Managing side effects of childhood cancer treatment☆☆☆

Immunosuppression and infection 

Immunosuppression is defined as the body's immune system inability to respond to pathogenic organisms and tissue damage. Children with cancer become immune impaired from a number of causes. Lymphocyte function can be altered by stem cell defects preventing normal lymphocyte development. Splenic dysfunction in the cancer patient can prevent maturation of the blood cells, and alterations in the inflammatory response can impair host resistance (Kline, 2002). Cancer therapy can decrease immunoglobulin concentrations and cause defects in cellular immunity.

Significant neutropenia can develop during chemotherapy creating an increased risk for infection in the child with cancer. Neutropenia occurs when the absolute neutrophil count decreases below 500 cells/mm3 or when the absolute neutrophil count between 500 and 1,000 cells/mm3 is expected to decline secondary to cancer therapy (for calculation of absolute neutrophil count see Table 1).

Table 1. Calculation of Absolute Neutrophil Count

	WBC = 7.4 K/UL (also expressed as 7,400 UL or 7.4 × 103/mm3); neutrophils (poly/segs) = 40%; nonsegmented neutrophils (bands) = 12%; lymphocytes = 39%; monocytes = 4%; basophils = 2%; esinophils = 3%.
	Step 1: Determine total percent neutrophils (poly/segs + bands) 40% + 12% = 52% (0.52)
	Step 2: Multiply WBC by % neutrophils
	ANC = 7,400 × 0.52
	ANC = 3,848 (normal)
	WBC = 0.9 K/ULC 900 or 0.9 × 103/mm3)
	Neutrophils (poly/segs) = 7%
	Nonsegmented neutrophils (bands) = 7%
	Lymphocytes = 76%; monocytes = 5%; basophils = 2%; esinophils = 3%.
	Step 1: 7% + 7% = 14% (0.14)
	Step 2: ANC = 900 × 0.14
	ANC = 126 (severely neutropenic)

WBC, white blood cell; ANC, absolute neutrophil count

Table 2. Neutropenic Precautions

	Call the Health Care Provider immediately if the child has a fever ≥ 38.5°C or if persistent fever ≥38.0°C over 2 to 3 hours (Pizzo & Alexander, 1999a, 1999b; Mendelson, 1998).
	Maintain strict handwashing by all caregivers before and after patient care.
	Avoid crowded areas and contact with individuals who are known to have infectious illnesses (e.g., varicella, influenza, respiratory syncytial virus, adenovirus, or herpes zoster or herpes simplex).
	Avoid urinary catheterization.
	Avoid rectal temperatures, suppositories, and enemas.
	Practice meticulous oral, personal, and perianal hygiene on a daily basis.
	Notify the health care provider immediately if the child is exposed directly to varicella (e.g., classmate, sibling, playmate, or hospital/clinic exposure).
	Avoid live virus vaccines (e.g., measles, mumps, rubella vaccine.
	Implement protective isolation as indicated by institution's policy.

Most neutropenic patients do not present with a confirmed site of infection and empirically are given broad-spectrum antibiotics. Multiple antibiotics and growth factors are given to the patients with prolonged neutropenia (i.e., 7 days or longer) owing to the increased incidence of developing secondary infections. Granulocyte colony stimulating factor (G-CSF), a frequently used growth factor, decreases the duration of neutropenia by stimulating the proliferation of the progenitor (ancestor) cells of the granulocytes, specifically the neutrophils. The most common dose and route of administration of G-CSF are 5 mcg/kg/d given subcutaneously beginning 24 hours after the last dose of myelosuppressive chemotherapy (Woolery-Antill, 2002). G-CSF is usually discontinued after the nadir occurs (point of the lowest neutrophil count after chemotherapy), at which time the neutrophil count usually returns to the patient's baseline values. Children receiving G-CSF require close monitoring of blood counts to evaluate the G-CSF response. Currently, there are no known long-term side effects, however, the only consistent side effect is bone pain. A dull, transient achy bone pain most often begins 2 to 3 days after the initiation of the G-CSF in response to neutrophil proliferation and is relieved once the neutrophils appear in the circulating blood (Woolery-Antill). The American Society of Clinical Oncology recommend the use of hemapoietic growth factors be reserved for high-risk patients experiencing prolonged fever and neutropenia (Woolery-Antill).

A major challenge for the nurse caring for a child with fever and neutropenia is monitoring for signs of sepsis (e.g., peripheral perfusion, temperature of extremities, level of consciousness, vital signs, and pulse oximetry). Sepsis is defined as the clinical suspicion of infection with evidence of a systemic response including hypotension, tachycardia, tachypnea, hyperthermia or hypothermia, leukocytosis, or leukopenia (Kline, 2002). Fever is the principal and sometimes only initial indication of serious infection or sepsis in the immunocompromised patient. These children should be examined daily by the nurse for signs of infection involving the oral cavity, lungs, gastrointestinal tract including the perineal area, skin, and soft tissues (Alexander, Freifeld, Walsh, & Pizzo, 2002). Because most infectious origins develop from the child's own endogenous flora, the nurse should encourage the parents/child to adhere to strict handwashing practices, perform frequent mouth care, perianal hygiene, and avoid the use of rectal thermometers owing to the chance of introducing pathogens through the rectal mucosa. Protective isolation and food sterilization have little impact on decreasing infectious rates in the neutropenic child. The child and family also are encouraged to verbalize their fears and anxieties related to the febrile life-threatening neutropenic event. Pneumocystis carinii pneumonia (PCP) is a serious life-threatening opportunistic infection that presents most commonly as a diffuse pulmonary infiltrate in the immunocompromised patient. This infection is thought to result from a reactivation of latent PCP cysts because almost all normal children possess detectable antibodies to the organism (Alexander et al., 2002). Children with lymphomas and those who are maintained on steroids as part of their therapy for acute lymphocytic leukemia appear to be at high risk for the development of PCP (Alexander et al., 2002). The incidence of PCP has been reduced significantly with the use of prophylactic agents, therefore, the nurse should stress with the parent and the child the importance of being compliant. Cancer centers routinely recommend trimethroprim-sulfamethoxazole 150mg/M2/d divided into two daily doses given 3 consecutive days per week during therapy. Other alternative prophylactic regimens include dapsone 2 mg/kg/d (maximum dose 100 mg/d), or monthly aerosolized pentamidine 300 mg/dose or intravenous pentamidine 4mg/kg/dose monthly (Hockenberry & Kline, 2002).

Varicella infections 

Varicella (chickenpox) is a highly contagious virus that causes pruritic, maculopapular, vesicular lesions. Infected persons shed the virus 24 to 48 hours before the lesions appear and continue until the vesicles have crusted over. The incubation period ranges from 7 to 21 days after direct exposure to the virus. Herpetic zoster (shingles) occurs in individuals who have had varicella previously. The virus remains dormant in the nerve roots in the latent form and can become reactivated during periods of immunosuppression or stress. Initial symptoms include pain along the involved dermatone and then a vesicular rash on an erythematous base evolves 48 to 72 hours later. If an immunosuppressed child with no history of varicella infection or varicella immunization has direct contact with an individual with chickenpox or shingles, varicella zoster immune globulin should be administered within 96 hours of the initial exposure (Pawlik, 1998). The dose of varicella zoster immune globulin is 125 U/10 kg given intramuscularly with a maximum dose of 625 U (Pawlik). Children who are exposed to varicella or shingles and treated with varicella zoster immune globulin require strict isolation from other immunosuppressed children for 8 to 28 days after initial exposure (American Academy of Pediatrics, 2000). The immunosuppressed child on therapy who develops varicella or zoster usually is treated with intravenous or oral doses of acyclovir. The dose of acyclovir is 1500 mg/M2/d in divided doses every 8 hours intravenously for 7 days or until lesions have crusted. Oral acyclovir usually is not used to treat immunocompromised children with varicella because of the poor oral bioavailability. However, some experts have used oral acyclovir in selected immunocompromised patients at a lower risk for developing severe varicella such as children with leukemia in whom careful follow-up evaluation is assured (American Academy of Pediatrics).

Nursing care of the immunosuppressed child with varicella includes assessing for signs of secondary bacterial infection (e.g., lesions, lung) and keeping the child well hydrated to prevent renal toxicity associated with acyclovir administration. Airborne and contact precautions should be implemented by using gowns, gloves, and masks as indicated by the institution. Other interventions, such as keeping the nails short and clean, applying topical antipruritics (i.e., calamine lotion, colloidal oatmeal baths), and administering intravenous fluids or oral antipruritics also are implemented.

Central venous access devices-related infections 

Approximately 2 decades ago, central venous access devices (CVAD) were introduced as an integral part of the pediatric oncology patient's treatment plan. These devices are used for administration of chemotherapy, blood components, antibiotics, intravenous fluids, total parenteral nutrition, medications, and blood sampling. CVAD-related infections typically are defined as the isolation of an organism from a blood sample, catheter tip, or the catheter exit site (Weiner & Albanese, 1998). Several types of CVAD including external catheters (e.g., Broviac® and Hickman® [Band Access Systems, Murray Hill, NJ] catheters) and implantable catheters (e.g., Port-a-cath [Deltec at deltec.com]) are used in the cancer patient. More recently, the temporary external catheters known as percutaneous central venous catheters are being used. The nurse is in a significant position to recognize and prevent CVAD-related infections by:

Immunizations 

Live vaccines are contraindicated in the immunosuppressed child until the immune system has recovered, which occurs 3 to 12 months after the completion of cancer chemotherapy. Administering inactivated vaccines (e.g., diphtheria, tetanus, acellular pertussis, and Haemophyllus influenzae type B) to the immunosuppressed child with an absolute lymphocyte count greater than 700 mm3 is at the discretion of the physician because mounting a response to the vaccination during cancer treatment is questionable (Hockenberry & Kline, 2002). A child's immune response to a vaccine can be determined by performing vaccine titers.

Children scheduled for spleen radiation or removal should be immunized with the pneumococcal and meningiococcal vaccines at least 2 weeks before the planned procedure. The influenza vaccine is recommended by cancer centers because it can be administered safely to the immunosuppressed patient as well as the staff that care for these children. The physician and nurse should provide guidance to parents regarding which immunizations can be given safely to the immunosuppressed child.

Anemia 

Many children with cancer will develop anemia or a reduction in red blood cells during the course of cancer treatment. Some common causes of anemia include erythroid hypoplasia caused by bone marrow suppression caused by cancer chemotherapy or radiation therapy. Nutritional deficiencies (e.g., iron, B12, or folate) and bone marrow infiltration with tumor/disease or blood loss may all contribute to the development of anemia.

Transfusions often are given when the hemoglobin concentration is between 6 to 8 g/dL and declining and/or when the child manifests signs of anemia such as severe fatigue, headache, irritability, or tachycardia. During radiation therapy, many institutions transfuse to maintain a hemoglobin level between 8 to 10 g/dL because radiation therapy is felt to be more effective in an oxygen-rich environment (Rieger & Haeuber, 1995). Transfusion therapy includes administration of leukocyte-depleted, irradiated, packed red blood cells (PRBCs) at a dose of 10 mL/kg, which usually increases the hemoglobin level 2 to 3 g/dL. Children with severe anemia (<6 g/dL) may need the PRBCs to be delivered slowly (2-3 mL/kg/h) in separate small multiple transfusions (aliquots) to avoid development of congestive heart failure and pulmonary edema. General guidelines for blood product administration are found in Table 3.

Table 3. Guidelines for Blood Component Administration

	Identify the patient.
	Obtain the ordered blood component from the blood bank.
	Administer premedications if indicated (e.g., acetaminophen, solunedrol, diphenhydramine hydrochloride). Question whether steroids can be used for premedication in patient on protocol.
	Before administration:
	Verify physician order.
	Compare donor identification numbers and ABO-Rh compatibility on transfusion record with information on blood component and double check with another nurse.
	Verify leukoreduction and/or irradiated product. Check with another nurse.
	Identify patient with full name using the identification band.
	Compare full name of patient with the identification on blood component and transfusion record
	Do not transfuse component if information does not exactly match
	Check expiration date and time on blood component.
	Once it is determined that everything is correct, sign the transfusion record.
	Inspect the blood component for color and consistency, turning component upside down to gently mix its contents.
	Prepare filter, tubing, and 0.9% normal saline flush solution.
	Record patient's baseline vital signs.
	Start transfusion and record date and time of initiation.
	Stay with the patient for the first 5 to 15 minutes to assess for an acute reaction.
	Record patient's vital signs 15 minutes after the initiation of the transfusion and as required by institutional policy.
	At completion, document patient's condition, vital signs, and complete transfusion record.
	Place copy of transfusion record in patient's chart and return copy to blood bank.
	Always use universal precautions when handling blood components and contaminated equipment.
	Disposal of bag and tubing per institutional policy.

Adapted from Jassak, P., & Godwin, J. (1991). Blood component therapy. In S. B. Baird, R. McCorkle, & M. Grant (Eds.), Cancer nursing comprehensive textbook (p. 38). Philadelphia: W.B. Saunders Co.

Methods of reducing the large number of leukocytes in a unit of PRBCs are performed primarily through filtration and irradiation. The use of microaggregate filtration during the collection and the administration of PRBCs removes almost all the leukocytes without damaging the red blood cells. Because cytomegalovirus travels by way of the lymphocytes, the use of the microaggregate filter has decreased significantly the incidence cytomegalovirus-transmitted infection (Norville & Bryant, 2002). PRBCs also are treated with irradiation (2,500-3,000 cGy), which renders the donor's lymphocytes incapable of replication, therefore preventing transfusion-associated graft-versus-host disease (Rossetto & McMahon, 2000). Graft-versus-host disease develops when viable T lymphocytes attack the host and occurs 1 to 2 weeks after the transfusion. It is manifested by fever, maculopapular skin rash, diarrhea, and hepatitis with or without jaundice (Rossetto and McMahon). Both filtration and irradiation methods have reduced greatly the number of transfusion reactions.

Thrombocytopenia 

Thrombocytopenia is defined commonly as a platelet count less than 100,000 mm3 that develops as a result of increased destruction, decreased production, or loss of platelets (Panzarella, Rasco-Baggot, & Comeau, et al., 2002). The principal cause of bleeding in children with cancer is the suppression of platelet production caused by chemotherapy or radiation therapy.

The pediatric oncology nurse plays an instrumental role in teaching the caregiver thrombocytopenic precautions (see Table 4). Platelet infusions are administered in the thrombocytopenic patient if there is active bleeding or if decreased platelet counts contribute to bleeding. Platelet transfusions are indicated for patients undergoing major surgery with a platelet count less than 50,000 mm3; patients receiving medications that interfere with platelet production, and brain tumor patients with platelet counts between 30,000 to 50,000 mm3 to avoid bleeding into the tumor (Norville & Bryant, 2002). Unless the child is bleeding or is at a high risk for bleeding, platelet transfusions usually are avoided to decrease the likelihood of alloimmunization (Norville & Bryant).

Table 4. Common Thrombocytopenic Precautions

	Observe for signs and symptoms of bleeding (excessive bruising, petechiae, bloody or black stools, hematuria, prolonged nosebleeds [> 10 min with continuous pressure], gingival bleeding).
	Avoid contact sports and rough activities (e.g., football, soccer, wrestling, bicycle riding, skate boarding, roller-blading, diving, tree climbing, trampolines, scooters, and go cart riding).
	Provide safe environment to prevent trauma (e.g., use of siderails, gates, helmets, and knee pads) and avoid rectal manipulation (thermometers, suppositories, and enemas) and urinary catheterization.
	Avoid oral mucosa trauma (use soft toothbrush or swab stick for oral care, avoid dental floss and eating sharp food items such as chips and ice).
	Use a nail file instead of clippers for nail trimming.
	Notify health care provider before invasive procedures (e.g., dental work, placement of nasogastric tube, endoscopy).
	Use an electric shaver rather than a razor blade (adolescent).
	Add stool softeners and increase fiber in diet to prevent constipation.
	Avoid use of aspirin/aspirin-containing products and cautiously use nonsteroidal anti-inflammatory agents (ibuprofen, motrin) under medical supervision only.
	Invasive procedures (i.e., lumbar puncture and bone marrow aspiration, nasogastric tube placement) should be performed with caution.

The nurse administers the platelet infusions as rapidly as possible depending on the age and clinical status of the patient. The frequency of taking vital signs tend to vary among institutions, but should be assessed before the platelet infusion and at the end of the infusion. The nurse should frequently assess the child's skin, gums, emesis, secretions, stool, and urine for blood as well as reinforce thrombocytopenic precautions (see Table 4).

Malnutrition 

Malnutrition in the pediatric oncology population has been reported to occur in 8% to 32% of patients (Han-Markey, 2000). Nutritional requirements vary among children with cancer, depending on the diagnosis, tumor location, and treatment regimen (e.g., surgery, radiation, and chemotherapy). At diagnosis, nutritional goals focus on maintaining normal growth and development as well as preventing nutritional deficiencies. These goals are accomplished by the assessment of the child's nutritional status and the development of an individualized nutritional care plan. The initial nutritional assessment includes a history of the child's eating habits, serum albumin/prealbumin levels, food allergies, use of nutritional supplements, and baseline weight and height measurements. Depending on the nutritional assessment of the patient, the use of the nutritional support algorithm can assist in determining the type of treatments to be used (e.g., enteral, parenteral, or a combination of these treatments) (Bowman, Williams, Sanders, et al., 1998) (see Figure 1).

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Fig. 1. Nutritional support algorithm. Adapted from Bowman, I. C., Williams, R., Sanders, M., et al. (1998). Algorithm for nutritional support: Experience of the metabolic and infusion support service of St. Jude Children's Research Hospital. International Journal of Cancer, 11(suppl.), 76-80. Reprinted by permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.

Enteral feedings, whether used as a supplement or as the sole means of nutritional intake, are a highly successful method of reversing malnutrition and maintaining adequate nutritional status in the pediatric cancer patient. Enteral feeding preserves the integrity of the intestinal mucosa by keeping it functional (Nitenberg & Raynard, 2000). The nurse should observe for enteral feeding complications such as nausea, vomiting, diarrhea, constipation, or tube irritation (nasal or gastrostomy button site). Treatment of the feeding complications include using sterile gauze to protect the gastrostomy button insertion site, adjusting the infusion rate of the feeds, adjusting the formula strength, adding an antiemetic, or changing the formula with the addition of fiber, lactose, or protein.

Because most pediatric patients have venous access devices, health care providers tend to use these devices for parenteral nutritional administration to avoid additional invasive procedures, and bleeding or mucosal damage associated with enteral feeds. Parenteral feedings are used primarily for nutritional support when the unavailability of the gastrointestinal tract owing to surgery, radiation, infection, mucositis, gastroenteritis, or excessive abdominal tumor burden. However, the higher incidence of septic complications and CVAD-related infections associated with parenteral feeding make the enteral feeding a preferred route owing to its ability to maintain gut integrity without significant gastroenteritis or mucosal damage (DeSwarte-Wallace, Firouzbakhsh, & Finkelstein, 2001).

In formulating individualized care plans, the oncology nurse should involve input from the multidisciplinary team that includes the caregiver, child, physician, dietary specialist, psychologist, and the child life specialist. Because intensive dietary counseling to improve nutritional intake in the child with cancer has been proven ineffective in past studies, the teaching focus should be aimed at the acceptance of the type of nutritional feeding by the child and family (Nitenberg & Raynard, 2000).

The nurse, along with the dietician and other multidisciplinary team members, should implement the following nutritional interventions:

Nausea and vomiting 

Nausea and vomiting is the most common side effect of cancer treatment and may be the most challenging. Nausea is controlled by the vomiting center in the medulla. Chemotherapy-associated vomiting is a reflex controlled by the chemoreceptor trigger zone that stimulates the vomiting center in the brain. Nausea and vomiting may be induced by several factors including tumor location (e.g., brain, gastrointestinal tract, and kidney), cancer therapy, pain, and anxiety. Radiation therapy to the brain, gastrointestinal tract, chest, and neck also may cause nausea and vomiting. Anticipatory nausea and vomiting may occur before chemotherapy and is triggered by sights, smells, tastes, and other environmental stimuli such as observing needles or the sight of the clinic. Anticipatory nausea and vomiting has been controlled by using behavioral interventions (e.g., guided imagery, muscle relaxation, and hypnosis) accompanied with benzodiazepines. Acute nausea and vomiting occurs within 24 hours of treatment whereas delayed nausea and vomiting occurs greater than 24 hours posttreatment and may last several days (Berde, Billett, & Collins, 2002).

Several classifications of antiemetics are used to control nausea and vomiting. The advent of serotonin-receptor antagonists such as ondansetron and granisetron have produced the most successful antiemetics available to date. Phenothiazines that include promethazine and chlorpromazine block dopamine receptors from stimulating the chemoreceptor trigger zone (Berde, Billett, & Collins, 2002). Antihistamines such as diphenhydramine and hydroxyzine that control extrapyramidal effects of phenothiazines also have some antiemetic effects. Benzodiazepines such as lorazepam are anxiolytic agents and central nervous system depressants. The antiemetic action of steroids such as dexamethasone is uncertain, but these agents are used in conjunction with other antiemetics to manage delayed nausea and vomiting. Cannabinoids (tetrahydrocannabinol or marinol) cause central nervous system depression resulting in decreased nausea and vomiting (Panzarella et al., 2002; Berde et al., 2002). Most patients benefit from an individualized plan consisting of a combination of antiemetic medications. The nurse's role includes an accurate assessment of hydration status, administration of antiemetic before chemotherapy, around-the-clock antiemetic dosing, anticipation of delayed nausea and vomiting with certain agents (i.e., Cisplatin, Doxorubicin), as well as management or avoidance of psychogenic factors that can trigger nausea. Because of the anticipatory nausea and vomiting some children benefit by administration of benzodiazepines at bedtime or in the morning before their visit to the clinic, and other children benefit from avoiding the use of such triggers as alcohol wipes, white uniforms, or laboratory coats (e.g., most pediatric nurses wear colorful smocks or shirts). Once the successful antiemetic regimen is identified, the nurse should document the plan and review it with the parents and staff. Other nursing interventions to minimize nausea and vomiting include frequent oral hygiene, especially after vomiting, minimizing pungent odors, encouraging small frequent meals, and avoiding highly spiced and fatty foods.

Mucositis 

Mucositis is a progressive, inflammatory, ulcerative condition of the oral and gastric mucosal tissue precipitated by chemotherapy, radiation therapy, physical trauma, poor dental hygiene, neutropenia, thrombocytopenia, or impaired nutritional status (Kennedy & Diamond, 1997). Mucosal damage as a result of cancer chemotherapy or impaired nutritional status occurs owing to the interruption of the cell renewal process of the epithelium leading to mucosal atrophy and ulceration (Madeya, 1996). Thrombocytopenia or physical trauma may lead to bleeding and further mucosal damage whereas neutropenia or poor dental hygiene predisposes the oral mucosa to secondary infection. Radiation therapy to the head and neck destroys the epithelial cells whereas radiation to other body cells leads to an inflammatory reaction causing generalized erythema and desquamation of the mucosal area. An initial assessment of the oral cavity includes inspecting the condition of teeth and gingival mucosa (see Table 5), obtaining a history of previous dental care, and assessing the frequency of routine dental examinations, brushing and flossing routine, and use of orthodontic appliances. If the child has a previous history of cold sores or fever blisters, these may recur throughout treatment (Kennedy & Diamond).

Table 5. Mucositis Care

	Grade	Description*	Nursing Interventions
	Grade 0	Mucosa and gingiva are pink, moist with no lesions or pain.	Assess oral mucosa (condition of buccal cavity, lips and tongue, teeth, gingiva, comfort status)
			Institute preventive dental hygiene after meals and bed time:
			Wash hands for 3 minutes before performing oral care;
			Brush teeth/tongue/gums using fluoride toothpaste, soft toothbrush;
			Rinse mouth after brushing with salt and soda solution (1/2 teaspoon salt and 1 teaspoon baking soda in 1 pint water) or chlorhexidine 5-10 mL) swish and spit;
			Use waxed floss daily if platelet count > 100,000 and ANC > 1,000;
			Apply lip moisturizer as needed;
			Avoid food and beverages for at least 30 minutes after oral rinsing;
			Avoid lemon-glycerin swabs and hydrogen peroxide owing to drying effect and irritation of grandulating tissue;
			Avoid electric toothbrushes and water piks;
			Removal of all orthodontic appliances usually is recommended to avoid mucosal trauma.
			Record observations and interventions.
	Grade I	Erythematous oral mucosa or whitish, swollen gingiva involving < 25% of mucosal area with slight or no pain.	Assess oral mucosa (condition of buccal cavity, lips and tongue, teeth, gingiva, comfort status).
			Continue preventive dental hygiene as described under grade 0.
			Record observations and interventions.
	Grade II	Erythematous focal ulcers or white, swollen patches involving 25-50% of mucosal area with mild pain.	Assess oral mucosa (erythema, swelling, lesions [describe], discomfort, ability to eat or drink).
			Monitor weight, vital signs, and laboratory studies (e.g., complete blood count, ANC, platelet count, electrolytes).
			Continue preventive measures listed under grade 0 but increase gentle brushing and rinse to include before AM meal and after all snacks.
			Use topical anesthetics in mouthwash (equal parts diphenhydramine/antacid suspension with or without viscus lidocaine) every 4-6 h and as needed.
			Acetaminophen, acetaminophen with codeine, or an opoid infusion may be ordered for pain control.
			Record observations and interventions

*Data from Kennedy, L., Diamond, J. (1997). Assessment and management of chemotherapy-induced mucositis in children. Journal of Pediatric Oncology Nursing, 14(3), 164-174; Parulekau, W., MacKenzie, R., Bjarnason, G., et al., (1998). Scoring oral mucositis. Oral Oncology, 34, 63-71.

Many institutions have adopted their own treatment plan for the prevention and treatment of mucositis. Agents used to prevent and/or treat mucositis include salt and soda rinse, chlorhexidine, and a mouthwash (e.g., diphenhydramine, antacid, with or without lidocaine). Nurses must be able to recognize the grade of mucositis and implement appropriate nursing care (see Table 5). They also must maintain the child's nutritional and hydration status by accurately recording and monitoring intake/output and weight measurements. Encouraging fluid intake including popsicles, sodas, jello, or yogurt can be both soothing and also moisturizing to lips and oral mucous membranes.

Pain 

Pain is an unpleasant sensory and emotional experience and can be acute or chronic. Acute pain is a primitive protective response of brief duration that usually is caused by a well-defined stimulus (e.g., surgery, trauma) that subsides as healing occurs (Sentivany-Collins, 2002). Chronic pain is a nonprotective response with long-term changes often involving the nervous system and persist for 3 to 6 months or longer (Sentivany-Collins). Four common types of pain are found in children with cancer. Tumor-related pain may occur owing to direct invasion of the bone, impingement of tumor on nervous tissue, or from metastatic disease (Patterson, 1992). Treatment-related pain is associated with side effects of cancer therapy such as mucositis, infections, drug-induced neuropathy, and post-lumbar puncture headaches (Patterson). Postoperative-related pain is caused by tumor removal or biopsy procedure, amputation, phantom pain, and central line placement. Procedural-related pain, identified by many children as the most anxiety provoking of all cancer-related pain, is caused by bone marrow aspiration and biopsy procedure, lumbar puncture, venous access, subcutaneous or intramuscular injection, and finger sticks (Macpherson & Lundbald, 1997). Because the pediatric oncology patient usually experiences some pain during the course of treatment, the nurse's assessment of pain must include the child's description of pain, a history of previous measures used to manage pain, cultural influences, parental responses to the child's pain, and the child's age and developmental stage to provide appropriate explanations and effective interventions (see Table 6). Uncontrolled pain often is managed best by a multidisciplinary pain team that includes patient and family, physicians, nurses, child life specialists, psychologists, psychiatrists, and social workers.

Table 6. Childhood Cancer Pain

	Nursing Interventions
	Assess signs and symptoms of pain before and after interventions
	Acute pain (heart rate, respiratory rate, blood pressure changes, dilated pupils, diaphoresis, location, intensity, duration)
	Chronic/prolonged pain (vital signs may normalize)
	Pain behaviors: facial expression (grimace, cry, moan) posture (rigidity, flair, stoic, squirming, tense), and signs of regression, aggression, decreased appetite. Self-report using:
	Pain-rating scales (Faces scale, Oucher scale ≥ 3 y)
	Number scale ≥ 8 y
	Verbal description (parent and child)
	Environmental factors (e.g., temperature, equipment, noise)
	Pharmacologic treatment
	Oral nonopioids:
	Use acetaminophen 10-15 mg/kg/dose every 4 h pm (maximum, 650 mg/dose) (take temperature before use to avoid masking signs of infection)
	Avoid salicylates and use NSAIDS sparingly owing to potential for bleeding
	NSAIDS: 10 mg/kg every 6-8 h pm (maximum, 800 mg/dose) with food
	Oral opioids:
	Codeine: 0.5-1 mg/kg every 4-6 h pm (maximum, 60 mg/dose)
	Morphine: starting doses 0.2-0.5 mg/kg every 4 h or sustained release 0.3-0.6 mg/kg every 12 h
	Intravenous analgesics (avoid intramuscular subcutaneous injections to treat pain)
	MSO4 0.05-0.1 mg/kg intravenous continuous or every 1-2 h
	Fentanyl 0.5-3 mcg/kg every 1-2 h
	For postsurgical pain: institute MSO4 or fentanyl patient-controlled anesthesia intravenously then slowly switch to oral opioids and/or NSAIDS
	Adjuvant therapy:
	Antiseptics and mouthwash for mucositis
	Stool softener/laxative
	Antifungal, antiviral, antibacterial agents
	Anitemetics
	Antipruritics
	Tricyclic antidepressants (e.g., amitriptyline, imipramine, or nortriptyline)
	Corticosteroids (e.g., prednisone or dexamethasone)
	Palliative radiation
	Nonpharmacologic interventions:
	Deep slow breathing and relaxation techniques
	Massage, positioning, heat
	Imagery and hypnosis
	Play therapy
	Lying flat for 30 minutes after lumbar puncture
	Increase oral fluid intake for 24 hours after lumbar puncture
	Daily oral care/institutional guidelines
	Distraction using video games, television, music
	Record response to interventions
	Invasive procedure
	Explain procedure to parents and child and use nonpharmacologic interventions listed above
	Use of oral analgesics
	Diazepam 0.1-0.3 mg/kg by mouth (maximum, 10 mg) at least 1 hour before procedure or Lorazapam 0.03-0.1 mg/kg every 4-6 h or 1 h before procedure (maximum 2 mg/dose)
	Midazolam 0.2-0.4 mg/kg every (maximum, 15 mg) 30-45 minimum,
	Use of local anesthesia:
	Lidocaine (1% subcutaneously 4-5 minimum before procedure)
	Emla (Lidocaine 2.5% and prilocaine 2.5%) cream at least 1-1 1/2 h before procedure
	Use of IV sedation*
	MSO4 0.05-0.1 mg/kg IV 5 minimum before procedure or fentanyl 0.5-1 μgm/kg IV 3 minimum before procedure
	Midazolam 0.05 mg/kg IV initial dose with subsequent doses 0.05 mg/kg IV pm (maximum, 0.15 mg/kg)
	Reversal agents available for conscious sedation:
	Naloxone 0.01 mg/kg IV repeat every 2-3 minimum for reversal MSO4 and fentanyl (maximum, 0.2 mg)
	Flumazenil 0.2 mg/kg IV every 1 min repeated (maximum, dose 3 mg/kg) for reversal of midazolam
	Record response to interventions
	*The American Academy of Pediatrics has set specific recommendations for monitoring of patients during conscious sedation: oxygen, pulse oximetry, suction, ambu bag, reversal agents, crash cart, and staff all available during procedure.

American Academy of Pediatrics, Committee on Drugs. (1992). Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics, 89 (6), 1110-1115. NSAID, nonsteroidal anti-inflammatory drugs; IV, intravenous

The most effective pain management strategies reported by children with cancer include the use of effective pain medications combined with adequate rest and sleep, massage, heat, distraction, and social support. Pharmacologic interventions should be based on frequent assessment and the step by step approach to pain as described by the World Health Organization (Galloway & Yaster, 2000; Hellsten, 2000) (see Figure 2).

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Fig. 2. Therapeutic ladder for pain management. Reprinted with permission from the World Health Organization and IASP. (1998). Cancer pain relief and palliative care in children. Geneva: World Health Organization.

Nonopioid medications act to block the peripheral generation of afferent nerve impulses in sensory neurons related to tissue injury and/or inflammation (Patterson, 1992). The most commonly used nonopioid medication in the pediatric cancer patient is acetaminophen. Salicylates are avoided because they affect platelet function and nonsteroidal anti-inflammatory agents are used with caution owing to effects on platelet aggregation. Children with analgesic dose requirements that exceed reasonable oral dosing or for whom oral medications are not tolerated should receive pain medications by an alternate route (Hockenberry-Eaton, Barrera, Brown, Bottomley, & O'Neill, 1999) other than intramuscular, subcutaneous, or rectal routes. It has been proven that patient-controlled analgesia alone or in conjunction with continuous morphine infusion is effective in children as young as 3 years of age (Patterson, 1992). It is the nurse's responsibility to be familiar with pain medications including the dose, side effects, potency and onset, and duration of action to ensure safe and effective pain management.

Fifty percent to 75% of children with cancer who experience pain state that it is related primarily to procedures and treatment (Wolfe, Grier, Klar, et al., 2000). One of the most significant improvements in the management of procedural-related pain is the topical anesthetic cream EMLA (Astra Zeneca at Astrazeneca-us.com), a eutectic mixture of local anesthetics (lidocaine and prilocaine in a 1:1 ratio) (Wong, Hockenberry, Wilson, Winklestein, & Schwartz, 2001). A thick layer of EMLA® cream of at least 2 mm is applied to the intact skin site and covered with an occlusive transparent dressing for a minimum of 1 hour. The nurse, however, must be aware that a 90- to 120-minute application of EMLA® is needed for procedural pain involving deeper skin penetration (e.g., bone marrow aspiration, lumbar puncture, intramuscular injection) or in dark-skinned children owing to their thicker statum corneum (Macpherson & Lundbald, 1997). The total anesthesia duration of the EMLA® is approximately 4 hours with mild side effects such as pallor, erythema, or edema at the application site. The nurse should assess the skin site after removal of the anesthetic cream just before implementation of the procedure for sensitivity by tapping or lightly scratching the skin to show the child that the needle will not be felt (Wong et al., 2001). In situations that are immediate or require a deeper anesthetizing effect, buffered or warmed lidocaine, which decreases stinging, used alone or in conjunction with EMLA® is indicated.

The nurse, child life specialist, and multidisciplinary pain team prepares the child and parents for the invasive procedure. The purpose and description of the procedure is discussed with the parent and an appropriate explanation of the procedure is given to the child. Developmentally appropriate interventions (see Table 6) are taught to the parent ranging from keeping the infant swaddled and warm, staying in the child's view, using a soothing voice with the toddler and preschooler, or using distraction with the school-aged and adolescent child (Dahlquist, Busby, Slifer et al., 2002). Moderate to deep sedation for pediatric patients undergoing invasive procedures allows the child to endure repeated painful procedures with minimal discomfort and anxiety. Fentanyl or morphine with midazolam (see Table 6) is used to provide adequate sedation. However, the most frequently used safe, effective analgesic agents for deep sedation are ketamine or propofol alone or in combination with an opioid such as fentanyl or midazolam (Jayabose et al., 2001; Tyc, Bieberich, Hinds, & Sifford, 1998). Regardless of the type of sedation, the nurse must evaluate vital signs, oxygen saturation, level of consciousness, cardiovascular status, and comfort level during administration of sedation. Other nursing responsibilities include maintaining a patent airway, stimulating the child to breathe, and administering 100% oxygen via mask as needed, and administering reversal agents (see Table 6) for prolonged sedation or respiratory distress. A combination of nonpharmacologic, pharmacologic, and adjuvant measures must be implemented by the nurse to provide a comprehensive management of cancer-related pain.

End-of-life pain occurs in the dying child and may comprise any of the four previously discussed types of cancer-related pain. Children with terminal cancer often experience considerable pain and suffering before they die (Morgan & Murphy, 2000). Suffering in the dying patient has been attributed partially to health care providers and family members who administer inadequate pain management owing to fears of addiction, respiratory depression, apnea, and death from analgesics, especially when analgesics exceeded maximum dosages (Hellsten, 2000; Sentivany-Collins, 2002). Because the nurse has close contact with the dying child, the nurse is in the best position to educate other health care providers and the family regarding proper pain management. It is the responsibility of the nurse to assess the pain status and share knowledge of pharmacologic and nonpharmacologic interventions with both family and health care providers. Allowing the family to participate in the child's pain management will keep the focus on maintaining comfort regardless of the analgesic dosage.

Psychosocial aspects 

The nurse plays an instrumental role in the supportive care team by encouraging the child and family to express their feelings regarding side effects of cancer treatment. The nurse creates a caring atmosphere by using listening skills, supporting the family, and providing resources for emotional support. The family and caregiver convey less anxiety to the child if taught the use of anxiety-reducing strategies (e.g., soothing words, gentle strokes, calm voice, holding the child, and providing warmth and nourishment) by the nurse. Before any medical procedure, both the preschooler and school-aged child require brief and honest descriptions of the procedure. It is important for children to express fears and anxieties by using play (i.e., imaginative and medical) with dolls, drawing and group games, as well as be given the opportunity to participate in the procedure (i.e., hold Band-Aid, choice of thigh for injection). Some children request a description of each action during the invasive procedure whereas others prefer music, story-telling, videos, or complete silence, all of which may provide comfort.

Most school-aged children and adolescents are able to understand the diagnosis, treatment plan, side effects, and the purpose of the invasive procedures. Because these children have an awareness of their bodies, the effects of cancer therapy such as alopecia, weight gain or loss, or skin changes may change the child's acceptance of self. Even though the supportive care team encourages the older child to express verbally feelings of anger, fear, denial, and disbelief, it is still more difficult for these children to accept the diagnosis and side effects of therapy than the younger child. Alopecia is the side effect of chemotherapy and radiation therapy that most children find devastating to their self-image. The nurse can help the child cope with the changed appearance by suggesting the use of hats, scarves, wigs, and allowing the child an opportunity to express feelings of anger and sadness related to hair loss. Also, the nurse should allow the child the opportunity to participate in medical decision making with the parents and encourage them to focus on future goals, promoting a healthy self-image and self-esteem despite having cancer.

Because most children with cancer grow up to become well-adjusted adults, the nurse encourages the child and family to focus on the child's work by encouraging a return to school as soon as medically possible. School re-entry can be a difficult task to accomplish by the child newly diagnosed with cancer. If the child returns to school physically different than when last seen by the classmates, the return to school may create increased anxiety for the child. Even though returning to school can be stressful, it conveys hope of survival to the child. The school environment provides the child with the opportunity to maintain peer relationships, continue school work, and facilitate acceptance by peers and teachers. Most centers provide a school re-entry program for the cancer patient. The typical school re-entry program supports staff (e.g., nurse, child life specialist, social worker) release time to visit the child's school to explain the type of cancer, treatment, and side effects to prepare the classmates, teacher, counselor, and principal for the child's return to the classroom.