Tumour Lysis Syndrome

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1 Tumour Lysis Syndrome Managment of Haematology Emergencies Geneva, 2012 Joachim Blankart, Hamburg (DE) Sylt St. Georg (Hamburg) Falkenstein Ini Hannover Bad Griesbach

2 Content 01 Definition 02 Symotoms and pathogenesis 03 Risk factors 04 Diagnosis 05 Prevention 06 Treatment 07 Role of Nurses 08 References 3. April 2012 Tumour Lysis Syndrome 2

3 01 Definition Tumour lysis syndrome (TLS) Tumor lysis syndrome (TLS) is a metabolic disorder characterized by hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia brought about by rapid tumor cell destruction that may result in a variety of musculoskeletal, renal, cardiac, and neurologic manifestations. 3. April 2012 Tumour Lysis Syndrome 3

4 Content 01 Definition 02 Symotoms and pathogenesis 03 Risk factors 04 Diagnosis 05 Prevention 06 Treatment 07 Role of Nurses 08 References 3. April 2012 Tumour Lysis Syndrome 4

5 02 Symptoms and pathogenesis Tumour lysis syndrome (TLS) Rapid breakdown of tumour cells can be caused by - Chemotherapy - Antibody therapy - Corticosteroid therapy - Radiotherapy - Spontaneous cell death due to rapid growth without sufficient growth of e.g. blood vessels 3. April 2012 Tumour Lysis Syndrome 5

6 02 Symptoms and pathogenesis The massive breakdown of cells sets free various intracellular contents - Potassium - phosphate - nucleic acids - lactate dehydrogenase etc. which enter the system of systemic fluids >>> ionic imbalance >>> catabolization of nucleic acids to urate 3. April 2012 Tumour Lysis Syndrome 6

7 02 Symptoms and pathogenesis Ionic imbalance Hyperkalemia serum K+ level >6.0 mmol/l or 25% increase from baseline Fatigue Muscle cramps Anorexia Paresthesias Irritability Cardiac arrythmia (atrioventricular dissociation, ventricular tachycardia, or ventricular fibrillation) 6-72 hours after treatment 3. April 2012 Tumour Lysis Syndrome 7

8 02 Symptoms and pathogenesis Hyperphosphataemia (serum phosphate level 4,5 mg/dl or 25% increase from baseline) + Hypocalcaemia (serum calcium level 7,0mg/dL or 25% decrease from baseline) hours after treatment Increased release of phophate due to breakdown of tumour cells Decreased phophate excretion due to impaired renal function Decreased use of phophate by malignant cell Precipitation of Calciumphosphate due to high phosphate concentration leads to hypocalcaemia o muscle cramps, tetany, seizures, cardiac manifestation (QTinterval, contractility ) o acute nephrocalcinosis 3. April 2012 Tumour Lysis Syndrome 8

9 02 Symptoms and pathogenesis Hyperuricaemia serum uric acid 8,0mg/dL or 25% increase from baseline Acute kidney injury from urate nephropathy hours after treatment 3. April 2012 Tumour Lysis Syndrome 9

10 Content 01 Definition 02 Symptoms and pathogenesis 03 Risk factors 04 Diagnosis 05 Prevention 06 Treatment 07 Role of Nurses 08 References 3. April 2012 Tumour Lysis Syndrome 10

11 03 Risk factors o High tumour burden o Rapidly proliferating and bulky haematologic malignancies (ALL, Burkitt-Lymphoma) o Aggressiveness of cytotoxic therapy o Dehydration o Pre existing renal impairment o Nephrotoxic substances 3. April 2012 Tumour Lysis Syndrome 11

12 Content 01 Definition 02 Symptoms and Pathogenesis 03 Risk factors 04 Diagnosis 05 Prevention 06 Treatment 07 Role of Nurses 08 References 3. April 2012 Tumour Lysis Syndrome 12

13 04 Diagnosis Laboratory features Urea Creatinine Uric acid / Urate Phosphate Potassium Albumin corrected Calcium Clinical features Cardiac manifestation Muscle Cramps Seizures etc. 3. April 2012 Tumour Lysis Syndrome 13

14 04 Diagnosis Cairo-Bishop definition (2004) Laboratory : abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy. uric acid > 8 mg/dl or 25% increase potassium > 6 mmol/l or 25% increase phosphate > 4.5 mg/dl or 25% increase calcium < 7 mg/dl or 25% decrease Clinic: laboratory tumor lysis syndrome plus one or more of the following: increased serum creatinine (1.5 times upper limit of normal) cardiac arrhythmia or sudden death seizure 3. April 2012 Tumour Lysis Syndrome 14

15 Content 01 Definition 02 Syptoms and Pathogenesis 03 Risk factors 04 Diagnosis 05 Prevention 06 Treatment 07 Role of Nurses 08 References 3. April 2012 Tumour Lysis Syndrome 15

16 05 Prevention Maintaining renal function Increased infusion volume aiming to maintain urine output above 100ml/m2/hour (ca. 3l/m² /day) Use of diuretics (furosemide, mannitol) if necessary Close monitoring of fluid in- and output Supporting Urate- secretion Allopurinol (dosage depending on risk) Rasburicase (high risk patients) Delaying Treatment Alkalinisation Not fully recommended as risk of precipitation of Calciumphosphate increases Avoiding additional nephrotoxic substances 3. April 2012 Tumour Lysis Syndrome 16

17 Content 01 Definition 02 Symptoms and Pathogenesis 03 Risk factors 04 Diagnosis 05 Prevention 06 Treatment 07 Role of Nurses 08 References 3. April 2012 Tumour Lysis Syndrome 17

18 06 Treatment Substitution of Calcium Lowering Potassium level Insuline + Dextrose, Sodium polystyrene sulphonate, e.g. Resonium, Kionex Reduction of Urate Uricase (Rasburicase e.g. Fasturtec, Uricase PEG 20, Puricase) Hydration to keep up flow of urine Dose modification or avoidance of nephrotoxic substances Renal replacement Therapy Haemodialysis, Haemofiltration 3. April 2012 Tumour Lysis Syndrome 18

19 Content 01 Definition 02 Symptoms and Pathogenesis 03 Risk factors 04 Di 05 Diagramme 06 Organisation 07 Role of Nurses 08 References 3. April 2012 Tumour Lysis Syndrome 19

20 07 Role of Nurses Awareness of TLS Stick to the protocol Monitoring Fluid intake and output Laboratory Watch your Patient!!! 3. April 2012 Tumour Lysis Syndrome 20

21 Content 01 Definition 02 Symptoms and Pathogenesis 03 Risk Factors 04 Diagnosis 05 Prevention 06 Treatment 07 Role of Nurses 08 References 3. April 2012 Tumour Lysis Syndrome 21

22 08 References Ramon V. Tiu, M.D.; Stavros E. Mountantonakis, M.D.; Andrew J. Dunbar, B.S. and Martin J. Schreiber, Jr., M.D. (2007): Tumor Lysis Syndrome; SEMINARS IN THROMBOSIS AND HEMOSTASIS/VOLUME 33, 4; Surrey, West Sussex and Hampshire Cancer Network NHS: Guidelines for the Management of Tumour Lysis Syndrome; 0Syndrome%20V2% pdf [ ] Mitchell S. Cairo and Michael Bishop (2004): Tumour lysis syndrome: new therapeutic strategies and classification; British Journal of Haematology, 127, April 2012 Tumour Lysis Syndrome 22

23 Thank you! Joachim Blankart Asklepios Klinik St. Georg, Hamburg, Germany Sylt St. Georg (Hamburg) Falkenstein Ini Hannover Bad Griesbach

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