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Supportive Care and management of Metabolic Emegrencies

Supportive Care and management of Metabolic Emegrencies. Prof:Mervat Atfy Mohamed. Haematology and oncology unit-Zagazig university Hospital. Metabolic Emergencies. Many metabolic and endocrinology problems can potentially occur in patients with cancer.

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Supportive Care and management of Metabolic Emegrencies

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  1. Supportive Care and management of Metabolic Emegrencies Prof:Mervat Atfy Mohamed. Haematology and oncology unit-Zagazig university Hospital

  2. Metabolic Emergencies Many metabolic and endocrinology problems can potentially occur in patients with cancer. Tumor Lysis Syndrome (TLS) is the most common of these problems found in the pediatric population, and emergency therapy is frequently required despite of prophylaxis management. Prof.Mervat Atfy Mohamed

  3. Objectives 1) Understand how to assess a patient’s risk for developing TLS based on tumor type and associated predictive factors 2) Describe the clinical manifestations and laboratory values suggestive of TLS in patients at risk 3) Summarize current treatment options for the prophylaxis and management of TLS Prof.Mervat Atfy Mohamed

  4. Introduction First TLS was reported in 1929 in adults with chronic leukemia • Tumor lysis syndrome (TLS) is an oncological emergency characterized by severe metabolic derangements • Destruction of malignant cells leads to rapid release of intracellular contents which can Disturb the body’s normal homeostatic Prof.Mervat Atfy Mohamed

  5. TLS Pathology Result of rapid breakdown of malignant cells 􀂄Cell membrane is disturbed 􀂄Lysis of tumor cells. 􀂄Release of intracellular ions: nucleic acids, proteins and their metabolites into circulation DNA Uric acid, Potassium ,phosphours. 􀂄Lead to multi-system organ failure 􀂄Hallmark sign is electrolyte abnormalities Prof.Mervat Atfy Mohamed

  6. TLS Pathology Prof.Mervat Atfy Mohamed

  7. Timing of TLS Treatment induced: Most likely to occur 24-48 hours after the initiation of therapy • Can persist for 4-7 days • Rarely occurs after 7 days from initiation of therapy • Rarely occurs after initial course of therapy • Can occur spontaneously Prof.Mervat Atfy Mohamed

  8. Timing of TLS Can occur spontaneously: in Highly proliferative ,poorly differentiated malignancies as :Burkitts lymphoma,ALL,Acute lymphoblastic lymphoma Prof.Mervat Atfy Mohamed

  9. Defining TLS: Broad definitions exists • Two classification schemes – Hande and Garrow (1993). – Cairo and Bishop (2004) Prof.Mervat Atfy Mohamed

  10. Defining TLS Hande and Garrow (1993) : Developed classification that distinguishes between Lab and Clinical TLS. Limitations: Only few patients developed CTLS. Narrow window exclude patients before day 1 and after day4 from beginning of therapy. LTLS require 25% increase in baseline labs. Prof.Mervat Atfy Mohamed

  11. Defining TLS Prof.Mervat Atfy Mohamed Cairo and Bishop “Laboratory TLS” as defined by two or more of the following occurring 3 days prior to and and up to 7 days following therapy: • Uric acid x > 8.1 mg/dL or 25% increase from baseline • Potassium x > 6 mEq/L or 25% increase from baseline • Phosphorus x > 4.5 mg/dL (adults) or x > 7.4 mg/dL (children) or 25% increase from baseline • Calcium x < 7 mg/dL or 25% decrease from baseline

  12. Defining TLS Cairo and Bishop (continued) – “Clinical TLS”is defined as the presence of laboratory TLS plus any one of the following (not directly or probably attributable to a therapeutic agent): • Elevated creatinine: x > 1.5 Upper Limit of Normal (age > 12 years or age adjusted) • Cardiac arrhythmia or sudden death • Seizure

  13. Risk of TLS – Tumor Characteristics High tumor burden – Large tumor size (> 10 cm) – Serum lactic dehydrogenase (LDH) > 1,500 IU/L – White blood cell count (WBC) > 25-50 x 109/L • Tumor that is highly sensitive to treatment • Tumor with a high proliferative rate • Extensive bone marrow involvement Prof.Mervat Atfy Mohamed

  14. Risk of TLS – Tumor Types

  15. Risk of TLS – Patient Characteristics Elevations in uric acid levels before treatment • Dehydration • Decreased urine output • Acidic urine • Pre-existing renal dysfunction • Acidosis • Tumor involvement of the kidney and/or renal vasculature • Advanced age Prof.Mervat Atfy Mohamed

  16. Risk of TLS – Therapies Cisplatin • Etoposide • Fludarbine • Paclitaxel • Rituximab • Interferon alpha • Corticosteroids and other endocrine agents • Radiation therapy Prof.Mervat Atfy Mohamed

  17. Clinical Manifestations &Consequences Clinical signs and symptoms – Gastrointestinal • Nausea, vomiting, anorexia, diarrhea – Cardiovascular • Edema, hypotension, congestive heart failure, arrhythmias, changes in blood pressure, acute myocardial infarction – Musculoskeletal/Central Nervous System • Lethargy, confusion, mental status changes, pruritis, muscle cramps, tetany, paresthesias, joint pain, back pain, syncope, seizure – Renal • Oliguria, anuria, cloudy urine, hematuria, renal failure Prof.Mervat Atfy Mohamed

  18. Pathophysiology of TLS Prof.Mervat Atfy Mohamed

  19. Hyperuricemia Rapid release and catabolism of intracellular nucleic acids (purines) • Typically occurs 2-3 days after starting therapy • Uric acid secretion occurs distal to the renal proximal tubule • High concentrations of uric acid may lead to the formation of uric-acid crystals in the distal tubules and collecting ducts, resulting in obstructive uropathy and uremia Prof.Mervat Atfy Mohamed

  20. Hyperuricemia Prof.Mervat Atfy Mohamed

  21. Hyperuricemia – Signs andSymptoms Nausea • Vomiting • Diarrhea • Anorexia • Pruritis • Lethargy • Agitation • Back pain •Joint pain • ↑ Serum creatinine • ↑ Blood urea nitrogen • Cloudy urine • Hematuria • Oliguria • Anuria • Edema Prof.Mervat Atfy Mohamed

  22. Hyperphosphatemia Intracellular concentrations of phosphate in malignant cells are released into circulation • Typically seen 24-48 hours after initiation of therapy • Kidneys initially respond to increase load of phosphate but transport mechanisms become Saturated • Most serious consequence is the formation of calcium-phosphate precipitates resulting in acute renal failure Prof.Mervat Atfy Mohamed

  23. Hyperphosphatemia – Signs andSymptoms ↑ Serum creatinine • ↑ Blood urea nitrogen • Oliguria • Renal dysfunction/failure • Pruritis • Arthritis • Gangrenous skin changes resulting from calcium-phosphate deposition Prof.Mervat Atfy Mohamed

  24. Hypocalcemia – Signs and Symptoms Ionized Calcium <1.5 mEq/L: due to extravascular deposition of po4 leads to hypocalcemia Muscle cramps Tetany • Paresthesias • Laryngospasm • Hypotension • Arrhythmias • Seizures Prof.Mervat Atfy Mohamed

  25. Hypercalcemia Hypercalcemia has three main causes: 1. Osteolytic bone lesions (particularly in T-cell leukemia and lymphoma) 2. Bone demineralization secondary to parathyroid-like factors (paraneoplastic syndrome) 3. Immobilization. Patients become symptomatic when serum calcium exceeds 12 mg/dL. Symptoms include:Nausea, vomiting, constipation,weakness,polyuria, , nephrogenic diabetes insipidus,Bradycardia, arrhythmias Prof.Mervat Atfy Mohamed

  26. Hyperkalemia Most detrimental effect of TLS: • Usually seen 6-72 hours after therapy has been started • Can be exacerbated by renal dysfunction, acidosis and hypocalcemia • Symptomatic patients need evaluation for dialysis Prof.Mervat Atfy Mohamed

  27. Hyperkalemia – Signs and Symptoms Nausea • Vomiting • Diarrhea • Anorexia • Weakness • Muscle cramps • Paresthesias • Ascending flaccid paralysis • Arrhythmias • Cardiac arres Prof.Mervat Atfy Mohamed

  28. Renal Dysfunction • Volume depletion – Nausea, vomiting, diarrhea – Cachexia – Insensible losses – Fasting prior to diagnostic procedures and tests • Precipitation in the kidney – Uric acid crystals – Calcium-phosphate • Other – Tumor infiltration – Sepsis Prof.Mervat Atfy Mohamed

  29. Cytokine release syndrome Side effects of chemotherapy: Massive release of intracellular cytokines Release ,Similar to the effect seen with monoclonal antibodies infusions Symptoms Hypotension Tachycardia Fever Respiratory distress: Prof.Mervat Atfy Mohamed

  30. Obtaining and assessing Lab:every 6-12 hours do: CBC LDH Potassium Phosphours Calcium Uric acid Bicarbonate Bun Creatinine Urine analysis(PH,SG ) Urine out put Prof.Mervat Atfy Mohamed

  31. Radiologic Examination Plain X ray Renal ultrasound Avoid IV contrast Prof.Mervat Atfy Mohamed

  32. Ongoing monitoring Vital signs at least every 4 hours Maintain urine output 3-5ml\kg\hour Urine PH\4hours Keep it(7-7.5) Weight every \12hours ECG Prof.Mervat Atfy Mohamed

  33. Principles of Managing Patients at Risk for TLS Prevention is key! – Identify patients at high risk – Institute prophylactic measures • Treat metabolic complications • Provide supportive care Prof.Mervat Atfy Mohamed

  34. Discontinue Exacerbating Medications Electrolyte supplementation in IV fluids • Vitamin and mineral supplements • Medications which cause electrolyte disturbances • Known nephrotoxins Prof.Mervat Atfy Mohamed

  35. Aggressive Hydration Initiate 24-48 hours prior to and continue for up to 72 hours after chemotherapy – Fluid volume ⇒ 3-3.6 L/m2/day D51:4NS – Reduces serum potassium, phosphate, and uric acid concentrations • Goals of hydration – Urine output> 3 mL/kg/min (children) – Urine specific gravity < 1.010 • Caution Risk of fluid overload (heart failure, renal failure) Prof.Mervat Atfy Mohamed

  36. Forced Diuresis If target urine output and/or specific gravity is not met with aggressive hydration alone – Furosemide 0.5 – 1 mg/kg IV Q 6 – 8 hours – Mannitol 0.5 g/kg IV Q 6 – 8 hours • Assists in avoiding fluid overload in high risk Prof.Mervat Atfy Mohamed

  37. Urinary Alkalinization Employed to reduce risk of uric acid crystallization • Agents – IV sodium bicarbonate 20-40mEq\l • Maintain urine pH 6.5-7.5 to allow solubility of uric acid Urine pH >7.5 should be avoided because it is associated with precipitationof hypoxanthine and calcium phosphate in renal tubules. Prof.Mervat Atfy Mohamed

  38. Electrolyte ManagementHypocalcemia Ca • In patients that are asymptomatic, the best method to correct hypocalcemia is to correct hyperphosphatemia • Hydration • Exogenous calcium Prof.Mervat Atfy Mohamed

  39. TLS Prof.Mervat Atfy Mohamed

  40. Electrolyte ManagementHyperphosphatemia Hydration • Phosphate binders 2. Aluminum hydroxide 150-300 mg/kg/day divided every 4–6 hours should be administered. 3. Urine output should be maintained ≥3 mL/kg/hour. • Dialysis for symptomatic patients Prof.Mervat Atfy Mohamed

  41. Electrolyte Management Hyperkalemia 1. Potassium should not be administered until tumor lysis is controlled. 2. The following measures to drive potassium into the cells are utilized: a. NaHCO3: 1–2 mEq/kg/IV. b. Insulin and glucose: Use dextrose 0.5 g/kg/h with insulin 0.1 units/kg/h.Monitor serum glucose closely. 3. For life-threatening arrhythmias, calcium as calcium chloride 10 mg/kg IV is 4. Sodium polystyrene sulfonate (Kayexalate) is administered to remove 1 mEq ofpotassium per liter per gram of resin over 24 hours Prof.Mervat Atfy Mohamed

  42. Uric Acid Reduction – Allopurinol Synthetic structural analog of hypoxanthine • Inhibits xanthine oxidase,preventing conversion of hypoxanthine and xanthine into uric acid • Considered gold standard for treatment of malignancy associate hyperuricemia . Allopurinol: 300 mg/m2/day orally divided tid or 200 mg/m2/day IV. Prof.Mervat Atfy Mohamed

  43. Uric Acid Reduction – Rasburicase Recombinant urate oxidase (Elitek™) – Catalyzes uric acid to allantoin – Allantoin is 5-10 times more soluble than uric The dose is 0.2 mg/kg/day as single daily infusion over 30 minutes for up to 5 days Prof.Mervat Atfy Mohamed

  44. Management of complications ARF Hemodialysis or hemofiltration Indications: An estimated glomerular filtration rate (GFR) less than 50%. Anuria, ● Congestive heart failure ● Symptomatic hypocalcemia with hyperphosphatemia ● Hyperkalemia with QRS internal widening and/or potassium level of>6.0 mEq/L ● BP >150/90 and inadequate urinary output at 10 hours from the start of treatment. Prof.Mervat Atfy Mohamed

  45. Supportive Care and management of Metabolic Emegrencies 2)Hyperleucocytosis

  46. Hyperleukocytosis 5-20% of children with new diagnosed patients of leukemia have WBC count > 100,000/m These patients at risk of severe complications from hyperviscosity of blood Prof.Mervat Atfy Mohamed

  47. Hyperleukocytosis - Complications • Blasts interact with endothelium to form aggregates, thrombi in microcirculation • Most problems in CNS and pulmonary circulation • Complications more common with AML than ALL • Myeloblasts and monoblasts larger, less deformible, “stickier” Prof.Mervat Atfy Mohamed

  48. Pulmonary leukostasis Pulmonary arteriole with leukostatic thrombus C|P: dyspnea, tachypnea, hypoxemia, acidosis, cor pulmonale CXR: diffuse interstitial infiltrates Prof.Mervat Atfy Mohamed

  49. CNS leukostasis Headache, mental status changes, seizures, coma High risk of intracranial hemorrhage, especially with AML and thrombocytopenia Prof.Mervat Atfy Mohamed

  50. Therapy for hyperleukocytosis • Decrease blood viscosity (directly related to morbidity) • Hydration • AVOID use of diuretics • AVOID PRBC transfusion (Hb goal < 10 gm/dL for viscosity) • Transfuse platelets to keep > 20,000/mm3 and treat coagulopathy (common with AML) to decrease risk of intracranial hemorrhage Prof.Mervat Atfy Mohamed

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