instruct to acquire a wig or hairpiece before hair loss. o Encourage use of attractive scarves and hats. Managing Malignant Skin Lesion: o Carefully assessing and cleansing the skin. o Reducing superficial bacteria. o Controlling the bleeding. o Reducing odor. o Protecting the skin from pain and further trauma. Promoting Nutrition: o Prepare foods that are appealing. o Patient s preferences as well as physiologic and metabolic requirements are considered when selecting foods. o Encouraged small frequent feedings. o Inform patient the advantage of receiving alternative methods of feeding by parenteral or enteral route. Relieving Pain: o Provide adequate rest and sleep o Promote diversional activities o Provide adequate rest and sleep o Offer Empathy o Give pain reliever medications as ordered Decreasing Fatigue o Help the patient and the family to understand that is an expected and temporary side effect of cancer process and of many treatments used. o Help patient identify sources of fatigue o Plan activities to conserve energy as well as alternate periods of rest. o Regular, light exercise is recommended Body Image and Self-Esteem o Positive approach is necessary o Encourage independence and continued participation in self-care decision making o Patient should be assisted to assume tasks and participate in those activities that are personally of most value. o Identify any negative feeling that that the patient has or threats to body image. o Referral to support groups Assisting in the Grieving process

III. Planning o Maintenance of tissue integrity o Maintenance of nutrition o Relief of pain o Relief of fatigue o Improve body image o Effective progression through grieving process o Absence of complications Nursing Interventions Managing Stomatitis o Provide good oral hygiene. o Use soft bristled toothbrushes and nonabrasive toothpaste. o Oral swabs with sponge like applicators maybe use in place of toothbrush. o Avoid alcohol based mouth rinses. o Lubricate cracked and dry lips o Adequate food and fluid intake is encouraged Maintaining Tissue Integrity o Handle affected area gently. o Avoid rubbing or use of hot or cold water, soaps, powder, lotion and cosmetics avoided o Avoid tissue injury by wearing loose-fitting clothing. o Aseptic technique should be observed during dressing and wound care.

Grieving is a normal response to fears and anticipated losses that include, loss of heath, normal sensations, body image, social interaction, sexuality and intimacy. o Assess response of patient and family about the diagnosis and planned treatment. o Assist in answering inquiries and questions, identifying resources and support people. o Assist patient and family acquire knowledge to cope with the disease process o Assist patient and family members to acknowledge and cope with their reactions and feelings. Managing and Monitoring Potential Complications 1. Infection o Strict asepsis technique o Health teaching on how to recognize signs and symptoms of infection o Maintain skin integrity. o Monitoring laboratory data. o Administration of antibiotics as ordered 2. Septic Shock o Assess signs and symptoms of septic shock. o Neurologic assessment o Fluids and electrolyte status monitoring o Administration of intravenous fluids, blood products, vasopressors, oxygen and broad spectrum antibiotic as ordered. 3. Bleeding and Hemorrhage o Monitor laboratory values especially platelet count o Assess the patient for bleeding o Taking steps to prevent trauma and minimize the risk for bleeding

The patient undergoing surgery for cancer requires general peri-operative nursing care with specific care related to the patient s age, organ impairment, nutritional deficits, disease of coagulation and altered immunity that may increase the risk.  Peri-operatively, the nurses asses the patient response to the surgery.  Monitor possible complication: Post-Operative teaching about wound care, activity nutrition and medications information is given. 2. RADIATION THERAPY Ionizing radiation that is used to:  Interrupt cellular growth  Cure cancer  Used to control malignant disease when tumor cannot be removed surgically used when local metastasis is present  Used prophylactically to prevent leukemia; infiltration to the brain and spinal cord. SOURCE OF RADITAION THERAPY  External Radiation therapy (Teletherapy) -administer through an x-ray machine  Internal Radiation Therapy -administer near or within the tumor Types:  Sealed Source (Brachytherapy )  Unsealed BRACHYTHERAPY - From the greek word bradys means, short - distance - Also known as internal radiotherapy, sealed source radiotherapy, curietherapyorendocurietherapy is a form of radiotherapy where a radiation source is a place inside or next to the area requiring treatment.

PROMOTING HOME AND COMMUNITY BASED CARE 1. Teaching Patients Self-Care 2. Continuing Care NURSING MANAGEMENT DIFFERENT MODALITIES OF TREATMENT 1. SURGERY Types: y y y y 5

Diagnostic Prophylactic Palliative Reconstructive

BRACHYTHERAPY - Is commonly used as an effective treatment for cervical, prostate, breast and skin cancer and can also be used to treat tumors in many other body sites. - Can be used alone or in combination with other therapy such as surgery EBRT and chemotherapy SIDE EFFECT OF RADIATION THERAPY AND IT S RESPONSE 1. Skin Reaction - Erythema, dry/moist desquamation - Atrophy telangiectasia, depigmentation - Necrotic or ulcerative lesion

SAFETY PRECAUTION IN RADIATION THERAPY        Assigning to a private room Posting notices Dosi meter badge must be worn Not assigning pregnant staff Prohibit children Limit visits 30 minutes daily Maintain 3 feet distance

3. CHEMOTHERAPY Anti-neoplastic agents that are used in an attempt to destroy tumor cells by interfering with cellular function and reproduction. Goal:Cure, Control, Palliation

Nursing Responsibility:  Observe for early signs of skin reaction and report immediately  Keep area dry  Was area with water, no soap and pat to dry and do not rub  Do not apply ointment, powders, lotion on the area  Do not apply heat, avoid sunshine or cold  Use soft fabric for clothing  DO NOT ERASE MARKING ON THE SKIN 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Infection Hemorrhage Fatigue (radiation cause exhaustion) Weight loss Stomatitis Diarrhea Nausea and Vomiting Headache Alopecia Cystitis Social Isolation

Route:Topical, Oval, IV, IM, Subcutaneous, Arterial, Intra-cavity, and Intrathecal. Special Problem:Extravasation Contraindication: 1. 2. 3. 4. 5. 6. Infection Recent Surgery Impaired Renal or hepatic functions Recent Rad. Therapy Pregnancy Bone Marrow Depression

2. CHEMOTHEPEUTIC AGENT 1. Alkylating - Busulfan, cabopatin, chlorambucilm, asplatin, cyclophosphamide, decabazine, hexamathyl, melamine, fosfamde nitrogen mustard, theothecin. - Alter DNA structure by misreading DNA code initiating breaks in DNA molecule, cross linking DNA strands. 2. Antimetablikes - Cytaraine 5-flourfacil (5-FU) Pentatastine - Interfere with biosynthesis of metabolic or nucleic acid necessary for RNA and DNA synthesis.

PRINCIPLES OF RADIATION PROTECTION 1. Distance - Maintain a distance of at least 3 feet when not performing nursing procedure 2. Time - Limit contact with the patient for 5 minutes each time, a total of 30 minutes per shift 3. Shielding - Use lead shield during contact with client 6

3. Plant alkaloids - etoposide, teniposide, vinblastine, vineristine - Arrest metaphase by inhibiting mitotic tubular formation (spindle) inhibit DNA and protein synthesis. 4. Anti-tumor Antibiotic - Bleomian, doxorubicin,mitomycin - Interfere with DNA synthesis by binding to DNA, prevent RNA synthesis Vesicant are those agent if deposited into the subcutaneous tissues can cause extravasation y y y y y y y Dactoinomycin Paunorubicin Doxorubicin Nitrogen mustard Mitomycin Vinblastine Vincristine

b. Diarrhea c. Constipation 2. Integumentary System a. Pruritus, Urticaria, and systemic signs b. Stomatitis c. Alopecia d. Skin Pigmentation e. Nail Changes 3. Hematopoetic System a. Anemia b. Neutropenia c. Thrombocytopenia 4. Genito Urinary System a. Hemorrhagic changes b. Urine color changes 5. Reproductive System a. Premature menopause or amenorrhea SAFETY PRECAUTIONS IN ADMINISTERING CHEMOTHERAPY *Use of biologic safety cabinet for the preparation of all chemotherapeutic agents *Wear surgical gloves when handling antineoplastic agent and the excretions of patients who received chemotherapy *Wear disposable long sleeved gown when prepares and administering chemotherapeutic agents *Use Leur lock fitting in all intravenous tubing used to deliver chemotherapy *Disposable of all equipment used in chemotherapy preparation and administration in appropriate, leak proof, puncture proof container. *Dispose of all chemotherapeutic waste as hazardous material. 4. THERMAL THERAPY or HYPERTHERMIA The generation of temperatures greater than physiologic fever range ( above 41.5 C ) has been used for many years to destroy tumors in human cancer. Using radio waves can produce heat, ultrasound, microwaves, magnetic waves, and hot water baths, hot wax immersions.

INDICATION OF EXTRAVASATION DURING ADMINISTRATON OF VESICANTS  Absence of blood return from the intravenous catheter  Resistance to flow of the intravenous fluid  Swelling, pain, and redness at the site Of the extravasation is suspected:  Medication administration must be stopped immediately  Ice applied on the site (expect for vesicant) vinca alkaloid  Physician may aspirate any infiltrate medication from the tissue and infect neutralizing solution onto the area reduce to reduce tissue damage Example of neutralizing solution: Sodium thiosulfate, Nyaluronidase, and Sodium Bicarbonate SIDE EFFECT OF CHEMOTHERAPY 1. Gastrointestinal System a. Nausea and Vomiting 7

Principles: 1. Malignant cells are sensitive to harmful effects of high temperatures. 2. Malignant cells lack repair mechanisms necessary to repair cell damage by elevated temperature. 3. Most tumor cells lack an adequate blood supply during periods if increased cellular demand such as during Hyperthermia. Nursing Management: o Local skin care 5. BIOLOGIC RESPONSE MODIFIERS - is also called IMMNUNOTHERAPY - Substances that are able to trigger the immune system to indirectly affect tumors. - These include cytokines such as interferons and interleukins. - The basis of BRM is restoration, stimulation, modification and augmentation of the body s natural defense against cancer - E.g. BCG treat bladder cancer BRM (Biological Response Modifiers) Nursing Management: Patients receiving BRM therapy have many of the same needs as cancer patients undergoing treatment approaches BRM therapies are still investigational a considered a last-chance effort by many patients. Essential that the nurse assess the need for education, support and guidance for the patient and family in planning and evaluating patient care. 6. PHOTODYNAMIC THERAPY - A ternary treatment for cancer involving 3 key components: a photosensitizer, light and tissue oxygen. - A photosensitizer is a chemical compound (Porfimer) that can be excited by a light of a specific wavelength. - Use as a treatment for basal cell carcinoma. MAJOR SIDE EFFECT: PHOTOSENSITIVITY FOR 4 TO 6 WEEKS AFTER TREATMENT NURSING MANAGEMENT: Instruct client to protect themselves from direct and indirect sunlight to prevent skin burns. 8

Liver and renal function should be monitor Offer emotional support and educate the client and family regarding the therapy

8. GENE THERAPY A technique for correcting defective genes responsible for disease development. A gene is inserted into the genome to replace an abnormal, disease causing gene. Viruses are used as a gene therapy vectors such as retrovirus, adenovirus,herpes simplex virus.

9. BONE MARROW TRANSPLANTATION Types 1. Autologous from patient 2. Allogenic - from a donor other than a patient. Eg.family member, matched unrelated donor,(bone marrow registry) 3. Syngeneic - from an identical twin Procedure: 1. Donor suitability is determined through tissue antigen typing of human leukocyte antigen (HLA) and mixed leukocyte culture (MLC) 2. Donor bone marrow is aspirated from multiple sites along iliac crest under general anesthesia 3. Donor marrow is infused IV into the recipient COMPLICATIONS: 1. Failure of engraftment 2. Infection: highest risk in 3 to 4 weeks 3. Pneumonia: non-bacterial or intestinal pneumonia are principal causes of death on the first 3 months post-transplant 4. (GVHD) Graft vs., host disease: principal complication caused by an immunologic reaction of engrafted lymphoid cells against the tissue of the recipient - Acute GHVD develops within first 100 days post-transplant and affects GUT, liver, marrow, and lymphoid tissue -Chronic GVHD Develops 100 400 days post-transplant manifested by multiorgan involvement 5. Recurrent malignancy 6. Late complications such as cataracts, and endocrine abnormalities

NURSING CARE PRETRANSPLANT 1. Recipient immunosuppression attained with total body irradiation (TBI) and chemotherapy to eradicate existing disease and create space in host marrow to allow transplanted cells to grow. 2. Provide protective environment. A. Client should be in laminar airflow room or strict reverse isolation. B. Objects must be sterilized before being brought to the room. C. When working with children, introduce new people were they can be seen, but outside child s room so they can see what they look like without isolation garb.

Nursing Management
 Trusting relationship, supportive care, and promotion of hope with the patient and family.  Truthful responses should be given in nonjudgmental manner to questions and inquiries about unproven methods.  The nurse should encourage any patient who uses unconventional therapies to inform the physician about such use. NURSING MANAGEMENT FOR ONCOLOGIC EMERGENCIES: 1. SUPERIOR VENA CAVA SYNDROME (SVCS)

3. Monitor central lines frequently. Check patency and observe signs of infection such as fever, redness around sight. 4. Provide care for client receiving chemotherapy and radiation therapy that induce immunosuppression. NURSING CARE POST TRANSPLANT 1. Prevent Infection. 2. Provide mouth care for stomatitis and mucositis. 3. Provide skin care. 4. Monitor carefully for bleeding. 5.Maintain fluid and electrolyte balance and promote nutrition. 6. Provide client teaching and discharge planning concerning: Home environment (cleaning, pets, visitors) Diet modifications Medication regimen schedule, dosage, effects, side effects. Communicable disease and immunizations Daily hygiene and skin care Fever Activity 9. UNPROVEN & UNCONVENTIONAL THERAPIES Also called Complementary and Alternative Medicine. CAM treatments are the diverse group of medical and health care systems, practices & products that are not presently considered to be effective by the standards of medicine.

INTERVENTIONS:  Assess for signs and symptoms of SVCS.  Monitor cardiopulmonary and neurologic status.  Promote energy conservation to minimize shortness of breath.  Prepare the patient for radiation therapy to the mediastinal area. 2. SPINAL CORD COMPRESSION INTERVENTIONS:  Assess for back pain and neurological deficits.  Prepare the client for radiation and/or chemotherapy.  Surgery may be needed to remove the tumor and relieve the pressure to spinal cord.  Instruct the client in the use of neck or back braces if they are prescribed. 3. HYPERCALCEMIA INTERVENTIONS:  Monitor calcium level.  Administer oral or parenteral Normal Saline fluids as prescribed.  Administer medications to lower the calcium level as prescribed.  Prepare the client for dialysis if the condition becomes life threatening or is accompanied by renal impairment.

4. PERICARDIAL EFFUSION & CARDIAC TAMPONADE INTERVENTIONS:  Monitor vital signs and oxygen saturation frequently.  Assess for pulsusparadoxus.  Monitor ECG tracings  Assess heart and lung sounds.  Monitor and record intake and output  Elevate the head of patient s bed.  Minimize patient s physical activity.  Reposition and encourage the patient to cough.  Provide frequent oral hygiene.  As needed, maintain patient IV access, reorient the patient, and provide supportive measures and appropriate patient instruction. 5. DIC/CONSUMPTION COAGULOPATHY

PSYCHOSOCIAL ASPECTS OF CANCER CARE When cancer becomes a part of life s journey it is hardwork. y Providing support for client (your presence as a caring person) y Providing support for the family y Promoting positive self-concept y Promoting coping throughout the cancer continuum A. Diagnosis and treatment (clients received diagnosis and treatment in different ways) B. Survivorship (client who entered successful treatment enter an indeterminate period of long term survivorship) C. Recurrent disease and progression (most clients live with the threat or reality of recurrent disease) D. Terminal illness, when everything is done that can be done, compassion is the only thing that brings beauty and meaning to our lives. It is the irreplaceable gift.

INTERVENTIONS:  Measure and document Intake & output  Inspect all body orifices & tubes for bleeding  Prevent bleeding  Administer anticoagulant as prescribed.  Administer cryoprecipitated clotting factors if DIC progress and hemorrhage is the primary problem. 6. SIADH INTERVENTIONS:  Monitor accurate recording of intake and output.  Initiate fluid restriction and increased sodium intake as prescribed.  Administer antidiuretic hormone antagonist as prescribed.  Monitor serum sodium levels. 7. TUMOR LYSIS SYNDROME INTERVENTIONS:  Monitor Intake and Output.  Encourage oral/IV hydration.  Administer diuretics as prescribed.  Administer medications that increase the excretion of purine as prescribed.  Prepare to administer IV infusion of glucose and insulin to treat hyperkalemia.  Prepare the client for dialysis if hyperkalemia and hyperuricemia persist despite treatment.

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