1. Oncology Emergencies in PICU Norah Khathlan MD Pediatric Intensivist Director PICU November 2006

2. Oncology Emergencies in the PICU MEDIASTINAL MASSES MEDIASTINAL MASSES SVC Syndrome SVC Syndrome HYPERLEUKOCYTOSIS HYPERLEUKOCYTOSIS TUMOR LYSIS SYNDROME TUMOR LYSIS SYNDROME SEPTIC SHOCK SEPTIC SHOCK ARDS ARDS SPINAL Cord Compression. SPINAL Cord Compression. CNS Events CNS Events

3. Oncology Emergencies in the PICU 1- TUMOR LYSIS SYNDROME Metabolic abnormalities occurring as a result of tumor cell death: Metabolic abnormalities occurring as a result of tumor cell death: –Spontaneously –Chemotherapy Starting chemotherapy on rapidly growing- chemo-sensitive tumors  release of intracellular contents into circulation. Starting chemotherapy on rapidly growing- chemo-sensitive tumors  release of intracellular contents into circulation.

4. TUMOR LYSIS SYNDROME Hyperkalemia. Hyperkalemia. Hyperphospatemia. Hyperphospatemia. 2 ry Hypocalcemia. 2 ry Hypocalcemia. Hyperuricemia. Hyperuricemia. Uremia. Uremia. High creatinine. High creatinine. Oliguria. Oliguria.

5. TUMOR LYSIS SYNDROME Incidence: Incidence: –70% of hematological malignancies  laboratory criteria of TLS. –3% with clinical TLS. Associated with hematological malignancies: Associated with hematological malignancies: –ALL –AML –Lymphomas –Solid tumors

6. TUMOR LYSIS SYNDROME Maybe precipitated by : Maybe precipitated by : –Chemotherapy –steroids –Radiotherapy. –Hormonal agents. Risk factors: Risk factors: –Tumor type –Dehydration –Preexisting renal insufficiency –Nephrotoxic medications High LDH in TLS is indicative of likely progression to ARF High LDH in TLS is indicative of likely progression to ARF

7. TUMOR LYSIS SYNDROME MANAGEMENT: MANAGEMENT: –Identify at risk patients. –Admit to PICU. –Consult Nephrology service –Establish good venous access prefer. CVC. –Frequent lab monitoring of: - Na + - Ca ++ - K + - Uric acid - Cl - - Creatinine - PO4 ++ - Urea - Bicarbonate- LDH

8. TUMOR LYSIS SYNDROME MANAGEMENT: cont. MANAGEMENT: cont. –Urine analysis and pH –HYDRATION THERAPY: 2-3 L/m 2 /day OR 1 1/2 to 2 x maintenance 2-3 L/m 2 /day OR 1 1/2 to 2 x maintenance Start 24-48 hrs prior to chemotherapy. Start 24-48 hrs prior to chemotherapy. Isotonic NS or Hypotonic saline if Urine Na <150 meq/L Isotonic NS or Hypotonic saline if Urine Na <150 meq/L Alkalinization of the urine to pH = 6-7 controversial ! Alkalinization of the urine to pH = 6-7 controversial ! Diuretics controversial ! Diuretics controversial ! Mannitol if suboptimal diuresis Mannitol if suboptimal diuresis Avoid P.O. or exogenous K +, potassium sparing diuretics, ACE inhibitors and uric acid tubular re-absorption blockers. Avoid P.O. or exogenous K +, potassium sparing diuretics, ACE inhibitors and uric acid tubular re-absorption blockers.

9. TUMOR LYSIS SYNDROME Specific management: Specific management: –Hyperkalemia: –Ca gluoconate –Na Bicarbonate –Insulin & Glucose –Salbutamol –K binding resins –DIALYSIS or CRRT “CVVHD” for K>5

10. TUMOR LYSIS SYNDROME Hyperphosphatemia & 2ry Hypocalcemia: Hyperphosphatemia & 2ry Hypocalcemia: –Phosphate binders eg. Aluminum antacids. –Avoid unnecessary Ca supplements. –PO4 > 4 is an indication for dialysis. –Consider CRRT.

11. TUMOR LYSIS SYNDROME Hyperuricemia: Hyperuricemia: Urine Alkalinization maximizes Uric acid solubility Urine Alkalinization maximizes Uric acid solubility Urine pH > 6 and 6 and < 7.5 Avoid urine pH more than 7.5 “may lead to massive phosphate crystalluria and phosphate precipitates”. Avoid urine pH more than 7.5 “may lead to massive phosphate crystalluria and phosphate precipitates”.

12. Tumor Lysis Syndrome Allopurinol: Allopurinol: –Xanthine oxidase inhibitor: Xanthine Hypoxanthine Xanthine Hypoxanthine X anthine oxidae -  X anthine oxidae -  -ve -ve allopurinol allopurinol Uric Acid Uric Acid –Blocks production of new Uric acid –Increased levels of uric acid precursors; Xanthine  nephrotoxic –Impairs chemotherapy metabolism

13. TUMOR LYSIS SYNDROME Hyperuricemia: cont. Hyperuricemia: cont. –Non recombinant urate oxidase (Uricozyme) urate oxidase Uric Acid --------------------------  Allantoins “highly soluble in urine” –Recombinant Urate Oxidase (Rasburicase) Effective: Single dose decreases uric acid from 15 to 0.4 mg/dl in 24 hrs Effective: Single dose decreases uric acid from 15 to 0.4 mg/dl in 24 hrs Costs Costs C.I. in G6PD deficiency C.I. in G6PD deficiency ==================== ====================

14. Oncologic Emergencies in PICU 2- Hyperleukocytosis WBC counts > 100,000/ul in 5-20% children ALL WBC counts > 100,000/ul in 5-20% children ALL Clinically significant if > 300,000 in ALL Clinically significant if > 300,000 in ALL Marked elevation of blood viscosity: Marked elevation of blood viscosity: erythrocyte + Leukocyte volumes and deformability of cells. erythrocyte + Leukocyte volumes and deformability of cells. Normal = 1.5 relative to water Normal = 1.5 relative to water Clinical manifestation if > 4 Clinical manifestation if > 4 Mainly affects CNS & Lungs Mainly affects CNS & Lungs –Leukocyte aggregation. –Small vessel obstruction. –Decreased perfusion of microcirculation. –Vascular stasis, Leukostasis. –Risk of Intra Cranial Hmg and /or IVH & SAH –Role of Cytokines !!

15. Hyperleukocytosis Management : Management : –Lack of controlled trials. –Avoid Packed RBCs transfusion –Avoid diuretics. –Maintain platelets > 20,000 –Correct coagulopathy –Hydration,? Alkalinization and allopurinol: Used in ALL & WBCs > 100,000  80% reduction in 36hrs no complications. Used in ALL & WBCs > 100,000  80% reduction in 36hrs no complications. –Exchange transfusion & Leukapheresis; Needs anticoagulants and vascular access. Needs anticoagulants and vascular access. Rebound WBC count. Rebound WBC count. No effect on pulmonary status, CNS outcome or mortality. No effect on pulmonary status, CNS outcome or mortality. NO ROLE FOR STEROIDS NOR emergency CRANIAL RADIATION

16. Oncology Emergencies in the PICU 3- Anterior Mediastinal Mass Airway & circulatory compromise posed by mediastinal masses provide some of the great challenges in the PICU and in OR This is a genuine emergency!!

17. Anterior Mediastinal Mass Anterior: Anterior: –Lymphomas –Teratomas Middle: Middle: –Lymphoma Posterior: Posterior: –neuroblastoma

19. Anterior Mediastinal Mass Signs & Symptoms: Signs & Symptoms: –Respiratory symptoms predominate: > 50% narrowing Air hunger Air hunger Dyspnea Dyspnea Wheezing Wheezing Anxiety Anxiety Position of comfort. Position of comfort. –SVC obstruction symptoms: Facial swelling Facial swelling Periorbital edema Periorbital edema Conjunctival suffusion Conjunctival suffusion Headache & Dizziness Headache & Dizziness

20. Anterior Mediastinal Mass Evaluation: Evaluation: –Quick & cautious approach is a must!!! –Inappropriate delay, investigation and /or management may be catastrophic !! CXR: PA & Lat.  wide mediastinum CT Chest: – –No sedation May lead to cardio- respiratory arrest – –No supine position

21. Anterior Mediastinal Mass CBC & blood film CBC & blood film LDH LDH Β-HCG & α-fetoprotein Β-HCG & α-fetoprotein BMA & biopsy BMA & biopsy Pleural fluid LOCAL Anesthetic Pleural fluid LOCAL Anesthetic Pericardial fluid Only Pericardial fluid Only Lymph node biopsy Lymph node biopsy

22. Anterior Mediastinal Mass If still no diagnosis: nearly 27% of cases Empiric therapy –Steroids –Chemotherapy –Radiation OR More Invasive testing

23. Anterior Mediastinal Mass Accurate diagnosis is preferable but Significant risk of induction of general anesthesia must be considered Predictors of safe G.A.: –Echo to evaluate cardiac motility & venous return –PFT : PEF rates > 5o% predicted –Tracheal cross-sectional area > 50% Different Protocols for different PICUs depending on the available support. Different Protocols for different PICUs depending on the available support.

24. Anterior Mediastinal Mass In a Study to assess risk of G.A in patients with SVC syndrome,163 children with anterior mediastinal masses were reviewed: –44 underwent G.A. prior to therapy: Seven (16%) developed life-threatening airway compromise. Seven (16%) developed life-threatening airway compromise. Three needed chemotherapy or radiation prior to extubation. Three needed chemotherapy or radiation prior to extubation. However all survived. However all survived. Ferrari et al; General Anesthesia prior to treatment of anterior mediastinal masses in Pediatric cancer patients, Anesthesiology 1990 Ferrari et al; General Anesthesia prior to treatment of anterior mediastinal masses in Pediatric cancer patients, Anesthesiology 1990

25. Anterior Mediastinal Mass Intubation should be performed: Intubation should be performed: – Awake with FOB. –Spontaneously breathing. –Sitting position. –Lower extremities venous access. –Standby ECMO or CPB If above is not feasible: If above is not feasible: Seriously consider empiric steroids +/- chemo or radiotherapy

26. Oncology emergencies in the PICU Coordination of care is essential for optimal care. Coordination of care is essential for optimal care. Communication and collaboration among the members of the health care team improves quality and efficiency of patient care. Communication and collaboration among the members of the health care team improves quality and efficiency of patient care. Everyone has an important role in the team, BUT there must be a “Captain of the Ship”. Everyone has an important role in the team, BUT there must be a “Captain of the Ship”.

27. NOW Back to our patient NOW Back to our patient