Preoperative Assessment of the Pediatric Patient With Cancer

Introduction

Childhood cancers make up less than 1% of all newly diagnosed cancers each year. However, with increasing survival rates, an increasing number of pediatric patients will present for surgery and/or procedures related to their cancer diagnosis. Many of these patients will require anesthesia, often multiple times, and thorough preoperative assessment and optimization is therefore essential to ensure successful outcomes from cancer surgery.

The preoperative assessment and optimization of a pediatric patient with cancer can be complex. The disease process itself along with associated cancer-related treatments can impact the preoperative physiologic reserve and the perioperative management of these patients. A comprehensive, multidisciplinary approach to evaluation and optimization needs to be undertaken for the best outcomes, including patient and parental satisfaction. However, since surgery or procedures related to a diagnosis of cancer are often not elective, a sense of urgency can sometimes preclude medical optimization.

Children with cancer are typically evaluated by their primary oncologist prior to being referred for procedures under anesthesia. As a result, details of their primary diagnosis, coexisting medical conditions, types of cancer-related treatment undergone, complications associated with those treatments, and the results of laboratory or diagnostic imaging procedures may be available for review. A preoperative clinic visit to evaluate patients prior to the day of surgery or procedure is ideal but not always feasible. This chapter will focus on the important aspects of preoperative evaluation and optimization as they specifically relate to the pediatric patient with cancer.

Neurologic Evaluation

An altered neurologic status may be secondary to tumor progression or related to cancer therapy. Platinum agents, l-asparaginase, ifosfamide, methotrexate, cytarabine, etoposide, vincristine, cyclosporine A, and craniospinal irradiation have been associated with neurotoxic side effects. Commonly associated acute complications include altered mental status, seizures, cerebral infarctions, encephalopathy, hearing loss, vision changes, and peripheral neuropathies. A comprehensive preoperative neurologic evaluation to document the baseline neurologic status, as well as to determine optimal perioperative management strategies, is encouraged.

Patients should continue their regular antiepileptic medications on the morning of surgery, and regular dosing should be reestablished as early as possible after surgery. When multiple doses are likely to be missed, antiepileptic drugs should be administered parenterally, if possible.

Cardiac Evaluation

Some chemotherapeutic agents, particularly cytotoxic antibiotics of the anthracycline class (doxorubicin, daunorubicin, idarubicin, and epirubicin), are commonly associated with cardiotoxicity. Other commonly used drugs in pediatric patients with cancer, for example methadone and the 5-HT3 antagonist ondansetron, may prolong the QT interval and potentially decrease the threshold for cardiac arrhythmias. Chest irradiation, with or without concurrent anthracycline treatment, can potentially lead to pericarditis, pericardial effusions, cardiomyopathy, endocardial fibrosis, valvular fibrosis, conduction abnormalities, and/or coronary artery disease. Children receiving cardiotoxic cancer therapies should undergo periodic cardiac evaluations starting with baseline electrocardiography and echocardiography. In children, physical examination alone has been shown to miss the early signs of chemotherapy-related congestive heart failure in more than 50% of patients. The stress of surgery can also unmask a subclinical cardiomyopathy. Therefore past cardiovascular physical examinations and laboratory studies should be thoroughly reviewed prior to induction of anesthesia.

Pulmonary Evaluation

Pulmonary dysfunction may be associated with the primary disease process or side effects of cancer therapies. A history of treatment with bleomycin, carmustine, lomustine, busulfan, cyclophosphamide, or chest irradiation should warrant an in-depth evaluation of pulmonary status. Symptoms of chronic cough, dyspnea on exertion, and wheezing should be further examined by chest radiography and possibly pulmonary function tests. Pulmonary function tests in children play an important role in evaluating the child with known or suspected lung dysfunction, and they provide baseline measurements, especially prior to undergoing a surgical treatment, which could potentially alter respiratory mechanics. Additionally, pulmonary function tests, chest radiography, and oxygen saturation measurement may be indicated in patients with unexplained symptoms or abnormal findings on physical examination. Obstructive lesions, such as anterior mediastinal masses, neck masses, or oropharyngeal masses, should be evaluated by computed tomography or magnetic resonance imaging. Clinically symptomatic pleural effusions may benefit from therapeutic thoracentesis prior to surgery to enhance physiologic reserve.

Gastrointestinal Evaluation

Gastrointestinal symptoms, such as vomiting, gastroparesis, and obstruction, may occur in pediatric patients with cancer. These symptoms may place the child at risk for malnutrition, electrolyte and acid-base disturbances, and increase the risk for pulmonary aspiration during anesthesia. Chemotherapy-associated nausea and vomiting has been estimated to occur in up to 70% of the pediatric population. The risk of postoperative vomiting has been shown to be higher in children than in adults. Factors that increase the risk of postoperative vomiting include age >3 years, girls who are postpubertal, a previous history of motion sickness, and those who have a personal or family history of postoperative vomiting. A focused gastrointestinal assessment should be performed preoperatively, and any pertinent imaging should be reviewed in order to formulate the safest anesthetic plan and perioperative management.

Hepatic/Renal Evaluation

Chemotherapy, radiation, and hematopoietic stem cell transplant, with associated preconditioning regimens, may be associated with hepatotoxicity, nephrotoxicity, or both. The most common agents associated with hepatic dysfunction in children are methotrexate, actinomycin D, and 6-mercaptopurine. Similar to patients with known liver dysfunction, impaired drug metabolism, hypoglycemia, and decreased coagulation factor production should be considered in children with potential hepatic impairment.

The most common nephrotoxic agents in children are alkylating agents, such as cisplatin, as well as ifosfamide, cyclophosphamide, and methotrexate. Patients with a history of previous nephrotoxicity have the potential for decreased renal excretion of drugs, electrolyte and/or acid-base derangements, and hypertension. Nephrotoxicity can be further compounded by factors such as perioperative administration of nephrotoxic medications and sustained perioperative hypotension. Renal and liver function tests may therefore be clinically indicated prior to surgery.

Endocrine Evaluation

Endocrine and neuroendocrine dysfunction may be seen in pediatric patients with cancer. Adrenal insufficiency, primary or secondary, is an important perioperative consideration. While primary adrenal insufficiency is rare and involves dysfunctional adrenal glands, secondary adrenal insufficiency is more common and often due to exogenous corticosteroid usage. Several chemotherapeutic protocols include glucocorticoids, which are not only used for their antitumor effects but also to treat side effects related to chemotherapy (e.g., nausea). A blunted stress response may persist for several months after exogenous corticosteroid use. The need for stress dose steroids is debated in the literature. However, considering that the stress response is unpredictable in children and that significant harm has not been shown from perioperative stress-dose steroids, the administration of hydrocortisone (1–2 mg/kg) preoperatively, plus every 6 h on the day of surgery for up to 72 h for more complicated surgeries, has been recommended if hypothalamic-pituitary axis suppression is suspected. In the postoperative period, steroid doses can be tapered depending on the degree of surgical stress and replaced with the child’s usual oral steroid dose when appropriate. Hydrocortisone is preferred in children because of its mineralocorticoid and antiinflammatory properties, ease of titration, shorter half-life, and fewer adverse effects when compared with more potent longer-acting glucocorticoids. The dosage, duration, and last dose of exogenous steroids should be verified in the preoperative interview to best determine appropriate coverage.

The primary or metastatic tumor, as well as treatment associated surgical/radiation therapies, can lead to central (neurogenic) diabetes insipidus with resulting vasopressin deficiency. Polyuria and polydipsia are typical clinical symptoms. These patients can present with severe dehydration and hypernatremia if there is inadequate free water intake, such as on the morning of surgery. Accordingly, surgery should be scheduled earlier in the day for these patients. Desmopressin (DDAVP), a vasopressin analogue, prevents water loss by helping the kidneys reabsorb water. For patients with preexisting diabetes insipidus, at home doses of oral/intranasal DDAVP should be verified and administered on the morning of surgery for minor procedures. However, for major surgical procedures, it should be withheld, and careful fluid management should take place intraoperatively. A vasopressin infusion can be titrated to effect intraoperatively or postoperatively, should intra/postoperative diabetes insipidus be suspected.

Concerns of endocrine dysfunction that might require further workup, including those conditions previously listed, or others, such as uncontrolled diabetes mellitus, thyroid dysfunction, and/or secondary electrolyte abnormalities, should be discussed with the patient’s primary physician or appropriate consultant prior to surgery.

Hematologic Evaluation

Radiation and chemotherapeutic agents may potentially cause myelosuppression. Neutropenia should prompt further workup for fever, sepsis, and immunosuppression. If anemia is present, its degree and duration should be considered in perioperative planning. The patient’s condition, comorbidities, type, and urgency of the surgical procedure, and the risk for bleeding should also be weighed to determine whether a preoperative transfusion is necessary. In thrombocytopenic patients, the type of procedure is an important determining factor in whether preprocedural platelet transfusion is warranted. For certain minor procedures such as lumbar punctures, platelet counts as low as 20 × 10 ⁹ per liter have been shown to be safe. Conditions that can induce coagulopathy include sepsis, leukocytosis, vitamin K deficiency, l-asparaginase treatment, or a new diagnosis of leukemia. The hematology service should be consulted for difficult questions regarding existing or potential coagulopathies.

Pain Evaluation

Tumor- or metastases-related pain is common at the time of cancer diagnosis in children. It can also stem directly or indirectly from chemo/radiation therapy. It is estimated that approximately 89% of children with advanced disease experience pain. Pain in the pediatric cancer patient is often underestimated and undertreated due to inadequate pain assessment tools, as well as physician reluctance to prescribe opioids due to the fear of respiratory complications and/or addiction. Self-reported pain scales work best for children >6 years of age but numerous observational pain scales exist for younger children. The reliability of the observational tool depends on the clinical context and the quality of the validation criteria, guiding the caregiver in choosing the correct tool.

Understanding the underlying etiology of a patient’s pain, determining what medication regimens have worked well (i.e., optimal analgesia with the least side effects), along with the current analgesic regimen being used, is important during the preoperative assessment to devise an appropriate analgesic plan. Tolerance to opioids can often exist; therefore a multimodal approach should be employed, if possible. Regional anesthesia, which can be safely provided for children while under a general anesthetic, should be incorporated when appropriate and discussed with the family and surgical team prior to the procedure.

Preoperative Laboratory Testing

Routine preoperative laboratory or radiologic testing is not recommended in pediatric oncology patients presenting for minor or noninvasive procedures but rather ordered on a case-by-case basis or if it is deemed that the results may influence the anesthetic management. A complete blood count should be considered in conditions that increase the likelihood of anemia such as newly diagnosed leukemia or lymphoma, recent chemoradiation, stem cell transplant, a recent episode of bleeding, or age less than 6 months. Additionally, it can be considered if there is a concern for thrombocytopenia, which is also possible with newly diagnosed leukemia, recent chemoradiation, or due to splenic sequestration. On the other hand, baseline complete blood counts are considered routine in children presenting for major surgical procedures.

Coagulation studies are rarely necessary, but may be considered if there is a clinical history of bleeding despite normal platelet counts, if there is potential for clinically significant blood loss, or if the expected blood loss would be poorly tolerated.

An electrolyte panel should be ordered if there is a known or suspected derangement. Common conditions associated with electrolyte abnormalities include syndrome of inappropriate antidiuretic hormone (SIADH), hypercalcemia (can be associated with bone tumors and neuroblastomas), pituitary tumors, malnutrition, hyperalimentation, dehydration, renal dysfunction, or existing or recent tumor lysis syndrome (hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia).

Fasting Guidelines

Practice guidelines for preoperative fasting in children undergoing elective procedures are shown in Table 46.1 . There has been recent interest in liberalizing the guidelines to 1 h for clear liquids in accordance with guidelines and consensus statements offered by some European societies. The argument for allowing clear liquids up to 1 h prior to anesthesia is that some studies have shown that there is complete gastric emptying at 1 h after ingestion of clear fluids; hence the practice would not increase the risk of pulmonary aspiration.

Table 46.1

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