3.Oncologic emergencies for nurse student .pptx

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1. Oncologic emergencies and their management Abinet Abebe (B.Pharm, MSc in Clinical Pharmacy) Department of Clinical Pharmacy and Pharmacy Practice School of Pharmacy, CHMS, Mizan Tepi University

2. ONCOLOGIC EMERGENCIES Due to complex nature of their disease and cytotoxicity of treatment, cancer patients may experience a range of potentially life-threatening conditions that require urgent intervention An oncologic emergency may be defined as any acute, potentially life-threatening incident, directly or indirectly related to a patient’s cancer or its treatment.

3. Oncologic emergencies may result in permanent morbidity or death. While some oncologic complications are subtle and take weeks or even months to develop, others can manifest in a few hours, and quickly lead to severe negative outcomes, including paralysis, coma, and death. Prompt identification and intervention can prolong survival and improve quality of life

4. Once recognized, the aggressiveness of management is influenced by reversibility of the immediate event, probability of long-term survival and cure Oncologic emergencies can be categorized as malignancy related (metabolic , hematologic, structural) or treatment related

5. Metabolic Emergencies Tumor Lysis Syndrome/TLS TLS is a condition that occurs when a large number of cancer cells die within a short period, releasing their contents in to the blood . TLS is triggered by rapid, acute cell lysis caused by cancer treatment. It is often associated with chemotherapy but can also occur after radiation and biologic therapies. The release of intracellular products (e.g., uric acid, phosphates, calcium, potassium) overwhelms the body’s homeostasis

6. Although the frequency of tumor lysis syndrome is increasing in those with solid tumors , it is most common with hematologic malignancies, particularly acute leukemia and high-grade lymphomas. Tumor lysis syndrome usually presents within seven days of cancer treatment, and patients with preexisting renal insufficiency are at increased risk

7. Patients commonly present with azotemia, hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, ARF ….. quantified by Cairo-Bishop definitions Prevention and stabilization are attempted by initiating vigorous rehydration, maintaining urine output, reducing baseline uric acid levels, and limiting potassium and phosphorus intake during high-risk periods (i.e., the three days before and the seven days after initiation of cancer treatment). Prompt referral to an inpatient oncology team is recommended. In setting of severe acute renal insufficiency, early hemodialysis can be key

8. Cairo-Bishop Definitions for Tumor Lysis Syndrome ≥ 2 of the following in one 24-hour period within 3 days before or 7 days after the initiation of chemotherapy Calcium ≤ 7.0 mg per dL (1.75 mmol per L) or 25% decrease from baseline Phosphorus ≥ 4.5 mg per dL (1.45 mmol per L) in adults, 6.5 mg per dL (2.10 mmol per L) in children, or 25% increase from baseline Potassium ≥ 6.0 mEq per L (6.0 mmol per L) or 25% increase from baseline Uric acid ≥ 8.0 mg per dL (476 μmol per L) or 25% increase from baseline

9. Clinical tumor lysis syndrome is laboratory criteria from above plus ≥ 1 of the following Cardiac arrhythmia or sudden death Creatinine ≥ 1.5 times the upper limit of normal for age Seizure Clinical Presentation TLS should be suspected in patients with a known malignancy (hematologic or solid tumor) who present with fluid overload, decreased urine output, lethargy, muscle cramps, arrhythmias or seizure Signs : Renal failure, Seizures, Fluid overload, Congestive heart failure, Arrhythmias Symptoms : Lethargy, Paresthesias, Muscle cramps, Tetany, Syncope, Nausea, Vomiting, Decreased urine output

10. Severe hypocalcemia is one of the most critical manifestations of TLS and may cause : Cardiovascular (ventricular arrhythmias, heart block, hypotension) Muscular (cramps, spasms), Neurological ( confusion, delirium, hallucinations, seizures) Investigations : CBC, Electrolytes, Urea, Creatinine, Phosphorus, Calcium, Albumin, ECG, Uric acid Diagnosis : Cairo-Bishop criteria

11. Management of TLS Treatment of TLS include: In the absence of acute renal dysfunction and oliguria, vigorous IV hydration (3L/m² per day) and dieuresis (≥100ml/m² per hour) should be maintained Diuretics (furosemide, mannitol) may be required to maintain urine output and prevent fluid overload, but should only be used if there is no evident of acute obstructive uropathy or hypovolemia

12. Hyperuricemia: Rasburicase [Elitek] 6mg IV infusion daily for 1-7 days Consider use of Allopurinol 300mg orally Hyperphosphatemia : Remove phosphate from IV fluids Administer oral/or NG phosphate binders (e.g. aluminum hydroxide or aluminum carbonate) for up to 2 days Calcium infusions should be withheld In severe cases continuous dialysis or venovenous hemofiltration may be required

13. Hyperkalemia : Close evaluation of ECG, cardiac rhythm and electrolytes Oral and IV supplements should be discontinued In asymptomatic patients : Sodium polystyrene sulfonate: 15-30g orally, 30-50g rectally In symptomatic patients : Regular insulin 10 units IV and 20-25g dextrose IV Sodium bicarbonate 1mEq/kg IV (induces influx of potassium into cells) Calcium gluconate 1g IV over 5 minutes may be used for life threatening arrhythmias (with continuous ECG monitoring for bradycardia) Consider dialysis

14. Symptomatic Hypocalcemia : IV calcium gluconate 1-2g IV (monitor for acute obstructive uropathy)

15. Hypercalcemia of Malignancy / MAH Hypercalcemia affects up to 10% to 30% of cancer patients It is the leading cause of hypercalcemia in hospitalized patients. Characterized by a serum calcium level of more than 10.5 mg per dL (2.63 mmol per L). Patients with breast cancer , lung cancer, and myeloma are most commonly affected, but hypercalcemia can also occur with other malignancies i.e squamous cell carcinomas of the head or neck, lung, kidney, or cervix

16. Hypercalcemia of malignancy has a poor prognosis, 80% of patients will die within a year with a median survival of 35 days from diagnosis The main pathogenesis of hypercalcemia in malignancy is increased osteoclastic bone resorption , which can occur with or without bone metastases. The main factor associated with cancer-related hypercalcemia is parathyroid hormone–related protein, which is produced by many solid tumours. Parathyroid hormone–related protein increases calcium by activating parathyroid hormone receptors in tissue: results in osteoclastic bone resorption; It also increases renal tubular resorption of calcium.

17. In most centers, total plasma calcium is measured, including proteinbound and ionized calcium As the measured plasma calcium is affected by the albumin level, the measured calcium needs to be corrected according to the serum albumin. The formula for this is as follows: Corrected calcium (mmol/L) level = Measured calcium (mmol/L) + ([40 - albumin (g/L)] × 0.02) MAH= corrected serum calcium >2.6 mmol/L

18. Signs/Symptoms Neurological : weakness/fatigue, memory/concentration difficulty drowsiness , confusion, delirium➞ coma Cardiovascular : shortened QTc interval, enhancement of digitalis effects ST segment elevation, hypotension, Bradyarrhythmias➞ heart block➞ cardiac arrest Gastrointestinal :anorexia, constipation, nausea, vomiting Genitourinary : polyuria, nocturia, dehydration➞ oliguria

19. Investigations : CBC Electrolytes Calcium Albumin Creatinine ECG Other as clinically indicated

20. Management of MAH Aggressive treatment as soon as possible depending on severity of hypercalcemia. P atients with calcium >14 mg/dL require therapy with volume expansion with isotonic saline to maintain sufficient urine output For short-term management (in the first 48 h), calcitonin can be used: increases renal calcium excretion and decreases bone resorption via interference with osteoclast function Bisphosphonates: F or longer term control of hypercalcemia, with a maximum effect after 2-4 days

21. Intravenous bisphosphonates Since bisphosphonates are potentially nephrotoxic, caution is warranted when used in patients with impaired renal function. Dose reduction in combination with adequate hydration may minimize risk They block osteoclast activity and decrease bone resorption. Additional benefits: possibly reduce malignant bone pain and delay onset of progressive bone disease in various cancers

22. Two commonly used drugs are pamidronate and zoledronate In a study comparing the 2 agents Z oledronate was proven to be superior at achieving normocalcemia faster, for longer, and for more patients Another advantage of zoledronate is that it only requires a 15-minute infusion versus a 2- to 4-hour infusion for pamidronate; however , zoledronate is more expensive . Either drug is a reasonable choice in treating cancer related hypercalcemia.

23. Dose Pamidronate 90 mg in 500 mL of normal saline infused intravenously over 2 to 4 hours. Zoledronate is 4 mg intravenously over 15 minutes. The dose might need to be adjusted for renal dysfunction. Using a bisphosphonate will start to decrease the serum calcium in approximately 12 hours, with the nadir being reached in 4 to 7 days.

24. Management in general medical unit: IV normal saline is usually administered at 250-500mL/ hr or 2 to 3 L of normal saline per 24 hours until the patient is drinking well Zoledronic acid 4mg IV infusion, if unavailable Pamidronate 90 mg IV infusion Calcitonin 4 units/kg subcut or IM Sources of calcium supplementation should be discontinued if possible Sedatives, hypnotics and analgesics ……………. caution Loop Diuretics: if there is evidence of fluid overload used to promote calciuresis Dialysis should be considered in the presence of acute or chronic renal failure

25. Hematologic Emergencies Neutropenic fever (NF) NF is defined as fever in a neutropenic patient either one episode of above 38.3°C or a temperature above 38°C sustained for more than 1 h . Neutropenia is defined as an absolute neutrophil count (ANC) below 1000 cells/ μL and severe neutropenia as ANC <500 cells/ μL NF has significant 5% mortality rate in high-risk and 1% in low-risk patients.

26. The highest-risk causative agents include anthracyclines, taxanes , topoisomerase inhibitors, platinums , gemcitabines and alkylating agents. Bacterial infections are common , fungal infections also occur in high risk patients Signs of NF: a single axillary/oral temperature of > 38.5°C or a sustained temperature of > 38°C for one hour, and ANC < 500 or an expected decrease of ANC < 500 in the next 48 hours

27. NF should be considered in solid tumours, currently on chemotherapy and presents with a fever The Multinational Association for Supportive Care in Cancer (MASCC) has developed a MASCC risk index , a validated tool for estimating the risk for NF-related complications Patients with NF with a MASCC score ≥21, without clinical alarm signs : C an be safely treated in the outpatient setting with a combination of oral fluoroquinolones and amoxicillin/clavulanate .

28. An alternative is the use of oral moxifloxacin. High-risk patients with NF require hospitalization and treatment with intravenous antibiotics . It is important that antibiotics are started within 1 h from NF diagnosis after taking blood and urine cultures

29. Multinational Association for Supportive Care in Cancer (MASCC) score: Variable Score Burden of illness No or mild symptoms 5 Moderate symptoms 3 Severe symptoms No hypotension (systolic BP>90mmHg) 5 No chronic obstructive pulmonary disease 4 Solid tumor/lymphoma with no previous fungal infection 4 No dehydration 3 Outpatient status (at onset of fever) 3 Age <60 years 2

30. Low Risk Criteria MASCC score of ≥ 21, who also meet ALL of the following criteria: Patient is not currently on antibiotics Patient has no history of adherence issues Patient is able to return to the facility for follow-up Patient has no significant nausea or vomiting Patient is able to take oral medication Patient has 24 hour live-in support

31. If the patient meet low risk criteria, can be treated with Ciprofloxacin 750 mg orally, bid, (adjusted for renal function) and Amoxicillin/Clavulanate 875 mg orally, bid, (adjusted for renal function) If serious allergy to penicillin, Ciprofloxacin 750 mg orally, bid, (adjusted for renal function) AND Clindamycin 600mg, orally, tid The patient should receive their first oral dose of antibiotic within the ED and monitored for 4 hours to verify stability and tolerability of treatment

32. High-risk patients Pipericillin-tazobactam 3.375 g IV q6h, if not available, Imipenem 500mg IV q6h If serious allergy to penicillin, Ciprofloxacin 400 mg IV q12h and Vancomycin 1 g IV q12h If the lab work is delayed, give the first dose of antibiotic before lab results are back

33. The source of infection is only identified in about 20% of patients and most of the identified infections are believed to arise from the endogenous flora . In high-risk patients fungal pathogens are also more common The use of colony stimulating factors (CSF) did not show any effect on the overall survival, but induced a faster recovery from fever and shorter hospital stay. Most guidelines do not recommend the use of CSF for the management with NF except in patients with high-risk features such as older age, pneumonia, hypotension, sepsis and being hospitalized at the time of development of fever

34. Neurological emergencies Spinal cord compression (SCC) SCC occurs in approximately 5% of cancer patients and is most often due to extradural spread from vertebral metastases It can cause pain and irreversible loss of neurologic function. Although all tumors can cause SCC, it most often occurs in patients with cancers with a tendency to metastasize to the spinal column such as breast cancer, lung cancer, lymphoma, prostate cancer and myeloma It develops in about 5% of patients with cancer

35. Malignant epidural SCC is a true oncologic emergency if left untreated, can lead to progressive pain, sensory loss, incontinence, and irreversible paralysis Clinical Presentation : Any new onset back in a patient with a history of cancer should increase suspicion of SCC Signs : Motor weakness Sensory impairment

36. Symptoms : Pain localized to the spine (due to neural compression) Pain may worsen with movement, lying down, coughing, sneezing or straining Limb heaviness or loss of balance Altered bowel and bladder function MRI is the preferred imaging modality to diagnose SCC

37. Treatment The goals of treatment for patients with malignant SCC are to decrease pain, maintain ambulation, and if possible, decrease tumour bulk Corticosteroids, radiation therapy, surgery, or a combination of these modalities As soon as SCC is suspected: Dexamethasone 10-20mg IV followed by 4-6 mg IV q4h…………..10 days Corticosteroids rapidly reduces edema and back pain and improve neurologic functioning Decompressive surgery followed by postoperative radiotherapy In patients not candidates for surgery, radiotherapy is recommended treatment

38. Mechanical Emergencies Superior vena cava (SVC) syndrome SVCO, which is a common complication of malignancy, refers to a constellation of signs and symptoms resulting from partial or complete obstruction of blood flow through the superior vena cava to the right atrium. The obstruction may be caused by compression, invasion, thrombosis, or fibrosis of this vessel. Lung cancer, both small cell and non-small cell, and non-Hodgkin lymphoma combined account for approximately 85% of all cases of SVCO

39. Presentation Signs : Facial or neck swelling Dilated chest vessels Stridor Symptoms: Facial fullness Swelling of trunk and upper extremities Headache or confusion Cough, Dyspnea, Orthopnea

40. Investigations Contrast enhanced CT scan of the chest: right hilar mass with SVC occlusion MRI is useful in patients who cannot tolerate the CT contrast medium On examination: Edema & Elevated JVP Increased number of collateral veins covering anterior chest wall Treatment Glucocorticoids (prednisone or methyl prednisolone) decrease the inflammatory response to tumor invasion and edema surrounding the tumor Dexamethasone 10mg IV followed by 4mg q6-8h

41. Radiotherapy is the preferred initial treatment for recurrent disease after chemotherapy or with tumours insensitive to chemotherapy, such as non-small cell lung cancer Emergency treatment with radiotherapy is also indicated if a histologic diagnosis cannot be established in a timely manner, and life-threatening situations, such as airway obstruction, spinal cord compression, or increased intracranial pressure Chemotherapy can also be used as the initial treatment of SVCO caused by malignancies sensitive to chemotherapy, such as small cell lung cancer and non-Hodgkin lymphoma .

42. Reading assignment Brain metastases Malignant airway obstruction Hyperviscosity syndrome Bleeding in a cancer patient Neutropenic enterocolitis (NE, typhlitis) Disseminated intravascular coagulation SIADH

43. Thank You !!!!