Pediatric emergency medicine trisk 682

CLINICAL PEARLS AND PITFALLS Tumor lysis syndrome can occur in patients who have undergone CAR-T cell therapy and is managed similarly to other oncology patients with this complication Cytokine release syndrome (CRS) presents with fever and multi-system organ failure and can mimic the presentation of septic shock Neurotoxicity related to CAR-T cell therapy includes nonspecific neurologic symptoms but can progress to coma Current Evidence CAR-T cell therapy uses a patient’s genetically modified T cells to express anticancer surface receptors Once developed, the CAR-T cells are infused back into the patient where they encounter target antigen, leading to rapid proliferation and release of cytokines Over the subsequent 28 days, these patients are at high risk for cytokine-mediated toxicities, particularly after the first weeks, and can present acutely ill Though this cellular therapy is not universally available, it is becoming more accessible and the ED clinician should be aware of this potential complication in patients who have undergone this therapy Clinical Considerations Clinical Recognition Patients with CRS may appear to be in septic shock Fever, chills, myalgias are typically the earliest symptoms, and when severe are followed by tachycardia, hypotension and signs of capillary leak including localized edema, pleural or pericardial effusions, altered mental status, and shock Neurotoxicity may occur concurrent with CRS and includes nonspecific symptoms including headache, confusion, and tremor Severe neurotoxicity symptoms include hallucinations, seizures, and signs of cerebral edema Patients can progress to coma Clinical Assessment As with any critically ill oncology patient, the stabilization of airway, breathing, and circulation is the highest priority Institutions using CAR-T cell therapy will likely have protocols in place for the initial response to patients who present after CAR-T cell infusion, and initial assessment and management should be approached in conjunction with oncologic consultation Laboratory assessment of organ function including a CBC, electrolytes and management of renal function, as well as measurement of inflammatory markers including ferritin and CRP Neuroimaging and CSF examination may be required in patients with neurotoxicity Management Patients who present with signs of CRS may be indistinguishable from patients with sepsis and concurrent treatment for presumed sepsis including administration of broad-spectrum antibiotics is important For mild symptoms, supportive care may be sufficient For patients with severe symptoms, evidence of organ dysfunction, or life-threatening illness, the addition of glucocorticoids and/or tocilizumab (an anti– IL-6 monoclonal antibody) may be indicated, in consultation with an oncologist All of these patients should be admitted and many will require a critical care setting METABOLIC COMPLICATIONS OF CANCER TREATMENT Complications affecting metabolic balance and the endocrinologic system are common in children with cancer These may be because of the neoplastic disease itself, as has been addressed in the sections on newly diagnosed cancer, or due to complications from cancer therapy TLS is probably the most noteworthy example of metabolic derangement in the setting of cancer (see “Leukemia” section) TLS can be present at the time of diagnosis or develop as chemotherapy is initiated and tumor cells begin to die in response Prevention of tumor lysis relies on protecting the function of the kidneys while preventing severe metabolic derangements ( Table 98.3 ) Hyperhydration should be initiated to achieve brisk, dilute urine output In addition to IV hydration, all patients should receive therapy with either allopurinol (10 mg/kg/day with maximum dose 300 mg) or rasburicase Allopurinol is a xanthine oxidase inhibitor that impairs the production of uric acid Rasburicase, a recombinant urate-oxidase enzyme, causes direct lysis of uric acid and leads to a rapid drop in uric acid levels The usual starting dose is 0.2 mg/kg IV Rasburicase is indicated in patients who are at higher risk of TLS complications such as patients with compromised renal function or an extremely elevated uric acid level, who have advanced Burkitt lymphoma, who cannot tolerate hydration (e.g., CNS hemorrhage or pre-existing cardiac dysfunction), or whose uric acid is rising despite allopurinol Rasburicase is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency as it can result in oxidative stress and hemolysis Use of alkalinized intravenous fluids is becoming less common as its efficacy is uncertain If using rasburicase, hydration with alkalinization is unnecessary Of note, not all electrolyte abnormalities in the setting of TLS should be corrected ( Table 98.3 ) Hyperphosphatemia can be treated using aluminum hydroxide as frequently as every to hours Hypophosphatemia should not be corrected unless it is in a critically low range (less than mEq/L) Serum potassium levels must be aggressively monitored Hyperkalemia in the setting of TLS should be managed as it would be in other disease states (see Chapter 100 Renal and Electrolyte Emergencies ) with Kayexalate, insulin and glucose, and dialysis, if needed Hypokalemia should not be corrected unless the patient’s serum potassium falls in a critically low range (less than mEq/L), significant muscular weakness develops, or if hypokalemia is associated with EKG changes Hypocalcemia should remain uncorrected as well, unless clinical signs or symptoms develop Supplemental calcium may increase the risk of formation of calcium phosphate precipitates in the kidney Renal tubular dysfunction is common in oncology patients Patients may waste electrolytes such as sodium, potassium, calcium, magnesium, and phosphorus through their kidneys as a result of specific treatment exposures or prior renal injury Antifungal agents such as amphotericin and ambisome cause potassium wasting, which may have clinical significance Calcineurin inhibitors, such as tacrolimus or cyclosporine, which may be used after stem cell transplantation, can cause significant magnesium wasting Patients with hypomagnesemia are more likely to experience seizures when on calcineurin inhibitors so the magnesium should be kept more than 1.8 mEq/L in these patients In addition, patients with tumors of the CNS may renally waste sodium so monitoring of serum sodium is crucial, especially in the postoperative period Patients receiving drugs that cause salt wasting are often prescribed oral electrolyte replacement However, inability to tolerate oral medications or nonadherence may allow electrolyte abnormalities to develop Most of these derangements are clinically asymptomatic with the notable exceptions of hypocalcemia, which can cause tetany or cardiac arrhythmias and hyponatremia resulting in refractory seizures For the most part, management and replacement strategies for these electrolyte abnormalities not differ from children who not have cancer (see Chapter 100 Renal and Electrolyte Emergencies ) However, when replacing calcium in pediatric oncology patients, the clinician should remember that hypomagnesemia, a common side effect of cancer therapies, could complicate efforts to address hypocalcemia Elevated blood sugar can be a transient side effect of corticosteroids as well as asparaginase therapy Asparaginase affects the body’s ability to make many proteins, including insulin In ALL treatment, steroids and asparaginase may be used together and hyperglycemia may result Treatment need not include insulin if dietary measures alone are sufficient to control the serum blood sugar If blood glucose is greater than 250 mg/dL or is significant enough to cause glycosuria or ketonuria, treatment with small doses of insulin may be considered However, the approach to insulin use in this setting should be conservative so as to limit the risks of hypoglycemia Diabetic ketoacidosis is rare in this situation High serum calcium levels are observed commonly in the setting of adult malignancy but are rare in children with cancer Hypercalcemia is usually related to the tumor destroying bone or to ectopic production of parathyroid hormone by the tumor itself This complication is more common if patients are also taking calcium supplements or calcium-containing medications such as antacids If asymptomatic, hypercalcemia does not always require intervention When present, symptoms may include nausea/vomiting, constipation, altered mental status, and renal failure Management in these cases is similar to strategies to address hypercalcemia outside of the oncology setting (see Chapters 89 Endocrine Emergencies and 100 Renal and Electrolyte Emergencies ) However, steroids should be avoided in patients with known or suspected leukemia or lymphoma Control of the underlying malignancy is the best way to address the hypercalcemia SIADH can develop as a result of some cancers themselves, particularly those involving the lungs or CNS, or from treatment with vincristine and cyclophosphamide Management of this complication hinges on fluid restriction and does not differ from that of SIADH developing in other settings (see Chapter 100 Renal and Electrolyte Emergencies ) PAIN Goals of Treatment Pain is a true emergency The relief of pain is a critical element of caring for children with cancer, and should be addressed even in patients who present to the ED for other concerns CLINICAL PEARLS AND PITFALLS NSAIDs and aspirin are generally avoided due to their antiplatelet activity Cancer patients are frequently not opioid naïve and may require higher starting doses than are standard Current Evidence Unfortunately, pain is a common symptom in oncology patients with data showing that more than 30% of pediatric cancer patients have experienced pain in the previous week When pain leads to visits to the ED, it requires careful and immediate management Severe pain is a true emergency in and of itself, and also may be particularly upsetting for cancer patients who may have already confronted significant pain as part of their cancer diagnosis, who may anticipate or fear future pain, and who may worry (usually needlessly) that their pain is a sign of progressive cancer In some cases, pain may be related to the tumor itself and therefore often will respond to chemotherapy or other cancer-directed therapies Tumors can cause ... than 30% of pediatric cancer patients have experienced pain in the previous week When pain leads to visits to the ED, it requires careful and immediate management Severe pain is a true emergency. .. settings (see Chapter 100 Renal and Electrolyte Emergencies ) PAIN Goals of Treatment Pain is a true emergency The relief of pain is a critical element of caring for children with cancer, and should... cancer (see Chapter 100 Renal and Electrolyte Emergencies ) However, when replacing calcium in pediatric oncology patients, the clinician should remember that hypomagnesemia, a common side effect