Te-Fu Weng, Kung-His Wu, Ching-Tien Peng Department of Hematology and Oncology Children s Hospital of China Medical University
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1 Successful resuscitation using extracorporeal membrane oxygenation for fetal hyperkalemia and refractory ventricular fibrillation due to severe tumor lysis syndrome Te-Fu Weng, Kung-His Wu, Ching-Tien Peng Department of Hematology and Oncology Children s Hospital of China Medical University
2 Introduction Tumor Lysis Syndrome (TLS) is the most common disease-related emergency encountered by physicians caring for children for adults with hematologic cancers. It usually develops most in non-hodgkin lymphoma or acute leukemia. TLS occurs spontaneously or response to therapy lead to the characteristic findings of hyperurecemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These electrolyte and metabolic disturbances can progress to clinical toxic effects, including renal insufficiency, cardiac arrhythmias, seizures, and death due to multiorgan failure.
3 Case Report Present Illness The 14 y/o male presented with easy ecchymosis over limbs for 3 weeks. Physical examination Slightly ill appearing adolescentnt with enlarged neck non-tender lymphadenopathy, hepatomegaly and multiple ecchymosis
4 Laboratory Data WBC: 28200/ul ANC: 1410/ul Segment: 5% Lymphocyte: 40% Monocyte: 3% Eosinophils: 3% Basophils: 1% Metamyelocytes: 1% Blasts: 35% RBC: 3.65x10 6 /ul Hb: 10.0 g/dl Hct: 31.0% MCV: 85.0 fl MCH: 27.5 pg MCHC: 32.3 g/dl RDW: 16.4% Platelet: 18000/ul Mean platelet volume (MPV):
5 Biochemistry Data GOT: 120 IU/L (10-40) GPT: 121 IU/L (5-45) BUN: 18 mg/dl (9-18) Cr: 1.03 mg/dl ( ) GFR: 98ml/min/1.73m2 LDH: 1194 IU/L ( ) Ca: 9.3 mg/dl ( ) P: 5.9 mg/dl ( ) Na: 138 mmol/l ( ) K: 4.1 mmol/l ( ) Uric acid: 16.5 mg/dl ( )
6 Peripheral Blood Smear Neutrophilic Segment: 12.7 % Lymphocyte: 31.7 % Monocyte: 3.0 % Eosinophil: 1.0 % Basophil: 1.0 % N.Band: 2.0 % N.Metamyelocyte: 2.0 % N.Myelocyte: 0.0 % Promyelocyte: 0.0 % Blast: 43.6 % Atypical Lymphocytes: 3.0%
7 Image Study CXR No mediastinal widening. Cardiac echo: Mitral valve relapsed Mild PR Abdominal echo: No hepatosplenomegaly
8 Bone Marrow Aspiration/Smear
9 Bone Marrow Biopsy/Pathology Microscopically, it shows a markedly hypercellular marrow (cellularity: %) with diffuse infiltration of blasts with fine chromatin and inconspicuous nucleoli. The normal hematopoietic cells are markedly depleted. Immunohistochemical study shows CD3(+), CD10(+), CD19(-), CD20(-), CD33(-) and TdT(+). T lymphoblastic leukemia/lymphoma is considered. Reticulin stain shows no myelofibrosis. Flow cytometry Chromosome Study CD20(B1): 0.64 % CD19(B4): 0.33 % CD10(J5): % CD5(Leu1): % CD3(T3): % CD4(T4): % CD8(T8): % CD13(My7): % CD33(My9): 7.58 % CD14(My4): 1.30 % CD34: % HLA-DR: 8.93 % Chromosome analysis of 12 cells (2 from direct harvest and 10 from overnight culture) of the bone marrow specimen showed an apparently normal male 46,XY karyotype. No other chromosomal abnormality is detected.
10 Diagnosis and Treatment Plan Diagnosis: T- cell lymphoblastic leukemia Treatment Plan: TPOG-ALL 2013 Protocol Initial treatment Rasburicase for hyperurecemia Allopurinol Fluid hydration: G/S 3000ml/m 2 /day Check CBC/DC, Biochemistry QD Induction Chemotherapy Prednisolone Epirubicin Vincristine
11 Laboratory Data before Induction chemotherapy 報告日期 CREA GFR K CA P LDH UA Rasburicase x 報告時間 WBC Hb HCT PLT. Blast
12 K 17 Rasburicase LDH UA Prophylaxis of Tumor Lysis Syndrome Fluid hydration 3000ml/m2/day Monitor urine output Give Rasburicase 1 does 0.1mg/kg Oral allopurinol Induction Chemotherapy Prednisolone Vincristine Epirubicin ,194 1, ,215 1,
13 16 hrs after beginning induction chemotherapy Patient complain of Illness appearing, pale looking Cooperated and response well, but drowsy Very discomfort, but couldn't describe Lower limbs weakness, loss of sensation Back pain Incontinence Vital signs HR SBP DBP RR BT 13: : :
14 報告日期 CREA GFR K CA P LDH UA > CREA K LDH UA Begin induction chemotherapy of TPOG-ALL , , , , ,
15 Management of Hyperkalemia EKG showed VF (K 9.2mmol/L) Begin sod. Bicarbonate 2ml/kg IVP D50W with Insulin 6U (0.1U/kg) Ventolin inhalation Ventricular Fibrillation
16 Resuscitation-1 Conscious loss after sedation before inserting endotracheal tube Refractory Ventricular tachycardia (VT), despite of DC shock 3 times Asystole and begin CPR (6:20 PM) (repeat sod. Bicarbonate, D50W+Insulin 6U, Cal. Gluconate, N/S challenge)
17 6:20 PM: K 10.22, Blood gas PH 6.83 BE: -25, Hb 10 persistent asystole CPR/Insulin/Sod Bicarbonate/Ca. gluconate/bosmin/set double lumen for emergency hemodialysis 7:00 PM: K: 10.14, Blood gas PH 6.96 persistent asystole (CPR>40 mins) Pupil 3.0/3.0, No light reflex Consult ECMO team for rescued fetal/refractory hyperkalemia with VF CVS: high risk of stroke, ICH and neurologic sequela 7:30 K: 8.55 Blood gas PH: persistent asystole
18 07:40 PM Heart beat recovered when ECMO online, recovery of severe acidosis: blood gas PH BE: (after 500cc Jusomin) hyperkalemia: K: :00 PM Begin CVVH connect with ECMO Dopamin/Mirinon for heart function after CPR (90mins)
19 Day 1 after ECMO Cardiac echo showed impairment of cardiac function, mild Cardiologist suggested removal of ECMO if possible. 報告日期 CREA GFR K CA P LDH UA > Rasburicase x3
20 Day 2 after ECMO Weaning ECMO and CVVH smoothly. Duration of ECMO: 36hrs Urine output >2ml/kg/hr 報告日期 CREA GFR K CA P LDH UA > <0.5 Rasburicase x1 Rasburicase x1
21 Day 3-5 after ECMO Day 3 Weaning ventilator setting and removal of endotracheal tube Day 4 Conscious recovered well Day 5 Eating McDonalds on the bed at PICU No neurologic sequela
22 Course of Tumor Lysis Syndrome Rasburicase Induction Therapy ECMO CVVH 1
23 Discussion
24 Warning of TPOG Protocol It is important to prevent or treat hyperuricemia and hyperphosphatemia with secondary hypocalcemia resulting from spontaneous or chemotherapy-induced leukemic cell lysis, especially in T-cell ALL. Patients with large leukemic cell burden should receive hydration and oral phosphate binder. Patients with large leukemic cell burden with or without hyperuricemia (e.g., WBC 100,000/mm3, uric acid 7.5 mg/dl or 6.5 mg/dl in patients <13 years old) may be treated with rasburicase if they have no history of G6PD deficiency or ongoing pregnancy.
25 Risk Factors for Tumor Lysis Syndrome Category of Risk Factor Risk Factor Cancer mass Cell lysis potential Features on patient presentation Supportive care Bulky tumor or extensive metastasis Organ infiltration by cancer cells Bone marrow involvement Renal infiltration or outflow-tract obstruction High rate of proliferation of cancer cells Cancer-cell sensitivity to anticancer therapy Intensity of initial anticancer therapy Nephropathy before diagnosis of cancer Dehydration or volume depletion Acidic urine Hypotension Exposure to nephrotoxins Inadequate hydration Exogenous potassium Exogenous phosphate Delayed uric acid removal Our patient V V V V V
26 Measure K, P, Ca, Cr, Uric acid and Urine output
27 Single Does Rasburicase is effective? Single does vs 5 daily does Enrolled 82 patients, 40 patients received single does and only 6 patients need further does. Single Does 5 Daily Does Annals of Oncology 23: , 2012
28 Commonly Used Agents for Treatment of Hyperkalemia
29 ECMO use in Pediatric Hematologic and Oncologic Disorders No Age Sex Disease Causes of ECMO CPR Outcome Neurologic Sequelae 1 5 Female Acute myeloid leukemia, Invasive fungal infection Severe pulmonaryry embolism Yes Alive Yes 2 13 Male Thymoma, stage III Cardiogenic shock after sedation Yes Alive No 3 9 Male Mediastinal yolk-sac tumor Pulmonary venous compression No Death NA 4 12 Male Mediastinal sclerosing mediastinitis Pulmonary venous compression No Death NA 5 17 Male Mediastinal T-cell lymphoma Prophylaxis (severe tracheal compression) No Alive No 6 15 Male T-cell leukemia Tumor lysis syndrome induced hyperkalemia, refractory VF Yes Alive No
30 ECMO rescued for Hyperkalemia and fetal arrhythmia Many reports about succinylcholline induced rhabdomyosis related hyperkalemic cardiac arrest. Rare report about TLS induced hyperkalemic cardiac arrest.
31 Conclusion TLS must be kept in mind despite patients without leukocytosis who was diagnosed as T-cell lymphoblastic leukemia/lymphoma despite of using rasburicase. The most important strategies for TLS related fetal hyperkalemia is prevention, however, ECMO permitted adequate time for hemodialysis if fetal hyperkalemia with refractory ventricular fibrillation occurred. Don t give up.
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