Pediatric emergency medicine trisk 685

HEPATIC AND GASTROINTESTINAL COMPLICATIONS OF CANCER TREATMENT Cancer treatment frequently affects the GI tract and liver The majority of complications are minor and fully reversible A few complications are potentially severe and/or have long-term consequences Chemotherapy frequently impairs the ability of the mucosal lining of the GI tract to regenerate itself Severity varies with different chemotherapy regimens Time to occurrence is similar to the timing of myelosuppression with onset to 10 days after treatment and recovery by 14 days Radiation also causes temporary injury to any areas of mucosa included in the radiation field This injury becomes evident after several weeks of treatment and will persist/worsen until treatment is complete Initial assessment must include a thorough oncology history to elicit chemotherapy or radiation exposures as well as localizing symptoms and a complete physical examination Chemotherapy-induced mucositis can affect part of or the entire GI tract from the oropharynx to the rectum and may manifest as oral ulceration, throat pain, esophagitis, gastritis, enteritis, or rectal ulceration Radiationinduced mucosal injury is often associated with skin manifestations in the treatment field Oropharyngeal involvement usually includes pain and visible mucosal injury ranging from irregular mucosal surfaces to scattered ulcerations to severe diffuse ulceration with swelling of the lips and inability to open the mouth Esophagitis may be evident only by refusal to swallow and/or retrosternal pain Enteritis, common with radiation fields that include the intestines, may be evident with crampy watery diarrhea Mucosal injury to the rectum leads to pain with defecation, tenesmus, or rectal pain There may be obvious perirectal erythema or ulceration As discussed elsewhere, avoid a digital rectal examination, which may cause an increased likelihood of bacteremia Management of moderate to severe mucositis usually requires pain control with parenteral narcotics Cancer patients may require higher than standard starting doses, especially if already on narcotics at home Patients and their families should be asked whether they have medication preferences based on prior episodes of pain PCA with both continuous and bolus dosing should be initiated in the ED if available Do not use NSAIDs for pain control since they usually have platelet inhibitory effects and the development of thrombocytopenia frequently coincides with mucositis Avoid regular use of acetaminophen, which may mask fever since neutropenia also often occurs at the same time Assess hydration and administer intravenous fluids as needed Patients with adequate oral pain control and oral hydration can be discharged to home Others will need to be admitted for pain control and/or hydration until the mucositis resolves Nausea and vomiting are common symptoms in oncology patients It is critical to consider the differential diagnosis and not just attribute all such symptoms to chemotherapy-induced nausea and vomiting (CINV) CINV can be divided into three categories: acute (within 24 hours of emetogenic treatment), delayed (2 to days after treatment), and anticipatory Anticipatory symptoms are conditioned symptoms that occur without emetogenic treatment with a variety of emotional or sensory triggers These anticipatory symptoms can become chronic in some patients Despite appropriate prophylactic therapy, almost all cancer patients experience some nausea and vomiting Radiation to the GI tract or the CNS is itself emetogenic Other causes of nausea and vomiting include GI injury from a variety of causes such as gastritis from steroids, obstipation/constipation, medication side effects (e.g., narcotics), pancreatitis (from asparaginase), GI obstruction (e.g., adhesions from prior surgery), or superior mesenteric artery syndrome in patients with severe malnutrition Management of CINV (or radiation induced) is outlined in Table 98.10 As with pain management, all medications are less effective when treating established symptoms Standard hydration and electrolyte management should be employed for all patients with severe nausea/vomiting An abdominal x-ray can be helpful if obstruction or obstipation/constipation is suspected Amylase and lipase should be measured in patients who are being treated with asparaginase Constipation is very common in oncology patients Contributing factors included decreased GI motility from vinca alkaloids, narcotics, poor oral intake, decreased activity, and/or withholding due to rectal pain from mucositis The evaluation should include a detailed history to elicit any of the contributing factors as well as a specific bowel history Physical examination should not include a digital rectal examination due to potential increased risk of bacteremia Abdominal x-ray may be helpful in establishing the amount of stool Treatment of constipation in the oncology patient should include only those agents that can be given by mouth Rectal suppositories and enemas should be avoided except in extreme circumstances Patients with severe symptoms may need to be admitted TABLE 98.10 MANAGEMENT OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV) Agents with a high therapeutic index Drug class Specific drug Serotonin -S3 receptor antagonists Ondansetron Pediatric dosage and frequency ( usual adult maximum ) 0.15 mg/kg ( mg ) q h or 0.45 mg/ kg ( 24 mg ) q24h 10-40|ig/kg ( mg ) q24h 10 mg/m ( 10 mg ) ql 2-24 h Route Comment IV/PO Ondansetron max IV dose: 16 mg Steroid Granisetron Dexamethasone NK receptor Aprepitant 125 mg on day 1, followed by 80 mg once daily on days and PO Scopolamine 1.5-mg fixed -dose transdermal TDP antagonist IV/PO IV/PO Should not be used in patients with steroid -sensitive malignancies without consultation with oncologist ( e.g., ALL, lymphoma ) Use should be avoided/minimized in patients at high risk of infection or if at increased risk of mucosal toxicity from chemotherapy ( e.g., AML, advanced lymphomas, ALL during induction ) For patients >20 kg May be combined with serotonin receptor antagonists Other patch For patients >40 kg Avoid concurrent use of anticholinergic drugs such as diphenhydramine Agents with a low therapeutic index Pediatric dosage and frequency Drug class Specific drug ( usual adult maximum ) Route Comment Benzodiazepine Lorazepam 0.05 mg/kg ( mg ) q h IV/PO Dopamine antagonist Metoclopramide 0.5 mg/kg q h IV/PO Other Dronabinol Olanzapine mg/m2 2.5-10 mg PO PO Overdosage may be common with weight -based dosing strategies Thus, also consider 0.25 mg for 25-50 kg, and mg for >50 kg More potent as an anxiolytic than as an antiemetic Children are at high risk of ext r a py mi dal r ea ctions Must be given with diphenhydramine prophylaxis No data in use younger than yrs Limited data in younger patients IV, intravenous; PO, per os; ALL, acute lymphoblastic leukemia ; AML, acute myeloid leukemia ; NK , neurokinin ; TDP, transdermal patch Transaminitis with elevations in AST and/or ALT is common in pediatric cancer patients Many chemotherapy agents cause a mild reversible transaminitis Treatment-related transaminitis is usually a laboratory-only finding without any clinical correlate Transfusion-associated viral transaminitis can also occur in the frequently transfused oncology population, but the direct and indirect screening of donor blood has reduced the incidence of viral transmission Immunosuppression from treatment can also increase the risk of CMV and EBV Isolated transaminitis may be noted during an evaluation in the ED but rarely is an indication for further laboratory evaluation Hyperbilirubinemia is common during cancer treatment, is usually mild and reversible and rarely requires any further ED evaluation Such elevations are likely multifactorial and may relate to chemotherapy, transfusion, or subclinical liver injury Unexpected moderate or severe hyperbilirubinemia should be fully assessed Diarrhea in an oncology patient may be triggered by a variety of causes including radiation injury, chemotherapy, and C difficile colitis due to prolonged hospitalizations and/or use of broad-spectrum antibiotics Venoocclusive disease (VOD) of the liver is a rare but important complication to recognize Risk factors include exposure to actinomycin-D chemotherapy and liver radiation Manifestations include hepatomegaly, transaminitis, thrombocytopenia, and ascites The thrombocytopenia is frequently more than what would be expected from the chemotherapy alone or may occur at the wrong timing relative to chemotherapy Once the diagnosis is suspected, a hepatic ultrasound with Doppler assessment of hepatic vein flow should be performed Reversal of flow in the small hepatic veins establishes the diagnosis in the appropriate clinical setting Management is supportive until the problem resolves on its own Most patients will require admission for both observation and support For a discussion of typhlitis, see section on “Infectious Complications of Cancer Treatment.” RENAL COMPLICATIONS OF CANCER THERAPY Renal injury from cancer treatment is very common and some degree of renal dysfunction is frequently present even in patients with normal creatinine for age Other patients will have documented renal dysfunction based on elevated creatinine, decreased glomerular filtration rate (GFR), or decreased 24-hour creatinine clearance Renal complications may also lead to metabolic disturbances (see “Metabolic Complications of Cancer Treatment” section) Uric-acid nephropathy can occur in patients with very high cell turnover (see “Leukemia” section) Drug-induced renal injury is common in oncology patients ( Table 98.8 ) Radiation injury to the kidney may cause renal insufficiency as well as radiation nephritis, to months after treatment Typical findings include the manifestations of vasculitis with hemolytic uremic syndrome (HUS) Oncology patients are also at risk for medical renal disease associated with poor perfusion, exposure to multiple nephrotoxic agents, and hypertension Since renal injury is common, it is appropriate to check BUN, creatinine, electrolytes, calcium, magnesium, and phosphate in all ill oncology patients If significant abnormalities are noted, the oncology-specific history should be reviewed to determine specific risk factors or exposures that may help explain the problem In general, the management of significant abnormalities is not unique in patients with cancer and should follow the guidelines in Chapter 100 Renal and Electrolyte Emergencies Consider the possibility of a decreased GFR (whether ... high therapeutic index Drug class Specific drug Serotonin -S3 receptor antagonists Ondansetron Pediatric dosage and frequency ( usual adult maximum ) 0.15 mg/kg ( mg ) q h or 0.45 mg/ kg ( 24... concurrent use of anticholinergic drugs such as diphenhydramine Agents with a low therapeutic index Pediatric dosage and frequency Drug class Specific drug ( usual adult maximum ) Route Comment Benzodiazepine... neurokinin ; TDP, transdermal patch Transaminitis with elevations in AST and/or ALT is common in pediatric cancer patients Many chemotherapy agents cause a mild reversible transaminitis Treatment-related